[Senate Hearing 112-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2012
----------
WEDNESDAY, MAY 11, 2011
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:59 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Reed, Mikulski, Brown, Shelby,
Kirk and Moran.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF DR. FRANCIS S. COLLINS, DIRECTOR
ACCOMPANIED BY:
HAROLD VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
SUSAN B. SHURIN, M.D., ACTING DIRECTOR, NATIONAL HEART, LUNG,
AND BLOOD INSTITUTE
DR. GRIFFIN RODGERS, DIRECTOR, NATIONAL INSTITUTE OF DIABETES,
DIGESTIVE AND KIDNEY DISEASES
OPENING STATEMENT OF SENATOR TOM HARKIN
Senator Harkin. The Senate Subcommittee on Labor, Health
and Human Services, and Education will now come to order.
First of all, Dr. Collins, welcome back to the
subcommittee. We welcome also Dr. Harold Varmus, Director of
the National Cancer Institute; Dr. Tony Fauci, Director of the
National Institute of Allergy and Infectious Diseases; Dr.
Griffin Rodgers, Director of the National Institute of
Diabetes, Digestive and Kidney Diseases; and Dr. Susan Shurin,
Director of the National Heart, Lung, and Blood Institute.
This subcommittee holds an appropriations hearing on the
NIH budget every year, and every year I am both inspired by the
dedication of the scientists who testify before us and proud
that their accomplishments have made America the world leader
in biomedical research. But in recent years, our Nation's
status in that regard has been threatened. While China and
Singapore make massive investments in research, here in the
United States we're pulling back.
The fiscal year 2011 appropriations bill that Congress
passed last month cut NIH funding by $322 million below the
fiscal year 2010 level. When you consider how much funding was
needed to keep up with inflation, the cut was more like $1.3
billion, taking inflation into account.
We should be thankful that the result wasn't significantly
worse. H.R. 1, the spending bill passed by the House majority,
would have cut NIH funding by $1.6 billion or $2.6 billion if
you counted inflation. Fortunately, the Senate rejected that
plan.
But even the compromise bill that was ultimately signed in
law will result in a success rate for NIH research grants, I'm
told, of just 17 or 18 percent, meaning just one out of every
six peer-reviewed application will be approved. And, again, I
am informed that that is the lowest success rate on record for
NIH.
What a dismal downturn from what Senator Specter and I, and
others did back in the late 1900s and early 2000 when we
doubled the funding of NIH and we got the success rate up, I
think--if I'm not mistaken. You correct me, Dr. Collins--up in
the 20-30 percent range, somewhere in there. And we thought we
were on a path to continue that kind of a success rate. Now,
it's down lowest on record.
And there is cause to fear even bigger cuts next year. The
budget plan approved by the House last month would cut health
funding by 9 percent in fiscal year 2012. If that plan were
approved, severe reductions to NIH research would be
unavoidable.
That doesn't make sense. Let's set aside for a moment any
thoughts about the moral value of trying to improve people's
health, and just look at the issue from a purely economic
standpoint. NIH research is one of the best investments this
country can make.
A study released yesterday by United for Medical Research
concluded that in fiscal year 2010, NIH funding supported
almost 500,000 jobs across country. And I always have to remind
people that only a small percentage of that goes to NIH in
Bethesda, Maryland. I want Senator Mikulski to know that. Most
is awarded to researchers at academic institutions all over the
United States.
Another study by Battelle examined the specific impact of
the Human Genome Project, which was overseen, again, by Dr.
Collins and completed in 2003. The Federal Government spent a
total of $3.8 billion on this historic initiative. A lot of
money, but the return on the investment is staggering.
According to the Battelle study that $3.8 billion translated
into an economic output of $796 billion between 1988 and 2010.
And, of course, we'll be seeing benefits from the Human Genome
Project for many more decades to come. In fact, when I was
reading all of your testimonies last night, what struck me in
each one of them there were references made back to genomic
research in every single case of the institutes who are
represented here.
So the lesson is clear. Biomedical research is one of the
engines that drive our economy. If we want our economy to grow,
both immediately and in the long term, that engine needs fuel.
Drastically cutting NIH, as the House budget would force us to
do, would be a classic case of penny wise and pound foolish
thinking. That, again, is just on the economic side.
On the human side, though, the great advances that have
been made in cancer research and what we have done to lessen
the threat of cancer--young kids now with leukemia are being
cured at an almost 100 percent rate. Maybe that's not quite
right, but pretty darn close, things that were unheard of just
a few years ago. The advances that we're making in infectious
diseases, unheard of 20 years ago when I first came on this
subcommittee. Well, that's been 25 years ago, but great
advances have been made. Just stark.
So, from the human standpoint, in helping people have
better lives and overcoming some of the dreaded diseases that
have plagued mankind for so long, on both fronts, biomedical
research is the place to go and we ought not to be penny wise
and pound foolish on that.
And so now I'll recognize my ranking member, Senator
Shelby, for an opening statement.
STATEMENT OF SENATOR RICHARD C. SHELBY
Senator Shelby. Thank you, Mr. Chairman. I appreciate you
holding this hearing today to discuss the vital mission carried
out by the National Institutes of Health.
We live in a world where there are thousands of
debilitating and life-threatening diseases, all that could use
additional funding for research and clinical trials.
I support Federal investment in basic biomedical research
and development. Research carried out by the NIH and its
network of 325,000 researchers at 3,000 institutions across the
country serves the Nation with the goal of improving human
health. As research becomes more expensive and private capital
dries up, I believe it's critical to ensure support for
translational research; that is, research that moves a
potential therapy from development to the market.
The NIH has developed an interesting proposal with the
establishment of the National Center for Advancing
Translational Sciences, NCATS. NCATS is intended to fill the
gap between advances in scientific understanding of disease and
the process to turn new scientific insights into products. I
believe the need for an entity to straddle the world's research
and industry is clear.
In the private market, pharmaceutical companies will
abandon drug development projects that are not initially
successful, become too complex or do not provide a lucrative
path forward.
For example, since 1949, there have only been two major
drug discoveries in mental health--lithium and Thorazine. Sixty
years later, researchers still do not know why these drugs
actually work. Hundreds of genes have been shown to play roles
in mental illness, too many for focused efforts by drug
developers.
Therefore, many drug manufacturers have dropped out of the
mental-health field. In particular, pharmaceuticals for rare
and neglected disease are often ignored because private
companies avoid this small market with little profit appeal
leaving patients with no treatment options.
Even promising new drugs discovered through basic research
often struggle during the translational stage of the process
because it's expensive, time consuming and prone to failure.
These barriers inhibit both the scientists dedicated to
improving health and the patients who ultimately need improved
cures and care.
The question remains, however, as to whether NCATS is the
right approach to solving the issue. Will NCATS be the right
mechanism for taking valuable discoveries that the taxpayer has
funded and giving it a greater opportunity to make it in the
marketplace? As we review this proposal, we need to consider
the fact that NIH is not a drug developer or an expert in the
therapeutics world.
Dr. Collins, I would like to continue to work with you to
make a thoughtful, informed decision regarding the NCATS.
Unfortunately, the fiscal year 2012 budget request, I believe,
does not provide adequate details on the reorganization.
It is May 11 and we've not received a budget amendment or
specific structural details of an NCATS, a program NIH wants to
implement by October 1. How can the subcommittee be expected to
support a program that does not yet exist in budget documents?
I understand that the transition from basic research to
clinical application requires interdisciplinary and
multidisciplinary expertise. Research that aims to transform
science is inherently difficult. If it were easy, the need for
transformation would not exist.
NCATS may be the answer to solve this complex issue, but it
also may not be. We don't know. Dr. Collins, I believe that
NCATS is a matter that we should contemplate, but we must
ensure that the steps forward are measured and in the best
interests of all stakeholders, especially those who are in need
of treatment and care.
I look forward to working with you and the chairman on this
very important issue. Thank you.
INTRODUCTION OF WITNESS
Senator Harkin. Thank you very much, Senator Shelby.
Now, welcome back to Dr. Collins.
Francis Collins was sworn in as the 16th Director of the
National Institutes of Health in August 2009 after being
unanimously confirmed by the Senate.
He is a physician geneticist noted for his discoveries of
diseased genes and leadership, of course, of the Human Genome
Project. Prior to becoming Director, he served as Director of
the National Human Genome Research Institute at NIH.
Dr. Collins received his bachelor's degree from the
University of Virginia, his Ph.D. from Yale and his M.D. from
the University of North Carolina at Chapel Hill.
Dr. Collins, again, welcome, and first I want to say that
your testimony, and all of the testimony of the Directors who
are here, will be made a part of the record in their entirety.
Again, due to time, Dr. Collins, we ask you to make a
fairly comprehensive statement. I'm not going to get the clock
going here, but if it goes too long and people start looking at
me funny, then I'll probably ask you to close it out. But
please take whatever time you need to give us an update on NIH
and a concise summation of your written testimony.
SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS
Dr. Collins. Well, thank you, Senator, and, Mr. Chairman,
and distinguished members of the subcommittee, it's an honor to
appear before you this morning, together with my colleagues, on
behalf of NIH.
And I'll try not to talk so long that people start looking
at you or looking at me, but I do have some things I really
wanted to put in front of this distinguished subcommittee,
because this is a very exciting time for biomedical research.
NIH is the largest supporter of biomedical research in the
world, and we're here to present the President's budget request
of $31.987 billion for fiscal year 2012.
NIH--Turning Discovery Into Health
Global Competitiveness--The Importance of U.S. Leadership in Science
and Innovation for the Future of Our Economy and Our Health
The National Science Board's 2010 Key Science and Engineering
Indicators, provide insight into how crucial decisions on R&D funding
may affect our Nation's ability to thrive in an increasingly
competitive and knowledge-driven global economy. While these trends
apply not just to bimoedical reserch, but also to research in
chemistry, physics, engineering, computer science, and many other
fields, the conclusion of most observers is that the 21st century will
be dominated by the life sciences, and the country that leads in this
area will have much to gain. Unfortunatley, the United States,
traditionally the dominant Nation in scientific resarch, has been
slipping in leadership recently.
Losing Ground.--R&D investment growth rates are rising sharply in
Asia.
For example, China's growth rate is 4 times higher than the U.S.
rate.
While the U.S. remains among the nations with the highest actual
R&D expenditures, Asia is rapidly closing the gap.
Employment Impact: The number of people engaged in scientific
research in China has increased dramatically. In 2007, China had 1.42
million researchers, while the US had 1.47 million. In 2010, it is
likely that China has surpassed the U.S. research workforce.
Knowledge Generation: The number of scientific articles published
is a common measure of scientific productivity. The average increase in
U.S. publications is significantly lower than for other key countries
and also below the world average. Meanwhile, China, Thailand, South
Korea, and others show impressive growth rates.
As a result of the previously mentioned trends, it is not
surprising that the U.S. share of world publications has significantly
decreased, and that China's share has grown.
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Share of world
articles (Percent) Percent
Country/Region ---------------------- Change
1998 2008
------------------------------------------------------------------------
United States.......................... 34 28.9 -5.1
EU..................................... 34.6 33.1 -1.5
China.................................. 1.6 5.9 4.3
Japan.................................. 8.5 7.8 -0.7
Asia-8................................. 3.6 6.8 3.2
------------------------------------------------------------------------
Source: SEI 2010
The number of times a scientific article is cited indicates its
scientific impact. One could argue that emerging countries are
publishing articles with limited impact. While this may be the case
from certain perspectives, the aggregate number of citations indicates
a worrisome plunge in the U.S. share of worldwide citations, which fell
8.6 percent from 1998 to 2008. In contrast, China and Asia-8 countries
displayed a noticeable increase in their share of citations, rising 3.7
percent and 3.1 percent respectively over the same time period.
Economic consequences: Reducing R&D investments when other nations
are rapidly increasing them has already had significant consequences on
exports, which are an important component of the U.S. economy and well
being of Americans.
IMPACTS ON U.S. ECONOMY
NIH is the largest funder and conductor of biomedical research in
the world.
The NIH fiscal year 2011 budget is $31 billion--84 percent of which
is awarded to the Nation's finest universities, institutes, and small
businesses through a rigorous peer review process. Every State, along
with almost every Congressional district, benefits.
NIH extramural program supports more than 40,000 competitive
research grants and 325,000 research personnel at more than 3,000
universities, medical schools, and other research institutions in all
50 states, U.S. territories, and around the world.
Approximately 10 percent of the NIH budget funds nearly 6,000
scientists working at the NIH campus in Bethesda, in laboratories in
Rockville and Frederick, Maryland, at Research Triangle Park in
Raleigh, North Carolina, and at the Rocky Mountain Laboratories in
Hamilton, Montana.
NIH spending increases business activity directly and indirectly:
According to Families USA, each dollar of NIH award money generates
about $2.21 of new business activity within 1 year, while each grant
awarded by NIH generates about 7 jobs.
NIH-driven advances have not only had profound effects on the
health and quality of life for all Americans, but also yielded economic
gains. The percentage of elderly with chronic disabilities has declined
(from 27 percent in 1982 to 19 percent in 2005). Since 1970, life
expectancy in the United States has risen from 71 to 78 years.
Economists estimate that these gains in life expectancy have been worth
approximately $95 trillion.
The economic potential of NIH-fueled advances in improved
treatments for disease is also clear in this projection: a reduction in
cancer deaths by one percent has a present value to current and future
generations of Americans of nearly $500 billion. A full cure would be
worth approximately $50 trillion--more than three times today's GDP.
Advances in disease diagnosis also illustrate the health-related
and economic benefits of NIH research: approximately $100 million in
health care costs annually are being saved through the use of a genomic
test that determines whether a particular type of breast cancer is
likely to be cured by surgery and radiation or by chemotherapy. As a
result of this test, thousands of women are being spared needless
exposure to toxic therapies--and millions of dollars are being saved.
NIH is an engine of innovation--and a crucial support for the
global competitive stature of the United States. In fiscal year 2010,
NIH filed 289 U.S. patent applications (of which 141 were new
applications). These are now included in a total of 3,186 NIH patent
applications in the United States and abroad that were pending
approval.
Key Facts on U.S. Competitiveness in the Global Research Arena
The United States still is the world leader in science and
engineering research. But that leadership role is being challenged by
China, India, and other nations as they recognize the economic, health,
and social benefits of investing in R&D.
Over the past decade, R&D intensity has grown in Asia, but remained
flat in the United States.
Growth of R&D expenditures in the United States averaged 5-6
percent annually from 1996-2007, lagging behind the worldwide average
of 7 percent per year. In contrast, growth in most Asian nations
exceeded the worldwide average, and China's R&D expenditures grew more
than 20 percent annually from 1996-2007.
The United States share of high technology exports fell by one-
third from 1996-2007. China's share more than tripled.
India exported $8.3 billion in pharmaceutical products and services
in fiscal year 2009, up 25 percent from the previous year.
About 277,000 people, ranging from scientists and to production
workers, are currently employed by pharmaceutical companies in the
United States, a decline of 5 percent from 2008. More than 340,000
people work in India's pharmaceutical manufacturing industry in 2009--
and the industry is projected to grow by 13 percent in 2010.
Between 1995 and 2007, the worldwide share of researchers working
in China, Singapore, South Korea, or Taiwan rose from 16 percent to 31
percent.
In 2007, the United States had 1.47 million people engaged in
scientific research; China had 1.42 million--and it was generating R&D
jobs at three times the rate of the U.S.
In the United States, the percentage of undergraduate students who
major in science and engineering is 15 percent; in China, it is 50
percent.
In 1995, China ranked 14th in the world in the production of
research publications. In 2008, it ranked second.
China's leading genome sequencing institute, BGI, is on track to
sequence more than 10,000 human genomes a year. That would surpass the
entire DNA sequencing output of the United States.
For more on how shifts in global research capacity are challenging
the United States to actively focus on maintaining its competitive
strength, go to http://www.nsf.gov/statistics/nsb1003/.
Health Improvements
In the last 25 years, NIH-supported biomedical research has
directly led to human health benefits that both extend lifespan and
reduce illnesses:
--Prolonging Life and Reducing Disability.--Our Nation has gained
about 1 year of longevity every 6 years since 1990. A baby born
today can look forward to an average lifespan of nearly 78
years--nearly three decades longer than a baby born in 1900.
Not only are people living longer, they are staying active
longer. From 1982 through 2005, the proportion of older people
with chronic disabilities dropped by almost a third.
--Heart Disease.--NIH research has generated new techniques for heart
attack prevention, effective drugs for lowering cholesterol and
controlling blood pressure, and strategies for dissolving blood
clots. As a result, the death rate for coronary disease is 60
percent lower--and for stroke, more than 70 percent lower--than
during the era of World War II. Better treatment of acute
conditions, better medications, and improved health-related
behaviors--all made possible by NIH research--account for as
much as two-thirds of this reduction.
--Chronic Disability.--From 1982-2004, the reported chronic
disability among American seniors dropped nearly 30 percent.
Health improvements from NIH research played a major role in
this, including better prevention and treatment of heart
attacks and strokes, advances in treatment of arthritis, and
improved technologies for cataract surgery.
--Age-Related Macular Degeneration (AMD).--Forty years ago there was
little or nothing one could do to prevent or treat advanced AMD
and blindness. Because of new treatments and procedures based
on NIH research, 750,000 Americans who would have gone blind
over the next 5 years instead will continue to have useful
vision.
--Breast Cancer.--The 5-year survival rate for women diagnosed with
breast cancer was 75 percent in the mid-1970s. Because of NIH-
supported research, the 5-year survival rate has risen to over
90 percent.
--Cervical Cancer.--Cervical cancer is a deadly cancer in women. Due
to groundbreaking NIH research, an FDA-approved vaccine
(Gardasil) now is available to prevent the development of
cervical cancer.
--Colon Cancer.--From 1974-1976, in an NIH-sponsored study, the 5-
year survival for patients with colon cancer was 50 percent. In
2009, based on NIH-supported clinical trials using new
diagnostics and treatments, a comparable patient group has a 5-
year survival rate of over 70 percent.
--Cochlear Implants.--Because of NIH-supported research, children who
are profoundly deaf but receive a cochlear implant within the
first 2 years of life now have the same skills, opportunities,
and potential as their normal-hearing classmates.
--Type 1 Diabetes.--Thirty to forty years ago, 30 percent of patients
died within 25 years of a diagnosis of type 1 diabetes. Today,
due to tight blood glucose control, heart disease and stroke in
patient with type 1 diabetes have been reduced by over 50
percent.
--Hepatitis B.--In the mid-1980s, hepatitis B infection caused
untreatable and fatal illness. Due to intensive vaccination
programs based on NIH research, the rate of acute hepatitis B
has fallen by more than 80 percent.
--HIV/AIDS.--In the 1980s, the diagnosis of HIV infection was a
virtual death sentence. Due to antiviral drugs developed by
NIH, today an HIV-positive 20-year-old can be expected to reach
the age of 70.
--Infant Health.--In 1976, the infant mortality rate was 15.2 infant
deaths per 1,000 live births. By 2006, that rate had fallen to
6.7 deaths per 1,000 live births. Much of this progress can be
attributed to NIH research in the areas of neonatal care unit
procedures and new drugs administered to women at risk for
premature birth.
--Childhood Leukemia.--Survival rates for children with the most
common childhood leukemia (acute lymphocytic leukemia) is now
90 percent.
Advances In Knowledge
NIH-funded research leads to thousands of new findings every year.
These incremental advances and technological developments are the
building blocks that ultimately yield significant improvements in
health. Highlighted below are just a few of the many recent advances
from NIH-supported research:
--Studies find possible new genetic risk factors for Alzheimer's
disease.--Scientists have confirmed one gene variant and have
identified several others that may be risk factors for late-
onset Alzheimer's disease, the most common form of the
disorder. In the largest genome-wide study, or GWAS, ever
conducted in Alzheimer's research, NIH-supported investigators
studied DNA samples from more than 56,000 study participants
and analyzed shared data sets to detect gene variations that
may have subtle effects on the risk for developing Alzheimer's.
Until recently, only one gene variant, Apolipoprotein E-e4
(APOE-e4), had been confirmed as a significant risk factor gene
for the common form of late-onset Alzheimer's disease, which
typically occurs after age 60. In 2009 and 2010, researchers
confirmed additional gene variants of CR1, CLU, and PICALM as
possible risk factors for late-onset Alzheimer's. This newest
GWAS confirms the fifth gene variant, BIN1, affects development
of late-onset Alzheimer's. The genes identified by this study
may implicate pathways involved in inflammation, movement of
proteins within cells, and lipid transport as being important
in the disease process.
--NIH scientist advance universal flu vaccine.--Significant progress
was made toward the development of a universal flu vaccine that
would confer longer term protection against multiple influenza
virus strains. NIH-supported researchers have identified the
regions of influenza viral proteins that remain unchanged among
seasonal and pandemic strains. These findings will inform the
development of influenza vaccines that might one day provide
universal protection against the broad range of influenza
strains. Such a universal influenza vaccine would provide
broader protection against multiple flu strains and make yearly
flu shots a thing of the past.
--Early detection of cancer is critical to provide effective
therapy.--NIH-supported investigators recently reported the
detection of a single metastatic cell from lung cancer in one
billion normal blood cells. These circulating tumor cells
(CTCs) may also be released into the bloodstream of patients
with invasive but localized cancers. The presence of CTCs may
be an early indicator of tumor invasion into the bloodstream
long before distant metastases are detected. Identifying CTCs
may be viewed as performing liquid biopsies, which can be
especially advantageous for prostate cancer. Researchers plan
to extend their work to develop a point-of-care microchip that
would allow non-invasive isolation of CTCs from patients with
many different types of cancer, to improve the management and
treatment of this devastating disease.
--Prenatal surgery reduces complications of spina bifida.--NIH-
supported scientists reported that a surgical procedure to
repair a common birth defect of the spine, if undertaken while
a baby is still in the uterus, greatly reduces the need to
divert, or shunt, fluid away from the brain. The fetal surgical
procedure also increases the chances that a child will be able
to walk without crutches or other devices. The birth defect,
myelomeningocele, is the most serious form of spina bifida, a
condition in which the spinal column fails to close around the
cord. The study, the Management of Myelomeningocele Study
(MOMS), was stopped after the enrollment of 183 women, because
of the benefits demonstrated in the children who underwent
prenatal surgery. In spite of an increased risk for preterm
birth, children who underwent surgery while in the uterus did
much better, on balance, than those who had surgery after
birth.
--Progesterone reduces rate of early preterm birth in at risk
women.--Preterm infants are at high risk of early death and
long term health and developmental problems including,
breathing difficulties, cerebral palsy, learning disabilities,
blindness and deafness. An NIH study found that progesterone
gel reduces the rate of preterm birth before the 33rd week of
pregnancy by 45 percent among women with a short cervix, which
is known to increase the risk of preterm birth. Women with a
short cervix can be identified through routine ultrasound
screening, and once identified could be offered treatment with
progesterone. In addition, infants born to women who received
progesterone had a lower rate of respiratory distress syndrome
than those in the placebo group.
--Daily dose of HIV drug reduces risk of HIV infection.--A daily dose
of an oral antiretroviral drug, currently approved to treat HIV
infection, was shown to reduce the risk of acquiring HIV
infection by 43.8 percent among men who have sex with men. The
findings, a major advance in HIV prevention research, came from
a large international clinical trial supported by NIH. The
study, titled ``Chemoprophylaxis for HIV Prevention in Men''
found even higher rates of effectiveness, up to 72.8 percent,
among those participants who adhered most closely to the daily
drug regimen. These new findings provide strong evidence that
pre-exposure prophylaxis with an antiretroviral drug, a
strategy widely referred to as PrEP, can reduce the risk of HIV
acquisition among men who have sex with men, a segment of the
population disproportionately affected by HIV/AIDS.
Prophylactic antiretroviral therapy has already been proven to
significantly reduce the transmission of HIV from a mother to a
child during childbirth through breastfeeding.
--Pocket-sized device makes medical ultrasound more accessible.--NIH-
supported research at General Electric supported the
development of a low-cost, portable, high-quality ultrasonic
imager. In the last year, this advance was extended even
further with GE's production of ``Vscan.'' This pocket-sized
device makes medical ultrasound even more accessible and has
enabled wireless imaging, patient monitoring, and prenatal care
applications.
--Lung cancer screening with CT scan reduces deaths.--The National
Lung Screening Trial found that screening with low-dose
computed tomography (CT) can decrease lung-cancer deaths among
current and former heavy smokers by 20 percent. Because of
earlier identification of cancerous tumors, screening was found
to reduce mortality from lung cancer, the most common cause of
cancer deaths.
--Nicotine vaccine shows promise in preventing tobacco addiction.--
Vaccines developed to combat drug addictions work by generating
drug-specific antibodies that bind the drug while in the
bloodstream and prevent its entry into the brain. A nicotine
vaccine recently found to improve smoking quit rates is now in
phase III trials to evaluate continued abstinence at 12 months.
--Nanotechnology demonstrates advances in the realm of materials
technologies.--Carbon nanotubes have been used to deliver
chemotherapeutic agents specifically to head and neck cancer
cells, causing rapid death of the cancer cells, but leaving
non-cancerous cells unharmed.
--Certain lipid molecules that show promise in controlling pain could
result in new treatments.--Researchers have demonstrated in
animal models that certain lipids called resolvins, which shut
down inflammation, are more potent than morphine in controlling
pain. Since these resolvins are normally found in the body,
they are likely to be safe and non-addictive when used
therapeutically. Additional research is under way to explore
these compounds further and translate into new analgesics for
pain management.
--Combined treatment improves vision in patients with diabetic
macular edema.--A comparative effectiveness study for diabetic
macular edema found that combined treatment with the drug
ranibizumab and laser therapy was substantially better at
improving vision in patients with diabetes than laser therapy
alone, and better than laser therapy with a different drug
(triamcinolone).
--Scientists develop a system for making functional hair cells from
stem cells, offering possible new treatment of deafness.--In
mammals, mechanically-sensitive ``hair cells'' in the inner
ear, which are essential for both hearing and balance cannot
regenerate when they die or are damaged. NIH supported
scientists have used mouse embryonic stem cells as well as
induced pluripotent stem cells and generated hair cells that
respond to mechanical stimulation, offering a new avenue for
the treatment of deafness.
--Experimental medication lifts depression symptoms in people with
bipolar disorder.--NIH intramural researchers discovered that
ketamine, an anesthetic medication, provides rapid and
effective treatment for depressive symptoms among patients with
bipolar disorders. While ketamine's side effects make it
impractical for long-term use, this class of drugs may be
invaluable for treating severe depressive symptoms in these
patients during the weeks it usually takes for typical
antidepressants to take full effect.
Proposed National Center for Advancing Translational Sciences
National Institutes of Health
Rationale
The development of new diagnostics and therapeutics is widely
recognized as a complex, costly, and risk-laden endeavor. Only a few of
the thousands of compounds that enter the drug development pipeline
will ultimately make it into the medicine chest.
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Mission
To advance the discipline of translational science and catalyze
development and testing of novel diagnostics and therapeutics across a
wide range of human diseases and conditions.
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In recent years, there has been a deluge of new discoveries of
potential drug targets, yet we still lack effective therapeutics for
many conditions, especially rare and neglected diseases. A major
problem is that the drug development pipeline is full of bottlenecks
that slow the speed of development and add expense to the process. To
address these challenges, the National Institutes of Health (NIH) has
proposed establishing the National Center for Advancing Translational
Sciences (NCATS).
NCATS will study various steps in the drug development pipeline,
identify bottlenecks amenable to re-engineering, and experiment with
innovative methods to streamline the process. Promising therapeutic
projects will be used to evaluate pipeline innovations.
NCATS will complement--not compete with-- translational research
being carried out elsewhere at NIH and in the private sector. In fact,
through its mission to use the power of science to advance the entire
discipline, NCATS will benefit all stakeholders, including academia,
biotechnology firms, pharmaceutical companies, the Food and Drug
Administration, and--most importantly--patients and their families.
Functions
NCATS will aim to improve the processes in the drug development
pipeline by:
--experimenting with innovative approaches in an open-access model;
--choosing therapeutic projects to evaluate these innovative
approaches; and
--promoting interactions to advance the field of regulatory science.
NCATS also will strive to catalyze the development of new drugs and
diagnostic tests by:
--encouraging collaborations across all sectors;
--providing resources to enable therapeutic development; and
--enhancing training in relevant disciplines.
----------------------------------------------------------------
NCATS will:
--facilitate--not duplicate--other translational research activities
supported by NIH;
--complement--not compete with--the private sector; and
--reinforce--not reduce--NIH's commitment to basic research.
----------------------------------------------------------------
Programs
NCATS will be formed by pulling together these existing NIH
programs: components of the Molecular Libraries initiative,
Therapeutics for Rare and Neglected Diseases, Office of Rare Diseases
Research, Rapid Access to Interventional Development, Clinical and
Translational Science Awards, and FDANIH Regulatory Science. In
addition, the Cures Acceleration Network will be part of NCATS if funds
are appropriated for fiscal year 2012. Relocated programs will have
their respective budgets transferred to the new center.
Background
On May 19, 2010, the NIH Director asked the NIH Scientific
Management Review Board (SMRB) to:
--identify the attributes, activities, and functional capabilities of
a translational medicine program for advancing therapeutics
development; and
--broadly assess the NIH landscape for existing programs, networks,
and centers for inclusion; and recommend their optimal
organization.
On Dec. 7, 2010, the SMRB recommended the creation of a new
translational medicine and therapeutics center. It also urged NIH to
undertake a detailed analysis, through a transparent process, to
evaluate the new center's impact on existing NIH programs.
Informed by the SMRB's recommendations, NIH initiated a planning
process to establish NCATS. The NIH Director established three panels
to guide and inform the process: the Institute and Center Directors'
(ICD) NCATS working group, the Advisory Committee to the Director (ACD)
NCATS working group, and the NIH Clinical and Translational Science
Awards (CTSA) Integration working group.
On Jan. 4, 2011, Dr. Collins charged the ICD working group with
making recommendations on the mission, functions, and organizational
design of NCATS. This panel presented its recommendations to Dr.
Collins on Feb. 17, 2011. The ACD working group, which has been asked
to provide high-level advice on how NCATS can best engage the private
sector in translational science, met for the first time on Feb. 4,
2011. This distinguished panel of outside experts will report its
findings to the ACD later this year.
The final working group, composed of leaders from across NIH, was
formed in mid-March to ensure a smooth transition of the CTSA program
into NCATS.
Next Steps
At every point along the way, NIH has sought input on NCATS from a
broad and diverse array of stakeholders. In addition, NIH will continue
to inform all stakeholders on new developments and seek their comments
through our interactive web site Feedback NIH.
Pending approval from the Health and Human Services Secretary, the
Office of Management and Budget, and the Congress, NCATS will be
included in the fiscal year 2012 budget and be formally established on
Oct. 1, 2011.
So in this brief statement today, I'd like to tell you
about four innovative areas, and I'm going to show some
pictures up on the screen in which NIH is investing in order to
carry out its mission of turning discovery into health.
First, dramatic advances in technologies, including
imaging, nanotechnology, computational biology, and, yes,
genomics, have recently made it possible for scientists to
understand the details of health and disease in breathtaking
new ways.
Consider this curve, the cost to sequence a human genome.
Look at the profound reduction over the past decade. In 2001,
it cost about $100 million to sequence a single human genome.
That cost now stands at about $10,000, and we anticipate it
will be less than $1,000 within the next few years.
That advance will give many Americans access to far more
personalized strategies for detecting, treating and preventing
disease than are now available.
Those new technologies not only reduce the cost of doing
science, but open up whole new frontiers in medicine. I'll tell
you about one of those later in a story about a 6-year-old boy
named Nic that I think you'll find quite compelling.
But, first, let's turn to the effects that this technology
has had on our understanding of cancer. Cancer is a disease of
the genome, comes about because of mutations in DNA.
Through a bold initiative, called the Cancer Genome Atlas,
or TCGA, my colleague, Harold Varmus, and others are analyzing
the DNA of tumors of hundreds of patients to identify
comprehensively the genetic mutations associated with the
specific cancers.
Brain and ovarian cancers were the first ones selected for
study through TCGA and the results have been stunning. Knowing
the molecular drivers of cancer gives us a chance to make much
more accurate diagnoses, prognoses, and predictions of response
to therapy. And in the longer run, this approach will lead to
development of a new generation of targeted therapies, those
magic bullets so dreamed of to treat this disease.
The plan for the next few years is ambitious. TCGA will
sequence, characterize, and understand the genomes of 20
different types of tumors.
New treatments are wonderful. Effective prevention can be
even better. NIH is dedicated to use the latest science to
improve America's health today by identifying effective new
strategies for disease prevention. The grave threat of diabetes
is a compelling example of how we are doing this.
This map shows the prevalence of diabetes in the United
States in 1995. As you can see from the color code, in most
States, less than 5 percent of adults were affected, but watch
what happened over just 15 years. Prevalence of diabetes has
gone up rapidly in every State, and it now stands at 9 percent
or more in many parts of the country.
The total costs of the disease, including medical care,
disability and premature death, were an estimated $174 billion
in the United States in 2007. If current trends continue, one
in three U.S. adults will have diabetes by 2020, just 9 years
from now, and the annual cost of care alone will have risen to
a breathtaking $500 billion.
But my colleague, Grif Rodgers, and I can offer some hope.
NIH spearheaded a landmark clinical trial on how to prevent
type 2 diabetes. The Diabetes Prevention Program, or DPP,
involved adults with pre-diabetes. That refers to a modest
elevation of glucose in the blood foreshadowing much worse to
come if nothing is done, but not yet frank diabetes.
The study participants were assigned personal coaches who
encouraged them to exercise about 30 minutes a day and to make
modest dietary changes resulting in an average weight loss of
just 7 percent. This simple approach lowered the chance of
full-blown diabetes by a whopping 58 percent, and that has been
sustained for more than 10 years.
Building on these results, NIH has joined with the Centers
for Disease Control and Prevention (CDC), the YMCA, Walgreens,
United Health Care and other partners to bring this program to
communities in 10 States. And we are now working with
colleagues at CMS to explore how a similar program could be
used to great advantage in Medicare and Medicaid.
Now, I'd like to turn your attention to another important
contribution of NIH research already mentioned by the chairman,
enhancing the economy and U.S. competitiveness worldwide.
NIH will be a key engine driving the U.S. economy in the
21st century. Many call this the century of biology. As
mentioned, just yesterday, a new economic impact study
published by United for Medical Research suggests that in
fiscal year 2010 NIH research funding supported an estimated
487,900 American jobs at 3,000 institutions and small
businesses across all 50 States of this Nation.
More than that, nearly 1 million U.S. citizens are employed
by the industries and companies that make up this sector of the
economy, earning $84 billion in wages and salary and exporting
$90 billion of goods and services annually. But despite this
impressive track record, our Nation today is at serious risk of
losing its position as the world's research leader.
As you can see in this slide, which shows the percent
growth of R&D expenditures on an annual basis, China and India
and other countries have been steadily increasing their R&D
expenditures by 10 percent or more per year, highlighting China
and India there. Whereas, the United States has been at a
substantially lower level. China's growth rate is now four
times greater than ours.
Let me give you a personal example of what this means. Last
fall, when I visited the BGI Genome Center in Shenzhen, China,
I saw an amazing facility built in just 3 years from an
abandoned shoe factory that is capable of sequencing more than
10,000 human genomes a year.
The capacity of that one Chinese institution now surpasses
the combined capacity of all genome sequencing centers in the
United States. This critical area of scientific innovation,
stimulated by the U.S.-led Human Genome Project, is now being
developed more aggressively in China than it is here, a
sobering story indeed, and one that I hope would inspire our
Nation to redouble its efforts on the research front.
A final area I wish to highlight in which our Nation faces
exceptional challenges, as well as exceptional opportunities,
is this field of translational science which Senator Shelby has
specifically highlighted in his opening statement. As a result
of years of steadfast support of NIH research by Congress and
the American people, we find ourselves in a paradoxical
situation.
This graph shows we've seen a deluge of discoveries about
the molecular basis of disease, both rare and common, which
provide us with the power to identify more therapeutic targets
than ever before; more than 4,000 diseases now having their
molecular basis discovered, much of that in the last decade.
But there's a serious problem. The process of taking those
basic discoveries to the point of clinical advances, as here
demonstrated by a diagram showing you what happens in the
development of new therapeutics, is far too slow--14 years on
the average--and the failure rate is far too high--more than 98
percent. We clearly need a new approach to therapeutic
development and a new partnership with the private sector.
So to meet this need, NIH is proposing the establishment of
a new national center for advancing translational sciences or
NCATS. NCATS will allow us to study the various steps in the
development of diagnostics, devices and therapeutics, identify
bottlenecks that might be reengineered and experiment with
innovative methods to streamline this process.
Through this new center, we can work in an open-access
model that will allow stakeholders, including industry and
academia, to access and apply the innovations that are
developed. NCATS will also advance the field of regulatory
science by promoting interactions among the NIH, FDA, patient
advocates, and pharmaceutical and biotechnology companies.
Importantly, NCATS will complement, not compete with, the
private sector. This is not Bethesda Pharm. It will facilitate
translational research being carried out elsewhere at the NIH,
extensive translational work already going on by many of the 27
Institutes, including those represented at this table. And it
will reinforce, not reduce, NIH's commitment to basic science,
a foundational part of our mission.
Most importantly, though, by advancing discipline of
translational sciences, NCATS will benefit patients and their
families.
So, Mr. Chairman, members of the subcommittee, I've spoken
today about the great promise of new technologies, how we're
applying science to prevention, NIH's role in maintaining U.S.
economy--world leadership, and the unique opportunity to pursue
a new paradigm in translation.
Let me close by sharing the story of one little boy to show
you what NIH research advances now allow us to do. So meet Nic
Volker, a brave boy from Monona, Wisconsin.
Starting about the age of two, Nic developed a mysterious
life-threatening disease that ravaged his body, making it
impossible for him to eat normally and causing unimaginable
pain and suffering.
At a loss to explain Nic's terrible affliction, researchers
at the Medical College of Wisconsin decided to sequence Nic's
DNA instruction book hoping to find an answer. After exacting
work over several months, the researchers identified a
misspelling of just one single letter in a little-studied gene
called XIAP. Now, glitches in this gene had been associated
with rare blood disorders, but not with intestinal symptoms.
Based on this new insight, the research team had an idea that,
as with the rare blood disorders, Nic's disease might be
curable with a bone-marrow transplant.
Transplantation of cord blood cells from--stem cells from a
matched donor occurred in July of last year. Although Nic is
still receiving some immunosuppressant drugs to prevent
rejection of the donated cells, his symptoms have largely
disappeared, and, today, as you can see here, he can eat
normally and vigorously.
What's more, he's now attending kindergarten, enjoying
outings with his family and friends, signing up for a T-Ball
team, and, this past Sunday, presenting his mother with a
flower for Mother's Day. Nic has given us all a glimpse of the
future.
PREPARED STATEMENTS
Thank you, Mr. Chairman. This concludes my formal remarks.
[The statements follow:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
INTRODUCTION
Good morning, Mr. Chairman and distinguished Members of the
Subcommittee. I am Francis S. Collins, M.D., Ph.D. and I am Director of
the National Institutes of Health (NIH).
It is a great honor to appear before you today to present the
administration's program level request of $31.987 billion for NIH in
fiscal year 2012, and to discuss the contributions that NIH-funded
biomedical research has made in improving human health. NIH is the
largest supporter of biomedical research in the world, providing funds
for more than 40,000 competitive research grants and more than 325,000
research personnel at more than 3,000 research institutions and small
businesses across our Nation's 50 States. I also want to offer a vision
of how NIH will catalyze innovation in basic and translational
sciences, and will ensure future U.S. economic strength and global
competitiveness.
On behalf of NIH and the biomedical research enterprise, I want to
thank you as Members of the Senate for sparing NIH from deeper cuts in
the final fiscal year 2011 continuing resolution (CR). We know that,
even as Congress and the administration wrestled with cuts of more than
3 percent to the Labor-HHS portion of the CR, NIH received a 1 percent,
or $321.7 million, cut from the fiscal year 2010 level, while other
programs and functions were cut more deeply.
NIH's mission is to seek fundamental knowledge about the nature and
behavior of living systems and to apply that knowledge to enhance human
health, lengthen life, and reduce the burdens of illness and
disability. I can report to you that NIH continues to believe
passionately in that mission and works tirelessly to achieve it.
Due in large measure to NIH research, our Nation has gained about 1
year of longevity every 6 years since 1990. A child born today can look
forward to an average lifespan of nearly 78 years--nearly three decades
longer than a baby born in 1900. And not only are people living longer,
but their quality of life is improving: in the last 25 years, the
proportion of older people with chronic disabilities has dropped by
almost one-third.
NIH research has enabled new techniques to prevent heart attacks,
newer and more effective drugs for lowering cholesterol and controlling
blood pressure, and innovative strategies for dissolving blood clots
and preventing strokes. As a result, the U.S. death rate for coronary
disease is 60 percent lower--and for stroke, more than 70 percent
lower--than three generations ago. Better treatment of acute heart
disease, better medications, and improved health-related behaviors--all
underpinned by NIH research--account for as much as two-thirds of these
reductions.
In recent years, largely as a result of NIH research, we have
succeeded in driving down mortality rates for cancer in the United
States. This progress comes despite the fact that cancer is largely a
disease of aging and our population is growing older. Over the 15-year
period from 1992 to 2007, cancer death rates dropped 13.5 percent for
women and 21.2 percent for men. According to an American Cancer Society
report released in July 2010, the continued drop in overall mortality
rates over the last 20 years has saved more than three-quarters of a
million lives.\1\ And in cancers that strike children we have made
near-miraculous progress--the 5-year survival rate for children with
the most common childhood cancer, acute lymphocytic leukemia, is now 90
percent.\2\
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\1\ http://pressroom.cancer.org/index.php?s=43&item=252.
\2\ http://seer.cancer.gov/csr/1975_2008/
browse_csr.php?section=28&page=sect_28_table.08.html.
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I would also like to offer a shining example of the Senate's strong
and consistent support of biomedical research at NIH by note that we
are celebrating a significant anniversary. This year marks the 10th
anniversary of the establishment of the Dale and Betty Bumpers Vaccine
Research Center (VRC) at NIH. Groundbreaking research performed at the
VRC is making great progress toward developing a universal flu vaccine
that confers longer-term protection against seasonal and pandemic
influenza strains.
Today, scientists have to make an educated guess about the make-up
of the coming winter's influenza viruses. These educated guesses become
the basis for the manufacture of each year's flu shot and mean that
everyone has to be re-immunized in anticipation of next year's strain
of flu. Recently, NIH scientists have identified pieces of influenza
viral proteins that consistently appear among seasonal and pandemic flu
strains. These findings raise the possibility that we might soon
develop an influenza vaccine that provides near-universal protection
against a broad range of current and future strains of influenza,\3\ as
well as make yearly flu shots a thing of the past. Most of this
exciting work was performed at the VRC. Scientists at that same center
are making important strides toward the development of the long-hoped-
for vaccine against the human immunodeficiency virus (HIV), the cause
of acquired immune deficiency syndrome (AIDS). While after so many
frustrations, no one would want to predict success just yet, recent
discoveries of VRC scientists about how to encourage production of
neutralizing antibodies against HIV have provided renewed hope that
this pressing problem may ultimately be solved.
---------------------------------------------------------------------------
\3\ http://www.niaid.nih.gov/news/newsreleases/2010/Pages/
UniversalFluVax.aspx.
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NIH AND ECONOMIC GROWTH
Mr. Chairman and Members of the Subcommittee, I recognize that,
given our Nation's fiscal situation, and the extraordinarily tough
decisions that you will have to make about our Nation's finances, you
need to be assured that NIH remains a worthwhile national investment.
Even as you make these decisions and even as our country recovers from
financial recession, I want to offer evidence that NIH and its research
provide two strong and ongoing benefits to our economy.
First, NIH research spending has an impact on job creation and
economic growth. A new economic impact study by United for Medical
Research suggests that in fiscal year 2010, NIH research funding
supported an estimated 487,900 American jobs, including researchers and
spin-off employment.
Second, NIH research funding has a longer term impact in its role
as the foundation for the medical innovation sector. Nearly 1 million
U.S. citizens are employed by the industries and companies that make up
this sector of the economy, earning $84 billion in wages and salary in
2008, and exporting $90 billion of goods and services in 2010. NIH
support for biomedical research institutions catalyzes business
activity in other ways as well. Such institutions constitute reservoirs
of skilled, knowledgeable individuals and, thereby, attract companies
that wish to locate their operations within such ``knowledge hubs.''
For example, in the 1990s, Federal funding through research grants
and the Small Business Innovation Research (SBIR) and the Small
Business Technology Transfer (STTR) programs transformed the academic
research environment and helped to launch new industrial sectors in
Silicon Valley and elsewhere that are flourishing today. Federal
funding has been crucial in stimulating the formation of start-up
companies and collaborations among academia and the private sector in
the development of innovative technology. A prime example is the
company Affymetrix.
In the late 1980s, a team of scientists led by Stephen P.A. Fodor,
Ph.D., developed methods for fabricating DNA microarrays, called
GeneChips, using semiconductor manufacturing techniques, melded with
advances in combinatorial chemistry to capture vast amount of
biological data on a small glass chip. In 1992, the first of several
NIH grants was awarded to Affymetrix; with this and an SBIR grant from
the Department of Energy, Dr. Fodor was able to demonstrate proof of
principle of using large arrays of DNA probes in genetic analysis.
Affymetrix and similar companies are building the machine tools of the
genomic revolution. In 2009, Affymetrix had annual revenue of $327
million and employed more than 1,100 people.
Furthermore, NIH research leads to better health outcomes that not
only ease human suffering, but also produce an economic return. A 2006
study by Kevin Murphy and Robert Topel of the University of Chicago
shows that a permanent reduction of 1 percent in cancer deaths has a
present value to current and future generations of Americans of nearly
$500 billion. The article states that if we were able to defeat cancer
completely, such cures would be worth approximately $50 trillion--more
than three times today's Gross Domestic Product.\4\
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\4\ Murphy, K.M., & Topel, R.H. (2006), The value of health and
longevity. Journal of Political Economy, 114(5), 871-904.
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We face a similar economic threat from diabetes. If current trends
continue, by 2050 as many as one in three U.S. adults will be diagnosed
with diabetes.\5\ Total costs of diabetes, including medical care,
disability, and premature death, reached an estimated $174 billion in
the United States in 2007.\6\ According to analysis from the
UnitedHealth Center for Health Reform & Modernization, more than 50
percent of Americans could have diabetes or pre-diabetes by 2020.\7\
Furthermore, the center's analysis predicts diabetes and pre-diabetes
will account for an estimated 10 percent of total healthcare spending
by the end of this decade, at an annual cost of almost $500 billion.
---------------------------------------------------------------------------
\5\ http://www.cdc.gov/media/pressrel/2010/r101022.html.
\6\ CDC National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/
pubs/pdf/ndfs_2011.pdf.
\7\ http://www.unitedhealthgroup.com/hrm/UNH_WorkingPaper5.pdf.
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But I can offer some hope. NIH spearheaded a landmark clinical
trial on type 2 diabetes prevention that showed that people at high-
risk for diabetes can dramatically reduce their risk of developing type
2 diabetes through modest exercise and dietary changes that achieve
modest weight loss. Called the Diabetes Prevention Program (DPP), the
clinical trial included 3,234 adults at high risk for developing type 2
diabetes, including those with a family history of diabetes, as well as
other risk factors. One-third of these individuals participated in a
lifestyle program that included exercise training and dietary change
implemented under the guidance of lifestyle coaches. The DPP research
team found that this approach lowered risk of diabetes by 58
percent.\8\ The DPP trial also demonstrated that the cost of the
lifestyle intervention was $3,540 per participant over 3 years, which
was significantly offset by the lowering of other healthcare costs as
lifestyle participants became healthier.\9\ The cost effectiveness of
the DPP has continued to be followed and 10-year results will be
published in the near future. Building on these critically important
results, NIH partnered with the Centers for Disease Control and
Prevention (CDC) and more than 200 private partners, including the
YMCA, Walgreens, and UnitedHealthcare, to bring these evidence-based
lifestyle interventions to communities in Ohio, Indiana, Minnesota,
Arizona, Oklahoma, New Mexico, New York, New Jersey, Connecticut, and
Georgia. In addition, the DPP Lifestyle Intervention is being used by
the Indian Health Service in a large demonstration project on many
American Indian reservations.
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\8\ Knowler WC, et al. Reduction in the incidence of type 2
diabetes with lifestyle intervention or metiformin. N. Engl J Med
346:393-403, 2002.
\9\ Diabetes Care. 2003 Jan;26(1):36-47.
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INVESTING IN BASIC SCIENCE
At NIH, we have always put our greatest percentage of our resources
into basic research. This is because the fundamental observations made
today become the building blocks of tomorrow's knowledge, therapies,
and cures. NIH's history has repeatedly demonstrated that significant
scientific advances occur when new basic research findings, often
completely unexpected, open up new experimental possibilities and
therapeutic pathways. Historically, NIH has put more than 50 percent of
its budget into basic research and the research discoveries that led to
the 132 Nobel prizes won by our intramural and university scientists
are evidence of the wisdom of this investment.
Basic research is precisely the type of work that the private
sector, which must see a rapid return on invested capital, cannot
afford to support. NIH provides the fundamental observations that
pharmaceutical and biotechnology companies can turn into diagnostics,
therapies, and devices that eventually reach patients. As the
Congressional Budget Office put it, ``Federal funding of basic research
directly stimulates the drug industry's spending . . . by making
scientific discoveries that expand the industry's opportunities for
research and development.'' \10\
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\10\ Congressional Budget Office, Research and Development in the
Pharmaceutical Industry, October, 2006, p. 3.
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Because we simply cannot predict the next scientific revelation or
anticipate the next opportunity, our basic research portfolio must be
diverse. We set scientific priorities by considering a wide array of
biomedical questions that we might try to answer. It is rather like
facing a series of doors, some of which lead to vast treasures and
others to much more modest payouts, without any sure way of knowing
what lies behind any particular door. To improve our odds of striking
scientific gold, we need a broad basic research portfolio that enables
our Nation to open as many doors as our resources allow.
Not all disease or scientific problems are equally ripe for new
advances, nor do such advances come at the same rate across the
portfolio, no matter how pressing today's public health challenges are.
We can only be sure that without a strong commitment to basic research
today, the new knowledge of tomorrow will remain hidden behind those
unopened doors and future therapies and cures will remain out of our
reach.
Let me offer a few of the exciting insights that NIH's support of
basic research have provided. On April 3, 2011, the online issue of
Nature Genetics presented the findings by a team of NIH-supported
scientists who had identified five new genetic variants that are risk
factors for late-onset Alzheimer's disease, which is the most common
form of the disorder. These findings doubled from 5 to 10 the number of
gene variants that we know are associated with Alzheimer's disease.\11\
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\11\ Naj, A.C. et al. Common Variants of MS4A4/MSA6E, CD2AP, CD33
and EPHA 1 are associated with late-onset Alzheimer's Disease. Nature
Genetics, EPUB April 3, 2011, and Holligworth, P., et al. Common
variants at ABCA7, MS4A/MS4A4E, EPHA 1, CD33 and CD2Ap are associated
with Alzheimer's disease. Nature Genetics. Epub April 3, 2011.S
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What is even more compelling is that these newly identified genes
strongly implicate inflammation and high cholesterol as risk factors in
the development of Alzheimer's disease. Although each of these newly
identified genes increases a given individual's risk of developing the
disease by no more than 10 to 15 percent, the unanticipated insight
that cholesterol and inflammation are contributing factors opens up new
research avenues to understand the disease process, and increases the
likelihood that we can glimpse potential preventions or therapies.
NIH's commitment to basic research has also provided us with one of
the most promising therapeutic strategies we have seen to date for the
deadliest form of skin cancer, melanoma. Since 2002, we have known that
many melanoma tumors exhibit a mutation in the BRAF gene and that this
mutation might provide a target for therapeutic intervention. A team
that included NIH-supported investigators used high-throughput
screening in combination with structural biology, to identify compounds
that inhibit the activity of the mutant form of the BRAF gene found in
most melanomas, but have little effect on the BRAF gene found in normal
cells. This basic cancer research supported by NIH contributed to the
development of the drug PLX4032, a drug designed to inhibit the
activity of a mutant form of the protein called BRAF. This is a
powerful example of how support for basic research can be translated
into therapeutic potential. In August 2010, Plexxikon, a small drug
development company, announced that PLX4032, had elicited a positive
response in more than 80 percent of melanoma patients in early phase
clinical trials. PLX4032 caused the tumors in 24 of the 30 trial
participants to shrink by at least 30 percent, while the tumors of two
patients disappeared. Another clinical trial involving hundreds of
participants across many institutions demonstrated that metastatic
melanoma patients treated with PLX4032 lived 6 to 8 months longer than
those who had been given the chemotherapy drug dacarbazine, which is
the current standard of care.
Whether it is with the hope of finding new ways to treat cancer,
prevent Alzheimer's disease, or help people suffering from countless
other rare and common conditions, we at NIH invest in basic research
because of our conviction that it will benefit our Nation in the long
term.
ADVANCING TRANSLATIONAL SCIENCE
NIH also has a longstanding commitment to translating fundamental
knowledge into cures and therapies for human disease. It should not be
surprising that NIH-supported science underpins many of the most
transformative drugs and therapies that have benefited millions of
Americans and people around the world, including statins to lower
cholesterol and drugs to treat depression. In 2010, we conducted a
trans-NIH inventory of therapeutics development activities and found
more than 550 such projects, of which approximately 65 percent were
pre-clinical and 35 percent were clinical research.
An analysis published in the February 10, 2011 issue of the New
England Journal of Medicine (NEJM) underscores the depth and breadth of
NIH's support for translational science that benefits patients.\12\ The
article's authors describe a new emphasis on ``public sector research''
that is almost exclusively supported or conducted by NIH, noting ``the
boundaries between the roles of the public and private sectors have
shifted substantially since the dawn of the biotechnology era, and the
public sector now has a much more direct role in the applied-research
phase of drug discovery.''
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\12\ Stevens, Ashley J. et al. The role of public-sector research
in the discovery of drugs and vaccines. New England Journal of
Medicine, 364,:6, February 10, 2011.
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Drugs that represent a major advance in treatment or offer
treatments for diseases for which no adequate therapy currently exists
are granted ``priority review'' by FDA. According to the NEJM article,
between 1990 and 2007, 20 percent of the FDA approvals of novel
compounds granted priority review were given to drugs discovered by
NIH. Examples include AZT for HIV/AIDS and the targeted leukemia
therapy Gleevec. Over the past 40 years, 153 new FDA-approved drugs,
vaccines, or new indications for existing drugs were discovered through
work carried out by NIH-supported biomedical research institutions.
Despite NIH's historic and growing commitment to translational
sciences, far more remains to be done. Millions of people still suffer
from diseases, such as cancers and diabetes, for which we have no
adequate treatments. There are nearly 7,000 rare diseases, yet we have
therapies for fewer than 200 of them. This staggering public health
need and attendant human suffering continues even as the pharmaceutical
industry, beset by economic stress, is investing less in research and
development, and the pool of venture capital needed by the biotech
industry is drying up.
At the same time, a deluge of discoveries about the molecular basis
of disease has been made possible by the sequencing of the human and
many other genomes, as well as breathtaking advances in research
technologies, such as high-throughput screening and bioinformatics.
These discoveries reveal hundreds of tantalizing potential therapeutic
targets. As the result of years of steadfast support of NIH research by
Congress and the American people, we find ourselves in a paradoxical
situation: we can uncover the molecular basis of common and rare
diseases better than ever before and we can more readily identify
therapeutic opportunities than at any point in history, but the
pipeline through which these new therapeutic agents must pass is
crimped and, in some places completely blocked.
Consequently, a new approach to therapeutic development, and a new
partnership with the private sector, is needed. That is why we have
proposed the establishment of NIH's new National Center for Advancing
Translational Sciences beginning in fiscal year 2012.
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
As previously noted, NIH has a long and rich history of significant
contributions to therapeutic development. In particular, the National
Cancer Institute (NCI) and the National Institute for Allergy and
Infectious Diseases (NIAID) have made major contributions over many
years to the discovery of new treatments. However, now is the time to
consider the therapeutic development process itself as a scientific
problem that is ripe for innovation. The mission of the National Center
for Advancing Translational Sciences (NCATS) will be to advance the
discipline of translational science and catalyze the development and
testing of novel diagnostics and therapeutics across a wide range of
human diseases and conditions. NIH has no intention of entering the
drug development arena that is rightly the province of private sector
companies. Indeed, given that it costs in the range of $ 1.3 billion to
$1.8 billion to bring one drug to market, it is clear that it would be
impossible for NIH to compete with private industry.\13\ What NCATS
intends to do is advance the science of therapeutic development and
determine if there are ways we can re-engineer the drug development
pipeline; creating new approaches and methods that will benefit
everyone interested in speeding the delivery of new medicines.
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\13\ DiMasi, JA, Hansen RW, Grabowski HG. Extraordinary claims
require extraordinary evidence. Journal of Health Economics
2005;24(5):1034-1044. Tonkens, R. An Overview of the Drug Development
Process. The Physician Executive May-June 2005.
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Today, the development of new diagnostics and therapeutics is a
complex, costly, and risky endeavor. Only a few of the thousands of
compounds that enter the drug development pipeline will ultimately make
it into the medicine chest or to the patient's bedside. NCATS will
study the various steps in the drug development pipeline, consult with
the private sector to identify bottlenecks amenable to re-engineering,
and experiment with innovative methods to streamline the process.
To offer one example of the kind of pipeline challenge we might
address, new ideas about assessing the toxic potential of drug
candidates using sophisticated cell-based methods, instead of animal
toxicology testing, hold out the promise of revolutionizing this step
in validating a new therapeutic agent--and such research can be
catalyzed by NIH in ways that might otherwise not be possible.
NCATS will attack the bottlenecks in the drug development pipeline
by experimenting with innovative approaches in an open-access model so
that all stakeholders, ranging from industry to patients, will be able
to access and apply its innovations. NCATS's open access operating
framework will also advance the field of regulatory science by
promoting interactions among the Food and Drug Administration (FDA),
NIH, patient advocates, and pharmaceutical and biotechnology companies.
NCATS will encourage collaboration across all sectors, provide
resources to enable therapeutic development, and support and enhance
training in the relevant translational science disciplines.
NCATS will complement--not compete with--translational research
being carried out elsewhere at NIH and in the private sector. In fact,
in pursuing its mission of using the power of science to advance the
entire discipline of translational science, NCATS will benefit all
stakeholders, including academia, biotechnology firms, pharmaceutical
companies, the FDA, and--most importantly--patients and their families.
NCATS will pull together existing NIH programs such as the
Therapeutics for Rare and Neglected Diseases program, the Office of
Rare Diseases Research, the Rapid Access to Interventional Development
program, the Clinical and Translational Science Awards, the FDA-NIH
Regulatory Science grants program, and components of the Molecular
Libraries initiative. These relocated programs will have their
respective budgets transferred to or implemented by the new center. In
addition, we are hopeful that funding for the new Cures Acceleration
Network will be provided within the NCATS appropriation in fiscal year
2012. The intent of this innovative program and its exceptional DARPA-
like flexibilities for supporting projects are a natural fit with
NCATS.
Aside from the new funding requested in fiscal year 2012 for the
Cures Acceleration Network, resources for NCATS will come from the
combination of already existing and appropriated programs and so be
budget neutral.
NCATS will bring the scientific method to bear on today's drug
development process and aim to improve and speed the therapeutic
development process of tomorrow.
CONCLUSION
This statement has provided you with a brief overview of NIH's past
successes and future commitment to basic and translational sciences,
along with a quick look at the important role that NIH plays in our
domestic economy and U.S. global economic and scientific leadership.
But I would like to close my testimony today with an example that
demonstrates the benefits to be reaped from our continuing pursuit of
``personalized medicine.'' It is the story of one individual, 6-year-
old Nic Volker of Monona, Wisconsin. Starting about the age of 2, Nic
developed a mysterious, life-threatening disease that ravaged his
intestines, making it impossible for him to eat normally and causing
unimaginable pain and suffering. At a loss to explain this terrible,
inflammatory condition, researchers and clinicians at the Medical
College of Wisconsin decided to sequence Nic's entire exome, that is,
all the parts of the genome that code for the proteins that become
life's building blocks. After exhaustive work over a period of months,
the researchers identified a mutation in Nic's XIAP gene. Such
mutations had been associated with rare blood disorders, but not with
bowel symptoms. Based on this new insight, the research team had an
idea that, as with the rare blood disorders, Nic's disease might be
curable with a bone marrow transplant.
NIH investment over the years in the sequencing of genomes--and the
technologies associated with such sequencing--has put us at the
threshold of ``personalized medicine.'' Young Nic Volker is one of a
handful of individuals who has crossed that threshold, and it was made
possible because of years of research and development supported and
performed by NIH.
Transplantation of cord-blood stem cells from a matched donor
occurred in July of last year and, although Nic is still on
immunosuppressant drugs to prevent rejection of the donated cells, his
symptoms have largely disappeared and today he can eat normally. Hot
dogs are his favorite!
The local newspaper, the Milwaukee Journal Sentinel, was so struck
by the saga of Nic and his family that they devoted a series of
articles to the little boy's struggles and therapy, coverage that
included posting photos, videos, blogs, and many other resources to the
web. The five Journal Sentinel journalists did such a good job that
they were awarded the Pulitzer Prize for Explanatory Reporting on April
18. Now, that is truly putting a face on the promise of today's
biomedical research, tomorrow's personalized medicine, and NIH's role
in making this promise possible.
Thank you Mr. Chairman. This concludes my formal remarks.
______
Prepared Statement of Harold Varmus, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National Cancer
Institute (NCI) of the National Institutes of Health (NIH). The fiscal
year 2012 request includes $5,196,136,000 for NCI, which reflects an
increase of $141,899,000 over the comparable fiscal year 2011 level of
$5,054,237,000.
We now know that cancer is a collection of diseases reflecting
changes in a cell's genetic makeup and thus its programmed behavior.
Sometimes the genetic changes occur spontaneously or are inherited;
sometimes they are caused by environmental triggers, such as chemicals
in tobacco smoke, ultraviolet radiation from sunlight, or viruses.
While cancers constitute an incredibly diverse and bewilderingly
complex set of diseases, we have at hand the methods to identify
essentially all of the genetic changes in a cell and to use that
knowledge to rework the landscape of cancer research and cancer care,
from basic science to prevention, diagnosis, and treatment. The funds
in the President's budget for NCI represent a bold investment strategy
critical for realizing that goal.
The emerging scientific landscape offers the promise of significant
advances for current and future cancer patients, and for preventing
cancer so that many never become cancer patients. And it offers
scientists at the National Cancer Institute--and in the thousands of
laboratories across the United States that receive NCI support--the
opportunity to increase the pace of lifesaving discoveries
dramatically.
In the past year alone, we have seen powerful examples of how
research dollars have translated into concrete advances against cancer
through basic science, prevention and early detection, and treatment.
Basic science.--In collaboration with NHGRI, the NCI is leading The
Cancer Genome Atlas (TCGA), the largest and most comprehensive analysis
of the molecular basis of cancer ever undertaken. TCGA aims to identify
and catalog all of the relevant genetic alterations in many types of
cancer. For instance, building on their recent reclassification of
glioblastoma multiforme (GBM), an aggressive form of brain cancer, this
year TCGA investigators discovered that about 10 percent of patients
with one of the four subtypes of GBM are younger at diagnosis and live
longer than patients with other subtypes of the disease, but their
tumors are unresponsive to current intensive therapies. The molecular
profile of this subtype offers new targets for developing drugs to
treat this form of the disease more effectively. TCGA scientists are
also preparing to publish similarly important findings about the major
form of ovarian cancer in mid-2011 and are in the midst of analyzing
nearly 20 other types of cancer.
Prevention and early detection.--NCI's intensive efforts to study
and reduce the use of tobacco products have contributed to a sustained
annual reduction in age-adjusted cancer mortality rates over the past
decade and more. But current and former heavy smokers remain at high
risk of developing lethal lung cancers, which are the leading cause of
cancer mortality. In late 2010, NCI announced initial results from the
National Lung Screening Trial, a large, multi-year randomized trial
that enrolled more than 53,000 subjects. Because early detection
provides the potential to intervene at the earliest, most treatable
stages of disease, thus reducing potentially difficult to treat
outcomes seen in more advanced disease, current and former smokers who
were screened with low-dose helical computed tomography were 20 percent
less likely to die of lung cancer than were peers who received standard
chest x-rays. These results provide the first clear demonstration that
a screening procedure can be effective in reducing mortality from lung
cancer--a finding that could save many lives among those at greatest
risk. Over the course of the $240 million study, NLST investigators
collected samples of early and advanced lung cancers from enrolled
subjects, and these specimens will be invaluable for determining
genetic alterations that may be used to predict which tumors are likely
to progress to an advanced stage.
Cancer treatment.--The potential therapeutic impact of basic
discoveries made by TCGA and other efforts in cancer genomics has been
dramatically illustrated this year by the development of effective
drugs against the most deadly form of skin cancer, melanoma. Almost a
decade ago, studies of cancer genomes first uncovered a common mutation
in a gene that encodes an enzyme called BRAF. Last year, early stage
clinical trials at NCI-designated Cancer Centers of drugs targeted
against the mutant BRAF enzyme showed that most melanomas with the
relevant mutation regressed dramatically. Although tumor regression
generally lasted less than a year, NCI-supported investigators have
already pinpointed some causes of resistance to BRAF inhibitors,
outlining a pathway to more sustained control of this lethal disease.
Another benefit of a prolonged and broad-based investment in cancer
research has also been realized in the context of malignant melanoma
this year, with the recent approval by the FDA of an antibody,
ipilimumab, which extends the lives of patients with metastatic
melanoma. Ipilimumab stimulates the immune system to act against cancer
by blocking natural inhibitors of the immune response, an approach that
would not be possible without a profound understanding of the immune
system and one that promises to harness immunological tools against
other cancers.
These examples of NCI's progress in understanding, treating, and
detecting different forms of cancer illustrate what can be achieved at
an accelerated pace with sustained investments across the cancer
research spectrum, such as proposed under the President's budget. While
those perspectives are only beginning to inform the American public's
perception about cancer and its treatment, the downward trajectory of
cancer deaths--reported by NCI and its partners in March--reflects real
and sustained reductions over more than a decade for numerous cancers,
including the four most common: breast, colorectal, lung, and prostate.
We have identified proteins and pathways that different cancers may
have in common and represent targets for new drugs for these and many
other cancers--since so often research in one cancer creates potential
benefits across others.
Additional progress against cancer also will require building these
research advances into clinical treatments and diagnostic tools for
better patient care and by our many connections with public and private
sector partners. The Institute's investments in translational research
are broad and deep, and will receive NCI's full energies, recognizing
that the publicly announced proposal for reorganizing services that
support translational science in general could give NIH additional
focus in this important area.
REVITALIZING THE CANCER CLINICAL TRIALS SYSTEM
For today's new understandings of cancer biology to benefit cancer
patients on a broad scale, they must be coupled with a modernized
system for conducting cancer clinical trials. This system must enable
clinical researchers across the Nation to acquire tumor specimens and
conduct genetic tests on each patient, to efficiently analyze molecular
changes in those samples, to manage and secure vast quantities of
genetic and clinical data, and to identify subsets of patients with
tumors that demonstrate changes in specific molecular pathways--
pathways that can be targeted by a new generation of cancer therapies.
As part of its effort to transform the cancer clinical trials
system, NCI asked the Institute of Medicine (IOM) in 2009 to review the
Clinical Trials Cooperative Group Program. This program involves a
national network of 14,000 investigators currently organized into nine
U.S. adult Cooperative Groups and one pediatric cooperative group that
conduct large-scale cancer clinical trials at 3,100 sites across the
United States. The IOM report, issued in April 2010, noted that the
current trials system--established a half-century ago--is inefficient,
cumbersome, underfunded, and overly complex. Among a series of
recommendations, the report urged that the existing adult cooperative
groups be consolidated into a smaller number of groups, each with
greater individual capabilities and with new means to function with the
others in a more integrated manner.
In December 2010, NCI announced its intent to begin consolidating
the current nine adult cooperative groups into four state-of-the-art
entities that will design and perform improved trials of cancer
treatments, as well as explore methods of cancer prevention and early
detection, enhance the ability of the cooperative groups to assess the
molecular characteristics of individual patients' tumors, and study
quality-of-life issues and rehabilitation during and after treatment.
The sole pediatric cooperative group was created by consolidating four
pediatric cooperative groups almost a decade ago, and that group will
not be affected by the current consolidation effort.
PROVOCATIVE QUESTIONS
This has been a challenging and hopeful time for NCI to lead the
Nation's cancer research program. Over the past two decades researchers
have unraveled some of the damage that occurs in the genome of a cancer
cell and how a cancer cell behaves in its local environment as a result
of those changes. With this better understanding of cancer and recent
technological advances in many fields, such as genomics, molecular
biology, biochemistry, and computational sciences, progress has been
made on many fronts, and a portrait has emerged for several cancers.
With sustained and accelerated funding, and NCI's strong leadership in
defining cancer research priorities, we can build upon today's cancer
advances with provocative thinking by asking better questions.
To that end, NCI is asking researchers in various disciplines to
pose and articulate ``provocative questions'' that can help guide the
Nation's investment in cancer. Provocative questions may be built on
older, neglected observations that have never been adequately explored,
or on recent findings that are perplexing, or on problems that were
traditionally thought to be intractable but now might be vulnerable to
attack with new methods.
Many of these provocative questions are being asked--and answered--
by young scientists who are early in their careers. The 2012 budget
will support NCI's commitment to ensuring that an equitable share of
our research grants will go to the young men and women, who are at the
forefront of understanding cancer.
We are now reaping the rewards of investments in cancer research
made over the past 40 years or more, even as we stake out an investment
strategy to realize the potential we see so clearly for the future. The
public has benefitted from past generous congressional stewardship of
biomedical research funding; cancer research over the past four decades
has provided the evidence required to lower the incidence and mortality
of many kinds of cancer, to improve the care of cancer patients, and to
establish the new understanding of cancer that is now beginning to
revolutionize control of cancer throughout the world.
No matter what the fiscal climate, NCI will strive to commit the
resources necessary to bring about a new era of cancer research,
diagnosis, prevention, treatment, and survivorship.
Thank you for the opportunity to provide you this testimony, and I
would be pleased to answer any questions you might have.
______
Prepared Statement of Susan B. Shurin, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Heart, Lung, and Blood
Institute (NHLBI) of the National Institutes of Health (NIH). The
fiscal year 2012 budget of $3,147,992,000 includes an increase of
$80,903,000 over the comparable fiscal year 2011 level of
$3,067,089,000.
The NHLBI provides global leadership for a research and education
program to promote prevention and treatment of heart, lung, and blood
diseases. Our vision is to enhance the health of all individuals and
thereby enable them to enjoy longer and more productive lives. The
Institute advances its objectives through an innovative program of
excellent science that addresses urgent public health needs,
capitalizes upon extraordinary opportunities, leverages strategic
assets, balances and integrates basic and clinical research approaches,
and calls upon the creativity, expertise, and dedication of thousands
of scientists here and abroad. The American people have generously
supported this work for many years, and tremendous progress has
resulted.
This testimony highlights three areas of particular current
emphasis: (1) genetics and genomics; (2) regenerative medicine; and (3)
translational medicine.
GENETICS AND GENOMICS
NHLBI-funded gene-sequencing projects and genome-wide association
studies have been extraordinarily productive. Scanning the genomes of
more than 100,000 people from all over the world, scientists recently
reported the largest set of genes yet discovered that underlie blood
lipid variations known to be major risk factors for coronary heart
disease. Altogether, the gene variants explain between one-quarter and
one-third of the inherited portions of cholesterol and triglyceride
measured in the blood. Of the variants, 59 had not been previously
identified and thus provide new clues for developing effective
medicines to combat heart disease. This exciting discovery follows upon
similar research, reported in 2009, regarding another heart disease
risk factor--hypertension. Using genomic analysis of over 29,000
participants from the Framingham Heart Study and other cohorts, an
international research team identified a number of unsuspected genetic
variants associated with systolic and diastolic blood pressure.
Although hypertension has long been known to run in families and have a
substantial genetic component, previous attempts to identify genes
associated with blood pressure had met with only limited success. The
new findings from both the lipid and the blood pressure studies
illustrate the potential of large-scale genome-wide scans to identify
genes that play roles in a complex disease of widespread public health
importance.
Smaller-scale genome-wide scans are also providing valuable new
information about less common disorders, such as thoracic aortic
aneurysm and dissection--a condition that is often asymptomatic until
an unpredictable catastrophic cardiovascular event occurs. Researchers
comparing 418 patients with non-familial thoracic aneurysms to normal
controls identified a number of genetic variants that appeared more
frequently in the patients. Many of the variants exist in genes that
are in some manner involved in contraction of smooth-muscle cells,
suggesting that genetic variants governing smooth-muscle cell function
are a potential target of predictive tests that could be developed in
the future.
Although genome-wide scans and sequencing have identified many
genetic variations that contribute to disease risk, much more research
is needed to understand the mechanisms underlying gene disease
associations. NHLBI is advancing this area by supporting a new program,
Next Generation Genetic Association Studies, to investigate cells that
have been reprogrammed into induced pluripotent stem cells to model
heart, lung, and blood diseases and explore the functional consequences
of genetic variation.
Another initiative, Getting from Genes to Function in Lung Disease,
will support characterization of the function of lung-disease
associated genes and their variants that have been identified through
GWAS or other genetic approaches. Multidisciplinary teams will use a
variety of experimental methods and tools to elucidate the mechanisms
that contribute to diseases such as asthma, chronic obstructive
pulmonary disease (COPD), sarcoidosis, and idiopathic pulmonary
fibrosis and thereby generate knowledge that may lead to more effective
ways to prevent and treat them. In fiscal year 2012, the Institute
plans to solicit research projects to study two severe and poorly
understood conditions that affect the lungs: The Genomic Research in
Alpha-1 Antitrypsin Deficiency and Sarcoidosis program will conduct
state-of-the-art genomic, microbiomic, and phenotypic studies with the
goals of understanding the molecular and cellular bases of the
diseases, facilitating classification of sub-types, and developing new
drug therapies.
Because genome-wide scans are not well suited to discovery of
extremely uncommon genetic variants, the Institute is pursuing other
avenues to explore the contributions of infrequent variants to both
common and rare diseases. A program planned for fiscal year 2012 in
collaboration with the National Human Genome Research Institute, Life
After Linkage: The Future of Family Studies, will use data from
existing family studies to identify and characterize genes, including
rare variants, that influence complex diseases. The potential success
of such an approach is illustrated by a recent breakthrough resulting
from a collaboration between the NHLBI intramural program and the NIH
Undiagnosed Diseases Program. Researchers identified the genetic cause
of a rare and debilitating vascular disorder, not previously explained
in the medical literature, that involves severe arterial calcification.
Analysis of DNA from members of three affected families revealed that
the variant is in a gene responsible for a product that protects
arteries from calcifying. It is hoped that this understanding of the
underlying defect will enable discovery of improved treatment for the
patients.
REGENERATIVE MEDICINE
Body components can malfunction because of inherent defects,
catastrophic or accumulated damage, or senescence, and chronic disease
is often the result. Restoring healthy function via delivery of
``replacement parts'' and helping organs repair injury with functional
tissue instead of scarring are high priorities of NHLBI. Recent
progress gives much reason for optimism. For example, heart attacks
cause permanent damage to heart muscle cells (cardiomyocytes) that
renders them useless for pumping blood. Although cardiomyocytes cannot
themselves be rejuvenated, NHLBI-supported scientists were able to
induce other heart cells (fibroblasts) to become pluripotent stem cells
that, in turn, were induced to become cells that looked and behaved
much like cardiomyocytes. The finding suggests the possibility that
fibroblasts--cells widely available throughout the body--could be
directly reprogrammed into functional cells to treat or prevent heart
failure and other adverse consequences of cell damage. Other NHLBI-
supported researchers recently reported progress toward engineering
lung tissue in a rat model, creating a scaffold populated with
multipotent neonatal rat cells to produce a transplantable organ
capable performing the fundamental lung function of gas exchange. The
success of this study and others using cadaveric human lung tissue and
immortalized cell lines suggests that such an approach might one day be
beneficial for patients who are awaiting lung transplant.
NHLBI is making considerable investments to advance regenerative
medicine research for cardiovascular, lung, and blood diseases. A
collaborative solicitation with the National Institute of Biomedical
Imaging and Bioengineering, New Strategies for Growing 3D Tissues, will
support highly integrated, multidisciplinary research to improve
understanding of how cells respond to their environment and how cell-
communication systems that enable blood-vessel and organ development
can be used to engineer 3D human cellular aggregates. Translation of
Pluripotent Stem Cell Therapy for Blood Diseases will promote the
development of technologies for translation of recent stem cell
advances into treatments for sickle cell disease and other blood
disorders. This new program will build upon the expertise, resources,
and infrastructure of the ongoing NHLBI Progenitor Cell Biology
Consortium, and it will encourage collaboration with two other
Institute initiatives--Production Assistance for Cellular Therapies and
the Gene Therapy Resource Program, which is slated for renewal in
fiscal year 2012.
A major initiative planned for fiscal year 2012, Consortium of Lung
Repair and Regeneration: Building the Foundation, will establish an
interactive group of multidisciplinary teams to formulate and test
innovative hypotheses about the mechanisms that control lung repair and
regeneration. The program will seek to leverage innovative technologies
such as tissue engineering, biomaterials and scaffolds, induced
pluripotent stem-cell technology, cell-directed therapy, and humanized
animal models that are not used widely in lung-regeneration research
but are being applied to investigate regeneration and repair in other
organ systems.
TRANSLATIONAL MEDICINE
NHLBI continues to place strong emphasis on translating basic
science findings into better diagnostic, therapeutic, and preventive
approaches and fostering their use in real-world clinical practice. A
number of initiatives are supporting these efforts. For example, a
program called Science Moving Towards Research Translation and Therapy
(SMARTT) has been launched to facilitate transition of potential new
therapies for heart, lung, and blood diseases from discovery in the lab
to the testing needed to establish their safety and effectiveness in
people. Pre-clinical development--that is, readying products for
testing in humans--is the first step in turning discoveries into cures,
but the processes involved can be expensive and baffling to academic
scientists. Connecting academic researchers with industry, the SMARTT
program will offer help with manufacturing, pharmacology and toxicology
testing, pre-clinical and early-phase clinical study design, and
administrative and regulatory matters.
The Translational Research Implementation Program, or TRIP, is
intended to facilitate well-designed clinical trials in heart, lung, or
blood diseases to demonstrate the safety and efficacy of promising
interventions that have emerged from fundamental studies. Its initial
phase, which began in fiscal year 2010, supported the planning of
trials; the second phase will fund the most promising of them beginning
in fiscal year 2012. A second new program will provide planning grants
to establish the feasibility of pivotal clinical trials with a major
focus on hemoglobinopathies such as sickle cell disease and
thalassemia. Another solicitation, planned for fiscal year 2012, would
provide an innovative mechanism for the development of clinical trials
for hemostatic and thrombotic disorders, including access to expertise
in clinical trial methodology and design through existing institutional
resources.
Several exceptionally promising new translational efforts in lung
diseases are also under way. Research Education in Sleep and Circadian
Biology is promoting the use of innovative educational tools and
programs to accelerate the transfer of recent scientific advances and
health knowledge in sleep and circadian biology into clinical and
public-health practice. Renewal of a solicitation titled Utilization of
a Human Lung Tissue Resource for Vascular Research will advance
translational efforts in lung vascular disease, using previously
collected biospecimens from patients with pulmonary hypertension. An
initiative slated for fiscal year 2012 would support dosing and
efficacy trials of promising but untested therapies for lung diseases,
including agents that have already been approved for use in treating
other diseases and combinations of common drugs with low toxicities,
neither of which would be likely candidates for testing by industry.
Such small proof-of-concept trials are vitally important for
translating basic research advances into clinical research, providing a
foundation for larger efficacy trials, and advancing understanding of
disease processes.
______
Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P.
I am pleased to present the President's fiscal year 2012 budget
request for the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) of the National Institutes of Health (NIH). The fiscal
year 2012 budget includes $1,837,957,000, which is $47,272,000 more
than the comparable fiscal year 2011 level. Complementing these funds
is an additional $150,000,000 also available in fiscal year 2012 from
the Special Statutory Funding Program for Type 1 Diabetes Research. The
NIDDK supports research on a wide range of common, chronic, costly, and
consequential diseases and health problems that affect millions of
Americans. These include diabetes and other endocrine and metabolic
diseases; digestive and liver diseases; kidney and urologic diseases;
blood diseases; obesity; and nutrition disorders.
UNCOVERING THE GENETIC AND ENVIRONMENTAL CAUSES OF DISEASE TO INFORM
THERAPY AND PREVENTION
Unprecedented discoveries in genetics continue to lead the way
toward the development of personalized treatments and prevention of
devastating diseases and disorders. Scientists revealed that certain
variants in the APOL1 gene may be responsible for the differential risk
of developing kidney disease for African Americans. These variants also
provide a degree of protection against African sleeping sickness, a
degenerative and potentially fatal condition caused by a parasite that
is endemic to Africa. This could explain why these variants are more
commonly found in individuals of African descent, despite the increased
risk of kidney disease they confer.
Many of the diseases within the NIDDK research mission result from
the interaction between multiple genetic and environmental factors.
Research on the human microbiome--the microorganisms associated with
the body--has demonstrated that the composition of bacterial
communities is determined mostly by their location on or in the body
and varied between people. In a separate study, scientists reported
that bacteria in the mouse gut contributed to changes in appetite and
metabolism. Therefore, excess calorie composition and obesity may be
affected by these bacterial populations. Researchers in The
Environmental Determinants of Diabetes in Youth are using newly
developed technologies to study the microbiome of children at high risk
for developing type 1 diabetes and explore whether viral or bacterial-
based treatments could be used to prevent or treat the disease. NIDDK
will continue to capitalize on recent genetics and environment
discoveries to transform prediction, prevention, diagnosis, and
treatment of diseases within the Institute's mission.
IMPROVING PATIENT CARE THROUGH RESEARCH
Obesity is a major health epidemic in the United States, and it
increases the risk for type 2 diabetes; kidney, heart, and liver
disease; and other health issues. Therefore, efforts to curb this
rising trend are vitally important. The NIDDK's HEALTHY study revealed
that while a middle school-based intervention did not reduce obesity
school-wide, it lowered the obesity rate in students with the highest
risk for type 2 diabetes. This important result will inform future
school-based efforts to reduce overweight and obesity in children.
Research also shows that weight loss can improve the health of people
with diabetes. NIDDK's Look AHEAD study showed that weight loss in
overweight and obese people with type 2 diabetes can lead, with lower
medication requirements, to long-term favorable effects on diabetes
control and cardiovascular risk factors.
NIDDK continues to support efforts to test potential treatments for
NIDDK-related diseases and disorders. Investigators demonstrated in a
preliminary trial that salsalate, an anti-inflammatory drug used for
years to manage arthritis pain, can help people with type 2 diabetes
control blood glucose levels. If the expanded trial is successful, it
could lead to a safe and inexpensive way to treat the disease. Non-
alcoholic steatohepatitis (NASH) is a form of fatty liver disease
associated with overweight and can lead to liver cirrhosis and liver
failure requiring a transplant. Currently, there are no specific, FDA-
approved treatments for NASH. NIDDK scientists compared vitamin E, the
insulin-sensitizing drug pioglitazone, and placebo for treatment of
adult NASH, and reported promising improvements in response to 2-year
therapy, especially for vitamin E.
It is important to compare available, effective treatments and
combine this knowledge with a patient's history to identify the best
option for treating an individual. A recent NIDDK study demonstrated
that, on average, a lower blood pressure goal was no better than the
standard goal at slowing progression of kidney disease among African
Americans who had chronic kidney disease resulting from high blood
pressure. However, the lower blood pressure goal did benefit patients
who had protein in their urine, a sign of kidney damage. In light of
the APOL1 results I described earlier, this and other findings suggest
that genetic traits more common in African Americans may subtly alter
the pathogenesis of kidney disease in this population, and new classes
of drugs that target these pathways might be more effective in
preventing the onset and progression of chronic kidney disease in these
patients.
Millions of American women suffer from stress urinary incontinence,
an underdiagnosed public health problem that is associated with
diminished quality of life. An NIDDK trial demonstrated that two
different surgical approaches were equally effective--although they had
different side effects--in treatment for stress urinary incontinence, a
major milestone in treatment for this condition. This information will
enable women and their doctors to weigh more accurately the benefits
and risks of available treatment options. In concert with identifying
the best treatment options, NIDDK research aims to ensure that patients
are able to take advantage of these results to improve their health and
care.
DISSEMINATING RESEARCH RESULTS TO IMPROVE PUBLIC HEALTH
It is critical that the results of research reach the American
public quickly and clearly to translate to real improvements in health.
NIDDK supports a number of public health campaigns such as the National
Kidney Disease Education Program, the Weight-control Information
Network, a Celiac Disease Awareness Campaign, and the National Diabetes
Education Program (NDEP).
Diabetes continues to be a growing worldwide public health concern;
rising rates of obesity and an aging populance are driving the
increasing prevalence of type 2 diabetes. There is hope, however:
research has shown that it is possible to delay--or even prevent--the
disease. The NIDDK's landmark Diabetes Prevention Program (DPP) was a
tremendous success, demonstrating that loss of 5-7 percent of an
individual's body weight--or treatment with the drug metformin--can
delay type 2 diabetes. By eating less fat and fewer calories and doing
moderate exercise, such as brisk walking, DPP participants were able to
lose body weight and maintain the loss. These lifestyle changes worked
particularly well for participants age 60 and older, and were equally
effective for all participating ethnic groups and for both men and
women.
To transfer the lessons of the DPP to the community level, NIDDK
supports translational research, which included a trial of less costly
delivery of the DPP intervention in YMCAs in group settings. The
results have led CDC and private organizations to fund the intervention
at more Ys and United Health Group to cover the cost for plan
participants to use the intervention at Ys. Additionally, the NDEP is
disseminating the good news from the DPP follow-up study that
development of type 2 diabetes continued to be reduced 10 years after
the intensive lifestyle change or treatment with metformin. NDEP has
partnered with NIH's Office of Research on Women's Health to also raise
awareness of the increased risk of type 2 diabetes for women who have a
history of gestational diabetes.
GENERATING RESEARCH OPPORTUNITIES
The future of public health depends critically on the development
of the next generation of scientists and the pursuit of scientific
opportunities. NIDDK continues to vigorously support new investigators,
and training and mentorship in biomedical research. NIDDK held its
second annual New Investigators' meeting to enhance their ongoing
research and spur future success. NIDDK also held its eighth annual
workshop for the Network of Minority Research Investigators to
encourage and facilitate participation of members of underrepresented
racial and ethnic minority groups in the conduct of biomedical research
in NIDDK-relevant fields. These new investigators will be poised to
take advantage of a wealth of opportunities to improve the health of
Americans; such opportunities have been identified by a number of
recent strategic planning efforts undertaken by the NIDDK.
The development and application of new technologies will also
improve patient care. Through support for small business innovation
research grants and other efforts, NIDDK will foster cutting-edge
research in this area. New technologies could facilitate analysis of
organs, tissues and biological molecules, and, with mobile
communication, help convey critical information quickly to patients and
healthcare providers. This research would enhance our ability to
monitor disease progression or how a therapy is working and would
improve diagnosis of disease or risk, to enable earlier intervention.
In closing, Mr. Chairman, NIDDK will continue to emphasize my
guiding principles: support a robust portfolio of investigator-
initiated research; vigorously support clinical trials to identify
better ways to prevent and treat disease; preserve a stable pool of new
investigators; disseminate science-based knowledge from research
through education programs; and foster research training and mentoring.
Thank you Mr. Chairman and members of the Committee for the
opportunity to share with you a few highlights of NIDDK's research and
outreach efforts to improve the health of Americans. I will be pleased
to answer any questions you may have.
______
Prepared Statement of Anthony S. Fauci, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute of Allergy and Infectious Diseases (NIAID), a component of
the National Institutes of Health (NIH). The fiscal year 2012 budget
includes $4,915,970,000, which is $144,100,000 more than the comparable
fiscal year 2011 level of $4,771,870,000.
NIAID conducts and supports biomedical research to understand,
treat, and prevent infectious and immune-mediated diseases, including
HIV/AIDS; tuberculosis; malaria; influenza; emerging and re-emerging
infectious diseases; asthma and allergies; autoimmune diseases; and the
rejection of transplanted organs. NIAID makes a major investment in
translational research, which seeks to accelerate the findings from
basic research into healthcare practice. This decades-long commitment,
together with NIAID's multidisciplinary collaborations with experienced
as well as new investigators at academic centers, the private sector,
and other governmental and non-governmental partners, continues to help
improve domestic and global health through the development of
diagnostics, therapeutics, and vaccines for infectious and immune-
mediated diseases. I appreciate the opportunity to highlight just a few
of our research successes and to describe some of our most promising
research programs aimed at improving public health and quality of life.
GLOBAL HEALTH
NIAID has been a leader in both basic and clinical HIV/AIDS
research ever since the disease emerged as a devastating public health
crisis 30 years ago. In 2010, NIAID support for HIV/AIDS research
resulted in landmark scientific advances in HIV prevention. The NIAID-
supported iPrEx study demonstrated that a daily dose of an oral
antiretroviral medication, a strategy known as pre-exposure prophylaxis
or PrEP, was effective at reducing the risk of HIV acquisition among
men who have sex with men. This finding was selected by the prestigious
journal The Lancet as one of the top six medical discoveries in the
world in 2010 and was named by Time magazine as the number one medical
breakthrough in 2010. A second important study, and another of The
Lancet's selections, CAPRISA 004, showed that a vaginal microbicide gel
of an antiretroviral drug could give women a measure of protection
against HIV infection. This important trial was funded by the U.S.
Agency for International Development and carried out using a research
infrastructure developed with NIAID support. In the area of HIV vaccine
development, researchers in NIAID's intramural Vaccine Research Center
and NIAID-funded extramural investigators discovered human antibodies
that can block a wide range of HIV strains from infecting human cells
in the laboratory and are now zeroing in on their precise mechanisms of
action. Coupled with last year's success from the RV 144 HIV vaccine
clinical trial conducted in Thailand, which found a ``prime-boost''
vaccine candidate to be safe and modestly effective in preventing HIV
infection, NIAID is making important strides in developing a robust
package of prevention modalities that can be used in combination. In
addition, research supported under NIAID's new initiative, the Martin
Delaney Collaboratory: Towards an HIV Cure, will provide insights into
how HIV hiding places in the body--so-called ``reservoirs''--are
formed, where they are located, how they are maintained despite
effective antiretroviral therapy, and how they might be eliminated.
NIAID makes a significant investment in research on the co-
infections and co-morbidities that often accompany HIV infection.
Tuberculosis (TB) occurs in about one-third of HIV-infected individuals
and is the leading cause of death in this group. The NIAID-sponsored
CAMELIA study demonstrated that survival of untreated HIV-infected
adults with weak immune systems and newly diagnosed TB can be prolonged
by starting antiretroviral therapy 2 weeks after beginning TB
treatment, rather than waiting the standard 8 weeks. This finding will
help to optimize treatment strategies for people co-infected with HIV
and TB and promises to save many lives in the developing world. A
significant number of adults at risk for HIV infection are also at risk
for hepatitis B and C infection. NIAID supports a robust research
program to understand the pathogenesis of and immune response to
hepatitis viruses and to develop novel therapeutics and vaccines
against the diseases caused by these viruses.
In 2009, there were approximately 9.4 million TB cases and 1.7
million TB deaths globally according to the World Health Organization
(WHO). NIAID has accelerated its TB research activities and is applying
21st century technology to a field that has lagged behind the study of
other infectious diseases. NIAID supports the development of several
promising TB vaccine candidates, and basic and clinical research has
contributed to both new and repurposed therapeutic approaches and
candidates. With NIAID support, researchers also have developed a tool
for diagnosing TB that provides more specific, sensitive, and rapid
results than currently available diagnostics.
In 2009, approximately 225 million cases of malaria resulted in
more than 780,000 deaths, 90 percent of which occurred in Africa,
according to WHO. More than a decade has passed since the newest class
of antimalarial drugs, artemisinins, entered widespread use worldwide;
unfortunately, malaria parasites are becoming increasingly resistant to
these medications. There is a pressing need for new malaria therapies
due to the constant threat of the emergence of drug resistance, which
NIAID is addressing by supporting domestic and international research.
For example, NIAID-supported researchers identified NITD609 as a
promising antimalarial drug with a mode of action that differs from the
current drugs used to treat malaria. NIAID-supported scientists also
discovered a novel metabolic pathway of the malaria parasite Plasmodium
falciparum that could lead to new drug targets. In 2010, NIAID
established ten International Centers of Excellence for Malaria
Research in malaria-endemic regions. In addition to research on HIV/
AIDS, TB, and malaria, NIAID supports research devoted to better
understanding, preventing, and treating other important diseases that
cause a significant burden of illness and death globally, including
neglected tropical diseases such as lymphatic filariasis, trachoma, and
leishmaniasis.
EMERGING AND RE-EMERGING INFECTIOUS DISEASES
NIAID continues its critical focus on advancing drugs, vaccines,
and diagnostics from concept to product development to fight emerging
and re-emerging infectious diseases. In response to the 2009 H1N1
influenza pandemic, NIAID played a key role in developing and testing
the 2009 H1N1 influenza vaccines, and in assessing their safety and
potential effectiveness in a variety of populations. NIAID researchers
also made important strides in the development of broadly protective
influenza vaccines. NIH intramural researchers in the Vaccine Research
Center demonstrated that a ``prime-boost'' vaccine strategy could
protect animals from infection with multiple strains of influenza.
NIAID-supported scientists also determined that individuals infected
with pandemic 2009 H1N1 influenza generated antibodies that neutralized
many different influenza virus strains. This adds to the evidence base
that a universal influenza vaccine may be possible, which would obviate
the need to modify the influenza vaccine each season. NIAID-supported
investigators also showed that vaccinating children against influenza
protects the wider community, underscoring the public health importance
of widespread vaccination with current and improved vaccines. The
Lancet chose this study as its top scientific advance of 2010.
Building on the experience and challenges of the 2009 H1N1
influenza pandemic, the Department of Health and Human Services
conducted a review of the Federal Government's efforts to develop
medical countermeasures (MCMs) such as drugs and vaccines for public
health emergencies, including bioterror attacks, culminating in a new
vision for MCM development. As part of this vision, NIAID--in
coordination with the Biomedical Advanced Research and Development
Authority and the Department of Defense--will lead the Concept
Acceleration Program to stimulate the translation of new scientific
concepts and discoveries to the development of MCMs for biodefense and
emerging infectious diseases.
The dengue epidemic in Puerto Rico and dengue cases in Florida and
Hawaii, as well as the cholera outbreak in earthquake-ravaged Haiti,
demonstrate the importance of understanding the factors that contribute
to disease emergence and re-emergence. NIAID dengue research includes
basic research, vector biology, translational research, as well as the
development of research tools, resources, and services. With NIAID
support, scientists are developing several vaccine approaches for
dengue. NIAID research on cholera spans basic research, genomics,
studies of environmental and climactic factors, and the development of
vaccines and therapeutics. An NIAID-supported study pinpointed the
genetic lineage of the cholera microbe that is causing the epidemic in
Haiti.
NIAID continues to support a robust basic, translational, and
clinical research portfolio to address the public health issue of
antibiotic resistance for key pathogens, including methicillin-
resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria. For
example, NIAID scientists recently identified a toxin from a community-
acquired strain of MRSA that could be a factor in the severity of MRSA
infections. NIAID also supports research to preserve the effectiveness
of currently used antibiotics, including studies to examine optimal
treatment of community-acquired pneumonia and infections caused by
Gram-negative bacteria such as Pseudomonas and Acinetobacter. NIAID-
supported researchers settled a medical controversy by recently showing
that antibiotics clearly reduce the severity and duration of acute
middle-ear infections in toddlers that were diagnosed using consistent
criteria.
IMMUNE-MEDIATED DISORDERS
NIAID is committed to furthering our understanding of the
immunologic mechanisms underlying autoimmune diseases, asthma and
allergic diseases, rejection of transplanted organs, and other immune-
mediated disorders; and to translating this knowledge into new
approaches for diagnosis, prevention, and treatment. In 2010, an NIAID-
sponsored expert panel produced much-needed comprehensive guidelines
for medical practitioners for the diagnosis and management of food
allergy that will be helpful to clinicians across a range of medical
specialties. NIAID also launched the Human Immunology Project
Consortium to better understand the human immune system and how it
reacts to infection or vaccination. The information gained from this
effort will provide insights into the development of safer and more
effective vaccines, including those for young children and the elderly.
In addition, researchers in the NIAID Immune Tolerance Network
demonstrated that Rituxan is a safe and effective therapy for two
forms of severe vasculitis, a rare and devastating disease of the blood
vessels. These data were instrumental in the recent Food and Drug
Administration-approval of Rituxan for this indication, representing
the first licensed treatment for this disorder in 40 years. Also, the
NIAID Inner-City Asthma Consortium determined that the addition of
Xolair to NIH guidelines-based asthma therapy for young children and
adolescents resulted in fewer asthma symptoms and severe asthma
attacks.
CONCLUSION
For more than 60 years, NIAID has conducted and supported basic and
clinical research on infectious and immune-mediated diseases leading to
the development of vaccines, therapeutics, and diagnostics that have
significantly improved the health and saved the lives of millions
around the world. NIAID will continue to support the highest quality
research with the aim of translating fundamental discoveries into
improved public health.
______
Prepared Statement of Josephine P. Briggs, M.D., Director, National
Center for Complementary and Alternative Medicine
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National Center
for Complementary and Alternative Medicine (NCCAM) of the National
Institutes of Health. The fiscal year 2012 budget includes
$131,002,000, which is $3,399,000 more than the comparable fiscal year
2011 appropriation of $127,603,000.
The National Center for Complementary and Alternative Medicine
(NCCAM) is the Federal Government's lead agency for scientific research
on complementary and alternative medicine (CAM). CAM includes a group
of diverse medical and healthcare interventions, practices, products,
or disciplines that are not generally considered part of conventional
medicine (sometimes called Western or allopathic medicine). The
boundaries between CAM and conventional medicine are not absolute;
instead, they are constantly evolving: interventions such as hospice
care or relaxation and breathing techniques in childbirth that were
once considered unconventional are now widely accepted. Furthermore,
there is growing interest in more integrative approaches that use both
CAM and conventional interventions. For example, both the Departments
of Defense \1\ and Veterans Affairs are integrating select CAM
modalities into treatments for pain, stress, and sleep disorders.
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\1\ Pain Management Task Force Final Report: Providing a
Standardized DOD and VHA Vision and Approach to Pain Management to
Optimize the Care for Warriors and Their Families, Office of the Army
Surgeon General, Department of Defense, May 2010.
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CAM is used by many in the United States, both in treating health
problems and in promoting better health and well-being. Data from the
2007 National Health Interview Survey \2\ (NHIS), developed under NCCAM
leadership in collaboration with the National Center for Health
Statistics at the Centers for Disease Control and Prevention (CDC),
show that nearly 40 percent of adult Americans and 12 percent of
children are using some form of CAM. The data also show that in 2007
out-of-pocket expenditures for CAM totaled $33.9 billion. While this
amount accounted for only 1.5 percent of total healthcare expenditures,
it was more than 11 percent of out-of-pocket expenditures. Finally,
NHIS data indicate that a large portion of CAM use is best described as
``self-care'' in that it occurs outside of the framework of a
relationship with a healthcare professional. The scope, associated
costs, and self-care nature of CAM use in the United States reinforce
the need to develop reliable, objective scientific evidence concerning
the usefulness and safety--or lack thereof--of CAM interventions, and
to ensure the public has access to accurate and timely evidence-based
information.
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\2\ Nahin RL, Barnes PM, Stussman BA, et al. Costs of complementary
and alternative medicine (CAM) and frequency of visits to CAM
practitioners: United States, 2007. CDC National Health Statistics
Report #18. 2009.
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NCCAM is shaping its research directions through our third
strategic plan, which was developed with considerable input from our
diverse stakeholder community and released in February 2011. The
strategic plan, Exploring the Science of Complementary and Alternative
Medicine (available at www.nccam.nih.gov), was built around three long-
range goals aimed at improving the state and use of scientific evidence
regarding the two major reasons for use of CAM in the United States--
treating health problems and supporting or promoting better health and
well-being. The three goals are to (1) advance the science and practice
of symptom management; (2) develop effective, practical, personalized
strategies for promoting health and well-being; and (3) enable better
evidence-based decisionmaking regarding CAM use and its integration
into healthcare and health promotion.
PAIN AND SYMPTOM MANGEMENT
CAM approaches, as treatments for health problems, are used most
often to manage symptoms such back or neck pain, arthritic or other
musculoskeletal pain, headache, and insomnia. These are all difficult
problems and there is broad agreement that existing options are less
than fully satisfactory for many patients. For example, chronic back
pain is, by far, the most frequent health problem for which Americans
turn to CAM. They might try CAM approaches after exhausting other
options such as opioids, injections, surgery, or physical therapy. More
often, however, they pursue CAM treatment options, including spinal
manipulation, yoga, acupuncture, and massage, in conjunction with
conventional approaches. Individuals suffering from chronic pain
conditions, their healthcare providers, and health policymakers all
need better evidence regarding the value and safety of these
complementary and integrative approaches in alleviating pain, and in
improving quality of life.
To address this critical need, NCCAM is intensifying its focus on
determining whether and how CAM interventions add value to existing
approaches and on understanding their biological mechanisms. In order
to advance the science and practice of symptom management, NCCAM plans
to support Centers of Excellence for Research on CAM for Pain in fiscal
year 2011. NCCAM is also working with our colleagues at the Department
of Defense to explore ways that CAM mind and body approaches can be
used in integrative approaches to treat pain, stress disorders, and
other symptoms. For example, we recently sponsored a joint workshop on
acupuncture for the treatment of acute pain. We are also investigating
potential collaborations with the Department of Veterans Affairs to
advance CAM research and to maximize our investments in bringing relief
to our wounded warriors.
STRATEGIES FOR PROMOTING HEALTH AND WELL-BEING
It is generally accepted and well established that sustaining
healthy behaviors (e.g., good eating habits and regular physical
exercise) and modifying unhealthy behaviors (e.g., smoking) reduce
risks of major chronic diseases. Many CAM and integrative medicine
practitioners and disciplines employ various interventions (e.g.,
meditation or yoga) to help motivate people to adopt and sustain
health-seeking behaviors, or to encourage dietary practices (sometimes
grounded in traditional medical systems) that incorporate a healthy
food philosophy. Newly emerging evidence suggests that CAM use may be
associated with greater degrees of health-seeking behavior. While
causal relationships between CAM use and healthy behavior have not been
established, the claims and preliminary data deserve investigation
given the formidable public health challenges in motivating behavior
change. Research is needed to explore, clarify, and examine the
hypothesis that certain CAM approaches or practices can, in fact, be
useful in encouraging better self-care, an improved personal sense of
well-being, and a greater commitment to a healthy lifestyle.
CAM RESEARCH CHALLENGES
Given the scope and self-care nature of CAM use by Americans, NCCAM
remains committed to supporting rigorous research that will address the
need for scientific evidence to help the public and their healthcare
providers make better-informed decisions about CAM use. For example,
herbal medicines, dietary supplements, and other CAM natural products
are readily available to and purchased by consumers, but evidence
regarding usefulness of many does not exist. In addition, some people
believe that herbal medicines, dietary supplements, and other CAM
natural products are inherently healthier or safer than drugs. In fact,
there are ongoing concerns about safety, including the presence of
contaminants or adulterants (e.g., conventional drugs) in some CAM
natural products, and the potential of toxic interactions with drugs or
other natural products.
Clinical research to address these needs will remain a cornerstone
of the CAM research enterprise, but these studies are complex,
expensive, and time-consuming. NCCAM's strategic approach is to ensure
that clinical trials of CAM natural products are based on a
scientifically sound hypotheses and methods that are grounded in basic
mechanistic and translational research. This foundation facilitates
design of maximally informative clinical trials that include measures
of biological effect relevant to the hypothesis (e.g., biomarkers or
surrogate markers), as well as measures of clinical outcomes.
Investigators studying mind and body interventions face other
scientific challenges in designing rigorous research that will address
the questions of greatest importance to consumers, providers, and
healthcare policymakers. These include identifying relevant study
endpoints and defining appropriate experimental designs to test
interventions. To address such challenges, NCCAM recently collaborated
with several NIH ICs to sponsor a workshop on control and comparison
groups for studies of non-pharmacological interventions.\3\
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\3\ NCCAM Workshop on Control/Comparison Groups for Trials of Non-
Pharmacologic Interventions, April 26, 2010.
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CONCLUSION
As established in its third strategic plan, NCCAM is focusing the
Center's efforts and resources on two compelling areas of public health
need: better strategies for managing symptoms such as chronic pain, and
better strategies for promoting health and well-being. In both areas
there exist promising scientific opportunities for research on CAM
interventions to contribute to real and meaningful progress in
addressing common and vexing individual and social problems, and in
developing more integrative approaches to healthcare and the support of
healthy behaviors and lifestyles.
Finally, NCCAM's plan looks to a vision in which scientific
evidence informs decisionmaking by the public, by healthcare
professionals, and by health policymakers regarding CAM use. NCCAM will
continue its multi-pronged efforts to provide world-class information
about the safety and usefulness of CAM interventions to consumers, and
to foster dialogue about CAM use between patients and their healthcare
providers. In addition, a new online resource, tailored to the needs of
healthcare professionals, is being launched on the NCCAM website. It
includes information on the safety and efficacy of a range of CAM
practices, and was developed in response to providers' needs for an
evidence-based, one-stop resource to help answer their patients'
questions on CAM.
______
Prepared Statement of Barbara M. Alving, M.D., Director, National
Center for Research Resources
Mr. Chairman and Members of the Committee: It is a privilege to
present to you the President's budget request for the National Center
for Research Resources (NCRR) programs for fiscal year 2012. The fiscal
year 2012 budget of $1,297,900,000 includes an increase of $41,225,000
over the comparable fiscal year 2011 level of $1,256,675,000. Funding
priorities for fiscal year 2012 include the continued support and
refinement of the Clinical and Translational Science Award program,
which will reach its targeted number of 60 consortium members later
this year. Funds will also sustain the range of activities supported by
the Center's other major programs, including the Research Centers in
Minority Institutions, the Institutional Development Awards, the
National Primate Research Centers, and the Biomedical Technology
Research Centers.
By uniting innovative research teams with the power of shared
resources across the Nation, NCRR programs provide laboratory
scientists and clinical researchers with the tools and training they
need to understand, detect, treat, and prevent a wide range of diseases
through clinical and translational research. NCRR's diverse yet
interconnected NCRR programs enable the research of more than 30,000
NIH-funded investigators nationwide by providing the resources, tools,
and networking connections.
This statement is submitted with the recognition of a publically
announced proposal for reorganization that would result in dissolution
of NCRR and the transfer of programs to other NIH ICs and Offices.
BUILDING CLINICAL AND TRANSLATIONAL RESEARCH CAPABILITIES
NCRR's Clinical and Translational Science Award (CTSA) program is
transforming biomedical research by building national clinical and
translational research capacity to speed the translation of laboratory
discoveries into better treatments for patients. Launched in 2006, the
CTSA program is a national clinical and translational research
consortium which now includes 55 medical research institutions in 28
States and the District of Columbia. The consortium supports research
by disseminating clinical research informatics tools, forging new
partnerships with healthcare organizations, and expanding outreach to
minority and medically underserved communities. The first cohort of
CTSAs, now re-competing for their next 5 years of funding, have pushed
scientific discoveries toward novel and promising treatments that
enable healthcare reform and more cost-effective treatments. For
instance, research conducted at the University of California, San
Francisco's CTSA found that reducing salt intake by just a half
teaspoon per day could help Americans significantly improve their heart
health, reduce a number of heart-related deaths and potentially save
millions in healthcare costs. The findings influenced the Food and Drug
Administration's decision to limit the amount of salt in prepared foods
and helped support the CDC's salt reduction campaign.
Importantly, the CTSA consortium serves as a communications hub
that ensures sharing among sites and accelerates adoption of best
practices for clinical and translational research. The CTSAs are
building biomedical research capability by generating new tools and
resources, such as ResearchMatch.org, a Web-based national recruitment
registry which matches volunteers with clinical studies seeking
participants, and the CTSA Pharmaceutical Assets Portal, a public-
private collaboration enabling scientists to learn more about existing
compounds that are not being actively developed and might be repurposed
to treat other types of diseases.
ENERGIZING RESEARCH COMMUNITIES
NCRR programs support new investigators and promote new ideas
through innovative networking collaborations, partnerships, training,
and career development for clinical and translational scientists.
Members of the Institutional Development Award (IDeA) program, which
supports rural and underserved communities, developed the Network of
IDeA-funded Core Laboratories (NICL) to address common challenges of
NCRR-funded core laboratories. NICL addresses, develops and
disseminates sustainable business models for efficient core operations
and expands access to advanced core resources and expertise. Now
extended to other NCRR programs, NICL supports, encourages, and
facilitates resource sharing and collaboration among NCRR-funded cores
and shared-resource facilities. NCRR programs are also energizing the
research community with the world's first physician-scholar training
program on wireless healthcare research, launched through a partnership
between The Scripps Translational Science Institute (STSI) CTSA and the
wireless telecommunications company Qualcomm. STSI is positioned to
become an invaluable resource for this emerging, high-impact field of
research.
ADVANCING INNOVATIVE BIOMEDICAL TECHNOLOGIES
The Biomedical Technology Research Centers (BTRCs) program is
producing leading edge technologies to accelerate discoveries that help
researchers who are studying virtually every human disease. At the
Resource for Magnetic Resonance and Optical Imaging at the University
of Pennsylvania, researchers are working closely with clinicians to
improve patient care by developing and promoting ready access to
imaging tools with the goal of translating novel approaches for imaging
blood flow through brain tissue and other organs.
NEW AND BETTER TREATMENTS THROUGH ANIMAL MODELS
The National Primate Research Center (NPRC) program advances
research and knowledge in HIV and AIDS, as well as in numerous other
diseases. The NPRCs have a close relationship with the CTSAs; one
example is the collaboration between the New England NPRC and the
Harvard CTSA. The two are jointly examining the observation that
insulin resistance appears to be a predictor of dementia utilizing a
monkey model of insulin resistance and an analysis of high-field MRI
scans in the monkey model conducted by the Harvard CTSA investigators
who have expertise with MRI in humans. NCRR continues to supply the
research community with animal models and resources. Through the Link
Animal Models to Human Disease Initiative (LAMHDI), a Web-based
resource, investigators can identify and locate useful animal models
that are essential to their research in treatments for human disease.
EXPANDING RESEARCH CAPABILITIES TO ADDRESS HUMAN HEALTH
Through the IDeA and Research Centers in Minority Institutions
(RCMI) programs, biomedical research capacities across the Nation are
expanding into States with historically low NIH funding and are having
a direct impact on human health. One example is from the National
Center for Genome Resources in New Mexico, home of the DNA sequencing
and bioinformatics core for the New Mexico IDeA Networks of Biomedical
Research Excellence (INBRE). Scientists used innovative whole-genome
sequencing and expression analyses to study Multiple Sclerosis (MS) in
identical twins resulting in the first published genome sequences of
female twins or individuals with autoimmune disease. It is also the
first systematic comparison of genomes in identical twins, including
epigenetic markers and expression profiles. Another study from the New
Mexico INBRE used next-generation sequencing methods to develop a pre-
conception genetic test for 500+ mutations known to increase the risk
of numerous rare diseases in children of carriers.
Another illustrative example is a pilot study, initiated by the
RCMI Translational Research Network, to study the effect of Vitamin D
on cardiovascular disease risk factors in African Americans. This study
is important because racial/ethnic minorities, especially African
Americans, continue to suffer a disproportionate burden of
cardiovascular disease. African Americans also tend to have low levels
of Vitamin D and these low levels have been associated with
cardiovascular disease risk. Supplementation with Vitamin D may be an
accessible and affordable intervention.
PROVIDING A CATALYST FOR RESEARCH COLLABORATION
Grantee institutions are adopting research networking tools as a
step toward national networking of people, resources, and data on the
web. The VIVO project, which is an initiative to enable national
networking of scientists and resource discovery, is driving the network
with availability of linked open data about scientists and their work.
The potential will be realized through their commitment to publish data
on the web so the information is more easily discoverable and
connections with other open linked data can be made. VIVO is an open
source semantic web application linking information automatically from
institutional and public systems of record to provide detailed profiles
of scholars and researchers. The power of this semantic web approach is
the ability for creative visualization of connections not previously
possible between diverse types of information and data.
This brief overview of NCRR's programs demonstrates our continuing
commitment to accelerating clinical and translational research. NCRR
will continue to advance research through partnerships among its
programs, other Institutes and Centers at the NIH, and with other
Federal and non-Federal agencies to advance training and translational
research opportunities.
______
Prepared Statement of Paul A. Sieving, M.D., Ph.D., Director, National
Eye Institute
Mr. Chairman and Members of the Committee:I am pleased to present
the President's budget request for the National Eye Institute (NEI).
The fiscal year 2012 budget of $719,059,000 includes an increase of
$18,832,000 over the fiscal year 2011 appropriation level of
$700,227,000. As the director of the NEI, it is my privilege to report
on the many research opportunities that exist to reduce the burden of
eye disease.
TECHNOLOGIES TO ACCELERATE DISCOVERY
The causes of common diseases are complex in that there are
potentially many different environmental factors and genetic variants
that can contribute to disease. New technologies such as genome-wide
association studies (GWAS) allow investigators to scan the genomes of
patients to identify genetic risk variants for common diseases.
Individually, each of these variants may only contribute to a small
percentage of cases, so GWAS require many subjects to identify low
frequency risk variants. In the largest GWAS study in vision research
to date, NEI investigators recently sequenced DNA from over 18,000
patients and control subjects and identified three new genes associated
with age-related macular degeneration (AMD), the most common cause of
vision loss in older Americans. Two of these genes are involved with
high-density lipoprotein cholesterol metabolism, implicating a new
biochemical pathway involved in the pathogenesis of AMD. These findings
will allow researchers to better understand the disease mechanisms
underlying AMD and develop therapies that address the root cause of
vision loss. Glaucoma is another heritable blinding disease where the
genetic underpinnings are poorly understood. The NEI Glaucoma Human
Genetics Collaboration, a consortium of clinicians and geneticists at
12 institutions throughout the United States dedicated to identifying
the genetic factors associated with glaucoma is conducting a large-
scale GWAS that involves scanning 5,000 DNA samples. The consortium is
using state-of-the-science technology to sequence the exome, the full
complement of protein coding regions in the human genome, in a subset
of patients. The data from these DNA samples are expected to be
available to the vision research community in 2011.
TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT
Positive results of ongoing, pioneering clinical trials of gene
therapy for Leber congenital amaurosis, a severe, early onset retinal
disease, have encouraged applications of this approach to many other
eye diseases. In the past year, NEI investigators demonstrated proof-
of-concept of gene therapy using animal models of AMD, achromatopsia,
Leber's hereditary optic neuropathy, retinitis pigmentosa, and red-
green color blindness. Previous work with animal models established the
utility of gene therapy in juvenile retinoschisis, optic neuritis, and
Stargardt disease. These studies now allow investigators to conduct the
pre-clinical work necessary to pursue regulatory approval for clinical
trials. In addition, novel gene delivery systems, such as the use of
nanoparticles, have shown promise in animal models. Such vectors will
be helpful in expanding the reach of gene therapy to target a variety
of ocular tissues such as retinal ganglion cells and the light-
sensitive photoreceptor cells.
ENHANCEMENT OF EVIDENCE-BASE FOR HEALTH CARE DECISIONS
For treating the blinding (``wet'') form of advanced AMD, monthly
ocular injections of a drug, Lucentis, was approved in 2007 by the FDA.
This was the first effective treatment that not only stopped
progression of the disease, but also improved vision for many patients.
Lucentis blocks formation of new, but abnormal blood vessels that leak
fluid into the central part of the retina that is responsible for keen
vision. It was developed from another inhibitor of blood vessels,
Avastin, which since its approval in 2004, has been used to block new
vessels that form to nourish growth of some cancers. Even before final
FDA approval of Lucentis, ophthalmologists began using Avastin ``off-
label'' for treating AMD, and today, most AMD patients receive Avastin.
Given the lack of data regarding the effectiveness of Avastin for AMD
treatment, in 2007, the NEI had an obligation to patients and
clinicians to compare the two drugs and to evaluate whether the drugs
could be used less frequently as needed--called PRN--rather than
monthly as originally approved for Lucentis. Visual acuity improvement
was virtually identical (within one letter difference on an eye chart)
for either drug when given monthly. When each drug was given PRN, there
also was no difference between drugs. For PRN dosing, patients required
four to five fewer injections per year compared to monthly treatment
and still had substantial gains in vision.
Lucentis was also studied in a comparative effectiveness trial for
diabetic macular edema (DME), a common sight-threatening complication
of diabetes in which fluid from leaky blood vessels causes the retina
to swell. For the past 25 years, DME has been treated with a laser to
destroy abnormal blood vessels. Although laser therapy slows disease
progression, the effects are temporary, and repeated treatments can
damage healthy retinal tissue and impair vision. In recent years,
ophthalmologists have been supplementing laser treatment with ocular
injections of either Lucentis, a drug that prevents blood vessel
growth, or triamcinolone, a corticosteroid to reduce inflammatory
complications. An ongoing clinical trial comparing the safety and
efficacy of these two drugs is being conducted by the Diabetic
Retinopathy Clinical Research Network (DRCR.net), a public-private
partnership funded by NEI, the Type 1 Diabetes Funding Program, and
industry collaborators. After 1 year, Lucentis plus laser treatment was
superior in both safety and efficacy compared to triamcinolone plus
laser or to laser alone. This landmark clinical trial identified the
first new safe and effective treatment regimen for DME in more than two
decades. In addition, the study demonstrated that intravitreal
triamcinolone, which had been used in 60 percent of patients with DME,
had significant side effects (cataract and glaucoma) and was not better
than laser alone. These results are already being used by community
ophthalmologists to greatly improve the vision and quality of life for
people living with diabetes.
Treatment of cataracts in infants is challenging for pediatric
ophthalmologists and parents. Replacing the opaque lens with an
artificial lens is critical to prevent permanent loss of vision in the
eye. After removing the cataract, contact lenses have been the
preferred method to overcome the loss of the natural lens. However, it
is difficult and stressful for parents to insert a contact lens into an
infant's eye. Removing the cataract and surgically implanting a
transparent intraocular lens (IOL) in adults is common but had not been
fully characterized in infants. An NEI-supported clinical trial found
no difference in visual acuity with contact lenses compared to IOLs 1
year after cataract removal. However, IOLs caused significant numbers
of surgical complications. Based on these results, the use of contact
lenses is considered the safest effective treatment for infants with
cataract.
NEW INVESTIGATORS, NEW IDEAS
The increasingly quantitative nature of the biomedical sciences and
the explosive growth of genomic, transcriptomic, proteomic,
metabolomic, neurophysiological and clinical data require that
investigators work at the interface of biology and computational
sciences. The NEI is committed to developing the next generation of
vision researchers and has expanded its institutional training grant
program with a program in ocular statistical genetics at several
universities. This program will partner researchers with expertise in
mathematics, modeling, and computation, fields that are not usually
affiliated with ocular research, with researchers in all areas of
vision science to provide state-of-the-art training for a new breed of
researchers.
______
Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National
Human Genome Research Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for the National Human
Genome Research Institute (NHGRI). The proposed fiscal year 2012 budget
is $524,807,000, an increase of $13,749,000 from the comparable fiscal
year 2011 level of $511,058,000.
This is an exciting time for biomedical research in general and for
genomics research in particular. NHGRI investments in the development
of genomic technologies and their application are generating innovative
and powerful approaches to address a diverse array of biological and
biomedical questions. In early 2011, after 2-plus years of rigorous
consultation and planning, NHGRI published a new strategic plan for the
field of genomics in the premiere scientific journal Nature. This
comprehensive strategic vision describes the next key steps in the
herculean journey to decipher the secrets within our genetic code and
to use those discoveries to empower health practitioners and patients
in a fashion that leads to improved human health. The strategic plan
also challenges the broader biomedical community to anticipate the
scientific and non-scientific achievements that will be necessary to
implement cost-effective and accessible genomics-based medical care
(i.e., genomic medicine).
ENABLING RESEARCH
Basic research lays the foundation for understanding the functional
features within our genome and how disruptions in them can lead to
disease. In fact, the knowledge gained from basic genomic
investigations enables scientists and clinical investigators from other
disciplines to pursue translational research programs to understand
particular biological pathways or address disease-specific questions.
The ENCyclopedia of DNA Elements (ENCODE) project and the related model
organism ENCODE (modENCODE) project are moving forward effectively
toward their goals of finding all the functional elements in the human
genome, as well as in the genomes of organisms that serve as important
models for human biology.
To stimulate and accelerate multi-disciplinary research, NHGRI has
funded several Centers of Excellence in Genomic Science (CEGS). In
addition to pursuing cutting-edge genomics research questions, these
centers are associated with rigorous training programs that focus on
groups under-represented in biomedical research. Such efforts aim to
reinvigorate the biomedical research community by engaging diverse
expertise and fostering the development of versatile young scientists.
The unprecedented decreases in the cost of DNA sequencing resulting
from the NHGRI-stimulated technology development efforts are moving us
steadily closer to the reality of using genome sequencing as a routine
part of clinical care. However, even with the three-to-four orders-of-
magnitude drop in DNA sequencing costs that has occurred, sequencing an
entire human genome remains too expensive for the kind of human
research studies needed to dissect the small genetic differences
between individuals that contribute to increased risk for common
diseases, such as cancer, heart disease, and asthma, because such work
often requires the study of thousands or tens of thousands of
individuals. To this end, NHGRI continues to push forward technology-
development initiatives, such as the $1,000 Genome program, to develop
novel and even more cost-effective DNA sequencing methods.
Concurrently, the NHGRI-funded large-scale sequencing centers continue
to use innovative approaches for improving available DNA sequencing
technologies. These efforts are projected to result in a substantial
drop in the cost of generating a human genome sequence--to less than
$25,000 by the end of fiscal year 2011 and less than or equal to
$15,000 by the end of fiscal year 2012.
To develop an appropriately broad catalog of information about the
variation within the genomes of different individuals across the world,
NHGRI continues to contribute substantially to the international 1000
Genomes Project. In addition, on behalf of NIH, NHGRI led the effort to
launch a research partnership with the Wellcome Trust, called the Human
Heredity and Health in Africa (H\3\Africa) Initiative. This new effort
seeks to stimulate research within African laboratories to enable
leading-edge genomic studies to be conducted across the continent. The
knowledge gained through a deeper understanding of genomic variation in
African populations will not only lead to improved abilities to study
genetic diseases in those populations, but will enhance our
understanding of the complex interplay between environmental and
genetic factors that influence disease susceptibility and drug
responses in many diverse populations.
BUILDING A FRAMEWORK FOR TRANSLATION
Building on the tools and knowledge created by these and other
basic research programs, the joint NHGRI-National Cancer Institute
(NCI) project, The Cancer Genome Atlas (TCGA), is providing important
new insights into some of the most vexing forms of malignancy,
including brain cancer and, more recently, acute myeloid leukemia and
ovarian cancer. Results from TCGA and associated cancer genomics
studies by NHGRI-funded investigators point to new therapeutic targets
and, as recently reported in the Journal of the American Medical
Association, demonstrate the potential for more precise modes of cancer
diagnosis and treatment. As a flagship program for NIH translational
research activities, TCGA is expanding its efforts and will focus on an
additional 20 major cancers over the next 5 years.
Beginning in fiscal year 2012, NHGRI will expand its large-scale
genome sequencing and analysis portfolio to include centers that target
the study of rare, single-gene (Mendelian) disorders using cutting-edge
genomic technologies. Rare disease research already is benefiting from
the new genomic technologies. For example, the causative genes for a
pair of developmental disorders were discovered recently: Miller
syndrome, which affects the development of the face and limbs, and
Kabuki syndrome, which affects facial and cognitive development. These
two discoveries represent the ``tip of the iceberg'' with respect to
the identification of altered genes that result in rare diseases, as
reports of such discoveries are published in the scientific literature
almost weekly. Another new NHGRI initiative in fiscal year 2012 will
pilot the use of genome sequencing in clinical care settings, an
important step towards implementing genomic medicine.
Complementing the genome sequencing initiatives, the NIH
Therapeutics for Rare and Neglected Diseases (TRND) program, which is
currently administered by NHGRI, aims to innovate and accelerate the
drug development pathway for rare and neglected diseases. As the TRND
pilot projects move toward their initial milestones, the first full-
scale project portfolio will be launched in collaboration with external
and internal partners. Likewise, the NIH Chemical Genomics Center
(NCGC) continues to serve as a national resource for the generation of
novel chemical ``leads'' to spur inventive directions in candidate drug
and biological assay identification. This statement is submitted with
the recognition of the Department's notification to the Congress of an
NIH reorganization that would establish a new National Center for
Advancing Translational Sciences (NCATS).
EARLY OPPORTUNITIES FOR GENOMIC MEDICINE
The clinical promise of genomics requires strong foundational
knowledge about the structure and biology of genomes as well as the
biology of disease. Increasingly, genomics will be used to advance
medical science and to improve the practice of medicine.
Cancer genomics (as previously discussed) and pharmacogenomics (or
genomically guided medication prescription) are anticipated to be
leading-edge examples of genomic medicine. Successes of the latter
include the use of genomic information for making decisions about
administering the antiretroviral drug abacavir, now the standard of
care for HIV-infected patients. Other promising examples of
pharmacogenomics involve the use of patient genomic information to
target the application and dose of tamoxifen to treat breast cancer,
clopidogrel to treat cardiovascular disease, and the blood-thinner
warfarin. For cancer genomics, it is expected that genomic profiling of
tumors will become increasingly routine for making decisions about
treatment strategies.
Major advances in the study of common, genetically complex diseases
also have been seen recently. Over the past 5 years, more than 4,000
validated associations have been made between a genomic region and a
common disease (or another specific trait). Studies that identify and
provide evidence to support the value-added connections between genetic
factors and observed phenotype (physical traits, clinical symptoms,
etc.) require substantial investments in time, funding, and resources,
but are fundamental to translating genomics investments into clinical
applications. One such initiative, the Electronic Medical Records and
Genomics (eMERGE) Network, aims to advance the efficiency of this
scientific approach. This program will enter its second phase in late
fiscal year 2011, during which it will not only link patients' DNA to
their electronic medical record information, but also will explore the
challenges of using the information to inform clinical care in a
respectful, responsible manner.
The new NHGRI strategic plan identified several critical cross-
cutting elements that are integral to navigating successfully the path
to genomic medicine: bioinformatics and computational biology,
education and training, and the continued study of the societal
implications of genomics. The major bottleneck in genome science is no
longer data generation; rather, it is the computational analysis of
data. Beyond the research setting, the public, and especially
healthcare providers, need to become much more conversant in genomics.
To help address the needs of healthcare professionals, NHGRI has
launched online tools to support genetic and genomic training in health
professional education programs, including bilingual case studies.
Moving forward, translating basic genomic knowledge to improve
human health will continue to rely on innovative technology
development, large-scale collaborative and, increasingly, multi-
disciplinary efforts, and robust attention to the societal implications
of genomic advances. Demonstrating utility and feasibility will be
critical for widespread adoption of genomic medicine; the thresholds
for defining benefit and harm will vary across stakeholders and
cultural perspectives. However, overcoming the challenges that
accompany such a paradigm-changing venture is within reach. The
research and related programs that NHGRI will pursue over the next year
will continue to lay the groundwork for an era where individualized
genomic medicine will become a reality, and the original promise of the
Human Genome Project will be fulfilled.
______
Prepared Statement of Richard Hodes, M.D., Director, National Institute
on Aging
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute on Aging (NIA) of the National Institutes of Health (NIH).
The fiscal year 2012 budget includes $1,129,987,000 which is
$30,450,000 more than the comparable fiscal year 2011 appropriation of
$1,099,537,000.
The National Institute on Aging leads the national effort to
understand aging and to identify and develop interventions that will
help older adults enjoy robust health and independence, remain
physically active, and continue to make positive contributions to their
families and communities. We support a comprehensive portfolio of
genetic, biological, clinical, behavioral, and social research related
to the aging process, healthy aging, and diseases and conditions that
often increase with age. We also carry out the crucial task of training
the next generation of researchers who specialize in understanding and
addressing the issues of aging and old age.
Approximately 39 million people age 65 and older live in the United
States, and data from the Federal Interagency Forum on Aging-Related
Statistics indicate that their numbers will double within 25 years. In
less than 50 years, the number of ``oldest old''--people ages 85 and
older--may quadruple. As record numbers of Americans reach retirement
age and beyond, profound changes will occur in our economic,
healthcare, and social systems.
TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT
NIA supports a comprehensive portfolio of research that builds upon
basic discovery to develop new preventive, diagnostic, and therapeutic
interventions for age-related diseases and conditions. For example,
investigators with the Alzheimer's Disease Neuroimaging Initiative
(ADNI) have found that changes in the structure of the hippocampus, a
brain area important to learning and memory, may reflect disease
progression and effectiveness of potential treatments, and have
established biomarker and imaging measures that may predict risk for
cognitive decline and conversion to dementia. Clinical, imaging, and
biological data from ADNI are available to qualified investigators
around the world; over 1,700 researchers have signed up for access to
the ADNI database, and global collaborations have resulted in over 170
published scientific papers since 2004.
NIA-supported research to identify Alzheimer's disease (AD)
biomarkers and gain a deeper understanding of the disease's pathology
and clinical course has made possible the first revision of the
clinical diagnostic criteria for AD in 27 years through a joint effort
of the NIA and the Alzheimer's Association. Unlike the criteria that
doctors and researchers have been using since 1984, the updated
guidelines cover the full spectrum of the disease as it gradually
changes over many years, from the earliest preclinical stages before
symptoms are apparent through mild cognitive impairment (MCI) and
advanced dementia. The new guidelines also address the use of imaging
and biomarkers to determine whether changes in the brain and body
fluids are due to AD.
Even under the new guidelines, however, diagnosis of AD remains
complex. NIA intramural investigators are working toward development of
an accurate, noninvasive, inexpensive blood test for AD. Last year,
they found that the amount of a protein called clusterin in the blood
of AD patients reflected the severity of disease, predicted the
progression of memory impairment, and may predict brain amyloid burden
long before the patient develops memory problems. These findings were
recently replicated by independent researchers, and research is ongoing
in this promising area.
A continuing translational research success story for NIH is the
ongoing development of the compound exendin-4. NIA intramural
investigators originally developed exendin-4 as a treatment for type 2
diabetes, but have since found that exendin-4 may act as a
neuroprotective agent in animal models, and they are now conducting a
phase II/III clinical trial of the compound in patients with MCI and
early AD. NIA also supports over 40 drug discovery and development
projects through our AD Translational and Drug Discovery Initiative,
including a number of AD pilot clinical trials.
Other NIA-supported researchers are pursuing the development of
interventions that will delay disease and dysfunction and even extend
lifespan. Investigators with the innovative Interventions Testing
Program found that the drug rapamycin, used to help prevent rejection
of transplanted organs in humans, extended life span in middle-aged
mice, and more recently demonstrated that the drug exerts beneficial
effects early in life. Rapamycin inhibits the mTOR pathway, which helps
regulate cell growth and proliferation. Building upon these findings,
in 2010 NIA began soliciting research to identify and characterize
molecular targets within the mTOR pathway with potential to impact
health span and lifespan.
NIA also partners with other agencies and organizations on
translational initiatives. For example, with the Administration on
Aging, NIA has established an initiative to support development of
evidence-based interventions, programs, policies, practices, and tools
that can be used by community-based organizations to help elderly
individuals remain healthy and independent in their own homes and
communities. NIA is also joining ``ambassadors'' from organizations
interested in the health and well-being of older people to promote
Go4Life, our new exercise and physical activity website
(www.nia.nih.gov/Go4Life.)
TECHNOLOGIES TO ACCELERATE DISCOVERY
New GWAS (genome-wide association study) technologies are
transforming our understanding of the origins of disease and disability
by facilitating rapid comparisons of the full genomes of thousands of
individuals. This research may lead to the identification of novel
disease pathways that can be targeted to develop new treatments. In the
largest GWAS ever conducted in AD research, scientists with the AD
Genetics Consortium found that a previously unconfirmed gene variant,
BIN 1, affects development of late-onset AD and identified four
additional genetic variants significant for the disease. The genes
identified by this study may implicate pathways involved in
inflammation and the movement of proteins and lipids both within and
between cells as being important in the disease process. In a another
large GWAS, NIA intramural researchers joined an international research
consortium to confirm six previously identified genes for Parkinson's
disease and identify five new genes or loci (an area on the chromosome
where a gene is thought to be located).
A new NIA-supported initiative is underway to develop technologies
to better understand the life span and fate of cells in various tissues
of aged mammals. In these studies, cells are permanently marked at a
specific point in the organism's life and those marked cells are
followed to determine their fate and traits over time. These studies
will provide important insights into aging at the cell and tissue
levels.
USING SCIENCE TO INFORM HEALTH CARE REFORM
Research that will lead to the identification of more effective and
less expensive clinical interventions is a high priority for NIA,
particularly through a broad portfolio of comparative effectiveness
research (CER). A major CER effort has been NIA's administration, on
behalf of the Agency for Health Care Research and Quality and the
Office of the DHHS Secretary, of an initiative identifying ways that
principles of behavioral economics could be used to encourage
healthcare providers to incorporate findings from CER studies into
their practices. Other ongoing CER studies include a randomized trial
of behavioral economic interventions to reduce risk of cardiovascular
disease; a study comparing various motivators to increase HIV
screening; and a study comparing the effects of an intensive exercise
program vs. stretching and range of motion exercises on ambulation in
hip fracture patients.
Surprisingly little definitive evidence exists on the impact
insuring the uninsured has on their health-related behaviors (including
healthcare usage) and outcomes. However, NIA-supported investigators
are currently taking advantage of a remarkable opportunity to develop
such evidence. For a brief period in 2008, Oregon opened a waiting list
for enrollment in its previously closed public health insurance program
for certain low income adults, and then offered randomly selected
people the opportunity to enroll. By comparing individuals who obtained
health insurance through this program with otherwise eligible
individuals who were not selected in the ``insurance lottery,'' the
investigators are assessing the impact of insurance on healthcare usage
and health outcomes, including the differing impacts on different
groups. Understanding the consequences of health insurance coverage
will be central to evaluating proposals to expand or modify health
insurance coverage in the United States.
Recently, NIA-supported investigators studying older populations in
the United States, England, and 11 European countries found that
retirement prior to age 65 was associated with a significant decline in
cognitive performance. The investigators suggest that this may be in
part because for many people retirement leads to a less stimulating
daily environment, and the prospect of retirement reduces the incentive
to engage in mentally stimulating activities on the job. It is possible
(although not yet proven) that the recent trend of American workers
delaying retirement may eventually lead to improved cognitive
performance in this group.
NEW INVESTIGATORS, NEW IDEAS
As the American population grows older, the need for healthcare
professionals who specialize in the unique needs of older individuals
is becoming ever more urgent. To address this increase in demand
effectively, we must foster the development of physician-scientists
whose research will lead to improved care and more effective treatment
options for older patients with complex medical conditions. Recently,
NIA established the Grants for Early Medical/Surgical Subspecialists'
Transition to Aging Research (GEMSSTAR) program to support physicians
who seek to become clinician-scientists in geriatric aspects of their
subspecialty. We anticipate supporting 18 to 20 emerging physician-
scientists in this program.
Once again, thank you. I welcome your questions.
______
Prepared Statement of Roger I. Glass, M.D., Ph.D., Director, Fogarty
International Center
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget for the Fogarty International
Center (FIC). The fiscal year 2012 budget of $71,211,000 reflects an
increase of $1,835,000 over the comparable fiscal year 2011
appropriation of $69,376,000.
When it comes to global health, there is no ``them''--only ``us.''
\1\ In an increasingly interdependent world, the United States and
nations around the globe share diseases, as well as the burden that
these diseases inflict on healthy people. In fact, the interests of the
American people are well-served when the United States promotes global
health, as healthy nations are more likely to succeed in economic
development and enjoy political stability. In addition, Americans have
a strong humanitarian tradition and have long supported efforts to
improve the health of people around the world. The U.S. Government
(USG) has recognized these realities, and has made global health a
national priority. For these investments to yield the maximum benefit
however, U.S. and foreign scientists must work together to generate the
scientific evidence that will inform how best to allocate resources.
These researchers will contribute the necessary local expertise and
knowledge to thwart pandemics and fight diseases that prevent societies
from achieving their full potential. They will also empower nations to
more effectively improve the health of their own populations. The
Fogarty International Center plays a unique role at the National
Institutes of Health (NIH) and in the USG by supporting the development
of global health research expertise in the United States and abroad.
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\1\ Global Health Council, Washington, DC.
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NEW INVESTIGATORS, NEW IDEAS
Research advances are more likely occur when investigators study
diseases onsite to develop health interventions that are responsive to
local and international priorities. Therefore, Fogarty supports long-
term research and training partnerships between United States and low-
and middle-income country (LMIC) research institutions, which has
resulted in the training of more than 5,000 researchers--many of whom
contribute to major scientific advances. For example, the first results
from a large clinical trial testing candidate microbicides that use
anti-retrovirals (ARVs) found that the incorporation of an ARV into a
vaginal gel was more than 50 percent protective against HIV infection
when used as directed. This advance is a key step toward empowering
women with a safe and effective HIV prevention tool. Notably, six of
the study's authors are current or former Fogarty-sponsored trainees.
To increase the pool of physicians who have the necessary skills to
conduct robust and critical health research, and to support country-
driven efforts that enhance the sustainability of gains made under
PEPFAR, Fogarty is also administering a major new program called the
Medical Education Partnership Initiative (MEPI)--a joint effort of the
Office of the Global AIDS Coordinator, HRSA, DOD, USAID, CDC, and NIH.
MEPI supports institutions in Sub-Saharan African countries and their
U.S. partners to develop new models of medical education, and to
strengthen the ability of medical students and faculty to conduct
research that responds to the health needs of their countries.
Non-communicable diseases--such as heart disease, stroke, cancer,
and diabetes--are in fact the leading causes of worldwide mortality,
accounting for 60 percent of all deaths. According to the World Health
Organization, 80 percent of this burden is in LMICs, where these
diseases affect people disproportionately during their most
economically productive years. Fogarty is addressing this challenge
through its expanded program on Chronic, Non-Communicable Diseases and
Disorders across the Lifespan, which will support training of in-
country scientists to conduct research on these diseases. Given the
high burden of non-communicable diseases in the United States,
knowledge gained from these research activities can inform domestic
efforts to prevent and treat these diseases--particularly in low-
resource settings.
Fogarty also supports the training of U.S. investigators to conduct
global health research and actively engage in international scientific
collaborations. These investments directly respond to the overwhelming
demand for global health opportunities on university campuses across
the United States, and are helping early career scientists to build
long-term relationships and acquire skills that will help to ensure
that the United States continues to be a global leader in health
innovation.
ENHANCEMENT OF EVIDENCE BASE FOR HEALTH CARE DECISIONS
There is a tremendous gap between scientific advances and health
outcomes in the developing world. Therefore, there is an urgent need to
bridge the gap between what we know and what we do. Fogarty has
expanded support for research training in implementation science, which
generates knowledge and methods to better integrate research findings
and proven health interventions into health policy and practice.
For example without a significant shift in global prevalence
patterns, smoking is projected to cause roughly 8 million deaths
annually by 2030; notably, more than 80 percent of these deaths will
occur in LMICs. Fogarty's International Tobacco and Health Research and
Capacity Building Program addresses the critical role of research and
local research capacity in reducing the global burden of tobacco
consumption and the need to generate a solid evidence base that can
inform effective local tobacco control strategies and health policies.
The program supports epidemiological and behavioral research, as well
as prevention, treatment, communications, implementation, health
services and policy research. In Delhi, India, researchers are testing
the efficacy and cost-effectiveness of a community-based behavioral
intervention for tobacco cessation among youth living in low-income
communities. Such studies can inform efforts to curb adolescent smoking
in the United States--particularly in resource-poor settings.
Another example is Fogarty's International Implementation,
Clinical, Operational, and Health Services Research Training Award for
AIDS and Tuberculosis program, which supports training of scientists
and health professionals in developing countries to conduct research-
related to implementation of prevention, care and treatment
interventions for HIV and/or TB. Researchers supported by this program
recently made a significant discovery regarding the treatment of
patients with both HIV/AIDS and TB. In these resource-limited settings,
a high proportion of patients begin antiretroviral therapy (ART) while
on TB treatment, and paradoxical tuberculosis-associated immune
reconstitution inflammatory syndrome (TB-IRIS) is a frequent
complication of the ART. To address this disease management challenge,
investigators in South Africa found that a 4-week course of prednisone
reduced the need for hospitalization and therapeutic procedures, and
hastened improvements in symptoms, performance, and quality of life--
all without excess adverse events.
Fogarty has also partnered with the Bill and Melinda Gates
Foundation and the Foundation for NIH on a study that examines the
relationship between malnutrition and intestinal infections, and also
the consequences of these conditions on various aspects of child health
and development. Investigators across multiple international research
sites seek to facilitate the design of more targeted, cost-effective
interventions that will reduce the burden of child morbidity and
mortality from diarrheal diseases. One area of focus is the impact of
malnutrition, along with damage to the gut (from repeated and
persistent episodes of diarrheal disease), on the effectiveness of
childhood vaccines. In many low-resource settings, the immunity
conferred by various vaccines is significantly lower than in high-
income countries. A better understanding of the links between nutrients
and the health and function of the intestinal immune system will likely
lead to the development of targeted and modified vaccine formulations
and delivery strategies (e.g., dosing, schedules) for improved control
of intestinal infections.
TECHNOLOGIES TO ACCELERATE DISCOVERY
With increasing globalization, the need to monitor, diagnose and
respond to epidemics has risen dramatically. Since 1998, Fogarty has
supported partnerships between the United States and LMIC research
institutions to increase the capacity of biomedical scientists to
design, access and use modern information technology in support of
health sciences research. These partnerships are training biomedical
and behavioral scientists, engineers, clinicians, librarians, and other
health professionals to access, manage, analyze, and share biomedical
information electronically. They are also training individuals who will
be capable of developing new informatics applications. This will
increase the ability of local scientists and institutions to conduct
multi-site clinical trials and perform international disease
surveillance and prevention programs. Several Fogarty-supported
informatics projects have now reached new levels of maturity, expanding
to form regional networks and leveraging tools and lessons learned to
benefit more researchers. For example, a program in Brazil is sharing
its materials with Mozambique, where Portuguese is also the national
language. Researchers in Peru are building a Latin American training
network, and a university in South Africa is forming a consortium to
strengthen biomedical informatics throughout Africa.
TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT
Fogarty's International Cooperative Biodiversity Groups program
supports natural products drug discovery and ethnomedical and
botanicals research. Investigators supported by this program are
generating new and exciting leads from natural products that may result
in new therapeutics for a range of diseases. For example, a promising
new weapon in the war against malaria may come from seaweed found in
Fiji, as discovered by Fogarty grantee Dr. Julia Kubanek, a chemical
ecologist at the Georgia Institute of Technology. She and her team
discovered that a type of red algae in Fiji has strong anti-malarial
properties. Animal studies have begun to further explore the compound's
potential as a new therapeutic.
In conclusion, to effectively confront complex health issues that
transcend national boundaries, more scientific collaborations must be
developed and strengthened. Deep regional expertise enables Fogarty to
facilitate these scientific collaborations. In the context of advancing
science and health, Fogarty seeks opportunities to bridge differences
between countries that might otherwise not engage and to build trust by
encouraging scientists from around the world to work together to
address shared health challenges. These partnerships promote goodwill,
stability and peace, and effectively harness science for diplomacy. As
the world continues to become more interdependent, international
scientific partnerships will play a critical role in building bridges
and in improving health for people worldwide. Working in partnership
with rest of the NIH, Fogarty's unique programs will continue to enable
scientists in the United States and abroad to work together to tackle
the most pressing and complex health challenges of our time.
______
Prepared Statement of Dr. Kenneth Warren, Ph.D., Director, National
Institute on Alcohol Abuse and Alcoholism
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute on Alcohol Abuse and Alcoholism (NIAAA), of the National
Institutes of Health (NIH). The fiscal year 2012 budget includes
$469,197,000 for the NIAAA, which reflects an increase of $11,304,000
over the fiscal year 2011 level of $457,893,000, comparable for
transfers proposed in the President's request.
ALCOHOL AND HEALTHCARE--TRANSFORMING THE LANDSCAPE
NIAAA-supported research is leading to dramatic changes in the
understanding of alcohol-related problems and their prevention and
treatment across the lifespan. By translating this research into new
and better prevention and treatment approaches we have the ability to
reduce the heathcare burden due to alcohol and enhance the well-being
of individuals, their families, and society-at-large.
SCOPE OF THE PROBLEM
According to the World Health Organization, alcohol is among the
ten leading causes of death and disability worldwide; and according to
the Centers for Disease Control and Prevention (CDC), alcohol is also a
major cause of preventable death and disability in the United States.
As the United States. implements healthcare reform, it is important to
recognize that alcohol misuse costs our Nation an estimated $235
billion annually.\1\
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\1\ Rehm J, et al. The Lancet 373(9682): 2223-2233, June 27, 2009-
July 3, 2009.
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The consequences of alcohol misuse can affect both drinkers and
those around them at all stages of life. NIAAA's National Epidemiologic
Survey on Alcohol and Related Conditions (NESARC) estimates that almost
18 million people in the United States. ages 18 and older suffer from
alcohol abuse or dependence (collectively known as alcohol use
disorders, AUDs). The highest prevalence of alcohol dependence, which
encompasses a broad spectrum of disease ranging from a single episode
of a few years duration to a chronic relapsing disorder, occurs among
18-24 year olds. Of note, more than 85 percent of individuals with an
AUD do not have another drug use disorder. Returning war veterans
represent a particularly vulnerable population for developing AUDs that
co-occur with Post Traumatic Stress Disorder (PTSD) and other mental
health problems. Chronic, heavy alcohol use can damage tissues and
organs, most notably in the brain, liver, heart, pancreas, and
esophagus. According to the CDC, in 2007, alcoholic liver disease
accounted for over 14,000 deaths and in 2008 was responsible for nearly
20 percent of U.S. liver transplants.
Alcohol misuse can also have second hand effects, both direct
effects of alcohol exposure such as damage to the developing embryo due
to drinking by the pregnant mother, as well as indirect effects
experienced by individuals other than the drinker such as car crashes,
sexual assault, and violence. According to an analysis of NIAAA's
NESARC, one in four children grow up in a household where alcohol is a
problem, putting them at risk for short and long-term adverse physical
and psychological health outcomes.
Research to Practice
NIAAA-supported research is increasing our understanding of how to
identify and address alcohol-related problems across the lifespan.
Research shows that early identification and intervention are key to
reducing future health problems and can dramatically reduce healthcare
and other costs for individuals who misuse alcohol and those around
them.
The Value of Screening and Brief Intervention
The medical and economic value of screening and brief intervention
(SBI) to identify and address high risk drinking behavior early has
been well documented. In fact, according to an analysis in the American
Journal of Preventive Medicine, SBI for alcohol misuse was ranked
similarly in cost-effectiveness to screening for colorectal cancer and
hypertension, and to influenza immunization. Using NIAAA's A
Clinician's Guide: Helping Patients Who Drink Too Much, SBI can be
performed efficiently and effectively by primary care clinicians. By
intervening early, providers are able to offer their patients more
appealing, accessible options to address their alcohol problems,
options that are less resource intensive and less expensive than those
needed to treat more severe forms of dependence. For individuals who
want to assess and address their drinking behavior on their own, NIAAA
has developed an interactive Web site and booklet, Rethinking Drinking,
http://rethinkingdrinking.niaaa.nih.gov. These tools offer evidence-
based information about risky drinking patterns, the alcohol content of
drinks, and the signs of an alcohol problem, along with other resources
to help people who choose to cut back or stop drinking. Tools such as
Rethinking Drinking may benefit those who could ultimately recover from
dependence without treatment by decreasing the severity and duration of
dependence. For others it may provide the motivation to seek
professional help.
Underage and College Drinking
According to the Substance Abuse and Mental Health Services
Administration, more than one-fourth of 16-17 year olds drank in the
past 30 days, and 17 percent engaged in binge drinking, i.e. drinking
more than five drinks on an occasion. For 18-20 year olds, over one-
third engaged in binge drinking in the past 30 days. According to The
Surgeon General's Call to Action to Prevent and Reduce Underage
Drinking, each year underage drinking results in the death of about
5,000 people under the age of 21 from alcohol-related injuries. This
number is equivalent to the incoming freshman class at Virginia Tech,
and greater than the total student body at the United States Naval
Academy. Given the widespread use of alcohol and high prevalence of
binge drinking by children and adolescents, and the link between early
alcohol use and later problems including alcohol dependence, it is
important to identify children and adolescents who are at high risk for
alcohol use and/or alcohol use disorders. NIAAA will soon release an
easy to use two question screener and guide for pediatricians and other
clinicians who provide medical care to children and adolescents. This
empirically based screening instrument is devised to identify children
at elevated risk for using alcohol as well as those who have already
begun to experiment or are more heavily involved with alcohol. In
addition to identifying individuals who need any level of intervention,
health practitioners can also use the screening process to provide
information to patients and their parents about alcohol's effects on
the developing body and brain. In collaboration with other Federal and
non-Federal partners NIAAA will implement and evaluate the new guide.
Alcohol use is also a serious public health and safety problem
among college students with adverse consequences that range from poor
academic performance to alcohol poisoning. NIAAA has an ongoing
research focus on reducing college drinking and its consequences.
Research encompasses both individual approaches, such as screening and
brief intervention in college health centers, and environmental
approaches including studies on college and community policies. NIAAA
has also established a College Presidents Working Group to advise the
Institute.
Exploiting Technology to Improve Treatment
For those who need treatment, NIAAA seeks to provide more and
improved options. Individuals experience alcohol differently, for some
it provides almost immediate euphoria, others can drink much higher
quantities yet feel relatively little effect. Both types may be at risk
for developing alcohol dependence. Clinical trials with alcohol
dependent patients testing a variety of medications suggest that, just
as their physiological response to alcohol differs, so too does their
response to a specific treatment; and genes appear to be responsible,
at least in part, for these differences. Given that alcohol dependence
is a complex disorder influenced by multiple genes, along with the
evidence that specific treatments only work for subsets of individuals,
NIAAA continues to seek additional medications that target different
molecules and pathways in the brain. A number of medications currently
prescribed for other indications are being evaluated as
pharmacotherapies to reduce heavy drinking including: the mood
stabilizing drug quetiapine, the antiepileptic drug levetiracetum, the
smoking cessation drug varenicline and the anti-nausea drug
ondansetron. Recently, clinical trials with ondansetron revealed that
individuals with specific variations in a gene which encodes the
serotonin transporter respond better to treatment than individuals
without these variants. Similarly, individuals with a specific variant
in the mu opioid gene respond better to the FDA-approved alcohol
dependence treatment naltrexone than those lacking the variant. The
identification of additional medications, along with the knowledge of
what works for whom, will soon make personalized treatment for alcohol
dependence a reality. NIAAA's efforts to make testing of compounds more
efficient, its active role in engaging the pharmaceutical industry in
concert with its willingness to test novel compounds, and its work with
the FDA to improve guidelines and methodology for alcohol clinical
trials have greatly accelerated the pace of medications development for
alcohol dependence.
In parallel, NIAAA is exploiting technological advances in genomics
to determine the multiple underlying genetic signatures that contribute
to the range and severity of alcohol use disorders. As part of the next
NIAAA NESARC, DNA samples will be collected from an estimated 46,000
people for use in genome-wide association analyses. The level and
complexity of information derived from new, large-scale, comprehensive
genomic studies will facilitate our ability to correlate genetic make-
up with subtypes of alcohol dependence improving our ability to match
patients with treatments.
Treating the medical consequences of heavy chronic drinking is also
a priority. For example, currently liver transplantation is often the
only viable option for treating advanced liver disease but it is a
prolonged, expensive and risky process only available to patients who
maintain abstinence. To expand treatment options, NIAAA is supporting
studies to test a number of compounds that target progressive stages of
liver disease including fatty liver and liver fibrosis. In addition,
seminal research is providing a better understanding of why some
individuals develop liver cirrhosis whereas others who consume similar
amounts of alcohol do not. Over-activation of the body's natural repair
mechanisms may actually promote liver disease, suggesting new targets
for prevention and treatment of alcoholic and non-alcoholic liver
disease.
______
Prepared Statement of Stephen I. Katz, M.D., Ph.D., Director, National
Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget for the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National
Institutes of Health (NIH). The fiscal year 2012 budget includes
$547,891,000 which is $14,002,000 more than the comparable fiscal year
2011 appropriation of $533,889,000.
INTRODUCTION
NIAMS addresses diseases that affect individuals of all ages, of
all racial and ethnic backgrounds, and across all economic strata; many
disproportionately affect women and minorities. Some are rare
disorders, but many are very common, and all have a major impact on the
quality of people's lives. Twenty-five years of NIAMS-funded research
has contributed greatly to a variety of new treatment and prevention
strategies that are reducing the burden the diseases place on
individuals, their families, and society.
LEVERAGING BASIC SCIENCE TO IMPROVE PATIENT CARE
NIAMS research has been the basis for the development and testing
of many new medications, including biologic therapies for autoimmune
diseases. The newly approved drug belimumab, the first lupus treatment
to receive U.S. Food and Drug Administration approval in over 50 years,
interferes with a molecule that NIAMS-funded researchers showed to be
involved in the immune dysfunction that characterizes this disorder.
Other, more recent basic research results suggest another existing
drug, omalizumab, may prevent lupus-associated kidney damage. NIAMS
investigators in Bethesda, Maryland, are planning to start testing the
drug's safety for lupus patients soon.
Basic research into disease mechanisms also is explaining why some
therapies do not work as well as expected. In 2003, investigators were
baffled when two NIAMS-funded clinical trials showed that combining two
medications (a bisphosphonate and parathyroid hormone) that each
improve bone mass and prevent fractures did not help people any more
than either drug did individually. Eight years later, research into the
mechanisms by which bisphosphonates preserve bone revealed that they
interfere with parathyroid hormone's bone-forming activity. This
discovery can help physicians choose drug regimens that are best for
their patients.
DEVELOPING TOOLS TO DIAGNOSE AND MONITOR DISEASE
Improvements in bone health have underscored the importance of
identifying which of the 40 million Americans \1\ who have low bone
mass are most likely to break a bone. Several large, NIAMS-funded
studies have indicated that spine fractures predict both future spine
fractures and debilitating hip fractures. Researchers recently
published evidence that women who have mild spine defects may also be
at risk of hip fractures and could benefit from lifestyle changes or
drugs that prevent bone deterioration. However, the ability to
distinguish between deformities related to fragile bones and those from
other causes is critical. If imaging tools that are under development
can make this distinction, clinicians will be better able to predict
patients' risk and monitor responses to therapies. Also, the new tools
potentially could reduce the cost of clinical trials by allowing
investigators to assess a medication's effects relatively quickly.
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\1\ Looker AC, et al. J Bone Miner Res. 2010 Jan;25(1):64-71. PMID:
19580459.
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Other researchers are testing whether a specific type of magnetic
resonance imaging can predict worsening of knee arthritis. Preliminary
work--using images that are available to the research community through
a public-private partnership supported by the NIH and various
companies--is promising. If confirmed, clinicians could use the
technology to identify patients whose knee cartilage is likely to
rapidly deteriorate due to osteoarthritis. Moreover, like the imaging
tools mentioned above, the discovery and validation of structural
changes that researchers can visualize could lead to shorter, more
efficient trials of promising disease-modifying agents that may help
the more than 27 million Americans \2\ who have osteoarthritis pain in
their knees or other joints.
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\1\*Lawrence RC, et al. Arthritis Rheum. 2008 Jan;58(1):26-35.
PMID: 18163497.
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Many diseases within the NIAMS mission involve pain, fatigue, and
other difficult-to-measure symptoms. A test to quantify changes in
these parameters could enhance clinical outcomes research and,
ultimately, clinical practice. NIAMS is one of several NIH components
engaged in the Patient-Reported Outcomes Measurement Information System
(PROMIS) initiative to develop such a tool. In addition to managing
PROMIS on behalf of the NIH, NIAMS encourages researchers to use the
resource. For example, NIAMS is funding a study to test questions for
fibromyalgia patients, along with information collected through PROMIS,
for development of disease-specific measures that allow investigators
and healthcare providers to monitor patients more effectively.
APPLYING GENETICS, GENOMICS, AND OTHER CUTTING-EDGE RESEARCH TO NEW
TREATMENTS
Researchers have been trying to determine for decades if pain and
itch send different signals to the brain. Difficulties distinguishing
the two symptoms at molecular and cellular levels had hindered this
effort, but a group of NIAMS investigators finally identified an itch-
specific molecule. Their work also illuminated a previously elusive
mechanism by which the itch message travels through the spinal cord to
be perceived by the brain. Such a discovery should pave the way for
studies into how chronic itch develops, and make it possible, for the
first time, to design better treatments.
Research is providing hope to patients with epidermolysis bullosa
(EB), a group of rare, inherited blistering skin conditions. When
investigators repaired the genetic defect in an EB patient, NIAMS-
funded scientists wondered if gene therapy might also work for another
form of the disease. The strategy seemed promising in a mouse model of
recessive dystrophic EB (characterized by large, painful blisters, open
wounds, and early death due to cancer). A first-in-human clinical trial
will begin this year.
NIAMS also is funding a Phase I clinical trial that suggests that a
different gene transfer approach may correct the molecular defect
underlying type-2 limb-girdle muscular dystrophy (LGMD-2D). The study,
supported through one of the Senator Paul D. Wellstone Muscular
Dystrophy Cooperative Research Centers, demonstrated that the procedure
could safely produce the corrected protein for at least 6 months. The
data provide a framework that investigators can use when designing
subsequent LGMD-2D clinical trials. Furthermore, researchers can
leverage the study's findings about immune responses as they develop
gene-based therapies for other diseases.
In the past 12 months, muscular dystrophy researchers also have
made considerable progress toward understanding the genetic
underpinnings of facioscapulohumeral muscular dystrophy (FSHD). Prior
findings from an NIH-funded FSHD patient registry showed that the
disease is associated with a shorter-than-normal series of repeated
genetic sequences. Recent technologic advances enabled researchers to
identify a genetic pattern within these sequences in FSHD patients.
This discovery, combined with findings that the defects cause FSHD by
activating a gene and allowing its product to accumulate in muscle, are
enabling new directions that will accelerate progress. For example,
researchers can now engineer animal models of the disease, something
that they could not do without a basic understanding of the genes
involved.
Like FSHD, many health problems are influenced by complex genetic
factors. Over the last few years, the ability of genome-wide
association (GWAS) approaches to identify gene variants related to
disease risk has matured from an intriguing concept to a widely used
scientific tool. These analyses can require thousands of patients, and
often entail data sharing among NIAMS-funded researchers and scientists
around the globe.
An international GWAS team including researchers at the NIH
Clinical Center showed that a gene involved in the body's immune
response underlies a person's susceptibility to a painful, inflammatory
condition called Behcet's disease, which primarily affects people of
Asian, Middle Eastern, Turkish, or European descent. The gene linked to
Behcet's disease is associated with other conditions for which
treatments exist or are being developed. Because of this connection,
therapies might be available sooner than if the investigators had found
a completely new disease mechanism.
In the past year, other genetic studies uncovered additional,
shared links among diseases. Investigators discovered that rare
variants of a gene encoding the enzyme sialic acid acetylesterase are
associated with rheumatoid arthritis and type 1 diabetes, and may play
a role in other autoimmune diseases. Likewise, researchers leveraging
the NIAMS-sponsored National Alopecia Areata Registry found that genes
associated with rheumatoid arthritis and type 1 diabetes are linked to
the development of alopecia areata, a disease in which the body's
immune system attacks the hair follicles and causes hair loss. As with
Behcet's disease, the possibility of a common mechanism is particularly
exciting because drugs under development for other diseases might also
be effective against alopecia areata.
GWAS also holds promise for understanding the genetic differences
that give rise to more common diseases, such as osteoporosis. The NIAMS
dedicated funds from the American Recovery and Reinvestment Act of 2009
toward developing a resource that investigators can use to identify
molecular changes that influence bone health. The discovery of gene
variants that protect against osteoporosis or increase a person's risk
of having low bone mass is likely to suggest targets that researchers
can pursue when exploring new ways to prevent fragility fractures.
Moreover, investigators could use genetic markers to identify
appropriate participants for clinical trials. Data from this effort is
likely to be available to the wider research community at the end of
this year.
CONCLUSION
Twenty-five years ago, a few months after Congress passed the
Health Research Extension Act of 1985 (Public Law 99-158), the NIH
established the NIAMS. Over the past two and one-half decades, the
increased emphasis on research on arthritis and musculoskeletal and
skin disorders has benefited nearly every household in our Nation. We
are proud of the scientific advances that our researchers have made
toward helping people who have diseases of the bones, joints, muscles,
and skin, and are excitedly looking forward to the discoveries they
will make in the future.
______
Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D., Director,
National Institute of Biomedical Imaging and Bioengineering
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the
National Institutes of Health (NIH). The fiscal year 2012 budget is
$322,106,000, which is $8,573,000 more than the fiscal year 2011
appropriation of $313,533,000. This statement is submitted with the
recognition of the Department's notification to the Congress of an NIH
reorganization that would establish a new National Center for Advancing
Translational Sciences and reallocate the remaining portions of the
National Center for Research Resources to other parts of NIH, including
NIBIB.
The mission of NIBIB is to improve human health by leading the
development and accelerating the application of biomedical
technologies. NIBIB invests resources in scientific and technological
research opportunities at the convergence of the quantitative and life
sciences, and in training the next generation of researchers. The
Institute is at the forefront of translating scientific advances into
engineered medical solutions. Ultimately, NIBIB seeks to realize
innovations that address healthcare challenges, reduce disease
mortality and morbidity, and enhance quality of life. To accomplish
this goal, NIBIB continues to fund bold and far-reaching projects that
facilitate discovery and translate basic science into new and better
healthcare.
TRANSLATIONAL SCIENCE AND THERAPEUTICS DEVELOPMENT
Biodegradable Home-Based Vaccination System.--Influenza is a major
cause of morbidity and mortality worldwide. Despite vaccination
campaigns, the CDC attributes 36,000 deaths and 226,000
hospitalizations per year in the United States to influenza, with an
associated cost of approximately $100 billion per year. The number of
cases could be greatly reduced if more people were vaccinated and if
the vaccine was more effective. Researchers at the Georgia Institute of
Technology are addressing both issues by developing a bio-dissolvable
micro-patch that will allow people to vaccinate themselves. The patch
is painless, has an application time of just seconds, has no
biohazardous waste, does not require refrigeration for storage, and
develops an enhanced immune response to flu. The patch combines cutting
edge technology and user-friendly simplicity to address this
significant public health problem.
Noninvasive Image-Guided Therapy: Focused Ultrasound.--NIBIB
supports research to develop and promote innovative image-guided
therapies. One of these technologies is High-Intensity Focused
Ultrasound (HIFU). HIFU is a non-invasive, image-guided and controlled
new therapy delivery system which consists of a highly focused beam of
high-intensity ultrasound that is capable of ablating tissue in a
targeted region of the body, without harming surrounding tissues.
Researchers are combining magnetic resonance imaging and HIFU to form
an image-guided therapy delivery system for non-invasive tumor
ablation, which can either replace or complement surgery or radiation
therapy. In addition, transcranial transmission of HIFU can also induce
the opening of the blood-brain barrier, which allows delivery of drugs
directly to specific locations in the brain. HIFU for treatment of
uterine fibroids is now an FDA-approved clinical procedure. These
developments could revolutionize surgery, cancer therapy and the
delivery of therapeutic agents in new targeted approaches.
Regenerative Medicine for Wounded Warriors.--The NIBIB is the lead
NIH institute for participation in the U.S. Military's signature Armed
Forces Institute for Regenerative Medicine (AFIRM), now in its third
year. AFIRM is a multi-institutional, interdisciplinary network to
develop advanced treatment options for our wounded servicemen and
women. Researchers are addressing many severe medical conditions
including burns, compartment syndrome, complex craniofacial injuries,
limb/digit salvage, and wound healing.
TECHNOLOGIES TO ACCELERATE DISCOVERIES
Monitoring Tumor Cells and Cancer Biology.--NIBIB Quantum Grant
investigators have successfully developed a test capable of detecting a
single cancer cell among the billions of normal cells in a blood
sample. The microchip device, known as the HB-Chip (after the micro
herringbone pattern on the chip surface), enables the isolation of rare
circulating tumor cells that may be the source of cancer metastasis.
Subsequent molecular characterizations of these cells have led to the
discovery of several subtypes of prostate, breast, and lung cancer.
These subtypes serve as the basis for customized cancer treatments that
are tailored to specific patients. The isolation and characterization
of circulating tumor cells has the potential to revolutionize the
management of care in cancer patients. Recently, Johnson & Johnson
announced a partnership with the researchers at Massachusetts General
Hospital to further develop and market this blood test. ``Stand Up to
Cancer,'' an organization focused on translational cancer research, is
supporting four leading cancer centers to launch clinical trials using
the HB-Chip to determine the sensitivity and specificity of the device
for various cancers.
Global Technologies for Disease at the Point of Care.--NIBIB has
partnered with the Department of Biotechnology and the Ministry of
Science and Technology in India to support the development of low-cost
diagnostic and therapeutic technologies that will be used in
underserved communities worldwide. As the prevalence of chronic
diseases in low-resource settings increases, PATH (Program for
Appropriate Technology in Health, a nonprofit organization that
improves the health of people around the world) is working on new
initiatives to tackle diabetes. NIBIB-supported researchers are
evaluating cost-effective technologies to monitor and screen for
gestational and type 2 diabetes in India. These technologies are also
applicable to rural and low resource settings in the United States and
can lead to more effective interventions and therapies.
In the United States, about 500 mothers die every year during
childbirth, and in Africa, childbirth-related deaths are nearly 300,000
annually. Many of these deaths could be prevented if these populations
had ready access to ultrasound exams, which identify mothers at high
risk for birth complications. In addition, cardiovascular disease and
abdominal illnesses could be broadly monitored and managed with wide
access to ultrasound exams. NIBIB has supported the successful
development by GE of a hand-held battery powered portable ultrasound
system (VSCANTM) that costs approximately $8,000 but has the
features of a conventional hospital or office based system costing
approximately $200,000. The broad goal is to make ultrasound imaging as
available as stethoscopes, to facilitate earlier detection and
monitoring response to therapies.
TECHNOLOGIES TO IMPROVE EVIDENCE-BASED CLINICAL DECISIONS
Patients routinely receive their healthcare at multiple locations
ranging from physician's offices to major medical centers. For optimal
care, medical records and medical imaging studies must be readily
available at different sites. To address the need for sharing of images
and to enhance the adoption of evidence and comparative effectiveness
in clinical decisions, NIBIB has funded several coordinated projects.
Patient Controlled Web-Based Access and Sharing of Medical
Images.--A contract with the Radiological Society of North America
(RSNA) includes five academic institutions: UCSF, University of
Maryland, Mayo Clinic, University of Chicago, and Mount Sinai. Two
additional grants provide support to Wake Forest University and the
University of Alabama at Birmingham. Each of these projects is
developing an approach to patient-controlled medical image sharing
systems for secured image sharing among radiologists and clinicians
across organizational boundaries. The project at Wake Forest University
has a special focus on image sharing in rural and under-served areas.
Validation testing of patient health records that can accept images
with the appropriate controls and privacy safeguards has begun and will
start enrolling patients in the near future.
On Line Decision Support Systems.--NIBIB is providing resources to
the Brigham and Women's Hospital and the Massachusetts General Hospital
to implement information technology systems that include clinical
decision support capability. These systems enable the care providers to
make clinical decisions that are based on the best available evidence
and the patient's comprehensive medical data set, including clinical
images.
NEW INVESTIGATORS, NEW IDEAS
Nanoparticles for Improved Drug Delivery: Overcoming the Mucus
Barrier.--The delivery of bioactive molecules to target tissues can
significantly improve drug effectiveness while reducing side effects by
concentrating medicine at selected sites in the body. While the barrier
properties of mucus provide protection against infection and other
potentially toxic particles, they also have thwarted efforts to achieve
uniform and sustained drug delivery to mucosal surfaces, and have
likely prevented successful delivery of genes that could potentially
treat fatal diseases, such as cystic fibrosis. The work of NIBIB
grantee Dr. Justin Hanes at Johns Hopkins University seeks to
understand the properties of mucosal barriers and use this knowledge to
guide the development of polymeric nanoparticulate carriers capable of
more efficient drug and gene delivery to the respiratory tract, female
reproductive tract, gastrointestinal tract, surface of the eye, and
other mucosal tissues for improved therapies. The delivery of bioactive
molecules to target tissues can significantly improve drug
effectiveness while reducing side effects by concentrating medicine at
selected sites in the body.
Robotic Prostheses for Amputees.--Despite significant technological
advances over the past decade, state-of-the-art transfemoral prostheses
are unable to provide power for joint motion. The absence of joint
power significantly impairs the ability of these prostheses to restore
many locomotive functions, including walking upstairs and up slopes,
running, and jumping, all of which require significant net positive
power at the knee joint, ankle joint, or both. Dr. Michael Goldfarb, an
NIBIB Edward C. Nagy Young Investigator, recently reported the
development of the first robotic transfemoral prosthesis with fully
powered knee and ankle joints. The device allows above-the-knee
amputees to walk 25 percent faster with less energy than is expended
with conventional prosthetics and provides increased balance, agility,
and recovery reflexes to prevent falls. In April, Freedom Innovations
announced a worldwide licensing agreement for exclusive rights to
commercialize this device.
The Institute's emphasis on interdisciplinary approaches to
biomedical research has provided unprecedented opportunities for
collaborations among the life and physical scientists leading to
advances in biology and medicine through the quantitative, physical
sciences, and engineering perspective, as well as the development of
technologies that reflect the translation of biological mechanisms.
These advances will produce remarkable improvements in the health of
individuals around the world.
______
Prepared Statement of Alan E. Guttmacher, M.D., Director, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD) of $1,352,189,000. This reflects an increase of $35,466,000
over the fiscal year 2011 level of $1,316,723,000.
In my short time as NICHD Director, the breadth and importance of
the Institute's mission have already impressed me. Our research changes
clinical practice and improves health for many people, particularly
those who may be under-represented in medical research--pregnant women
and their offspring; adolescents; and people with intellectual,
developmental, and physical disabilities. Our research shows that even
simple approaches can have significant impact. For example, a recent
study found that an inexpensive program teaching newborn care to
Zambian midwives reduced deaths in the first week of life by 40
percent. Today, I would like to highlight a few other examples of
NICHD's recent progress toward improving health, and describe a new
effort to position our research to continue to contribute to a
healthier Nation and world.
IMPROVING HEALTHCARE FOR WOMEN AND CHILDREN
Thanks partly to NICHD research, Centers for Disease Control and
Prevention (CDC) data show that the preterm birth rate in the United
States declined for the second year in a row in 2008. Still, 12 percent
of all pregnancies end in preterm birth, a leading cause of infant
death in our country. Preterm infants have greater risk for breathing
problems, life-threatening infections, cerebral palsy, and
developmental disabilities. In recent years, NICHD research showed that
treating pregnant women with a prior history of preterm birth with a
type of progesterone reduced their risk of another preterm delivery.
Now, a new study shows that a vaginal gel containing another type of
progesterone substantially reduces the risk of premature delivery in
women with a short cervix. With adoption of such treatments, the
preterm birth rate should drop further.
Spina bifida, which occurs when the fetal spinal column does not
close properly, affects nearly 1,500 U.S. infants a year, according to
the CDC. The most common and severe form of spina bifida,
myelomeningocele, can cause paralysis, problems with nerve function,
and brain damage. Recently, the NICHD reported an important trial, the
Management of Myelomeningocele Study (MOMS). MOMS researchers compared
standard surgical repair of the spinal cord after birth to repair while
the fetus is in utero. They found that repairing the spinal cord in the
womb greatly reduced risk of death and the need to divert fluid from
the brain. It also doubled the chance of walking and improved later
motor and cognitive development. Infants undergoing prenatal surgery,
however, were also more likely to be born preterm, and their mothers
more likely to experience a uterine tear in childbirth. While
researchers continue to study this specialized surgery, the initial
findings promise to improve the quality of life for thousands of
children.
New findings also can improve healthcare for women: NICHD
researchers recently showed that women's cholesterol levels correspond
with monthly changes in estrogen levels. On average, the total
cholesterol level of the women studied varied 19 percent over the
course of the menstrual cycle. Although previous data showed that
estrogen-containing oral contraceptives or menopausal hormone therapy
could affect cholesterol levels, this was the first study to show
conclusively that the cyclical levels of naturally occurring hormones
have similar effects. This natural variation suggests that clinicians
should consider the phases of a woman's monthly cycle when evaluating
her cholesterol levels and before prescribing treatment to help protect
women against heart disease.
NEW TECHNOLIGES ADVANCE HOPE FOR AUTISM AND PARKINSON'S
Autism spectrum disorder (ASD) encompasses a range of conditions
involving impaired social interactions and communication, atypical
behaviors, and health problems. While ASD is known to have genetic
components, researchers have not identified a consistent pattern of
variant genes. In fact, dozens of gene variants, along with other
factors, are now linked with ASD, complicating, but also advancing, our
understanding of the condition and ability to develop new treatments.
Using advanced imaging technology, NICHD-supported researchers
identified a gene that impairs communication between parts of the
brain. Additional genetic studies may reveal ASD subtypes and how
certain genes function and interact with each other. This research
could help individualize treatments based on a child's genetic profile.
New technologies also hold promise for other neurologic conditions,
such as Parkinson's disease, which results from a loss of brain cells
that help coordinate movement. NICHD-supported researchers injected
stem cells from the endometrium (lining of the uterus) into the brains
of mice with a laboratory-induced form of the disease. These new cells
took over the function of the brain cells eradicated by Parkinson's.
This is the first time that scientists showed endometrial stem cells
could assume the properties of the tissue into which they were
transplanted. Since endometrial stem cells are widely available, this
suggests that women with Parkinson's disease might serve as their own
stem cell donors, or healthy endometrial stem cells might be stored and
later matched to individuals with the disease.
TRANSLATING SCIENCE TO ADVANCE REHABILATION
Applying basic scientific findings to clinical problems can help
scientists develop new diagnostics or therapeutics for many conditions.
For instance, NICHD researchers seeking to understand how the vitamin
folate is metabolized found that the vitamin appears to promote healing
in rats with damaged spinal cord tissue. Up to 20,000 people yearly
suffer a spinal cord injury, and about 200,000 people currently live
with such injuries, according to the National Center for Injury
Prevention and Control. Folate, a B vitamin that naturally occurs in
leafy green vegetables and other foods, plays an important role in
early embryonic brain and spinal cord development. Further
translational studies on folate could lead to new techniques to help
regenerate nerve fibers and heal damaged nervous system tissue.
THE NATIONAL CHILDREN'S STUDY (NCS)
The NCS is designed to examine the effects of genetic factors and a
broad range of environmental factors such as physical environment and
family, community, and cultural influences on the development and
health of children in the United States over time. The NCS will yield a
rich repository of environmental and genetic/genomic data and
biospecimens that can be mined by scientists for years to come and help
answer questions concerning the earliest origins of health and disease.
Over the past year, the NCS has been in a pilot phase, known as the
``Vanguard Study,'' enrolling about 650 children in 37 sites as of
February 2011. Three separate recruitment strategies are being tested
to optimize participation and cost management. During the coming year,
a range of experts will review ongoing findings, allowing staff to
develop, by late summer 2011, evidence-based cost-estimates and
recommendations for the initial phase of the Main Study.
VISION FOR THE FUTURE
The NICHD has embarked on crafting a vision for the future that
inspires the institute and its partners to achieve critical scientific
goals and meet pressing public health needs. In early 2011, in a series
of workshops, we asked leading scientific and health experts to
identify what the scientific future should look like in 10 years and
what knowledge must be obtained to reach these new frontiers. We
focused on such areas as plasticity, development, cognition, behavior,
reproduction, pregnancy and pregnancy outcomes, developmental origins
of health and disease, environment, and diagnostics and therapeutics.
Resultant white papers are posted on our website for additional public
comment. In June, we will assemble another diverse group of experts to
refine these concepts and identify those that are most promising. We
will publish the final vision document by early 2012, helping to ensure
that NICHD addresses the most important science for the Nation's women,
children, families, and individuals with special needs.
Mr. Chairman and members of the Committee, thank you for your
continued support of NICHD's important work. I would be pleased to
respond to any questions.
______
Prepared Statement of Nora Volkow, M.D., Director, National Institute
on Drug Abuse
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute on Drug Abuse (NIDA). The fiscal year 2012 budget of
$1,080,018,000 includes an increase of $30,377,000 over the comparable
fiscal year 2011 level. The following statement updates NIDA's
scientific progress in addressing drug abuse and addiction. These
public health problems cost our society more than $600 billion annually
in health- and crime-related costs and losses in productivity, not to
mention incalculable personal and social devastation (ONDCP 2004; Rehm
et al. 2009; CDC 2007). NIDA has crossed a threshold into a new
research era, unprecedented in its scope, and transformative in its
prevention, treatment, and policy implications for substance use
disorders (SUDs).
RETURN ON INVESTMENT: TECHNOLOGIES TO SPEED DISCOVERY
New technologies and scientific breakthroughs continue to generate
actionable information about the genetics, chemistry, and circuitry of
the human brain. This knowledge has dramatically enhanced our
understanding of the underlying vulnerabilities and the long-term
effects of addiction on neurophysiology and behavior. Continuing
advances in DNA sequencing and analytical tools have transformed the
landscape of genomic exploration. For example, we can now engage in
high resolution and accurate sequencing of vast genomic tracts, from
many different individuals, to systematically search for and identify
addiction risk variants, which may open up new targets for medications.
Also, we are dissecting the epigenetic processes that can affect gene
expression through persistent but reversible changes. Epigenetics
research has started to help explain the deleterious impact of known
environmental risk factors, like poverty or chronic stress, on
vulnerability for SUDs. The burgeoning availability of genetic,
epigenetic, and environmental data heralds new opportunities for
translational applications. NIDA is committed to optimizing this
potential through harmonization efforts that help ensure the
comparability of pooled data.
Harmonized databases are crucial for individualized medicine. This
is clear in the genomics field, but also in the emerging field of
globally connected biomarkers, or the ``human connectome,'' and for
brain imaging. NIDA is supporting research to develop biomarkers to
screen for drug exposure and addiction vulnerability that would be more
accurate, reliable, and sensitive than current tests (i.e. bodily
fluids, hair, questionnaires) and would help transform the way SUDs are
identified and treated.
Other innovations, such as wireless remote sensing and virtual
technologies, offer opportunities for transforming how prevention
messages, real-time monitoring, and even some treatment modalities are
delivered to the public. Having real-time, objective measures of drug
use could have a huge impact on SUD treatments. One example is remote
physiological monitoring (RPM), a rapidly evolving form of telemedicine
that can track patients' health status (e.g., heart rate, blood
pressure, skin temperature, and glucose levels) remotely, using devices
that can store and transmit the results in real-time. NIDA is
supplementing studies on the use of RPM for monitoring drug use to
evaluate the effects of treatment interventions and their relationship
to clinical outcomes. Such data could support the establishment of non-
abstinence endpoints, which in turn could inform the Food and Drug
Administration (FDA) addiction medications approval process.
EMERGING PSYCHOACTIVE THREATS TO PUBLIC HEALTH
The past few years have witnessed several alarming trends,
particularly prescription drug abuse. Although opioid analgesics are
among the most effective medications for pain management, they are also
associated with serious and growing public health problems, including
drug abuse, addiction, and overdose deaths. The Substance Abuse and
Mental Health Services Administration reports a six-fold increase in
treatment admissions for opioid analgesics, from nearly 20,000 in 1998
to about 120,000 in 2008, while the Centers for Disease Control and
Prevention acknowledge that unintentional poisonings involving opioid
analgesics have more than tripled from 1999 through 2007, exceeding the
total number of deaths involving heroin and cocaine. These trends
illustrate the challenge of balancing access to critical medications
for those who need them and preventing their abuse, particularly when
the public does not perceive their dangers and has much greater access
to them from a decade-long surge in availability. In 2009, 202 million
opioid prescriptions were dispensed in the United States making opioids
the most prescribed class of medications. NIDA is committed to helping
reverse this trend by providing information on the patterns and
motivations behind their abuse, sponsoring research on developing pain
medications with less abuse potential, and creating curricula to
minimize diversion through better prescribing practices.
Lingering public misperceptions, particularly among youth, continue
to hinder our marijuana prevention efforts. The latest Monitoring the
Future survey of 8th, 10th, and 12th graders reveals that daily
marijuana use is up for all grades. These teens are not only at higher
risk of becoming addicted, but they are functioning below optimal level
at a time when their future depends on peak cognitive performance. Why
is this happening now? We do not know for sure, but it is reasonable to
infer that the public debates surrounding medical marijuana have
increased confusion and lowered the perception of risk, an important
factor in curtailing use.
Meanwhile, new drugs routinely emerge and gain rapid notoriety
thanks to the Internet. Recent examples include ``bath salts'' and
``spice,'' which are synthetic stimulants and cannabinoids,
respectively.
IMPROVING PUBLIC HEALTHCARE--DELIVERY AND PERFORMANCE
NIDA will continue to leverage our knowledge base into better
strategies for battling addiction. To further this goal, NIDA takes
advantage of collaborative research infrastructures designed to deploy
proven strategies rapidly and effectively. For example, NIDA's Drug
Abuse Treatment Clinical Trials Network (CTN) tests evidence-based
treatments in community settings with diverse patient populations,
optimizing the utility and cost-effectiveness of treatments and
fostering their adoption. Similarly, NIDA's Criminal Justice-Drug Abuse
Treatment Studies (CJ-DATS) network promotes multilevel collaborations
to bring proven treatment models into the criminal justice system,
disproportionately affected by both drug abuse and HIV. These
infrastructures allow for the broad testing of promising new
strategies. One example, called ``Seek, Test, and Treat,'' has great
potential to improve the public health by expanding access to HIV
testing and treatment, and ultimately reducing HIV spread.
Another cornerstone of our strategy is to engage physicians as
``frontline'' responders to patient substance abuse, providing the
science-based tools they need to identify potential substance abuse in
their patients and offering better options for treatment. Recent
research shows, for example, that compared with methadone,
buprenorphine results in fewer neonatal abstinence symptoms among
babies born to opioid-addicted mothers, and is associated with
decreased hospital stays and thus, costs. To bolster education in the
treatment of pain, NIDA is leading a multi-Institute effort to create
Centers of Excellence (CoEs) to develop curricula for medical students,
nurses, resident physicians, and others. Part of our NIDAMED physician
outreach initiative, CoEs have also developed and are helping to
disseminate substance abuse training curricula, woefully neglected in
most medical training. NIDA continues to encourage physician screening
of drug abuse with the help of a Web-based interactive screening tool
that generates clinical recommendations. The broad availability of
these resources is an important step toward integrating substance abuse
screening, brief intervention, and referral to treatment (SBIRT) into
medical care, which will enable better healthcare decisions and
outcomes.
TRANSLATION--THERAPEUTICS DEVELOPMENT
To help those affected by the disease of addiction, we need to
expand the pharmacological and behavioral tools available to treat
SUDs. Thus, medications development is one of the main areas that
benefits from new discoveries. For example, the century-old practice of
vaccination has recently been found to be a viable approach for
treating addiction. In this case, the body itself is coaxed to produce
antibodies that bind a drug while still in the bloodstream, blocking
its psychoactive effects in the brain. Already, a nicotine vaccine that
reduces craving and withdrawal symptoms is in advanced stages of
development and will be market-ready following approval by the FDA.
Another strategy has been the development of long-acting, or depot,
formulations of medications that serve to overcome poor compliance. One
example is Vivitrol, an extended-release opioid antagonist
(naltrexone), recently FDA-approved for treating opioid addiction. NIDA
is now testing the use of depot medications in high-risk groups, such
as criminal justice offenders, and in regions of the world that have
high rates of HIV infection and are resistant to treatment with opioid
agonist medications.
In parallel, NIDA is supporting research on drug combinations, an
effective strategy for treating many diseases (e.g., HIV/AIDS, cancer)
and one starting to show success with addiction. For example, the
combination of lofexidine (a hypertension medication) and marinol (a
synthetic form of marijuana's THC) shows promise in treating withdrawal
symptoms among marijuana-addicted individuals. Early results also
suggest that a buprenorphine-naltrexone combination could be effective
in treating cocaine addiction.
NEW INVESTIGATORS, NEW IDEAS
To help sustain our commitment to the next generation of biomedical
research scientists, NIDA supports multiple training initiatives at
various career levels and areas of need (e.g., physician scientists,
computational neuroscience, and medicinal chemists). Examples include
efforts aimed at mentoring minority investigators and international
HIV/AIDS researchers, as well as multi-Institute training programs. To
identify and encourage the next generation of addiction scientists,
NIDA also awards special prizes at the annual Intel International
Science and Engineering Fair to high school students whose projects
exemplify excellent achievement in addiction science.
In closing, NIDA pledges to continue to tackle the emerging and
significant public health needs related to drug abuse and addiction,
taking advantage of unprecedented scientific opportunities to close the
gaps in our knowledge base and develop and disseminate more effective
strategies to prevent and treat drug abuse and addiction.
______
Prepared Statement of James F. Battey, Jr., M.D., Ph.D., Director,
National Institute on Deafness and Other Communication Disorders
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's budget request for the National Institute on
Deafness and Other Communication Disorders (NIDCD) of the National
Institutes of Health (NIH). The fiscal year 2012 NIDCD budget of
$426,043,000 includes an increase of $11,244,000 over the comparable
fiscal year 2011 appropriation of $414,799,000. This statement is
submitted with the recognition of the Department's notification to the
Congress of an NIH reorganization that would establish a new National
Center for Advancing Translational Sciences (NCATS).
The NIDCD conducts and supports research and research training in
the normal and disordered processes of hearing, balance, smell, taste,
voice, speech, and language. Our Institute focuses on disorders that
affect the quality of life of millions of Americans in their homes,
workplaces, and communities. The physical, emotional, and economic
impact for individuals living with these disorders is tremendous. NIDCD
continues to make investments to improve our understanding of the
underlying causes of communication disorders, as well as their
treatment and prevention. It is a time of extraordinary promise, and I
am excited to be able to share with you some of NIDCD's ongoing
research and planned activities on communication disorders.
AFFORDABLE HEARING HEALTHCARE
Hearing loss is a serious public health issue and has significant
social and economic impacts. Approximately 17 percent of American
adults, or 36 million individuals, report a hearing loss, and only
about one in five of those individuals who could benefit from a hearing
aid wears one. Additionally, hearing healthcare and hearing aids are
only rarely covered by health insurance, and are not covered by
Medicare. A recent industry survey found that the average cost per
hearing aid to an individual is $1,600, and for many, the cost is much
higher. Hearing aids are also consumable devices, often requiring
replacement every 4-6 years, and frequent battery replacement. This
makes hearing aids potentially the third highest cost item for an
individual, following just behind the purchase of a home and car. In
2009, NIDCD sponsored a workshop, Accessible and Affordable Hearing
Health Care for Adults with Mild to Moderate Hearing Loss, to examine
the factors that contribute to hearing healthcare access,
affordability, and usage; and to develop a set of research objectives
which could be explored in the future. Based on the recommendations,
NIDCD published several targeted research initiatives for hearing
healthcare: to explore new approaches that could lead to improved
access, assessment, and intervention; to develop methods to determine
the success of new or improved approaches; and to create small business
technologies to improve access for underserved patients. The research
supported through these and other NIDCD-sponsored efforts will enhance
the evidence-base for hearing healthcare decisions, and provide a
strong research base for future policy decisions related to affordable
hearing healthcare.
TINNITUS
Tinnitus--a perceived ringing, buzzing or roaring in the ears--is a
major public health concern, affecting more than 25 million American
adults. It can range in severity from a mild condition, requiring no
medical intervention, to a severe debilitating disease with significant
physical, emotional, and economic impacts. The Department of Veterans
Affairs reports tinnitus as the most prevalent service-connected
disability for veterans receiving disability compensation. More than
744,000 veterans received service-connected disability compensation for
tinnitus in fiscal year 2010, presenting a significant cost burden for
the Nation. Past research has shown that tinnitus is often associated
with hearing loss; however, little is known about the specific neural
dysfunctions that lead to the disorder. There are also limited
treatment options available, and their effectiveness varies widely. In
response to this need, NIDCD is supporting a strong research portfolio
on tinnitus. In 2009, NIDCD sponsored a research symposium, Brain
Stimulation for the Treatment of Tinnitus, to explore the potential
translation of existing brain stimulation technologies for the
treatment of tinnitus. Recently, NIDCD supported scientists have
demonstrated that stimulation of the vagus nerve (a large nerve that
runs from the head to the abdomen) with an implantable electrode, in
combination with the playing of tones, is able to ``reset'' the brain,
eliminating tinnitus in a rat model of the disease. (Vagus nerve
stimulation is already in use for the treatment of epilepsy and
depression in more than 50,000 individuals). By varying the tones
played and the co-stimulation of the vagus nerve, scientists were able
to abolish the tinnitus sensation and restore the normal function of
the brain. These exciting findings are the first demonstration of a
treatment that specifically erases the tinnitus, rather than simply
masking the sound or providing coping mechanisms for the individual.
Scientists are now working to translate these findings from the animal
model into a novel therapeutic strategy for people with severe
tinnitus.
VESTIBULAR PROSTHESIS
Based on the recent 2008 National Health Inventory Survey, Balance
and Dizziness Supplement, about 15.5 percent of U.S. adults, or about
33.6 million individuals, reported they had a problem with dizziness or
balance in the past 12 months. Balance disorders are one of the reasons
older people fall, and falls and fall-related injuries, such as hip
fracture, can have a serious impact on an older person's life. One
balance disorder which has been particularly difficult to treat is
Meniere's disease. This disorder causes severe dizziness (vertigo),
tinnitus, hearing loss, and a feeling of fullness or congestion in the
ear. NIDCD estimates that approximately 615,000 individuals in the
United States are currently diagnosed with Meniere's disease and that
45,500 cases are newly diagnosed each year. While many individuals are
able to manage the symptoms associated with Meniere's disease through
diet, drugs, or surgery, up to 2 in 10 do not find adequate relief from
their symptoms after exhausting all treatment options. NIDCD-supported
scientists are working to adopt cochlear implant technologies to
produce a vestibular implant that could counteract vertigo attacks that
persist despite other treatments. Scientists have already demonstrated
the ability of a vestibular implant to induce, and provide recovery
from, vertigo attacks in animal models of Meniere's. Most recently,
scientists have translated this technology to humans and performed
their first implantation into an individual. While clinical trials are
still several years away, this recent breakthrough provides hope to
many for whom traditional treatments have failed.
STUTTERING
The popularity of the recent Academy Award winning movie, ``The
King's Speech,'' has brought to light the communication challenges
faced by approximately 3 million Americans each day. Stuttering can
affect individuals of all ages, but occurs most frequently in young
children between the ages of 2 and 6, with boys 3 times more likely
than girls to stutter. Most children, however, outgrow their
stuttering, and it is estimated that less than 1 percent of adults
stutter. For those individuals who continue to stutter into adolescence
and adulthood, there are limited treatment options. NIDCD supports a
research portfolio on stuttering to understand the underlying genetic,
neurologic, and physiologic causes of stuttering, to predict which
children will continue to stutter, and to develop novel and effective
therapies for treatment of stuttering. Recently, NIDCD intramural
scientists pinpointed the first specific genes that underlie
stuttering. Building on previous studies which identified a genetic
region linked to stuttering, and harnessing new technologies in genetic
sequencing, the researchers found mutations in three genes important in
the recycling of cellular breakdown products inside cells. Different
mutations in two of these genes are related to severe metabolic
disorders, called mucolipidosis II and III, which cause joint,
skeletal, heart, liver, and other health problems, including speech
problems. The findings may result in the development of new drug
therapies for individuals who stutter.
OLFACTORY DEFICITS EARLY WARNING OF ALZHEIMER'S DISEASE
For several years, it has been know that individuals with
Alzheimer's disease (AD) often exhibit an impaired sense of smell
(olfaction), making a smell screening test an attractive opportunity
for development as a biomarker of disease. However, it was not known
why AD impacts olfaction. Recently, NIDCD-supported scientists used a
mouse model of AD to identify pathological changes in the olfactory
system very early in the animals' lives, indicating a sensitivity of
the olfactory system to this type of damage. These changes manifested
well in advance of the onset of changes in other areas of the brain
involved in memory, and were predicted by the animals' performance on a
smell discrimination task. In addition, NIDCD-supported scientists have
used brain imaging of humans to examine changes in brain activity
during smell discrimination tasks. These imaging studies have
identified a significant blunting of response in individuals with AD.
Both of these discoveries could lead to new, non-invasive tools to
enhance the early diagnosis of AD, and better inform healthcare
decisions for affected individuals.
NEW STRATEGIC PLAN FOR NIDCD
NIDCD has initiated the development process for a new Strategic
Plan. In March 2011, NIDCD convened a series of working groups of
scientific experts in the smell and taste; voice, speech, and language;
and hearing and balance fields to advise us on emerging scientific
opportunities in four priority areas: understanding normal function of
communication systems; understanding diseases and disorders of
communication systems; improving diagnosis, treatment, and prevention
of communication disorders; and accelerating translation of research
findings into practice. In addition, we remain committed to continuing
our leadership in fostering the development of new investigators in the
communication sciences. Our staff is currently working to compile these
priority areas into a document that will guide our research investments
from fiscal year 2012 through 2016. A draft will be made available for
public comment later this year and we anticipate publication of our new
Strategic Plan in January 2012.
Mr. Chairman, I would like to thank you and Members of this
Subcommittee for giving me the opportunity to present examples of
recent research progress and to highlight some programs made possible
through your support of the NIDCD.
______
Prepared Statement of Dr. A. Isabel Garcia, D.D.S., M.P.H., Director,
National Institute of Dental and Craniofacial Research
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Dental and
Craniofacial Research (NIDCR) of the National Institutes of Health
(NIH). The fiscal year 2012 budget request for NIDCR is $420,369,000,
which reflects an increase of $11,113,000 over the fiscal year 2011
enacted level of $409,256,000 comparable for transfers proposed in the
President's request.
The NIDCR goal of improving the Nation's dental, oral, and
craniofacial health is an ambitious one. It demands that we address the
wide array of diseases and conditions that affect the oral cavity and
craniofacial structures, including diseases such as dental caries
(tooth decay) and periodontal diseases that are endemic in the United
States, as well as birth defects such as cleft lip and palate, chronic
oral-facial pain conditions, oral and pharyngeal cancers, and oral
manifestations of systemic diseases, such as Sjogren's syndrome,
diabetes, and HIV infection. NIDCR is committed to identifying
effective preventive, diagnostic, and treatment approaches for these
diseases and conditions. Today, I will describe how we are investing in
basic discovery and preclinical studies across these myriad areas and
applying new knowledge to the development of clinical trials and
studies in humans.
ACCELERATING BASIC DISCOVERY
Joshua Lederberg, who shared the 1958 Nobel prize for discovering
that bacteria can mate and exchange genes, once quipped about microbes
that ``you know one when you see it.'' The problem, he explained, is
that microbes were largely ``invisible'' and noticed only after their
damage had been wrought. NIDCR-supported researchers and others
recently identified--made ``visible''--more than 600 distinct microbial
species as residents of the human mouth. NICDR scientists are also
systematically exploring how the individual bacterial species assemble
into biofilms. Biofilms are the living, mat-like microbial communities
found on many parts of the human body, including our teeth and gums,
and play a major role in the development of dental and oral disease.
Microbial biofilms can form on any surface, including on medical
devices, and are implicated in more than 80 percent of human
infections. The oral cavity offers tremendous potential both as a
diagnostic window and an easily accessible model for research aimed at
understanding the host of bacteria associated with biofilm-mediated
disease throughout the body. Researchers now possess the tools to
extract a biofilm sample and determine the identities of most of its
microbial inhabitants.
Recently, NIDCR grantees devised a new fluorescent imaging system
that successfully distinguished among 28 oral microbes within a single
field of view and that soon will be able to distinguish among at least
100, providing spatial analysis in three dimensions. Enhanced imaging
of the oral biofilm will accelerate discovery in studies of biofilm
formation, organization, and composition and thus the keys to their
control. This structural understanding will form the basis for research
aimed at development of tools to combat oral and other infectious
diseases and improve health.
An NIDCR grantee and colleagues recently performed a novel type of
systematic genetic analysis to better elucidate microbial behavior. The
researchers collected over 4,000 mutant bacterial strains and tested
them in 324 different environmental conditions. Pulling all the data
together, the scientists gained a fuller understanding of the
functional molecular networks governing bacterial response. They also
gleaned new information about a gene involved in antibiotic resistance
and the synergy of three common antibiotic drugs.
Both of the exciting advances described above were spearheaded by
young investigators on NIDCR training grants, offering prime examples
of the vital importance of continuing to support new investigators and
new ideas. NIDCR is committed to developing and strengthening the
workforce of researchers that can leverage the latest tools of
discovery and are dedicated to solving urgent problems in oral, dental
and craniofacial health. To enhance this critical pipeline further,
NIDCR continues to create innovative new training and career programs,
such as a new transition path for clinical researchers, as well as an
initiative to catalyze the formation of multidisciplinary teams led by
new investigators researching temporomandibular disorders and orofacial
pain.
TRANSLATING BASIC SCIENCE INTO IMPROVED PUBLIC HEALTH
Advances in studying oral microbial communities have the potential
for rapid impact on research for new, more personally targeted,
clinical treatment. A team of NIDCR-supported scientists recently
reported that a microbe called Scardovia wiggsiae appears to be linked
with severe forms of early childhood caries (ECC), the most prevalent
chronic childhood disease in the United States. For decades, the oral
bacterium Streptococcus mutans has been singled out as the primary
pathogen involved in ECC. The scientists found that S. wiggsiae often
was present in children with decayed teeth in the absence of S. mutans.
The discovery of this bacterium's role in ECC offers a future target in
efforts to identify children at risk and to prevent or stop progression
of this disease before it leads to destruction of the teeth.
The burden of craniofacial, oral, and dental disease, particularly
untreated disease, falls heaviest on lower socioeconomic status (SES)
groups, which include disproportionately large numbers of racial and
ethnic minorities. Researchers, including those at the five NIDCR-
supported Centers for Research to Reduce Disparities in Oral Health,
continue working to identify creative, practical approaches to deal
with pressing oral health issues, including ECC and oral and pharyngeal
cancer. These approaches must be inexpensive, easily applied, and
readily tailored to meet individual and community needs. Three of these
Centers recently initiated clinical trials to test new interventions to
prevent ECC among American Indian and Hispanic children and in
residents of public housing. Children in low SES families are
particularly vulnerable to ECC's painful and costly impact. Three
additional trials will launch in fiscal year 2012.
ENHANCING THE EVIDENCE BASE FOR ORAL HEALTH CARE
Tackling real-world clinical issues and generating evidence that
will be of immediate value to practitioners and patients is the central
goal of the NIDCR-supported dental Practice-based Research Networks
(PBRNs). Conducting research in dental practices draws on the
experience and insight of practicing clinicians to help identify and
frame research questions. Because PBRN studies address practice-based
problems, their results tend to be more quickly translated into daily
clinical care.
Leveraging the infrastructure of established dental practices for
conducting PBRN studies also can be a powerful and cost-effective means
to conduct clinical research. For example, the past decade brought
reports that people who take bisphosphonates, a class of drug
prescribed for osteoporosis or to treat the bone-wasting effects of
cancer, can develop osteonecrosis (bone death) of the jaw, or ONJ. To
address the problem, the three regional PBRNs, taking advantage of
their presence in practices spanning multiple States, teamed up to
carry out a collaborative study on ONJ. The study results, published in
2010, confirmed that bisphosphonate use is a risk factor for ONJ, and
provided additional important evidence to guide clinicians in their
treatment of this challenging condition.
In fiscal year 2012, NIDCR will launch a new National Dental PBRN.
This single network, more national in scope and more representative of
a greater variety of practice settings, will provide a framework to
study and improve the delivery of oral care and will build upon the
collaboration among the regional networks that was crucial to the
successes to date. Critical to this effort is an improved capacity to
collect data electronically. Using an adaptable electronic platform for
enhanced connectivity, data sharing, and communication within and
between networks will help providers conduct research effectively and
efficiently and strengthen the PBRN enterprise.
DEVELOPING NEW CLINICAL TREATMENTS
Each year, about 400,000 people worldwide are diagnosed with cancer
in the head and neck region. In an effort to identify new treatments
and improve the stagnant 5-year survival rate that hovers only slightly
above 50 percent, NIDCR scientists focused their research on the
immunosuppressive drug rapamycin. This research is now moving from the
basic and preclinical phases, which included studies in an NIDCR-
developed mouse model, to clinical studies. By fiscal year 2012,
scientists will be recruiting subjects for a clinical trial to assess
rapamycin's safety and efficacy in humans.
Research is also needed to combat harmful treatment side effects
for head and neck cancers. Many patients with head and neck cancers
will receive radiation therapy, which has the significant long-term
side effect of xerostomia (dry mouth). The salivary glands, damaged by
the radiation used to kill nearby tumor cells, can become less
permeable to the fluid that naturally flows through them and yield less
saliva, or stop working altogether. Many functional and quality-of-life
problems occur when oral tissues are deprived of saliva's protective
properties, including difficulty chewing and swallowing, burning mouth,
and greater risk of dental caries and oral fungal infections. Despite
continuing efforts to eliminate this problem, many patients continue to
suffer.
Moving from bench to bedside, NIDCR scientists began the first
gene-transfer study in people with radiation-induced xerostomia. The
transferred gene, Aquaporin-1, encodes a protein that conveys fluid by
forming pores, or water channels, in the cell membrane. The study
assesses whether the transferred gene will open water channels in the
duct cells, allowing the rapid movement of water through the duct. In
fiscal year 2012, NIDCR will issue an initiative to stimulate
additional research on restoring damaged salivary gland structure and
function to complement this important clinical advance.
As these highlights illustrate, NIDCR has made a strong commitment
to advancing oral health science through efforts in the laboratory, in
training sites, in dental practices, and in the community. This
investment is providing new tools and scientific approaches that may
greatly accelerate the next breakthroughs in oral health research.
NIDCR will continue to support research that provides new and exciting
leads that can translate into better ways to prevent, diagnose, and
manage oral, dental, and craniofacial diseases and disorders. In so
doing, NIDCR seeks to improve the oral health of the Nation.
______
Prepared Statement of Linda S. Birnbaum Ph.D., D.A.B.T., A.T.S.,
Director, National Institute of Environmental Health Sciences and
Health Services
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute of Environmental Health Sciences (NIEHS) of the National
Institutes of Health (NIH). The fiscal year 2012 budget includes
$700,537,000; an increase of $17,400,000 over the comparable fiscal
year 2011 enacted level of $683,137,000, comparable for transfers
proposed in the President's request.
INTRODUCTION
Good health is vitally important for all Americans, and it depends
on a clean and safe environment. Currently, our healthcare system
expends huge resources controlling a variety of diseases and
dysfunctions that are known to be at least partially connected with
environmental exposures: asthma, cancer, developmental disabilities,
neurological/cognitive deficits, heart attack, and many others.
Preventing these diseases through prevention of adverse environmental
exposures could make an enormous difference in reducing healthcare
costs. At NIEHS, and through NIEHS-funded projects in research
institutions across the United States, we are bringing all the tools of
biomedical science to bear on the fundamental questions of the effects
of environmental exposures to toxic substances on biological systems.
Environmental health science is advancing at a tremendous rate and new
tools--genetics, genomics, proteomics, metabolomics, informatics, and
computational biology, just to name some of these new disciplines--give
us new insights on how environmental effects happen in our bodies. They
also point the way toward technologies and testing procedures to
provide better and more timely information for the use of our agency
partners who are responsible for policy decisions and regulations.
ADVANCES IN TOXICOLOGY AND EXPOSURE ASSESSMENT
With our rapidly increasing understanding of the subtleties of
biological effects of environmental exposures, we are moving toward a
new kind of toxicological testing that is less expensive and time-
consuming than our current methods, and also gives us an improved
understanding of the actual effects on humans. Toxicology is becoming a
more powerful predictive science focused on making target-specific,
mechanism-based, biological observations. Alternative assays are
targeting the key pathways, molecular events, and processes linked to
disease or injury and incorporating them into a research and testing
framework. Our National Toxicology Program (NTP) at NIEHS is laying the
foundation for this new testing paradigm in partnership with the
National Human Genome Research Institute, the Environmental Protection
Agency, and the Food and Drug Administration. We are using quantitative
high-throughput screening assays to test a large number of chemicals.
The resulting data are being deposited into publicly accessible
relational databases. Analyses of these results will set the stage for
a new framework for toxicity testing.
The NIEHS-led Exposure Biology Program (EBP), part of the NIH
Genes, Environment and Health Initiative, has resulted in the
development of dozens of new technological advances for personalized
measurement of environmental exposures. At a recent workshop, EBP
investigators presented their prototypes: miniaturized personal
monitors for black carbon and other air pollutants; a wearable
nanosensor array for real-time monitoring of exposure to diesel and
gasoline exhaust; a personal aerosol sensor platform to link children's
exposures to asthma severity; personal exposure assessment systems for
chemical toxicants; gene expression biomarkers of airway response to
tobacco exposure; and biomarkers of organophosphate-linked proteins.
One prototype of a continuously operating wearable badge that provides
real-time measurements of chemical toxicants has attracted subsequent
R&D funding from the Department of Defense to develop this model for
use by military personnel. Others are being moved into validation
studies as a next step toward their deployment in environmental health
research.
EPIGENETICS, ENDOCRINE DISRUPTERS, AND ENVIRONMENTAL HEALTH
Our understanding of chemical toxicity has been challenged by the
new science of epigenetics, which is the study of changes to the
packaging of the DNA molecules that influence the expression of genes,
and hence the risks of diseases and altered development. Studies
indicate that exposures that cause epigenetic changes can affect
several generations.\1\ This new understanding heightens the need to
protect people at critical times in their development when they are
most vulnerable. NIEHS is making key investments in understanding basic
epigenetic processes and how they are influenced by environmental
factors. Recently, some of this work has provided a critical resource
for understanding and characterizing properties of human induced
pluripotent stem cells.\2\ The development of pluripotent stem cells
shows promise for research and clinical applications in lieu of
embryonic stem cells, but many questions remain to be answered about
their structure, utility, and safety. NIEHS-funded investigators have
established genome-wide reference maps of DNA methylation (an
epigenetic marker) and gene expression in previously derived human
embryonic cell lines and human iPS cell lines, to assess their
epigenetic and transcriptional similarity and predict their
differentiation efficiency. A separate report by another NIEHS-funded
group reported ``hotspots'' of aberrant epigenomic reprogramming in
human iPS cells.\3\ There are still many questions about the role of
these important epigenetic processes which will need to be answered
before iPS cells can be confidently used in research and therapy.
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\1\ Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic
transgenerational actions of endocrine disruptors and male fertility.
Science 308:1466-1469.
\2\ Bock C, Kiskinis E, Verstappen G, et al. (2011) Reference maps
of human ES and iPS cell variation enable high-throughpu
characterization of pluripotent cell lines. Cell 144(3):439-52.
\3\ Lister R, Pelizzola M, Kida YS, et al. (2011) Hotspots of
aberrant epigenomic reprogramming in human induced pluripotent stem
cells. Nature 471(7336):68-73.
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Related to the field of epigenetics is the key concept of ``windows
of susceptibility.'' Research shows that the developmental processes
that occur at fetal and early life stages are especially vulnerable to
disruption from relatively low doses of certain chemicals.\4\ \5\ \6\
We first saw this in the case of lead and other metals, such as mercury
and arsenic, which we learned decades ago could harm neurological
development as a result of fetal and childhood exposures. This concept
also applies to hormonally active agents which disrupt the endocrine
system. This is an active area of our research program. For example,
NIEHS and NTP are funding important studies to fill the gaps in our
knowledge about bisphenol A (BPA), a widely distributed compound used
in plastics, can linings, thermal paper, and more. NTP's Center for
Evaluation of Risks to Human Reproduction determined that there was
``some concern'' about effects to the brain, behavior, and prostate
gland in fetuses, infants, and children exposed to BPA.\7\ NIEHS is now
supporting an aggressive research effort to fill the research gaps in
this area, especially concerning BPA effects on behavior, obesity,
diabetes, reproductive disorders, development of prostate, breast and
uterine cancer, asthma, cardiovascular diseases and transgenerational
or epigenetic effects.
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\4\ Rogan WR, Ragan NB (2003) Evidence of effects of environmental
chemicals on the endocrine system in children. Pediatrics 112:247-252.
\5\ Dolinoy DC, Weidman JR, Jirtle RL (2007) Epigenetic gene
regulation: Linking early developmental environment to adult disease.
Reproductive Toxicology 23:297-307.
\6\ Committee on Environmental Health, American Academy of
Pediatrics (1999) Pediatric environmental health, 2nd edition, pp 9-23.
\7\ http://www.niehs.nih.gov/news/media/questions/sya-bpa.cfm See
``What does some concern mean?''.
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Any consideration of important public health issues in the United
States. has to include obesity. Environmental exposures are beginning
to be implicated in the obesity epidemic.\8\ \9\ NIEHS is supporting
research on the developmental origins of obesity and the theory that
environmental exposures during development play an important role in
the current epidemic of obesity, diabetes, and metabolic syndrome.
There are data showing weight gain in adult rats and mice following
developmental exposure to a number of different chemicals, such as
tributyltin compounds,\10\ which have been termed ``obesogens'' by some
researchers. A groundbreaking workshop on environmental factors in
obesity and diabetes was sponsored by NIEHS in January 2011. Many
research gaps still need to be filled, but if these early research
results are confirmed, we may find it more useful to expand our
approach to fighting obesity to include not just educating about diet
and lifestyle but also reducing early life exposure to these
``obesogenic'' chemicals that might be setting the stage for us to gain
weight later in life.
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\8\ Grun F, Blumberg B (2009) Endocrine disrupters as obesogens.
Mol Cell Endocrinol 304:19-29.
\9\ Verhulst SL, Nelen V, Hond ED, Koppen G, Beunckens C, Vael C,
Schoeters G, Desager K (2009) Intrauterine exposure to environmental
pollutants and body mass index during the first 3 years of life.
Environ Health Perspect 117:122-126.
\10\ Iguchi T, Watanabe H, Ohta Y, Blumberg B (2008) Developmental
effects: oestrogen-induced vaginal changes and organotin-induced
adipogenesis. Int J Androl 31:263-268.
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PLANNING FOR THE FUTURE
NIEHS recently began work on the development of a new Strategic
Plan to set goals for guiding our research investments over the next 5
years. Our process is designed to bring in information and perspectives
from a wide variety of sources: community members, advocacy groups,
agency partners, and scientists from all disciplines.
In summary, understanding the connection between our health and our
environment, with its mixture of chemicals, diet and lifestyle
stressors, is a complex and intricate scientific endeavor. At NIEHS, we
remain committed to leading the evolution of the field of environmental
health sciences to meet emerging public health challenges.
______
Prepared Statement of Thomas R. Insel, M.D., Director, National
Institute of Mental Health
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Mental
Health (NIMH) of the National Institutes of Health (NIH). The fiscal
year 2012 NIMH request of $1,517,006,000 includes an increase of
$40,981,000 over the fiscal year 2011 appropriated level of
$1,476,025,000. In my statement, I will underscore the impact that
mental disorders have on public health in the United States; outline
examples of NIMH's strategies for reducing the burden associated with
mental disorders; and, highlight examples of research activities that
are advancing us toward this goal. I submit this statement with the
recognition of the Department's notification to the Congress of an NIH
reorganization that would establish a new National Center for Advancing
Translational Sciences.
PUBLIC HEALTH BURDEN OF MENTAL ILLNESS
NIMH's mission is to transform the understanding and treatment of
mental illnesses through basic and clinical research, paving the way
for prevention, recovery, and cure. The burden of mental illness is
enormous. In 2009, an estimated 11 million American adults
(approximately 1 in 20) suffer from serious mental illness.\1\
According to the World Health Organization, mental disorders are the
leading cause of medical disability in the United States and Canada.\2\
In contrast to many other chronic medical conditions, mental disorders
typically begin at an early age, usually before the age of 30. Mental
disorders, such as schizophrenia, depression, and bipolar disorder, are
increasingly recognized as the chronic medical illnesses of young
people.
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\1\ SAMHSA. Results from the 2009 National Survey on Drug Use and
Health: Mental Health Findings (Office of Applied Studies, NSDUH Series
H-39, HHS Publication No. SMA 10-4609). Rockville, MD; 2010.
\2\ The World Health Organization. The global burden of disease:
2004 update, Table A2: Burden of disease in DALYs by cause, sex and
income group in WHO regions, estimates for 2004. Geneva, Switzerland:
WHO, 2008.
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The annual economic costs of mental illness in the United States
are enormous. The direct costs of mental health treatment represent an
estimated 6.2 percent of all healthcare spending,\3\ which, according
to the Centers for Medicare and Medicaid Services, totals 15.8 percent
of the gross domestic product. Indirect costs, which include all non-
treatment-related costs such as Social Security disability payments,
lost earnings, and incarceration, account for an even greater expense
than the direct costs associated with mental healthcare. A conservative
estimate places the total direct and indirect costs of mental illness
at well over $300 billion annually.\4\
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\3\ Mark TL, et al. National Expenditures for Mental Health
Services and Substance Abuse Treatment, 1993-2003. SAMHSA Publication
No. SMA 07-4227. Rockville, MD: SAMHSA, 2007.
\4\ Insel TR. Assessing the economic cost of serious mental
illness. Am J Psychiatry. 2008 Jun;165(6):663-5.
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NIMH's mission is not merely to reduce the symptoms and disability
associated with mental disorders, but to promote recovery, to extend
healthy life, and ultimately, to discover preventive interventions. In
the year ahead, NIMH will work toward this mission by fostering and
facilitating a collaborative approach across the spectrum of mental
health research approaches--from discovery to dissemination--to make a
positive change in the lives of people with mental disorders and their
families.
TECHNOLOGIES TO ACCELERATE DISCOVERY
Funding from the American Recovery and Reinvestment Act of 2009 has
enabled NIMH to support infrastructure development that will provide a
framework for future discoveries. One large, collaborative project that
promises to provide researchers with an invaluable reference tool is
the Transcriptional Atlas of Human Brain Development. This atlas is
mapping when and where genes are switched on and off during normal
brain development, because to understand disorders, scientists must
first understand what the normal patterns of gene expression are during
development. The atlas will contain data from 16 brain regions at 11
developmental stages--ranging from embryonic development to mid-
adulthood. These maps will highlight differences between prenatal and
postnatal brains, changes across adolescence, and unique patterns of
gene expression that only occur during development. The first maps from
the atlas were released this year and will form the foundation for
future maps and releases.
TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT
NIMH-funded researchers are working to translate discoveries from
basic science into targeted, rapidly acting therapeutics. Current
antidepressant medications and cognitive behavioral therapies often
require 6 to 8 weeks to have an effect. Previous NIMH research has
shown that the drug ketamine can reduce depression, including thoughts
of suicide, within 6 hours. However, long-term use is associated with
side effects, and the mechanism by which ketamine works remained
unclear, until NIMH-funded researchers made a significant discovery in
2010. They identified how the brain responds to ketamine, as well as
the molecular mechanism for this rapid response--the rapid activation
of an enzyme, mTOR, which regulates cell growth, proliferation, and
survival. The discovery of this cellular mechanism today helps point
the way to developing practical, rapid-acting treatments for depression
tomorrow.
In tandem with this cutting-edge discovery-to-treatment research,
NIMH is looking into ways to personalize and optimize current
treatments for depression. While effective interventions do exist,
there is considerable variation in individual treatment outcomes. The
Establishing Moderators/Mediators for a Biosignature of Antidepressant
Response in Clinical Care (EMBARC) study is working to develop a
collaborative approach among researchers who are focusing on biological
indicators (biomarkers) of depression. EMBARC researchers hope to
identify a standard set of biomarkers and other measures that can be
used to predict which interventions will produce the best treatment
outcomes for an individual. Taken together with our advancing knowledge
of ketamine, we can say with confidence that rapid, personalized, and
effective treatments for depression are close at hand.
ENHANCEMENT OF EVIDENCE-BASE FOR HEALTHCARE DECISIONS
NIMH's basic and translational research will improve U.S. public
health only when they lead to improved mental healthcare. To improve
the outcomes for people suffering from schizophrenia, NIMH is funding
the Recovery After an Initial Schizophrenia Episode (RAISE) project--a
large-scale clinical trial designed to alleviate the long-term
disability associated with schizophrenia by intervening as early as
possible after the first onset of symptoms, so that people with the
disorder can lead more productive, independent lives. RAISE addresses
the effectiveness of providing early, sustained, and integrated care to
improve health and life functioning outcomes, and develops strategies
to facilitate implementation of successful, cost-effective early
interventions in the U.S. healthcare system. RAISE incorporates
features necessary for rapid dissemination into community settings,
thus accelerating the transition from research to practice.
NIMH has also launched the Mental Health Research Network to
encourage scientific collaboration among nine established research
centers that are based in integrated, not-for-profit healthcare
systems. These systems provide care coverage to a diverse population of
10 million people in 11 States, and they share rich and compatible data
resources to support a range of effectiveness research. Researchers
have begun to use this network to address vital issues, including the
development of a geographically and ethnically diverse autism research
registry; a pilot study for a new type of therapy for postpartum
depression; and, a longitudinal analysis of how suicide warning labels
on antidepressants affect later suicidality among youth.
NEW INVESTGATORS, NEW IDEAS
The future of discovery and translational research lies in the next
generation of mental health researchers. NIMH's Biobehavioral Research
Awards for Innovative New Scientists (BRAINS) program provides support
to early stage investigators to foster innovative research aimed at
critical gaps identified by the NIMH Strategic Plan. NIMH also
recognizes the importance of ensuring that our workforce reflects the
diversity of backgrounds and perspectives that has made the United
States a source of innovation. NIMH is leading an NIH Blueprint for
Neuroscience initiative to enhance diversity in neuroscience through
undergraduate research education experiences, and has established a
supplemental funding program to provide underrepresented minority
scholars with mentored research training in strong institutional
training programs.
WORKING COLLABORATIVELY TO COMBAT SUICIDE
NIMH is committed to collaborating with other Federal agencies and
private partners to hasten the development of interventions and to
facilitate their widespread use by those most in need. As an example,
NIMH has been concerned by the high rate of suicide among our Nation's
military personnel, and has partnered with the Army to conduct the
Study to Assess Risk and Resilience of Service Members (Army STARRS)--
the largest mental health study of military personnel ever conducted.
Early examination of Army STARRS data has begun to reveal potential
predictors of risk for suicide among soldiers. Researchers plan to
analyze additional historical data and new survey data collected by
Army STARRS to confirm and expand upon these findings.
Suicide among civilians is also of significant concern.
Approximately 34,500 American lives are lost to suicide each year,
nearly twice the number lost due to homicide, making it the 10th
leading cause of death in the United States.\5\ \6\ To combat this
issue, under the leadership of the Substance Abuse and Mental Health
Services Administration, NIMH joined the Army, the Centers for Disease
Control and Prevention, other NIH Institutes, and private partners to
form the National Action Alliance for Suicide Prevention. NIMH is
spearheading a Research Prioritization Taskforce on behalf of the
Action Alliance to develop a strategic research agenda that could
reduce suicide-related mortality by 20 percent in 5 years, or 50
percent in 10 years, if fully implemented.
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\5\ CDC, National Center for Injury Prevention and Control. Web-
based Injury Statistics Query and Reporting System.
\6\ U.S. Department of Justice, Federal Bureau of Investigation.
(September 2009). Crime in the United States, 2008.
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Successfully combating mental disorders requires collaboration
across multiple levels of society; Federal agencies, the research
community, private industry, and the individuals and families affected
each day. Despite the tremendous burden of mental disorders, NIMH is up
to the challenge of bringing all stakeholders to the table, harnessing
scientific advances, and directing the next generation of research to
improve the lives of people affected by mental disorders.
______
Prepared Statement of John Ruffin, Ph.D., Director, National Institute
on Minority Health and Health Disparities
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute on Minority
Health and Health Disparities (NIMHD) of the National Institutes of
Health (NIH). The fiscal year 2012 budget of $214,608,000 includes an
increase of $5,073,000 over the fiscal year 2011 comparable
appropriation level of $209,535,000.
This statement is submitted with the recognition of the
Department's notification to the Congress of an NIH reorganization that
would establish a new National Center for Advancing Translational
Sciences and reallocate the remaining portions of the National Center
for Research Resources to other parts of NIH, including NIMHD.
INTRODUCTION
Health disparity is an issue of immense proportions with health,
economic, social and environmental impact for the Nation. Disparities
in the burden of illness and premature death experienced by racial and
ethnic minorities, low-income, and rural populations, apply to a broad
spectrum of disease types. Evidence-based research reveals that health
disparities are the result of interacting factors that may be genetic,
biological, environmental, social, economic, or psychological in
nature. The causes of and solutions to health disparities are
multidimensional and require multidimensional approaches to improve
health and eliminate the disparities.
Health disparities have had a longstanding economic burden on the
healthcare system. The Affordable Care Act (ACA) included several
provisions aimed at mobilizing the Nation around actions to confront
health disparities in order to overcome the multiple barriers faced by
underserved communities in obtaining quality healthcare. One provision
in the ACA re-designated the National Center on Minority Health and
Health Disparities (NCMHD) at the NIH to an Institute--named the
National Institute on Minority Health and Health Disparities. The NIMHD
was created to strengthen the base for the acceleration of scientific
discovery already initiated by the predecessor organization, the NCMHD,
to understand health disparities and to identify and implement
strategies to eradicate them across the Nation. In accordance with the
Affordable Care Act, NIMHD is charged to plan, review, coordinate, and
evaluate minority health and health disparities research activities
conducted by the NIH Institutes and Centers (ICs). As health
disparities transcend many diverse areas of biomedical science and
public health, this work must involve all of the NIH ICs, and numerous
Federal Government and non-Federal Government partners.
BUILDING ON A DECADE OF PROGRESS
During the past decade, under the aegis of the NCMHD, the NIMHD
launched its congressional mandates, and established new programmatic
initiatives and partnerships, allowing it to create the infrastructure
required to be at the cutting edge of scientific discovery through its
independent programs and support for collaborative research, research
infrastructure development, and outreach projects with partners within
the NIH, HHS, and beyond.
The foundation of the NIMHD's research portfolio is the NIMHD
Exploratory and Comprehensive Centers of Excellence (COE) programs.
Research in the COEs spans the wide array of diseases, health
conditions, and complex non-biological factors contributing to health
disparities. Translational research and the development of appropriate
health interventions is a particular strength of the NIMHD COEs. The
NIMHD University of Puerto Rico-Cambridge Health Alliance Research
Center of Excellence has focused its research on Latino health and
healthcare disparities, specifically mental disorders, substance abuse
and asthma. This COE has generated and tested models aimed to improve
health service delivery to eliminate these disparities. This includes
multi-level interventions at the provider, individual/family and policy
levels to reduce health services disparities and has provided
invaluable data to understand the magnitude of substance abuse
treatment disparities and the social and economic burden of these
disparities.
In addition, NIMHD COEs have assisted in emergency response to
disasters with health disparities implications such as Hurricane
Katrina in 2005, and the Haiti earthquake in 2010. NIMHD COEs responded
to the Haitian earthquake crisis with assistance to Haitian communities
in south Florida and beyond the borders of the country. These efforts
have improved the understanding of the global nature of health
disparities.
To effectively conduct research, individuals, institutions and
organizations must have the capacity and access to the resources that
are necessary to conduct research. NIMHD is a leader in advancing the
NIH efforts to increase the number of underserved populations
represented in science and medicine. The NIMHD Health Disparities
Research and the Clinical Research for Individuals from Disadvantaged
Backgrounds Loan Repayment Programs (LRP) have supported more than
2,300 individuals representing multiple disciplines through loan
repayment of educational loans. More than 60 percent of the LRP
scholars represent racial/ethnic minority populations. The program has
incentivized the pursuit of a scientific or health disparities research
career and many former LRP recipients have been successful in competing
for other NIH grants. Also, NIMHD offers the opportunity for LRP
recipients to transition into becoming independent investigators
through its Disparities Research and Education Advancing our Mission
(DREAM) program in its Intramural Research Program (IRP). During their
2-year appointment at the NIH conducting research on health
disparities, the DREAM fellows work with mentors within the NIH
Intramural Research Program across different NIH Institutes and
Centers. After the 2-year period, the DREAM fellows have the option of
returning to their originating academic institution or to a health
disparity community to further hone their research skills and complete
the final 3 years of the program.
In addition, programs such as the Research Centers in Minority
Institutions and the new NIMHD Science Education Initiative which
focuses on promoting science education and increasing the pool of
individuals from health disparity populations in the science field
starting from kindergarten through the post-doctoral level, will play a
key role in advancing the NIMHD's activities in this area.
There is growing interest in scientific research including health
disparities research at academic institutions throughout the Nation.
However, many institutions have limited or no current capacity to
conduct scientific research. Recognizing the variance in capacity among
institutions of higher education, the NIMHD has invested considerable
resources in the enhancement of research infrastructure and capacity of
less research-intensive institutions through programs such as the NIMHD
Building Research Infrastructure and Capacity (BRIC) program. Over
time, the BRIC awards have been instrumental in transforming the
abilities of some institutions to conduct health disparity research.
For example, San Francisco State University (SFSU) through the
development of shared research facilities has resulted in the
publication of approximately 70 research articles on a variety of
scientific topics, 76 SFSU students have entered highly competitive
Ph.D. programs, and BRIC-supported faculty have received more than $13
million in support to conduct health disparity research. Importantly,
BRIC support has provided a strong base for institutions to expand
their graduate level educational programs to include new doctorate
opportunities to advance health disparities research, as well as the
development of NIMHD Centers of Excellence.
A NEW ERA IN THE FIGHT AGAINST HEALTH DISPARITIES
The next decade will focus on bridging persistent gaps in health
disparities, sustaining effective investments, and developing and
adapting innovative approaches to health disparities. NIMHD will lead
the development, implementation and evaluation of the agency's health
disparities research agenda in collaboration with the other NIH
Institutes and Centers. Research on minority health and health
disparities, research capacity-building and outreach/information
dissemination priorities across the NIH will emphasize areas such as:
translational research, genetics and biological factors, global health,
social determinants of health, behavioral and social sciences,
innovative health technologies, developing a diverse scientific
workforce, health informatics capacity, public-private partnerships,
social networking, and diverse participation in clinical trials.
NIMHD will advance this health disparities research agenda through
translational research and dissemination of research findings for the
benefit of clinical practice and health disparity communities.
Community and population health intervention studies that map social,
economic and environmental determinants will provide greater insight
into the underlying causes of health disparities. In addition, primary
care and prevention research to inform healthcare reform, improve
healthcare quality, reduce costs and ultimately improve health outcomes
for health disparity populations will be examined.
In today's culturally diverse and technologically advanced society,
the construction of health messages that do not consider culture,
history, environments, or literacy levels of certain health disparity
communities can result in the inability of those communities to receive
health information. NIMHD is committed to supporting and developing
vehicles to translate and deliver research findings and health
information to health disparity communities in a culturally and
linguistically appropriate manner.
CONCLUSION
While many health disparities concerns of the past decade remain
pervasive, the NIMHD sees opportunities to accelerate the pace of
scientific discovery and translation. Within the context of the NIH and
HHS priorities for eliminating health disparities, the NIMHD will
intensify and diversify its research focus to elucidate the Nation's
understanding of health disparities. Research strategies must continue
to be innovative and the results of this research must reach the
community at a faster pace. The NIMHD is committed to strengthening its
research efforts to realize these goals.
______
Prepared Statement of Story C. Landis, Ph.D., Director, National
Institute of Neurological Disorders and Stroke
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for NINDS. The fiscal
year 2012 budget is $1,664,253,000. Our mission is to reduce the burden
of neurological disorders through research. NINDS research has improved
diagnosis, prevention, and treatment, but the best of medical science
is still far from optimal for most nervous system disorders.
Fortunately, advances in understanding the brain and its disorders are
providing extraordinary opportunities for progress.
ENHANCING THE EVIDENCE BASE FOR MEDICAL DECISIONS
U.S. Centers for Disease Control and Prevention statistics show
that from 1997 to 2007 the stroke death rate in the United States
decreased 34.3 percent, and the number of stroke deaths declined 18.8
percent, which translates to thousands of lives saved and thousands
with reduced disability every year. For decades, NINDS clinical trials
have contributed to this trend by providing evidence that enables
physicians to choose the best stroke prevention interventions according
to each person's risk factors. In April, NINDS stopped a stroke
prevention clinical trial early because the results were already clear
\1\. The trial included patients at high risk because of a prior non-
disabling stroke and severe narrowing of arteries to the brain.
Angioplasty combined with stenting, which opens clogged arteries with a
tiny balloon and inserts a device to prop them open, plus aggressive
medical therapy led to a higher risk of stroke than the medical therapy
alone. Another recent NINDS clinical trial showed that a procedure
using stents is as safe and effective in preventing stroke as carotid
endartarectomy, a more invasive surgical procedure to clear arteries,
in people with certain risk factors.\2\ Follow up to monitor longer
term results is continuing for both trials. NINDS clinical trials are
similarly guiding treatment for other diseases. A recent clinical trial
showed that an older drug, ethosuximide, may be the best first drug to
test to prevent seizures with minimum side effects in children with
absence epilepsy, providing much needed guidance for treating this
common disorder \3\. An NINDS-Department of Veterans' Affairs trial
showed that surgical implantation of deep brain stimulators (DBS) can
yield better movement and quality of life than drug treatment for
people with advanced Parkinson's disease, and more recent results of
this trial provided information about choosing the best site in the
brain to implant electrodes for each patient \4\. NINDS currently
supports 32 multi-site clinical trials to test the safety and
effectiveness of interventions in stroke, epilepsy, traumatic brain
injury, multiple sclerosis, muscular dystrophy, and other diseases, and
more than 120 earlier phase trials that are essential steps toward
large efficacy trials.
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\1\ http://www.nlm.nih.gov/databases/alerts/
intracranial_arterial_stenosis.html.
\2\ Brott TG et al. Stenting Compared to Endarterectomy for
Treatment of Carotid Artery Stenosis, New England Journal of Medicine
363:11-23 2010.
\3\ Glauser et al. Ethosuximide, Valproic Acid, and Lamotrigine in
Childhood Absence Epilepsy. New England Journal of Medicine. 362:790-
799 2010.
\4\ Weaver F. et al. Best Medical Therapy versus Bilateral Deep
Brain Stimulation for Patients with Advanced Parkinson's Disease: A
Randomized Controlled Trial. JAMA 301:63-73 2009; Follett et al.
Pallidal versus Subthalamic Deep Brain Stimulation for Parkinson's
Disease. New England Journal of Medicine 362:2077-91 2010.
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ADVANCING TRANSLATIONAL SCIENCE
Since long before the term ``translational'' became common, NINDS
has pushed development of basic science advances into drug, biologic,
and device therapies. The first enzyme therapy for inherited metabolic
diseases, several drugs for epilepsy, the first emergency treatment for
stroke, and pioneering technology for devices that replace lost nervous
system function are among advances that NINDS translational research
made possible. Often, industry capitalizes on NIH basic science
findings to develop a new therapy. However, rare diseases, bold new
therapeutic strategies, and new uses for existing drugs are all
challenges that NINDS is more likely than industry to take on. This is
especially so now because drug companies, citing the extraordinary
challenges of brain research, are reducing programs to develop nervous
system drugs \5\.
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\5\ ``R&D Cuts Curb Brain-Drug Pipeline,'' The Wall Street Jounal,
March 27, 2011.
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NINDS launched the Cooperative Program in Translational Research in
2003 to exploit increasing opportunities from neuroscience research.
This program supports teams of academic and small business
investigators to carry out milestone-driven, preclinical therapy
development for a broad range of neurological disorders. The first
candidate therapies from this program have moved into clinical testing
for disorders including stroke, Batten disease, and muscular dystrophy.
Several NINDS programs meet special translational needs for
particular diseases. Among these are the Anticonvulsant Screening
Program, the Specialized Centers of Translational Research in Stroke
(SPOTRIAS), the Udall Centers of Excellence in Parkinson's Disease, and
the Wellstone Centers for Muscular Dystrophy Research. NINDS chose
spinal muscular atrophy (SMA) as the disease to pilot another
innovative approach to drug development. With experts from academia,
industry, and FDA, the SMA Project designed a drug development plan and
is implementing the plan through a ``virtual pharma'' organization that
engages resources via contracts. Promising drug candidates are now in
advanced pre-clinical testing, and the Project is working toward
certification for a clinical trial in 2012. Building on the SMA Project
strategy, NINDS is leading the NIH Blueprint for Neuroscience in a
larger scale Grand Challenge on Neurotherapeutics. The challenge goal
is to develop truly novel drugs that will transform the treatment of
nervous system diseases. The NINDS Intramural Research Program, which
has a long record of therapy development, is also accelerating
translational research under a new Clinical Director. NINDS
translational programs work closely with all of the NIH-wide programs
and resources that will become part of the National Center for
Advancing Translational Sciences (NCATS), and will certainly benefit
from NCATS programs to catalyze translational research.
Because novel therapies for several neurological diseases are
moving toward readiness for clinical testing, NINDS is developing a
multi-site clinical network to improve the speed and effectiveness of
the early steps in clinical testing of novel therapies for neurological
disorders. Better early phase testing will increase the likelihood of
success in larger and more expensive phase III clinical trials of
effectiveness. This network will test promising interventions, whether
they arise from academia, foundations, or industry, and will engage
expertise much greater than the Institute could dedicate to separate
networks for each of the many neurological diseases. This is especially
important for rare disorders, including pediatric diseases. A project
to validate biomarkers for SMA will be among the network's first
studies.
Another major clinical initiative will develop and validate
biomarkers for Parkinson's disease, that is, measurable indicators of
the disease process. Biomarkers research, which NINDS supports for many
disorders, exemplifies another way that NINDS programs can catalyze
both NIH and industry therapy development efforts. With biomarkers for
neurodegenerative disorders, clinical trials can determine in months,
rather than years, whether drugs are slowing the progression of disease
and understand why a new treatment worked or did not. Better biomarkers
can reduce the cost of research and speed the development of better
treatments in NIH and industry.
ACCELERATING PROGRESS THROUGH TECHNOLOGY
An extraordinary array of technologies has accelerated progress in
neuroscience. These range in scale from imaging activity of the
thinking human brain as people carry out complex tasks, to
understanding atom by atom how molecules control electrical activity in
brain cells. This year research demonstrated the power of whole genome
sequencing to understand Charcot-Marie-Tooth disorder, a peripheral
nerve disease \6\. This is a harbinger of personalized genomics for
many diseases. Next generation genomics research is underway for
several neurological disorders. A ``Center without Walls'' will bring
together the best possible team, regardless of geography, to apply
advanced genomics to epilepsy. On another technological frontier, ARRA
enabled NINDS to accelerate research on induced pluripotent stem cells
(iPSC's) that can be derived from patients with Parkinson's,
Huntington's, ALS, epilepsy, and other disorders. A spate of new
technologies, from methods that label nerve cells with more than a
hundred different colors, to computerized three-dimensional
reconstruction of intricate nerve cell circuits, to techniques that
control the activity of individual nerve cells with light, are arming
neuroscientists to meet the longstanding challenge of understanding how
circuits of nerve cells underlie memory, perception, complex movement,
and other higher brain functions. This has implications for
understanding autism, epilepsy, Parkinson's, Alzheimer's, and many
other diseases.
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\6\ Lupski JR et al. Whole-genome sequencing in a patient with
Charcot-Marie-Tooth neuropathy. New England Journal of Medicine
362:1181-91 2010.
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ENCOURAGING NEW INVESTIGATORS AND NEW IDEAS
When progress against disease is not forthcoming, a gap in basic
understanding of the normal brain or the disease process is often the
cause. Physicians and scientists across academia and industry agree
that basic research propels long-term progress against disease. The
insight and ingenuity of the research community is the key. Supporting
a vigorous scientific community and investigator-initiated research are
thus high priorities throughout NINDS programs and policies. To
encourage innovative research, for example, the EUREKA (Exceptional
Unconventional Research Enabling Knowledge Acceleration) program
complements the NIH Pioneer Awards, New Innovator Awards, and
Transformative R01's, all of which support neuroscientists. To prepare
the next generation of neuroscientists, NINDS training and career
development programs are tailored to the needs of basic and clinical
researchers, and funding policies favor early stage investigators.
NINDS encourages cooperative research and promotes sharing through
several programs. Examples include the Common Data Elements program,
Human Genetics Resource Center, consortia on induced pluripotent stem
cells, disease centers programs, and other grants to multi-investigator
teams. NINDS is improving programs on workforce diversity and health
disparities based on guidance from an external review and planning
process that was completed in 2011.
CONCLUDING REMARKS
Neurological disorders present formidable challenges. Nonetheless,
prospects for progress have never been more encouraging because of
progress in understanding the nervous system and its diseases at every
level from molecules through the working human brain. NINDS is
aggressively pursuing better prevention and treatment with a balance of
basic, translational, and clinical research, supported through
investigator-initiated and priority-targeted programs.
______
Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN, Director,
National Institute of Nursing Research
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Institute of Nursing Research (NINR) of the National Institutes of
Health (NIH). The fiscal year 2012 budget includes $148,114,000 which
is $3,857,000 more than the comparable fiscal year 2011 appropriation
of $144,257,000.
INTRODUCTION
I appreciate the opportunity to share with you some of the exciting
areas of research that we support at the National Institute of Nursing
Research (NINR). As you know, a unique combination of societal trends
challenges our Nation's health, including an aging population,
increased chronic illness and obesity rates, and shortages in the
healthcare workforce. At NINR, we address these issues by supporting
research across the life span that: builds the scientific foundation
for clinical practice; improves quality of life through managing and
easing symptoms of illness; promotes health and prevents disease
through biological and behavioral interventions; and enhances end-of-
life and palliative care. We also seek to ensure future discoveries by
training the next generation of nurse scientists. NINR's emphasis on
clinical research and training places NINR in a position to make major
contributions to trans-NIH initiatives to enhance the evidence-base for
healthcare decisions, promote translational research, and support new
investigators and new ideas. NINR was established 25 years ago, in
1986, as the National Center for Nursing Research. This year, we are
commemorating our 25th anniversary through a series of scientific
outreach events to celebrate our longstanding emphasis on translating
science to improve health and clinical practice. In our first event, a
scientific symposium entitled ``Bringing Science to Life,'' some of our
distinguished scientists presented cutting edge research on topics as
varied as: the role of sleep in health and safety; managing chronic
illness in racially/ethnically diverse groups; testing interventions to
educate and support parents with premature infants; and understanding
the biological underpinnings of muscular dystrophy. This Anniversary is
an opportunity to review what NINR science has accomplished, and more
importantly, to envision and plan the next phase of evidence-based
research to meet future health and healthcare needs, challenges, and
priorities. As we look forward to the next 25 years, we are confident
that NINR-supported science will play an ever-increasing role in
addressing the most pressing issues facing our Nation's health. I
would, next, like to share with you some examples of the research that
we support and how it improves quality of life.
CHILDHOOD AND ADOLESCENCE: RISK AND RESILIENCE
From birth through young adulthood, children and adolescents face
many health challenges and also demonstrate incredible resilience. NINR
supports research to promote positive outcomes for children and
families facing a myriad of challenges. For example, chronic health
conditions in children, such as diabetes, arthritis, and obesity, pose
challenges for the entire family and require sustained attention to
treatment adherence and health assessment. NINR-funded scientists have
made advances both in understanding the family's role in children's
health and in improving assessment strategies. One study found that
although parents detected significant pain in their child following the
child's surgery, they tended to under-treat it, suggesting that
educating parents about pain management may be beneficial. Another
study found that screening children's waist circumference, which can be
easily implemented in schools, identifies more cases of high blood
pressure than the usual measure of body mass index alone. A current
initiative led by NINR aims to improve self-management of chronic
illness in children. An increasing challenge later in childhood comes
from HIV, with adolescents and young adults comprising one-third to
one-half of new infections in the United States,\1\ despite numerous
prevention campaigns. Moreover, adolescents from racial/ethnic minority
groups are disproportionately affected.\2\ A new NINR initiative
supports projects to examine psychosocial, cognitive, and neurological
predictors of HIV/AIDS risk decisionmaking in adolescents. This
research will provide an evidence-base to guide future culturally and
developmentally relevant interventions to prevent HIV/AIDS.
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\1\ National Institute for Child Health and Human Development.
AIDS/HIV. 2008.
\2\ Centers for Disease Control and Prevention. 2008. HIV/AIDS
among youth.
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CHALLENGES AND CHANGES IN AN AGING POPULATION
The population of our Nation is aging rapidly, due in large part to
increased longevity and the aging of the baby boomers. These changes
are giving rise to significant challenges, resulting in a need for:
improved strategies to manage co-occurring chronic illnesses; better
interventions to support family caregivers; and new ways to address
health disparities and meet the needs of an elderly population that is
more racially and ethnically diverse than ever before. One pressing
challenge is the increase in the number of older adults with multiple
chronic illnesses, such as heart disease, diabetes, and arthritis. Such
older adults have complex care needs, face long-term self-management of
illness, and may experience poor coordination of care in the community.
In a recent NINR-supported Nurse Coordinated Care Intervention,
advanced practice nurses developed individualized care plans for older
adults, which included family members and ongoing follow-up care. The
intervention improved health outcomes and reduced costs of care for
Medicare patients. A new NINR initiative, that benefits not only older
adults but individuals across the life span, supports research that
translates basic genomic science to clinical practice with the goal of
preventing and alleviating symptoms of chronic illness. Such efforts
have the potential to improve quality of life for older adults and
families. Another challenge is Alzheimer's disease (AD), which is
incurable, affects up to 5.1 million Americans, and is expected to
dramatically increase in incidence by the year 2030.\3\ NINR is
addressing the quality of care for AD patients, and the quality of life
of, and burden on, family caregivers. For example, researchers funded
by NINR and the National Institute on Aging (NIA) developed an
intervention to teach caregivers about AD, stress management, and
maintaining their own health. The intervention showed promising
improvements in emotional, mental, and physical health in racially
diverse groups.
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\3\ National Institute on Aging. 2009 Progress report on
Alzheimer's disease: Translating new knowledge.
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END OF LIFE: SUPPORTING INDIVIDUALS AND FAMILIES
As a society we are living longer lives than ever before; however,
we are also more likely to die from chronic and sometimes painful
illnesses \4\ that require families to make complex decisions about
life and death issues, often without adequate support and information.
As the lead NIH Institute on issues related to end-of-life research,
NINR supports research leading to evidence-based end-of-life and
palliative care that ultimately assists individuals, families, and
healthcare professionals in alleviating symptoms, planning for end-of-
life decisions, and promoting psychological, social, spiritual, and
physical well-being. NINR's Office of Research on End-of-Life Science
and Palliative Care, Investigator Training, and Education coordinates
research, training, and educational efforts in end-of-life and
palliative care science. One NINR-supported study recently examined the
effectiveness of a program to communicate patient preferences for end-
of-life decisions to clinicians. Compared to traditional practices such
as Do-Not-Resuscitate orders, the program led to fewer unwanted life-
sustaining treatments without affecting quality of remaining life. In
addition, a new NINR initiative begun in 2011 will support research to
address issues related to end-of-life and palliative care for
individuals with chronic illness who also experience life-threatening
acute illness. Finally, on August 10-12, 2011, NINR, with support from
partners across the NIH, will convene a forum entitled ``The Science of
Compassion: Future Directions in End-of-Life and Palliative Care.''
This forum is intended to energize and mobilize end-of-life and
palliative care research and to draw attention to the end-of-life and
palliative care processes, the care options available to patients and
their families, and the obligations of health service communities to
address these complex needs.
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\4\ Centers for Disease Control and Prevention and The Merck
Company Foundation. The state of aging and health in America 2007.
Whitehouse Station, NJ: The Merck Company Foundation; 2007.
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TRAINING THE NEXT GENERATION OF SCIENTISTS
NINR places strong emphasis on equipping the next generation of
scientists with the necessary skills to conduct research that improves
the Nation's health. In light of the societal trends that will
characterize the coming decades, NINR recognizes that tomorrow's nurse
scientists need to be trained in rigorous, innovative, and
interdisciplinary research that reaches diverse individuals, families,
and communities. NINR supports young scientists and junior and senior
scholars through grant funding, fellowships, and career development
awards. NINR also offers an intensive summer training program, the
Summer Genetics Institute, to improve research and clinical practice
among graduate students and faculty by providing a foundation in
molecular genetics. Additionally, our Pain Boot Camp, held for the
first time in 2010, is a 1-week research intensive program where
participants learn innovative pain research methodology from nationally
and internationally known scientists. NINR's efforts to invest in new
investigators and new ideas are critical investments in preparing a
nursing workforce to address the healthcare challenges of the coming
years.
FUTURE DIRECTIONS IN NURSING SCIENCE
Nursing science is at the forefront of efforts to improve health
and healthcare practice. NINR is currently formulating its new
strategic plan and will continue its focus on the unique social,
cultural, societal, genetic, and biological factors that contribute to
disease prevention, health promotion, and self-management of illness.
We look forward to the next 25 years in which nursing science, focused
on individuals, patients and families, will make critical contributions
to improving healthcare practice and quality of life across the disease
spectrum and across the lifespan. Thank you, Mr. Chairman. I will be
happy to answer any questions that the Committee might have.
______
Prepared Statement of Donald A.B. Lindberg, M.D., Director, National
Library of Medicine
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2012 budget request for the National
Library of Medicine (NLM) of the National Institutes of Health (NIH).
The fiscal year 2012 NIH request includes $387,153,000 for NLM, which
is $24,420,000 more than the comparable fiscal year 2011 NLM
appropriation of $362,733,000.
As the world's largest biomedical library and the producer of
internationally trusted electronic information services, NLM delivers
trillions of bytes of data to millions of users every day. Many who
begin a search in Google, another search engine, or a mobile ``app''
actually receive health information from an NLM website. Now in its
175th year, NLM is a key link in the chain that makes the results of
biomedical research--DNA sequences, clinical trials data, toxicology
and environmental health data, published scientific articles, and
consumer health information--readily available to scientists, health
professionals, and the public worldwide. A leader in biomedical
informatics and information technology, NLM also conducts and supports
leading-edge informatics research and development in electronic health
records, clinical decision support, information retrieval, advanced
imaging, computational biology, telecommunications, and disaster
response.
NLM's programs and services directly support NIH's four key
initiatives. The Library organizes and provides access to massive
amounts of scientific data from high throughput sequencing; assembles
data about small molecules to support research and therapeutic
discovery; provides the world's largest clinical trials registry and
results database; and is the definitive source of published evidence
for healthcare decisions. Research supported or conducted by NLM
underpins today's electronic health record systems. The Library has
been the principal funder of university-based informatics research
training for 40 years, supporting the development of today's leaders in
informatics research and health information technology. NLM's databases
and its partnership with the Nation's health sciences libraries deliver
research results wherever they can fuel discovery and support health
decisionmaking.
RESEARCH INFORMATION RESOURCES
NLM's PubMed/MEDLINE database is the world's gateway to research
results published in the biomedical literature, linking to full-text
articles in PubMed Central, including those deposited under the NIH
Public Access Policy, and on publishers' websites, as well as
connecting to vast collections of scientific data. Through its National
Center for Biotechnology Information (NCBI), NLM is a hub for the
international exchange and use of molecular biology and genomic
information, with databases accessed by more than 2 million users
daily. NCBI meets the challenge of organizing, analyzing, and
disseminating scientific research data with more than 40 integrated
databases and analysis tools that enable genomic discoveries in the
21st century. These databases are fundamental to the identification of
important associations between genes and disease and to the translation
of new knowledge into better diagnoses and treatments. Resources such
as dbGAP and the upcoming Genetic Testing Registry (GTR) create a
bridge between basic research and clinical applications. dbGaP links
genotype and phenotype information from clinical studies to identify
genetic factors that influence health and serves as the public
repository for data from genome wide association studies (GWAS)
supported by NIH and other research funders. The GTR will be a central
source for healthcare providers and patients to find detailed
information about genetic tests and the laboratories that offer them.
NLM also stands at the center of international exchange of data
about clinical research studies. NLM's Lister Hill National Center for
Biomedical Communications builds ClinicalTrials.gov, the world's
largest clinical trials database, including registration data for more
than 106,000 clinical studies with sites in 174 countries.
ClinicalTrials.gov has novel and flexible mechanisms that enable
submission of summary results data for clinical trials subject to the
Food and Drug Administration Amendments Act of 2007. To date, summary
results are available for about 3,400 completed trials of FDA-approved
drugs, biological products, and devices--providing a new and growing
source of evidence on efficacy and comparative effectiveness.
HEALTH DATA STANDARDS AND ELECTRONIC HEALTH RECORDS
Electronic health records with advanced decision-support
capabilities and connections to relevant health information will be
essential to achieving personalized medicine and will help Americans to
manage their own health. For 40 years, NLM has supported seminal
research on electronic health records, clinical decision support, and
health information exchange, including concepts and methods now used by
MicroSoft Health Vault and Google Health. As the central coordinating
body for clinical terminology standards within HHS, NLM works closely
with the Office of the National Coordinator for Health Information
Technology (ONC) to facilitate adoption and ``meaningful use'' of
electronic health records (EHRs). NLM supports, develops, and
disseminates key data standards for U.S. health information exchange in
ONC's criteria for certification of electronic health records. NLM is
actively engaged in research on Next Generation EHRs, while also
developing tools and frequently used subsets of large terminologies to
help EHR developers and users implement health data standards right
now. Most recently, NLM released MedlinePlus Connect, which allows
application developers to establish direct links from a patient's view
of his or her EHR to high quality health information relevant to that
person's specific health conditions, medications, and (coming soon)
recent tests.
INFORMATION SERVICES FOR THE PUBLIC
This new EHR connection builds upon NLM's extensive information
services for patients, families and the public. The Library's
MedlinePlus website provides integrated access to high quality consumer
health information produced by all NIH components and HHS agencies,
other Federal departments, and authoritative private organizations and
serves as a gateway to specialized NLM information sources for
consumers, such as the Genetic Home Reference and the Household
Products database. Available in English and Spanish, with selected
information in 40 other languages, MedlinePlus averages well over
600,000 visits per day. Covering nearly 900 health topics, MedlinePlus
has interactive tutorials for persons with low literacy, an illustrated
medical encyclopedia, surgical videos and links to the scientific
literature in PubMed. Mobile MedlinePlus, also in both English and
Spanish, reaches the large and rapidly growing mobile Internet
audience.
The NIH MedlinePlus quarterly magazine is an outreach effort made
possible with support from many parts of NIH and the Friends of the
NLM. Like MedlinePlus itself, the magazine is free and contains no
advertising. It is distributed to the public via physician offices,
community health centers, libraries and other locations and has a
readership of up to 5 million nationwide. Each issue focuses on the
latest research results, clinical trials and new or updated guidelines
from the 27 NIH Institutes and Centers. A Spanish/English version, NIH
MedlinePlus Salud, launched with support from the National Alliance for
Hispanic Health and the National Hispanic Medical Association,
addresses the specific health needs of the growing Hispanic population
and showcases the many Hispanic outreach efforts and relevant research
results funded by the NIH.
To be of greatest use to the widest audience, NLM's information
services must be known and readily accessible. The Library's outreach
program, with a special emphasis on reaching underserved populations,
relies heavily on the more than 6,300-member National Network of
Libraries of Medicine (NN/LM). The NN/LM is a network of academic
health sciences libraries, hospital libraries, public libraries and
community-based organizations working to bring the message about NLM's
free, high-quality health information resources to communities across
the Nation.
DISASTER INFORMATION MANAGEMENT
Events of the past year, such as the Deepwater Horizon oil spill
and the earthquake, tsunami, and radiation event in Japan, demonstrated
yet again the importance of rapid, organized response to natural
disasters and other emergencies. NLM has a long history of providing
health information to prepare for, respond to, and recover from
disasters and has tools and advanced information services designed for
use by emergency planners, responders and managers. Through its
Disaster Information Management Resource Center, NLM builds on proven
emergency backup and response mechanisms within the National Network of
Libraries of Medicine to promote effective use of libraries and
disaster information specialists in disaster preparedness and response.
NLM also conducts research on new methods for sharing health
information in emergencies as its contribution to the Bethesda Hospital
Emergency Preparedness Partnership, a model of private-public hospital
collaboration for coordinated disaster planning. NLM partners with the
Pan American Health Organization (PAHO) and other bodies in the Latin
American Network for Disaster and Health Information to promote
capacity-building in the area of disaster information management.
Within 2 days of the gulf oil spill, NLM launched a web page
focused on the potential effects of oil on human health, which quickly
became a highly regarded resource for evidence-based information by
Federal, State, and local agencies and communities. NLM continued to
support information needs in Haiti, including onsite assistance to PAHO
in setting up a system for collecting information from cholera
treatment centers. The Radiation Emergency Medical Management (REMM)
tool, previously developed by NLM, the HHS Office of the Assistant
Secretary for Preparedness and Response, CDC and NCI, was deployed in
Japan, via the web and on mobile devices, to assist with assessing and
managing the health effects of radiation. NLM also activated the
Emergency Access Initiative, a partnership with publishers and medical
libraries which provides free temporary access to key electronic
medical journals and books when disasters interrupt regular health
information services, and provided practical advice to Japanese
libraries and archives on rescuing water-damaged books and documents.
In summary, NLM's information services and research programs serve
the Nation and the world by supporting scientific discovery, clinical
research, education, healthcare delivery, public health response, and
the empowerment of people to improve personal health. The Library is
committed to the innovative use of computing and communications to
enhance public access to the results of biomedical research.
______
Prepared Statement of Jack Whitescarver, Ph.D., Director, Office of
AIDS Research
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for the trans-NIH AIDS
research program, which is $3,159,531,000. This amount is an increase
of $100,254,000 over the fiscal year 2011 enacted level. It includes
the total NIH funding for research on HIV/AIDS and the wide spectrum of
AIDS-associated malignancies, opportunistic infections, co-infections,
and clinical complications; intramural and extramural research;
research management support; research centers; and training. It also
includes a transfer of approximately $27 million to the HHS Office of
the Assistant Secretary of Health to foster collaborations across HHS
agencies and finance high priority initiatives in support of the
President's National HIV/AIDS Strategy.
THE AIDS PANDEMIC
Nearly 30 years since the recognition of AIDS and the
identification of HIV as its causative agent, the HIV/AIDS pandemic
remains a global scourge. UNAIDS reports that in 2009, more than 33
million people were estimated to be living with HIV/AIDS; 2.6 million
were newly infected; and 1.8 million people died of AIDS-related
illnesses. The majority of cases worldwide are the result of
heterosexual transmission, and women represent more than 50 percent of
HIV infections worldwide. More than 1,000 children become infected each
day, most of them as newborns. More than 25 million men, women, and
children worldwide have already died.
In the United States, CDC reports that more than 1.1 million people
are estimated to be HIV-infected; approximately 56,300 new infections
occur each year; and someone is infected with HIV every 9\1/2\ minutes.
HIV/AIDS continues to be an unrelenting public health crisis,
disproportionately affecting racial and ethnic populations, women of
color, young adults, and men who have sex with men. The number of
individuals aged 50 years and older living with HIV/AIDS is increasing,
due in part to antiretroviral therapy, which has made it possible for
many HIV-infected persons to live longer, but also due to new
infections in individuals over the age of 50.
NIH AIDS RESEARCH PROGRAM
To address this pandemic, NIH has established the most significant
AIDS research program in the world, a comprehensive program of basic,
clinical, translational, and behavioral research in domestic and
international settings--a multi-disciplinary, global research program
carried out by every NIH institute and center in accordance with their
mission. This diverse research portfolio requires an unprecedented
level of trans-NIH planning, scientific priority-setting, and resource
management. The Office of AIDS Research (OAR) was authorized to plan,
coordinate, evaluate, and budget all NIH AIDS research, functioning as
an ``institute without walls,'' to identify the highest priority areas
of scientific opportunity, enhance collaboration, minimize duplication,
and ensure that precious research dollars are invested effectively and
efficiently.
NEW SCIENTIFIC ADVANCES AND OPPORTUNITIES
The past year has been a significant one for AIDS research. The NIH
investment in the priority areas of HIV prevention research and in
basic science over the past several years has resulted in important
progress in critical areas of the NIH AIDS research program. Recent
research advances by NIH intramural and extramural investigators have
opened doors for new and exciting research opportunities in the search
for strategies to prevent, treat, and ultimately cure HIV infection.
These advances include:
Technologies to accelerate discovery--
--Vaccines.--A team of scientists led by researchers at the NIAID
Vaccine Research Center discovered two potent human antibodies
that can stop more than 90 percent of known global HIV strains
from infecting human cells in the laboratory and determined the
structural analysis of how they work. The novel techniques used
in this research may accelerate HIV vaccine research as well as
the development of vaccines for other infectious diseases. An
HIV vaccine clinical trial conducted in Thailand by NIH and the
Department of Defense demonstrated the first indication of a
modest but positive effect in preventing HIV infection. The
trial marked the first step in proving the concept that a
vaccine to prevent HIV infection is feasible.
--Microbicides.--For the first time in nearly 15 years of research,
scientists discovered a vaginal microbicide gel that gives
women a level of protection against HIV infection. The study,
sponsored by USAID and conducted by the Centre for the AIDS
Programme of Research in South Africa (CAPRISA), found that the
use of a microbicide gel containing the antiretroviral drug
tenofovir resulted in 39 percent fewer HIV infections compared
with a placebo gel. NIH provided substantial support and
resources to establish the infrastructure and training for
CAPRISA. Ongoing and future NIH clinical trials will build on
these study results with the goal of bringing a safe and
effective microbicide to licensure.
--Basic Science.--This past year, using genome-wide association
studies, NIH-sponsored researchers made an important discovery
related to the genetics of an individual's immune system. These
genes appear to be involved in the control of HIV disease
progression among a group of individuals considered ``elite
controllers,'' who have been exposed to HIV over an extended
period, but whose immune systems have controlled the infection
without therapy and without symptoms. These findings will
contribute to the development of potential HIV prevention
strategies.
Translational sciences and therapeutic development.--New lymphoma
regimens have been developed that can be tailored to specific tumor
types. This development has markedly improved the therapeutic outcome
and survival of patients with AIDS-related lymphoma. In addition,
progress in both basic science and treatment research aimed at
eliminating viral reservoirs has been significant enough that
scientists are now, for the first time, planning to conduct research
aimed at a cure. NIH has announced several initiatives to generate new
ideas for curing HIV infection through domestic and international
partnerships among government, industry, and academia.
Enhancement of evidence-base for healthcare decisions.--In the
critical area of treatment as prevention, two recent studies have
demonstrated the effectiveness of new multi-drug antiretroviral
regimens for the prevention of mother-to-child-transmission of HIV
during pregnancy and breastfeeding. In addition, a large international
NIH clinical trial provided strong evidence that the use of pre-
exposure prophylaxis (PrEP), that is, the use of antiretroviral
treatment before exposure to prevent infection, can reduce risk of HIV
acquisition in men who have sex with men. Additional and continued
research is needed to determine whether PrEP will be similarly
effective at preventing HIV infection in other at-risk populations and
assist healthcare workers in providing these potential options.
TRANS-NIH PLAN AND BUDGET
These advances, while preliminary and incremental, provide the
groundwork for further scientific investigation and the building blocks
for the development of the trans-NIH AIDS strategic Plan, developed by
OAR in collaboration with both government and non-government experts.
The priorities of the strategic Plan guide the development of the
trans-NIH AIDS research budget. OAR develops each IC's AIDS research
allocation based on the Plan, scientific opportunities, and the IC's
capacity to absorb and expend resources for the most meritorious
science--not on a formula. This process reduces redundancy, promotes
harmonization, and assures cross-Institute collaboration. The
priorities of the Plan will establish the biomedical and behavioral
research foundation necessary to implement the major goals of the
President's National HIV/AIDS Strategy and to implement the NIH
Director's themes.
FISCAL YEAR 2012 SCIENTIFIC PRIORITIES
A growing proportion of patients receiving long-term antiretroviral
therapy (ART) are demonstrating treatment failure, experiencing serious
drug toxicities and side effects, and developing drug resistance.
Recent studies have shown an increased incidence of malignancies, as
well as cardiovascular and metabolic complications, and premature aging
associated with long-term HIV disease and ART. NIH research will
address the need to develop better, less toxic treatments and to
investigate how genetic determinants, sex, gender, race, age, pregnancy
status, nutritional status, and other factors interact to affect
treatment success or failure and/or disease progression.
NIH-funded research is needed to address the causes of HIV-related
health disparities, their role in disease transmission and acquisition,
and their impact on treatment access and effectiveness. These include
disparities among racial and ethnic populations in the United States;
between developed and resource-constrained nations; between men and
women; between youth and older individuals; and disparities based on
sexual identity. In addition, specific fiscal year 2012 research
priorities include: biomedical and behavioral research focused on the
domestic AIDS epidemic, particularly in racial and ethnic populations
of the United States; research to build on important research advances
in prevention research in the past year in the areas of microbicides,
vaccines, and treatment as prevention; research to prevent and treat
HIV-associated co-morbidities, malignancies, and clinical
complications; research to address the complex issues around AIDS and
aging; research to better understand the issues of adolescents and
AIDS; basic and therapeutic research focused on elimination of viral
reservoirs leading toward a cure; genetic studies to delineate the
genetic basis for immune responses to HIV and to sequence HIV-
associated tumors; and research on feasibility, effectiveness, and
sustainability required for the scale-up and implementation of
interventions in communities at risk.
SUMMARY
The OAR has utilized its authorities to shift AIDS research program
priorities and resources to meet the changing epidemic and scientific
opportunities. This investment in AIDS research has produced
groundbreaking scientific advances. AIDS research also is helping to
unravel the mysteries surrounding many other cardiovascular, malignant,
neurologic, autoimmune, metabolic, and infectious diseases as well as
the complex issues of aging and dementia. Despite these advances,
however, AIDS has not been conquered, and serious challenges lie ahead.
The HIV/AIDS pandemic will remain the most serious public health crisis
of our time until better, more effective, and affordable prevention and
treatment regimens are developed and universally available. NIH will
continue its efforts to prevent, treat, and eventually cure AIDS.
Thank you for your continuing support for our efforts.
______
Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal
Deputy Director, National Institutes of Health
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for the Office of the
Director (OD). The fiscal year 2012 budget includes $1,298,412,000; an
increase of $132,451,000 over the comparable fiscal year 2011 enacted
level of $1,165,961,000, comparable for transfers proposed in the
President's request.
The OD promotes and fosters NIH research and research training
efforts in the prevention and treatment of disease through the
oversight of the Intramural Research program and through coordination
of program offices responsible for stimulating specific areas of
research throughout NIH to complement the ongoing efforts of the
Institutes and Centers. The OD also develops policies in response to
emerging scientific opportunities employing ethical and legal
considerations; maintains peer review policies; provides oversight of
grant and contract award functions; coordinates information technology
across the Agency; and coordinates the communication of health
information to the public and scientific community. Moreover, the OD
provides the core management and administrative services, such as
budget and financial management, personnel, property, and procurement
services, ethics oversight, and the administration of equal employment
policies and practices.
The principal OD offices providing these activities include the
Offices of Extramural Research, Intramural Research, Science Policy,
Communications and Public Liaison, Legislative Policy and Analysis,
Equal Opportunity and Diversity Management, Financial Management,
Budget, Management, Human Resources, Chief Information Office, and the
Executive Office. This request contains funds to support the functions
of these offices as will be outlined in the Program, Project and
Activities Table which follows.
The statement is submitted with the recognition of the Department's
notification to the Congress of an NIH reorganization that would
establish a new National Center for Advancing Translational Sciences
and reallocate the remaining portions of the National Center for
Research Resources to other parts of NIH, including the OD.
DIVISION OF PROGRAM COORDINATION, PLANNING, AND STRATEGIC INITIATIVES
(DPCPSI)
The DPCPSI mission includes identifying the most compelling
scientific opportunities, emerging public health challenges, and
scientific knowledge gaps that merit further research or would
otherwise benefit from strategic coordination and planning across the
Agency. DPCPSI provides key support of research that is consistent with
the NIH Director's Themes. The Division is comprised of the Office of
AIDS Research, Office of Research on Women's Health, Office of
Behavioral and Social Sciences Research, Office of Disease Prevention,
Office of Medical Applications of Research, Office of Dietary
Supplements, Office of Rare Diseases Research, and the Office of
Strategic Coordination (OSC). The OSC is responsible for the oversight
and management of the NIH Common Fund. The Division is responsible for
agency-wide effort in portfolio analysis and also manages NIH-wide
evaluation and performance activities, including the Evaluation Set-
Aside program and the Government Performance and Results Act plans and
reports. The fiscal year 2012 budget for DPCPSI/Office of the Director
is $8,401,000. Descriptions of the eight programmatic offices within
DPCPSI, and their separate budgets, follow.
THE OFFICE OF AIDS RESEARCH
The Office of AIDS Research (OAR) plays a unique role at NIH,
establishing a plan for the AIDS research program. OAR coordinates the
scientific, budgetary, legislative, and policy elements of the NIH AIDS
research program. OAR's response to the AIDS epidemic requires a unique
and complex multi-institute, multi-disciplinary, global research
program. This diverse research portfolio demands an unprecedented level
of scientific coordination and management of research funds to identify
the highest priority areas of scientific opportunity, enhance
collaboration, minimize duplication, and ensure that precious research
dollars are invested effectively and efficiently, allowing NIH to
pursue a united research front against the global AIDS epidemic. The
fiscal year 2012 budget for OAR is $65,760,000.
THE OFFICE OF RESEARCH ON WOMEN'S HEALTH
The Office of Research on Women's Health (ORWH) mission is to
enhance and expand research supported by the NIH to adequately address
women's health. This is done by identifying gaps in knowledge, and
collaborating with the ICs to stimulate and support innovative research
including interdisciplinary scientific approaches to women's health and
studies of sex and gender differences in health and diseases. ORWH
continues to lead efforts to ensure adherence to policies for the
inclusion of women and minorities in clinical research The fiscal year
2012 budget for ORWH is $43,811,000.
THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH
The Office of Behavioral and Social Sciences Research (OBSSR) was
established by Congress to stimulate behavioral and social science
research at NIH and to integrate it more fully into the NIH research
enterprise. The Office furthers the NIH mission by emphasizing the
critical role that behavioral and social factors play in health,
healthcare, and well-being. The Office supports the activities of the
NIH Basic Behavioral and Social Science Opportunity Network, a trans-
NIH initiative to expand the agency's funding of basic behavioral and
social sciences research. The fiscal year 2012 budget for OBSSR is
$27,949,000.
THE OFFICE OF DISEASE PREVENTION
The primary mission of the Office of Disease Prevention (ODP) is to
stimulate disease prevention research across the NIH and to coordinate
and collaborate on related activities with other Federal agencies as
well as the private sector. The fiscal year 2012 budget for ODP is
$1,400,000. The Office of Medical Applications of Research (OMAR),
Office of Dietary Supplements (ODS), and Office of Rare Diseases
Research (ORDR) are within the ODP organizational structure.
The Office of Medical Applications of Research (OMAR) mission is to
work with NIH Institutes, Centers, and Offices to assess, translate and
disseminate the results of biomedical research that can be used in the
delivery of important health interventions to the public. The fiscal
year 2012 budget for OMAR is $4,877,000.
The Office of Dietary Supplements (ODS) promotes study of the use
of dietary supplements by supporting investigator-initiated research,
and through other major mechanisms. The fiscal year 2012 budget for ODS
is $28,691,000.
The Office of Rare Diseases Research (ORDR) supports activities
that stimulate research on rare diseases by collaborating with the
research institutes, research investigators, patient advocacy groups,
the pharmaceutical industry, and Federal regulatory and research
agencies. The fiscal year 2012 budget for ORDR is $18,423,000.
THE OFFICE OF STRATEGIC COORDINATION AND THE COMMON FUND
The Office of Strategic Coordination (OSC) facilitates strategic
planning and management of Common Fund-supported programs by working
with groups of staff from across the NIH to develop and implement each
individual program while providing central management for the Common
Fund as a whole. The NIH Common Fund was enacted into law by Congress
through the 2006 NIH Reform Act to support cross-cutting, trans-NIH
programs that require participation by at least two NIH Institutes or
Centers (ICs) or would otherwise benefit from strategic planning and
coordination. The Common Fund provides limited-term funding for new
programs that are intended to catalyze research in the ICs through the
development of cross-cutting resources, technologies, and data sets.
Common Fund programs do not address any particular disease or
condition, but rather, are designed to be broadly relevant. The fiscal
year 2012 budget for the Common Fund is $556,890,000.
THE OFFICE OF SCIENCE EDUCATION
The Office of Science Education (OSE) develops science education
programs, instructional materials, and career resources that serve our
Nation's science teachers, their students (kindergarten through
college), and the public. OSE's activities are an important component
to the overall Agency effort to achieve the NIH Director's goal to
reinvigorate and empower the biomedical research community and enhance
America's competitiveness in the global economy. The OSE creates
programs to improve science education in schools (the NIH Curriculum
Supplement Series) that stimulate interest in health and medical
science careers (LifeWorks Web site); and advance public understanding
of medical science, research, and careers; and advises NIH leadership
about science education issues. The OSE website is a central source of
information about available education resources and programs. http://
science.education.nih.gov. The fiscal year 2012 budget for OSE is
$4,120,000.
LOAN REPAYMENT AND SCHOLARSHIP PROGRAMS
The Office of Intramural Training and Education administers the NIH
Intramural Loan Repayment and Undergraduate Scholarship Programs
(UGSP). The Loan Repayment Programs (LRPs) seek to recruit and retain
highly qualified physicians, dentists, and other health professionals
with doctoral-level degrees. These programs offer financial incentives
and other benefits to attract highly qualified physicians, nurses, and
scientists into careers in biomedical, behavioral, and clinical
research as employees of the NIH. The NIH UGSP offers competitive
scholarships to exceptional college students from disadvantaged
backgrounds that are committed to biomedical, behavioral, and social
science health-related research careers at the NIH. The fiscal year
2012 budget is $7,653,000 for the Intramural Loan Repayment and
Undergraduate Scholarship Programs.
I am happy to answer any questions you may have about the OD's
programs and activities as well as our plans for the upcoming year.
______
Prepared Statement of Jeremy M. Berg, Ph.D., Director, National
Institute of General Medical Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2012 President's budget request for the National
Institute of General Medical Sciences (NIGMS). The fiscal year 2012
budget request includes $2,102,300,000, an increase of $70,263,000
above the fiscal year 2011 appropriation of $2,032,037,000, which has
been adjusted comparably to reflect NIH proposed transfers. This
statement is submitted with the recognition of the Department's
notification to the Congress of an NIH reorganization that would
establish a new National Center for Advancing Translational Sciences
and reallocate the remaining portions of the National Center for
Research Resources to other parts of NIH.
Since the mid-20th century, NIGMS has played a leading role as
NIH's ``basic research institute.'' Spanning a broad spectrum, the
Institute's mission supports discovery ranging from how cells work to
how diseases affect communities across towns, nations, and countries.
NIGMS-supported scientists probe the unknown to solve mysteries about
fundamental life processes. This effort goes well beyond the need to
satisfy innate curiosity; answering basic research questions such as
how bacterial and human cells divide, move, and communicate has
increased our knowledge about infections, cancer, birth defects, and
heart disease in ways that would have been difficult to achieve with
more directed studies. Other ongoing NIGMS research investments, such
as in chemistry, continue to provide tangible benefits to society and
our economy. This past year, an NIGMS-supported scientist shared a
Nobel Prize for his discovery of a ground-breaking chemistry method
that is used routinely in the pharmaceutical, electronic and
agricultural industries.
Continued investment in basic research is vital because many of
today's therapies, although effective, nevertheless have significant
limitations. Treatments that are applied after the onset of serious
illness--kidney transplants and dialysis, bypass surgery for coronary
artery disease, surgical removal of tumors--though often lifesaving,
are still not optimal. Treating disease before such interventions are
needed would likely improve both outcomes and quality of life. Basic
biomedical and behavioral research has the power to move treatments in
this direction, and in the coming years, emerging biotechnology and
nanotechnology tools will give researchers unprecedented precision to
detect and derail disease at its earliest stages.
TECHNOLOGIES TO ACCELERATE DISCOVERY
Basic research on stem cells remains one of the most rapidly
advancing areas of biomedicine, in large part because of the knowledge
base scientists already have about how cells behave and change. NIGMS-
supported research on stem cells continues to provide hope that these
multitalented cells will find use in customized therapies for a range
of conditions. In the near term, stem cells are providing researchers
powerful tools for understanding diseases and developing drugs to treat
them. This past year, NIGMS-funded researchers made important progress
on several fronts:
--Stem cell research pioneer James Thomson, D.V.M., Ph.D., created a
powerful tool to trace the individual steps in a deadly cancer
by turning the clock back on blood cells from a person with
leukemia.
--Chemist Laura Kiessling, Ph.D., developed an inexpensive and simple
synthetic culture system for growing embryonic stem cells in
the laboratory.
--NIH Director's New Innovator Awardee Alysson Muotri, Ph.D., used
cells from a person with Rett syndrome to create a cellular
model of autism.
Another area showing great promise is molecular diagnosis. This
past year, NIH Director's Pioneer Awardee Thomas Kodadek, Ph.D.,
applied a unique and creative strategy that conducts an ``immune
surveillance'' of human blood to look for early signs of disease before
symptoms appear. To date, he has obtained exciting evidence that
Alzheimer's disease may be detectable by this approach, and he has
licensed the technology to further its development and application.
The study of systems--of cells, organs, and diseases--is an
important area of basic discovery within the NIGMS mission. In 2010,
the Institute grew its support of systems biology by adding two new
National Centers for Systems Biology. All 12 centers integrate
approaches from engineering, genomics, and systems and synthetic
biology to identify principles and architectural features involved in
common cellular behaviors, including the response to disease-causing
microorganisms, poisons, and metabolic imbalances.
Computer modeling is a key element of all systems biology, and a
central aspect of the NIGMS-led Models of Infectious Disease Agent
Study (MIDAS). This international effort continues to add new research
expertise to increase its capacity to simulate disease spread, evaluate
different intervention strategies, and help inform public health
officials and policymakers. This past year, two MIDAS findings are
worth highlighting:
--One MIDAS study used computer modeling to analyze the spread of
H1N1 flu in a Pennsylvania elementary school. The researchers
collected extensive data from seating charts, school
timetables, bus schedules, nurse logs, attendance records and
questionnaires. The findings indicated that transmission occurs
mostly through girl-to-girl and boy-to-boy interactions and
that sitting directly next to a child with the flu does not
raise a child's risk of getting it.
--In another MIDAS study, researchers learned that the Haiti cholera
outbreak that followed that Nation's colossal earthquake in
2010 could have been blunted with the use of a mobile stockpile
of oral cholera vaccine.
TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT
Since the landmark discovery of the structure of DNA in the 1950s,
our increasing knowledge of how all living things share a basic set of
working parts has catalyzed progress in biomedicine. Large-scale
efforts to scan and compare genomes are teaching scientists about
individual differences in DNA scripts that predispose us to disease.
However, such sequence information is only useful if it can be properly
interpreted. NIGMS has been at the forefront of supporting research
that facilitates this interpretation, leading to numerous discoveries
that have revealed new, unforeseen mechanisms by which DNA information
is made operational.
As one example, the NIGMS Protein Structure Initiative (PSI) has
been creating knowledge and providing tools to researchers for more
than 10 years. This past year, NIGMS enhanced this signature effort by
launching PSI:Biology, a new program that supports research
partnerships between groups of biologists and high-throughput structure
determination centers to solve medically important problems. Already
this investment is bearing fruit, yielding new structures that show how
the largest class of drug receptors functions.
Another example is a pilot study by an individual scientist that
searched systematically for environmental factors--nutrients, chemicals
and toxins--that may be linked to diabetes. Based conceptually on the
Genome-Wide Association Studies approach, Atul Butte, M.D., Ph.D.,
developed a new technique he calls Environment-Wide Association
Studies. In this method, he considered many different factors at once,
using health survey data from the U.S. Centers for Disease Control and
Prevention, which led him to identify 266 environmental factors linked
to type 2 diabetes. This example highlights the tremendous potential
benefits of integrating existing data sources and asking the right
questions.
ENHANCEMENT OF EVIDENCE BASE FOR HEALTHCARE DECISIONS
Although medicines have been revolutionary in humankind's ability
to stay healthy, we now know that people having widely varying
responses to the drugs they take to heal their various ills. NIGMS has
been a long-time supporter of pharmacogenomics, the study of how our
DNA influences the way we respond to medications. This area of research
is an especially important focus in our country today, as the baby-boom
generation gets older and is more likely to take multiple medicines
routinely. NIGMS leads the trans-NIH Pharmacogenomics Research Network
(PGRN), a nationwide collaborative of scientists looking for clues to
inherited variability in the response to medicines used to treat heart
disease, asthma, cancer, depression and addiction.
This past year, two new groups joined the network, adding
rheumatoid arthritis and bipolar disorder as new focus areas. Over the
next 5 years, the PGRN plans to expand to pursue cutting-edge DNA
sequencing methods and statistical analysis, as well as to perform
pilot studies to learn about medication response from de-identified
medical records in healthcare systems. Furthermore, previous PGRN-based
discoveries are now moving further into clinical application with
evidence accumulating on improved outcomes and lower costs.
NEW INVESTIGATORS, NEW IDEAS
Biomedical and behavioral research is a human endeavor, and NIGMS
has a long-standing commitment to supporting and sustaining the people
behind the research. Creativity comes from the sparks of individual
minds, and thus the Institute has always adhered to the principle that
a healthy workforce is an essential ingredient for good science that
leads to better health for all.
Science and the conduct of research continue to evolve, though, as
do workforce needs. It is our responsibility to stay attuned to these
new needs and opportunities. In 2010, NIGMS launched a process to
examine its activities and general philosophy of research training--to
assure that all of the Institute's activities related to the training
of scientists are aligned with our commitment to build an excellent,
diverse research workforce to help achieve the NIH mission, now and in
the long term.
NIGMS gathered data and input from the scientific community through
a series of regional meetings across the country, as well as through
other means of electronic communication including a webinar, online
postings, and comment submissions via e-mail. The resulting plan,
Investing in the Future, the NIGMS Strategic Plan for Biomedical and
Behavioral Research Training, was released in early 2011.
A key focus of this plan is the importance of putting the needs of
trainees first--by focusing on mentoring, career guidance, and
diversity. The plan also affirms the Institute's strong assertion that
there are multiple avenues in which a well-trained scientist can make
meaningful contributions to society. These include research careers in
academia, Government, or the private sector, as well as careers
centered on teaching, science policy, patent law, communicating science
to the public, and other areas.
In closing, and on the cusp of my departure from Federal service, I
want to note how proud I have been to play a role in furthering the
basic research that has had such a profound effect on the health and
well-being of our Nation. I will treasure the time and effort spent
leading the fine institution that is NIGMS.
AVERAGE COST OF RESEARCH PROJECT GRANTS
Senator Harkin. Well, thank you, Dr. Collins. Very poignant
ending for your testimony.
We will now begin a round of 5-minute questions.
Dr. Collins, in addition to drastically cutting NIH
funding, the House Appropriations bill would have required NIH
to fund a minimum number of new competing research grants and
put a ceiling on the average cost to them.
I have a letter here from a number of different entities--
American Association for Cancer Research, American Medical
Colleges, American University--a whole list of different people
who've written us a letter saying that this would really hamper
the ability of NIH to fund the best, the most innovative, the
brightest by putting a cap on it. Now, you have to fund so many
and you have to--I think it was 9,000--and then they put a cap
on it of, I think, $400,000, if I'm not mistaken.
Again, I'd like you to speak to that. We've been down this
road before over the last 25 or 30 years that I've been on this
subcommittee, in saying that NIH really ought to do this on a
peer-reviewed basis. Some of the projects cost more, some cost
less, but to limit it and then to say you have to do so many,
takes away the ability to really do a good peer-reviewed
systematic approach to this.
I would like you to respond to that and what that would
mean to NIH if, in fact, we were to set a limit on how much and
to mandate that you have to fund at least so many grants.
Dr. Collins. Senator, I appreciate the question. This is a
very serious issue and you've set it up quite well in terms of
what the risks might he here.
Certainly, that feature of the language that was part of
H.R. 1 was deeply troubling to those of us at NIH, because, as
you have just said, the goal of all of us who tried to carry
out our responsibilities to support the very best biomedical
research is to utilize the tools of peer review, to seek advice
from the scientific community and our advisory councils about
how best to utilize the resources that the taxpayers, through
this Congress gives to us.
The idea that we would have to manage that enterprise in an
arbitrary way to try to hit a certain number of grants, and
particularly to try to hit some average cost of a new and
competing grant could potentially seriously interfere with the
flexibility that we believe is necessary for the best science
to be supported.
For instance, clinical trials tend to be more expensive.
Would this kind of a limit on the average costs of a new and
competing grant find its way into conversations about, well,
maybe we should do fewer clinical trials and more grants that
happen to be inexpensive, like conference grants? That would
be, I think, a serious intrusion into the ways in which,
really, scientific decisions should be made.
So I agree with you that that particular kind of way of
tying NIH's hands would be very unfortunate. Given all of the
scientific opportunities that we have right now, we should be
able to pursue them in a way that represents the best decisions
and not managed in this sort of arbitrary way by trying to hit
certain numerical grant limits.
DIABETES
Senator Harkin. I appreciate that.
Dr. Rodgers, on diabetes, I think we saw that chart there
about moderate changes in diet and exercise resulting in a huge
decrease in the incidence of the disease. I had 71 percent and
the chart said 58 percent, so I have to figure out why there's
a difference here. When you testified a few years ago on this,
you said you would be undertaking a follow-up study to see
whether these could be sustained over time. What's happened?
Dr. Rodgers. That's correct, Senator, and thanks for the
question.
First of all, the 71 percent, even though the average
improvement in terms of a reduction with that intensive
lifestyle modification was 58 percent for all comers, among the
people over 60 years of age, it was 71 percent. So they really
enjoyed the best benefit of all of the subsets of the patients
studied.
Now, the initial trial, the diabetes prevention trial, was
published in 2002, and, at that point, the reduction was 58
percent for intensive lifestyle, 31 percent for a drug,
metformin.
But, more recently, the 10-year follow-up, which is what I
was referring to at that hearing, was just published in the
Lancet in 2009, and that shows, as Dr. Collins mentioned, a
durable effect out 10 years. These patients who engaged in the
intensive lifestyle still showed a reduction of their going on
to develop diabetes, and the patients, in fact, who were on the
metformin also continued to show an improvement.
Senator Harkin. Very good.
Now, my 5 minutes is up, but I have other questions for
other people here. I'll do that on my second round.
Senator Shelby.
NCATS BUDGET AMENDMENT
Senator Shelby. Thank you, Mr. Chairman.
Dr. Collins, I'm going to get back into NCATS for a minute.
I think it's very important, and I think it has great promise.
I think that NCATS proposal requires thoughtful
consideration to the effect that it will have on NIH, the
extramural research community and the private pharmaceutical
market. You've alluded to this a little.
As I stated, I remain concerned that this announcement was
made in December, yet we don't have some details before the
subcommittee yet.
The reorganization will impact all of NIH's 27 Institutes
and Centers and will shift at least $1.3 billion. I believe the
subcommittee needs to review such a proposal, especially one
that has such a potential impact on the NIH community.
My question is when will we receive some more details that
we can renew--for the staff and the subcommittee--or do you
have a timeline? I know it's a difficult transition.
Dr. Collins. Senator, it's a very fair question, and I had
certainly hoped that by the time of this hearing we would have
been able to provide the full details about the budgetary
consequences of standing up this new and exciting new center.
It is a complicated process. The recommendation to do this
came forward from my Scientific Management Review Board last
December 7.
Rather than putting this off until fiscal year 2013, which
I thought would really have wasted an opportunity, we decided
we would try to move as quickly as possible. Although some
people said, ``Hey, this is the Government. You can't possibly
do that by October'', well, they used to say that about the
Genome Project. So I decided that we could, and we should,
because this is the best way to move the science forward.
But, of course, what this means is taking a number of
components that already exist in various institutes and in the
common funded NIH and moving them together into this new
synergistic entity. That's important to point out.
Actually, what we're talking about is not to create new
budgetary implications, with the one exception of the Cures
Acceleration Network, which is in the President's fiscal year
2012 budget at $100 million, and which we hope this
subcommittee and others will see fit to support, because it'll
give us some flexibilities in terms of how we manage the budget
that we would dearly love to have.
But the other pieces of NCATS are basically derived from
existing programs that are moved together in a way that are
going to be highly complementary and synergistic.
We needed, of course, to consult with our communities, with
our constituencies, and, as we figured out how to do the
shifting right down to every employee to make sure that the
programs were encouraged and nurtured, we had to be sure we had
that right.
We are at the point now where we believe we have that
together. It needs, of course, to be reviewed by the Department
of Health and Human Services (HHS) and Office of Management and
Budget (OMB) experts. We hope to get that to you, Senator, in
the fairly near future, within, certainly, the next few weeks
and, hopefully, a very few weeks.
COST OF DE-RISKING PHARMACEUTICALS
Senator Shelby. Dr. Collins, you've also described the
NCATS mission as one of what you call de-risk--that moves basic
scientific discoveries beyond the lab to a point where the
private pharmaceutical market feels confident enough to jump
in.
What is the policy or what would you think the policy would
be if a selected project is successfully de-risked, but no
companies produce the drug or medical product? I know you've
thought about that.
Dr. Collins. And, indeed, I should point out that this is
an activity which NIH has been engaged in for some long periods
of time, and my colleagues, particularly from the National
Cancer Institute (NCI) and National Institute of Allergy and
Infectious Diseases (NIAID), have been supporting this kind of
translational effort in always looking for a commercial partner
at the earliest moment in order to be able to carry a project
through to completion and limit the amount of dollars that the
taxpayers have to cover.
I would say projects that get undertaken at this point need
to think about that from the very beginning. There will be
instances perhaps where no commercial partner can be found,
even all the way through to the end of a phase III trial, but
they will be rare indeed, because those are very expensive
enterprises.
But for very rare diseases, where the economic incentives
are simply going to be very limited, and especially if one is
in a circumstance where you could conduct such a clinical trial
by repurposing a drug that's already been approved for
something else, then NIH may very well find it worthwhile to
undertake that effort.
But you're quite right to point this out. We have to get
the balance----
HEALTH PREPAREDNESS AND OBESITY
Senator Shelby. Absolutely.
Just want to touch on health disparities. You got into it a
little. Health disparities most often associated with the ethic
population persist in rural United States. Stroke, diabetes,
kidney disease and cancer are all more prevalent in both the
African-American community as well as the South.
One of the root causes to health disparity is the obesity
epidemic that is rampant in our Nation. You pointed it out in
your slides. Southern States have the highest rates in the
Nation.
My question is should we be looking for a new paradigm that
broadly addresses this critical national issue at multiple
levels for molecules to behavior to policy? You touched on it
with your slide. And how can NIH help the American people meet
that challenge?
Dr. Collins. So, Senator, I really appreciate the question
because this is an enormous public-health challenge for all
communities, but particularly so for certain underserved
communities.
I'm going to turn to my colleagues, Dr. Rodgers and Dr.
Shurin, who lead the Obesity Task Force at NIH, who are just
putting forward a new research plan that's quite exciting.
Dr. Rodgers. Thank you, Senator.
Because of the extreme importance of this project, and
particularly the recognition that obesity is occurring much
more frequently in children in this country, we've also asked
Dr. Collins for his permission to have the Director of the
Child Health Institute on board as a co-chair of this obesity
research task force.
As Dr. Collins indicated, we just put out this last month a
strategic plan which highlights a blueprint for research in
these critical areas related to prevention and potential
treatment of obesity, particularly in health disparities or in
certain ethnic and racial groups, in older adults, in young
children.
And it recognizes the fact that obesity is a multifaceted
problem, and, therefore, you need multifaceted solutions,
including behavioral, medical, surgical and others.
Senator Shelby. How important is behavioral here----
Dr. Rodgers. Behavioral research is extremely important.
For example, we know that for childhood obesity just decreasing
screen time, the amount of time kids are in front of the
television, the computer, video games can greatly reduce the
risk. Increasing physical activity is another important
component to this.
Let me turn to my colleague, Dr. Shurin, who actually has a
very active program involving children.
Dr. Shurin. Thank you, Senator. We share your very deep
concerns about this.
One of the things that Dr. Rodgers and I have done is to
convene a group, a collaborative on obesity with the CDC and
the Department of Agriculture with the support of the Robert
Wood Johnson Foundation, which has a particular interest in
childhood obesity.
So we have a multifaceted research program. Much of it is
community-based research, but it also ties in to many
biologically and behaviorally oriented research programs really
looking at the factors that impact obesity.
As Dr. Rodgers has said, we've got several studies now
which show a very profound influence of screen time. Physical
activity is at least as important as diet, but dietary issues
are obviously of major importance. And we have a very rich
portfolio of research projects looking at what are the most
effective interventional strategies.
Many of these are site-based, worksite-based and school-
based programs. I think one of the things that's particularly
important is that many of the projects that we get into which
look very promising don't actually pan out. It's very helpful
for us to know what doesn't work, so we can really be fairly
aggressive in pursuing the ones that do.
The impact of policy changes, the engagement of the food
industry and of preventive health services we think are
particularly important. We initiated a program called We Can,
which is ways of enhancing childhood activity and nutrition,
which we have now several thousand community partners aimed
very heavily at reducing screen time and increasing physical
activity and focusing very heavily on dietary activities.
We have several collaborations with the food industry, with
several partners in the food industry which have become
increasingly responsive, but we think that there are probably
going to have to be some policy approaches that will have an
impact on this, that simply relying on individual choices is
not going to be sufficient.
Senator Shelby. Thank you. Thank you, Mr. Chairman.
Senator Harkin. Thank you. In keeping with the
subcommittee's policy in order of appearance here at the
subcommittee be Senator Reed, Senator Moran, Senator Mikulski,
Senator Brown.
Senator Reed.
GLOBAL COMPETITIVENESS
Senator Reed. Thank you very much, Mr. Chairman, and thank
you, doctors.
Dr. Collins, just a quick point, that Chinese facility that
you mentioned to is supported by the Chinese Government or do
we know?
Dr. Collins. Interesting. It is partly supported by the
Government, but they actually have put this in place by taking
out a bank-supported loan to allow them to purchase 128 of
these----
Senator Mikulski. They didn't get it here.
Dr. Collins. Senator Mikulski is correct. It was not at an
American bank. And they have purchased 128 of these sequencing
machines, the largest collection in the world, and they are
quite confident that the value economically will fully justify
the cost of buying the machines.
They've also hired about 4,000 of the smartest young
scientists that I've ever seen in one place from all over China
who are in their 20s and who are prepared to change the world
and probably are going to.
And we should celebrate that. I don't mean in any way to
say I think this is a bad thing, but it worries me to see that
China has taken that kind of initiative and we have not.
Senator Reed. But the financing might be considered quasi
private and public together, but this is clearly an initiative
at the highest levels of the Chinese Government to get this
done.
Dr. Collins. Yes.
Senator Reed. And we are at this debate here in the United
States about what we will commit as a Government to not only
the genome sequencing, but so many of the innovative proposals
you've talked about.
Dr. Collins. That's correct----
NIC VOLKER TREATMENT DETAILS
Senator Reed. Just want to clarify that.
I thought also, joining the chairman, that the poignant
story of Nic--I wonder did he or his doctors avail themselves
to the National Cord Blood Registry, CDC's the MATCH? Was that
a----
Dr. Collins. I don't know in terms of where his stem cell
transplant came from. I can find that out for you, Senator.
PEDIATRIC RESEARCH
Senator Reed. But that's an initiative that Senator Hatch
and I worked on and I hope it contributed to that great story.
[The information follows:]
Nic and the National Blood Cord Registry
David A. Margolis, M.D., professor of pediatrics and director of
the Bone Marrow Transplant Program at the Children's Hospital of
Wisconsin, said, ``Our donor coordinator says `Yes. If it were not for
the National Marrow Donor Program, and the single access that it
provides, the search (for Nic's cord blood stem cell donor) would have
been more difficult, time consuming, and may not have yielded the same
results.' ''
Senator Reed. But this raises a larger question, then, in
terms--that I have with respect to the amount of resources
going to pediatric research. You've cited several examples. Dr.
Rodgers, Dr. Shurin have talked about, you know, the research
you're doing in children's obesity, et cetera.
For example, I'm told that only about 4 percent of the
funds in the National Cancer Institute are for pediatric
cancers. That might be good news, because it might represent
that it's a relatively healthy population, but just generally a
sense do you think we're making the right allocation of
resources to pediatric research?
If we're not, are there structural issues; that is, is the
peer-based review tilted toward adult experts rather than
pediatric experts? Any comments I'd appreciate.
Dr. Collins. Well, quickly, and then I'll ask Dr. Varmus to
address the pediatric oncology issue, but we have an entire
Institute at NIH, the National Institute of Child Health and
Human Development, which has as its major focus pediatric
research and which certainly is a place of a great deal of
interest and excitement right now because there are so many
promising developments in childhood illness.
We also are investing in a very large national project, an
unprecedented one, the National Children's Study, which will
enroll 100,000 kids beginning even before conception through
pregnancy and up to age 21 in order to comprehensively collect
the kind of information about environmental exposures and
genetics that may shed light on diseases like autism and
diabetes that have continued to vex us.
I would say, yes, there's a lot of investment. Could there
be more? You bet there could, but that would probably be true
in virtually every area that we're looking at. With these 17 to
18 percent success rates that were mentioned by the chairman,
we are clearly not able to support a lot of great science that
we'd like to support.
Senator Reed. Before Dr. Varmus, I must say that Brown
University Medical School is participating along with Women and
Infants Hospital, and Dr. Rodgers is their commencement
speaker, because he's one of the most illustrious Brown
University medical graduates in the history of the program. I
had to put that in the record. Forgive me, Dr. Collins.
Dr. Varmus.
Dr. Varmus. Senator Reed, thank you very much, and I
appreciate your honoring my colleague, Dr. Rodgers.
You're correct that the amount of money we specifically
identify as being devoted to pediatric cancer research is about
4 percent of our budget, which is about $200 million a year,
but, of course, a great deal of other funding that we're
involved in addresses cancer more generally and is applicable
to pediatric problems.
Let me say a few words more broadly about pediatric cancer.
Chairman Harkin alluded to the fact that we do cure most
patients with leukemia. Pediatric cancers, in general, are much
more effectively treated, whether they're brain tumors or
neuroblastomas or Wilms tumor or leukemias, but, nevertheless,
there still is an increased incidence of childhood cancers over
the last several years by about 30 percent, but a continuing
decline in mortality.
Nevertheless, mortality figures do not tell us the whole
story. There are severe consequences of being treated for
cancer at an early age--developmental defects, loss of mental
capacity in some individuals, and, of course, a very high
incidence of second tumors, particularly in survivors' 20s and
30s.
We're trying to address these problems in a variety of
ways. We're trying to understand the cancers more profoundly
with some of the genomic-sequencing techniques that Dr. Collins
alluded to.
We, in fact, have spent Recovery Act money on a new project
to study pediatric cancers in great detail. And we have new
therapeutic maneuvers that are based on more targeted, bullet-
specific drugs and antibodies that have been very effective in
reducing mortality rates in neuroblastoma and leukemias with
therapies that are less toxic.
We have paid a lot of attention to the survivors of
pediatric cancer. We have a nationwide survivors study for
pediatric cancer that has enrolled over 20,000 patients in
roughly 37 different centers. So with these and other projects,
we think we're making a pretty good effort to control the
consequences of treatment of pediatric cancer and to do a
better job in treating pediatric cancers in a less toxic
manner.
But you're correct, we could do more, but, as you know, we
have budget constraints this year. It's unlikely that we'll see
a very significant increase in that domain or any other in the
coming year.
BIOMEDICAL RESEARCH RESOURCES AND WORKFORCE
Senator Reed. Thank you very much. Thank you, gentlemen.
Thank you, Dr. Shurin. Thank you, Mr. Chairman.
Senator Moran. Chairman Harkin, thank you.
Dr. Collins and your colleagues, fellow doctors, I
appreciate the opportunity to have this conversation with you
this morning.
This is a beginning course for me. I have 4 months of being
a United States Senator and being a member of this
subcommittee, but I'm excited about joining Senator Harkin and
Senator Shelby and my colleagues here.
I think medical research is a huge component of the future
of our country. I think it matters greatly, and I commend you
for your efforts to date.
In my healthcare reform bill, we would support medical
research in a dramatic way. I think it's a cost-saving measure.
It's about saving people's lives, improving the quality of
their life. And so from an economic--as you point out--but also
from a personal, humanitarian point of view, what we do here in
this subcommittee and what you do at NIH matters greatly.
And I would welcome the opportunity to become better
acquainted with NIH, its personnel, its mission. Maybe the
people in the rows behind you--I want my doctors out there
doing the research, but I'm happy to have others at NIH devote
some time to educating me so that I can better understand how
we can advance the cause of medical research here in the United
States.
I would ask first if there is something missing. We're here
in an appropriations subcommittee, but other than money, is
there something missing at NIH or here in our country, in the
United States, that makes it much more difficult or makes it
difficult for you to reach the goals that you outlined for us
today or is this just a financial issue, how many dollars do we
devote? What are the other, if any, impediments toward success?
Dr. Collins. Well, Senator, I appreciate the question and
certainly appreciate your strong statement of support, and you
are most welcome to come and visit us at NIH. We'd love to host
you for a visit and show you some of the things that are going
on in the laboratories and in the clinical center, the largest
research hospital in the world, that's up there in Bethesda.
Senator Moran. Thank you.
Dr. Collins. But as you know, most of the money that NIH
sends out in grants goes to the 50 States, including Kansas,
and we're very proud of the research that's going on there in
your State.
Senator Moran. Thank you.
Dr. Collins. In terms of other things that potentially are
barriers, certainly we do not have what I would call a vigorous
pipeline of young scientists coming into our field, and part of
that is the sad state of K through 12 science education in this
country, which has certainly, by any measure, slipped badly
over where it used to be back in the--30 or 40 years ago in the
sort of post-Sputnik arena where science education was really
emphasized.
Now, in many schools, it is unfortunately quite
rudimentary, and I think we lose, therefore, the chance to
capture young people's imagination that science would be a
place they wanted to spend their own careers. And that means we
have fewer American-born individuals who are clamoring to come
in to our laboratories and make the next great discoveries.
We have lots of interest from individuals born in other
countries to do that, but that interest has actually declined a
bit as more opportunities are present in their own countries.
Some of them, certainly in large numbers, still come to
train in our universities, but they often now go back to their
original homes and carry out research instead of staying in the
United States. And some of our visa practices have not helped
in that regard in terms of making such talented scientists from
other countries feel less welcome than we wish they were.
It seems to me that would be a very important area for us
to, again, try to get right, because it is to our advantage to
recruit such individuals--and our universities are still seen
as the very best in the world--to come and do their research,
but then for us to also be able to capture their talents in an
ongoing way I think would be a great advantage. That is just
one of the areas.
But, frankly, the major concern that I think we have is
just the lack of sufficient resources to chase down all of the
great ideas that are now potentially possible.
INTERDISCIPLINARY RESEARCH
Senator Moran. I appreciate that answer and look forward to
finding solutions in that regard and understand now the
importance you place upon the resources.
I did visit the University of Kansas last week and one of
the research facilities there, the Molecular Libraries Program,
and I'm very interested in what the ranking member pursued in
regard to NCATS.
And when I heard your testimony today, my assumption is
that this will take a lot of different kinds of scientists
engaged in this effort, and I guess an initial question would
be what steps would you anticipate being taken to ensure that
the best of American science in as many areas will have that
opportunity to contribute to this new program?
Dr. Collins. Well, a very appropriate point. It will take
an interdisciplinary effort of a considerably revolutionary
sort.
It means bringing together biologists and chemists--as no
doubt you saw at the Molecular Libraries Program in Kansas--
along with computational experts, structural biologists who can
actually figure out the shape of molecules and figure out which
shapes fit together in a way that might make a particular drug
work, immunologists who can help us with monoclonal antibody
development, engineers who can work on devices that will be the
next generation of what we need for all manner of medical
applications, and those disciplines traditionally haven't had
such an easy time talking to each other, and one of our goals
through this program and many others is to do that.
Maybe this is also partly in answer to your first question
about what are some of the barriers. In some way our own
traditional disciplines have presented some of that problem,
although I think those barriers are coming down.
Clearly, there's a lot of excitement--and I suspect you
perceived that in your visit to the Kansas center--about the
potential here of bringing those disciplines together with
these new comprehensive sciences to enable academic
investigators to play a larger role in reengineering this
broken pipeline to try to make it possible to come up with
therapeutics and devices and diagnostics in a shorter time
period.
This resonates with me for the same kind of feeling I had
about the Genome Project 20 years ago. It was controversial
then, too, of course. A lot of people wondered whether this was
biting off more than the Government could chew, but it
recruited into the effort some of the best and brightest minds
of that generation because they could see the potential.
I think that same atmosphere is beginning to appear in
translational science, and I suspect once we have the programs
in place it will not be hard to recruit some really brilliant
minds to play a role in this.
Harold, did you want to add to that?
Dr. Varmus. I think it might be important to reassure you,
Mr. Moran, about the effort that's being made in translational
research across the institutes.
As Francis alluded to in his testimony, a great deal of
work--interdisciplinary work, indeed--has gone on in the
Institutes and will continue to go on, while NCATS provides a
catalytic advantage to the efforts that we're making by
providing new methodologies, ways to analyze how translational
research is done, some core facilities.
But, as you probably know from going to your cancer center
at the University of Kansas, that there is a lot of
translational research going on there, and that's done by
interdisciplinary teams.
So all of us at the NIH are engaged in this process and
we've had a lot of experience in gathering multidisciplinary
teams over the last decade or so to do this kind of work.
Senator Moran. So it's not new and we know it can be done.
It's being done today.
Dr. Varmus. But we're all engaged in the process, and it's
not going to fall solely on the head of NCATS.
Senator Moran. And, unfortunately, I'm on the social
science in my education and I detect that the same thing may be
there between chemistry and biology as there is between history
and political science.
Dr. Varmus. Well, there could well be. Yes----
Senator Moran. But I appreciate that, and I did see the
enthusiasm. That was perhaps the takeaway of my visit is the
excitement that is there and the belief in the potential of
what can be accomplished.
Dr. Varmus. Yes.
Senator Moran. It's very appealing to me.
Dr. Collins. Dr. Fauci wants to add something.
Dr. Fauci. There is one other thing that sometimes gets
misunderstood. We mention--and Dr. Varmus mentioned also that
there's a lot of translational research going on.
What the center is going to be directing itself at is to
really advance what we call the discipline of translational
research, in other words, to help us to do more innovative ways
of approaching translational research. So translational
research goes on to the tune of many billions of dollars at the
NIH, mostly in the big Institutes, but some of the smaller
Institutes also.
What we want to do is advance the discipline of how it's
done, making it a 21st century approach toward translational
research as opposed to relying on many of the methodologies
that have been good, but that we think we can do better on.
That's what it's really all about, putting forth the discipline
and improving the discipline of translational research.
Senator Harkin. Thank you. Thank you, Senator Moran.
Senator Mikulski.
SUPPORT OF NIH
Senator Mikulski. Thank you very much, Mr. Chairman. I'm
very proud of the fact that NIH is located in the State of
Maryland. And for more than 25 years, I've visited NIH
regularly, and every time I come, my eyes pop with wonder, my
heart beats with excitement and I just--one of the reasons I
wanted to be here today was to tell you and all of the people
who work at NIH how proud I am of you, and how America ought to
be proud of you.
Dr. Collins, you did path-breaking pioneering work when
mapping the genome. And we were in a race. You had another
competitor down the street. You broke the code and we
invented--not only mapped the code, but came up with new fields
called computational biology, bioinformatics, new exciting
careers that help both us in particularly the private sector be
able to come up with new products.
And, Dr. Fauci, you, what you've done. You were the guy who
broke the AIDS code. You were the guy that came here when we
were gripped in fear and near panic when we were shut down due
to anthrax and we had no place to turn in our United States
Government for information, but we turned to you and you kept
us on the right path, so that we could keep the doors of the
Capitol----
Dr. Varmus, a former head of NIH. You know, NIH Directors
don't leave. They leave legacies, and then they come back to
create new ones, and we're so glad to see you. And we note that
when you were at Sloan-Kettering you had a lot of other zeros
behind your compensation package, which says something about
why you came back.
And to Dr. Rodgers and Dr. Shurin, who also was educated at
Hopkins, we're just glad to see you.
And, Mr. Chairman, and what they do is the work that helps
us manage the biggest budget busters in our healthcare budget--
diabetes, heart disease, the chronic conditions that lead to
chronic problems in the way we live, in the way we have to fund
healthcare.
So I wanted to be here today to say for all the people work
at the institutes, all the people work at the various offices,
all the lab techs, the security guards, the fire department,
we're really proud of you.
So having said that, I want to make sure we help NIH be
NIH. So I want to stick to the basic mission in addition to
these exciting new ideas.
Dr. Collins, how many research grants did NIH fund last
year, and how many requests did you get for funding? In other
words, what is the funding gap, and particularly not only with
the tried and true research, but also with those promising
young, maybe more upstart type thinking?
Dr. Collins. So in fiscal year 2010, we funded
approximately 9,300 research grants. The success rate in fiscal
year 2010 came out at just about 20 percent; that is, one out
of five that were able to be supported.
With the fiscal year 2011 budget now in front of us, now
that it's been decided, we won't do that well, because, of
course, as you know, after the dust all settled, we ended up
with a 1-percent cut of $320 million, although I really want to
express my appreciation----
Senator Mikulski. So that's what one percent means, $320
million?
Dr. Collins. That's correct. But I do want to express my
appreciation to members of this subcommittee, because I know
there was a great deal of debate about exactly where the dust
would all settle out, and certainly many of the proposals were
vastly worse than this, and I know many people really went to
bat for NIH, and we appreciate that enormously.
But we do believe that in fiscal year 2011--with some
uncertainty in the number, because we don't actually know how
many grants we will receive, and, of course, we're talking
about a proportionality here--that the success rate will fall
to approximately 17 to 18 percent, and that will be the lowest
in history.
We will do our best to try to manage the resources that
we've got, and we've made a number of adjustments to try to
keep that number----
Senator Mikulski. But for every one grant that you can
fund, let's even go to before fiscal 2011, how many are
unfunded?
Dr. Collins. So it would be five out of the six. If you
have six grants in front of you, we're going to fund one of
them and five of them are going to go begging.
WORKFORCE PIPELINE
Senator Mikulski. All of which are quite promising.
Now, let's go to much is made about recruiting young people
into science, and we want a lot of initiatives in that, but
young people follow opportunity. So when we look at your
internship, your fellowship program, both for high school,
undergraduates and so on, again, how many students can you have
come in to NIH? And how many--In other words, how many can you
take and how many apply? What's the enthusiasm gap here?
Dr. Collins. Well, there is enormous enthusiasm. Certainly,
we run a number of internship programs on the NIH campus. We
have a program for high school students and college students
who come and spend 10 weeks in the summer. That is always
oversubscribed by at least a factor of five in terms of the
number of slots that we have available and the space that's in
the labs.
We also have a program for individuals who are finishing
college, who are really interested in science, but they're not
sure whether they want to go to graduate school or medical
school. They come and spend 1 year, sometimes 2 years doing
full-time research in the lab.
I have three of those students in my lab right now. They're
enormously energized, excited about what they're doing, and
they go on to do great things. This is a really important
program.
But there again, the number of applications we have for
that so-called post bac program is at least four or five times
greater than the number of slots that we have available to
offer.
Senator Mikulski. So while we're busy--You know, we like to
pound our chest and come up with all kinds of things in
education to encourage people for science, but our young people
are going in it, but they need opportunity, both in the public
as well as in the private sector.
Dr. Collins. So, Senator, I've just set up, as part of my
advisory committee to the Director, a working group to look at
our workforce issues, and I've asked Dr. Shirley Tilghman, the
president of Princeton, to co-chair that, because I think we
need a better handle on what the supply-and-demand issues are
in terms of the biomedical research workforce.
We want to be sure that we're looking forward with a clear
eye toward all of the different pathways that are going to need
well-trained, doctoral-level biomedical researchers and that
we, NIH, as a major source of training support are
appropriately tuning our programs so that we have the numbers
right in terms of how many people we are bringing in and what
kinds of careers we're preparing them for.
EFFECTS OF A GOVERNMENT SHUTDOWN
Senator Mikulski. Well, I think this would be enormously
useful to this subcommittee, Mr. Chairman, because, as you
know, this is a topic--a big public-policy topic they ponder
all of the time.
My last just comment or question is with all the talk of
the shutdown and during H.R. 1, a cut to the National Cancer
Institute, which was stunning to many people, including me,
what is the morale at NIH now that they thought that they might
be sent home and told that they were non-essential and the cuts
might be coming?
I mean, I must say both the chairman and the ranking member
were enormously supported to minimize the disaster, but it was
not a victory.
Dr. Collins. So I would say this was a very difficult
period to go through. We were required, of course, in
preparation for what appeared to be a very high likelihood of a
shutdown, to define how we would manage that, and that meant
defining which particular employees were considered essential
and which were excepted, was the term that was used, and which
were non-excepted.
And, of course, those who were involved in patient care or
management of animals couldn't very well just not come to work,
but others were told, ``I'm sorry. If there is a shutdown, you
can't come to work.''
Think about how that feels if you're a post-doctoral fellow
who's in the middle of an experiment that you've been working
on for 2 or 3 weeks and has another couple of weeks to go and
you're being told, ``I'm sorry. You're not allowed to come to
work tomorrow if the Government shuts down.'' It did have a
very significant effect. People were quite shaken up by that.
I think people are--in the aftermath of that--feeling a
little uncertain about what it's like to work in this
environment and hoping that we won't face that again. But,
again, I think everybody understands these are terribly,
terribly difficult times for our country.
INFLATION EFFECTS ON PURCHASING POWER
I just want to show you one image because I think it might
be actually useful.
[The information follows:]
Senator Mikulski. Okay. I'm going to just--chairman
regulate the time, but I'm fine with it, but if that's okay
with the chairman.
Dr. Collins. It'll take 1 second. This is basically why we
are in such a crunch.
Senator Mikulski. Well this is a terrific slide.
Dr. Collins. So this is--this shows----
Senator Mikulski. It's more like the way my heart went up
during the shutdown mode.
Dr. Collins. So in blue, you see the appropriations for NIH
going back to 1998. You see the doubling that happened between
1998 and 2003, and then you see that since 2003 the NIH budget
has been much more in a flat trajectory.
But in yellow, you see the effects of inflation, the
biomedical research and development index, which has been
eating away at our buying power since 2003, placing us now,
even with the President's budget, in the range of what we were
at 2001. So we're sort of where we were 10 years ago.
You see the Recovery Act dollars there in 2009 and 2010,
which were a wonderful boost to the scientific community, but,
of course, that was 2-year money.
That is why the success rates are now dropping to where
they are. It's all pretty much clear what the consequences
would be once one considers what's happened to buying power for
research.
Senator Mikulski. Thank you. Mr. Chairman, thank you.
Senator Harkin. Senator Mikulski.
Senator Mikulski. You are the genius club. I mean, you
really are. So thank you.
Dr. Collins. Thanks.
Senator Harkin. Senator Brown.
NEW INVESTIGATORS
Senator Brown. Thank you, Mr. Chairman. And I've always so
enjoyed having panels from NIH, some of the smartest people in
the country, especially those who used to teach in Cleveland,
Dr. Shurin.
But thank you. I mean, it really is illuminating and we
thank you so much for your service. This is such an example of
public service and why government matters.
And when I hear some of the know-nothings that hold jobs
like we hold say that the Government is broke and that
Government can't function and Government doesn't contribute
anything and Government doesn't create jobs, you know, I think
about the special forces. Those were Government employees that
were in Abbottabad, but I think primarily of what NIH does and
what you contribute to public health and to wealth of our
country.
I want to take up on what Senator Mikulski said, and Dr.
Collins' response, on the one out of five grants. I was in the
House, ranking Democrat on the subcommittee back when we
actually wanted to fund public health bipartisanly in this
country 15 years ago, doubled the budget at NIH.
And I remember in those days those numbers that some of
your predecessors--well, some of you and some of your
predecessors--would cite, now that we fund one out of five
grants or one out of six grants. It's gotten a bit worse than
what Senator Mikulski said.
The other part of that story that I remember is the young
researchers that you are always looking to attract when you
teach at med schools and you counsel people and you mentor
people, those are the least likely to be the one out of five
that gets the grants--or the one out of six--because my
understanding is that people that have done these grants over
time kind of know how to win the grants better than the young,
bright researcher also applying for the grant. So the numbers,
in some sense, among younger, hungry researchers are even
worse, the ratios, and too many of these young people leave the
field.
And I think that's, to me, the most compelling reason that
this fervor to cut budgets as--we need to address our budget
deficit, but we're creating terrible deficits in young
scientists and terrible deficits in the public body of
knowledge, I just want to say.
COST OF PHARMACEUTICALS
Let me go--two issues I want to talk briefly about. One is
the issue of the Makena drug, the progesterone that was
developed over time into a--produced by compounding pharmacies
as you know, has made a huge difference, provable huge
difference, clinically trialed--if that's a verb or adverb--
huge difference in preventing early birth, pre-term births.
We know what this KV Pharmaceuticals in St. Louis did. We
also know that you at NIH have invested $21 million on now four
clinical trials, in the midst of the fourth one and still
investing in this and finding, I think, more indications,
perhaps, to use this drug, this progesterone, this compounded
pharmacy drug.
Well, just give me your thoughts, briefly, if you would,
how do we prevent this from happening? The Food and Drug
Administration (FDA) has stepped in and done something pretty
unusual and pretty gutsy by saying they're not going to enforce
the cease-and-desist order on compounding pharmacies.
So when I talk to obgyns and visit hospitals--I was at
University Hospitals yesterday in Cleveland--2 days ago--
talking about they're still compounding it, still producing
this.
When taxpayers invest in this and it's clearly a drug in
the public interest and one company can get exclusivity for 7
years, while you continue to do these clinical trials
expanding--in a sense expanding their market on this fourth
clinical trial you're doing--and I know this cuts across FDA,
HHS as a whole and you and CDC and all, but what do we do about
this?
Dr. Collins. Well, Senator, I think you spoke out quite
strongly about the Makena situation and I think brought a lot
of attention to a circumstance that really was deeply
troubling, that a drug--let's just call it 17P--that was
previously available and compounded by pharmacists and then was
put into a clinical trial, ultimately ended up, after FDA
approval and orphan-drug status, going up in cost from
something that cost $10 or $20 to something that costs $1,500.
We were also deeply alarmed to see that and quite pleased
to see FDA step in and say they were not going to go after
pharmacists that continued to provide the compounded material.
And that, by the way, also, and along with your strong
statements and that from some of the professional groups, did
cause KV Pharmaceuticals to drop their costs, but still at a
much higher level than they were in the old days.
NIH has its hands a bit tied in this situation. Back in the
1990s, when Harold Varmus was NIH Director, we had a big
discussion about whether drugs that NIH plays a role in
developing should have some sort of reasonable pricing clause
attached to any kind of licensing that we would do to a
company.
And while that might have seemed like a way to avoid
another kind of Makena outcome, it was a poison pill for any
serious relationship that NIH would have with a company. No
company in this country or elsewhere would be interested in a
partnership with NIH under those circumstances.
What we can do is to make sure that if profits ensue and
NIH has made a contribution to that, in terms of genuine
intellectual property discoveries, that there should be royalty
sharing on that basis.
But when it comes to setting the price, as KV did, even
though we supported the clinical research, we are probably not
the agency in a position to be able to do something to step in
and interfere with their pricing decision.
It was the public outcry, your outcry, Representative
DeLauro, the professional societies that I think actually
turned the tide.
Senator Brown. But that outcry only brought the price from
$1,500 multiplied times 20, with 20 weeks of treatment, as you
know----
Dr. Collins. Yes.
Senator Brown [continuing]. $1,500, $30,000, when it was 20
times $10 or $20--depending on the compounded pharmacy's
charge--down to $690. So the outcry worked with FDA. The outcry
barely worked with KV.
But is there a way to sort of cross the--I understand that
you don't want to engage in partnering and price-setting and
all that, but--or maybe you do--but when a company so
overreaches like this, it was such an affront to the public
interest, if there's a way, sort of across help agencies we
could find some solutions or----
I mean, Dr. Hamburg was in here and she said, well, you
know, FDA didn't do this. She wasn't defensive at all, but then
FDA did something. This was before they made that decision.
But I just will follow up with you, but I'd like to see if
there's a way to----
CANCER CLUSTERS
My other question--I'm sorry to go over the 5 minutes, Mr.
Chairman--Dr. Varmus, you had talked about pediatric cancers
and Senator Reed had asked you about that.
There's a cancer cluster in Clyde, Ohio, where many, many
children, under 12 in most cases, have developed cancer, and I
know you see these. There are four or five believed to be
cancer clusters. I don't know if that's a particular medical
term, but is certainly what we talk about.
What is NIH's role in sort of examining these, exploring
these, finding out the environmental cause, if it is that, as I
presume--I guess I presume it is. What is your role in that?
Dr. Varmus. Well, we do investigate that. We have a
Division of Epidemiological Cancer Research that will look at
these clusters to ascertain whether or not the cluster is real.
Because, as you might expect, if cancers are distributed in
their frequency across the country, there are going to be some
places that just, by chance, have a particularly high or
particularly low incidence, and there are several classical
examples of clusters that turned out only to be arithmetic
aberrations, but without any clear indication of causes.
On the other hand, there have been clusters of cancers that
are linked to certain practices or to exposure to industrial
mutagens, and we would go in with collaboration with the
National Institute of Environmental Health Sciences and try to
ascertain what might be a precipitating cause.
So we do have a role and we would--I don't know about the
one you're citing, but we can certainly look into it and report
back to you on what----
Senator Brown. We have talked to NIH overall, but we will
specifically talk to you.
Thank you, Mr. Chairman.
[The information follows:]
Clyde, Ohio Cancer Cluster
State and Federal Responses to Cancer Cluster Reports.--State and
local health departments respond to cancer cluster reports and provide
the first level of response and review of the most current local data
for the area. If needed, these local health departments can request
assistance from Federal agencies, including the National Center for
Chronic Disease Prevention and Health Promotion (NCCDPHP) of the
Centers for Disease Control and Prevention (CDC), the Agency for Toxic
Substances and Disease Registry (ATSDR), and the U.S. Environmental
Protection Agency (EPA). CDC's role in investigating potential cancer
clusters is to provide technical assistance to States at their request
as they conduct their investigations. In State cancer registries,
States have the data needed to determine whether a cluster exists.
National Cancer Institute (NCI).--NCI does not investigate
anecdotal clusters of individual cancer cases in neighborhoods, but
rather clusters of counties with elevated rates as part of the
geographic mapping strategy to identify and investigate high-risk
populations for etiologic insights. However, upon occasion NCI's
Division of Cancer Epidemiology and Genetics (DCEG) may be called upon
to consult with local and State health officials and CDC experts as
they investigate purported cancer clusters.
DCEG's research portfolio includes analysis of cancer treands in
human populations, and DCEG investigators conduct studies both within
the U.S. and around the world where the incidence of certain cancers is
significantly higher than might be expected. Examples of such
investigations include lung cancer in coastal communities in the U.S.,
which was linked to asbestos exposure in ship yards, and oral cancer in
women in the rural south, which was linked to smokeless tobacco use.
DCEG researchers are currently investigating the reasons for the very
high rates of bladder cancer in northern New England; they will soon be
reporting data from this effort. They are also conducting a study to
explore the elevated rates of Burkitt's lymphoma in regions in Africa.
Regarding the Clyde, Ohio Investigations.--It is our understanding
that there was a multi-year analysis of a suspected cancer cluster in
Clyde, Ohio by the Ohio Department of Health (ODH). Both CDC and ATSDR
provided technical assistance to the State officials over the course of
the multi-year assessment. While NCI has not received any reports or
conclusions, it is our understanding that the assessment's final
conclusion was that the data were inconclusive and there was no cancer
cluster identified. These Federal public health agencies are continuing
their collaboration with ODH and are available to provide support as
needed.
FLU VACCINE
Senator Harkin. Thank you, Senator Brown.
Dr. Fauci, for years, you've been here, year after year,
and we've talked about flu vaccines, and, some time ago, I
remember you talked about progress being made toward a--perhaps
a universal type flu vaccine. You mentioned it in your written
statement, which I read last night. Again, how close are we?
Dr. Fauci. Well, I can't give you an exact time in years,
because every time a vaccinologist does that, he or she gets
burned. So I'll refrain from that, but I can tell you that we
clearly are considerably closer than when I spoke to you last
time at a hearing when we were talking about the possibility of
getting away from that very frustrating situation where each
year you have to hopefully guess right, and we do most of the
time, but not all the time.
But even more importantly, when we're faced with a pandemic
flu like we were with the 2009 H1N1, when we made a vaccine
after isolating the virus, but the production issues were such
that by the time we got enough to distribute, unfortunately,
the pandemic had already peaked. Fortunately for us, it was a
relatively mild one, but that's not going to happen all the
time.
So what's happened in the last year since we spoke, Mr.
Chairman, is that there have been a number of experiments that
have been conducted both at the NIH and by our grantees and
contractors, which have really identified components of the
influenza virus that the body generally does not make a very
good response to readily, and that part of the virus is the one
that would give you protection against virtually all strains.
And one of the reasons is is that it's sort of hidden from
the view of the immune system. The thing that the immune system
sees really clearly is the part of the virus that changes from
season to season, and that really changes a lot when you get a
pandemic. There's a part of the virus that the body can make an
immune response to that it doesn't usually see very well.
So what investigators have done, in a very simple way, is
that to put that particular component of the virus in a form
that the body would see it much more sharply and clearly. This
has been done in animal models and proven to be inducing
responses that are good against decades of changes of
influenza.
And, now, those studies are being done in what we call
phase I trials in humans, and the early work indicates that,
clearly, it looks quite safe, and, second, it is inducing
responses that span multiple years.
So I believe it's really just a matter of time. As you
know, clinical trials, when you want to prove safety and
efficacy over a period of time, naturally would take years, but
it's on a track that I believe it's going to happen. I don't
think it's going to be a question of if. It's going to be a
question of when. So we're really quite excited about it.
And that's a very good example of that transition from
fundamental basic research observations on molecules and their
confirmation and how that ultimately gets translated into
something that, if successful, is going to have enormous public
health benefit.
Senator Harkin. Well it would. I mean, the amount of just
savings alone on annual flu shots would be incredible, aside
from the fact that you wouldn't--I would, from what I
understand is if this was really developed, the threat of
pandemics would not be as large as they are now either.
Dr. Fauci. The ultimate goal is to have on the shelf, ready
for utilization a vaccine that does have the universal
characteristics to it, so that if you do get a change with a
pandemic, that you can actually have that particular virus be
covered by it.
So we'd like to get it to the form--I don't think it's
going to be perfectly this way, Mr. Chairman, but it's going to
be close. I don't think it's going to be one flu vaccine and
that's it for the rest of your life.
It'll probably be having to be given every several years to
continue to boost the immune system, but we would like to be
the way we are, for example, with measles or hepatitis or
polio, where you just make a lot of it, you have it available
and when you need it, you deploy it, as opposed to having to
play catch up every single time a new virus emerges.
MEDICAL MILESTONES
Senator Harkin. Very good.
Dr. Varmus, in 2001, Gleevec was on the cover of all our
national news magazines, talked about it being the magic bullet
that would herald in a new age in the war against cancer. For
the first time, we had a drug that specifically targeted a
known cancer gene. It took this deadly blood disease, turned it
into a chronic, but survivable condition.
We were told that Gleevec was the promise of the future. We
talked about it in our subcommittee hearings at that time, but
that was 10 years ago. We haven't had any other Gleevecs.
What's happened? How come no more Gleevecs?
Dr. Varmus. Well, I wouldn't characterize it quite that
way, Senator. Gleevec remains the poster child for targeted
therapy.
Senator Harkin. Yes.
Dr. Varmus. And just to give you a brief update, it's used
not only for the treatment of chronic myeloid leukemia, the
leukemia you heard about, it's used for the treatment of
several other diseases in which potential targets for the drug
are mutated, and that includes gastrointestinal stromal tumors,
a number of other blood diseases, and, indeed, a few other
diseases in a few cases in which certain genes are known to be
mutated as a result of analysis of the genome of those cancers.
Moreover, it's recently been shown that we can deal with
drug resistance, a common problem in cancer therapy, by using
drugs closely related to Gleevec but not identical to it and to
treat patients who become resistant to Gleevec.
Second, it's been shown recently that a person in their 40s
or 50s who develop--leukemia now have a normal life expectancy,
which was previously 5 years. That's a dramatic change and it
shows that the efficacy of Gleevec has been sustained over the
last 10 years, and, actually, the evidence that it's effective
is only strengthened.
There are a number of other targeted therapies. They tend
to work quite well initially. Patients become--their tumors
become resistant to therapy. Let me give you a couple of
examples.
One happens to involve my own work on lung cancer, which is
a significant percentage, perhaps 10 percent, of cancers have
mutations in some specific genes against which we have
effective inhibitors, but, generally speaking, within 1 year or
so, on average, patients become resistant to those drugs. We
don't have good therapies to counter the tumors that are
resistant.
Recently, in the case of a disease called metastatic
melanoma, a disease that is secondary to finding a skin tumor,
but the tumor has spread to the liver, bones, and other sites,
it's been found as recently as 7 or 8 years ago, that about 60
percent of those cancers have a mutation in a specific gene
against which an inhibitor has been developed.
It's extremely effective, again, in inducing remissions in
a fairly non-toxic way. This is, again, an orally available
drug that promotes a dramatic regression in the size of tumors.
There are two drugs that do this. They are very likely soon
to be approved by the FDA. They don't cause persistent
regressions, but there's every reason to hope that additional
drugs will be on the way to help counter drug resistance.
So I would say that we've had a number of other targeted
therapies. They have not, in general, been quite as dramatic as
Gleevec, but most of us who are working in this area are quite
optimistic about a number of new drugs, some of which I haven't
mentioned, that are in the pipeline.
Senator Harkin. That drug you mentioned about metastatic
melanoma, you mentioned it in your written testimony.
Dr. Varmus. Correct.
Senator Harkin. What's the name of the drug? I forget----
Dr. Varmus. Well, there are two things that I mentioned in
my testimony, Senator, first was these so-called inhibitors of
BRAF. These drugs are not yet on the market. One comes from
Flexicon, one from GlaxoSmithKline (GSK).
Senator Harkin. Yes.
Dr. Varmus. There's also a new immunotherapy called
ipilimumab, which has been approved by the FDA. That's not the
same kind of targeted therapy, but it's a dramatic development,
because it's one of the first immunological approaches.
There are others, but this is one of the first that
actually displays how we can manipulate our understanding of
the immune system to galvanize the response of the immune
system against a variety of cancers, including melanoma.
Senator Harkin. But I can't even pronounce that word,
ipilimumab?
Dr. Varmus. Ipilimumab.
Senator Harkin. Thank you very much.
Dr. Varmus. Yes, I'm not responsible for that, Senator. It
would not have been my choice. Ipi for short.
Senator Harkin. It seems to me this is about as important
as Gleevec. I mean, this attacks metastatic melanoma in later
stages.
Dr. Varmus. Correct.
Senator Harkin. And this has always been a death sentence
before.
Dr. Varmus. As does the drug that inhibits the BRAF
mutation. But ipilimumab does not work in all cases, but does
prolong life significantly in a very substantial 15 to 30
percent of patients who have metastatic melanoma. It is a major
development, no question about it.
One of the open questions is why do a certain subset of
patients with this disease respond and others not respond.
There are other inhibitors of the so-called brakes on the
immune system that are in development, and I think may be
combined with ipilimumab or used as an alternative when
ipilimumab doesn't work.
So we're quite optimistic after many years of trying to
manipulate the immune system that we have some very serious
handles on how the immune system works that we can use in
cancer therapies.
Senator Harkin. Very good. Thanks, Dr. Varmus.
Recognize Senator Shelby, then I see Senator Kirk has
joined us. I'll go to Senator Kirk next.
ACADEMIA-INDUSTRY COLLABORATION TO REPURPOSE DRUG COMPOUND
Senator Shelby. Thank you.
Dr. Collins, repurposing drugs, you alluded to that
earlier. As we have searched for treatments, as you do, and
others, investigators, to the healthcare challenges, one of the
clear ways that some people believe we can continue drug
development is by finding new uses for drugs that were
discontinued or halted mid-development. By leveraging existing
compounds, researchers in industry can develop and have new,
novel treatments for patients.
It's my understanding that the NIH recently held a
roundtable discussion regarding rescuing and repurposing
compounds. Seems like that's an ideal opportunity for academia
to team with industry to bring treatments to patients faster.
Could you expand on that? What are you doing here and how?
Dr. Collins. I'd be happy to, Senator, because this is a
really exciting potential area to speed up the process of
developing new treatments for diseases that currently lack
effective interventions, and it's another example of the kind
of thing that NCATS will be able to catalyze just by its
convening power.
Yes, we did have this meeting just about 10 days ago. We
invited major leaders from pharmaceutical and biotech
industries to meet with NIH investigators, with academic
experts and to ask the question: Are there in fact, already
sitting in medicine bottles or in freezers of companies that
have tried various compounds and abandoned them along the way
opportunities to take molecules about which we already know a
lot and find a new use for them?
Senator Shelby. Do you have any examples or is it too
early?
Dr. Collins. We have some very striking examples. Maybe
I'll even ask Dr. Shurin to tell the example of Marfan
syndrome. So let me set this up.
Marfan syndrome is a genetic condition caused by a single
glitch in a gene called fibrillin and is characterized by very
tall stature, and, unfortunately, by a high risk of an aortic
dissection, which is often fatal. So Flo Hyman, the volleyball
star, died suddenly because of that condition, and it's not
that rare.
And many of us thought, well, we'll never come up with a
therapy for that in the next 50 years, because it's too rare
for there to be much economic interest, but something pretty
interesting happened. Do you want to tell that story?
Dr. Shurin. One of our investigators at Johns Hopkins, Dr.
Hal Dietz, discovered that a drug, losartan, which is used for
blood pressure--it's an approved drug--actually cures Marfan
syndrome, not only in the test tube, but also in mice.
And so we were able, using our existing Pediatric Heart
Network, to rapidly launch a clinical trial. We had the first
patient enrolled about 5 months after we had opened the trial
and, working very closely with the Marfan Foundation, have been
able to complete enrollment.
The results are not yet fully available. The trends are
looking very good, and we've been very excited by this. But the
ability to do this with the cooperation of the drug
manufacturer and the patient advocacy groups has been really
quite spectacular.
Dr. Collins. So that's an example.
My own lab works on a disease called Progeria, the most
dramatic form of premature aging. These kids age about seven
times the normal rate and usually die by age 12 or 13 of heart
attack or stroke.
By discovering the genetic cause of that disease,
understanding the pathway that's involved, it became clear that
a drug class developed for cancer might actually turn out to be
beneficial in this premature-aging disease.
They've just completed a 2-year clinical trial on kids with
Progeria using this supposed cancer drug, and while the results
are not yet published, I'm hearing very encouraging noises. So
it's repurposing a very different idea of what that drug would
be used for for a new application.
I am sure that if we had a systematic way of trolling the
landscape to identify other such opportunities there would be
lots more.
INTER-AGENCY COLLABORATIONS
Senator Shelby. Dr. Collins, dealing with NIH-FDA
collaboration, which is, I think, is very important, what do
you think would be the best results to come from increased NIH-
FDA collaboration? Are there topics in particular that you're
working on with the NIH and partnering there to move--I assume
moving drugs to market and getting them approved safely is very
important.
Dr. Collins. Commissioner Margaret Hamburg and I have been
meeting for now almost 2 years to talk about ways that our
agencies could work more closely together. And she is a strong
advocate, and I share that same view with her, that regulatory
science--that is, applying science to how reviews are done of
drugs and devices--is very much a possible solution to the
current logjam of trying to get products through that pipeline.
Senator Shelby. We would all benefit from that, wouldn't
we?
Dr. Collins. We would, indeed.
And so she and I have together started a regulatory science
research program. We formed a leadership council between the
two of us which involves the senior leadership of both of our
agencies. We've identified six areas that we think are
particularly ripe for progress, such things as how do you do
toxicology more efficiently? How do you deal with combination
therapies like Dr. Varmus was mentioning may be necessary for
cancer when, in fact, that's hard to review. You have to come
up with new ways to look at that.
And I think together, working as sister agencies, we can
make progress that neither of us could have done alone, and
we're totally committed to making that happen.
Senator Shelby. How do you collaborate with CDC?
Dr. Collins. Oh, quite intensively.
Senator Shelby. I know you do.
Dr. Collins. Tom Frieden, the head of CDC, and I were on
the phone yesterday, and that happens regularly, about areas of
shared interest, and that includes global health as well as
domestic issues.
He and I have exchanged people by going back and forth to
look at shared projects. We obviously work very closely in the
area of infectious disease.
Maybe Dr. Fauci would want to make a comment about your
relationship with CDC, because it's so important.
Dr. Fauci. Yes. We have very strong and long-standing
collaborations, particularly in the arena of global health with
the emphasis on infectious diseases, even though global health
certainly encompasses more than just infectious diseases.
An example of that is we share some of our sites. The CDC
has epidemiological sites and posts for surveillance of
disease. We are now incorporating many of those sites in our
clinical trials of drugs, so many of the trials that take place
are really strong collaborations between the CDC and the NIH,
and that's worked very well.
CYSTIC FIBROSIS
Senator Shelby. Dr. Collins, I enjoyed seeing you last
night, and you know better than anybody that they've come out
with a new drug in the treatment of lupus for many things.
That's a breakthrough of many, many years.
What about cystic fibrosis? Where are you in this area? I
know you've done a lot of research in that area, too.
Dr. Collins. Senator, I appreciate the question. I enjoyed
the experience of chatting with you last night at the Lupus
Foundation of America event. And they are very excited, and
justifiably so, at the approval of Benlysta, this first drug
for lupus in a long time.
Cystic fibrosis is an area of intense interest for me,
because I was part of the team that found the cause of that in
1989, and that has now, finally, after many years of struggle,
led to a very exciting time therapeutically.
So just in the last few months, a drug developed using this
same approach to try to identify small molecules, the same kind
of thing that Senator Moran was seeing in Kansas, this, in this
case, done as a partnership with a company called Vertex, found
a molecule which goes by a not terribly friendly name, VX-770,
which, in fact, for that category of patients with cystic
fibrosis who have a particular mutation in the gene, appears to
be highly effective, and taken over the course of just a month
improves lung function. It reduces the sweat chloride, which
has been the diagnostic hallmark of cystic fibrosis----
Senator Shelby. This has been out how long now?
Dr. Collins. This is still in clinical trials. It hasn't
yet been approved by the FDA, but the phase III trial results
look extremely promising.
Senator Shelby. That would herald, if it were approved by
FDA--It's in clinical trials now.
Dr. Collins. That would be an enormous step forward.
Senator Shelby. A huge breakthrough, hopefully, for cystic
fibrosis.
Dr. Collins. Now, the down side is that this particular
drug is only likely to be effective in that subset of patients
with cystic fibrosis who have a particular mutation in the
cystic fibrosis gene. The common mutation would not necessarily
respond to this drug. You wouldn't expect it would.
There is another drug in the pipeline a few steps behind,
VX-809, which is targeted toward the common mutation. We all
have high hopes that that will turn out to be just as
effective, but we have to wait and see what the clinical trials
show.
Senator Shelby. But it holds promise for the people with
cystic fibrosis and their families.
Dr. Collins. I've been in this field for 25 years. I've not
seen more excitement and hope about a therapeutic intervention
in that whole time until now.
Senator Shelby. Thank you.
Senator Harkin. Thank you.
Senator Kirk.
HEALTHCARE SPENDING POLICY OPTIONS
Senator Kirk. Thank you, Mr. Chairman, and I'm sort of
overawed to see this group here. I followed in the Congress
Congressman John Porter, very much a supporter of NIH and
Research!America.
And, to me, it's interesting, in these times of deficits
and debt in which the largest bond purchaser in America, Pimco,
has now divested itself of all U.S. Treasury securities,
because he's worried about the long-term future of us being
able to borrow money.
I just met with one of the Chinese top officials in meeting
Secretary Clinton, and they also talked about how they were
making moves to leave U.S. debt.
And so it's--over the long term, I wonder how we might be
able to borrow the kind of monies that are being thought of.
With these kind of limitations, you wonder, then, what
direction you take with regard to healthcare policy. And there
are obviously two main directions, if the Government is to
support it, and that is to subsidize care or to subsidize
research.
Now, in subsidizing care, I guess the rough numbers are
Medicare is now $370 billion and Medicaid is $300 billion. So
that's very, very expensive now and growing quite rapidly, but
$670 billion in the subsidizing care path.
In the subsidizing research, NIH comes in at $26 billion,
and yet I think offers a much brighter future of a virtuous
cycle of better and better patient outcomes, faster and faster
innovation and dramatic reversals in disease outcomes, as we've
seen in several cancers or, for example, in juvenile diabetes.
And so in a resource-constrained area--and I think either
the Congress is going to make budget cuts or the bond market is
going to make budget cuts to the Federal budget--you then say
do we double down on subsidizing care or do we continue on the
funding research side, and because this also has a huge
economic benefit to the United States, I very much favor NIH,
where I worry about the long-term sustainability of other parts
of the budget.
So let me ask you somewhat of a theological question on
how we move forward in this environment, which is the
President's healthcare bill set up an independent payment
advisory board to ration care and basically to deny care in
several areas. Its goal, I think, over time will be to
replicate the power and authority of the British NIH's NICE
rationing board.
Have we thought about NIH's relationship to IPAB and how we
would advise the people who would be denying care under
Medicare how they would keep up with medical research and
technology?
Dr. Collins. So these are difficult questions indeed,
Senator. NIH's role as the prime supporter of biomedical
research is to provide the evidence that is necessary for
making wise healthcare decisions, but, obviously, those
decisions depend on more than just the scientific evidence.
They also depend on how society wants to expend its resources.
But I think we can help in substantial ways with the very
frightening cost curve that otherwise faces us. If you'll
permit me, I'd just like to show you one example of the kind of
looming problem that we have in front of us if nothing is done.
This curve shows you for one disease, Alzheimer's disease,
what we are currently spending, which in 2010 is about $180
billion, and which by the projections that many people have
made, if nothing is done, if research is unsuccessful or not
supported, will rise to more than $1 trillion just for that one
disease in 2050, and the number of effected individuals at that
point will be in the neighborhood of 13 million. One disease.
And, yet, at the present time, our investments in research
on Alzheimer's disease fall somewhat less than $1 billion. So,
clearly, we feel a great responsibility to move that curve in a
different direction. If we could even come up with a
therapeutic approach that would slow the onset of disease,
delay it by 5 years, you could cut these costs almost in half,
and, obviously, something more dramatic would have an even more
beneficial effect. That's what we see as our mission----
Senator Kirk. I'm just wondering--My time has run out, but
if we--I think IPAB's future depends on the presidential
election. Should the President prevail, then IPAB and the
healthcare bill is with us. Should the President be defeated, I
think that much of the healthcare bill will be wiped out and
IPAB with it.
But on the potential that the President is reelected, have
you thought about--because what I'm worried about is IPAB will
become an incredibly bureaucratic, stultified organization. It
will review diseases and protocols, but the danger is that they
will be working on heart disease and a breakthrough comes in
cancer that revolutionizes research and they will not have the
bureaucratic means to switch and then advise for a new payment.
And we have such a pace of innovation that a huge state
bureaucracy inevitably will slow down and be unable to keep
pace with medical innovation.
In fact, I would actually argue it probably will kill a lot
of medical innovation as it locks in payment methodologies the
way Medicare has.
But have you begun to think about how you might relate to
this new bureaucracy?
Dr. Collins. Well, again, Senator, I think our best answer
to that is to do the rigorous research that actually not only
tries new therapeutic approaches, but also does comparisons,
when there's more than one alternative, to see what works, and
then to do what we do routinely, and which we believe is a
strong part of our job, is to make that data immediately
available, publish it, make sure it's propagated so that nobody
is left in the dark about knowing what the results have been.
And then I guess I'm just enough of an optimist to think if
the data is there and if it's compelling, it'll be hard to
ignore. But I hear your concern.
Senator Kirk. I would just simply finish up by saying
should IPAB not survive--I hope it doesn't, but should it
survive I think we might want to think about a more formal data
transmission between NIH and IPAB, because, otherwise, IPAB, I
think, will rapidly cause Medicare to fall behind technology
and innovation.
Thank you, Mr. Chairman.
Senator Harkin. Senator Moran.
EFFECTS OF RESEACH ON HEALTHCARE COSTS
Senator Moran. Mr. Chairman, thank you again.
Dr. Collins, perhaps my question is in ways related to the
Alzheimer's chart you just showed, which was a request that do
you have information to substantiate my suggestion or a belief
that money spent on biomedical research results in cost savings
in healthcare? Is there that kind of science-based fact that
substantiates my feelings?
Dr. Collins. So those are complex economic analyses, and
even economists will tend to disagree with each other about the
right way to do it. Let me just cite a couple of figures,
though.
If you look, for instance, at heart disease, what's
happened in the last 40 years, Dr. Shurin will tell you we've
seen a 60-percent drop in mortality from heart attack during
those 40 years. The cost of that, if you average it out per
American per year, in terms of the research that led to those
advances, beginning with the Framingham Study, going through
with the development of understanding about cholesterol and
ultimately the development of statins, was about $3.70 per
American per year, the cost of a latte, and not even a grande
latte, that would be a tall, I think.
So and if you add up the economic benefits that have
resulted from the increase in longevity that have occurred
between 1970 and 2000, I am told credible economists believe
that adds up to $91 trillion. Michael Milken, in a recent
editorial in The Wall Street Journal runs through a lot of
those figures and they seem to be cited by reasonable experts.
If we were to diminish the frequency of cancer by just one
percent--and that's actually happening each year. Each time the
frequency of cancer goes down by 1 percent, economists say
that's saving our country $500 billion in terms of economy that
is sustained as a result of having those people with us. So the
return is enormous.
I could cite you specific examples of new technologies, but
the big picture is quite compelling.
RARE AND NEGLECTED DISEASES
Senator Moran. Well, I'm not surprised by that. It would be
very helpful to have that--I don't like the word sound byte,
but that phrase that says for every dollar spent, here's what
we're able to save in otherwise spending on healthcare.
Let me go back to something more specific and just ask you
to elaborate upon the value of academic and nonprofit research
institutions' role in developing therapies and treatments for
rare and neglected diseases through NCATS, as you propose, and
through your therapeutic and rare neglected disease program
that you already have.
I mean, is this something that you envision as having a
significant role in the future as you develop NCATS are these
neglected diseases?
Dr. Collins. Indeed. And, in fact, the 27 Institutes and
Centers at NIH have been engaged in such efforts for rare and
neglected diseases for some time.
We expect that the advent of NCATS serving as a hub of this
activity will further encourage that and hopefully contribute
innovations that will result in more rapid progress and also a
lower failure rate.
The TRND Program, Therapeutics for Rare and Neglected
Diseases, which the Congress authorized 2 years ago, is
specifically devoted to identifying projects that might
otherwise sit there untouched, where there's a real promise in
taking a therapeutic and moving it into the preclinical space,
which is often called the Valley of Death, because that's where
often good projects go to die.
Take example sickle-cell disease. There's a TRND Program
right now pursuing an interesting therapeutic for sickle-cell
disease originally identified at a university, Virginia
Commonwealth University, then licensed out to a biotech
company, AESRX.
The biotech company carried it to a certain level and then
ran out of money, and venture capital is hard to find these
days unless you have something that's going to result in
profits within a couple of years.
So the company has now partnered with the NIH to move this
forward. The preclinical studies look very good. This will, as
I understand it, be submitted to the FDA for an IND application
later this year, and clinical trials may well get under way
within 1 year at our NIH Clinical Center.
If this were successful, this would be a radical new
approach to sickle-cell disease. The way this molecule works is
unlike anything that's been tried for this disease before.
And while this is certainly a neglected and relatively rare
disease, it still affects tens of thousands, hundreds of
thousands of individuals in this United States and many more
across the world. So it's a good example of a way in which NIH
may be able to assist in the current scientific environment to
move projects forward that otherwise would have languished.
Senator Moran. Thank you very much. Mr. Chairman, thank
you. And let me express my gratitude to all of you for your
public service.
Senator Harkin. Well, I want to thank you all for being
here, again, for another enlightening session.
ADDITIONAL COMMITTEE QUESTIONS
I have some other questions I won't propound now, but I'll
submit those in writing, and the record will remain open for a
week for other Senators to submit further questions or
statements.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted by Senator Tom Harkin
NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE (NCCAM)
ADVISORY COUNCIL
Question. The statute for the NCCAM stipulates that of the 18
appointed members of the Center's Advisory Council, 9 must be
practitioners licensed in one or more of the major systems with which
the Center is concerned, and at least three shall represent the
interests of individual consumers of complementary and alternative
medicine. Is the NCCAM meeting this requirement? Of the four new
members announced on June 6, 2011, how many meet one of the two
categories described above?
Answer. The composition of the National Advisory Council for
Complementary and Alternative Medicine meets the statutory requirements
concerning membership. Collectively, its membership includes the
expertise required for it to carry out its requirements to provide
second level peer review and other advice across the broad and varied
spectrum of clinical practice and scientific disciplines which fall
under the Center's mandate.
On Friday, June 3, 2011, four new members joined the NCCAM Advisory
Council. Brian M. Berman, MD, LAC, is a licensed physician and
acupuncturist. James Lloyd Michener, MD, is professor and chairman of
the Department of Community and Family Medicine and Director of the
Duke Center for Community Research. Dr. Michener also represents the
interests of individual consumers of complementary and alternative
medicine (CAM). Daniel C. Cherkin, Ph.D., is an epidemiologist and
highly experienced clinical researcher who has conducted a number of
major studies that have provided evidence for benefit of CAM therapies
(including chiropractic manipulation, acupuncture, and massage) for low
back pain. David G.I. Kingston, Ph.D., is a widely respected natural
products chemist whose research focuses on the chemistry of
biologically active natural products and the discovery of new therapies
for cancer and malaria from plants.
THE NCCAM RESEARCH SUCCESSES
Question. Under the statute that created the NCCAM, the general
purposes of the Center include ``identifying, investigating, and
validating complementary and alternative treatment, diagnostic and
prevention modalities, disciplines and systems.'' Please identify all
instances in the past 10 years in which the NCCAM-supported research
has validated complementary and alternative treatment, diagnostic and
prevention modalities, disciplines and systems.
Answer. The NCCAM is strongly committed to the highest standards of
evidence-based medicine. Validating health interventions is a process
that begins with evidence developed in peer-reviewed basic and clinical
research. Next, the evidence from multiple studies is collectively
assessed through formal systematic review methods. Finally, if these
earlier steps indicate sufficient usefulness and safety, professional
organizations and health policy makers undertake the development of
guidelines and recommendations regarding use and clinical practice.
This process, collectively referred to as evidence-based medicine,
entails assimilation of the body of scientific evidence; almost never
does a single study result in consensus that an intervention is valid.
Eleven years ago, when the NCCAM was created, there was no
significant evidence-base on the biological properties, safety, and
efficacy of the vast majority of CAM modalities. The Center's first
decade was therefore focused on the conduct and support of basic and
applied research that addressed this lack of scientific information.
The results of that investment now include an emerging evidence base
that is dramatically stronger in terms of both quality and quantity.
Basic research and clinical trials, large and small, have yielded
results--both ``positive'' and ``negative''--regarding the effects,
efficacy, safety, and in some cases, promise regarding CAM
interventions.
Critically, sufficient evidence regarding some CAM interventions
has now been developed to permit informative evidence-based analyses
and systematic reviews by independent organizations (e.g., the Cochrane
Collaboration) using the rigorous standards of evidence-based medicine.
Indeed, such analyses now point increasingly toward clinically helpful
conclusions regarding usefulness and safety--or lack thereof--of
specific CAM interventions and practices.
Notably, the expanding evidence base now includes a large body of
science that points toward specific, very promising opportunities to
improve healthcare and health promotion using CAM-inclusive strategies.
These opportunities are reflected directly in the NCCAM's recently-
released third strategic plan. Important examples include the
following:
Mind and Body Practices
--Developing better, comprehensive strategies for management of
chronic back pain and defining the roles of acupuncture, spinal
manipulation, and massage in those strategies
--Exploring the role of specific promising CAM practices or
disciplines (e.g., meditation, yoga, or acupuncture) in
developing better strategies for alleviating symptoms (e.g.,
chronic pain, stress) or in promoting healthier lifestyles
--Exploring the associations between well-characterized pathways of
pain processing and acupuncture analgesia or the placebo
response
--Exploring the associations of major pathways of cognitive
processing and emotion regulation by meditative practices
--Studying the influence of the provider-patient/client interaction,
context effects, and the placebo response on outcomes of CAM
interventions
Natural Products
--Studying the molecular targets and biological effects of
potentially beneficial small molecules that are constituents of
natural products or diet (e.g., quercetin, curcumin, or other
polyphenols and flavonoids)
--Defining the anti-inflammatory actions of omega-3 fatty acids
--Employing state-of-the-art tools and technologies to study the
effects of probiotics on the human microbiome
--Developing evidence regarding the safety profile of certain widely
used natural products, including interactions with drugs and
other herbals or dietary supplements
The growing evidence base is clearly influencing professional
practice guidelines of mainstream professional medical societies, and
the practice of integrative medicine. Complementary and alternative
therapies are increasingly being accepted and integrated into
conventional healthcare systems. For example, recent data show that
approximately half the hospices in the United States and 9 out of 10
Department of Veterans Affairs facilities offer some complementary or
alternative therapies. The Consortium of Academic Health Centers in
Integrative Medicine, an organization of integrative medicine
departments at academic medical centers, has grown from 11 members in
2002 to 43 members in 2011. Medical societies such as the American
College of Physicians, the American Academy of Pediatrics and the
American Academy of Family Physicians have formulated policies
regarding complementary therapies and offer educational material about
these forms of treatment. The Departments of Defense and Veterans
Affairs are also actively pursuing care and research initiatives that
include various CAM interventions in treatment and prevention of
problems such as chronic pain and post-traumatic stress disorder
afflicting our wounded warriors.
In the appendices, we have included a status report on the process
of validation of selected interventions. In Appendix A, we present
examples of specific complementary and alternative interventions for
which a sufficient number of individual studies exist for systematic
reviews to conclude the interventions appear to offer benefit. In
Appendix B, we list numerous additional examples of individual NCCAM-
supported studies that provide preliminary evidence of benefit in other
indications. We feel it important to provide both types of information
in addressing the subcommittee's specific questions because the
processes of evidence-based validation of health practices and
decisionmaking regarding their use are iterative, and draw on a variety
of such sources rather than merely single studies.
APPENDIX A: THE STATUS OF THE EVIDENCE BASED REVIEWS AND PROFESSIONAL
GUIDELINES FOR SELECT COMPLEMENTARY AND ALTERNATIVE THERAPIES
The examples of systematic reviews and professional assessments
cited here all include evidence derived from clinical and mechanistic
research supported by the NCCAM. As is true with the evidence in most
areas of healthcare, there continues to be controversy about some of
these conclusions, and not all systematic reviews come to the same
conclusions.
Role of Complementary Therapies in the Management of Chronic Low Back
Pain
Management of chronic low back pain is a critical challenge for our
healthcare system and a major driver of healthcare costs. Complementary
interventions are increasingly being integrated into the care of
chronic back pain patients, and there is substantial recognition,
supported by findings from the NCCAM research, that complementary
therapies, particularly chiropractic and osteopathic spinal
manipulation, massage, acupuncture, and meditative exercise forms such
as yoga, can make important contributions to improved outcomes for
patients. Many systematic reviews have assessed these therapeutic
approaches. The Joint Clinical Practice Guideline for low back pain,
developed by the American College of Physicians and the American Pain
Society, reflects the strength of this evidence base and the emerging
professional consensus for the value of the incorporation of
complementary approaches. To quote directly from the summary:
``For patients who do not improve with self-care options,
clinicians should consider the addition of nonpharmacologic therapy
with proven benefits-for acute low back pain, spinal manipulation; for
chronic or sub-acute low back pain, intensive interdisciplinary
rehabilitation, exercise therapy, acupuncture, massage therapy, spinal
manipulation, yoga, cognitive-behavioral therapy, or progressive
relaxation.''--Joint Clinical Practice Guideline, American College of
Physicians and American Pain Society. Annals of Internal Medicine,
2007: 147,478.
Nevertheless, there is also a consensus among healthcare providers,
both conventional and complementary, that, current approaches are not
satisfactory for many patients suffering with back pain. Moving
forward, a major area of emphasis for the NCCAM, as described in the
NCCAM's 2011 Strategic Plan, will be improving management of chronic
back pain. Research is needed to optimize complementary therapies, to
understand better who benefits from them, and to develop better systems
of integrated care that improve real world application of these helpful
therapeutic techniques.
Role of Natural Products in Promotion of Health and Wellness
The NCCAM's natural product research portfolio, carefully assessed
during our strategic planning process, has yielded many important
lessons that will guide us moving forward. Fundamental scientific
understanding of potential beneficial mechanisms of many dietary
supplements and natural products has increased markedly, with some
notable examples described below. New high-throughput technologies and
modern genomic tools have created important new scientific
opportunities. We have learned much about the challenges of translation
of these findings to clinical efficacy research. The future emphasis,
as described in our strategic plan and strongly supported by both
academic investigators and leaders of the botanical and dietary
supplement industry, is on the development of strong biological
mechanistic hypotheses, sensitive biological signatures of effect, and
carefully optimized trial designs.
A few examples of the independent systematic reviews that have
provided validation of the potential value of natural products or other
dietary supplements are as follows:
--Fish Oil for the Prevention of Cardiovascular Disease.--``Dietary
supplementation with omega-3 fatty acids should be considered
in the secondary prevention of cardiovascular events.''--
Clinical Cardiol. 2009: 32, 365.
--Melatonin for the Prevention and Treatment of Jet Lag.--``Melatonin
is remarkably effective in preventing or reducing jet lag, and
occasional short-term use appears to be safe.''--Cochrane
Database Syst Rev 2002: 1520.
--Probiotics for Prevention of Necrotizing Enterocolitis in Preterm
Infants.--``Enteral supplementation of probiotics prevents
severe necrotizing enterocolitis and all cause mortality in
preterm infants.''--Cochrane Database Syst Rev 2008: 5496.
--Prebiotics and Probiotics for Hepatic Encephalopathy.--``The use of
prebiotics, probiotics and synbiotics was associated with
significant improvement in minimal hepatic encephalopathy.''--
Ailment Pharmacol Ther 2011: 33.
--Probiotics for Acute Infectious Diarrhea.--``Used alongside
rehydration therapy, probiotics appear to be safe and have
clear beneficial effects in shortening the duration and
reducing stool frequency in acute infectious diarrhea.''--
Cochrane Database Syst Rev 2010: 3048.
--Zinc for the Common Cold.--``Zinc administered within 24 hours of
onset of symptoms reduces the duration and severity of the
common cold in healthy people.''--Cochrane Database Syst Rev
2006: 1364.
Role of Complementary Therapies in the Management of Pain and Other
Troublesome Symptoms
Concern is often voiced that the processes of evidence-based
medicine could not accommodate the evidence emerging from research on
many complementary therapies. In fact, this is a challenge common to
evaluation of the evidence of many nonpharmacological interventions,
including psychotherapy and surgery. The NCCAM's strategic plan
addresses this challenge by calling for increased use of outcomes and
effectiveness research methodology, and collaboration with experts who
work in other fields facing similar challenges. Nonetheless, several
examples are provided below which illustrate that rigorous research on
these complicated therapies is possible and can meet the exacting
standards of evidence-based review.
--The Cochrane Collaborative has reviewed the evidence that
acupuncture may provide benefit for migraine prophylaxis and
for treatment of tension-type headache, and concluded that it
has value in both situations.--Cochrane Database Syst Rev 2009:
1218, Cochrane Database Syst Rev 2009: 7587.
--The Cochrane Collaborative has reviewed the evidence that
acupuncture may be useful for postoperative nausea and
vomiting, as well as for nausea and vomiting which has been
induced by cancer chemotherapy. Systematic reviews conclude
benefit in both cases.--Cochrane Database Syst Rev 2009, 3281,
National Cancer Institute, PDQ summary.
--A systematic review published in the British Journal of Anesthesia
concluded that perioperative acupuncture is a useful adjunct
for acute postoperative pain management.--Br. J Anaesth 2008:
101, 151.
APPENDIX B: THE NCCAM-SUPPORTED STUDIES THAT CONTAIN EVIDENCE OF VALUE
OF CAM
Listed below are the NCCAM-supported studies, which contain
evidence of the value of CAM. Consistent with the priorities of the
NCCAM's strategic plan, these findings are grouped into three major
categories: Mind and Body Interventions; Natural Products
Interventions; and Population-Based Research. Within each category, the
findings are listed in reverse chronological order by the publication
date.
Mind and Body Interventions
Chronic Pain
Review of CAM Practices for Back and Neck Pain Shows Modest
Benefit.--According to a recent review published by the Agency for
Healthcare Research and Quality, the benefits of complementary and
alternative therapies for back and neck pain--such as acupuncture,
massage, and spinal manipulation--are modest in size but provide more
benefit than usual medical care. While these effects are most evident
following the end of treatment, the authors of the report noted that
very few studies looked at long-term outcomes. Back and neck pain are
important health problems that affect millions of Americans, and back
pain is the most common medical condition for which people use
complementary and alternative medicine (CAM). They noted that more
well-designed studies are needed to draw more definitive conclusions
regarding the benefits of CAM therapies for pain. http://nccam.nih.gov/
research/results/spotlight/100110.htm.--AHRQ Publication No.
10(11)E007. Rockville, MD: Agency for Healthcare Research and Quality.
October 2010.
Tai Chi May Benefit Patients With Fibromyalgia.--Fibromyalgia is a
disorder characterized by muscle pain, fatigue, and other symptoms.
Researchers, funded in part by the NCCAM, evaluated the physical and
psychological benefits of tai chi (which combines meditation, slow
movements, deep breathing, and relaxation) in 66 people with
fibromyalgia. The participants were assigned to one of two groups: an
attention control group that received wellness education and practiced
stretching exercises, or a tai chi group that received instruction in
tai chi principles and techniques and practiced 10 forms of Yang-style
tai chi. Compared with the attention control group, the tai chi group
had a significantly greater decrease in total score on the Fibromyalgia
Impact Questionnaire at 12 weeks. In addition, the tai chi group
demonstrated greater improvement in sleep quality, mood, and quality of
life. Improvements were still present at 24 weeks. No adverse events
were reported. The researchers concluded that these findings support
previous research indicating benefits of tai chi for musculoskeletal
pain, depression, and quality of life. The underlying mechanisms are
unknown, and the researchers noted that larger, longer term studies are
needed to evaluate the potential benefits of tai chi for patients with
fibromyalgia. http://nccam.nih.gov/research/results/spotlight/
081810.htm.--New England Journal of Medicine. 2010;363(8):743-754 and
783-784.
Analysis of National Survey Reveals Perceived Benefit of CAM for
Back Pain.--According to an analysis of the 2002 National Health
Interview Survey, approximately 6 percent of U.S. adults used
complementary and alternative medicine (CAM) to treat their back pain
during the previous year. The data from this analysis also revealed
that a majority (60 percent) of survey respondents who used the most
common CAM therapies for back pain perceived ``a great deal'' of
benefit. The most common CAM therapies used for back pain--in
descending order of perceived benefit--were chiropractic (66 percent),
massage (56 percent), yoga/tai chi/qi gong (56 percent), acupuncture
(42 percent), herbal therapies (32 percent), and relaxation techniques
(28 percent). The specific factors associated with a greater perception
of benefit from CAM use were having an improved self-reported health
status, and using CAM because ``conventional medical treatment would
not help.'' Back pain is the most common medical condition for which
people use CAM, and these data give more insight into the use and
perceived benefit of CAM therapies for this condition. The researchers
suggested that this analysis demonstrates the need for future studies
that include both self-reported outcomes and observer-based performance
measures of patients using CAM therapies for back pain. http://
nccam.nih.gov/research/results/spotlight/060110.htm.--Journal of the
American Board of Family Medicine. 2010;23(3):354-362.
Study of Spinal Manipulative Therapy for Neck-related Headaches
Reports Findings on Dose and Efficacy.--Previous research suggests that
spinal manipulative therapy (SMT) may be helpful for various types of
chronic headaches, including cervicogenic headache (CGH), which is
associated with neck pain and dysfunction. This randomized controlled
trial evaluated the dose (number of treatments) and relative efficacy
of SMT in a group of 80 patients with chronic CGH. Compared with
massage, participants receiving SMT had greater improvements in CGH-
related pain and disability, lasting to 24 weeks. These differences
were clinically important and statistically significant. The dose
effects of SMT treatments (i.e., differences between 8 and 16
treatments) were small but significant. The mean number of headaches
reported by SMT subjects decreased by more than half during the study.
The researchers concluded that their findings support SMT as a viable
option for treating CGH, but also point out that these findings should
be considered preliminary. They suggest additional research to
determine whether SMT results for patients with CGH are affected by
treatment intensity and duration, use of other therapies, lifestyle
changes, and an integrative care approach. http://nccam.nih.gov/
research/results/spotlight/041310.htm.--Spine Journal. 2010;10(2):117-
128.
Preliminary Trial Finds Possible Benefits of Osteopathic Treatment
for Back Pain During the Third Trimester of Pregnancy.--Most pregnant
women experience low-back pain, which often is associated with sleep
disturbance and can affect daily activities. Researchers investigated
the effects of osteopathic manipulative treatment on back pain during
the third trimester of pregnancy. They found that back-specific
functioning deteriorated significantly less in the osteopathic
manipulative treatment group than in the usual care or usual care with
sham treatment groups. Although the results of this preliminary study
suggest that osteopathic manipulation may have benefits for back-
specific functioning, but not pain, in the third trimester of
pregnancy, larger trials are needed before definitive conclusions can
be drawn about its efficacy or effectiveness for this purpose. http://
nccam.nih.gov/research/results/spotlight/032210.htm.--American Journal
of Obstetrics and Gynecology. 2010;202(1):43.e1-43.e8.
Tai Chi May Benefit Older Adults With Knee Osteoarthritis.--Knee
osteoarthritis (OA) is an increasing problem among older adults,
causing pain, functional limitations, and reduced quality of life.
Researchers conducted a long-term, randomized, controlled trial
comparing tai chi and conventional exercise in a group of 40 adults
(mean age 65) with symptomatic knee OA. The tai chi group learned and
practiced Yang-style tai chi, modified slightly to eliminate excess
stress on the knees. The control group received wellness education and
did stretching exercises. Compared with the control group, tai chi
patients had greater improvement in measures of pain, physical
function, self-efficacy (belief in one's own abilities), depression,
and health-related quality of life. Although most differences between
the two groups were statistically significant only at 12 weeks, the
differences for self-efficacy and depression remained statistically
significant at 24 and 48 weeks. No serious adverse events were
reported. The researchers recommend additional studies of biologic
mechanisms and approaches of tai chi, so its benefits can be extended
to a broader population. http://nccam.nih.gov/research/results/
spotlight/011510.htm.--Arthritis & Rheumatism. 2009;61(11):1545-1553.
Iyengar Yoga for Chronic Low-back Pain Shows Promising Results.--
Researchers conducted a clinical trial to evaluate the effects of
Iyengar yoga (a popular style of yoga that uses props to help support
the body during postures) on chronic low-back pain. They found that
compared with the control group, the yoga group had significantly
greater reductions in functional disability, pain, and depression, at
weeks 12 and 24 and at the 6-month followup. There were no significant
differences in pain medication usage between the groups; however, there
appeared to be a trend toward decreased usage in the yoga group. The
researchers concluded from their results that yoga decreases functional
disability, pain, and depression in people with chronic low-back pain.
However, they noted potential limitations of their study (e.g., heavy
reliance on self-report instruments, and differential demands on yoga
vs. control groups in terms of attention and group support) and suggest
design considerations for future research. http://nccam.nih.gov/
research/results/spotlight/112409.htm.--Spine. 2009;34(19):2066-2076.
Managing Low-Back Pain: an Evidence-Based Approach for Primary Care
Physicians.--A physician's response to a patient with low-back pain
(LBP) should take into account psychological and social factors as well
as physical symptoms, according to an article that looked at two case
studies in light of evidence-based clinical guidelines developed by
Roger Chou et al. for the American Pain Society and the American
College of Physicians. The article's authors, recommend a measured
approach to the use of imaging (x-rays and MRI/CT scans) and
medication. The authors outline considerations in evaluating each
patient and choosing action steps. The authors also noted that most
people with chronic LBP will not become pain free. Physicians can help
patients have a realistic outlook that focuses on improving functioning
in addition to reducing pain. http://nccam.nih.gov/research/results/
spotlight/040209.htm.--Journal of Family Practice. 2009;58(4):180-186.
Study Finds Benefits of Therapeutic Massage for Chronic Neck
Pain.--In a research study, 64 adults with neck pain persisting for at
least 12 weeks were randomly assigned to receive either massage or a
self-care book. The massage group had up to 10 treatments over a 10-
week period, provided by licensed practitioners who used a variety of
common Swedish and clinical massage techniques and also made typical
self-care suggestions. After 10 weeks, the massage group was more
likely than the self-care-book group to have clinically significant
improvement in function and symptoms. At 26 weeks, the massage group
tended to be more likely to report improvement in function but not in
specific symptoms. For both function and symptoms, mean differences
between the two groups were strongest at 4 weeks and not evident by 26
weeks. At all followup points, the massage group was more likely than
the self-care-book group to report global improvement ratings of
``better'' or ``much better.'' At 26 weeks, medication use had
increased 14 percent for the self-care-book group but had not changed
for the massage group. The researchers concluded that therapeutic
massage is safe and may have benefits for treating chronic neck pain,
at least in the short term. They recommended studies to determine
optimal massage treatment, as well as larger, more comprehensive
studies to follow patients for at least 1 year. http://nccam.nih.gov/
research/results/spotlight/051809.htm.--Clinical Journal of Pain.
2009;25(3):233-238.
Massage Therapy May Ease Pain and Improve Mood in Advanced Cancer
Patients.--Researchers investigated the benefits of massage versus
simple touch therapy (placing both hands on specific body sites) in
patients with advanced cancer. This multisite study--conducted at 15
U.S. hospices in the Population-based Palliative Care Research
Network--included 380 participants with advanced cancer who were
experiencing moderate-to-severe pain. Results of the study showed that
both the massage and simple touch therapy groups experienced
statistically significant improvements in pain relief, physical and
emotional distress, and quality of life. Immediate improvement in pain
and mood was greater with massage than with simple touch; however,
sustained effects of these therapies were not observed. The researchers
concluded that massage therapy may provide some immediate relief for
patients with advanced cancer. They also suggest that simple touch,
which can be provided by family members and volunteers, may benefit
these patients. http://nccam.nih.gov/research/results/spotlight/
110608.htm.--Annals of Internal Medicine. 2008;149(6):369-379.
Study Points to Cost-effectiveness of Naturopathic Care for Low-
Back Pain.--Researchers who studied treatment alternatives for low-back
pain in a group of 70 warehouse workers found that a naturopathic
approach (incorporating a range of treatment options--acupuncture,
exercise and dietary advice, relaxation training, and a back-care
booklet) was more cost-effective than the employer's usual patient
education program. Both the workers and the employer benefited from the
naturopathic approach, which was associated with better health-related
quality of life, less absenteeism, and lower costs for other treatments
and pain medication. The study consisted of workers ages 18 to 65 who
had experienced low-back pain for at least 6 weeks. The workers were
randomly assigned to receive naturopathic care or patient education
visits over a 3-month period. The 30-minute, onsite visits were
conducted semiweekly (naturopathic) or biweekly (patient education).
The researchers conclude that naturopathic care is more cost-effective
than a patient education program in treating low-back pain. They also
recommend further studies of the economic impact of naturopathic
medicine, particularly to address the limitations of their evaluation.
http://nccam.nih.gov/research/results/spotlight/070708.htm.--
Alternative Therapies in Health and Medicine. 2008;14(2):32-39.
Acupuncture Relieves Pain and Improves Function in Knee
Osteoarthritis.--Acupuncture provides pain relief and improves function
for people with osteoarthritis of the knee and serves as an effective
addition to standard care, according to a landmark study. The
researchers enrolled 570 patients with osteoarthritis of the knee, aged
50 and older, to receive one of three treatments: acupuncture,
simulated acupuncture (procedures that mimic acupuncture, sometimes
also referred to as ``placebo'' or ``sham''), or participation in a
control group. The control group followed the Arthritis Foundation's
self-help course for managing their condition over 12 weeks.
Participants in the actual and simulated acupuncture groups received 23
treatment sessions over 26 weeks. All study participants continued to
receive standard medical care from their primary physicians, including
anti-inflammatory medications and opioid pain relievers. At the start
of the study, participants' pain and knee function were assessed using
standard arthritis research survey instruments and measurement tools.
After 26 weeks participants in the acupuncture group had a 40 percent
decrease in pain and a nearly 40 percent improvement in function
compared to their assessments at the start of the study. Findings from
this study begin to shed more light on acupuncture's possible
mechanisms and potential benefits, especially in treating painful
conditions such as arthritis. http://nccam.nih.gov/research/results/
spotlight/052504.htm.--Annals of Internal Medicine. 2004;141(12):901-
910.
Stress/Anxiety
Long-term Yoga Practice May Decrease Women's Stress.--Research has
shown that women who practice hatha yoga (a common type of yoga
involving body postures, breath control, and meditation) regularly
recover from stress faster than women who are considered yoga
``novices.'' The research also showed that yoga may boost the mood of
both yoga experts and novices. The researchers found that the novices'
blood had 41 percent higher levels of the cytokine interleukin-6 (IL-6)
than those of the experts. IL-6 is a stress-related compound that is
thought to play a role in certain conditions such as cardiovascular
disease and type 2 diabetes. In addition, the novices' levels of C-
reactive protein, which serves as a general marker for inflammation,
were nearly five times that of the yoga experts. Experts had lower
heart rates in response to stress events than novices. The researchers
suggested that this study offers insight into how yoga and its related
practices may affect health. Regularly performing yoga could have
health benefits, which may only become evident after years of practice.
http://nccam.nih.gov/research/results/spotlight/051510.htm.--
Psychosomatic Medicine. Feb 2010;72(2):113-121.
A Form of Acupuncture May Help in Opioid Addiction.--Transcutaneous
electric acupoint stimulation (TEAS), a form of acupuncture that uses
skin electrodes to apply electrical stimulation at different points on
the body, may help people addicted to opioid drugs. This study,
supported in part by the NCCAM, also suggests that combining this
technique with prescribed drugs that ease withdrawal symptoms may
improve other outcomes for people addicted to opioids. Further,
participants who received active TEAS were more than two times less
likely to have used any drugs than those who received simulated TEAS.
In addition, patients in the active TEAS group reported they were less
bothered by pain and that they experienced greater improvements in
overall health. However, the researchers noted that drug abstinence may
have contributed to these improvements. The researchers noted several
limitations of this study, including a small number of participants and
brief duration of treatment. Despite these limitations, they suggested
that additional studies with larger, more diverse populations and
longer treatment durations are needed. http://nccam.nih.gov/research/
results/spotlight/010410.htm.--Journal of Substance Abuse Treatment.
2010;38(1):12-21.
Transcendental Meditation Helps Young Adults Cope With Stress.--A
study found that Transcendental Meditation (TM) helped college students
decrease psychological distress and increase coping ability. For a
group of students at high risk for developing hypertension, these
changes also were associated with decreases in blood pressure. Compared
with controls, the TM group had significant improvement in total
psychological distress, anxiety, depression, anger/hostility, and
coping ability. Changes in psychological distress and coping paralleled
changes in blood pressure. According to the researchers, these findings
suggest that young adults at risk of developing hypertension may be
able to reduce that risk by practicing TM. The researchers recommend
that future studies of TM in college students evaluate long-term
effects on blood pressure and psychological distress. http://
nccam.nih.gov/research/results/spotlight/051410.htm.--American Journal
of Hypertension. Dec 2009;22(12):1326-1331.
Mantram Instruction May Help HIV-positive Individuals Handle
Stress.--Repeating a mantram (also known as a mantra--the practice of
silently focusing on a spiritual word or phrase frequently throughout
the day)--may help HIV-positive individuals develop coping skills and
reduce anger. Researchers analyzed the effects of a group-based mantram
training program, based on data from a study involving 93 HIV-positive
individuals. After the 5-week intervention, the mantram group reported
a significant increase (25 percent on average) in use of positive
reappraisal coping (handling stressful situations by focusing on
positive aspects), while the control group reported a significant
decrease. At a 22-week followup, anger levels had decreased in the
mantram group (13 percent on average) but not in the control group.
According to the researchers, these findings suggest that repeating a
mantram may help HIV-positive individuals examine stressful situations
in a more nonjudgmental and accepting way, reducing the likelihood of
an angry response. This is significant because reducing reactive anger
may help individuals preserve supportive social relationships as well
as maintain adherence to antiretroviral treatments. The researchers
suggested additional studies to explore the effects of mantram on
attention, cognitive processing, and acceptance-based responding.
http://nccam.nih.gov/research/results/spotlight/010609.htm.--
International Journal of Behavioral Medicine. 2009;16(1):74-80.
Stress Management Interventions May Enhance Immune Function in
People With HIV.--Stress management interventions may help to improve
immune function and coping skills in HIV-positive individuals.
Researchers assessed three interventions: cognitive-behavioral
relaxation training (physical and mental relaxation techniques and
active coping skills); focused tai chi training (exercises for balance,
breathing, posturing and movement, and relaxation); and spiritual
growth (discussions and personal journals to enhance spiritual
awareness). None of the intervention groups differed from controls on
measures of HIV-related psychological distress, quality of life, and
health status, or on physiological stress response (cortisol levels).
However, compared with controls, all three treatment groups had
significant increases in lymphocyte proliferation (production of white
blood cells), indicating enhanced immune function. The researchers
noted the potentially important clinical implications of this finding.
They recommend additional research to examine specific effects of
stress management interventions in people with HIV. http://
nccam.nih.gov/research/results/spotlight/060208.htm.--Journal of
Consulting and Clinical Psychology. 2008;76(3):431-441.
Acupuncture May Help Symptoms of Post-traumatic Stress Disorder.--A
pilot study shows that acupuncture may help people with post-traumatic
stress disorder. Post-traumatic stress disorder (PTSD) is an anxiety
disorder that can develop after exposure to a terrifying event or
ordeal in which grave physical harm occurred or was threatened.
Traumatic events that may trigger PTSD include violent personal
assaults, natural or human-caused disasters, accidents, or military
combat. Researchers conducted a clinical trial examining the effect of
acupuncture on the symptoms of PTSD. The researchers analyzed
depression, anxiety, and impairment in 73 people with a diagnosis of
PTSD. The participants were assigned to receive either acupuncture,
group cognitive-behavioral therapy, or were put on the wait list as a
control group. The people in the control group were offered treatment
or referral for treatment at the end of their participation. The
researchers found that acupuncture provided treatment effects similar
to group cognitive-behavioral therapy; both interventions were superior
to the control group. Additionally, treatment effects of both the
acupuncture and the group therapy were maintained for 3 months after
the end of treatment. The limitations are that the study consisted of a
small group of participants that lacked diversity and that the results
do not account for outside factors that may have affected the
treatments' results. http://nccam.nih.gov/research/results/spotlight/
092107.htm.--The Journal of Nervous and Mental Disease, June 2007.
Self-hypnosis Beneficial for Women Undergoing Breast Biopsy.--
Researchers have found that women who used self-hypnosis during a type
of core needle breast biopsy experienced anxiety relief and reduced
pain when compared with standard care. A large core needle breast
biopsy is usually an outpatient procedure that limits the use of
anesthetic. Women having this procedure often experience anxiety
because of the possibility of a cancer diagnosis in addition to the
anxiety that patients typically experience during a medical procedure.
In this randomized, controlled trial researchers recruited 236 women
who were randomly assigned to receive standard care, structured
empathic attention from a research assistant, or guided self-hypnotic
relaxation during the biopsy. The study found that both self-hypnosis
and empathic attention reduced pain and anxiety during the procedure.
Self-hypnosis provided greater anxiety relief than empathic attention.
Neither intervention increased procedure time or significantly
increased cost. As a result, the researchers suggest that self-hypnosis
appears attractive for outpatient pain management. http://
nccam.nih.gov/research/results/spotlight/122606.htm.--Pain, December
2006.
Basic and Translational Research
Basic and translational research provides important insights into
how CAM interventions can benefit human health. For example, animal
studies help to identify biomarkers or signatures of biological effects
that can be applied to future studies in humans.
Mindfulness Meditation is Associated With Structural Changes in the
Brain.--Practicing mindfulness meditation appears to be associated with
measurable changes in the brain regions involved in memory, learning,
and emotion, according to a research study that compared brain images
of participants who participated in a mindfulness-based stress
reduction program with those who did not. Specifically brain images in
the meditation group revealed increases in gray matter concentration in
the left hippocampus, which is an area of the brain involved in
learning, memory, and emotional control, and is suspected of playing a
role in producing some of the positive effects of meditation. The
researchers concluded that these findings may represent an underlying
brain mechanism associated with mindfulness-based improvements in
mental health. Additional studies are needed to determine the
associations between specific types of brain change and behavioral
mechanisms thought to improve a variety of disorders. http://
nccam.nih.gov/research/results/spotlight/012311.htm.--Psychiatry
Research: Neuroimaging. 2011;191(1):36-43.
Study Examines the Effects of Swedish Massage Therapy on Hormones,
Immune Function.--Massage is used for many health purposes, but little
is known about how it works on a biological level. This study examined
the effects of one session of Swedish massage therapy--a form of
massage using long strokes, kneading, deep circular movements,
vibration, and tapping--on the body's hormonal response and immune
function. Researchers randomly assigned 53 healthy adults to receive
one session of either Swedish massage or light touch (in which the
therapist used only a light touch with the back of the hand). The
researchers found that participants who received Swedish massage had a
significant decrease in the hormone arginine-vasopressin (which plays a
role in regulating blood pressure and water retention) compared with
those who were treated with light touch. Study data, although
preliminary data, led the researchers to conclude that a single session
of Swedish massage produces measurable biological effects and may have
an effect on the immune system. However, more research is needed to
determine the specific mechanisms and pathways behind these changes.
http://nccam.nih.gov/research/results/spotlight/090110.htm.--The
Journal of Alternative and Complementary Medicine. 2010;16(10):1-10.
Electroacupuncture Relieves Cancer Pain in Laboratory Rats.--
Electroacupuncture (acupuncture combined with electrical stimulation)
has been used to treat cancer pain; however, the existing data on its
efficacy and how it works are unclear. Researchers investigated the
effects of electroacupuncture on cancer pain in rats and also looked at
the underlying biomechanisms. The results showed that compared with the
sham control, electroacupuncture significantly reduced cancer-induced
bone pain. The researchers also examined the rats spinal cords to see
whether electroacupuncture affected chemical processes thought to play
a role in pain. They found that compared with the sham control,
electroacupuncture inhibited up-regulation of two substances involved
in these processes: spinal cord preprodynorphin mRNA and dynorphin. In
a separate experiment, they found that injection of an antiserum
against dynorphin also inhibited cancer-induced pain in the rats. The
researchers concluded that electroacupuncture eases cancer pain in
rats, at least in part by inhibiting spinal dynorphin. They note that
their findings support the clinical use of electroacupuncture in the
treatment of cancer pain. http://nccam.nih.gov/research/results/
spotlight/040109.htm.--European Journal of Pain. 2008;12(7):870-878.
Brain-Imaging Study Explores Analgesic Effect of Acupuncture.--
Researchers used two imaging technologies--functional magnetic
resonance imaging (fMRI) and positron emission tomography (PET)--to
investigate how specific areas of the brain might be involved in
acupuncture analgesia. The imaging results showed acupuncture-related
changes in both of the brain's pain networks: the lateral network,
which is associated with sensory aspects of pain perception, and the
medial network, which is associated with affective aspects. However,
the fMRI and PET results pointed to different areas in these networks,
with one exception: both imaging technologies showed changes in the
right medial orbitofrontal cortex--an indication that this area of the
brain may be important in acupuncture analgesia. The researchers note
that their preliminary findings demonstrate that imaging studies using
more than one imaging technique have potential for clarifying the
neural mechanisms of acupuncture. They point out that similar studies
with much larger samples might reveal other areas of the brain where
fMRI and PET results converge. http://nccam.nih.gov/research/results/
spotlight/121208.htm.--Behavioural Brain Research. 2008;193(1):63-68.
Green Tea May Help Protect Against Rheumatoid Arthritis.--
Investigators examined the effects of green tea polyphenols on
rheumatoid arthritis (RA) by using an animal (rat) model. The animals
consumed green tea in their drinking water (controls drank water only)
for 1 to 3 weeks before being injected with heat-killed Mycobacterium
tuberculosis H37Ra to induce arthritis. The researchers found that
green tea significantly reduced the severity of arthritis. They suggest
that green tea affects arthritis by causing changes in various
arthritis-related immune responses--it suppresses both cytokine IL-17
(an inflammatory substance) and antibodies to Bhsp65 (a disease-related
antigen), and increases cytokine IL-10 (an anti-inflammatory
substance). Therefore, they recommend that green tea be further
explored as a dietary therapy for use together with conventional
treatment for managing RA. http://nccam.nih.gov/research/results/
spotlight/120808.htm.--The Journal of Nutrition. 2008:138(11):2111-
2116.
Electroacupuncture May Help Alcohol Addiction.--Researchers
examined the effects of electroacupuncture on alcohol intake by
alcohol-preferring rats. After being trained to drink alcohol
voluntarily and then subjected to alcohol deprivation, the rats
received either electroacupuncture or sham electroacupuncture, and
their alcohol intake was monitored after the intervention. Some rats
were also pretreated with naltrexone (a drug that blocks the effects of
opiates), so researchers could look for evidence that opiate mechanisms
are involved in electroacupuncture's effects. The results showed that
electroacupuncture reduced the rats' alcohol intake. The researchers
also found that injecting the rats with naltrexone blocked the effect
of electroacupuncture on alcohol intake-an indication that this effect
may be through the brain's opiate system. On the basis of their
findings, the researchers recommend rigorous clinical trials to study
the effects of electroacupuncture in alcohol-addicted people. They also
recommend further investigation of how electroacupuncture affects the
brain. http://nccam.nih.gov/research/results/spotlight/022609.htm.--
Neurochemical Research. 2008;33(10):2166-2170.
Lifestyle Changes May Affect Cell-level Processes Related to
Disease.--Disease risk, progression, and premature mortality--in many
types of cancer and in cardiovascular and infectious diseases--have
been linked to telomeres, which are protective DNA-protein complexes
that keep cells genetically stable. The cellular enzyme telomerase is
an important part of the body's maintenance system for these essential
complexes. In a pilot study researchers investigated the effects of
lifestyle changes on telomerase levels in 24 men with low-risk prostate
cancer. The participants underwent a comprehensive lifestyle
modification that included: improved nutrition, moderate aerobic
exercise, stress management, and increased social support. After 3
months, the study participants' telomerase activity had increased 29.8
percent. Decreases in psychological distress and low-density
lipoprotein (LDL) cholesterol were associated with the increase in
telomerase activity. This is the first longitudinal study to suggest
that lifestyle modifications (or any intervention) might significantly
increase telomerase activity. The researchers emphasize that additional
research is needed and recommend larger randomized controlled trials to
confirm the findings. http://nccam.nih.gov/research/results/spotlight/
100908.htm. The Lancet Oncology. Published online September 16, 2008.--
Journal of Immunology. 2007;179(6):4249-4254.
New Research Gives Insight Into How Acupuncture May Relieve Pain.--
In the first study of its kind, researchers evaluated the effects of
acupuncture on brain activity following active stimulation. The
researchers used functional magnetic resonance imagery (fMRI) to
monitor brain activity in 15 healthy adults before and after true
acupuncture and sham acupuncture. The procedure lasted 150 seconds, and
the rest period was 5.5 minutes. Analysis of the fMRI images showed
that following true acupuncture--but not sham--there were increased
connections among the parts of the brain involved in the perception and
memory of pain. The subjects also reported stronger sensations with
true acupuncture than with sham. The researchers concluded that
acupuncture changes resting-state brain activity in ways that may
account for its analgesic and other therapeutic effects. http://
nccam.nih.gov/research/results/spotlight/111408.htm.--Pain.
2008;136(3):407-418.
Prostate Genes Altered by Intensive Diet and Lifestyle Changes.--A
pilot study suggests that intensive lifestyle and diet changes may
alter gene expression (the way a gene acts) in the prostate--possibly
affecting the progression of prostate cancer. This pilot study included
a group of 31 men with low-risk prostate cancer. These men declined
immediate surgery, hormonal therapy, or radiation, and participated in
an intensive 3-month nutritional and lifestyle intervention while
researchers monitored their tumor progression. The men stuck to a low-
fat, plant-based diet and took dietary supplements including fish oil,
selenium, and vitamins C and E. They also participated in stress
management activities, did moderate aerobic exercise, and attended
group support sessions. The researchers found that there were changes
in the men's RNA following the lifestyle and diet modifications.
Certain RNA transcripts that play a critical role in tumor formation
had ``up-regulated'' (increased) and others ``down-regulated''
(decreased). The researchers concluded that intensive nutrition and
lifestyle changes may alter gene expression in the prostate. They
believe that understanding how these changes affect the prostate may
lead to more effective prevention and treatment for prostate cancer,
and recommend larger, randomized controlled trials to confirm the
results of this pilot study. http://nccam.nih.gov/research/results/
spotlight/100808.htm.--Proceedings of the National Academy of Sciences
of the United States of America. 2008;105(24):8369-8374.
Meditation May Increase Empathy.--Previous brain studies have shown
that when a person witnesses someone else in an emotional state--such
as disgust or pain--similar activity is seen in both people's brains.
This shows a physiological base for empathy, defined as the ability to
understand and share another person's experience. Now, research using
advanced brain images (functional magnetic resonance imaging) have
shown that compassion meditation--a specific form of Buddhist
meditation--may increase the human capacity for empathy. In the study,
researchers compared brain activity in meditation experts with that of
subjects just learning the technique (16 in each group). They measured
brain activity during meditation and at rest, in response to sounds
designed to evoke a negative, positive, or neutral emotional response.
The researchers found that both the novice and the expert meditators
showed an increased empathy reaction when in a meditative state.
However, the expert meditators showed a much greater reaction,
especially to the negative sound, which may indicate a greater capacity
for empathy as a result of their extensive meditation training. An
increased capacity for empathy, the authors say, may have clinical and
social importance. The next step, they add, is to investigate whether
compassion meditation results in more altruistic behavior or other
changes in social interaction. http://nccam.nih.gov/research/results/
spotlight/060608.htm.--PLoS ONE [online journal], 2008.
Meditation May Make Information Processing in the Brain More
Efficient.--``Attentional-blink'' occurs when two pieces of information
are presented to a person in very close succession, and the brain
doesn't perceive the second piece of information because it is still
processing the first. Researchers attempted to determine if intensive
mental training through meditation could extend the brain's limits on
information processing, reducing ``attentional-blink.'' Two groups of
people--17 expert meditators and 23 novices--were compared to see if
either was better at recognizing two pieces of information shown in
quick succession. The participants were tested at the beginning and end
of a 3-month period. For the intervening 3 months, the meditation
practitioners participated in a retreat, during which they meditated
for 10-12 hours a day. The novices participated in a 1-hour meditation
class, and were asked to meditate for 20 minutes a day for the week
before each test. The researchers found that intensive training did
reduce ``attentional-blink.'' The participants who had gone through the
mental training were more likely to perceive both pieces of information
instead of just the first because the brain used fewer resources to
detect the first piece of information--leaving more resources available
to detect the second. The researchers also note that this study
supports the idea that brain plasticity, or the ability of the brain to
adapt, exists throughout life. http://nccam.nih.gov/research/results/
spotlight/082307.htm.--PLOS Biology, June 2007.
Quality of Life and Other Factors
Quality of Life and Safety of Tai Chi and Green Tea Extracts in
Postmenopausal Women.--For postmenopausal women with osteopenia (low
bone mineral density), practicing tai chi and/or taking green tea
polyphenols appears to be safe. Further, practicing tai chi by itself
or in combination with green tea polyphenol supplements may improve
quality of life; however, taking green tea supplements by themselves
has no significant improvement in quality of life. The researchers
noted that this is the first placebo-controlled, randomized study to
evaluate the safety of long-term use of green tea supplements in
postmenopausal women. Based on these findings, the researchers
concluded that green tea polyphenols at a dose of 500 mg daily for 24
weeks, alone or in combination with tai chi, appears to be safe in
postmenopausal women with low bone mineral density. http://
nccam.nih.gov/research/results/spotlight/121410.htm.--BMC Complementary
and Alternative Medicine. 2010;10(1):76. [Epub ahead of print]
Tai Chi and Qi Gong Show Some Beneficial Health Effects.--A review
of scientific literature suggests that there is strong evidence of
beneficial health effects of tai chi and qi gong, including for bone
health, cardiopulmonary fitness, balance, and quality of life. Both tai
chi and qi gong (also known as qigong) have origins in China and
involve physical movement, mental focus, and deep breathing.
Researchers analyzed 77 articles reporting the results of 66 randomized
controlled trials of tai chi and qi gong. The studies involved a total
of 6,410 participants. Of the many outcomes identified by the
reviewers, current research suggests that the strongest and most
consistent evidence of health benefits for tai chi or qi gong is for
bone health, cardiopulmonary fitness, balance and factors associated
with preventing falls, quality of life, and self-efficacy (the
confidence in and perceived ability to perform a behavior). The
reviewers concluded that the evidence is sufficient to suggest that tai
chi and qi gong are a viable alternative to conventional forms of
exercise. http://nccam.nih.gov/research/results/spotlight/071910.htm.--
American Journal of Health Promotion. 2010;24(6):e1-e25.
Hypnosis May Reduce Hot Flashes in Breast Cancer Survivors.--
Researchers investigated the effects of hypnosis on hot flashes among
women with a history of primary breast cancer, no current evidence of
detectable disease, and at least 14 hot flashes per week over a 1-month
period. Sixty women were assigned to receive either hypnosis (weekly
50-minute sessions, plus instructions for at-home self-hypnosis) or no
treatment. The women who received hypnosis had a 68-percent reduction
in self-reported hot flash frequency/severity and experienced an
average of 4.39 fewer hot flashes per day. Compared with controls, they
also had significant improvements in self-reported anxiety, depression,
interference with daily activities, and sleep. The researchers
concluded that hypnosis appears to reduce perceived hot flashes in
breast cancer survivors and may have additional benefits such as
improved mood and sleep. They recommend long-term, randomized, placebo-
controlled studies to further explore the benefits of hypnosis for
breast cancer survivors. The researchers are currently conducting a
randomized clinical trial with 200 participants. http://nccam.nih.gov/
research/results/spotlight/102308.htm.--Journal of Clinical Oncology.
Published online September 22, 2008.
Tai Chi May Help Heart Failure Patients Sleep Better.--People with
heart failure may benefit from practicing tai chi, according to
researchers who analyzed sleep in 18 patients with chronic heart
failure. All patients were on maximal medical therapy. The patients
were assigned into one of two groups: a usual care group (the control)
that received medication and diet/exercise counseling, or a tai chi
group that received usual care plus 12 weeks of tai chi training.
Compared with the usual care group, the tai chi group had significant
improvements in sleep stability. The tai chi group also demonstrated
significant quality-of-life improvements over the usual care group. The
researchers concluded that a 12-week tai chi exercise program may help
heart failure patients sleep better. They noted that it remains to be
determined if any single component of tai chi--meditation, relaxation,
or physical activity--may be responsible for the observed benefit. They
suggested further research to better understand the mechanisms of tai
chi's effects on sleep should include more conventional sleep testing
to document sleep stages and patterns of sleep disruption. http://
nccam.nih.gov/research/results/spotlight/072508.htm.--Sleep Medicine.
2008;9(5):527-536.
Tai Chi Chih Improves Sleep Quality in Older Adults.--Researchers
conducted a randomized controlled trial to determine whether tai chi
chih could improve sleep quality in healthy, older adults with moderate
sleep complaints. In the study, 112 individuals aged 59 to 86
participated in either tai chi chih training or health education
classes for 25 weeks. Participants rated their sleep quality based on
the Pittsburgh Sleep Quality Index, a self-rate questionnaire that
assesses sleep quality, duration, and disturbances. The results of the
study showed that the people who participated in tai chi chih sessions
experienced slightly greater improvements in self-reported sleep
quality. The researchers concluded that tai chi chih can be a useful
nonpharmacologic approach to improving sleep quality in older adults
with moderate sleep complaints, and may help to prevent the onset of
insomnia. http://nccam.nih.gov/research/results/spotlight/031109.htm.--
Sleep. 2008;31(7):1001-1008.
Acupuncture Shows Promise in Improving Rates of Pregnancy Following
IVF.--A review of seven clinical trials of acupuncture given with
embryo transfer in women undergoing in vitro fertilization (IVF)
suggests that acupuncture may improve rates of pregnancy. An estimated
10 to 15 percent of couples experience reproductive difficulty and seek
specialist fertility treatments, such as IVF. According to researchers
who conducted the systematic review, acupuncture has been used in China
for centuries to regulate the female reproductive system. With this in
mind, the reviewers analyzed results from seven clinical trials of
acupuncture in women who underwent IVF to see if rates of pregnancy
were improved with acupuncture. The studies encompassed data on over
1,366 women and compared acupuncture, given within 1 day of embryo
transfer, with sham acupuncture, or no additional treatment. The
reviewers found that acupuncture given as a complement to IVF increased
the odds of achieving pregnancy. According to the researchers, the
results indicate that 10 women undergoing IVF would need to be treated
with acupuncture to bring about one additional pregnancy. The results,
considered preliminary, point to a potential complementary treatment
that may improve the success of IVF and the need to conduct additional
clinical trials to confirm these findings. http://nccam.nih.gov/
research/results/spotlight/020808.htm.--British Medical Journal.
Published online February 2008.
Tai Chi May Help Maintain Bone Mineral Density in Postmenopausal
Women.--Tai chi may be a safe alternative to conventional exercise for
maintaining bone mineral density (BMD) in postmenopausal women. Bone
mineral density is one of the key indicators of bone strength and low
BMD is associated with osteoporosis. Exercise is an important component
of osteoporosis prevention and treatment. Researchers conducted a
systematic review of research looking at the effect of tai chi, a mind-
body practice that originated in China, on BMD. They found that tai chi
may be an effective, safe, and practical intervention for maintaining
BMD in postmenopausal women. The authors further note that the benefits
of tai chi appeared similar to those of conventional exercise. However,
tai chi may also improve balance, reduce fall frequency, and increase
musculoskeletal strength. They note that the evidence is preliminary
because the research they reviewed was of limited scope and quality,
but enough evidence of effectiveness exists to warrant further
research. http://nccam.nih.gov/research/results/spotlight/081407.htm.
Archives of Physical Medicine and Rehabilitation, May 2007.
Tai Chi Boosts Immunity to Shingles Virus in Older Adults.--Tai
chi, a traditional Chinese form of exercise, may help older adults
avoid getting shingles by increasing immunity to varicella-zoster virus
and boosting the immune response to varicella vaccine. The study is the
first rigorous clinical trial to suggest that a behavioral
intervention, alone or together with a vaccine, can help protect older
adults from the varicella virus, which causes both chickenpox and
shingles. The randomized, controlled trial included 112 healthy adults
ages 59 to 86. Each person took part in a 16-week program of either tai
chi or health education with 120 minutes of instruction weekly. After
the tai chi and health education programs, with periodic blood tests to
determine levels of varicella virus immunity, people in both groups
received a single injection of the chickenpox vaccine, VARIVAX. Nine
weeks later, the investigators assessed each participant's level of
varicella immunity and compared it to immunity at the start of the
study. Tai chi alone was found to increase participants' immunity to
varicella, and tai chi combined with the vaccine produced a
significantly higher level of immunity, about a 40 percent increase,
over the vaccine alone. The study also showed that the tai chi group's
rate of increase in immunity over the course of the study was double
that of the health education group. Finally, the tai chi group reported
significant improvements in physical functioning, bodily pain, vitality
and mental health. http://nccam.nih.gov/research/results/spotlight/
040607.htm.--Journal of the American Geriatrics Society, April 2007.
Study Compares Year-long Effectiveness of Four Weight-loss Plans.--
The very low carbohydrate diet known as the Atkins diet may contribute
to greater weight loss than higher carbohydrate plans without negative
effects such as increased cholesterol. The study consisted of 311
premenopausal women, all of whom were overweight or obese who were
randomly assigned to 1 of 4 diets. Each of the diets used were selected
for their different levels of carbohydrate consumption: the Atkins
diet, the Zone diet, the LEARN diet and the Ornish diet. Participants
in each group received books that accompanied their assigned diet plan,
and attended hour-long classes with a registered dietitian once a week
for the first 8 weeks. The researchers recorded body mass index (BMI);
percent body fat; waist-hip ratio; as well as metabolic measures such
as, insulin, cholesterol, glucose, triglyceride, and blood pressure
levels. The Atkins diet group reported the most weight loss at 12
months with an average loss of just over 10 pounds. They also had more
favorable overall metabolic effects. Average weight loss across all
four groups ranged from 3.5 to 10.4 pounds. The authors note that
``even modest reductions in excess weight have clinically significant
effects on risk factors such as triglycerides and blood pressure.''
http://nccam.nih.gov/research/results/spotlight/030607.htm.--Journal of
the American Medical Association. March 2007.
Natural Products Interventions
Treatment or Enhancement of Treatment
New Approach for Peanut Allergy in Children Holds Promise.--
Currently, there are no treatments available for people with peanut
allergy. A new treatment may be a safe and effective form of
immunotherapy for those children. The double-blind, placebo-controlled
study investigated the safety, clinical effectiveness, and immunologic
changes with sublingual immunotherapy--a treatment that involves
administering very small amounts of the allergen extract under a
person's tongue. Though these findings are promising, more study is
needed to determine whether sublingual immunotherapy can increase long-
term tolerance to peanuts in children with peanut allergy. http://
nccam.nih.gov/research/results/spotlight/022011.htm.--The Journal of
Allergy and Clinical Immunology. 2011.
Magnesium Supplements May Benefit People With Asthma.--Some
previous studies have reported associations between low magnesium
consumption and the development of asthma. This study provides
additional evidence that adults with mild-to-moderate asthma may
benefit from taking magnesium supplements. Researchers found that
participants who took magnesium experienced significant improvement in
lung activity and the ability to move air in and out of their lungs.
Those taking magnesium also reported other improvements in asthma
control and quality of life compared with people who received placebo.
The researchers noted that this study adds to the body of research that
shows subjective and objective benefits of magnesium supplements in
people with mild-to-moderate asthma. http://nccam.nih.gov/research/
results/spotlight/021110.htm.--Journal of Asthma. 2010;47(1):83-92.
Study Shows Chamomile Capsules Ease Anxiety Symptoms.--Researchers
conducted a randomized, double-blind, placebo-controlled trial to test
the effects of chamomile extract in patients diagnosed with mild to
moderate generalized anxiety disorder (GAD). Researchers used the
Hamilton Anxiety Rating (HAM-A) and other tests to measure changes in
anxiety symptoms over the course of the study; dosage adjustments were
based on HAM-A scores. Compared with placebo, chamomile was associated
with a greater reduction in mean HAM-A scores--the study's primary
outcome measure. The difference was clinically meaningful and
statistically significant. Chamomile also compared favorably with
placebo on other outcome measures (although the differences were not
statistically significant), and was well tolerated by participants.
These results suggest that chamomile may have modest benefits for some
people with mild to moderate GAD. As this was the first controlled
trial of chamomile extract for anxiety, the researchers note that
additional studies using larger samples and studying effects for longer
periods of time would be helpful. They also point out that other
chamomile species, preparations (e.g., extracts standardized to
constituents other than apigenin), and formulations (e.g., oil or tea)
might produce different results. http://nccam.nih.gov/research/results/
spotlight/040310.htm.--Journal of Clinical Psychopharmacology. 2009
Aug;29(4):378-382.
Study Indicates Cranberry Juice Does Not Interfere With Two
Antibiotics Women Take for Recurrent Urinary Tract Infections.--
Cranberry juice, a popular home remedy for urinary tract infections
(UT), is often taken along with low-dose antibiotics as a preventive
measure. Because little is known about the potential of cranberry juice
to interact with drugs, researchers studied cranberry's effects on two
antibiotics frequently prescribed for UTI: amoxicillin and cefaclor.
The data showed that cranberry juice did not significantly affect
either antibiotic's oral absorption or renal clearance (i.e., how
completely the body processed the drugs in the intestine and kidneys).
Absorption took somewhat longer with cranberry juice, but the delay was
small, and the total amount of antibiotic absorbed was not affected.
Based on these results, the researchers concluded that cranberry juice
cocktail, consumed in usual quantities, is unlikely to change the
effects of these two antibiotics on UTIs. They noted that the same may
or may not be true of other antibiotics, or when people who take
antibiotics also drink a large quantity of concentrated cranberry
juice. http://nccam.nih.gov/research/results/spotlight/081009.htm.--
Antimicrobial Agents and Chemotherapy. 2009 Jul;53(7):2725-32.
Traditional Chinese Herbs May Benefit People With Asthma.--
Scientists reviewed research evidence on traditional Chinese medicine
(TCM) herbs for asthma, focusing on studies reported since 2005. They
determined that preliminary clinical trials of formulas containing
Radix glycyrrhizae in combination with various other TCM herbs have had
positive results. Laboratory findings on TCM herbal remedies suggest
several possible mechanisms of action against asthma, including an
anti-inflammatory effect, inhibition of smooth-muscle contraction in
the airway, and modulation of immune system responses. http://
nccam.nih.gov/research/results/spotlight/061609.htm.--Journal of
Allergy and Clinical Immunology. 2009;123(2):297-306.
A Review of St. John's Wort Extracts for Major Depression.--
Researchers reviewed the scientific literature on St. John's wort for
major depression and analyzed findings from randomized, double-blind
studies comparing St. John's wort extracts with placebo and standard
antidepressants. The researchers reviewed a total of 29 studies in
5,489 people. The studies came from a variety of countries, tested
several different St. John's wort extracts, and mainly included people
with minor to moderately severe symptoms of depression. According to
this literature review, St. John's wort extracts appeared to be
superior to placebo, were as effective as standard antidepressants, and
had fewer side effects than antidepressants. However, the findings from
studies in German-speaking countries were disproportionately favorable,
possibly because some subjects had slightly different types of
depression, or because some of the small studies were flawed and overly
optimistic in reporting their results. The authors noted the need to
investigate the reasons for the differences between study findings from
German-speaking countries and those from other countries. http://
nccam.nih.gov/research/results/spotlight/120908.htm.--Cochrane Database
of Systematic Reviews. 2008 8;(4):CD000448.
Study Suggests Vitamin E May Help People With Asthma.--A form of
vitamin E (gamma-tocopherol) commonly found in foods may be a useful
additional treatment for asthma, according to preliminary research.
Researchers investigated the biological activity of a gamma-tocopherol
supplement in asthma patients. The researchers gave a daily dose of a
vitamin E preparation rich in gamma-tocopherol to 16 volunteers. Eight
healthy volunteers and eight volunteers with allergic asthma received
one supplement daily during the first week, followed by a week with no
treatment, and then two supplements daily for another week. They found
similar results for both doses--the vitamin E supplements prevented
inflammation and decreased oxidative stress without any adverse health
effects. This research was an initial step in extending previous
findings of gamma-tocopherol's anti-inflammatory effects in animals.
Further research on vitamin E in patients with asthma is under way.
http://nccam.nih.gov/research/results/spotlight/070208.htm.--Free
Radical Biology & Medicine. 2008;45(1):40-49.
Omega-3 Fatty Acids May Be Helpful in Psychiatric Care.--Omega-3
fatty acids may hold promise for use in psychiatry, particularly for
depression and bipolar disorder. Researchers conducted a meta-analysis
of research looking at omega-3 fatty acid supplements as treatments for
psychiatric conditions, such as depression, bipolar disorder,
schizophrenia, dementia, and attention-deficit hyperactivity disorder.
Omega-3 fatty acids are essential nutrients that the body cannot make
on its own, so they must come from food sources. The richest source of
these fatty acids is fish and seafood, but they can also be found in
flaxseeds and some eggs. The authors suggest that omega-3 supplements
may be helpful for people with depression or bipolar disorder as a
complement to standard care. However, they were unable to determine
benefits for other conditions such as schizophrenia and dementia. They
also ``strongly recommend that patients with psychiatric disorders
should not elect supplementation with omega-3 fatty acids in lieu of
established psychiatric treatment options.'' They further recommend
studies to look at how the nutrient may work, and large trials to
conclusively determine the utility of omega-3 fatty acids in
psychiatric care. http://nccam.nih.gov/research/results/spotlight/
121506.htm.--Journal of Clinical Psychiatry, December 2006.
Polyunsaturated Fatty Acids for Depression.--Omega-6 and omega-3
fatty acids (also called PUFAs, short for polyunsaturated fatty acids)
are among the CAM therapies used with the intent to help symptoms of
depression. A team reviewing the evidence found five randomized
controlled trials to be of sufficient quality for review, although all
were small and of short duration. All but one of these trials found
some improvement from using PUFAs for symptoms of depression,
particularly from omega-3 fatty acids. The authors concluded that while
the evidence to support using PUFA supplements as a treatment for
depression is not strong, enough potential exists to merit further
research. http://nccam.nih.gov/research/results/spotlight/050106.htm.--
Journal of Affective Disorders, May 2006.
Disease Prevention
Ginkgo Does Not Shield Seniors' Hearts, But It May Protect Their
Leg Arteries.--While findings from the Ginkgo Evaluation of Memory
(GEM) study show that the herbal supplement Ginkgo biloba did not
prevent heart attack, stroke, or death in a group of older adults, the
herb may reduce the risk of developing peripheral arterial disease
(also known as peripheral vascular disease), a painful and potentially
life-threatening condition affecting blood circulation in the legs,
arms, stomach, and kidneys. Of the 35 cases of peripheral arterial
disease observed in the study, 23 patients received placebo and 12
patients received ginkgo, a difference that was statistically
significant. The researchers reported that this finding was consistent
with European studies that reported improvements in patients with
peripheral arterial disease who received ginkgo versus placebo. But,
due to the small number of patients in whom this was seen, the
researchers suggest larger trials to evaluate the herb before they
would recommend it as a treatment for peripheral arterial disease. This
study was a planned secondary outcome of the GEM study. http://
nccam.nih.gov/research/results/spotlight/052110.htm.--Circulation:
Cardiovascular Quality and Outcomes. 2010;3(1):41-47.
Chinese Herbal Medicine May Benefit People With Pre-Diabetes.--In
China and other Asian countries, Chinese herbal medicines have long
been used to prevent or delay the onset of diabetes, and there is
anecdotal evidence regarding efficacy for this purpose. A recent
review, funded in part by the NCCAM, examined related clinical trials
to see whether scientific evidence supports recommending Chinese herbal
medicine as a treatment option for people with pre-diabetes. The review
looked at 16 clinical trials involving 1,391 participants with pre-
diabetes, 15 different herbal formulations, and various comparisons
(i.e., lifestyle modification, drug interventions, placebo). Analysis
of data from eight trials that included lifestyle modification as a
comparison found that lifestyle modification combined with Chinese
herbs was twice as effective as lifestyle modification alone in
normalizing blood sugar levels. Participants who received herbal
formulations were also less likely to develop full-blown diabetes
during the study period. Due to limitations among the studies reviewed,
the reviewers concluded that while their findings are promising,
further, well-designed trials are needed to clarify the potential role
of Chinese herbal medicines in glucose control and diabetes prevention.
http://nccam.nih.gov/research/results/spotlight/110309.htm.--Cochrane
Database of Systematic Reviews. 2009(4):CD00066690.
Red Yeast Rice May Help Patients With High Cholesterol Who Cannot
Take Statin Drugs.--In light of previous findings that red yeast rice
can reduce levels of low-density lipoprotein (LDL, or ``bad''
cholesterol), researchers investigated the effects of this supplement
in patients with high cholesterol and a history of statin-associated
myalgia (SAM). Compared with placebo, red yeast rice significantly
decreased blood levels of LDL and total cholesterol over a 24-week
period, without increasing the incidence of myalgia. Red yeast rice did
not significantly affect levels of high-density lipoprotein (HDL, or
``good'' cholesterol), triglycerides, weight loss, or pain severity.
This was the first randomized, double-blind, placebo-controlled trial
to evaluate red yeast rice in patients who cannot take statin drugs
because of muscle pain. The results suggest that red yeast rice may be
a cholesterol-lowering alternative for these patients, but additional,
larger studies are needed to establish long-term safety and efficacy.
The researchers also suggest studies to compare red yeast rice directly
with statins and to explore the role of lifestyle change therapy.
http://nccam.nih.gov/research/results/spotlight/071709.htm.--Annals of
Internal Medicine. 2009;150(12):830-839.
Flaxseed Reduces Some Risk Factors of Cardiovascular Disease.--
Flaxseed is rich in alpha linolenic acid (ALA), a plant-based omega-3
fatty acid, as well as fiber and lignans (phytoestrogens), making it a
possible functional food for reducing cardiovascular risk factors. A
double blind, randomized, controlled clinical trial by researchers
explored the effects of flaxseed on various cardiovascular risk factors
in adults. Researchers found that flaxseed positively affected
lipoprotein A and insulin sensitivity. They also found a modest but
short-lived lowering effect in participants' LDL (``bad'') cholesterol
levels. However, the researchers also noted that flaxseed significantly
lowers HDL (``good'') cholesterol levels in men, although not in women.
There were no changes noted in markers of inflammation or oxidative
stress. The authors suggest that additional investigation of the HDL
lowering effect among men may be warranted. http://nccam.nih.gov/
research/results/spotlight/062308.htm.--Nutrition, 2008.
Basic and Translational Research
Basic and translational research provides important insights into
how CAM interventions can benefit human health. For example, animal
studies help to identify biomarkers or signatures of biological effects
that can be applied to future studies in humans.
Laboratory Study Suggests Potential Anti-cancer Benefit of White
Tea Extract.--White tea extract increased a specific type of cell death
in laboratory cultures of two different types of nonsmall cell lung
cancer cells, indicating that the tea may have an anti-cancer effect.
Although white tea comes from the same plant as green and black teas
(Camellia sinensis), white tea goes through much less processing,
resulting in a higher concentration of polyphenols. This study, for the
first time, showed the roles of the PPAR-gamma and 15-LOX signaling
pathways in white tea-induced apoptosis. (A reduction in PPAR-gamma in
a tumor is linked to poor prognosis in patients with lung cancer.) The
researchers also compared green tea extract with white tea extract and
found that white tea extract was significantly more effective in
increasing certain RNA transcripts (e.g., PPAR-gamma) that play a
critical role in cell death. They noted, however, that the components
in white tea extract that may be responsible for this outcome are not
yet known. They noted that the findings from this preliminary study
provide an important basis for more investigation of the anti-cancer
properties of white tea extract and whether it may help prevent the
development of lung cancer. http://nccam.nih.gov/research/results/
spotlight/092110.htm.--Cancer Prevention Research. 2010;3(9):1132-1140.
Laboratory Study Shows Turmeric May Have Bone-Protective Effects.--
Turmeric--an herb commonly used in curry powders, mustards, and
cheeses--may protect bones against osteoporosis. This study, which used
an animal (rat) model of postmenopausal osteoporosis, builds on
previous laboratory research examining turmeric's anti-arthritic
properties. Funded in part by the NCCAM, the study tested two turmeric
extracts containing different amounts of curcuminoids--(components of
the herb) in female rats whose ovaries had been surgically removed
(ovariectomy--a procedure that causes changes associated with
menopause, including bone loss). Tests showed that while nonenriched
turmeric extract did not have bone-protective effects, curcuminoid-
enriched turmeric extract prevented up to 50 percent of bone loss, and
also preserved bone structure and connectivity. Other physiological
changes associated with ovariectomy (weight gain and shrinking of the
uterus) were unaffected--an indication that the bone-protective effects
did not involve an estrogen-based chemical pathway. The researchers
concluded that turmeric may protect bones, but that the effect depends
on the amount of curcuminoids present. However, they emphasized that
clinical research is needed to evaluate the use of turmeric-derived
curcuminoid products to guard against osteoporosis in humans. http://
nccam.nih.gov/research/results/spotlight/093010.htm.--Journal of
Agricultural and Food Chemistry. 2010;58(17):9498-9504.
Effects of Milk Thistle Extract on the Hepatitis C Virus
Lifecycle.--A laboratory study suggests that silymarin--an extract from
the milk thistle plant--has multiple effects against the lifecycle of
the hepatitis C virus. Hepatitis C is a chronic (long lasting) disease
that primarily affects the liver and is often difficult to cure. This
study examined the antiviral properties and mechanisms of silymarin on
cultured (grown in a lab) human liver cells infected with the virus. By
analyzing the interactions between silymarin and the virus, the
researchers observed that silymarin prevented the entry and fusion of
the hepatitis C virus into the target liver cells. They also found that
silymarin inhibited the ability of the virus to produce RNA (a chemical
that plays an important role in protein synthesis and other chemical
activities of the cell), interfering with a portion of the virus's
lifecycle. These findings build on previous research of silymarin's
antiviral and anti-inflammatory properties and provide more information
about the potential mechanisms involved in silymarin's antiviral
actions. Further research, particularly in clinical trials, is needed
to determine if silymarin could be a safe and effective supplement for
treating hepatitis C in humans. http://nccam.nih.gov/research/results/
spotlight/061610.htm.--Hepatology. 2010;51(6):1912-1921.
Fish Oil Enhances Effects of Green Tea on Alzheimer's Disease in
Mice.--Fish oil, when combined with epigallocatechin-3-gallate (EGCG--a
polyphenol and antioxidant found in green tea), may affect chemical
processes in the brain associated with Alzheimer's disease. This study,
which used an animal (mouse) model of Alzheimer's disease, builds on
previous research linking the disease to peptides (amino acid chains)
called beta-amyloids and laboratory studies suggesting that EGCG
decreases memory problems and beta-amyloid deposits in mice.
Researchers found that the mice fed the combination of fish oil and
EGCG had a significant reduction in amyloid deposits that have been
linked with Alzheimer's disease. Upon examination of blood and brain
tissues of the mice, the researchers found high levels of EGCG in the
mice that were fed the combination of fish oil and low-dose EGCG
compared with those fed low-dose EGCG alone. A possible explanation,
according to the researchers, is that fish oil enhances the
bioavailability of EGCG--that is, the degree to which EGCG was absorbed
into the body and made available to the brain. This effect, in turn,
may contribute to the increased effectiveness of this combination.
Further research is necessary, however, to determine if the combination
of fish oil and EGCG affects memory or cognition, and whether it might
have potential as an option for people at risk of developing
Alzheimer's disease. http://nccam.nih.gov/research/results/spotlight/
031610.htm.--Neuroscience Letters. 2010;471(3):134-138.
Laboratory Study Suggests Potential Anti-Cancer Benefit of
Ginseng.--American ginseng (Panax quinquefolius) extract caused
laboratory cultures of colorectal cancer cells to die, indicating that
the herb may have an anti-cancer effect. Although results from the
study suggest that combining ginseng with antioxidants such as vitamin
C may potentially enhance this effect, there is no evidence yet that
this laboratory research can be extended to treatments in people.
Researchers treated two types of colorectal cancer cells with steamed
American ginseng root extract. This caused damage to the cells'
mitochondria, the internal structures that are involved with energy
production, and led to apoptosis (cell death). It also increased levels
of reactive oxygen species (ROS)--a byproduct of the processes in which
cells use and break down oxygen (increased levels of ROS can either
bring on cell death or activate the survival pathways that protect
against it). Whether ROS acts to induce cell death or survival in
response to ginseng depends on the specific biochemical pathways that
are activated, and how this happens remains unknown. Further studies
are needed. The researchers also noted the need for additional
investigations to test whether combining ginseng and antioxidants might
help prevent the development of colorectal cancers. http://
nccam.nih.gov/research/results/spotlight/032510.htm.--Cancer Letters.
2010;289(1):62-70.
Mouse Study Shows Green Tea Polyphenols May Repair DNA Damage
Caused by Ultraviolet (UV) Radiation.--Antioxidants found in green tea
may help repair DNA damage caused by sun exposure, according to a
recent study in mice. Exposure to UV radiation can damage DNA and, in
turn, trigger suppression of the immune system--a risk factor for
developing skin cancer. The study, funded in part by the NCCAM,
examined the effects of polyphenols from the leaves of the green tea
plant, which are thought to fight free radicals (highly unstable
molecules that can damage cells) and have anticarcinogenic activity.
Compared with the control group, the mice treated with green tea
polyphenols had reduced immunosuppression from the UV radiation. This
same group of mice also showed more rapid repair of DNA damaged by UV
radiation. Further, the study showed that green tea polyphenols
increased the levels of some nucleotide excision repair genes, which
allow for DNA repair. The researchers noted that this study is the
first to show that preventing skin cancer with green tea polyphenols in
water may be due to the blocking of UV-induced immunosuppression in
mice. More studies are needed to determine if green tea has any
potential chemopreventive effect on skin cancer in people. http://
nccam.nih.gov/research/results/spotlight/022110.htm.--Cancer Prevention
Research. 2010;3(2):179-189.
Cinnamon Bark and Ginseng in Herbal Formulas Increase Life Span of
Roundworms.--Researchers used a roundworm that has some genetic and
biochemical similarities to humans to examine complex herbal
preparations thought to combat adverse effects of aging. The worms,
called Caenorhabditis elegans, or C. elegans, have a brief life span
(about 20 days). The researchers assessed two traditional Chinese
multiherbal formulas--Huo Luo Xiao Ling Dan (HLXL), taken for chronic
inflammatory pain (e.g., joint pain from arthritis); and Shi Quan Da Bu
Tang (SQDB), taken to reduce fatigue and improve general wellness. They
found that cinnamon bark, a component of both formulas, increased the
worms' life span. Of all the individual components tested, two
significantly prolonged life span: Cinnamomum cassia bark (present in
both formulas) and Panax ginseng root (present in SQDB only). In light
of these findings, the researchers concluded that C. elegans is a valid
model for evaluating complex herbal preparations and may provide
insight for future studies on longevity-promoting herbs. http://
nccam.nih.gov/research/results/spotlight/052510.htm.--PLoS ONE [online
journal]. 2010;5(2):9339.
Laboratory Study Explores Anti-HIV Potential of Palmitic Acid.--In
a laboratory study, a fatty acid from seaweed reduced the ability of
HIV-1 viruses to enter immune system cells. Researchers evaluated
palmitic acid (from Sargassum fusiforme, a type of seaweed that grows
off the coasts of Japan and China) to see if palmitic acid reduced the
ability of HIV-1 viruses to enter CD4+ T-cells (white blood cells that
are HIV-1's main target). Palmitic acid blocked both X4-tropic and R5-
tropic viruses, the HIV viruses that use a particular receptor (X4 or
R5) to enter a cell. In addition, the study's findings showed that
palmitic acid protected other cells against HIV-1, reducing X4
infection in primary peripheral blood lymphocytes and R5 infection in
primary macrophages (white blood cells). In all cases, the extent of
the blocking effect depended on the concentration of palmitic acid, and
most cells remained viable (alive) after treatment. The researchers
noted that understanding the relationship between palmitic acid and CD4
may lead to development of an effective microbicide product for
preventing sexual transmission of HIV. http://nccam.nih.gov/research/
results/spotlight/121409.htm.--AIDS Research and Human Retroviruses.
2009;25(12):1231-1241.
Study Uses Rat Liver Cells To Explore Cholesterol-Lowering
Mechanisms of Tea.--There is evidence that tea consumption can reduce
the risk of cardiovascular disease, apparently by lowering cholesterol
levels in the blood. Researchers examined extracts from both green tea
and black tea, as well as some components of green tea, for their
effects on the synthesis of cholesterol in liver cells from rats. The
study's finding that black tea was more effective than green tea in
decreasing cholesterol synthesis in rat liver cells was unexpected, as
was the finding that EGCG alone was less effective than whole green
tea. Additional research may reveal more about the cholesterol-lowering
mechanisms of both kinds of tea. http://nccam.nih.gov/research/results/
spotlight/040510.htm.--Journal of Nutritional Biochemistry. 2009
Oct;20(10):816-822.
Evidence in Mice May Spur More Research on Fish Oil and Curcumin
for Alzheimer's Disease.--A popular dietary supplement and a curry
spice may affect Alzheimer's disease--related chemical processes in the
brain, according to research findings. This study, which used an animal
(mouse) model of Alzheimer's disease, builds on previous research
linking the disease to peptides (amino acid chains) called b-amyloids
and to defective insulin-processing by the brain. A particular b-
amyloid, Ab-42, is associated with Alzheimer's disease. Funded in part
by the NCCAM, the study looked at two dietary supplements: fish oil
rich in the omega-3 fatty acid docosahexaenoic acid (DHA); and
curcumin, a component of turmeric. Researchers fed the Alzheimer's
disease--model mice a regular or fatty diet; some of the mice also
received fish oil and/or curcumin. They found that the high-fat diet
increased Alzheimer's disease--related chemical processes in the brain,
and that fish oil and curcumin, alone or in combination, counteracted
this effect. DHA and curcumin also protected cognitive performance for
mice on the high-fat diet--i.e., how well the mice remembered a maze.
http://nccam.nih.gov/research/results/spotlight/070109.htm.--Journal of
Neuroscience. 2009;29(28):9078-9089.
Animal Study Shows Connection Between Vitamin E, Lung Inflammation,
and Asthma.--Citing study results in mice, researchers reported for the
first time that the form of vitamin E found primarily in food (gamma-
tocopherol) increased lung inflammation in induced asthma, while the
form of vitamin E found primarily in dietary supplements (alpha-
tocopherol) reduced inflammation. The researchers found that compared
with placebo, alpha-tocopherol significantly reduced inflammation while
gamma-tocopherol significantly increased inflammation. The researchers
also found that the mechanism by which both forms of vitamin E work
involves the regulation of endothelial cell signals during leukocyte
(white blood cell) recruitment--a process that occurs during
inflammation. Endothelial cells line the inner walls of blood vessels.
The researchers concluded that the opposing activities of the two
common forms of vitamin E on inflammation found in this study are
consistent with the contradictory outcomes of vitamin E on asthma in
previous clinical trials. They also noted that the information gained
from this study could have a significant impact on designing and
interpreting future clinical studies on vitamin E. http://
nccam.nih.gov/research/results/spotlight/041109.htm.--The Journal of
Immunology. 2009;182(7):4395-4405.
Researchers Investigate Anti-inflammatory Effects of Pineapple
Extract.--Previous research indicates that bromelain--an enzyme
extracted from pineapple stems--may help inflammatory conditions such
as allergic airway disease. Bromelain's anti-inflammatory effects have
been attributed to its ability to alter the activation and expansion of
the immune system's CD4+ T cells (a type of lymphocyte). To better
understand the processes involved, the NCCAM-funded researchers
conducted in vitro experiments with mouse cells, using bromelain
derived from a commercially available, quality-tested product. The
results show that bromelain reduces CD25 (a protein involved in
inflammation) expression via proteolytic (enzymatic) action, in a dose-
and time-dependent manner. The researchers' analysis of the mechanism
involved found that bromelain apparently splits CD25 from the CD4+ T
cells, and that the T cells remain functional--i.e., they can still
divide--after bromelain treatment. The researchers concluded that the
novel mechanism of action demonstrated in their experiment explains how
bromelain may exert its therapeutic benefits in inflammatory
conditions. http://nccam.nih.gov/research/results/spotlight/
080309.htm.--International Immunopharmacology. 2009;9(3):340-346.
Grape Seed Extract May Help Neurodegenerative Diseases.--In light
of previous studies indicating that grape-derived polyphenols may
inhibit protein misfolding, researchers examined the potential role of
a particular grape seed polyphenol extract (GSPE) in preventing and
treating tau-associated neurodegenerative disorders. The results of
their in vitro study showed that GSPE is capable of interfering with
the generation of tau protein aggregates and also disassociating
preformed aggregates, suggesting that GSPE may affect processes
critical to the onset and progression of neurodegeneration and
cognitive dysfunctions in tauopathies. The researchers concluded that
their laboratory findings, together with indications that this GSPE is
likely to be safe and well-tolerated in people, support its development
and testing as a therapy for Alzheimer's disease. http://nccam.nih.gov/
research/results/spotlight/031209.htm.--Journal of Alzheimer's Disease.
2009;16(2):433-439.
Chinese Herbal Formula Shows Anti-Arthritis Effects in Animal
Study.--Researchers analyzed the effects of a modified version of the
classic Chinese formula Huo Luo Xiao Ling Dan (HLXL) in an animal (rat)
model of adjuvant arthritis, which shares some features with human
rheumatoid arthritis. The researchers induced adjuvant arthritis in
male rats by injecting them with a complete Freund's adjuvant solution
containing heat-killed Mycobacterium tuberculosis. On days 16 to 25,
the rats were given a daily oral dose of either a quality controlled,
11-herb HLXL preparation or liquid only. Compared with controls, the
HLXL-treated rats had significantly decreased arthritis symptom scores;
reduced paw edema; and lower TNF-a and IL-1b levels. No adverse effects
were observed. Based on their results, the researchers concluded that
this HLXL formula may have benefits for treating arthritis and related
inflammatory disorders. http://nccam.nih.gov/research/results/
spotlight/071609.htm.--Journal of Ethnopharmacology. 2009;121(3):366-
371.
Echium Oil Reduces Triglyceride Levels in Mice.--In light of
previous research indicating that oil from the seeds of the Echium
plantagineum plant can lower triglycerides in people, researchers used
an animal model--mice with mildly elevated triglyceride levels--to
investigate how echium oil achieves this effect. The researchers fed
the mice diets supplemented with either echium oil, fish oil, or (as a
control) palm oil. They found that both echium and fish oils had the
following effects: reduced triglycerides in blood plasma and the liver;
enriched EPA in plasma and the liver--echium less so than fish oil; and
``down-regulated'' (decreased the expression of) several genes involved
in synthesis of triglycerides in the liver. The researchers concluded
that echium oil may provide a botanical alternative to fish oil for
reducing triglycerides. http://nccam.nih.gov/research/results/
spotlight/022509.htm.--Journal of Nutritional Biochemistry.
2008;19(10):655-663.
Laboratory Study Shows Black Cohosh Promotes Bone Formation in
Mouse Cells.--Results of laboratory research are the first to indicate
that extracts of the herb black cohosh (Actaea racemosa) may stimulate
bone formation. Researchers added an extract of black cohosh to a
culture of bone-forming mouse cells. The researchers observed that a
high dose (1,000 ng/mL) of the extract suppressed the production of
these bone-forming cells, yet a lower dose (500 ng/mL) significantly
increased the formation of bone nodules. When the cells were treated
with a protein whose molecules attach to estrogen receptors in place of
estrogen, this effect on bone nodule formation disappeared. Thus, the
researchers suggest that ingredients within black cohosh contain a
component that acts through estrogen receptors. The researchers
concluded that their results provide a scientific explanation at the
molecular level for claims that black cohosh may protect against
postmenopausal osteoporosis. They also noted that studying extraction
methods and identifying black cohosh's active components may make it
possible to develop new ways to prevent and treat this condition.
Although results from the study suggest that black cohosh may have
potential implications for the prevention or treatment of
postmenopausal bone loss, there is no evidence yet that this laboratory
research can be extended to treatments in people. http://nccam.nih.gov/
research/results/spotlight/090408.htm.--Bone. 2008;43(3):567-573.
Pomegranate Extract May Be Helpful for Rheumatoid Arthritis (RA).--
RA is an autoimmune disease characterized by joint pain, stiffness,
inflammation, swelling, and sometimes joint destruction. The
pomegranate has been used for centuries to treat inflammatory diseases,
and people with RA sometimes take dietary supplements containing a
pomegranate extract called POMx. However, little is known about the
efficacy of POMx in suppressing joint problems associated with RA.
Researchers used an animal model of RA--collagen-induced arthritis
(CIA) in mice--to evaluate the effects of POMx. They found that POMx
significantly reduced the incidence and severity of CIA in the mice.
The arthritic joints of the POMx-fed mice had less inflammation, and
destruction of bone and cartilage were alleviated. Consumption of POMx,
the researchers also concluded, selectively inhibited signal
transduction pathways and cytokines critical to development and
maintenance of inflammation in RA. Although previous studies of POMx
found cartilage-protective effects in human cell cultures, this is the
first study to observe positive effects in a live model. The
researchers note that the data from this study suggest the potential
efficacy of POMx for arthritis prevention, but not for treatment in the
presence of active inflammation; future studies will address disease-
modifying effects of POMx. They also note that clinical trials are
needed before POMx can be recommended as safe and effective for RA-
related use in people. http://nccam.nih.gov/research/results/spotlight/
120508.htm.--Nutrition. 2008;24(7--8):733-743.
Two Studies Explore the Potential Health Benefits of Probiotics.--
In two studies, researchers investigated how probiotics may have a role
in treating gastrointestinal illnesses, boosting immunity, and
preventing or slowing the development of certain types of cancer. In
one study, researchers investigated how Lactobacillus reuteri ATCC PTA
6475 might work to slow the growth of certain cancerous tumors. Their
study documented the molecular mechanisms of the probiotic's effects in
human myeloid leukemia-derived cells--i.e., how it regulates the
proliferation of cancer cells and promotes cancer cell death. The
researchers noted that a better understanding of these effects may lead
to development of probiotic-based regimens for preventing colorectal
cancer and inflammatory bowel disease. In another study, researchers
looked at whether Lactobacillus acidophilus might enhance the immune-
potentiating effects of an attenuated vaccine (a vaccine prepared from
a weakened live virus) against human rotavirus infection--the most
common cause of severe dehydrating diarrhea in infants and children
worldwide. The investigators' tests on newborn pigs found that animals
given both a vaccine and the probiotic had a better immune response
than the animals given the vaccine alone. The researchers concluded
that probiotics may offer a safe way to increase the effectiveness of
rotavirus vaccine in humans. In both studies, the investigators called
for additional research into the mechanisms behind the health-related
effects of probiotics. http://nccam.nih.gov/research/results/spotlight/
110508.htm.--Cellular Microbiology. 2008;10(7):1442-1452.--Vaccine.
2008;26(29--30):3655-3661.
Research Shows Promise of Pineapple Extract for Inflammatory Bowel
Disease (IBD).--IBD, including Crohn's Disease (CD) and ulcerative
colitis (UC), are characterized by inflammation of the gastrointestinal
tract. Researchers have found that bromelain--an enzyme derived from
pineapple stems--might be able to reduce inflammation in IBD.
Researchers recruited patients with a confirmed diagnosis of CD or UC
as well as a normal, non-IBD control group. In total, this pilot study
recruited 51 participants: 8 controls, 20 with UC, and 23 with CD. To
assess the effect of a bromelain preparation on the production of
cytokines, colon biopsies obtained from patients with UC, CD, and
normal controls were treated in the lab (in vitro) with bromelain. The
researchers report that bromelain reduced production of several pro-
inflammatory cytokines and chemokines that are elevated in IBD and play
a role in the progression of IBD. The authors conclude that bromelain
treatment could potentially benefit IBD patients if similar changes
also occur when colon tissues are exposed to bromelain inside the body.
The researchers also suggest that additional research is needed to
understand how bromelain influences chemokine and cytokine production.
http://nccam.nih.gov/research/results/spotlight/070108.htm.--Clinical
Immunology (2008) 126, 345-352.
Grape Seed Extract May Help Prevent and Treat Alzheimer's.--
Emerging research shows a correlation between red wine consumption and
reduced risk of Alzheimer's disease-type cognitive decline. Researchers
found that grape seed-derived polyphenolics--similar to that in red
wine--significantly reduced Alzheimer's disease-type cognitive
deterioration in mice. Researchers conducted experiments in mice with
Alzheimer's disease to see if a highly purified polyphenolic extract
from Vitis vinifera (cabernet sauvignon) grape seeds, could affect
Alzheimer's disease-type cognitive deterioration. The mice received 5
months of either water containing grape seed extract or water alone as
a placebo treatment. The mice were then given behavioral maze tests to
determine cognitive function and brain tissue samples were tested to
determine evidence of disease. The researchers found that mice treated
with grape seed extract had significantly reduced Alzheimer's disease-
type cognitive deterioration compared to the control mice. This is due
to the prevention of a molecule called amyloid forming in the brain
that has been shown to cause Alzheimer's disease-type cognitive
impairment. http://nccam.nih.gov/research/results/spotlight/
062408.htm.--The Journal of Neuroscience. 2008. 28(25);6388-6392.
Chinese Herbal Formula May Be Helpful for Peanut Allergies.--A
study in mice shows that a Chinese herbal formula may help prevent
dangerous reactions to peanuts. Peanut allergies affect as many as 6
percent of young children and are a major cause of anaphylaxis--a
severe allergic reaction with respiratory symptoms that can be fatal.
Researchers conducted experiments in mice with established peanut
allergies to see if a formula of nine Chinese herbs, called FAHF-2,
could reduce sensitivity to peanuts. The peanut-sensitive mice received
7 weeks of oral treatment with FAHF-2 or water as a placebo treatment.
The mice were then exposed to peanuts at 2 different times to see if
they would have anaphylactic reactions. The researchers found that
FAHF-2 completely protected the mice from a dangerous reaction on both
occasions--showing that protection lasted at least 4 weeks after the
treatment finished. The mice treated with the placebo (water) had
anaphylactic reactions. The researchers note that the protection of
FAHF-2 may result from a shift in the immune balance away from the
allergic response. http://nccam.nih.gov/research/results/spotlight/
012908.htm.--Clinical and Experimental Allergy, June 2007.
Turmeric and Rheumatoid Arthritis Symptoms.--More than 2 million
Americans suffer from rheumatoid arthritis (RA), a condition in which
the body's immune system attacks the joints, causing pain, swelling,
stiffness, and loss of function. The herb turmeric has been used for
centuries in Ayurvedic medicine (a whole medical system that originated
in India) as a treatment for inflammatory disorders, including RA. To
study the effects of turmeric, researchers created symptoms in rats
that mimic those of RA in humans. In a series of experiments, they
treated the rats with different preparations and dosages of turmeric
extracts. The results, measured in terms of joint swelling, suggested
that an extract containing only curcuminoids (a family of chemicals
that is the major component of turmeric) may be more effective for
preventing RA symptoms than a more complex extract containing
curcuminoids plus other turmeric compounds. They also noted that the
curcuminoids-only formulas appeared safer and more effective at lower
doses. Also, the researchers found that the compounds had greater
effectiveness when the rats were treated before instead of after the
onset of inflammation. The authors identified a need for well-designed
preclinical and clinical studies to look further into turmeric for
anti-inflammatory use. http://nccam.nih.gov/research/results/spotlight/
030106.htm.--Journal of Natural Products, March 2006.
Other Research
Botanicals May Help Conditions Associated With Aging.--To evaluate
the effectiveness of botanicals in relation to conditions such as high
blood pressure, cardiovascular disease, cognitive decline, insulin
resistance, and excess fats in the blood, researchers conducted a
literature review and examined studies from their own laboratory. The
researchers looked at effects of dietary soy; soy isoflavones (daidzein
and genistein); grape seed extract, which has a high concentration of
polyphenols; and puerarin, an isoflavone found in kudzu. The literature
review found that soy seemed to lower blood pressure in men and
postmenopausal women, help protect against cardiovascular diseases
(including heart disease and atherosclerosis), and benefit people with
diabetes. The researchers' own animal studies found that soy
isoflavones protected against salt-sensitive hypertension in male rats
and in female rats whose ovaries had been removed (OVX); grape seed
extract reduced blood pressure and improved cognitive functioning in
OVX female rats; and puerarin improved glucose control in male mice.
The researchers concluded that the botanical compounds reviewed appear
to have beneficial effects in animal models of disease (soy also has
shown benefits in humans), and that the compounds may be more effective
in relation to cardiovascular, metabolic, and cognitive function than
for menopausal symptoms. They recommended that the compounds' safety
and mechanisms of action should be carefully tested in the context of
the disease status of potential users. http://nccam.nih.gov/research/
results/spotlight/121008.htm.--Gender Medicine. 2008;
5(suppl A):76S-90S.
Botanical Research Centers Featured in American Journal of Clinical
Nutrition.--The February 2008 issue of the American Journal of Clinical
Nutrition features eight articles from the NIH Botanical Research
Centers Program, which is co-funded by the NIH Office of Dietary
Supplements and the NCCAM. The articles highlight different areas
related to the Centers' research into botanical use, safety, and
efficacy. They include evaluation of botanicals for improving health;
technologies and experimental approaches to evaluating botanicals;
botanicals and metabolic syndrome; echinacea in infection; botanicals
for age-related diseases; ways in which botanical lipids affect
inflammatory disorders; botanicals to improve women's health; and
ensuring botanical dietary supplement safety. The Botanical Centers are
intended to advance research activities in plant identification, as
well as preclinical research and early phase clinical studies. Each
Center has a broad interdisciplinary research program that focuses on
collaborative activities. Each of the Centers was created with a high
potential for translating findings into public health benefits. http://
nccam.nih.gov/research/results/spotlight/042308.htm.--American Journal
of Clinical Nutrition, 2008. Volume 87, Number 2, 463.
Population-based Research
Cancer Survivors Are More Likely Than General Population To
Use CAM, According to National Survey Analysis
A recent analysis of the 2007 National Health Interview Survey
revealed that cancer survivors are more likely to use complementary and
alternative medicine (CAM) compared with the general population. Cancer
survivors are also more likely to use CAM based on a recommendation by
their healthcare providers and to talk to their healthcare providers
about their CAM use. Although cancer survivors communicated more about
their CAM use than the general population, the study authors emphasized
the overall need for improving communication between patients and
providers about CAM use to help ensure coordinated care. http://
nccam.nih.gov/research/results/spotlight/032011.htm.--Journal of Cancer
Survivorship: Research and Practice. 2011;5(1):8-17.
Analysis of National Survey Shows CAM Use in People With
Pain or Neurological Conditions
According to an analysis of the 2007 National Health Interview
Survey, approximately 44 percent of American adults with pain or
neurological conditions, compared to about 33 percent of people without
those conditions, used complementary and alternative medicine (CAM)
during the previous year. The most common CAM therapies used by people
with these conditions were mind-body therapies (25 percent), such as
deep breathing exercises, meditation, and yoga; biologically based
therapies (21 percent), such as herbal therapies; manipulative and
body-based therapies (19 percent), such as massage and chiropractic
care; and alternative medical systems (4 percent). In addition,
respondents with pain or neurological conditions indicated that they
used CAM because conventional treatment did not work (20 percent vs. 10
percent) and was too expensive (9 percent vs. 4 percent). The
researchers noted that this analysis demonstrates the need for more
robust studies on the efficacy of CAM therapies for people with these
conditions. http://nccam.nih.gov/research/results/spotlight/
111010.htm.--Journal of Neurology. 2010;257:1822-1831.
Study Asks Adolescents With Inflammatory Bowel Disease
About Use of Complementary and Alternative Medicine
(CAM) Mind-body Therapies
This study found that many adolescents with inflammatory bowel
disease are currently using or would consider using CAM--specifically
mind-body therapies such as relaxation and guided imagery--to help
manage their symptoms. This disease is actually a group of disorders
(including Crohn's disease and ulcerative colitis) that cause
inflammation of the intestines. The physical and emotional problems
associated with irritable bowel disease in adolescents often affect
quality of life. The researchers noted that their findings provide
groundwork for future studies to determine the effect of CAM therapies
on health outcomes in adolescents with inflammatory bowel disease.
http://nccam.nih.gov/research/results/spotlight/031110.htm.--
Inflammatory Bowel Disease. 2010;16(3):501-506.
Certain Categories of Complementary Therapies Appear To
Benefit Older Adults
According to a recent analysis of data from the 2002 National
Health Interview Survey and the 2003 Medical Expenditure Panel Survey,
use of biologically based therapies (e.g., herbs or megavitamins) and
manipulative/body-based therapies (e.g., chiropractic or massage) may
be associated with better health outcomes among individuals age 55
years and older. The analysis showed a statistical association between
ability to function and use of biologically based therapies and
manipulative/body-based therapies. The researchers concluded that some
categories of complementary therapies may be more beneficial than
others for older adults. They cautioned that these findings should not
be interpreted as evidence for the efficacy of specific therapies.
Although the findings indicate that the use of certain kinds of CAM
therapies is associated with better health outcomes for older adults,
only clinical trials can determine the efficacy of specific therapies.
The researchers also noted that this is the first longitudinal
assessment (analysis of data collected from the same people at
different points in time) of possible connections between complementary
therapy use and health outcomes in a national sample of older adults.
They recommended additional population-based research in this area.
http://nccam.nih.gov/research/results/spotlight/070810.htm.--Journal of
Alternative and Complementary Medicine. 2010;16(7):701-706.
Many Older People Use Both Prescription Drugs and Dietary
Supplements
Researchers analyzed the use of prescription drugs and dietary
supplements in a sample of 3,070 people aged 75 and older. The data had
been gathered during the Gingko for the Evaluation of Memory (GEM)
study, a clinical trial that examined the effects of Gingko biloba on
the development of dementia. Nearly 75 percent of the GEM study
participants took at least one prescription drug and one dietary
supplement. Approximately 33 percent used three or more prescription
drugs and three or more supplements. Furthermore, 10 percent of the
participants combined five or more prescription drugs with five or more
dietary supplements. Although supplements were taken along with all
types of prescription drugs, individuals using prescribed nonsteroidal
anti-inflammatory drugs (NSAIDs), thyroid drugs, and estrogens were
more likely to use dietary supplements. Individuals who used
prescription drugs for high blood pressure and diabetes were less
likely to use dietary supplements. Based on these data, they recommend
that patients discuss dietary supplement use with their healthcare
providers. In addition, the researchers emphasized the need for further
investigations to better define the clinical importance of interactions
between drugs and supplements. http://nccam.nih.gov/research/results/
spotlight/071509.htm.--Journal of the American Geriatric Society.
2009;57(7):1197-1205.
Translating CAM Research Results Into Clinical Practice:
Results From a National Survey of Physicians and
CAM Providers
In an initial investigation of the potential for information from
CAM research to influence clinical practice, a 2007 national survey
asked acupuncturists, naturopaths, internists, and rheumatologists
about their awareness of CAM clinical trials, their ability to
interpret research results, and their use of research evidence in
decisionmaking. The survey focused on awareness of two major NCCAM-
funded clinical trials that studied acupuncture or glucosamine/
chondroitin for osteoarthritis of the knee. Fifty-nine percent of the
1,561 respondents were aware of at least one of the two clinical trials
but only 23 percent were aware of both trials. The acupuncture trial
was most familiar to acupuncturists and rheumatologists, the
glucosamine/chondroitin trial to internists and rheumatologists.
Overall, awareness was greatest among rheumatologists and those
practicing in institutional or academic settings. All groups regarded
clinical experience as ``very important'' in their decisionmaking,
although CAM providers were more likely to rate it ``most important.''
Physicians were much more likely than CAM providers to consider
research results very important or ``very useful'' in their clinical
decisionmaking. The survey team concluded that CAM research has the
potential to make a difference in both conventional and alternative
medicine clinical practice. They recommend concerted efforts to better
train all clinicians in interpretation and use of evidence from
research studies, and to improve the dissemination of research results.
http://nccam.nih.gov/research/results/spotlight/041309.htm.--Archives
of Internal Medicine. 2009;169(7): 670-677.
National Survey Reports on CAM Use by Adults and Children
The 2007 The National Health Interview Survey (NHIS) found that
approximately 38 percent of adults and 12 percent of children use some
form of CAM. Among both adults and children, the most commonly used CAM
therapy is nonvitamin/nonmineral natural products; fish oil/omega-3 is
the most popular natural product for adults, while echinacea is the
most popular for children. Back pain is by far the most common
condition prompting adults to use CAM. Among children, back or neck
pain is the most common reason for using CAM, followed closely by head/
chest colds. The 2002 NHIS also included a supplement on CAM use by
adults. Overall usage among adults in 2002 (36 percent) was about the
same as in 2007. Since 2002, usage has increased for some therapies,
including deep breathing, meditation, massage, and yoga. Adult use of
CAM for head/chest colds showed a marked decrease between 2002 and
2007. The 2007 survey was the first to ask about CAM use by children.
http://nccam.nih.gov/research/results/spotlight/123108.htm.--CDC
National Health Statistics Report #12. 2008.
New Findings on Sleep Disorders and CAM
Based on a national survey, the NCCAM scientists found that over
1.6 million American adults use some form of CAM to treat insomnia or
trouble sleeping. The authors key findings are:
--More than 17 percent of adults reported insomnia or trouble
sleeping in the past 12 months. In this group, 4.5 percent used
some form of CAM to treat these problems.
--The CAM users were most likely to use biologically based therapies
(nearly 65 percent), such as herbal therapies, or mind-body
therapies (more than 39 percent), such as relaxation
techniques. Most who used these two types of therapies said
they were at least somewhat helpful for insomnia or trouble
sleeping.
http://nccam.nih.gov/research/results/spotlight/090106.htm.--Archives
of Internal Medicine, September 2006.
CAM Use High Among Adolescents
Researchers conducting the first national survey of CAM use among
adolescents in the United States analyzed responses from 1,280
adolescents aged 14 to 19. They found that 79 percent had used at least
one form of CAM during their lifetime and that females used CAM more
than males. Among all participants, almost 30 percent had used one or
more dietary supplements, and almost 10 percent had used supplements
along with prescription medications in the preceding month. Many of the
supplements the teens reported using were related to attempts to change
body shape (e.g., creatine and weight-loss products). The authors urged
that healthcare providers be aware of CAM and dietary supplement use by
their adolescent patients, because of the lack of standardization in
supplements, as well as their potential for safety risks and
interactions with prescription medications.http://nccam.nih.gov/
research/results/spotlight/040106.htm.--Journal of Adolescent Health
April 2006.
More Than One-third of U.S. Adults Use Complementary and
Alternative Medicine, According to a 2002
Government Survey
According to the 2002 National Health Interview Survey (NHIS), 36
percent of U.S. adults use some form of CAM. The most commonly used
form of CAM was natural products (such as herbs and other botanicals).
Other popular CAM therapies included deep breathing, meditation,
chiropractic care, yoga, massage, and special diets. Echinacea was the
most commonly used natural product. CAM was most often used to treat
back pain, colds, neck pain, joint pain, and anxiety or depression. The
survey also revealed variations in CAM use by population subgroups. For
example, CAM use overall was more common among women, people with
higher education, people who had been hospitalized in the past year,
and former smokers (compared to current smokers or those who had never
smoked). The authors noted that the information from this survey is a
foundation for future studies of CAM as it relates to health and
disease among population subgroups. http://nccam.nih.gov/research/
results/spotlight/050810.htm.--CDC Advance Data Report #343. 2004.
THE NCCAM RESEARCH APPROACHES
Question. Individualized therapies that involve multiple approaches
often do not lend themselves to traditional double-blind studies but
are frequently used in integrative medicine. Please describe work that
the NCCAM is doing to support research on these kinds of treatments.
Answer. The NCCAM recognizes that assessing some of the
individualized therapies used in integrative medicine in double-blind
studies is challenging. Similar challenges confront other disciplines
of healthcare research that employ individualized or multifaceted
interventions, complex procedures, or system approaches (e.g.
cognitive-behavioral therapy, surgery, or behavior change strategies).
There is broad interest within the biomedical and behavioral research
communities in applying effectiveness and outcomes approaches and
pragmatic trial designs to such questions.
Addressing this challenge is a high priority for the NCCAM as
evidenced by its inclusion as one of our strategic plan objectives: to
``develop research examining the contributions of specific promising
CAM approaches to better treatment and health promotion using the real-
world methods and tools of the disciplines of observational, outcomes,
health services, and effectiveness research.'' These methods and
approaches also offer potential to address the challenges of conducting
CAM research that reflects practice in the real world.
Health provider networks, practice-based clinical research
networks, and integrative medicine practices provide important venues
in which to develop real-world evidence across a broad array of outcome
measures regarding the effects and effectiveness of CAM approaches and
their integration into strategies for treatment and health promotion.
Practice-based research provides an important setting in which to study
the complex interplay of intervention, the patient-provider
relationship, and other important contextual and environmental factors
involved in healthcare and health promotion. Indeed, many CAM and
integrative care practices actively seek to employ these factors.
Population-based and practice-based research strategies also offer
great potential for developing evidence regarding the effectiveness of
CAM-related interventions in engaging individuals in health-promoting
behaviors and practices.
The NCCAM is pursuing these approaches in the context of CAM and
integrative medicine practice through collaboration with experts who
confront similar challenges and opportunities. For example, the NCCAM
is working with our colleagues at the Departments of Defense and
Veterans Affairs to explore ways that CAM mind and body approaches can
be used in integrative approaches to treat pain, stress disorders, and
other symptoms. Further, the NCCAM has released a funding opportunity
announcement to foster development of CAM research methodology titled,
``Translational Tools for Clinical Studies of Mind/Body and Manual
Therapy CAM Interventions.'' It will ``encourage the development of
improved research methodology to study safety, efficacy, and clinical
effectiveness of mind-body interventions.''
Additionally, the NCCAM has substantially increased its investment
in research which advances our understanding of the usefulness of CAM
interventions in real world settings. For example, in one promising
study being funded by the NCCAM at the Mount Sinai School of Medicine,
researchers are studying methods to utilize all available information
regarding CAM treatments in patients with HIV. By utilizing randomized
controlled trials along with observational studies, expert judgment and
other types of data, they seek to develop a clinical prediction model
to determine which CAM interventions are beneficial. Another study,
this one at Brigham and Women's Hospital, is looking at the
effectiveness of an integrative healthcare team at improving outcomes
for chronic low back pain by focusing on observational data. These are
just two examples of studies funded by the NCCAM that go beyond
traditional double-blind studies by using real world data to support
CAM research.
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS) AND
PREVENTATIVE MEDICINE
Question. One goal of the NCATS is to accelerate the process by
which scientific discoveries are turned into treatments and cures--
moving discoveries more quickly through the ``valley of death'' or the
time between discovery and available cures. In particular, the NIH has
indicated that the NCATS would focus on the drug development pipeline
with a hope of understanding and addressing the reasons that so many
drugs fail in development. Meanwhile, research has increasingly shown
how a healthy lifestyle, exercise or better nutrition can help prevent
the onset of disease or the use of expensive medicines or treatments.
Will translational research that focuses on prevention or disease
control through lifestyle changes be incorporated into the new vision
for the NCATS? If so, how? Or will the NCATS focus exclusively on drug
development?
Answer. As you point out, the prevention of diseases as well as
their successful treatment may often require behavioral and lifestyle
interventions or strategies. As such, a clear understanding of, and
further research into, the role of behavioral and lifestyle factors in
human health will be critical to the NCATS' success in catalyzing the
development of new strategies to address human health and disease. The
NCATS will support research to generate new methods and approaches
aimed at accelerating the development, testing, and implementation of
diagnostics, therapeutics, and prevention strategies. The NCATS
prevention and behavioral research will be coordinated with the related
work of the other NIH Institutes and Centers as well as with the Office
of Disease Prevention and the Office of Behavioral and Social Sciences
Research and carried out in part through the 60 institutions with
Clinical and Translational Science Awards.
BUDGETARY CONSTRAINTS ON UNIVERSAL FLU VACCINE
Question. The NIH-supported scientists are making significant
progress toward developing a universal flu vaccine that would confer
longer term protection against multiple influenza virus strains and
make yearly flu shots a thing of the past. What would be the impact on
public health if research on the universal flu vaccine were delayed or
scaled back due to budget constraints at the NIH?
Answer. The costly and time-consuming annual process of
manufacturing, distributing, and administering millions of doses of
seasonal influenza vaccine would become obsolete if researchers could
design a vaccine that provides protection against a broad range of
influenza strains over multiple influenza seasons. One strategy to
overcome the need for a yearly influenza vaccine is to develop a
vaccine against the common components of the influenza virus that do
not change from year to year or from strain to strain. Recently,
researchers supported by the National Institute of Allergy and
Infectious Diseases (NIAID) have made significant breakthroughs in
identifying the specific parts of influenza viral proteins that are
unchanged among both seasonal and pandemic strains. So-called
``universal'' influenza vaccines that capitalize on these findings
might one day provide protection against the broad range of viruses
arising from seasonal antigenic drift (minor changes) and pandemic
antigenic shift (major changes) that are the hallmark of influenza
viruses.
The NIAID is supporting a number of research projects to develop a
vaccine that induces a potent immune response to the common elements of
the influenza A virus that undergo very few changes from season to
season and from strain to strain. Conserved internal proteins of the
virus such as the M2 protein and conserved regions of the influenza
envelope protein hemagglutinin (HA) have been identified as promising
vaccine targets. For example, the NIAID-supported researchers found
that a vaccine based on the M2 protein of H5N1 avian influenza virus
elicited strong immune responses in mice. The HA protein of influenza
virus, which is the protective antigen of the virus, has both a
``head'' region and a ``stem'' region. The NIAID-funded researchers
recently generated a novel form of HA that elicited broadly cross-
reactive antibodies against the stem region of a number of divergent
seasonal and pandemic influenza subtypes and provided protection
against disease in mouse challenge studies. In addition, the NIAID
intramural researchers in the Vaccine Research Center demonstrated that
a ``prime-boost'' vaccine strategy based on conserved regions of the HA
protein could protect animals from infection with multiple strains of
influenza that had been prevalent over many years. This ``prime-boost''
vaccine strategy involves first priming the immune system with a
vaccine containing the DNA of an influenza surface protein (HA) and
then administering a second vaccine made from a seasonal influenza
virus or from a weakened cold virus, to amplify the immune response
generated by the first vaccine.
Budget reductions could adversely affect the NIAID's ability to
continue support of these activities in a robust and timely manner.
Funding cuts could delay the development of new candidate vaccines for
universal influenza and improved vaccines for seasonal influenza, as
well as delay initiation of clinical trials necessary to test these
vaccines. However, if budget reductions do materialize, the NIH would
have to reevaluate its research priorities, and thus, the specific
research areas to be impacted by such reductions would be determined at
that time.
BUDGETARY CONSTRAINTS ON VACCINE RESEARCH
Question. What other types of vaccine research underway at the NIH
might also have to be delayed or scaled back due to budget constraints?
Answer. Vaccines provide a safe, cost-effective, and efficient
means of preventing illness, disability, and death from infectious
diseases. The NIH is recognized as a worldwide leader in basic
immunology research that underpins all vaccine development, and
conducts or supports preclinical and clinical research on a broad
spectrum of new and improved vaccine candidates. Recent progress in
global vaccine research--from the RV 144 trial in Thailand that
demonstrated that an HIV vaccine regimen provided a modest preventive
effect, to the NIH-sponsored research advances that may unlock
neutralizing antibody targets for a range of infectious diseases--
highlights the need for a robust vaccine research portfolio at the NIH
to pursue these and other advances in the field. A reduction in vaccine
research funding at the NIH could slow the pace of ongoing efforts to
develop new tools to prevent infectious diseases and could erode our
ability to capitalize on scientific progress toward the development of
vaccines.
HIV vaccine research activities that could be slowed by reduced
funding levels include the conduct of additional and important Phase
IIb trials that are planned to further assess and improve upon the
results of the RV144 HIV vaccine trial, especially in other risk groups
and in countries other than Thailand. Reduced funding could also
undermine other important HIV vaccine trials. For example,
investigators conducting the HIV Vaccine Trials Network (HVTN) 505
trial would likely be unable to expand the study to include 2,200
participants at 21 sites in 18 U.S. cities in order to assess whether
the candidate vaccine regimen can prevent HIV infection and/or reduce
viral load. Decreased funding could also limit the NIH's ability to
support efforts to identify other promising HIV vaccine candidates, and
curtail our ability to test those candidates that hold the most promise
and advance them into clinical trials. Again, however, specific
research areas that may be impacted by budget reductions are subject to
priority assessments and cannot be precisely predetermined.
In addition to research to develop an HIV vaccine, the NIH is also
supporting vaccine research across a range of other globally important
diseases, including dengue, pandemic influenza, malaria, and
tuberculosis, as well as diseases that might occur as a result of acts
of bioterrorism. A reduction in funding could force the NIH to scale
back efforts across many of its infectious disease research programs.
Potential adverse effects include a reduced ability to support
preclinical product development, which is intended to assist companies
and academic investigators in developing essential products to prevent
and treat infectious diseases. Reduced funding levels could limit the
development of new and improved preclinical products required to
confront and keep pace with emerging and re-emerging infectious
diseases, including a planned array of vaccine-related product
development services. Funding constraints could also adversely affect
clinical research efforts at the NIH, limiting our ability to support
clinical trials designed to assess influenza and malaria vaccines, and
slowing the progress of trials. Finally, budget constraints could
result in significant delays in advancing research projects focused on
the development of next-generation vaccines for biodefense purposes.
GUIDANCE FOR USE OF CLASS B CATS
Question. On March 18, the NIH released guidance on its plan to
transition from the use of USDA Class B dogs to other legal sources
(Notice NOT-OD-11-055). Why is there no mention of cats? The transition
plan, as the NIH notes, is in accordance with the National Academy of
Sciences report, Scientific and Humane Issues in the Use of Random
Source Dogs and Cats in Research. The NIH notice also quotes from
Senate report language regarding research on both dogs and cats, but
the mention of cats was excised from the quotation. Does the NIH plan
to issue a separate guidance dealing with cats?
Answer. The NIH believes that sufficient numbers of cats currently
are available through Class A vendors to support the needs of the NIH-
supported research. Therefore, no plan for phase out is needed nor a
plan for developing sufficient animals from Class A vendors. At
present, the NIH has no plans to issue separate guidance dealing with
cats.
LUPUS RESEARCH
Question. How are the different NIH Institutes NIAID, National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
National Heart, Lung, and Blood Institute (NHLBI), National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), General
Medicine, among others) working together to increase support for
research on lupus? How will the new Translational Center work to
address diseases like Lupus that cross multiple Institutes?
Answer. Lupus is an autoimmune disease that affects the lives of
many Americans. Ninety percent of Americans with lupus are women. Lupus
can affect many parts of the body, including the joints, skin, kidneys,
heart, lungs, blood vessels, and brain. Although people with the
disease may have different symptoms, some of the most common ones
include extreme fatigue, painful or swollen joints (arthritis),
unexplained fever, skin rashes, and kidney problems.
A wide range of basic, translational, and clinical research on
lupus is being supported by many of the Institutes, Centers, and
Offices at the NIH. Highlights of collaborative efforts include:
--The Lupus Federal Working Group, established on behalf of the
Department of Health and Human Services (HHS) Secretary by the
NIH, facilitates collaboration among the NIH components, other
Federal agencies, voluntary and professional organizations, and
industry groups with an interest in lupus. The group is
coordinated by the NIAMS and includes participation from nine
other NIH Institutes and Centers.
--The NIAID chairs the NIH Autoimmune Diseases Coordinating
Committee, established by the Congress in fiscal year 1998 to
increase collaboration and facilitate coordination of
autoimmune diseases research among 21 NIH Institutes and
Centers (ICs), other Federal agencies, and private health and
patient advocacy groups.
--In September 2010, the NIAMS, the National Cancer Institute (NCI),
the NIAID, and the NIH Office of Research on Women's Health
(ORWH) hosted a 2-day scientific meeting in Bethesda, Maryland,
``Systemic Lupus Erythematosus: From Mouse Models to Human
Disease and Treatment.'' Clinicians and basic scientists from a
variety of disciplines came together to discuss the clinical
and molecular similarities and differences seen in human
disease and animal models. Participants also discussed advances
in lupus genetics, challenges and advances in the treatment of
lupus, and emerging areas warranting further study.
--The Autoimmunity Centers of Excellence (ACEs), sponsored by the
NIAID, the NIDDK, the NIAMS, the National Institute of
Neurological Disorders and Stroke (NINDS), and the ORWH,
conduct collaborative research on autoimmune diseases,
including lupus. This research includes clinical trials of
immunomodulatory therapies and associated studies to understand
the mechanism of disease and therapeutic effects.
--The Human Leukocyte Antigen (HLA) Region Genomics in Immune-
Mediated Diseases Consortium, a cooperative research group
sponsored by the NIAID and the NINDS, focuses on defining the
association between variations in the HLA genetic region and
immune-mediated diseases, including lupus.
--The Cooperative Study Group for Autoimmune Disease Prevention,
sponsored by the NIAID, the NIDDK, and the Juvenile Diabetes
Research Foundation International, focuses on research for the
prevention of human autoimmune diseases, including lupus.
Projects include the creation of improved models of disease
pathogenesis and therapy to better understand immune mechanisms
that will provide opportunities for prevention strategies.
--The NIDDK and the NIAMS organized an April 2010 meeting, ``Novel
Therapies to Enhance ESRD (End Stage Renal Disease) Patient
Survival,'' which included a session on ``Lessons for
Nephrologists from Lupus.'' The NIDDK is planning a meeting in
mid-2012 that will focus on glomerular disease, including that
arising from lupus.
--The NIDDK-supported Chronic Kidney Disease Biomarkers Consortium--
which seeks to discover and validate biomarkers for chronic
kidney disease--is assessing inflammatory mediators as
biomarkers for progression of kidney disease in patients with
lupus who have had kidney biopsies. The Consortium will cross-
validate its findings using a variety of patient cohorts,
including those funded by the NIDDK (such as the Chronic Renal
Insufficiency Cohort) and other ICs (such as the
Atherosclerosis Risk in Communities Study, funded by the
NHLBI).
The proposed NIH NCATS has been designed to catalyze the
development of innovative methods and technologies that will enhance
the development, testing, and implementation of diagnostics and
therapeutics across a wide range of conditions, including diseases such
as lupus. The NCATS will encourage collaborations across all sectors,
provide resources to enable therapeutics development, and support and
enhance training in the relevant translational science disciplines.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) RESEARCH
Question. COPD is the third leading cause of death in the United
States, killing approximately 141,075 Americans annually. Despite the
growing burden of COPD, the United States does not currently have a
comprehensive public health action plan on the disease. What activities
are the NIH currently conducting on COPD and what is missing from the
Federal response? Would a Federal action plan on COPD provide insights
on how we could better address this leading killer?
Answer. The NHLBI--the NIH component with primary responsibility
for lung diseases--supports a wide range of research and education
activities on COPD. Its programs include basic science and animal
studies of underlying disease mechanisms; clinical studies of COPD risk
factors, genetics, molecular and cellular defects, disease progression,
and co-morbidities; translational studies of pathways and drugs that
may lead to better treatments; clinical trials; comparative
effectiveness research; and public and professional educational
programs to increase awareness of COPD and knowledge about its
symptoms, diagnosis, and treatment. Several other NIH components,
including the NCI, the National Institute on Aging (NIA), the National
Institute on Drug Abuse (NIDA), the National Institute of Environmental
Health Sciences (NIEHS), the National Institute of General Medical
Sciences (NIGMS), and the National Institute of Nursing Research
(NINR), also support research relevant to COPD. For example, the NCI
and the NHLBI are collaborating on an investigation of lung cancer and
COPD. The NHLBI also cooperates with a number of other Federal agencies
on this disease. The NHLBI Long Term Oxygen Treatment Trial is carried
out in collaboration with CMS. The FDA collaborates with the NHLBI in a
program called SPIROMICS, which is performing extensive molecular and
clinical phenotyping of subjects with COPD to indentify biomarkers and
characterize the heterogeneity in the patient population. VA Medical
Centers participate in a number of the NHLBI clinical trials in COPD.
The CDC is a partner in the NHLBI's COPD Learn More Breathe Better
national public health education campaign. The NHLBI--CDC collaboration
has led to the introduction of a module on COPD in the Behavioral Risk
Factor Surveillance System Survey and to a recently released public
health strategic framework for COPD prevention. Investigators supported
jointly by the NHLBI and the AHRQ are setting up a large registry for
comparative effectiveness research. Finally, the reports of the Surgeon
General on the health effects of smoking are a constant guide for the
NHLBI programmatic directions for COPD.
These examples illustrate the extent and diversity of existing
Government programs related to COPD, the cooperative and complementary
interactions among Federal agencies in this area, and the central role
that the NHLBI plays in the Government's efforts to control this
disease. The NHLBI will continue to provide strong leadership for
research and education activities to address this growing public health
epidemic in collaboration with other components of the Federal
Government. In particular, the NHLBI plans to host a forum of
representatives from Federal Government agencies in fiscal year 2012 to
share information regarding current activities related to COPD and to
discuss opportunities for increasing cooperation among stakeholders and
enhancing effectiveness of the Federal response to this debilitating
and deadly disease. Whether a Federal action plan should be developed
will almost certainly be a topic of discussion at the forum.
clinical trials cooperative group program reorganization impact on the
GYNECOLOGICAL COOPERATIVE GROUP
Question. The Institute of Medicine (IOM) of the National Academies
was asked by the National Cancer Institute (NCI) to review the
Institute's Clinical Trials Cooperative Group Program. One of the
recommendations from that report is a reorganization of the Cooperative
Group Structure that would entail restructuring and consolidating some
of the cooperative groups. We understand that the reorganization may
merge the Gynecological Cooperative Group (GOG) with the NSABP
(National Surgical Adjuvant Breast and Bowel Project) and the RTOG
(Radiation Therapy Oncology Group). Gynecological cancers are generally
diagnosed by gynecologists and the GOG is the only cooperative group
that studies gynecological cancers. Is our understanding of the
reorganization plan for the GOG correct and, if so, what is the
rationale for the planned merger of the GOG with these other groups?
What is the scientific basis for it? If not, what is the current plan
for the GOG? In general, what has been the process for making these
reorganization decisions, what are the primary considerations and what
is the timeframe and next steps for finalizing the reorganization
decisions?
Answer. For more than 50 years, the NCI has supported a standing
infrastructure--the NCI Cooperative Group Program--to conduct large
scale cancer clinical trials across the Nation, with successful
completion of many important trials that have led to new treatments for
cancer patients. Over time, however, oncology has evolved into a more
molecularly based discipline including genetic sub-classification of
tumors and individualized treatments. Accordingly, the NCI must ensure
that the Cooperative Groups are optimally situated and well-prepared to
continue to design, enroll and complete state-of-the-art trials for
cancer patients.
In 2009, the NCI commissioned the Institute of Medicine to review
the Cooperative Group Program in order to gather independent and expert
perspectives on the state of cancer clinical trials and to obtain
advice about improvements in the NCI Cooperative Group Program. The IOM
report ``A National Cancer Trials System for the 21st Century:
Reinvigorating the NCI Cooperative Group Program'' was issued in April
2010. The report called for a series of changes to the clinical trials
program, including restructuring and consolidation of the adult
Cooperative Groups.
Transforming the NCI's Cooperative Group System into a highly
integrated National Clinical Trials Network is one of the Institute's
major initiatives. Enhancing the scientific basis for the clinical
trials that the NCI supports is essential if marked improvements in
cancer diagnosis, prevention, and therapy are to continue unabated. The
increasing need for molecular screening of large patient populations to
define categories appropriate for intervention provides an important
rationale for consolidating the NCI-supported clinical research groups
into a coordinated network. Furthermore, the NCI's commitment to
strategic consolidation includes the requirement for a shared, and
standardized, clinical trials data management IT infrastructure, for a
facile process by which the phase III clinical trials portfolio is
prioritized, and for the conduct of clinical investigations that are
multimodal in nature, and involve understudied and underserved patient
populations. The NCI's restructured clinical trials network, as
envisioned, will be organized to move such studies forward both
efficiently and with the necessary resources to conduct correlative
scientific investigations capable of increasing the potential of these
trials to change current medical practice.
In addition to the ability to screen large patient populations, a
coordinated network of a smaller number of consolidated Cooperative
Groups will be better able to prioritize specific trials across all
disease areas and to efficiently develop and complete multicenter
trials. Consolidation will also enable optimal use of crucial
biospecimens from the NCI-supported clinical trials. Finally,
consolidation will address current disincentives to study less common
diseases or to enroll patients to another Cooperative Group's trials.
The NCI began a discussion with the Cooperative Group Chairs in
November 2010 about changes to the Group structure and has participated
in multiple discussions with the public. Throughout the process, the
NCI has been--and remains--committed to having an open dialogue about
changes to the Cooperative Group Program. The NCI has not dictated
mergers among groups and instead has encouraged groups to voluntarily
consolidate on their own. The Gynecological Oncology Group (GOG), the
National Surgical Adjuvant Breast and Bowel Project (NSABP), and the
Radiation Therapy Oncology Group (RTOG) have entered negotiations about
consolidation, and as background for those discussions, the NCI program
leadership met with the GOG Chair in May 2011 to discuss GOG concerns
and to provide assurances that funding for gynecological cancers will
be protected. The NCI expects that consolidation will greatly
strengthen the overall program and will provide each of the
consolidated Cooperative Groups with unique capabilities and a greatly
expanded network of clinical sites to recruit patients for trials
across the entire program.
Since December 2010, the NCI has been gathering input from
stakeholders and the cancer community about the plans to restructure
the program. The comment period will close in July 2011, at which point
the NCI will develop a concept proposal about the new structure and
proceed with the NCI leadership review and presentation to the Board of
Scientific Advisors in November 2011. The Funding Opportunity
Announcement for the new Clinical Trials Program will be developed over
the next several months, and released in July 2012. Applications will
be accepted in November 2012 and reviewed over the next few months,
with the consolidated Cooperative Groups being funded in fiscal year
2014.
CREATION OF SUAA
Question. Based on recommendations from the Scientific Management
Review Board, the NIH has been considering the formation of a single
institute that would be devoted to research related to substance use,
abuse and addiction. The focus at the NIH seems to have turned away
from this reorganization as attention has shifted to the creation of
the NCATS. Is the NIH still considering the formation of this institute
and, if so, what is the latest thinking on the creation of such an
institute? What is the process and timeframe for making a decision and
developing a plan?
Answer. The NIH is actively considering the formation of a single
Institute that will focus on substance use, abuse, and addiction-
related research. After receiving the SMRB recommendations, Dr. Collins
formed a Task Force of scientific experts to begin a comprehensive
review of the NIH substance use, abuse, and addiction research
portfolio. The Task Force has met with subject matter experts from
across the NIH to gain a better understanding of the breadth and
diversity of NIH's substance use, abuse, and addiction portfolio. This
review has made it clear that this portfolio is very complex and taken
together with the administrative steps that would be required to
implement a reorganization of this magnitude, we determined that
additional time would be advantageous. Additionally, during the last
few months, many stakeholders have requested additional input into the
development of the scientific plan for the new Institute.
The NIH will continue to analyze our substance use, abuse, and
addiction portfolio to provide a framework for a new proposed
Institute. We will also develop a new scientific strategic plan to
provide a framework for substance, use, abuse, and addiction-related
research at NIH. This scientific strategic plan will be directed by the
relevant Institute or Center Directors and will include extensive
consultation with stakeholders, including scientists, patients, and the
community, in addition to soliciting information from the Advisory
Councils of the potentially affected Institutes and Centers. It is our
intent to release the portfolio integration plan and the scientific
strategic plan in the fall of 2012 for public comment, obtaining the
Secretary's formal approval in December 2012 with the ultimate goal of
notifying Congress through inclusion in the proposed reorganization in
the fiscal year 2014 President's budget and standing up the new
Institute at the beginning of fiscal year 2014 (October 1, 2013).
USE OF CHIMPANZEES IN BIOMEDICAL RESEARCH
Question. In response to a request from the NIH, the Institute of
Medicine (IOM) is conducting a study on the use of chimpanzees in
biomedical and behavioral research. The study will assess the current
and anticipated uses of chimpanzees in the NIH research and determine
whether chimpanzees are and will be necessary for research needed to
advance public health. The IOM is expected to release the report by the
end of this year, in December 2011. Some interest groups have suggested
that a moratorium be put in place on new funding for invasive research
using chimpanzees pending the release of the IOM report. What would be
the impacts of this type of temporary moratorium on the NIH research?
Answer. NIH appreciates the Senator's continued interest in the use
of chimpanzees in research. As you know, chimpanzees have been used in
important research such as key studies on hepatitis, malaria, and
vaccine research. The Senator wisely requested that NIH initiate an in-
depth analysis to be performed by the Institute of Medicine (IOM) to
assess the scientific need for the continued use of chimpanzees in
biomedical research. The NIH has followed this advice and anticipates a
thoughtful analysis and rigorous review that will be a valuable input
as NIH charts the future course for the use of chimpanzees in research.
In the interim, while the IOM study is ongoing, we believe it would
be unwise to make any abrupt changes in our primate research programs.
Therefore, we think it best to await the IOM report before making
decisions that could have potentially far reaching implications.
______
Questions Submitted by Senator Daniel K. Inouye
THE NATIONAL INSTITUTES OF HEALTH (NIH) RESEARCH SUPPORT TO HAWAII
ACADEMIC INSTITUTIONS
Question. Over the years the subcommittee has urged the NIH to pay
particular attention to developing a cadre of scientific investigators
from rural America and in the case of Hawaii, from the neighbor
islands. This month the College of Pharmacy at the University of Hawaii
at Hilo will graduate its first class and I appreciate the ongoing
efforts by the leadership of several of your Institutes to ensure that
basic research infrastructure will be made available for their faculty
and students. In order to attract the next generation of scientists, it
is absolutely necessary that they be exposed to caring mentors and the
joy of scientific inquiry in their early academic years. Those of us
who represent rural America appreciate how difficult it can be to
provide this critical nurturing experience, especially when bright high
school students and undergraduate students have to face significant
transportation barriers, such as exist in an island State. At this
time, I would appreciate receiving a report detailing the extent to
which your Institutes have been able to provide scientific resources to
Hawaii, and particularly to the educational campuses on the various
islands.
Answer. The NIH has provided considerable support to Hawaii in an
effort to ensure that Native Hawaiian and other Pacific Islanders have
access to the clinical benefits of the NIH research. While research and
training investments represent the majority of the NIH support to
institutions in Hawaii, technical assistance to Hawaiian institutions
has also been important. Periodically over the past decade, the NIH
through the Office of Policy for Extramural Research Administration
(OPERA) has provided workshops in Hawaii on the topics of the NIH
policies, grant writing skills, and human subjects research issues
including adverse event reporting, vulnerabilities of pediatric
populations, and cultural issues involving Native Hawaiians
participating in research studies. Also, the Office of Laboratory
Animal Welfare (OLAW) presented several comprehensive overviews of the
laws, regulations, and policies that govern the humane care and use of
laboratory animals.
The breadth of the research enterprise in Hawaii is quite
impressive. In fiscal year 2010, more than 17 of the 27 NIH Institutes
and Centers have provided support for academic institutions to conduct
research activities ranging from basic biomedical science to behavioral
interventions. For example, Chaminade University has a National
Institute on Minority Health and Health Disparities (NIMHD) Building
Research Infrastructure and Capacity grant which supports renovations,
research training, student academic enrichment programs, and junior
faculty career development activities. The University of Hawaii Hilo
has received funding from the National Institute on Drug Abuse (NIDA)
for the mentoring of clinical investigators and to conduct patient-
oriented mental health services research, including post-traumatic
stress disorder. The National Institute on Alcohol Abuse and Alcoholism
(NIAAA) is supporting a project to develop research capabilities in the
area of substance use and indigenous youth populations (e.g., Native
Hawaiian) at Hawaii Pacific University.
The University of Hawaii Manoa plays a pivotal role since it has
the most robust research enterprise of all the Hawaiian institutions of
higher education. They have received over 70 NIH awards over the past
year. The NIMHD Center of Excellence, Partnerships for Cardiometabolic
Disparities in Native and Pacific Peoples, has a focus on
cardiometabolic health and eliminating health disparities among Native
Hawaiians and other Pacific Islanders including Filipinos, Samoans, and
Tongans. The Cancer Research Center of Hawaii is an NCI-designated
Clinical Cancer Center and is the only such institution in the State of
Hawaii. Moreover, the University of Hawaii Manoa Research Centers in
Minority Institutions (RCMI) Multidisciplinary and Translational
Research Infrastructure Expansion in Hawaii serves as the integrated
``home'' for clinical and translational science in the State of Hawaii.
In addition, Hawaiian small business concerns have received NIH support
for innovative ideas to improve health through the NIH Small Business
Innovative Research and Small Business Technology Transfer programs.
For example, Hawaii Biotech is taking the knowledge gained through its
dengue fever and West Nile virus vaccine programs and applying it to
tick-borne encephalitis. This project, Recombinant Subunit Vaccine for
Tick-Borne Encephalitis, addresses an important unmet biodefense need
within the United States since there is no registered tick-borne
encephalitis vaccine.
The NIH is pleased to be able to support biomedical research and
student training programs to help further the health of Native
Hawaiians and other Pacific Islanders. Recent discussions between the
NIH Deputy Director and several faculity at the University of Hawaii
Hilo may help identify additional gaps that could be filled through the
NIH-University partnerships.
Below is a list of all the NIH awards to Hawaiian institutions in
fiscal year 2010.
FISCAL YEAR 2010 HAWAII NIH AWARDS
----------------------------------------------------------------------------------------------------------------
Organization name Grant number Institute/center Project title
----------------------------------------------------------------------------------------------------------------
CARDAX PHARMACEUTICALS, INC...... 4R44AA018922-02..... NIAAA.............. Heptax for Alcoholic Liver Disease
CHAMINADE UNIVERSITY OF HONOLULU. 1P20MD006084-01..... NIMHD.............. Chaminade University BRIC Project
EAST-WEST CENTER................. 5R01HD042474-06..... NICHD.............. Innovations in Early Life Course
Transitions
HAWAII BIOTECH, INC.............. 5R44AI055225-04..... NIAID.............. Recombinant Subunit Vaccine For
Tick-Borne Encephalitis
HAWAII PACIFIC UNIVERSITY........ 3K01DA019884-04S1... NIDA............... Ecological Factors and Drug Use of
Native Hawaiian Youth
HAWAII PACIFIC UNIVERSITY........ 5K01DA019884-05..... NIDA............... Ecological Factors and Drug Use of
Native Hawaiian Youth
KUAKINI MEDICAL CENTER........... 5U01AG017155-10..... NIA................ Epidemiology of Aging and
Dementia--Autopsy Research
KUAKINI MEDICAL CENTER........... 5U01AG019349-09..... NIA................ Epidemiology of Brain Aging in the
Very Old
KUAKINI MEDICAL CENTER........... 3R01AG027060-04S1... NIA................ Defining the Healthy Aging
Phenotype
NEUROBEHAVIORAL RESEARCH, INC.... 5R01AA013659-08..... NIAAA.............. Brain Morbidity in Treatment--
Naive Alcoholics
NEUROBEHAVIORAL RESEARCH, INC.... 5R01AA016944-03..... NIAAA.............. Long-Term Abstinence Clinical
Issues and CNS Disinhibition
NEUROBEHAVIORAL RESEARCH, INC.... 5R01AA016303-04..... NIAAA.............. Effects of heavy alcohol abuse on
adolescent brain structure and
function
PACIFIC HEALTH RESEARCH INSTITUTE 5U10NS044448-08..... NINDS.............. Parkinson's Disease
Neuroprotection Trial: Hawaii
Center
PACIFIC HEALTH RESEARCH/EDUCATION 3U10NS044448-09S1... NINDS.............. Parkinson's Disease
INST. Neuroprotection Trial: Hawaii
Center
PACIFIC HEALTH RESEARCH/EDUCATION 3R01NS041265-10S1... NINDS.............. Risk Factors for Pathologic
INST. Markers of Parkinson Disease
PACIFIC HEALTH RESEARCH/EDUCATION 6U10NS044448-09..... NINDS.............. Parkinson's Disease
INST. Neuroprotection Trial: Hawaii
Center
PACIFIC HEALTH RESEARCH/EDUCATION 1R01DK089347-01..... NIDDK.............. Reducing Cost-Related Medication
INST. Nonadherence in Persons with
Diabetes
PANTHERA BIOPHARMA, LLC.......... 5U01AI078067-03..... NIAID.............. Antidotes to Anthrax Lethal Factor
Intoxication
PAPA OLA LOKAHI.................. 3U01CA114630-05S3... NCI................ IMI HALE NATIVE HAWAIIAN CANCER
NETWORK
PAPA OLA LOKAHI.................. 1U54CA153459-01..... NCI................ IMI HALE NATIVE HAWAIIAN CANCER
NETWORK
PAPA OLA LOKAHI.................. 3U01CA114630-05S4... NCI................ IMI HALE NATIVE HAWAIIAN CANCER
NETWORK
QUEEN'S MEDICAL CENTER........... 5R01GM063954-08..... NIGMS.............. Molecular and functional
properties of the TRPM2 catioin
channel
QUEEN'S MEDICAL CENTER........... 5R21CA139687-02..... NCI................ Treatment Effects on Tumor 18F-
Choline Metabolism in Advanced
Prostate Cancer
QUEEN'S MEDICAL CENTER........... 5R01GM080555-03..... NIGMS.............. Molecular components of the store-
operated CRAC channel
UNIVERSITY OF HAWAII AT HILO..... 5K24MH074468-05..... NIMHD.............. Mentoring/Career Development in
PTSD Services Research
UNIVERSITY OF HAWAII AT MANOA.... 2P20RR016467-09A1... NCRR............... INBRE II: Hawaii Statewide
Research & Education Partnership
(HSREP)
UNIVERSITY OF HAWAII AT MANOA.... 3R01NS063932-03S1... NINDS.............. HIV and Global Drug Therapies:
Peripheral Neuropathy
Complications and Mechanisms
UNIVERSITY OF HAWAII AT MANOA.... 5R01NS053345-05..... NINDS.............. HIV-1 Proviral DNA and Monocyte
Phenotype in Relation to
Neurocognitive Function
UNIVERSITY OF HAWAII AT MANOA.... 5U54NS056883-04..... NINDS.............. Imaging Studies in Neurotoxicity
and Neurodevelopment
UNIVERSITY OF HAWAII AT MANOA.... 5R01NS063932-03..... NINDS.............. HIV and Global Drug Therapies:
Peripheral Neuropathy
Complications and Mechanisms
UNIVERSITY OF HAWAII AT MANOA.... 5R01NS053359-04..... NINDS.............. HIV-1 Specific Immune Responses in
Thai Individuals with HIV
Dementia
UNIVERSITY OF HAWAII AT MANOA.... 5P20NR010671-04..... NINR............... Center for 'Ohana Self-Management
of Chronic Illnesses Hawaii
(COSMCI0): Building
UNIVERSITY OF HAWAII AT MANOA.... 5R01MH081845-02..... NIMH............... The Genetic Control of Social
Behavior in the Mouse
UNIVERSITY OF HAWAII AT MANOA.... 5R01MH079717-02..... NIMH............... Modeling monocyte and macrophage
based gene therapy for neuroAIDS
UNIVERSITY OF HAWAII AT MANOA.... 1R01EB011517-01..... NIBIB.............. Spectral Spatial RF Pulses for
Gradient Echo fMRI
UNIVERSITY OF HAWAII AT MANOA.... 5R24MD001660-06..... NIMHD.............. PILI 'Ohana Project: Partnerships
to Overcome Obesity Disparities
in Hawai'i
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA115614-04..... NCI................ Physical Activity in Women with
Infants
UNIVERSITY OF HAWAII AT MANOA.... 1U13HD063139-01..... NICHD.............. Community-Based Capacity Building:
Academic-Community Partnerships
Using Partici
UNIVERSITY OF HAWAII AT MANOA.... 5G11HD054969-04..... NICHD.............. Office of Research Development
(EARDA)
UNIVERSITY OF HAWAII AT MANOA.... 5F32HD055000-03..... NICHD.............. Origins of neuronal patterning in
animal development
UNIVERSITY OF HAWAII AT MANOA.... 2T34GM007684-29A1... NIGMS.............. Minority Access to Research
Careers
UNIVERSITY OF HAWAII AT MANOA.... 1R01GM093116-01..... NIGMS.............. Gene regulatory network evolution
and the origin of biological
novelties
UNIVERSITY OF HAWAII AT MANOA.... 1P41GM094091-01..... NIGMS.............. Accessing Cyanobacterial Chemical
Diversity: A Unique Natural
Product Library
UNIVERSITY OF HAWAII AT MANOA.... 5R01GM083158-03..... NIGMS.............. Transposon Based Mammalian
Transgenesis and Transfection
UNIVERSITY OF HAWAII AT MANOA.... 1R01GM088266-01A1... NIGMS.............. RSK-2 regulates integrin-mediated
adhesion and migration
UNIVERSITY OF HAWAII AT MANOA.... 1K01DK090091-01..... NIDDK.............. Neighborhood Characteristics and
Diabetes Incidence in the
Multiethnic Cohort Stu
UNIVERSITY OF HAWAII AT MANOA.... 5R25DK078386-04..... NIDDK.............. High School Students STEP-UP To
Biomedical Research
UNIVERSITY OF HAWAII AT MANOA.... 5R01DK079684-04..... NIDDK.............. Multimedia intervention to
motivate ethnic teens to be
designated donors
UNIVERSITY OF HAWAII AT MANOA.... 3U10CA063844-17S1... NCI................ Hawaii Minority-Based Clinical
Community Oncology Program
UNIVERSITY OF HAWAII AT MANOA.... 5P01CA114047-05..... NCI................ Pathogenesis of mesothelioma
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA058598-12..... NCI................ Collaborative Genetic Study of
Ovarian Cancer Risk
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA120799-04..... NCI................ Testing Alternative Stage Models
of Smoking Cessation: An
Intervention Study
UNIVERSITY OF HAWAII AT MANOA.... 5R37CA054281-18..... NCI................ Multiethnic Cohort Study of Diet
and Cancer
UNIVERSITY OF HAWAII AT MANOA.... 1R03CA150041-01..... NCI................ Urinary Estrogen Metabolites in a
2-year Soy Trial Among
Premenopausal Women
UNIVERSITY OF HAWAII AT MANOA.... 3U54CA143727-02S1... NCI................ University of Guam/Cancer Research
Center of Hawaii Partnership (1
of 2)
UNIVERSITY OF HAWAII AT MANOA.... 3P30CA071789-12S9... NCI................ Cancer Research Center of Hawaii
UNIVERSITY OF HAWAII AT MANOA.... 3P30CA071789-12S8... NCI................ Cancer Research Center of Hawaii
UNIVERSITY OF HAWAII AT MANOA.... 5U24CA074806-12..... NCI................ The Colon Cancer Family Registry:
Hawaii
UNIVERSITY OF HAWAII AT MANOA.... 1R01CA153154-01..... NCI................ Self-Control as a Moderator for
Effects of Mass Media on
Adolescent Substance Use
UNIVERSITY OF HAWAII AT MANOA.... 3U24CA074806-11S1... NCI................ The Colon Cancer Family Registry:
Hawaii
UNIVERSITY OF HAWAII AT MANOA.... 7R01CA124687-03..... NCI................ The Sphingolipid Pathway in Colon
Cancer Chemoprevention
UNIVERSITY OF HAWAII AT MANOA.... 2U10CA063844-17..... NCI................ Hawaii Minority-Based Clinical
Community Oncology Program
UNIVERSITY OF HAWAII AT MANOA.... 5R21AT004844-02..... NCCAM.............. Mechanisms by which selenium
influences T helper cells during
immune responses
UNIVERSITY OF HAWAII AT MANOA.... 5R21AT005139-02..... NCCAM.............. Exploratory Studies on the Anti-
Breast Cancer Function of Bamboo
Extract
UNIVERSITY OF HAWAII AT MANOA.... 7R01AI054128-06..... NIAID.............. Mechansim of activation of innate
immunity by ISS-DNA
UNIVERSITY OF HAWAII AT MANOA.... 5R01AI075057-03..... NIAID.............. Intraspecies Transmission and
Infectivity of Insectivore-Borne
Hantaviruses
UNIVERSITY OF HAWAII AT MANOA.... 5R01AI071160-04..... NIAID.............. Malarial Immunity in Pregnant
Cameroonian Women
UNIVERSITY OF HAWAII AT MANOA.... 1R01AI089999-01..... NIAID.............. Selenoprotein K modulates calcium-
dependent signaling in immune
cells
UNIVERSITY OF HAWAII AT MANOA.... 5R01AI074554-03..... NIAID.............. Global HIV Drug Therapies and
Mitochondrial Complications and
Mechanisms
UNIVERSITY OF HAWAII AT MANOA.... 5U01HG004802-03..... NHGRI.............. Epidemiology of Putative Causal
Variants in the Multiethnic
Cohort
UNIVERSITY OF HAWAII AT MANOA.... 5R01DA021146-04..... NIDA............... RGR-based motion tracking for real-
time adaptive MR imaging and
spectroscopy
UNIVERSITY OF HAWAII AT MANOA.... 5R01DA021856-04..... NIDA............... The Project Success Model:
Evaluation of a Tiered
Intervention
UNIVERSITY OF HAWAII AT MANOA.... 5K02DA020569-05..... NIDA............... Parallel MRI for Substance Abuse
Research
UNIVERSITY OF HAWAII AT MANOA.... 5K23DA020801-05..... NIDA............... Neurodevelopment of
Methamphetamine Exposed Children
UNIVERSITY OF HAWAII AT MANOA.... 5R01DA019912-04..... NIDA............... Parallel MRI for High Field
Neuroimaging
UNIVERSITY OF HAWAII AT MANOA.... 5K24DA016170-07..... NIDA............... Neuroimaging and Mentoring in Drug
Abuse Research
UNIVERSITY OF HAWAII AT MANOA.... 1R24DA027318-01..... NIDA............... Factors for enhanced neurotoxicity
in methamphetamine abuse in HIV
infection
UNIVERSITY OF HAWAII AT MANOA.... 5K01DA021203-04..... NIDA............... Impact of Marijuana Exposure on
Brain Maturation
UNIVERSITY OF HAWAII AT MANOA.... 3R25RR024281-03S1... NCRR............... Pacific Education and Research for
Leadership in Science (PEARLS)
UNIVERSITY OF HAWAII AT MANOA.... 5P20RR024206-03..... NCRR............... Institute for Biogenesis Research:
COBRE
UNIVERSITY OF HAWAII AT MANOA.... 5P20RR016453-09..... NCRR............... COBRE: Center for Cardiovascular
Research
UNIVERSITY OF HAWAII AT MANOA.... 5R25CA090956-08..... NCI................ Nutritional & Behavioral Cancer
Prevention in a Multiethnic
Population
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA126895-03..... NCI................ Whole Genome Scan for Modifier
Genes in Colorectal Cancer
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA129063-03..... NCI................ Inflammation and Innate Immunity
Genes and Colorectal Cancer Risk
UNIVERSITY OF HAWAII AT MANOA.... 5R03CA135699-02..... NCI................ A pooled analysis of mammographic
density and breast cancer risk
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA140636-02..... NCI................ Characterizing Mitochondrial DNA
Susceptibility to Breast,
Colorectal, and Prosta
UNIVERSITY OF HAWAII AT MANOA.... 5R01CA080843-09..... NCI................ Effects of Soy on Estrogens in
Breast Fluid and Urine
UNIVERSITY OF HAWAII AT MANOA.... 5U54CA143727-02..... NCI................ University of Guam/Cancer Research
Center of Hawaii Partnership (1
of 2)
UNIVERSITY OF HAWAII AT MANOA.... 5K23HL088981-03..... NHLBI.............. Cardiovascular autonomic function
in HIV virologic failure
UNIVERSITY OF HAWAII AT MANOA.... 5R01HL095135-03..... NHLBI.............. Role of Oxidative Stress and
Inflammation in HIV
Cardiovascular Risk
UNIVERSITY OF HAWAII AT MANOA.... 1R01HL098423-01A1... NHLBI.............. Role of mTOR in the diabetic heart
UNIVERSITY OF HAWAII AT MANOA.... 5UH1HL073449-07..... NHLBI.............. University of Hawaii Research
Scientist Award in Molecular
Cardiology
UNIVERSITY OF HAWAII AT MANOA.... 5R21HL087289-02..... NHLBI.............. Pseudoxanthoma elasticum: Elastic
fibers alterations and
characterization of seru
UNIVERSITY OF HAWAII AT MANOA.... 5R01HL081863-05..... NHLBI.............. Rho kinase in immune-mediated
atherosclerosis
UNIVERSITY OF HAWAII AT MANOA.... 5R01AI068525-05..... NIAID.............. Role of macrophages in HIV
Lipoatrophy
UNIVERSITY OF HAWAII AT MANOA.... 5G12RR003061-25..... NCRR............... Research Outcomes Accelerating
Discoveries for Medical
Applications and Practice
UNIVERSITY OF HAWAII AT MANOA.... 1R01HD060722-01A1... NICHD.............. Contribution of Sperm Nucleus to
Paternal DNA Replication
UNIVERSITY OF HAWAII AT MANOA.... 5R21AG032405-02..... NIA................ A Needle in a Haystack: New
approaches to Alzheimer's Drug
Discovery from Natural
UNIVERSITY OF HAWAII AT MANOA.... 2P20RR018727-06A1... NCRR............... Pacific Center for Emerging
Infectious Diseases Research
UNIVERSITY OF HAWAII AT MANOA.... 5P20MD000173-09..... NIMHD.............. Partnerships for Cardiometabolic
Disparities in Native and Pacific
Peoples
UNIVERSITY OF HAWAII AT MANOA.... 5R01GM057873-11..... NIGMS.............. Cyclopentannelation in Total
Synthesis
UNIVERSITY OF HAWAII AT MANOA.... 1U54RR026136-01A1... NCRR............... RCMI Multidisciplinary And
Translational Research
Infrastructure EXpansion Hawaii
UNIVERSITY OF HAWAII AT MANOA.... 5R25RR024281-03..... NCRR............... Pacific Education and Research for
Leadership in Science (PEARLS)
----------------------------------------------------------------------------------------------------------------
THE NATIONAL INSTITUTE OF NURSING RESEARCH (NINR) SUPPORT FOR END-OF-
LIFE CARE AND HEALTH DISPARITIES RESEARCH
Question. The NINR will soon be celebrating its 25th anniversary.
The late Senator Quentin Burdick and I were active in establishing the
original Center and I am confident he would share my enthusiasm for how
nicely it has matured over the years. At this time I would appreciate
an update on the extent to which the NINR has been able to co-fund
various initiatives with other NIH Institutes, particularly in the
areas of end-of-life issues and racial and geographical disparities.
Answer. Improving palliative and end-of-life care and eliminating
health disparities are critical components of the NINR's research
mission. Consistent with this mission, as well as the Institute's
longstanding practice of extensive collaboration with other NIH ICs,
the NINR co-funds numerous scientific efforts with other ICs focused on
these two important topics.
As the lead NIH Institute on issues related to end-of-life care
research, the NINR, with support from partners across the NIH, will
convene a forum on August 10-12, 2011, entitled ``The Science of
Compassion: Future Directions in End-of-Life and Palliative Care.'' A
part of the NINR's 25th Anniversary commemoration, this forum is
intended to energize and mobilize palliative and end-of-life care
research and to draw attention to palliative and end-of-life care
processes, options available to patients and their families, and the
healthcare community's obligation to address these complex needs. This
event is co-sponsored by the following NIH partners: National Institute
on Aging (NIA), Office of Rare Diseases Research, Office of Research on
Women's Health, National Center for Complementary and Alternative
Medicine, and the NIH Clinical Center Department of Bioethics.
In addition, the NINR and the NIH Common Fund recently awarded $7.1
million in funding provided by the American Recovery and Reinvestment
Act to support a Palliative Care Research Cooperative (PCRC), a multi-
institution effort to conduct collaborative research on palliative and
end-of-life care. The PCRC will bring together experienced,
multidisciplinary investigators to facilitate innovative, high-impact,
clinically useful palliative care research to inform practice and
health policy. The PCRC will address challenges associated with
conducting research with individuals with life-limiting conditions, and
could lead to significant improvements in the evidence base for
palliative and end-of-life care.
NINR also collaborates with other ICs to support basic, clinical,
and translational research to address health disparities across the
life span. The NINR currently co-funds an initiative focused on
reducing health disparities in minority and underserved children,
including children from: racial/ethnic minority groups; rural and low-
income populations; and geographically isolated locations. The NINR,
and other Institutes, have supported various important projects under
this initiative. For example, the NINR-supported investigators are
testing interventions to improve the well-being of African American,
Hispanic, and White families where grandmothers are raising
grandchildren. These custodial grand-families are at high risk for
psychological difficulties and limited access to needed services. This
initiative is co-funded with the following NIH Institutes: National
Institute of Child Health and Human Development; National Heart, Lung,
and Blood Institute; National Institute on Alcohol Abuse and
Alcoholism; and the National Institute on Deafness and Other
Communication Disorders.
Additionally, researchers funded by the NINR and the NIA developed
the Resources for Enhancing Alzheimer's Caregivers Health (REACH) II
program which teaches caregivers about Alzheimer's disease, managing
stress, and maintaining their own health. In a large sample of African
American and White caregivers for Alzheimer's patients, those in the
REACH II intervention reported better physical, emotional, and overall
health and had lower scores for depression which contributed to
reducing caregiving burden. To address the need for support of
caregivers, particularly in racially/ethnically diverse families,
multiple efforts across the Federal Government are currently underway
to implement REACH in the community.
HEALTH MESSAGES FOR THE NATIVE HAWAIIAN POPULATION
Question. According to the fiscal year 2012 NIH CJ, the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
``supports a robust information dissemination and outreach program to
distribute research-based information to the public, patients, and
their healthcare providers.'' The NIAMS supported National
Multicultural Outreach Initiative ``is creating a sustainable network
of partners to assist in the development and dissemination of health
messages and materials for racial and ethnic minority populations.''
The Initiative will focus its efforts on reaching many different
minority/ethnic populations including Native Hawaiians. ``Working with
existing NIAMS partners, the Institute will develop research-based
self-care messages and products, and ensure their distribution through
trusted health and multicultural community channels. The NIAMS
implemented critical phases of the Initiative in fiscal year 2011,
namely, the development and pretesting of culturally and linguistically
appropriate health messages and materials through audience research.''
The NIAMS and its National Multicultural Outreach Initiative are
supporting the development of health messages for racial and ethnic
minority populations. What types of health messages are being developed
and tested for the Native Hawaiian population?
Answer. In fiscal year 2011, the NIAMS completed qualitative
research with members of multicultural communities, including Native
Hawaiians, to help inform the development of culturally appropriate and
useful health education products for adults with medical conditions
affecting the bones, joints, muscles, and skin. The NIAMS conducted a
total of 18 focus groups (2 with Native Hawaiians), and 20 in-depth
interviews (2 with Native Hawaiians) to gather feedback from
individuals on preferences for different message concepts and formats
for communicating health messages. The information gleaned from this
audience research will enable the development of tailored products that
raise awareness about the availability of reliable, research-based
health information and resources from the NIAMS and partner
organizations to help patients and their families manage their
conditions.
The NIAMS National Multicultural Outreach Initiative relies on the
guidance and input from its working groups for the development and
dissemination of health messages and products. These groups are
comprised of national experts from multicultural communities, and
include representation from the Native Hawaiian community.
THE NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES
(NIMHD) CENTERS OF EXCELLENCE (COE) IN HAWAII
Question. The fiscal year 2012 congressional justification states
that the NIMHD has supported 91 COE sites in 35 States, the District of
Columbia, Puerto Rico, and the U.S. Virgin Islands. According to the
CJ, the ``types of institutions are diverse and include Historically
Black Colleges and Universities, Hispanic-Serving Institutions, Tribal
Colleges and Universities, Alaskan Native, and Native Hawaiian Serving
Institutions.'' In fiscal year 2010, the 51 active COEs conducted
transdisciplinary research on high priority diseases/conditions
including ``cardiovascular disease, stroke, cancer, diabetes, HIV/AIDS,
infant mortality, mental health, and obesity that disproportionately
affect racial/ethnic minority and other health disparity populations.''
Is the NIMHD currently supporting a COE at a Native Hawaiian
Serving Institution? What high priority diseases or conditions are the
focus of research at a COE in a Native Hawaiian Serving Institution?
Answer. The NIMHD COE represent a scientific platform for
innovative research projects, research training, and effective
community engagement to address the health status of health disparity
populations. The NIMHD has provided funding for a COE at the University
of Hawaii Manoa since September 2002. This COE, Partnerships for
Cardiometabolic Disparities in Native and Pacific Peoples, is a
regional focal point for improving cardiometabolic health and
eliminating health disparities among Native Hawaiians and other Pacific
Islanders, including Filipinos, Samoans, and Tongans.
The primary focus of the COE is obesity and diabetes which are
known risk factors for cardiovascular disease. Eighty-two percent of
Native Hawaiians are overweight or obese, which is considerably higher
than the national average of 53 percent. Pacific Islander women with
diabetes have a higher risk of myocardial infarction. Through dedicated
efforts over the years, Partnerships for Cardiometabolic Disparities in
Native and Pacific Peoples has made significant contributions to the
improvements in the health of Native Hawaiians and other Pacific
Islanders.
In addition, supplemental funding was provided in July 2010 to
support the establishment of the Comparative Effectiveness Research
Approaches to Eliminate Cardiometabolic Disparities initiative as part
of the COE. The intent of the project is to train researchers in
comparative effectiveness research, to conduct innovative research, to
establish diabetes and cardiometabolic disease registries, and to
disseminate research results to communities with health disparities in
Hawaii.
HEREDITARY ANGIODEMA RESEARCH SUPPORT
Question. Dr. Collins, I would like to thank you for your
leadership of the National Institutes of Health, including its
continuing emphasis on rare diseases. As you are aware, the NIH
provides critical opportunities for research surrounding orphan
conditions which otherwise may not have an opportunity for significant
research. Recently, constituents and members of the U.S. Hereditary
Angioedema Association (USHAEA), based in Honolulu, brought to my
attention the absence of Federal support since 2009 for hereditary
angioedema (HAE) research. I would appreciate receiving a report on why
funding for this disease was eliminated and what your efforts are
toward reinvigorating hereditary angioedema research support.
Answer. HAE is a rare genetic disorder. HAE patients suffer from
swelling of the hands, feet, abdomen, face and/or throat. Especially
the latter is a major medical emergency that may be fatal. Estimates
for the prevalence of HAE range from 1 in 10,000 to 1 in 50,000 people
in the United States.
In 2009, a number of research projects focusing on hereditary
angioedema came to a natural end. For example, the most extensive
project, sponsored by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, C1 Inhibitor Gene and Hereditary
Angioneurotic Edema, was last funded in 2008 after 23 years of research
and concluded in 2010. The Principal Investigator did not apply for
renewed funding for this project.
The National Center of Research Resources (NCRR) funded Mount Sinai
General Clinical Research Center project: CHANGE Trial (C1-Inhibitor in
Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy):
Open-Label Safety/Efficacy Repeat Exposure Study of C1 Esterase
Inhibitor (Human) in the Treatment of Acute Hereditary Angioedema (HAE)
Attacks participant visits ended in March 2009 and closed in September
2009. The results were published in the NEJM in August 2010 (PMID
20818886). Currently, the NCRR-funded Mount Sinai Clinical and
Translational Science Award supports the Phase III Randomized Double
Blind, Placebo controlled Multicenter Study of Icatibant for
Subcutaneous Injection in Patients with Acute Attacks of Hereditary
Angioedema.
The NCRR General Clinical Research Center at the University of
Texas Medical Branch at Galveston (UTMB) conducted the Randomized,
Placebo-Controlled, Double-blind Phase II Study of the Safety and
Efficacy of Recombinant Human C1 Inhibitor for the Treatments of Acute
Attacks in Patients with Hereditary Angioedema. The study ended in May
2009.
The NCRR-funded University of Texas Medical Branch at Galveston
(UTMB) Clinical and Translational Science Award represents an
additional site which conducted the Phase III Randomized Double-Blind,
Placebo-Controlled Multicenter Study of Icatibant for Subcutaneous
Injection in Patients with Acute Attacks of Hereditary Angioedema
(HAE). This study was completed in May 2011.
Currently, we also are supporting three training grants with
projects investigating HAE, two from National Institute of Allergies
and Infectious Diseases and one from the National Heart, Lung, and
Blood Institute. These training grants are critical since they train
the next generation of investigators. The trainees are expected to
continue their careers with a research emphasis on HAE. The NIH would
welcome the opportunity to support meritorious research studies
focusing on hereditary angioedema (HAE).
To stimulate future research activities and applications we would
encourage investigators and advocates of HAE research to submit an
application for a scientific conference grant. In addition to helping
to identify research opportunities and needs and develop a research
agenda and research priorities for HAE, such a conference could create
significant research interest in this particular rare disease. The
Office of Rare Diseases Research (ORDR), collaborating with other NIH
research institutes, would be pleased to confer with the U.S.
Hereditary Angioedema Association (U.S. HAEA) and interested research
investigators about your concerns.
CANCER PREVELANCE AND RESEARCH IN HAWAII
Question. Over the years the NCI has systematically invested in
research activities targeting the unfortunately high incidence of
cancer among my State's Native Hawaiian population. At one point the
NCI researchers reported that Native Hawaiian women had the highest
incidence of breast cancer in the world. I am confident that progress
has been made and would appreciate a report describing the NCI's future
plans for targeting the special needs of these indigenous people.
Answer. The NCI funds research that focuses on Native Hawaiian,
other Pacific Islander, and Asian American populations. These studies
are supported to illuminate the causes of cancer in these populations;
to improve screening rates so that when cancer appears, it can be
treated at an early stage; to increase knowledge about treatment
options so that patients and their physicians can make more informed
choices about their care; to fund registries, surveys, and reports that
generate the latest statistics and inform researchers, policy makers,
and the public; to support cohorts that provide a population base from
which to conduct important future research, and ultimately to prevent
cancers in these populations.
Current Efforts
The NCI's Prostate, Lung, Colorectal, and Ovarian Cancer Screening
Trial (PLCO) and National Lung Screening Trial (NLST) studies, with
more than 200,000 participants, include programs in Hawaii and from
diverse ethnic populations. At the Pacific Health Research and
Education Institute in Honolulu, of the 13,200 study participants in
Hawaii, approximately half were Asians (5,553) and Native Hawaiians and
other Pacific Islanders (1,053).
In the area of clinical trial recruitment of minorities, the
University of Hawaii Minority-Based Community Clinical Oncology Program
(MB-CCOP), funded since 1994, provides access to the NCI clinical
trials in cancer prevention, treatment, and control to both children
and adults.
The NCI Community Network Program (CNP) Centers address disparities
at the community level with outreach, research, and training. Two CNPs
are oriented to Pacific Islanders (Imi Hale and Weaving an Islander
Network for Cancer Awareness, Research and Training, or WINCART) and
two other CNPs are focused on underserved Asians (Asian American
Network for Cancer Awareness, Research, and Training, or AANCART, and
the Asian Community Cancer Health Disparities Center, or ACCHD).
National Outreach Program (NOP) supported by the Imi Hale Native
Hawaiian Cancer Network is designed to reduce cancer incidence and
mortality among Native Hawaiians by maintaining and expanding an
infrastructure that:
--Promotes cancer awareness within Native Hawaiian communities;
--Provides education and training to develop Native Hawaiian
researchers; and
--Facilitates research that aims to reduce cancer health disparities
experienced by Native Hawaiians.
The Imi Hale Native Hawaiian Cancer Network made progress toward
reducing cancer incidence and mortality among Native Hawaiians through
a project, ``Woman to Woman-Micronesians United Lay Educator Program''
for Native Hawaiians focused on increasing breast and cervical cancer
screening. Six months of outreach activities resulted in screening of
150 women. CNP-Southern California developed culturally tailored
educational resources specifically for Native Hawaiians and the
Marshallese, in colorectal cancer screening, which resulted in a
library of culturally relevant resources. In addition to these primary
efforts, the CNP Native Hawaiian trainees have submitted 40 grant
applications and a total of 12 were ranked high enough for funding.
Imi Hale has a dedicated Community Health Educator, who seeks to
bridge the gap between the community and the research community by
developing culturally tailored cancer information. For instance, to
help women learn to do self-breast exams to detect lumps early, Imi
published Breast Health Shower Cards in nine languages. In terms of
breast cancer education, Imi Hale has produced a DVD entitled ``A
Journey of Hope: When a Young Woman Gets Cancer.'' Seeking creative
ways to educate women about breast cancer, Imi Hale created a breast
cancer computer game (http://imihale.org/game/click_to_start.html). In
addition, a series of brochures for Native Hawaiian breast cancer
survivors called ``Talking Story Booklets'' has been developed. The
outreach component works closely with such partners as the five Native
Hawaiian healthcare Systems positioned on five islands.
--Imi Hale Clinical partners include: Community Health Centers
serving Native Hawaiian clients, the Queen`s Cancer Center and
other hospitals, and the State-contracted Breast and Cervical
Cancer Control Programs; and
--Imi Hale Community partners include: Association of Hawaiian Civic
Clubs, Hawaii State Tobacco Coalition, Office of Hawaiian
Affairs, and other community agencies.
A Comprehensive Partnership to Reduce Cancer Health Disparities
Program between the University of Hawaii Cancer Center (UHCC) and the
University of Guam (UOG) have an NCI-funded partnership with the aim of
enhancing the awareness of cancer and cancer prevention and ultimately
reducing the impact of cancer on the population in Hawaii, the
Territory of Guam and the other U.S.-associated Pacific Island
territories. The partnership supports projects designed to develop
culturally appropriate guidelines for tobacco use prevention and
cessation in youth with the underlying hypothesis that interventions to
prevent tobacco use are more likely to succeed if they conform to
culturally relevant guidelines developed with the active participation
of the target youth themselves. The long-term goal of the community-
based participatory outreach program is to engage the community as
equal partners in tobacco control and cancer prevention research. The
partnership also supports investigator-initiated cancer research
projects that address different aspects of cancers in Hawaii and Guam
including the development of protocols for studying oral precancerous
lesions and other health risks among betel nut users in Hawaii, the
Territory of Guam and the other U.S.-associated Pacific Island
territories.
The NCI Community Cancer Centers Program (NCCCP) is designed to
create a community-based cancer center network to support basic,
clinical and population-based research initiatives, addressing the full
cancer care continuum--from prevention, screening, diagnosis,
treatment, and survivorship through end-of-life care. The NCCCP pilot
has added the Queen's Medical Center, Honolulu, Hawaii (The Queen's
Cancer Center) to its 30 hospital network.
Future Research
The NCI will be launching a program to foster evidence-based
research, data collection, and analysis within Asian American and
Pacific Islander (AAPI) populations and subpopulations through a unique
collaboration with the University of Guam, the University of Hawaii,
the Pacific Regional Central Cancer Registry, and the Pacific Island
Cancer Council. The NCI developed the Health Information National
Trends Survey (HINTS) to monitor changes in the rapidly evolving field
of health communication by collecting data across the Nation. The
HINTS-Guam program will pilot test a localized survey instrument geared
specifically to AAPI populations and subpopulations, including
Chamorros and other Pacific Islanders living on Guam. Data collected
from this survey will increase understanding of cancer information
seeking, experiences, and behaviors (prevention, screening, treatment,
etc.) among AAPI populations. Discussions have also begun on a HINTS
pilot project to be conducted in Hawaii.
KIDNEY DISEASE AND DIABETES RESEARCH IN HAWAII
Question. It has recently come to my attention that my State's
Filipino population has an extraordinarily high incidence of kidney
disease. Similarly, several ethnic groups in Hawaii (including Native
Hawaiians) have been found to have high incidences of diabetes.
Accordingly, I would appreciate receiving a report on your efforts to
develop initiatives targeting these populations, and particularly those
which would stress prevention and perhaps diet.
Answer. Data show that Filipinos in Hawaii seem to have a
disproportionate burden of kidney disease. The NIDDK is naturally very
concerned about kidney disease in Hawaiians, including the health
disparity in the Filipino population, and has several initiatives in
place to address the problem. First, our National Kidney Disease
Education Program (NKDEP) provides materials that can be used in
Hawaii's high risk populations. The NKDEP's materials aim to raise
awareness of the seriousness of kidney disease, the importance of
testing those at high risk (those with diabetes, high blood pressure,
or a family history of kidney failure), and the availability of
treatment to prevent or slow kidney failure. NKDEP's extensive new
offerings on dietary intervention in chronic kidney disease for
providers and patients would be particularly useful.
The National Diabetes Education Program (NDEP) is sponsored by the
NIDDK and Centers for Disease Control and Prevention (CDC) and includes
more than 200 partners working together to improve the treatment and
outcomes for people with diabetes, promote early diagnosis, and prevent
or delay the onset of type 2 diabetes, a leading cause of kidney
disease. The NDEP has a major focus on Asian Pacific Islanders; it has
translated educational materials into Tagalog, one of the languages
spoken in the Fillipino population. These materials address both
prevention of diabetes and prevention of complications such as kidney
disease. The University of Hawaii is a site for the Diabetes Prevention
Program Outcomes Study, which recently reported data showing durability
of effect of lifestyle intervention and the drug metformin at
preventing or delaying onset of type 2 diabetes at 10 years follow-up.
People whose disease progresses to kidney failure can be treated
with a kidney transplant, though limitations on available donor organs
is a chronic problem. The NIDDK's ``Minority Organ Donation Program''
initiative supports an investigator at the University of Hawaii, Dr.
Cheryl Albright, whose research focuses on educating Filipino high
school students about signing up (on drivers' licenses) to donate
organs. Students from Honolulu and other smaller Islands (including
rural areas) are participants. The grant is in the fourth year and
results are quite encouraging. The Filipino community is very
interested in kidney transplants, and participated in the original
National Minority Organ and Tissue Transplant Education Program (http:/
/mottep.org/) to rally the community around kidney donation from
relatives and friends.
In another initiative, the NIDDK, in collaboration with the CDC and
the Indian Health Service, has funded eight Tribal Colleges and
Universities in the initiative ``Diabetes Education in Tribal
Schools.'' This effort developed supplemental curricula, to be used in
K-12 schools in American Indian and Alaska Native communities, about
prevention and better management of diabetes, the most common cause of
kidney failure. Although the cultural content is directed primarily
toward American Indians, some Hawaiian schools participated in piloting
the curricula. The project is completed and the curricula are being
fielded in tribal schools. Also, the curricula were distributed to and
currently are being used in Hawaiian schools, primarily on the Big
Island of Hawaii.
STROKE DISPARITIES IN THE UNITED STATES
Question. I am concerned that stroke apparently remains the number
two killer in the United States and a major cause of disability. In
addition, stroke affects some segments and regions of our population
more than others. I understand that the State of Hawaii ranks 20 out of
52 highest in our Nation for age-adjusted stroke deaths. Death rates
from a certain type of stroke (intracerebral hemorrhage) are higher
among Asians/Pacific Islanders than among Whites. More than 20 percent
of Native Hawaiians or other Pacific Islanders have high blood
pressure, a leading risk factor for stroke. Yet, the NIH invests only 1
percent of its budget on stroke research. What is your Institute doing
to address the disparities that exist in stroke burden among different
cultural and racial populations in the United States?
Answer. Stroke research at the NIH is comprehensive and includes
research on basic disease mechanisms; epidemiology studies to assess
stroke risk, occurrence and outcomes in the population; clinical
research to develop effective prevention and acute treatment
approaches; and development of strategies for improving recovery and
rehabilitation in stroke patients. Clinical research in stroke is
particularly a high priority at the National Institute of Neurological
Disorders and Stroke (NINDS)--approximately 50 percent of its large
Phase III trials are on stroke.
The NINDS also supports major research initiatives aimed at better
defining stroke risk, incidence and outcomes in the United States and
among different subpopulations. Collections of population-based data
help identify and explain health disparities in stroke, and inform the
development of preventive interventions that target high risk
populations.
--In the Reasons for Geographic and Racial Differences in Stroke
(REGARDS) study, investigators are exploring the geographical
and racial influences on stroke risk in a cohort of about
30,000 individuals, about half of whom live in the ``stroke
belt'' region of the Southeastern United States. This large
study has produced over 70 publications that have led to a
better understanding of disparities in stroke in the United
States. Data generated from this study continue to help
researchers pinpoint why the stroke rate is higher in this
region, and among African Americans, and to develop targeted
strategies for intervention. Recent data from REGARDS indicated
that overall time spent in the stroke belt is more predictive
of hypertension--a powerful risk factor for stroke--than is
current residence in the stroke belt. Data from the REGARDS
study have also revealed that stroke survivors were more likely
to have unrecognized hypertension and diabetes.
--The Stroke Disparities Program is a multi-component program to
address major stroke challenges in the African American
community. The three projects in this program include:
--an intervention strategy to increase stroke knowledge and reduce
the time from symptom onset to hospital arrival (ASPIRE);
--an intervention utilizing navigators for secondary stroke
prevention that targets adherence to poststroke care
(PROTECT DC); and
--an observational imaging study to better understand racial and
ethnic differences in risk, occurrence and outcomes of
small brain hemorrhages (DECIPHER).
--The NOrthern MAnhattan Study (NOMAS) investigators have been
following a cohort of stroke-free adults, including whites,
African Americans and Caribbean Hispanics in a Northern
Manhattan community. Researchers are collecting imaging,
biological and neuropsychological data to evaluate the
relationship between biological and imaging predictors for
stroke, heart attack and death, as well as cognitive decline.
Using these markers in combination with other factors such as
diet, alcohol use, smoking, and history of peripheral vessel
disease, investigators are developing risk factor and cognitive
ability assessment tools. Genetic studies involving this and
other cohorts, have suggested that there may be genetic
susceptibilities underlying left atrium size and
atherosclerosis of the carotid arteries that contribute to
stroke.
--BASIC (Brain Attack Surveillance in Corpus Christi) investigators
are comparing trends in recurrent stroke, as well as functional
and cognitive outcomes following stroke, in 5,000 non-Hispanic
whites and Mexican Americans in Corpus Christi, Texas. Data
from this study have shown that Mexican Americans with atrial
fibrillation are more likely to have recurrent strokes than
whites, and the strokes are more likely to be severe. The
investigators are also exploring associations between
biological and social stroke risk factors, and recently found,
for example, that the density of fast food restaurants was
associated with neighborhood stroke risk.
--Ethnic and Racial variation in Intracerebral Hemorrhage (ERICH), a
study that was initiated in 2010, will identify differences in
intracerebral hemorrhage (ICH) risk factor distribution and
outcomes by race and ethnicity. This project will compare 3,000
cases of ICH, among African Americans, Hispanics and non-
Hispanic whites, to 3,000 demographically matched controls in
order to identify differences in risk factor distribution and
ICH outcome by race, ethnicity and location of ICH and to
determine differences in imaging characteristics among African
Americans and Hispanics compared to whites. The investigators
will also collect DNA in order to combine with other cohorts to
perform a genome-wide association study (GWAS) to identify
genes that affect risk of ICH in whites, African Americans and
Hispanics.
--The Alaska Native Stroke Registry (ANSR) is a population-based
surveillance study on the epidemiology of stroke in Alaska
Natives. Comprehensive assessment of the stroke epidemiology,
vascular risk factors, cultural understandings of vascular
health and lifestyle, and structural barriers to risk reduction
strategies has informed the development of a community level
prevention intervention pilot program that aims to reduce the
burden of stroke in the Alaska Native population.
______
Questions Submitted by Senator Herb Kohl
COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS
Question. The National Institutes of Health (NIH) recently released
results of the Comparison of Age-Related Macular Degeneration
Treatments Trials (CATT), which found that Lucentis and off-label
Avastin are similarly efficacious at treating neovascular age-related
macular degeneration (wet AMD). Now that the CATT study is released,
what is the NIH going to do with the results? The taxpayers spent
millions of dollars on the CATT study to determine the comparative
effectiveness of the drugs. I believe the trial results ought to be
actionable.
Answer. The National Eye Institute (NEI) recognizes its
responsibility to fund and conduct scientifically valid clinical
research and to disseminate the study results to the professional
clinical community and the public.
We collaborate extensively with ophthalmic organizations to apprise
their members of CATT results. In particular, outreach to professional
groups was the most effective and efficient means of reaching the
clinical ophthalmic community regarding CATT findings. For example, the
American Academy of Ophthalmology (AAO) has 30,000 member
ophthalmologists who are the primary eye care professionals that treat
wet AMD. The NEI worked with AAO to disseminate CATT results through
the AAO's Website, newsletters, press releases, and its upcoming annual
meeting. Additionally, the AAO Executive Director has written
extensively to the membership in support of CATT. We will continue to
work with AAO as they develop ``preferred practice plans'' for the
treatment of wet AMD. The Association for Research in Vision and
Ophthalmology (ARVO) is a 12,500 member eye research organization
comprised of clinicians and investigators. CATT investigators presented
their results at ARVO's annual meeting in May 2011. These two
organizations will continue to provide information and guidance to
their members about CATT so that the results can inform clinical care
decisions.
The NEI is also working to inform the public about the CATT
findings. The release of the study was accompanied by an extensive
media outreach campaign. For example, the NEI hosted a news briefing
for journalists where the NEI Director and CATT investigators presented
study findings and fielded questions from more than 60 media outlets.
Supplemental background video footage was made available to broadcast
outlets. A press release was also distributed widely to media outlets.
The NEI generated robust media coverage for CATT, coverage that has
been intense and more widespread than for other recent studies (see
accompanying table), despite media competition from the royal wedding
and the death of Osama Bin Laden. As follow-up to the initial media
coverage, the NEI distributed CATT results to members of the National
Eye Health Education Program (NEHEP), a partnership of 60 public and
private organizations dedicated to eye health education. This program
provides the NEI with direct access to community-based public health
education efforts, and we are preparing an NEI webpage devoted to CATT
along with a brochure including public health information about CATT.
Of note, the May publication of CATT reported on first year
results. The second year results will be published in the spring of
2012. At that time, the NEI will repeat its efforts with professional
organizations and the media to disseminate CATT results.
NEI CLINICAL TRIAL MEDIA COVERAGE
----------------------------------------------------------------------------------------------------------------
Number of Pick-up of
Study name Impressions original news original news
(millions) \1\ stories stories \2\
----------------------------------------------------------------------------------------------------------------
CATT.--Comparison of AMD Treatment Trials (2011)................ 296 157 234
ETROP.--Early Treatment for Retinopathy of Prematurity Study 257 20 138
(2010).........................................................
DRCR-DME.--Ranibizumab plus laser therapy for diabetic macular 232 42 29
edema (2010)...................................................
ACCORD.--Action to Control Cardiovascular Risk in Diabetes Eye 8 9 ( \3\ )
Study (2010)...................................................
GWAS-AMD.--Genome-wide association study genes associated with 16 13 6
AMD (2010).....................................................
LALES.--Los Angeles Latino Eye Study (2010)..................... 3 7 ( \3\ )
Myopia.--Increased pevalence of myopia in United States (2009).. 158 76 ( \3\ )
SCORE.--Standard Care vs. Corticosteroid for Retinal Vein 150 27 79
Occlusion (2009)...............................................
LCA.--Leber Congenital Amaurosis (2009)......................... 155 32 37
CITT.--Convergence Insufficiency Treatment Trial (2008)......... 44 117 183
CDS.--Cornea Donor Study (2008)................................. 63 118 74
AREDS2.--Age Related Eye Disease Study 2 (2006)................. 17 92 ( \3\ )
----------------------------------------------------------------------------------------------------------------
\1\ Impressions.--Number of people exposed to the news story in print, online, or on television based on
expected readership or viewers.
\2\ Pick-up.--When an original story is reprinted in another outlet (i.e., an Associated Press article is
printed in The Washington Post), it is counted as a pick-up.
\3\ Not applicable.
Question. How does the NIH share this information with other
agencies within the Federal Government?
Answer. In the preparation for the release of CATT, the NEI held a
teleconference with relevant Department of Health and Human Services
(HHS) agencies (FDA, CMS, CDC, and AHRQ) to inform them of CATT results
and to coordinate the HHS response to media. In accordance with
standard HHS and NIH operating procedures, the NEI distributed a draft
press release for clearance within DHHS and responded to various issues
prior to approval for release. This effort helped ensure a coordinated
HHS response to CATT. Since this initial interaction, both the NEI
staff and CATT leadership have been contacted by CMS staff to discuss
the implications of the CATT study results.
Question. Has the NIH's National Eye Institute considered what
effect, if any, the CATT study might have on future physician
prescribing behavior regarding Lucentis vs. off-label Avastin to treat
wet AMD?
Answer. Avastin, which inhibits the formation of new blood vessels,
was approved by the FDA in 2004 for the treatment of colon cancer.
Avastin is effective as an anti-cancer agent because inhibiting the
blood supply to tumors inhibits their growth. Since wet AMD is due to
leakage from new, abnormal blood vessels, ophthalmologists began trying
Avastin off-label to treat this form of AMD in 2006 on the basis of
both the cancer data and clinical trial results for Lucentis during the
FDA approval process. At that time, Avastin off-label was the only
available treatment for wet AMD that led to improvement in vision.
The vast majority of patients treated for wet AMD participate in
Medicare. After Lucentis was FDA-approved in 2007, most
ophthalmologists continued to use Avastin because the cost was
significantly lower than for Lucentis and because a number of reported
cases demonstrated Avastin efficacy that appeared similar to that
reported in the Lucentis clinical trials. Last May, Dr. Ross Brechner
and colleagues (Centers for Medicare and Medicaid Services) and Dr.
Phillip Rosenfeld (Bascom Palmer Eye Institute, University of Miami)
published an analysis of Medicare claims for wet AMD during 2008.\1\
They found that 64.4 percent of patients received Avastin and 35.6
percent received Lucentis and concluded that despite its off-label
designation, intravitreal Avastin is currently standard-of-care
treatment for wet AMD. Medicare payments totaled $536.6 million for
Lucentis and $20.3 million for Avastin.
---------------------------------------------------------------------------
\1\ Brechner, R. J, P. J. Rosenfeld, J. D. Babish, and S. Caplan.
Pharmacotherapy for Neovascular Age-Related Macular Degeneration: An
Analysis of the 100 percent Medicare Fee-For-Service Part B Claims
File. American Journal Ophthalmology 151:887-895, 2011.
---------------------------------------------------------------------------
CATT was a very tightly controlled, well-designed study, which
compared the two drugs in more than 1,100 patients. The exceptionally
wide dissemination of CATT results means that the retinal specialists
who treat AMD and the patients they care for are undoubtedly well aware
of the equivalence. As such, an increase in the number of patients
receiving Avastin as first line therapy is to be expected. Careful
monitoring of use of the drugs by CMS is expected.
Importantly, some patients with wet AMD respond better to Avastin,
while others to Lucentis. In practice, if one is ineffective, the other
may be tried. The fact that more than one drug is available is
beneficial and allows ophthalmologists and patients treatment choices.
______
Questions Submitted by Senator Mary L. Landrieu
INTERIM STATUS OF IDEA PROGRAM
Question. Scientists have expressed their concern about programs
that have been placed before under ``interim'' status and tend to lose
direction and in some cases have disappeared. I am particularly
concerned about the Institutional Development Award (IDeA) Program,
which is so important to Louisiana. What is the reason for placing a
program that serves 23 States and Puerto Rico on an interim status?
Answer. The IDeA Program has not been placed in an interim status.
Under the proposed creation of the National Center for Advancing
Translational Sciences (NCATS), we considered moving the program to a
new unit called the Office of Research Infrastructure Programs within
the Office of the Director, Division of Program Coordination, Planning,
and Strategic Initiatives. However, following extensive consultation
and feedback from multiple stakeholders, including grantees,
professional organizations, and the public, we concluded that the IDeA
program is most closely aligned scientifically and programmatically
with the mission and goals of the National Institute of General Medical
Sciences (NIGMS). Therefore, the National Institutes of Health (NIH)
intends on moving the IDeA program and the IDeA program staff to the
NIGMS. We are confident the program will flourish as a vital component
of the NIGMS.
PLACEMENT OF NATIONAL CENTER FOR RESEARCH RESOURCES (NCRR) PROGRAMS
Question. For many years the programs housed at the NCRR have
worked synergistically to serve the IDeA community. Can this synergy
continue by placing these programs under a single NIH institute?
Answer. There is no reason why synergies established between IDeA
and other NCRR programs will not continue to flourish at both the
national level through programmatic communication and collaboration
across institutes and centers and at the local level through
institutional collaborations and interactions. Fostering collaborative
research networks is an inherent part of the IDeA mission, and it
excels at establishing connections and linkages. IDeA institutions
currently collaborate with grantees of the Research Centers in Minority
Institutions (RCMI) program as well as the Science Education
Partnership Award Program (SEPA). The NIH encourages such
collaborations, and they will continue.
PLACEMENT OF IDEA WITHIN THE NATIONAL INSTITUTE OF MINORITY HEALTH
DISPARITIES (NIMHD)
Question. It has been made public that some institute directors who
have been approached to house IDeA programs have voiced reservations
about housing these programs in their institutes based on their
programmatic mission and staffing needs. We also know that the Advisory
Council for the NIMHD has enthusiastically endorsed the idea of placing
these programs in the NIMHD. Have you considered the possibility of
placing these programs under the management of the NIMHD?
Answer. An NIH National Center for Research Resources (NCRR) Task
Force, charged with identifying the optimal new home for the IDeA
program, considered a range of options, including its placement within
the NIMHD. After careful analysis, fact-finding, and consultation, the
Task Force recommended that this program be transferred to the National
Institute of General Medical Sciences (NIGMS). The IDeA program fosters
health-related research and enhances competitiveness of investigators
at institutions located in States in which the aggregate success rate
for applications to the NIH has been historically low. By its nature,
the program extends beyond traditional capacity building in supporting
research projects that are designed to strengthen future investigator-
initiated research applications, most of which are focused on
addressing basic science questions. The NIGMS has a basic science focus
as well as a longstanding focus on institutional capacity building and
career development. Given these synergies, the Task Force determined
that the mission of the IDeA program is most closely aligned with the
mission of the NIGMS and that the NIGMS would be the optimal new home
for the IDeA Program.
THE CLINICAL AND TRANSLATIONAL SCIENCE AWARDS (CTSAS) AND THE NATIONAL
CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)
Question. With the final five CTSAs expected to be announced in the
near future, I have a couple of questions for Dr. Collins on this
program's future direction now that it is being moved to the new NCATS.
Because the NCATS is primarily focused on drug development, what
will become of the community research and integration aspect of the
CTSAs' mission? Will community involvement continue to be a central
focus of this program?
The CTSAs represent translational research across the country, but
there are no centers in the gulf south--an area with significant health
needs that would benefit greatly from a CTSA and could contribute much
to the network of centers. Is geographic distribution considered as
CTSA sites are being selected?
Answer. The mission of the NCATS will be to catalyze the
development of innovative methods and technologies that will enhance
the development, testing, and implementation of diagnostics and
therapeutics across a wide range of human diseases and conditions. In
addition to strengthening and streamlining the therapeutics development
process, the NCATS will support research aimed at accelerating the
development, testing, and implementation of products and techniques,
including diagnostics, drugs, biologics, medical devices, and
behavioral interventions, for the diagnosis, treatment, and prevention
of disease. The CTSAs possess the requisite expertise across the full
spectrum of translational research, and they will be integral to the
success of the NCATS. The involvement of research sites across the
Nation and the study of the integration of research findings at the
community level will continue to be an important focus of the CTSA
program.
Institutions with CTSAs that are either close to or interact with
communities and populations along the Gulf include the University of
Texas Medical Branch in Galveston and the University of Alabama in
Birmingham. The CTSA at the University of Texas Health Sciences Center
at Houston serves gulf communities through its strong connections to
UT's Brownsville campus.
With regard to the selection of the CTSA sites, NCRR has used the
peer review process to establish priority scores to guide funding
decisions. All applications, together with their priority scores, were
then reviewed by the National Advisory Research Resources Council,
which is able to make recommendations, where needed, concerning
geographic distribution. Going forward, scientific merit will continue
to be the principal selection criterion, and considerations of program
relevance and public health need will be factored in at subsequent
levels of review.
GEOGRAPHIC DISTRIBUTION OF SMALL BUSINESS INNOVATIVE RESEARCH (SBIR)
GRANTS
Question. As one of the largest funders of SBIR grants, can you
tell me what the NIH is doing to ensure that there is a more balanced
portfolio and increased participation from States that have
traditionally received a small number of SBIR grants?
Answer. The NIH prioritizes SBIR and Small Business Technology
Transfer (STTR) outreach to States that historically have submitted a
small number of SBIR applications and/or have lower success rates than
the overall SBIR/STTR success rates. Each year, we hold an annual SBIR/
STTR conference, this year on the NIH's campus in Maryland, but in past
years in Ohio, Nebraska, Nevada, Georgia, and North Carolina. We also
participate in direct one-on-one contact with current and potential
applicants/grantees in several national, State, and regional SBIR
events per year. Currently in fiscal year 2011, the NIH staff have
already attended, presented, or participated on the SBIR program in
Arizona, California, Florida, Kansas (via webinar), Kentucky, Maine,
Maryland, Michigan, Missouri, Nebraska, New York, Virginia, Washington,
DC, and Wisconsin. On the horizon is an event in Louisiana. These
conferences attract attendees from across the country, and offers
attendees an opportunity for one-on-one consultations with the NIH
SBIR/STTR program, review and grants management staff. In addition,
there are a number of other conferences/meetings in which the NIH
offers consultation to SBIR/STTR applicants and similar outreach is
conducted by the individual NIH Institutes and Centers. In all venues,
the NIH educates as many current and potential applicants/grantees as
possible about the SBIR program.
In addition to these in-person opportunities, the NIH staff are
available to provide assistance to all applicants from concept
development through grant life-cycle by phone, email, webinars, and our
Web sites. SBIR funding decisions ultimately are made at the NIH
Institute level and are based on scientific merit (as determined by our
two level peer-review system), available funding, and programmatic
priority. Information about all NIH grant awards, including State
location, can be accessed through our RePORTER Web site at http://
projectreporter.nih.gov/reporter.cfm.
ANTIVIRAL DEVELOPMENT FOR FLU
Question. Discussions regarding the prevention of a flu pandemic
frequently focus on vaccine development, but it is my understanding
that effective management of influenza will require the continued
development of new antiviral drugs. I was pleased to learn that the
National Institute of Allergy and Infectious Diseases (NIAID) recently
held a workshop on the influenza antiviral research pipeline. Are we
making progress in the development of antiviral drugs for influenza and
does the NIAID have plans for any new initiatives in this area?
Answer. In March 2011, the NIAID held the Influenza Antiviral
Research Pipeline Workshop, which brought together stakeholders from a
variety of sectors including academia, business, and government.
Discussions focused on the state of influenza antiviral research and
spanned all aspects from discovery to advanced clinical development.
Workshop proceedings will be posted on the NIAID Web site in the near
future.
Currently, there are four drugs licensed to treat influenza:
oseltamivir (Tamiflu), zanamivir (Relenza), rimantadine (Flumadine),
and amantadine (Symmetrel). Ongoing NIAID efforts in influenza drug
development include combination studies with licensed and experimental
drugs, studies of the safety of antiviral drugs in infants and
children, studies of broad-spectrum antivirals, studies of antibody
therapeutics, and evaluation of novel drug targets. For example, the
NIAID also supports in vitro and in vivo antiviral screening and other
preclinical services to identify new antiviral candidates. In fiscal
year 2010, more than 100,000 compounds were evaluated by high-
throughput screening assays against multiple influenza A strains, and
several hundred compounds were tested for their efficacy against
influenza in animal models. Also, the NIAID is supporting the
preclinical and clinical development of a novel antiviral drug
candidate; a safety study has been completed and a Phase II clinical
trial is ongoing.
To meet the need for effective influenza management strategies, the
NIAID will continue to support a robust influenza antiviral research
portfolio, including discovery of drug targets, identification of
compounds with novel mechanisms of action, and clinical studies to
evaluate promising drug candidates.
STROKE IN WOMEN
Question. My State of Louisiana lays in the Stroke Belt, a group of
Southeastern States where stroke death rates are the highest in our
Nation. I am concerned about the seriousness of stroke, particularly
among women who account for 61 percent of stroke fatalities. Please
tell this subcommittee what studies the NIH is conducting to combat
stroke in women, including prevention and rehabilitation efforts. In
addition, please highlight planned activities in these areas.
Answer. The National Institute of Neurological Disorders and Stroke
(NINDS) supports a large and broad portfolio of stroke research that
includes numerous efforts to better understand and address the
substantial burden that stroke places on women.
The NINDS supports multiple research studies on the physiological
basis for gender-related differences in stroke risk and outcomes. One
study funded by the NINDS and the National Heart, Lung, and Blood
Institute (NHLBI) will follow a cohort of women to identify biological
and physiological markers associated with ischemic stroke, and to
establish which of those are influenced by sex hormones or menopausal
status. This study will inform future development of gender-specific
predictors for stroke risk. In another study, investigators will
explore how biological functions programmed by sex-specific chromosomes
are related to gender differences observed in cell death pathways
activated by a stroke. The NINDS also funds a study to investigate the
role of estrogen receptors in gender-related differences in incidence
of stroke associated with cardiovascular surgical procedures.
The NINDS supports a number of surveillance studies that aim to
illuminate differences in stroke knowledge, risk and outcomes among
different sub-populations, including women, in order to inform
development of tailored prevention intervention strategies. For
example, the Reasons for Geographical and Racial Differences in Stroke
Study (REGARDS) is a large cohort of more than 30,000 participants,
more than half of whom are women. This comprehensive assessment of
disparities in stroke risk and incidence is one of the largest
longitudinal cohort studies of African Americans and the only national
study of the epidemiology of cognitive change. The large representation
of women in this important population-based study is significant as it
allows for data analyses of gender-specific differences, as well as
among different racial populations. For example, a recent publication
from this study revealed that markers for inflammation led to more
accurate vascular disease risk stratification, particularly in blacks
and women, since they are at higher risk for increased levels of this
marker. Studies from REGARDS will continue to improve our understanding
of differences in stroke risk among a diverse U.S. population.
The NINDS supports a large number of clinical studies to improve
acute management and long-term outcomes in stroke. All of the NIH-
funded clinical trials are required to set and justify target
enrollment by race, ethnicity, and gender and to report on enrollment
progress. Approximately half of the participants in all of the NINDS-
supported stroke clinical trials are women so that data can be analyzed
for gender-specific differences. These trials are investigating new
approaches to treat acute stroke and brain hemorrhage, to reduce brain
damage due to stroke and to improve rehabilitation strategies, which
will provide all patients, including women, and their physicians with
more therapy options and a better chance of survival and recovery after
a stroke.
The NINDS is embarking on a new stroke planning effort in 2011 to
update research progress and activities in response to prior research
recommendations, and to identify a specific set of high priority areas
for advancing stroke research over the next 5-10 years. The planning
effort will specifically address stroke prevention, treatment, and
recovery in subpopulations, with a special emphasis on women and gender
differences. Recommendations from this planning effort will inform
future NINDS research investment and activities related to stroke in
women.
NCI PRIORITIES
Question. Dr. Varmus, you have stated a desire for the NCI to
continue to fund as many grants as in previous years, even if this
means cuts in other areas, such as the Cancer Center program. Could you
tell us a bit more about your plans and priorities for the institute
and possible changes on the horizon?
Answer. Cancer is a complex disease requiring many approaches to
make progress. It is important to fund as many meritorious grants as we
possibly can within the resources we are given, because individual
grants allow us to pursue new ideas effectively. We will be finding
savings across the Institute by taking money away from routine
administrative expenses, making cuts to the intramural and Cancer
Centers programs, and by conducting reviews of large programs and
cutting where possible. This will allow us to achieve acceptable grant
levels and to protect certain imperatives.
In addition, realignment of the clinical trial cooperative groups,
as recommended by the Institute of Medicine report in 2010, will
improve the efficiency of the overall system and enable the cooperative
groups to conduct state of the art oncology research more consistently.
Funding for this effort is a priority for the NCI. A second imperative
is maintaining the pace of work on cancer genomics. The Cancer Genome
Atlas (TCGA), a project undertaken by the National Cancer Institute and
the National Human Genome Research Institute to gain an understanding
of the molecular basis of cancer, has already produced results in brain
cancer and ovarian cancer. The rate of discovery is dependent on the
level of funding. Therefore, we place a high priority on protecting
funding for this project and other meritorious efforts in cancer
genomics. As TCGA is expanded to include many cancer types, the
ultimate goal is to ensure that genetic information is applied to
prevention, diagnosis, and treatment of cancer in clinical practice.
______
Questions Submitted by Senator Richard J. Durbin
ECONOMIC BENEFITS OF BIOMEDICAL RESEARCH
Question. According to a recent Families USA report, every $1
investment in medical research stimulates $2.43 in business activity--
such as support staff, supplies, food services, and building
development. Are you aware of other studies that attempt to quantify
the local impact of the Federal investment in medical research? Are
there any efforts underway at the NIH to capture the return-on-
investment that taxpayers receive as a result of the Federal commitment
to research?
Answer. To the best of our knowledge, there are two comprehensive
published studies that attempt a quantification of the economic effects
of the NIH spending at the State level, both supported by research
advocacy groups. Both studies rely on the Regional Input-Output
Modeling System (RIMS II), developed by the Bureau of Economic Analysis
at the Department of Commerce. RIMS II measures, at a State level, the
economic multiplier effect generated by local demand. National
aggregate averages are extrapolated from State data.
The first report was released in June 2008 by Families USA and was
titled ``In your own backyard.'' \1\ The report found, among other
things, that in fiscal year 2007, the NIH funding supported more than
350,000 jobs that generated wages in excess of $18 billion in the 50
States. The average wage for these jobs was $52,000. It also found that
$1 spent by the NIH funding generates $2.21 of business activity at the
State level. This $2.21 figure is an average; individual States may
vary (e.g., in Illinois, the figure is $2.43.)
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\1\ FamiliesUSA. (2008). In Your Own Backyard: How NIH Funding
Helps Your State's Economy. Washington, DC. Retrieved December, 2008
from http://www.familiesusa.org/issues/global-health/publications/in-
your-own-backyard.html.
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More recently, in May 2011, the organization ``United for Medical
Research'' released a report, titled: ``An Economic Engine. NIH
Research, Employment and the Future of the Medical Innovation Sector.''
\2\ The report draws three conclusions: the NIH extramural research is
an important source of income and employment around the country; the
complementary relationship between public NIH investment and private
industry development is critical to the health and well-being of our
Nation; and the U.S. medical innovation sector is facing increasing
challenges in maintaining America's competitiveness and position as the
world leader in medical research. The report found that in fiscal year
2010, the NIH directly and indirectly supported nearly 488,000 jobs and
produced $68 billion in new economic activity and that $1 of the NIH
investments generated, on average, $2.60 of business activity, at the
national level.
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\2\ Ehrlich, E. (2011). United for Medical Research from http://
www.unitedformedicalresearch.com/wp-content/uploads/2011/05/
UMR_Economic-Engine.pdf.
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The NIH has worked closely with experts in the field of labor and
health economics and R&D evaluation on several projects. One of the
studies found that a one dollar increase in the NIH funding leverages
an additional 35 cents in funding from non-Federal sources.\3\
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\3\ Blume-Kohut, M., Kumar, K. B., & Sood, N. (2008). The Impact of
Federal Funding on University R&D. Retrieved November 7, 2009 from
http://www.rand.org/labor/seminars/brown_bag/pdfs/2008_sood.pdf
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Another study determined that 33 percent of all drugs approved by
FDA and 58 percent of approved priority review new molecular entities
(which tend to be the most innovative drugs) cite an NIH-funded
publication or an NIH patent.\4\
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\4\ Lichtenberg, F. R., & Sampat, B. (2011). What are the
respective roles of the public and private sectors in pharmaceutical
innovation? Health Affairs, 30(2), 332-338.
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Another study showed that multinational companies in the
pharmaceutical sector tend to locate their R&D facilities next to hubs
of skilled workers. This finding underscores the importance of the NIH
investments in sustaining a strong research infrastructure system in
the United States and avoiding the loss of private sector investments
in R&D that could be moved abroad.\5\
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\5\ Thursby, J. G., & Thursby, M. C. (2009). Is the US a Target of
R&D Globalization? Location, Type and Purpose of Biomedical Industry
R&D in New Locations: NBER. Report prepared for the NIH Office of
Science Policy Analysis.
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Another study, Economic Impact of the Human Genome Project (http://
www.battelle.org/publications/humangenomeproject.pdf), which was
commissioned by the Life Technologies Foundation and prepared by the
Battelle Technology Practice Foundation, assessed the benefits of the
Federal investment of the Human Genome Project (HGP). Finding that the
benefits are widespread and increasing over time, the report cites
among other factors, the production of 3.8 million job-years of
employment (one job-year for each $1,000 invested) and the generation
of personal income (wages and benefits) exceeding $244 billion over the
last 7 years, an average of $63,700 per job-year.
With regard to whether there are other efforts underway at the NIH
to capture the return-on-investment that taxpayers receive as a result
of the Federal commitment to research, the NIH is also participating in
the STAR METRICS Project.\6\ \7\ STAR METRICS is a collaboration
between Federal science agencies and research institutions to document
how Federal science investments support knowledge creation, economic
growth, workforce development and a broad range of societal outcomes.
The program's goal is to build a data infrastructure that will bring
together inputs, outputs, and outcomes from a variety of sources in as
open a fashion as possible.
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\6\ https://www.starmetrics.nih.gov/.
\7\ Lane, J., & Bertuzzi, S. (2011). Research funding. Measuring
the results of science investments. Science, 331(6018), 678-680.
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STAR METRICS has two levels and the NIH participates in both. Level
I documents the initial effect of S&T investments on employment using
administrative records from research institutions. This approach goes
beyond the RIMSII model, capturing the actual, rather than estimated,
number of jobs supported. Level II builds on Level I by connecting
sources of funding, recipients of funding, interactions among
scientists (in both the public and private sector) and the products of
research over time ranging from the most proximal (such as meeting
presentations and publications) to more distal (such as the development
of a new drug).
CONGENITAL HEART DISEASE (CHD)
Question. Congenital Heart Disease (CHD) is one of the most
prevalent birth defects in the United States and a leading cause of
birth defect-associated infant mortality. Due to medical advancements
more individuals with congenital heart defects are living into
adulthood. Please provide an update of research within the NIH,
particularly the National Heart, Lung, and Blood Institute (NHLBI)
related to congenital heart defects across the life-span. The
healthcare reform law included a provision, which I authored, that
authorizes the CDC to track the epidemiology of congenital heart
disease, with an emphasis on adults with CHD and expanding
surveillance. If adequately funded, how could a population-surveillance
system for adults with CHD support the NIH's ability to investigate CHD
across the life-course and across subgroups?
Answer. The NIH supports research on CHD across the lifespan. For
example, as part of its Pediatric Heart Network, the NHLBI is following
participants in an earlier study of the Fontan surgical procedure to
assess functional health status, neurocognitive performance, and
transitions from pediatric care to adult care for CHD. Through its
Bench-to-Bassinet program, the NHLBI is examining the genetic causes of
CHD and the effects of genetic variation on the long-term clinical
outcomes of affected children as they grow older. The NHLBI also funds
a research partnership between the Adult Congenital Heart Association
and the Alliance of Adult Research in Congenital Cardiology that seeks
to improve care delivery and long-term outcomes for adults with CHD and
also to inform research designs for studies in adults. Through its
Pumps for Kids, Infants, and Neonates (PumpKIN) program the NHLBI
supports development of pediatric devices for congenital heart disease.
In addition, an investigator-initiated project seeks to develop a blood
pump for patients who have undergone the Fontan surgery. Patients who
have had the surgery experience significant morbidity due to diminished
blood flow, especially as they grow into adulthood, and a device to
assist blood flow could dramatically improve care.
An adequately funded population-surveillance system for adults with
CHD could facilitate the NIH research. The surveillance data would help
the NIH ensure that its research efforts address the full range of
heart conditions, risk factors, and complications across the lifespan;
provide the potential to link genetic and other biological information;
permit monitoring of the effectiveness of new preventive and
therapeutic strategies; and identify a potential pool of patients who
could benefit from participation in various research activities.
However, funding was not provided for this provision in the Affordable
Care Act, and no funds have been requested within the budget for the
Centers for Disease Control and Prevention to implement it.
THE CANCER GENOME ATLAS
Question. The National Cancer Institute is making tremendous
progress with the Cancer Genome Atlas (TCGA) in sequencing cancer
genomes and then using scientific discoveries to further specific
fields of cancer research. What is the status of the TCGA gastric
cancer project? Specifically, the pilot project to utilize contiguous
biopsies to sequence the genome for the diffuse gastric cancer subtype?
How will the NCI utilize these groundbreaking discoveries to further
the field of gastric cancer research? What other initiatives and steps
is the NCI taking to investigate gastric cancer?
Answer. TCGA staff and extramural researchers have been steadily
working on identifying, collecting, and assessing the quality of
gastric cancer biospecimens for inclusion into TCGA's genotyping and
molecular characterization pipeline. However, due to the difficulty in
obtaining qualifying biospecimens from patients with diffuse gastric
cancer, the NCI began to explore a pilot project for collection of
diffuse gastric cancer biospecimens. The challenges involved in this
pilot project of multiple gastric biopsies was discussed in detail in
May 2011 when the NCI hosted a workshop on gastric and esophageal
cancer, bringing together a group of international experts to explore
and discuss the basic biology, epidemiology, and clinical research
aspects of these cancers across the world. There was tremendous
interest in the pilot study from the gastric cancer researchers, and in
June 2011 the NCI approved TCGA to proceed with the pilot study to
collect biospecimens on a small number of diffuse gastric cancers from
the United States. The extent of the project will depend on the cost
per case and the number of centers willing to participate. We are
hopeful that analysis of these biospecimens will yield valuable
information that will stimulate novel research approaches for this
challenging disease and will lead to advances in the prevention,
diagnosis, and treatment of diffuse gastric cancer.
In addition to the TCGA-related efforts, an NCI Genome-Wide
Association Study (GWAS) on gastric adenocarcinoma and esophageal
squamous cell carcinoma has already revealed a common cancer
susceptibility region at PLCE1, and the NCI is funding follow-up
mechanistic studies on the effect of the gene variations in this
location. A second GWAS will be conducted in a mostly Caucasian cohort
to provide further clues about susceptibility regions and whether they
differ between populations that experience different rates of gastric
cancer. The NCI also funds broad based research at four
Gastrointestinal Cancer Specialized Programs of Research Excellence
(SPOREs), two of which include a focus on esophageal cancers.
EOSINOPHILIC-ASSOCIATED DISORDERS RESEARCH
Question. Eosinophilic-associated disorders were identified in the
last decade. Consequently many people go undiagnosed for years, due to
lack of information and awareness about these diseases. Please describe
current efforts at the NIH, particularly the National Institute for
Allergy and Infectious Diseases (NIAID) to investigate eosinophilic-
associated disorders. Last year, the Senate budget included report
language urging the NIAID to convene a working group to develop a
research agenda aimed at improving the diagnosis and treatment of
eosinophilic-associated disorders. What strides are the NIH and the
NIAID making to develop a research agenda focused on these conditions?
Answer. As the lead institute at the NIH responsible for research
on immunologic and allergic disorders, the NIAID is committed to
research to better understand the mechanisms that mediate tissue injury
when eosinophils accumulate, including eosinophilic gastrointestinal
disorders, a group of recently recognized allergic diseases associated
with the production of IgE antibodies and other immune responses to
food. The NIAID works closely with other NIH Institutes and Centers
supporting research on eosinophilic disorders. Although these
collaborations and communications do not occur through a formal working
group or a predetermined research agenda, they have led to jointly
sponsored workshops and research initiatives on eosinophilic disorders.
In fiscal year 2012, the NIH, with the NIAID as the lead, will
establish a working group with participation by relevant NIH Institutes
and Centers, to develop a trans-NIH strategy to improve the diagnosis
and treatment of eosinophilic disorders.
As part of its overall research agenda on immunologic and allergic
diseases, the NIAID pursues research on eosinophilic disorders through
a variety of efforts and collaborations. For example, the Consortium of
Food Allergy Research (CoFAR), co-funded with the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), and renewed in
fiscal year 2010, develops new approaches to treat and prevent food
allergy. A new CoFAR project is examining the genetic aspects of
eosinophilic esophagitis. The NIAID Asthma and Allergic Diseases
Cooperative Research Centers (AADCRC) support basic and clinical
research on the mechanisms, diagnosis, treatment, and prevention of
asthma and allergic diseases, including food allergy and anaphylaxis.
Many of these disorders are associated with eosinophilia. In addition,
the NIAID-supported investigators are conducting a pilot clinical trial
to determine the efficacy of swallowed glucocorticoids for the
treatment of eosinophilic esophagitis, and developing novel noninvasive
diagnostic tools for eosinophilic gastrointestinal diseases to reduce
the number of endoscopies and biopsies that are currently performed.
Also, on behalf of more than 30 professional organizations, Federal
agencies, and patient advocacy groups, including the American
Partnership for Eosinophilic Disorders, the NIAID coordinated the
development of Guidelines for the Diagnosis and Treatment of Food
Allergy in the United States. This document includes clinical practice
guidelines for the diagnosis and management of eosinophilic esophagitis
associated with food allergy. The guidelines were published in the
December 2010 issue of the Journal of Allergy and Clinical Immunology
and can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21134576.
The NIAID will continue its commitment to research and trans-NIH
research collaborations on eosinophilic disorders to understand the
mechanisms that mediate tissue injury when eosinophils accumulate. As
part of this effort, in fiscal year 2011, the NIAID will recompete the
AADCRC program.
______
Questions Submitted by Senator Mark Pryor
EXTRAMURAL RESEARCH BUDGET
Question. What percentage of the NIH's funding leaves the greater
Washington, DC area and goes to medical research in States and local
communities?
Answer. In fiscal year 2010, the NIH awarded 82 percent ($25.6
billion of $31.2 billion) of its budget to more than 3,000 institutions
and organizations across the United States, as well as several other
countries throughout the world, 71 percent ($22.1 billion) in grants
and 11 percent ($3.5 billion) in research and development contracts.
The percentage of the fiscal year 2011 budget devoted to extramural
research is also expected to be approximately 82 percent. An overview
of the NIH funding allocations by Institute and Center in fiscal year
2010, fiscal year 2011, and the fiscal year 2012 budget is available
at: http://officeofbudget.od.nih.gov/pdfs/FY12/
COPY%20of%20NIH%20BIB%20Chapter%202-9-11-%20FINAL.PDF.
PERSONALIZED MEDICINE AS A PRIORITY
Question. As you well know, we are currently in a very difficult
economic time. The Congress is in the process of making many decisions
related to addressing the Nation's budget problems. We are considering
many ways to control our costs and minimize additional debt, but at the
same time, we have to prioritize and ensure that important programs are
adequately funded. Having said that, do you believe advances in
personalized medicine could be threatened should the Congress enact
cuts to the NIH's budget?
Answer. Through the application of genomic research and high-
throughput technologies, breakthroughs in our understanding of the
causes of many diseases and the identification of new targets and
pathways for the development of new therapeutics are within reach. For
example, a decade ago, diagnosis of cancer was based on the organ
involved and treatment depended on broadly aimed therapies that often
greatly diminished a patient's quality of life. Today, research in
cancer biology is moving treatment toward more effective and less toxic
therapies tailored to the genetic profile of each patient's cancer. The
NIH research is also identifying genetic markers that can predict
whether an individual will respond well to a particular medication or
will be at risk of having an adverse reaction. The NIH-funded
researchers are also uncovering information about genes and the
environment that will help point the way toward more personalized,
targeted treatments for other diseases. The new National Center for
Advancing Translational Sciences (NCATS) will provide the
infrastructure and technologies to bring these critical basic
discoveries to fruition through new diagnostics and therapeutics.
Significant budget cuts could threaten the NIH's ability to continue to
support these advances. However, the specific research areas that would
be affected in the event that budget cuts materialize cannot be
determined now since the NIH would need to re-evaluate its research
priorities.
______
Questions Submitted by Senator Richard C. Shelby
REORGANIZATION OF NCRR PROGRAMS
Question. There remain concerns within the Congress and the
research community with the decision to eliminate the National Center
for Research Resources (NCRR). Can you explain the rationale behind
this decision and where the National Center for Research Resources'
assets will be moved?
Answer. With the decision to move the Clinical And Translational
Science Awards (CTSAs) into the proposed National Center for Advancing
Translational Sciences (NCATS), it was necessary to consider the impact
of its transfer on NCRR and whether there were long-range benefits that
could be achieved by relocating its remaining programs within other NIH
components. A task force was formed to determine if the remaining
programs should be kept in a separate organization or if there was an
opportunity for greater scientific synergies by moving the remaining
programs to other NIH components. The task force was guided by the
following considerations and principles in developing its
recommendations:
--The scientific synergies that could be achieved by placing the NCRR
program in adjacency to existing (or in the case of the NCATS,
proposed) portfolio/mission of the recipient IC versus the
existing synergies among the NCRR programs.
--The ``goodness of fit'' for the NCRR program within the recipient
IC versus the negative effects of adding a program that is
disproportionately large and/or not well aligned to the
recipient IC's current (or in the case of the NCATS, proposed)
mission.
--The level of disruption to long-standing NCRR programs led by
dedicated NCRR staff versus the disruptive innovation from
reassigning NCRR staff to enable interactions with new
colleagues and/or new programs.
The Task Force agreed with the SMRB recommendation that the CTSAs
be placed in the proposed Center. The Task Force then determined that
the greatest scientific synergies could be achieved by placement of the
remaining programs to other components of the NIH. The Research Centers
in Minority Institutions (RCMI) program was proposed for placement in
the National Institute for Minority Health and Health Disparities; the
Institutional Development Award (IDeA) program was proposed for
placement in the National Institute for General Medical Sciences
(NIGMS); the Imaging and Point-of-Care Biomedical Technology Research
Center (BTRC) grants, and Biomedical Imaging, and Point-of-Care
research grants for Technology Research and Development were proposed
for placement in the National Institute of Biomedical Imaging and
Bioengineering; the remaining BTRCs and all other research grants for
Technology Research and Development, and the BIRN network grants were
proposed for placement in the NIGMS; the Gene Vector Repository was
proposed for placement in the National Heart, Lung, and Blood
Institute; and the Comparative Medicine Program, Extramural
Construction and Animal Facilities Improvement, Shared and High-End
Instrumentation, and Science Education Partnership Awards (SEPA) were
proposed for placement in a new Office of Research Infrastructure
Programs in the Division of Program Coordination, Planning, and
Strategic Initiatives in the Office of the Director.
The Task Force implemented a transparent process to collect and
consider input from a wide range of internal and external experts, as
well as stakeholders ranging from members of the public to members of
the extramural research community. As the deliberations progressed, the
NIH made information available to the public through a feedback page
available on its website. The final Task Force recommendations were
accepted by the NIH Director and the Secretary, and transmitted to the
House and Senate Appropriations Committees in a letter dated June 6,
2011. Additional budget details on the reorganization were provided to
the subcommittees on June 23, 2011.
BASIC AND APPLIED RESEARCH BALANCE
Question. How do you balance the NIH's goals in research aimed at
knowledge generation (basic research) versus translation of that
knowledge toward cures and improving human health (applied research)?
Will the NCATS help to achieve a better balance?
Answer. Basic research advances knowledge of fundamental biological
processes and elucidates the molecular underpinnings of human health
and disease. Basic research makes it possible to understand the causes
of disease onset and progression and opens up new avenues for
developing new and improved diagnostics, therapeutics, and preventive
strategies. Realizing the benefits of fundamental biomedical
discoveries depends on the translation of that knowledge into
strategies and products that treat disease and sustain and improve
health. It is important to understand that ``basic'' and
``translational'' research are inherently interrelated and comprise a
cyclical process. There are important feedback loops between the fields
so that advances in one ultimately yield new avenues for scientific
inquiry and discovery in the other. Breakthroughs in our understanding
of therapeutic targets and pathways also stimulate new avenues for
basic scientific inquiry. By studying the process of developing new
therapeutics and diagnostics in an open access environment, the NCATS
will ultimately catalyze the cycle of discovery in order to advance
public health.
From a funding standpoint, 54 percent of the NIH budget is devoted
to basic research and 46 percent to applied research, a ratio that has
not varied appreciably for decades. The NIH does not intend to shift
resources currently devoted to basic research to fund translational
research. The NCATS will be formed through the realignment of existing
translational research programs and, as such, will not affect the
balance of basic and applied research supported by the NIH. It will
certainly use discoveries made through basic research to advance its
work while also providing important insights for basic scientists to
pursue.
MOLECULAR LIBRARIES PROGRAM AS PART OF THE NCATS
Question. Dr. Collins, can you discuss the NIH Roadmap Molecular
Libraries Probe Production Center Network component of the NCATS. I
understand that this national network of centers provides for the first
time a sophisticated infrastructure for drug discovery to the academic
and nonprofit research community. What role will this program play in
the NCATS going forward?
Answer. The NIH Molecular Libraries Probe Production Center Network
(MLPCN), a component of the NIH Molecular Libraries Program (MLP), is a
collaborative research network that enables the generation of effective
and useful small molecule chemical probes for the entire biomedical
research community. Through support from the NIH Common Fund, the MLPCN
offers biomedical researchers access to large-scale screening capacity,
along with medicinal chemistry and informatics needed to convert the
large number of active compounds identified by high-throughput
screening into useful probes for studying the functions of genes,
cells, and biochemical pathways. Traditionally, these resources and
associated expertise have resided exclusively within the private
sector.
By providing early stage chemical compounds to the biomedical
research community, the NIH anticipates that the components of the MLP
can further enable researchers in both the public and private sectors
to validate new drug targets, which could then move into the drug-
development pipeline. This is particularly true for rare diseases,
which may not be attractive for development by the private sector. For
this reason, several components of the Common Fund's MLP are
transitioning to be funded and managed through the NCATS. These include
the Small Molecule Repository, Cheminformatics/PubChem, and the NIH
Chemical Genomics Center (NCGC), an intramural high-throughput
screening Center. The Common Fund will continue to provide support for
the Chemical Diversity technology development program, the Imaging
Probe Database, and the extramural Specialized Screening Centers.
THE NIH, ACADEMIA, AND INDUSTY RELATIONSHIP
Question. Much of the country's translational research has been
within the pharmaceutical industry and the biotechnology community. Can
you elaborate on the relationship between the NCATS and these entities?
Is there a change in roles in academia and the commercial world?
Answer. The process of translating fundamental knowledge into new
or better clinical applications is an exceedingly complex, costly, and
risk-laden endeavor. Moreover, the average length of time from target
discovery to FDA approval of a new drug is 14 years and the failure
rate exceeds 95 percent, i.e., fewer than one out of twenty projects
that enter the drug development pipeline will result in a new FDA-
approved product. At the same time, recent progress in genomics,
biotechnology, and other fields of biomedical research has advanced the
potential for development of new diagnostics and treatments for a wide
range of diseases, opening a wide door of opportunity in translational
science.
There is a growing recognition on the part of all those involved in
translational medicine that the current model for development is not
sustainable and that novel partnerships and collaborations are critical
to progress. The NIH is uniquely positioned to help bring about the
changes by complementing the translational efforts of each sector. To
achieve this goal, the NCATS will bring together resources and skilled
scientists to study the steps in the therapeutics development and
implementation process, consult with experts in academia and the
biotechnology and pharmaceutical industries to identify bottlenecks in
the processes that are amenable to re-engineering, and develop new
technologies and innovative methods for streamlining the processes.
Cross-sector collaborations will be an essential part of how the NCATS
operates.
FUTURE OF R01 FUNDS
Question. Will the establishment of the NCATS result in the loss of
R01 funds?
Answer. No. Funds for research project grants will not be affected
by the establishment of the NCATS, which is being created by realigning
several existing NIH translational research programs. The NCATS will
stimulate the pursuit of new avenues of scientific inquiry by
facilitating and complementing translational research efforts carried
out elsewhere at the NIH. It will not diminish the agency's commitment
to basic science. Moreover, the NIH requested an additional $100
million for the operation of the Cures Acceleration Network within the
NCATS, some of which would be used for research project grants.
PROCESS INNOVATION AND THE NCATS
Question. Dr. Collins, you have stated that ``process innovation''
is an important component of the NCATS. Can you explain what this is
and why it is important? How will process innovation relate to
individual disease-focused projects the NCATS may do?
Answer. Process innovation involves studying the therapeutics
development process with the goal of developing new approaches and
technologies that can strengthen and streamline the development
pipeline itself. By approaching the development pipeline as a
scientific question, the NCATS will identify bottlenecks in the
processes that are amenable to re-engineering and develop new
technologies and innovative methods for improving and advancing the
discovery, testing, and implementation of new therapeutics. Among the
specific developmental steps that may be addressed are target
validation, preclinical toxicology testing, clinical trial design, and
drug rescue and repurposing. In order to evaluate these innovations and
new approaches, the NCATS will undertake targeted therapeutics
development and implementation projects that may have relevance to
individual disease-focused projects.
REORGANIZATION OF THE COMPARATIVE MEDICINE PROGRAM
Question. I have heard from several elite schools of medicine,
including Stanford, MIT, UAB, and Auburn that splitting the components
of the National Center for Research Resources' Comparative Medicine
program into different administrative entities would have a negative
impact on the NIH's critical scientific infrastructure. Dr. Collins,
can you address their concerns and share with the subcommittee a
solution to ensure components of the Comparative Medicine program
remains intact and together within the new organizational structure?
Answer. Initially, we had considered a number of options with
regard to the placement of the programs within the Division of
Comparative Medicine, including dividing them among relevant institutes
and centers. However, following extensive consultation with multiple
stakeholders, including grantees, professional organizations, and the
public, we concluded that it was important to keep the programs within
the Division of Comparative Medicine together because of their
intrinsic uniqueness and synergies. As such, the Division of
Comparative Medicine is to be transferred in its entirety to the new
Office of Research Infrastructure Programs in the Division of Program
Coordination, Planning, and Strategic Initiatives within the Office of
the Director.
BROADENING THE IDEA PROGRAM
Question. The National Center for Research Resources' Institutional
Development Award program broadens the geographic distribution of the
NIH funding for biomedical and behavioral research. It is my
understanding that the goal of the program is to expand biomedical
research capabilities to areas that currently lack it through research
and infrastructure funding opportunities and faculty development.
In its entirety, Alabama is a significant recipient of the NIH
funding, mainly due to the research funding received by its two medical
schools. While they provide great benefit to my State and Nation
through medical breakthroughs and economic investment, I am concerned
that their success puts other Alabama institutions at a competitive
disadvantage with similar institutions in IDeA-eligible States.
Has the NIH considered ways to include institutions in this program
from non-IDeA eligible States? If not, are there other avenues within
the NIH that could serve a similar role to IDeA for schools in States
where one or two universities' significant NIH funding limits their
access to preliminary support?
Answer. The current authorization language for the IDeA program
limits participation in the program to institutions located in States
with low aggregate success rates for obtaining NIH funding or States
that do not attain a particular level of support from the NIH. It does
not allow for participation by institutions from States with high
success rates or States that receive substantial support from the NIH.
In 2008, a working group of NCRR's advisory council, which was formed
to review the eligibility criteria for the IDeA program, explored
whether it would be possible to base eligibility on institutional or
regional success rates. The group was unable to identify an alterative
approach that met the intent of the law.
In States that are not eligible for IDeA, institutions with limited
NIH funding are encouraged to participate in are encouraged to apply
for Academic Research Enhancement Awards (AREA) http://grants.nih.gov/
grants/funding/area.htm which supports projects in the biomedical and
behavioral sciences conducted by faculty and students in health
professional schools, and other academic components that have not been
major recipients of the NIH research grant funds. In addition,
institutions could try to increase the NIH grant support by partnering
with institutions with more significant NIH funding. Such partnerships
can help build the experience and capacity necessary to successfully
compete independently for the NIH funding in the future.
GULF OIL SPILL HEALTH EFFECTS RESEARCH
Question. According to the NIH press statement, of the 40 known oil
spills in the past 50 years, the health effects have been studied from
only eight of those spills. I am pleased to see the NIH will begin to
review health effects of people impacted by the Deepwater Horizon oil
spill in the Gulf of Mexico. It is critical to understand how being
exposed to the oil and the dispersants may have affected the health of
cleanup workers and volunteers. Could you discuss how this study will
be conducted and what you are hoping the GULF Study will help us learn?
Answer. The Gulf Long-term Follow-up Study (GuLF STUDY) will help
determine if oil spills and exposure to crude oil and dispersants
affect physical and mental health. The National Institute of
Environmental Health Sciences (NIEHS) is leading this research. A major
facet of the study is to compare the health of clean-up workers and
others who did not do clean-up work to learn if health problems are
more common in workers. GuLF STUDY researchers will also examine other
factors that may explain why some people are more likely than others to
get sick and how stress affects health. The NIEHS will send
approximately 90,000 invitation letters to people to be included in the
study. Of this group it is expected that 55,000 will be enrolled and
complete telephone interviews. Participants will be interviewed about
their oil-spill clean-up jobs, demographic and socioeconomic factors,
occupation and health histories, and current health, including stress
and mental health. About half of the cohort will be asked to complete a
brief clinical examination in their home. The home exam will include
additional health questionnaires and collection of biological samples,
such as blood and urine, and environmental samples, e.g., house dust.
The exam will include basic clinical measurements such as height,
weight, blood pressure and tests of lung function. The home exams will
largely target workers residing in the four most affected Gulf States--
Louisiana, Mississippi, Alabama, and Florida). All cohort members will
be followed for development of a range of health outcomes. Follow-up of
the entire cohort is initially planned for 10 years, with extended
follow-up possible depending upon scientific and public health needs
and the availability of funds.
GuLF STUDY researchers are hoping to learn if exposure to
constituents of oil, dispersants, and oil-dispersant mixtures during
oil spill clean-up is associated with adverse health effects,
particularly respiratory, neurological, hematologic, and mental health.
In addition, this research is anticipated to reveal biomarkers of
potentially adverse biologic effects associated with oil spill-related
exposures. Results of the study will provide further insight into how
stress and job loss can affect health, including mental health.
Overall, the findings may influence long-term public health responses
in Gulf communities or responses to other oil spills in the future.
CYSTIC FIBROSIS RESEARCH
Question. In February, the NIH announced that federally funded
research led to the development of a very promising therapy that
targets the genetic defect that causes Cystic Fibrosis. How will the
fiscal year 2012 NIH budget request support additional research on
Cystic Fibrosis?
Answer. Cystic fibrosis (CF) research continues to be a high-
priority area. The NIH estimates the fiscal year 2012 budget request
would support about $88 million for CF research, ranging from basic
science studies through clinical trials. The results of our prior
investments have provided enormous benefit to affected patients.
Whereas years of life expectancy for children born with CF could once
be counted on the fingers of one hand, today average survival is 37
years and some patients live into their 50s and beyond. Evidence-based
improvements in nutrition, infection control, and symptom management
have substantially enhanced the quality of life of affected persons.
Newborn screening for cystic fibrosis, now universal in the United
States, is not only enabling early interventions but also providing
unprecedented opportunities for effective translation of new research
advances into clinical practice.
With improved understanding of CF biology, advances in experimental
methods, and growing availability of new targets for interventions, we
anticipate that CF research will be especially productive in the next
few years and that tangible improvement in patient outcomes will
follow. The recent NHLBI workshop ``Future Research Directions in the
Pathogenesis, Treatment, and Prevention of Early Cystic Fibrosis Lung
Disease'' identified a number of important topics for future research
that can be pursued as funding permits. They include work with animal
models to understand how early lung disease develops, identification of
genetic and environmental factors that modify the manifestations and
course of CF, examination of the role of mutant CFTR (the defective
gene product in CF) in airway growth and development, and exploration
of the mechanisms that underlie CF-related diabetes and liver disease.
The NIH will continue to adjust its research portfolio in CF to ensure
that needs and opportunities for advancing research are addressed.
THE NIH-FDA COLLABORATIONS
Question. The development of treatments for diseases, especially
rare diseases, is an expensive and lengthy process. A very small
percentage of potential medicines even make it to the clinical research
stage, let alone to FDA review. What can the NIH do to reduce some of
the regulatory requirements that both slow the pace and increase the
cost of medical research, but that add little meaningful
accountability?
Answer. The NIH is taking a multi-pronged approach to promote
efforts to address unnecessary, inconsistent, and duplicative
regulatory requirements. We work closely with FDA and the Office for
Human Research Protections to enhance the consistency of regulations
governing clinical research. Through the NIH-FDA Joint Leadership
Council, we are working with FDA to help ensure that regulatory
considerations are a component of scientific research at all phases of
development and they are informed by the most current science and
technologies. Such efficiencies along with targeted support for the
development of novel technologies including new and improved
preclinical toxicology approaches for testing safety should quicken the
pace and reduce the human-related costs of medical research. The
proposed National Center for Advancing Translational Sciences will be
focused on studying diagnostics and therapeutics development, testing,
and implementation; identifying bottlenecks amenable to re-engineering;
and formulating innovative methods to streamline the process.
CLINICAL TRIAL PROCESS
Question. One of the priorities of the Joint NIH-FDA Leadership
Council is to optimize and maximize data from clinical trials. Would
you consider working with the FDA to grant greater flexibility
regarding the approval of orphan drug therapies on the basis of a
single, well-designed trial?
Answer. The FDA and the NIH have complementary roles and
functions--the NIH supports and conducts biomedical and behavioral
research and the FDA ensures the safety and effectiveness of medical
and other products. The NIH does not share regulatory authorities with
the FDA, i.e., we do not make decisions about regulatory pathways or
the approvability of investigational products. However, we certainly
have common goals and are working closely in a number of ways to
address issues related to therapeutics development and regulatory
science. As you noted, the agencies are working at the leadership level
through the NIH-FDA Leadership Council, formed in 2010, to help ensure
that regulatory considerations form an integral component of biomedical
research planning and that the latest science is integrated into the
regulatory review process. The challenges associated with the
development and review of therapies for rare and neglected diseases,
such as the availability of alternative regulatory pathways for trials
of rare diseases and the level of scientific evidence needed for
approval of a new orphan therapy, are among the specific topics of
mutual interest. We also collaborate closely on issues associated with
the development of new cancer diagnostics and therapeutics through an
interagency oncology task force and, in accord with the provisions the
Best Pharmaceuticals for Children Act, to advance the development of
preclinical and clinical methodologies that provide optimal approaches
for treating diseases in childhood. We believe all of these efforts can
go a long way toward achieving our common goal of advancing public
health by promoting the translation of basic and clinical research
findings into medical products and therapies.
______
Questions Submitted by Senator Thad Cochran
TRANSFER OF THE IDEA PROGRAM TO THE NATIONAL INSTITUTE OF GENERAL
MEDICAL SCIENCES (NIGMS)
Question. The NIH has proposed the elimination of the National
Center for Research Resources (NCRR). I am particularly concerned that
this elimination will affect the Institutional Development Award
(IDeA), which has benefitted my home State of Mississippi. Under the
proposal, the IDeA program will be moved to the National Institute of
General Medical Sciences. There have been concerns expressed that the
IDeA program should not be placed in an Institute with a defined
constituency. Dr. Collins, can you elaborate on the decision process
for moving IDeA to the National Institute of General Medical Sciences?
Why do you think this is the best Institute to house the IDeA program?
Answer. The IDeA program fosters research and enhances the
competitiveness of investigators at institutions located in States in
which the aggregate success rate for applications to the NIH has
historically been low. By its nature, the IDeA program extends beyond
traditional capacity building in supporting research projects that are
designed to strengthen future investigator-initiated research
applications, most of which are aimed at addressing basic science
questions. The National Institute of General Medical Sciences (NIGMS)
has a basic science mission as well as a longstanding focus on
institutional capacity building and career development. Given these
synergies, the NIGMS was determined to be the optimal new home for the
IDeA program. The NIH reached this conclusion based on a careful
analysis of existing NCRR programs as well as extensive consultation
with stakeholders across the scientific community and input from the
NIH Institutes and Centers, including NCRR leadership and staff.
JACKSON HEART STUDY IMPACTS
Question. African Americans are more likely to be diagnosed with
coronary heart disease, and they are more likely to die from heart
disease. Due to this greater prevalence, the Jackson Heart Study is
exploring the reasons for this disparity and uncovering new approaches
to reduce it. Can you discuss the impacts this study will have?
Answer. The goals of the Jackson Heart Study (JHS) are to determine
the roles of established risk factors such as obesity, dyslipidemia,
and high blood pressure in the development and progression of
cardiovascular disease (CVD) and to identify factors related to the
emergence of such risk factors. Moreover, the study seeks to shed light
on the contributions of sociocultural factors (e.g., stress, racism,
discrimination, and coping strategies) and familial/hereditary factors,
genetic variants, and gene--environment interactions to the development
of CVD and its risk factors. Based on our experience with other NHLBI-
funded epidemiological studies of CVD such as the Framingham Heart
study, we expect the JHS to provide important information that will
help researchers to generate new hypotheses and design studies to test
interventions to prevent CVD. Ultimately, we expect the results of the
JHS to benefit not only Mississippians but also African Americans
beyond the participants in the study.
The JHS also seeks to build research capabilities in minority
institutions, address the critical shortage of minority investigators
in epidemiology and prevention, and reduce barriers to dissemination
and use of health information in a minority population. The JHS
educational and community outreach components are very strong;
consequently, the research findings will be efficiently disseminated
among participants. The JHS training component continues to provide
outstanding opportunities to inspire, motivate, and educate students to
become research leaders and to study and disseminate important findings
on prevention of CHD.
STAFFING THE JACKSON HEART STUDY
Question. The Jackson Heart Study is the largest epidemiologic
investigation of Cardiovascular Disease among African Americans in the
United States. The National Heart Lung and Blood Institute opened a
field office in Jackson to provide scientific investigators and support
staff to the study. It is my understanding that this one-person office
will soon have no staff due to the staffer leaving Jackson. I am
concerned that the National Heart Lung and Blood Institute may not fill
the position quickly which would result in an adverse effect on the
Jackson Heart Study. It is vital that the field site maintain strength
to support scientific research at the Jackson Heart Study. Dr. Collins,
can I have your assurance that the National Heart Lung and Blood
Institute will replace this position in a timely manner?
Answer. At present, the National Heart, Lung, and Blood Institute
(NHLBI) medical officer stationed at the Jackson Heart Study site plans
to remain there indefinitely. Should the position become vacant in the
future, the NHLBI would promptly pursue recruitment via standard
competitive procedures.
GEOGRAPHIC HEALTH DISPARITIES FOR STROKE AND OBESITY
Question. Health disparities are persistent across ethnic
populations as well as geographically. Geographic isolation,
socioeconomic status, and health risk behaviors contribute to health
disparities in these rural communities. Mississippi is part of the
``Stroke Belt'' and has the highest rate of obesity in the Nation. Both
of these issues are persistent problems in the rural South, with 10 out
of 11 States with the highest rates of obesity being in the South. Dr.
Collins, how is the NIH addressing the geographic issues associated
with many of the most serious diseases affecting our Nation?
Answer. The NIH supports a broad portfolio of research to
understand the complex factors that contribute to obesity, stroke, and
related health problems, and to develop and evaluate prevention and
treatment strategies for diverse populations.
The Look AHEAD clinical trial, supported by the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) and other NIH
components, is determining whether lifestyle intervention improves
health in overweight/obese people with type 2 diabetes, and in
particular the impact of the intervention on the incidence of
cardiovascular events, including stroke, heart attack, hospitalized
angina, and cardiovascular-related death. For the first four years of
this long-term study, participants in the lifestyle intervention group
lost more weight and improved their blood pressure, fitness, glucose
control, and good cholesterol, with less use of medication, compared
with those in the control group. Look AHEAD includes sites across the
country, including in Alabama, Louisiana, and Tennessee.
A major National Institute of Neurological Disorders and Stroke
(NINDS)-funded epidemiological study related to the ``Stroke Belt'' is
the REGARDS study (REasons for Geographic and Racial Differences in
Stroke) in which investigators are exploring the geographical and
racial differences in stroke risk in a cohort of about 30,000
individuals, about half of whom reside in the Stroke Belt region of the
United States. This study also includes measures of functional
cognitive decline, which may be a risk factor for stroke as well as a
marker for unrecognized stroke. Data generated from this study has led
to more than 70 publications, and will continue to help researchers
pinpoint the reasons that the stroke death rate is higher in this
region, and among African Americans, and to develop targeted strategies
for intervention. Recent data from REGARDS indicated that overall time
spent in the Stroke Belt is more predictive of hypertension--a powerful
risk factor for stroke--than is current residence in the Stroke Belt.
Data from the REGARDS study have also revealed that stroke survivors
were more likely to have unrecognized hypertension and diabetes.
To improve stroke care utilization and patient outcomes among
vulnerable populations, the NINDS also invests in research to increase
stroke awareness and reduce the time from symptom onset to hospital
arrival, so that patients can be evaluated and treated in a timely
manner.
In one such study, a novel behavioral intervention will be tested
in which children in high risk, minority communities are taught through
Hip Hop Stroke (stroke rap songs and animated musical cartoons) to
recognize and act on the five cardinal stroke symptoms and the
importance of early treatment, with the hopes that they will
communicate this information to their parents. Preliminary pilot data
indicated that 74 percent of children communicated the material to
their parents, which significantly improved their stroke knowledge.
In the SWIFT (Stroke Warning Information and Faster Treatment)
study, a culturally sensitive educational intervention focused on
improving knowledge retention and time of arrival to the emergency
department has been tested in minority communities. The outcome and
results of this study are currently under review in a major medical
journal.
The ASPIRE program (Acute Stroke Program of Interventions
addressing Racial and Ethnic disparities) is currently testing
strategies to overcome community/socio-cultural and system barriers to
stroke treatment with the goal of increasing the number of stroke
patients treated with the clot-busting drug, tissue plasminogen
activator (tPA), in six Washington, DC, hospitals.
Ten years ago, the NINDS convened a Stroke Progress Review Group
(SPRG) to identify and prioritize scientific opportunities in stroke
research. In 2011, the NINDS will embark on a new stroke planning and
evaluation effort, which will identify a specific set of high priority
areas for advancing stroke research over the next 5-10 years. The topic
of health disparities in stroke will be included as a cross cutting
topic in this effort.
CARDIOVASCULAR DISEASE RESEARCH
Question. Cardiovascular Disease is the leading cause of death in
Mississippi, accounting for more than 40 percent of all deaths. In
2004, the State of Mississippi implemented a 10-year plan to address
Cardiovascular Disease risk factors in a two-fold approach: prevention
of potential risk factors and management of existing risk factors. In
addition, the Jackson Heart Study is the largest investigation of
causes of Cardiovascular Disease in an African-American population.
While both initiatives are good starts to addressing this health issue
in my home State, Cardiovascular Disease is the number one killer in
the United States and we need comprehensive research to fight the
disease nationwide. What plans do you have to increase research in the
area of Cardiovascular Disease?
Answer. The NHLBI is committed to supporting a comprehensive
research program on the causes, prevention, diagnosis, treatment,
monitoring, and management of cardiovascular disease (CVD). We invest
63 percent of the NHLBI extramural budget in CVD research, and we
intend to continue that high level of support. This year, the Institute
has launched a number of new projects, including two major clinical
trials:
--The International Study of Comparative Health Effectiveness with
Medical and Invasive Approaches (ISCHEMIA) addresses management
of patients with stable coronary heart disease who have
substantial ischemia on a cardiac stress test. The trial will
evaluate whether an invasive approach (performing an angiogram
and then opening or bypassing any blockages with stents or
surgery) plus optimal medical therapy is better than optimal
medical therapy alone in forestalling CVD events. Quality of
life and cost-effectiveness will also be assessed.
--The Cardiovascular Inflammation Reduction Trial (CIRT) addresses
cardiovascular disease risk reduction in heart-attack survivors
with persistently high levels of C-reactive protein, an
indicator of inflammation. The trial will evaluate whether a
very low dose of the anti-inflammatory drug methotrexate
reduces rates of recurrent heart attack, stroke, and
cardiovascular death. Several other conditions that have an
inflammatory basis, such as diabetes, venous thromboembolism,
and atrial fibrillation, will also be assessed.
The NHLBI has responsibility for cardiovascular, lung, and blood
diseases that affect millions of people worldwide. We will continue our
longstanding emphasis on the support of a balanced research portfolio
that addresses the many public health needs and scientific
opportunities that fall within our mandate.
______
Questions Submitted by Senator Lamar Alexander
REORGANIZATION OF NATIONAL CENTER FOR RESEARCH RESOURCES (NCRR)
PROGRAMS
Question. In my State of Tennessee, the largest single Federal
grant at one of the State's largest medical research institutions is a
Clinical and Translational Science Award (CTSA), for $40 million. How
will this program and others like it be affected by the dissolution of
the NCRR, and the creation of the National Center for Advancing
Translational Sciences (NCATS)?
Answer. The NIH is committed to supporting each program currently
housed within the NCRR; the proposed reorganization will not adversely
affect the individual programs. Indeed, a careful programmatic
evaluation concluded that important scientific synergies could be
gained by moving NCRR programs to other NIH components with adjacent
scientific missions. Staff responsible for administering and directing
these programs will transfer with their respective programs to ensure
continuity and oversight. With regard to the Clinical and Translation
Science Awards (CTSA) program specifically, it is to be transferred to
the proposed National Center for Advancing Translational Sciences
(NCATS). The transfer was recommended by the NIH Scientific Management
Review Board, a congressionally-mandated advisory committee to the NIH
Director, and further supported by an internal NIH task force charged
with assessing the optimal location for NCRR programs. The task force's
analysis confirmed that the goals of the CTSA program were in close
alignment with those of the new center. Decisions regarding the
selection of individual CTSAs will continue to be made based upon each
proposal's scientific merit and program relevance.
CTSA PROGRAM MISSION
Question. Given the established focus of the NCATS on drug
development, will the CTSA's continue to be able to build on the
programs of training, career development for young investigators,
research informatics, community engagement and clinical research
infrastructure?
Answer. The focus of the NCATS is to develop new and innovative
approaches to conducting research across the therapeutic development
pipeline, in the context of strengthening and streamlining the process
itself. The CTSAs have the infrastructure and diverse expertise that
supports translational research, including training and career
development for the next generation of clinical investigators,
informatics, and community engagement, and they will be integral to
fulfilling the NCATS mission. The CTSAs are making important
contributions in transforming translational research across the
country, and the NIH is committed to building upon the program's
successful efforts. Ensuring that the pipeline of new investigators is
sufficiently equipped to tackle the challenges associated with
translational science through training and mentoring is an inherent
part of the NCATS mission and will continue to be an essential
component of the CTSAs.
PERSONALIZED MEDICINE
Question. Physicians and researchers in Tennessee are investing a
great deal in the science of personalized medicine. Can you tell us
what the term ``personalized medicine'' means to you, and what role you
see for the NIH?
Answer. The concept of ``personalized medicine'' is based on the
idea that one size does not fit all when it comes to the practice of
medicine. Knowledge gathered from basic research and clinical studies
have demonstrated that individuals are highly unique in their
susceptibility to disease, reaction to medical treatments, and response
to environmental and social factors. More than ever before, and largely
thanks to research supported by the NIH, we now have the tools to
understand, describe, and quantify these biological differences as well
as the power to better predict which available treatments are optimal
for certain patients and to design rationale-based new targeted-based
therapies.
The NIH will continue to play a pivotal role in the advancement of
personalized medicine. For example, our support for pharmacogenomics
research will advance understanding of the predictive roles and
influences of genes in drug response. Findings from such research can
help identify the right drug for the right patient at the right time.
Increasingly, this information will help doctors calculate dosages that
match a person's unique physiology. Pharmacogenomic information already
is contained in approximately 10 percent of FDA-approved drug labels,
helping to prevent the inappropriate use of diagnostics and therapies.
Pharmacogenomic knowledge can also reduce the financial, emotional, and
physical costs associated with the current trial-and-error based
approach to treatment. Knowing each patient's DNA sequence is expected
to add efficiencies and new research capabilities to current endeavors.
As such, we are also fostering technological advances that are expected
to bring down the cost of sequencing an individual genome to under
$1,000. These advances will help make genetic analysis a routine part
of medical care and a revolutionary factor in approaches to basic
research and practice.
DNA DATABANKS
Question. Several major research institutions are creating
databanks that allows researchers to access a large collection of human
DNA. How does the NIH also plan to build on the mapping of the human
genome by optimizing unique resources such as this?
Answer. In support of its mission to improve public health through
research, the NIH has a longstanding policy of making data publicly
available from the research that it funds. The NIH recognizes that data
sets are not only valuable for addressing the questions that the
experiments that generated them were designed to ask, but also can be
powerful resources when combined with other data sets or used to answer
other scientific questions. This is particularly true of DNA data sets
that consist of information across the full sequence of the human
genome. Consequently, building on the data sharing practices that
characterized the Human Genome Project, the NIH launched research
programs to stimulate the creation of genomic resources and created
policies and tools for facilitating the sharing of genomic data to
capitalize on the databanks created by other institutions with or
without the NIH funding.
For example, under the leadership of the National Human Genome
Research Institute (NHGRI) the International HapMap Project used the
reference human genome sequence to build a comprehensive map (database)
of the variation within human DNA sequences, so that ``spelling''
differences in the DNA code of those with disease and those without
disease could be identified and studied. The 1000 Genomes Project is
now capitalizing on technological advances to extend and deepen the
HapMap data. All data from each of these projects are publicly
available to any investigator through the web with regular updates as
new data are generated.
In addition, to leverage the infrastructure and databank resources
created at other research institutions, the NIH has introduced funding
programs, such as the NHGRI-supported Electronic Medical Records and
Genomics (eMERGE) Network. This consortium of U.S. medical research
institutions has the primary goal of developing, disseminating, and
applying approaches to research that combine existing DNA
biorepositories with electronic medical record (EMR) systems for large-
scale, high-throughput genomic research. eMERGE Network institutions
use their own databanks (e.g., Vanderbilt University's BioVU DNA
databank) for this program, but all data are shared through an NIH
database, the database of Genotypes and Phenotypes (dbGaP), which
provides centralized and consistent access to researchers around the
globe. Importantly, dbGaP includes not only eMERGE data, but data from
studies across the disease spectrum. Extremely rich databanks from
studies such as the Framingham Heart Study, The Cancer Genome Atlas,
and many other projects reside within dbGaP, enabling many more
investigators to analyze the data as independent or combined data sets.
The standardization of access supported by the NIH facilitates cross-
study analyses, enables expansion of the study design beyond the
initial research focus of the individual databanks, and increases the
statistical power to identify the genetic contributors to common
diseases that create substantial public health burden. And,
importantly, all of these benefits are achieved through robust data
sharing policies intended to protect the interests of the research
participants who contribute their personal information to the
individual databanks.
INDUSTRY INVESTMENT IN GENOME SEQUENCING
Question. How does private investment in genome sequencing help to
leverage the Federal investment of genomic research through the NIH
funding?
Answer. The sequencing of the human genome has rightly been
regarded as one of the most important scientific undertakings of the
modern era. The NIH's investment in genomics has been, and continues to
be wide-ranging, from basic research to uncover and understand the
structure of our genome to translational science aimed at using a
patient's DNA code to tailor treatment. Enabling all of this research
are innovative new tools for DNA sequencing that have precipitated a
drop in the cost of sequencing an individual genome from hundreds of
millions of dollars to $15,000 or less.\2\ In the process, an entire
industry of genomics-focused companies has been created, one that,
according to a recent study conducted by Battelle Technology
Partnership Practice, has generated an economic contribution of almost
$800 billion since the start of the Human Genome Project.\3\ \4\
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\2\ Additional information on sequencing costs is available at
http://www.genome.gov/27541954.
\3\ http://www.battelle.org/publications/humangenomeproject.pdf.
\4\ Additional information on the economic impact of the human
genome project is available at http://www.genome.gov/27544383.
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The field of genomics has benefited from a combination of public
and private investment. During the course of the last 10 years, the
National Human Genome Research Institute's Genome Technology Program
has provided support for the development of almost all of the currently
commercialized, as well as several yet-to-be-commercialized or
emerging, sequencing technologies. Private investment during and since
that initial period of the NIH support has and will continue to bring
these innovative advances to the market. Newer and increasingly cheaper
sequencing machines and reagents have increased both capacity and
productivity, enabling the NIH grantees to answer more research
questions in the same period of time and for the same cost as
previously. Illumina and Life Technologies, for example, have now
developed smaller and less expensive sequencing machines that are
bringing DNA sequencing within reach of single-investigator research
labs. Affordable access to these technologies will greatly amplify the
number of researchers that can employ genomic sequencing within their
research plans, expanding the benefit of the Federal investment in
genomic sequencing into yet more basic, translational, and clinical
research domains. Companies like Illumina and Complete Genomics are
also offering sequencing services that the NIH-funded researchers have
used to great effect, such as the discovery last year of the causative
genes behind rare disorders like Miller syndrome, something that had
eluded science until now.\5\
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\5\ http://www.sciencemag.org/content/328/5978/636.
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______
Questions Submitted by Senator Lindsey Graham
EOSINOPHILIC DISORDERS WORKING GROUP
Question. I have heard from individuals in my State about the
enormous challenges to children with eosinophilic disorders and their
families. I understand that these conditions are often misdiagnosed and
there is no cure for these children, many of whom suffer from extreme
pain and are unable to eat normal food. This subcommittee has asked
that the NIH convene a working group on this topic. When will this
group meet and when can we expect to have a report of the group's
recommendations?
Answer. Eosinophilic gastrointestinal disorders (EGID) are a group
of diseases characterized by a wide variety of gastrointestinal
symptoms including abdominal pain, swallowing problems, food impaction
(food lodged or wedged in the esophagus), vomiting, diarrhea, growth
impairment and bleeding. EGIDs are associated with increased numbers of
eosinophils, a type of white blood cell, in the gastrointestinal
lining. The most common EGID, eosinophilic esophagitis, is
characterized by inflammation and accumulation of eosinophils in the
lining of the esophagus. This disease and other EGIDs are diagnosed by
a patient's clinical history plus endoscopy with biopsy.
As the lead Institute at the National Institutes of Health (NIH)
responsible for research on immunologic and allergic disorders, the
National Institute of Allergy and Infectious Diseases (NIAID) works
closely with other NIH Institutes and Centers supporting research on
eosinophilic disorders. Although these collaborations and
communications do not occur through a formal working group or a
predetermined research agenda, they have led to jointly sponsored
workshops and research initiatives on eosinophilic disorders. In fiscal
year 2012, the NIH, with the NIAID as the lead, will establish a
working group with participation by relevant NIH Institutes and
Centers, to develop a trans-NIH strategy to improve the diagnosis and
treatment of eosinophilic disorders.
As part of its overall research agenda on immunologic and allergic
diseases, the NIAID pursues research on eosinophilic disorders through
a variety of efforts and collaborations. For example, the Consortium of
Food Allergy Research (CoFAR), co-funded with the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), and renewed in
fiscal year 2010, develops new approaches to treat and prevent food
allergy. A new CoFAR project is examining the genetic aspects of
eosinophilic esophagitis. The NIAID Asthma and Allergic Diseases
Cooperative Research Centers (AADCRC) support basic and clinical
research on the mechanisms, diagnosis, treatment, and prevention of
asthma and allergic diseases, including food allergy and anaphylaxis.
Many of these disorders are associated with eosinophilia. In addition,
the NIAID-supported investigators are conducting a pilot clinical trial
to determine the efficacy of swallowed glucocorticoids for the
treatment of eosinophilic esophagitis, and developing novel noninvasive
diagnostic tools for eosinophilic gastrointestinal diseases to reduce
the number of endoscopies and biopsies that are currently performed.
Also, on behalf of more than 30 professional organizations, Federal
agencies, and patient advocacy groups, including the American
Partnership for Eosinophilic Disorders, the NIAID coordinated the
development of Guidelines for the Diagnosis and Treatment of Food
Allergy in the United States. This document includes clinical practice
guidelines for the diagnosis and management of eosinophilic esophagitis
associated with food allergy. The guidelines were published in the
December 2010 issue of the Journal of Allergy and Clinical Immunology
and can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21134576.
The NIAID will continue its commitment to research and trans-NIH
research collaborations on eosinophilic disorders to understand the
mechanisms that mediate tissue injury when eosinophils accumulate. As
part of this effort, in fiscal year 2011, the NIAID will recompete the
AADCRC program.
______
Question Submitted by Senator Jerry Moran
BUDGETARY EFFECTS ON THE NCI PROGRAMS
Question. Dr. Collins, I recently visited the University of Kansas
and was given a tour of the University's drug discovery, delivery, and
development operation. This visit helped demonstrate to me not only the
many elements that will become part of the application by the
University for National Cancer Institute (NCI) comprehensive cancer
center designation, but also the impressive role that the NCI's cancer
centers play across the Nation. This network of centers drives basic
research, brings individuals into clinical trials, and, most
importantly, leads to the development of new treatment advances that
will change the course of cancer for all Americans and individuals
across the globe.
While I understand that the University of Kansas' application for
the NCI designation will be determined on its scientific merits, can
you please explain how the NCI cancer center program will be affected
by the proposed budgets of the NIH and the NCI?
Additionally, considering possible scenarios for the fiscal year
2012 budget, what will the effects of such scenarios be on current NCI
programs and on the prospect for funding the review of new
applications?
Answer. The the NCI-designated Cancer Centers are an important part
of the NCI's research portfolio, and they play a unique and valuable
role in providing cutting-edge cancer care and access to the NCI-
sponsored clinical trials across the country. The final fiscal year
2011 appropriation has already necessitated a 5 percent reduction in
funding below fiscal year 2010 for the cancer centers, and it is
difficult to predict how they will be affected by the resolution of the
fiscal year 2012 budget.
The NCI's first priority must be to preserve funding for Research
Project Grants (RPGs). Ensuring support for as many new RPGs as
possible will enable investigators, especially new investigators, to
pursue novel ideas that will preserve the pipeline of innovative cancer
research. This year, nearly every NCI program budget has had to be
trimmed in order to award adequate, though reduced, number of new RPGs.
SUBCOMMITTEE RECESS
Senator Harkin. Is there anything else that any one of you
would like to state for the record now? If not--Yes.
Dr. Collins. Well, Senator, I'd just like to thank you and
this subcommittee for your steadfast support for biomedical
research.
All of us involved in this enterprise sitting here at this
table, and many others who are not at the table, but who are
engaged every day in this effort to try to find interventions
for people with disease appreciate your support and your strong
voice that, even in difficult times, medical research is
basically a societal good.
I think a society ultimately will be judged by the ways in
which, even in difficult times, priorities are chosen.
We think, in terms of alleviating suffering as well as
encouraging our American competitiveness and our economic
growth, that what we are able to do through NIH is a very good
story indeed, but we appreciate the fact that you have convened
this hearing and given us a chance to tell some of that story.
Senator Harkin. Well, thank you very much, Dr. Collins, and
I can just reciprocate then I'll join all my colleagues in
thanking you and all of you and all your colleagues at the NIH,
all the Directors, the people who work there, and through you
the whole network of researchers, young and old, some of who
have just come on, some who have been there for many years, to
thank you for your outstanding public service. All of you,
every single person engaged in NIH, thank you.
The subcommittee will stand recessed.
[Whereupon, at 11:45 a.m., Wednesday, May 11, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]