[Senate Hearing 114-160]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2017
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THURSDAY, APRIL 7, 2016
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:04 a.m., in room SD-138, Dirksen
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
Present: Senators Blunt, Moran, Cochran, Alexander,
Cassidy, Capito, Murray, Durbin, Mikulski, Shaheen, and Schatz.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
WALTER KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
RICHARD HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
CHRISTOPHER AUSTIN, M.D., DIRECTOR, NATIONAL CENTER FOR
ADVANCING TRANSLATIONAL SCIENCES
NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE
opening statement of senator roy blunt
Senator Blunt. The Appropriations Subcommittee on Labor,
Health and Human Services, Education, and Related Agencies will
come to order.
Thank you all for being here. Thank you, Dr. Collins, for
bringing your team and the other institute directors you have
with you for appearing today before the subcommittee. No
surprise to any of you from comments I've already made that I'm
troubled by the NIH budget request, a request that reduces
discretionary funding for medical research by $1 billion. I
certainly would not think that would be the way we would want
to follow our effort last year to increase research by $2
billion, and I'm confident, without asking you this, though I
may ask it later, if you really want us to fulfill the request
here, which would cut research by $1 billion.
The increase we were able to make last year for the year
you're working in now was really the first significant increase
in over a decade. During that decade, based on your numbers,
the real buying power of those research dollars had decreased
by about 20 percent, and I'm glad we could make a step back in
the right direction with the work that Senator Murray and I and
the rest of the committee struggled with and produced what I
thought was a big step in the right direction last year.
Certainly, the budget, as it's submitted, leans heavily on
new mandatory spending proposals that would bypass the current
spending caps. I think instead of making difficult funding
choices, the administration here has come up with proposals
that are unlikely to happen. It's a risky decision. It's a
decision that I don't support and hope that at the end of this
process our committee will not look at what the administration
has asked for, but look at what we would hope to be able to do.
Mandatory spending largely has been put on autopilot when
we go in that direction. I think it's a big obstacle to
addressing debt issues and other issues because we just simply
don't have to revisit it once we make it a mandatory topic.
Short-term mandatory funding for NIH, Senator Alexander and
I have talked about it. A surge, a focus on specific projects
might be different than that, but anytime you create a
mandatory cliff, it's possible to go over the cliff, and we've
seen that happen in these areas before.
Over the next 10 years, CBO, the Congressional Budget
Office, estimates that mandatory spending will already increase
from 13 percent of gross domestic product to 15 percent, and at
the same time, they anticipate that discretionary spending will
decrease by 1.3 percent of gross domestic product for our
entire economy. I think that means it's even more important for
us to be willing to put a structure together where we look at
priorities. If everything is a priority, nothing is a priority,
and the hard work of this committee, with really lots of talent
on both sides of the aisle, is to figure out what we can do
about those priorities.
After last year's significant increase in the National
Institutes of Health, it's time to again make research funding
a national priority. You can't develop a pattern, at least you
can't develop an annual pattern, if you don't do something in
year 2, and so year 2 becomes increasingly important.
I believe strongly in the promise of medical research and
what that medical research does for individuals and families
and the economy and taxpayers. It represents hope for millions
of patients who suffer from everything from cancer to kidney
disease, from Alzheimer's to autism. National Institutes of
Health (NIH)-funded research has raised life expectancy and
improved the quality of life for all Americans. It has the
power to transform the U.S. economy in significant ways as
well.
By 2050, according to figures from NIH, the cost to treat
and care for those suffering from just Alzheimer's alone is
anticipated to be $1.1 trillion of today's dollars. Now, I
think most of us have a hard time grasping with what $1.1
trillion may be. You know, when you hear $10 billion or $100
billion or $1.1 trillion, my guess is not much happens
different in anybody's brain to distinguish the difference, but
to put it in perspective, $1.1 trillion is twice what we
currently spend to defend the country. So if you're putting
your mind somewhere, every military base, every ship, every
plane, every uniform, every paycheck for the Army, Air Force,
Coast Guard, Marines, the Navy, the Reserves, the National
Guard, and double all over the world, all over the world, and
double that, that's what we would be spending on Alzheimer's in
2050 if research doesn't produce a different way forward.
I used this statistic in a speech this week where Senator
Murray and I were being appreciated for what we were able to do
here last year, and, you know, if with Alzheimer's you can
delay onset by an average of 5 years, you would reduce that
number by 42 percent and have great impact on the lives of
people that would get Alzheimer's and maybe even greater impact
on the caregivers that are so impacted by what happens with
that. And that's just one thing. There are numbers that we
could relate and we ask you to talk to us about on all of these
issues, but hopefully we'll make a renewed commitment to what
you're doing, but also we want to keep track of what you're
doing, and I'm sure that's one of the reasons that you know
you're here today. We'll have questions about how you're doing,
what you're doing, and what you plan to do going forward as
well as what is part of the budget request.
[The statement follows:]
Prepared Statement of Senator Roy Blunt
Good morning. Thank you, Dr. Collins and the other Institute
Directors, for appearing before the Subcommittee today to discuss the
National Institutes of Health's fiscal year 2017 budget request.
I am deeply troubled by the National Institutes of Health's budget
submission to reduce discretionary funding for medical research by $1
billion. Last year, this Subcommittee made great strides to begin to
restore the NIH's buying power with a $2 billion increase. This was the
first significant increase for the National Institutes of Health in the
Labor/HHS bill in over a decade. Yet the Administration's fiscal year
2017 request destroys this step forward by proposing a budget that
reduces annual funding for the National Institutes of Health.
The Department of Health and Human Services submitted a budget that
leans heavily on new, mandatory spending proposals to bypass current
spending caps. Instead of making the difficult funding decisions
necessary to live within the budget caps agreed to by the
Administration less than 6 months ago, the Department decided to cut
programs that receive bipartisan support in the hopes they would
receive funding outside the annual appropriations process. This was a
risky decision and one that I do not support.
The reliance on mandatory spending to supplant discretionary
funding contributes to exactly what is wrong with our Federal budget.
Mandatory spending, largely put on autopilot, is the biggest obstacle
in addressing our national debt. Over the next 10 years, the
Congressional Budget Office estimates mandatory spending will increase
from 13 percent of Gross Domestic Product to 15 percent. Conversely,
discretionary spending is expected to decrease 1.3 percent over the
next decade. The annual appropriations process allows, and forces,
Congress to address spending levels every year. It is the responsible
way to address funding priorities. Further, reducing discretionary
spending only to increase mandatory spending does nothing but remove
the accountability of the appropriations process.
After last year's significant investment in the NIH, this is the
time to make research funding a national priority. I strongly believe
in the promise of medical research. It represents hope for millions of
patients who suffer from conditions ranging from cancer to kidney
disease. NIH-funded research has raised life expectancy and improved
the quality of life for all Americans.
It also has the power to transform the U.S. economy. By 2050, the
cost to treat and care for those suffering from Alzheimer's disease is
expected to top $1.1 trillion a year. To put this figure in
perspective, this is twice what the Federal Government currently spends
to defend the Nation.
Last year's funding increase cannot and should not be a one-time
investment. A pattern is started in a second year, and I believe we
must seize the opportunity this year to start a pattern of sustained
increases for the National Institutes of Health. It is time for a long-
term commitment to medical research.
Thank you for being here today.
Senator Blunt. And I am pleased to turn to Senator Murray,
who she and I have had really the first year we've had a chance
to work closely together, and it's been a significant
partnership for me.
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Well, thank you, Mr. Chairman. It's good to
work with you as well.
And, Dr. Collins, thank you for being here. We are so
grateful for all you've done to champion the critical work of
the NIH. You have been a great partner, and I really appreciate
all of your team who is here today, and look forward to hearing
from all of you.
The investments that we make here in this subcommittee
really help keep our families and our communities healthy by
supporting programs that reduce infant mortality, train doctors
and nurses, provide care in rural communities, prevent the
spread of infectious diseases, and so much more. The NIH
accounts for the largest share of our subcommittee's resources,
and its work is vital to all these efforts. The basic research
that it supports leads to discoveries and breakthroughs that
give hope to those living with chronic and life-threatening
disease and help drive economic growth and competitiveness.
Today, the NIH is taking advantage of the achievements made
in human genetics, neuroscience, and other fields to make major
advances in our understanding of the human brain, and diseases
like cancer and Alzheimer's disease. Its Precision Medicine
Initiative is using the genetics of cancer to find effective
therapies.
I recently heard from a woman named Janet in my home State
of Washington who benefited from this focus on targeted
treatment. Although she had been in good health, was a non-
smoker, she was diagnosed with stage 3 lung cancer that quickly
advanced to stage 4. With her treatment options exhausted, she
learned online about a mutation testing opportunity, and that
led to a treatment that successfully targeted her cancer
mutation, and it saved her life. That was 3 years ago, and
thankfully Janet's illness remains under control.
NIH's MATCH trial is taking the testing of cancer mutations
to a national level with the hope that many more patients will
be helped. The Vice President's Moonshot initiative will
accelerate these efforts, expand access to clinical trials, and
improve data sharing, all with the goal of saving more lives.
I'm really proud that my home State of Washington is home
to several institutions that are on the cutting edge of this
field. It includes the Fred Hutchinson Cancer Research Center,
Seattle Children's Hospital, and the University of Washington,
which are using Precision Medicine to tackle breast cancer,
leukemia, and Alzheimer's disease, among others. Nearby, the
Allen Institute is working with support from the NIH to map and
unlock the secrets of the human brain. I recently visited
there, and it is amazing.
We are on the cusp of major breakthroughs on so many of the
illnesses that cost lives and hurt families each day, and I
think we should make sure that our researchers and our
scientists have all the tools and resources they need.
I know members on both sides of this aisle agree, so this
is not a partisan issue. And I'm really pleased that in the
recent budget deal, Democrats and Republicans were able to come
together to boost discretionary investments in the NIH. That
was really an important step forward, and I don't see any
reason to stop there. That's why I've made very clear in my
discussions with Chairman Alexander about legislation we're
working on to advance medical innovation in the HELP Committee,
that if we really want to get patients safer, more effective
treatments and cures, we have to take advantage of every
funding opportunity, including mandatory investments in the
NIH. It is really a make-or-break priority.
So I remain hopeful that we'll be able to write a
bipartisan appropriations bill in this subcommittee for fiscal
year 2017 and continue strong support for NIH and the many
other critical investments in this bill.
I'm also committed to working on a bipartisan agreement on
our innovations package, my chairman is here on that, to build
on the progress that we have made in the recent months with
additional sustained funding.
Patients and families across the country are waiting and
hoping for better cures and treatments, and here in Congress,
we should do our part to deliver. So I really appreciate all
the bipartisan work on this and look forward to working with
everyone.
And, Mr. Chairman, thank you for holding this hearing.
Senator Blunt. Thank you, Senator Murray.
Dr. Collins, it's wonderful to have you here, and your
institute directors. If you would introduce everybody at the
table with you, I would be pleased for you to do that. And then
I look forward to your testimony.
SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS
Dr. Collins. Thank you, Mr. Chairman. I'm happy to
introduce my colleagues, starting to my left, your right.
Dr. Richard Hodes is the Director of the National Institute
on Aging.
Dr. Walter Koroshetz, the Director of the National
Institute of Neurological Disorders and Stroke.
Dr. Christopher Austin, the Director of the National Center
for Advancing Translational Sciences.
Dr. Douglas Lowy, the Acting Director of the National
Cancer Institute.
And Dr. Nora Volkow, who is the Director of the National
Institute on Drug Abuse.
It's an honor to appear before you today. And before I
begin, I want to thank this subcommittee for the recent $2
billion boost in the fiscal year 2016 omnibus appropriation
bill. That investment so energized our community and came at an
unprecedented time of scientific opportunity, and we are truly
grateful for your leadership.
Furthermore, I would be remiss not to acknowledge the
efforts of many on this subcommittee who also serve on our
authorizing committee, which marked up important and necessary
new authorities for biomedical research just yesterday. That
was very much appreciated.
So in this hearing on the last budget of this
administration, and potentially my last opportunity to appear
before you, I hope to reflect more broadly than usual on NIH's
contribution to the Nation's health, so today I am going to
break with a more cautious tradition and make some bold
predictions, 10 areas in which I believe we can make major
advances in the next 10 years given a sustained commitment of
resources. So this is 10 for 10. So here we go.
First, the long arc of scientific discovery must begin with
basic science. Just last week, all 27 NIH institute and Center
directors and I published a letter in the Journal of Science to
underline how essential it is for NIH to invest vigorously in
basic research. That's how progress happens. Experiments that
are going on right now in labs all across this Nation contain
the seeds of breakthrough discoveries that will transform
medicine. We don't know which ones they are, but we know
they're there.
So let's fast-forward to 2026 and the first of our 10
breakthroughs. Advances in the detailed molecular analysis of
individual cells. Cells are the unit of life. Cells are for
biology like atoms are for chemistry. But through most of the
long history of medical research, we've had very limited
technical ability to study the intricate life of single cells.
We've had to deal with millions of cells, sometimes billions.
That's all changing with new technologies just invented in the
last couple of years. That's just one example.
We can now decode the process by which individual immune
cells attack and destroy healthy tissue in autoimmune
disorders. We knew the immune system was involved, but now we
can track each cell and see what it's up to, and then we can
transform the ways we approach diseases like lupus and
rheumatoid arthritis and many other conditions.
On to breakthrough number two. In 10 years' time, tools
developed through the BRAIN Initiative, which I'm sure we're
going to talk about this morning, have identified hundreds of
different types of brain cells, and more than that, major
circuits that are responsible for motor function, vision,
memory, emotion, all functioning at the speed of thought. As a
result, we will be able to diagnose neurological conditions
earlier and more precisely and we'll have new targets to
explore for prevention and treatment of conditions like autism,
traumatic brain injury, prescription drug addiction,
schizophrenia, and Parkinson's disease.
Number three. Aided by the BRAIN Initiative's new imaging
techniques and discoveries made with our private sector
collaborators, I believe we will be able in the next few years,
Mr. Chairman, to identify individuals at high risk of
Alzheimer's disease even before any symptoms appear, and, most
importantly, provide them with effective therapies aimed at
slowing or preventing the disease. Personal and family
tragedies will be delayed or averted, and the economic savings
from this alone with add up to hundreds of billions of dollars.
Number four. I predict that 10 years from now, safety
testing for newly developed drugs, as well as assessment of the
potential toxicity of numerous environmental exposures, will be
largely carried out using human biochips that are loaded with
cells accurately representing heart, liver, kidney, muscle,
brain, and other tissues. This approach, made possible by the
dramatic development of induced pluripotent stem cells, iPS
cells, will mostly replace animal testing for drug toxicity and
environmental sensing, giving results that are more accurate,
at lower cost, and with higher throughput.
Prediction number five. Speaking of iPS cells, hope is also
on the horizon for heart failure, a major cause of death in
this country. Early experiments suggest that a patient's heart
could even be rebuilt using his or her own iPS cells. This
personalized rebuilt heart would make transplant waiting lists
and anti-rejection drugs obsolete.
Number six. We will see the introduction of a safe and
effective artificial pancreas. For those with diabetes, such a
device will continually track changes in blood glucose levels
and provide precise doses of insulin, significantly improving
the management of their disease and preventing countless
complications.
Number seven. New vaccines will be readily available. An
effective Zika vaccine will have been developed and made widely
available by 2018. Universal flu vaccines will protect against
all strains of the virus, preventing that looming next
worldwide pandemic and saving millions of lives, building on
research just published last week. I'm also optimistic that an
effective vaccine for HIV/AIDS will be available at last,
giving us the opportunity to bring an end to this most
frightening and costly global epidemic.
Prediction number eight. Genomics, neuroscience, and
structural biology will collaborate to unveil entirely new
targets for the treatment of pain, allowing researchers in the
public and private sectors to develop highly effective, non-
addictive medications for pain management. Having just attended
and spoken at the Prescription Drug Abuse Summit last week, I
can underline the urgency of reversing the alarming trend of
opioid addiction in America, leading to 28,000 overdose deaths
in 2014. We need new alternatives for pain management, and NIH
and our partners will develop them.
Number nine. Ten years from now, we will have developed and
broadly applied approaches to medicine that acknowledge not all
people are the same, thanks in large part to the Precision
Medicine Initiative and the more than 1 million volunteers that
will have joined this unprecedented national research cohort.
The willingness of these participants to share a wide variety
of their health-related information will ensure that major new
insights emerge, and Americans from all walks of life will be
healthier than ever 10 years from now.
And, finally, for advance number 10, I predict that a
decade from now, hundreds of thousands of individuals, like
Janet in Washington, will be thriving, who, without NIH's
research efforts, would have succumbed to cancer. Powerful new
prevention strategies and targeted therapies will arise from
the research described in the just published article which you
see at your places, all of this accelerated by the Vice
President's personal leadership of this Cancer Moonshot.
If that sounds bold, consider what's happening right now.
Seven months ago, President Jimmy Carter revealed that melanoma
had spread to his brain and that he was beginning a course of
therapy to boost his immune system's ability to destroy his
cancer cells. All of our hearts sank to hear that news. Last
month, President Carter announced he is cancer-free and no
longer needs treatment.
I could tell you a lot more stories like that of President
Carter, but there are still millions out there waiting and
hoping for a breakthrough to happen for them. At NIH, we seek
to turn those hopes into reality. We are the National
Institutes of Health, but we are also the National Institutes
of Hope, and hope, wrote Peter Levi, in every sphere of life is
a privilege that attaches to action. At NIH, we are all about
action, and supported by this committee, who is also all about
action, and your sustained efforts, we believe we can implement
a strong, stable trajectory for NIH research, and the world can
look forward over the coming decades to a healthier and happier
future.
Well, thank you, Mr. Chairman. My colleagues and I welcome
your questions.
[The statement follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good morning, Chairman Blunt, Ranking Member Murray, and
distinguished Members of the Subcommittee. As you know, I am Francis S.
Collins, M.D., Ph.D., and I am the Director of the National Institutes
of Health (NIH). It is an honor to appear before you today to present
the Administration's fiscal year 2017 budget request for the NIH, and
provide an overview of our central role in enhancing the Nation's
health through scientific discovery.
Before I discuss our diverse investments in biomedical research and
the exciting scientific opportunities on the horizon, I want to thank
this Subcommittee for the recent $2 billion boost in the fiscal year
2016 Omnibus Appropriation bill. This investment comes at a time of
unprecedented scientific opportunity and we are truly grateful for your
leadership.
As the Nation's premier biomedical research agency, 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 illness and disability. I can report to you
today that NIH leadership, employees, and grantees continue to believe
passionately in our mission.
As a Federal research agency, we are acutely aware that in order to
achieve our mission we must be effective and efficient stewards of the
resources we have been given by the American public. In December 2015,
we released the NIH-Wide Strategic Plan, fiscal years 2016-2020:
Turning Discovery into Health, an overarching, strategic plan that
reflects the rapid progress in bioscience. This plan ensures our agency
remains well positioned to capitalize on new opportunities for
scientific exploration and address new challenges for human health.
Developed after hearing from hundreds of stakeholders and scientific
advisers, and in collaboration with leadership and staff of NIH's
Institutes, Centers, and Offices (ICOs), the plan is designed to
complement the ICOs' individual strategic plans that are aligned with
their specific congressionally mandated missions.
The plan focuses on four essential, interdependent objectives that
will help guide NIH's priorities over the next 5 years as it pursues
its mission and optimizes return on public investment. The objectives
are to:
--advance opportunities in biomedical research, from basic science to
prevention and treatment;
--use all available information to set NIH priorities nimbly and
wisely;
--enhance stewardship of the resources provided by the American
people; and
--excel as a Federal science agency by managing for results.
Our strategic plan concludes with a bold vision of advances we will
strive to deliver over the next 5 years including: enhanced survival of
cancer patients from applications of precision medicine, critical steps
toward universal flu and HIV vaccines, and crucial progress on the
artificial pancreas that will lead to better management of diabetes.
NIH will pursue these and many other forward-looking measures to
enhance our role as a visionary steward of the resources entrusted to
us by the American people. Such actions will ensure that the U.S.
biomedical research enterprise remains on the pathway to a bright and
sustainable future.
Today, I want to share with you a few of the many promising
opportunities before us that will lead to that healthier future for
all. First, of all, many recent breakthroughs stem from our Nation's
commitment to investing in basic science research. Basic science lays
the foundation for advances in disease diagnosis, treatment, and
prevention by providing the building blocks for clinical applications.
Basic science is generally not supported in the private sector, and
NIH's focus on understanding fundamental biological processes not only
has led to no less than 145 Nobel Prizes to our grantees, but fosters
innovation and ultimately leads to effective ways to treat complex
medical conditions.
A compelling example of how we are trying to unravel life's
mysteries through basic science is with the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative, which
continues to address basic neuroscience questions. We are grateful to
this subcommittee for its support of this initiative since its launch
in fiscal year 2014, and we look forward to ramping this up further in
fiscal year 2017. This bold, multi-agency effort to revolutionize our
understanding of the human brain will enable the development and use of
innovative technologies to produce a clearer, more dynamic picture of
how individual cells and neural circuits interact in both time and
space. By measuring activity at the scale of neural networks in living
organisms, we can begin to decode sensory experience and, potentially,
even memory, emotion, and thought. Ultimately, the technologies
developed under the BRAIN Initiative may help reveal the underlying
pathology in a vast array of brain disorders and provide new
therapeutic avenues to treat, cure, and prevent neurological and
psychiatric conditions such as Alzheimer's disease, autism,
schizophrenia, epilepsy, traumatic brain injury, and addiction.
Scientific advances are also accelerating progress toward a new era
of personalized medicine. President Obama announced the Precision
Medicine Initiative (PMI) in January 2015, and we are thrilled to have
a lead role in this multi-agency effort. As a long-term goal of this
Initiative, NIH is building a national research cohort of one million
or more volunteers who will play an active role in how their genetic,
environmental, and medical information is used for the prevention of
illness and management of a wide array of chronic diseases.
Capitalizing on the alignment of scientific opportunities created by
advances in genomics, the widespread adoption of electronic health
records, the recent revolution in mobile health technologies, and the
emergence of computational tools for analyzing large biomedical data
sets, precision medicine is poised to usher in a new era in how we
treat and diagnose disease. Ramped up funding in fiscal year 2017 will
support several activities that are critical to the scope of the PMI
Cohort Program, including enrolling and consenting participants, core
phenotyping, expanded informatics, building a biorepository, and
incorporating the use of wearable sensors.. A cohort of this size will
capture data on a wide range of diseases and be large enough to detect
genetic and environmental effects that are difficult to discern from
research on smaller groups. Scientists will be able to use data from
this cohort to identify trends and understand health and disease on a
much larger scale, and that will lead to new ideas for diagnostic
tests, treatments, and prevention strategies.
A final area of exceptional scientific opportunity I want to
highlight today involves one of our Nation's most feared killers:
cancer. During his 2016 State of the Union Address, President Obama
announced the establishment of the National Cancer Moonshot--a bold
initiative to tackle this often life-threatening disease. Too many
American families know all too well the devastation cancer can bring.
More than 1.6 million new cases of cancer will be diagnosed and cancer
will kill an estimated 600,000 Americans in 2016. With passionate and
principled leadership from Vice President Biden, and in partnership
with the Food and Drug Administration (FDA) and other Federal agencies,
NIH's National Cancer Institute (NCI) is launching a bold and promising
cancer research initiative to accelerate research to prevent, diagnose,
and treat cancer. In fiscal year 2017, $755 million in mandatory funds
for new cancer-related activities are proposed at the Department of
Health and Human Services (HHS). Within NIH, investments of $680
million will support cutting-edge opportunities, such as prevention and
cancer vaccine development, early cancer detection, cancer
immunotherapy, genomic analysis of tumor cells, enhanced data sharing,
and new approaches to pediatric cancer. Our sister agency, the FDA,
will develop a virtual Oncology Center of Excellence to expedite the
development of new diagnostics and therapeutics that will be safe and
effective. We are at an inflection point in cancer research, and the
science is ready for the concerted new effort this initiative will
bring.
While all of these exciting research efforts and scientific
opportunities are leading to a much deeper understanding of health and
human disease, much more work needs to be done.
To this end, the President's fiscal year 2017 budget request for
the NIH is $33.136 billion, $825 million or 2.5 percent above the
enacted fiscal year 2016 level. This budget request reflects the
President's and the Secretary's commitment to improving the health of
the Nation and to maintaining our Nation's leadership in the life
sciences. The request highlights investments in innovative research
that will advance fundamental knowledge, and speed the development of
new therapies, diagnostics, and preventive measures to improve public
health, including an additional $100 million to ramp up the PMI Cohort
Program to a total of $230 million, an increase of $45 million for the
BRAIN Initiative, bringing the total to $195 million, and $680 million
for the National Cancer Moonshot.
The fiscal year 2017 budget request will enhance NIH's ability to
support cutting-edge research and training of the scientific workforce.
Within this budget, we will increase Research Project Grants (RPGs),
NIH's funding mechanism for investigator-initiated research. NIH
expects to support 36,440 total RPGs in fiscal year 2017, an increase
of 600 above the fiscal year 2016 estimate. The budget request
allocates resources to areas of the most extraordinary promise for
biomedical research, while maintaining the flexibility to pursue
unplanned scientific opportunities and address unforeseen public health
needs.
I have provided you with examples of how investments in biomedical
research through NIH are advancing human health, spurring innovations
in science and technology, stimulating economic growth, and laying the
groundwork for the future of the United States biomedical research
enterprise. We have never witnessed a time of greater promise for
advances in medicine than right now. With your support, the future of
medicine can be very bright.
This concludes my testimony, and I look forward to answering your
questions.
______
Prepared Statement of Douglas R. Lowy, M.D.
Mr. Chairman and Members of the Committee, I am pleased to present
the President's fiscal year 2017 budget request for the National Cancer
Institute (NCI) of the National Institutes of Health (NIH).
nci budget overview
The fiscal year 2016 budget that this subcommittee approved for NCI
reflects a genuine understanding that this is a transformational moment
for cancer patients and cancer research, and that the era of precision
oncology is within reach. The $70 million that you approved to fund the
precision medicine for oncology initiative will foster a new era of
medical practice where detailed genetic and other information about a
patient's cancer is routinely used to deploy effective, patient-
specific remedies to treat it. Other increases for fiscal year 2016
will allow NCI to broadly advance and successfully integrate the many
disciplines necessary to improve outcomes for patients with all types
of cancer.
For fiscal year 2017, NCI is advancing a new $680 million
initiative--known as the Cancer Moonshot Initiative--to accelerate
progress across the entire field of cancer prevention, treatment, and
discovery. However, in addition to the resources for the Moonshot
initiative, NCI's $5.9 billion budget supports a range of other
research that is essential to achieving sustained progress in cancer.
This includes:
--basic research, including genetics, cell biology, and cancer
pathogenesis;
--translational and clinical sciences to prevent, screen, and
diagnose cancer, and to develop and test drugs, biomarkers,
imaging, diagnostics, and radiotherapies; and
--population studies, including epidemiological, environmental, and
behavioral research.
Cancer Prevention: During fiscal year 2017 and beyond, preventing
cancer and screening for cancer will remain a central priority for NCI.
Prevention takes many forms, such as controlling tobacco use,
vaccinating against cancer-causing infectious agents such as human
hepatitis B virus and human papillomaviruses, limiting exposure to
sunlight, and limiting exposure to asbestos and other carcinogens.
These priorities have contributed to reducing the incidence and
mortality rates for many cancers. NCI continues to invest heavily in
cancer screening and prevention because we know that much more progress
is possible for those at risk of cancer.
In parallel with our focus on prevention, NCI also will give
increased attention to cancer health disparities--the differences in
cancer incidence, prevalence, treatment response, and mortality among
different population groups. Reducing and eliminating cancer health
disparities requires a deeper understanding of the complex interplay
among a range of factors--biological, behavioral, environmental, and
socioeconomic--that may contribute to the unequal burden of disease.
vice president's cancer moonshot initiative
For fiscal year 2017, NCI will launch a bold and promising cancer
research initiative designed to make broad advances across a range of
exciting opportunities to prevent, diagnose, and treat cancer. The
resources supporting this fiscal year 2017 initiative will allow NCI to
accelerate the pace of discovery in ways that produce tangible benefits
for patients with all types of cancer, those at risk of cancer, and the
growing population of cancer survivors.
The NCI budget justification identifies seven elements that form
the core of the fiscal year 2017 initiative. These seven elements also
can be organized into two broad themes: research on cellular analysis
and research on novel approaches to prevent, diagnose, and treat
cancer. In addition, some elements of the initiative contribute to both
of these themes.
Theme I--Cellular Analysis: Three elements of the fiscal year 2017
NCI initiative support the cellular analysis theme.
A. Detecting Cancer Earlier: Even small tumors shed biomarkers into
fluids of the body, such as the blood, saliva, and urine. Recent
advances in genomic and proteomic technologies have greatly increased
the sensitivity of methods to detect biomarkers in fluids, which raises
the possibility of using such methods to screen for and identify
cancers earlier. Such minimally invasive methods have recently been
used for assessing whether cancer has recurred in individuals who were
previously diagnosed and treated. The exciting new opportunity, for
which NCI will use the resources in this fiscal year 2017 initiative,
is to now apply these methods to cancer screening. The goal is to
detect at a very early stage a range of cancer types for which we do
not yet have effective screening methods and to improve the detection
of cancer types for which screening is already established practice.
B. Research on Mutations: The resources in the fiscal year 2017
initiative also will allow NCI to support discoveries related to
mutations and the mechanisms of cancer. Gaining a greater understanding
of the mutations that occur within the cancer cell, the changes that
occur within surrounding stromal tissues, and the nature of the immune
system's response to cancer will serve as a springboard to advance
immunotherapy and targeted drug therapy.
Such research also can identify mechanisms used by cancer cells to
co-opt the vascular tissue and other parts of the micro-environment
near the cancer. Moreover, this approach can identify what type of
immune response is already present, but may need a boost to combat the
cancer. Coupling this information with the clinical response to drug
therapy and immunotherapy could greatly enhance our understanding of
the therapeutically relevant interplay between the tumor and the many
cell types that surround it, leading to an increased ability to improve
patient responses to treatment.
C. Speeding Progress on Childhood Cancers: Cancer in children poses
unique challenges. Childhood cancers generally possess many fewer
mutations than adult cancers and are less likely to have activation of
enzymes known as kinases, which are the most frequent targets of cancer
drugs for adult tumors. Furthermore, characteristic molecular changes
that drive many childhood cancers arise in transcription factors and
other cellular targets that are often considered ``undruggable.''
However, new technologies, built upon advances in chemistry that allow
the preparation of libraries of small chemical molecules with a much
more complex arrangement of molecular shapes, offer the promise of
identifying inhibitors for the abnormalities found in pediatric
cancers. The resources in NCI's fiscal year 2017 initiative will
support research such as this to deliver advances and treatments for
pediatric cancers.
Theme II--Novel Approaches to Prevent, Diagnose, and Treat Cancer:
Two elements of the fiscal year 2017 NCI initiative will advance the
novel approaches theme.
A. Cancer Immunotherapy and Combination Therapies: For fiscal year
2017, NCI will provide increased support to promising research that
employs the cells of the immune system to attack cancer. Immunotherapy
is based on the principle that a patient's immune system, when properly
primed, can often detect and destroy cancer cells.
However, the challenge of immunotherapy is two-fold: first, tumors
often effectively blunt anti-tumor immune responses, and second, the
immune system must be successfully primed to recognize the tumor.
Despite these challenges, during the past few years there have been
some remarkable successes in overcoming these problems. NCI is working
to extend these early successes in cancer immunotherapy to virtually
all tumor types through improved understanding of the mechanisms that
enable and limit immunotherapy.
This element of the initiative will also support advanced research
on combination therapies. Compared with single agent treatment,
combinations of drugs that impair the growth and development of tumors
along multiple molecular pathways are more likely to prevent the
development of resistance and to produce long-lasting remissions.
However, to benefit more patients, we urgently need to identify and
understand the most effective combinations of targeted agents or
targeted agents used in combination with immune-modulating molecules.
B. Vaccines to Prevent or Treat Cancer: Vaccines against cancer-
causing infections can prevent certain cancers. The NCI research that
led to pediatric vaccines to prevent infection with human
papillomavirus (HPV)--and thereby prevent cervical and some other
mucosal cancers--represents an important milestone in cancer
prevention. The most advanced HPV vaccine prevents the infections that
account for about 90 percent of these cancers. Cancer vaccine
development will receive increased resources under NCI's fiscal year
2017 initiative.
Developing vaccines to treat early stage cancers and pre-malignant
lesions not related to infections is another exciting opportunity that
NCI will target with additional resources under the fiscal year 2017
initiative. Such vaccines can target unique or signature genetic
changes found in cancers and premalignant lesions. Candidate lesions
include those found in patients with early prostate cancer, patients
with premalignant lesions such as ductal carcinoma in situ (DCIS) in
the breast, and patients with genetic abnormalities that place them at
high risk of colorectal cancer.
III--Important Cross-Cutting Elements: Finally, two elements of the
NCI fiscal year 2017 initiative will broadly contribute to both of the
themes identified above.
A. Data Sharing to Speed Discovery and Verify Treatment Response:
Robust data science--managing enormous sets of molecular and clinical
data--is essential in modern cancer research. ``Big data'' is a
critical requirement for work that ranges from cancer genomics to
research on cell signaling and to clinical trials, using efficient
collection, storage, retrieval, analysis, and distribution of
information. Without robust data science and a strong informatics
infrastructure, the pace and scope of cancer research will be limited.
Establishing this advanced information technology capability will
allow NCI to assemble tens of thousands of cases that have been
carefully annotated with clinical and detailed molecular information.
These shared bioinformatic resources will greatly increase our
understanding of cancer and improve our ability to select the most
appropriate treatment for patients.
B. Exceptional Opportunities--Funding Other Promising Research: The
Exceptional Opportunities element of the initiative will allow NCI to
capitalize on exciting scientific opportunities by awarding research
funding--prioritized through a competitive process--to pursue
innovative new ideas that target intractable problems in cancer
science. NCI will examine novel opportunities in any area of oncology
research ripe for expansion, from basic science, through translational
approaches, to clinical trials. NCI will support Exceptional
Opportunities research at academic sites and through public-private
partnerships as a means of generating breakthrough results in cancer
science and treatment.
the role of ncab
The National Cancer Advisory Board (NACB) will provide advice and
recommendations to NCI on the Moonshot initiative. In addition, on
April 4, 2016, NCI announced the membership of a Blue Ribbon Panel of
scientific experts, cancer leaders, and patient advocates as a working
group of NCAB. The panel will share their insights on the scientific
direction and goals for all elements of the initiative and offer
recommendations on other compelling research opportunities. This will
allow NCI to receive broad scientific counsel about the design and
implementation of the initiative and its research and resource
priorities, including the Exceptional Opportunities Fund.
We are eager to receive recommendations from NCAB and the Blue
Ribbon Panel about the direction and emphasis for proposed research
under the fiscal year 2017 initiative.
conclusion
The NCI budget supports core, ongoing biomedical research that will
advance scientific discovery and continue to reduce the burden of
cancer in America. Our budget will also fund a compelling new
initiative that offers the potential to accelerate the rate at which we
translate discoveries into cancer clinical practice and deliver
benefits to patients.
Despite meaningful progress in recent years, too many Americans
face a cancer diagnosis, and far too many die from the disease. There
will be more than 1.6 million new cases of cancer in the United States
during 2016, and more than 600,000 will die from cancer. As these
statistics demonstrate, much work remains to meet the needs of those
suffering from cancer, those at risk of cancer, and the growing
population of cancer survivors. The fiscal year 2017 budget will allow
NCI to advance our cancer research mission and deliver important
results for the patients we serve.
______
Prepared Statement of Walter J. Koroshetz, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of Neurological Disorders and Stroke (NINDS) of the National
Institutes of Health (NIH). NINDS supports research to better
understand the brain and nervous system and to improve the diagnosis,
treatment, and prevention of nervous system disorders. The burden of
stroke, traumatic brain injury (TBI), dementia, chronic pain, epilepsy,
Parkinson's disease, multiple sclerosis, and other all too familiar
disorders of the nervous system is enormous. Hundreds of rare diseases
add to the collective impact. The number, variety, and complexity of
neurological disorders present formidable challenges, and the
inaccessibility of the brain and its sensitivity to intervention
compound the difficulty. Nonetheless, NIH research is delivering
progress, directly and by catalyzing private sector investment.
Moreover, with increasing recognition of commonalities among underlying
disease mechanisms, progress against each disorder will spur advances
against others.
stroke, dementia, and tbi
The United States' age-adjusted stroke death rate fell by 77
percent from 1969 to 2013, and NIH research is sustaining this
trend.\1\ In 2015, the Systolic Blood Pressure Intervention Trial
(SPRINT) showed that, for people with certain common risk factors, more
stringent than usual blood pressure control lowered the risk of death
from heart attack or stroke by almost a quarter, and in 2016 the
Insulin Resistance Intervention after Stroke (IRIS) trial demonstrated
that pioglitazone, a diabetes drug, prevents many recurring strokes in
people with insulin resistance. Also last year, decades of public and
private research led to the most significant advance in acute stroke
care since NINDS clinical trials of the clot busting drug tPA showed
that stroke is a treatable emergency. The recent results show that
intravascular devices can remove an offending clot from a blocked brain
artery and provide striking benefit when tPA alone does not restore
blood flow in severe strokes. StrokeNet, a new clinical network, is
investigating who should receive this intervention, and other stroke
prevention and treatment trials are underway.
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\1\ JAMA 314:1731-1739 2015.
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The National Alzheimer's Project Act recognized the impact of not
just Alzheimer's disease, the most common dementia, but also
Alzheimer's disease-related dementias (ADRDs). The National Plan to
Address Alzheimer's Disease includes research recommendations from a
2013 NINDS-led summit on ADRDs, implementation has begun, and a follow
up ADRD Summit in 2016 will continue to guide NIH dementia research.
ADRD's include, for example, Lewy Body dementia, Parkinson's dementia,
and frontotemporal dementia (FTD), which is the most common dementia in
people younger than age 60. The most common ADRD, Vascular Cognitive
Impairment and Dementia (VCID), like stroke, affects brain blood
vessels. VCID is so intertwined with Alzheimer's disease that most
elderly people with dementia have a combination of the two. The new NIH
Molecular Mechanisms of the Vascular Etiology of Alzheimer's Disease
(M2OVE-AD) Consortium will investigate how the brain's blood vessels
contribute to dementias to identify new targets for treatment and
prevention.
The growing recognition of intersections among stroke and VCID is
encouraging in light of the progress in preventing stroke. Although
increases in dementia loom as our population ages, there are indeed
hopeful signs. In the Framingham Heart Study, the rate of dementia fell
by 44 percent from the late 1970s to the early 2010s, and age of
dementia onset was delayed by 5 years over that period.\2\ What
accounts for this progress is not fully understood, but converging
evidence from the Reasons for Geographic and Racial Differences in
Stroke (REGARDS) study, the Honolulu-Asia Aging study, the
Atherosclerosis Risk in Communities (ARIC) study, the Northern
Manhattan study, and other research suggests that controlling blood
pressure reduces risk for cognitive decline in later life. A new public
health campaign ``Mind Your Risks'' promotes controlling blood pressure
for maintaining a healthy brain.
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\2\ New England Journal of Medicine 374:523-32, 2016.
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Nearly a century ago, physicians recognized another type of
dementia, called dementia pugilistica, in boxers. In the modern era,
neuropathologists are detecting this disorder, now called chronic
traumatic encephalopathy (CTE), in autopsied brains of professional
(and a few younger, amateur) athletes from contact sports. This has
heightened the urgency of understanding the long-term consequences of
mild TBI, or concussion, for the millions of people who have been
exposed through sports, military service, or the risks of daily life.
Despite decades of NIH research, including laboratory studies, brain
imaging, and helmet impact monitoring in college athletes, many aspects
of concussion are poorly understood. To augment ongoing research, NINDS
and the Foundation for NIH's Sports and Health Research Program, which
was launched with a donation from the National Football League,
established two multi-institution research consortia on CTE. In 2015,
these neuropathologists took a major step forward by developing
criteria that identify CTE and reliably distinguish it from other
diseases in autopsied brain tissue. Studies applying these criteria on
brains donated to brain banks for neurological disorders are
reinforcing the concern that these long-term consequences of TBI may be
more common than previously thought. The CTE consortia and a multi-site
longitudinal study funded by NINDS in 2015 are addressing a major
impediment to progress by testing brain imaging methods to diagnose CTE
reliably in living people. A brain protein called tau, which
accumulates abnormally in the brain in CTE, is the focus of a promising
imaging method. Tau is also implicated in Alzheimer's and other
neurodegenerative disorders, reflecting the wider theme that abnormal
protein degradation, accumulation, and propagation are involved in many
brain diseases.
brain connections and brain disorders
Stroke and TBI are also among the many causes of the epilepsies,
which are characterized by abnormal brain activity that causes
seizures, and epilepsy-like brain activity may occur in Alzheimer's
disease. The epilepsies have many different causes. Hundreds of gene
mutations cause epilepsy, including many identified by the NINDS Center
without Walls (CWOW) on epilepsy genetics. Anti-seizure drugs,
including ten that the NINDS Anticonvulsant Screening Program helped
develop, can treat epilepsy. However, all epilepsy drugs have
troublesome side effects, no existing drugmodifies the underlying
disease, and a third of people who have epilepsy do not respond well to
any drug. A new CWOW will develop strategies to prevent epilepsy or to
modify the disease process, rather than suppressing seizures.
Some diseases, like autism and epilepsy, are fundamentally
disorders of brain cell activity and circuitry, and others, such as
TBI, stroke, Parkinson's, and Alzheimer's disease, disrupt brain
circuits as nerve cells or their connections are compromised. Despite
our limited understanding of brain circuits and the imprecise
technologies for altering brain cell activity in people, interventions
that compensate for malfunctioning brain circuits produce remarkable
results. Deep brain stimulation (DBS) dramatically reverses some
symptoms for many people with essential tremor, Parkinson's disease,
and dystonia, and shows promise for epilepsy, Tourette syndrome, and
several other disorders. Decades ago the NINDS Neural Interfaces
Program led development of cochlear implants, which restore useful
hearing to thousands of people by translating sound into electrical
signals that brain circuits can interpret. More recently, that program
pioneered devices that allow paralyzed people to control a robotic arm
by commands directly monitored from their brains' movement control
circuits.
Better understanding of brain circuits and more precise means to
control them would greatly improve these interventions and likely
reveal unforeseen therapeutic strategies. Basic neuroscience research
has made remarkable discoveries at the molecular level about how brain
cells and synapses operate. And brain imaging, such as The Human
Connectome Project, has driven advances in understanding how areas of
the normal brain work together. Until recently, however, researchers
have had limited tools to map the intricate synapse by synapse
structure of brain circuits or to monitor or control the activity of
the large numbers of nerve cells in a working brain circuit. New
methods are essential to understand precisely how brain circuit
dysfunction underlies brain diseases. The Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative is providing
scientists with tools that are transforming understanding of how
circuits work. Researchers have already, for example, turned on and off
specific memories in laboratory animals, and found important clues to
what goes wrong in movement control circuits in Parkinson's disease.
Public-private partnerships have been facilitated to develop and test
cutting edge stimulation and recording technologies for patients with
epilepsy and Parkinson's disease.
people
NINDS carries out its mission within an ecosystem that includes the
public, nongovernmental organizations, for profit companies, and the
academic research community. NINDS engages all stakeholders in
strategic planning and planning for specific diseases and issues,
including heath disparities and workforce diversity. NINDS also works
closely with other parts of NIH and with other Federal agencies. The
Federal Interagency TBI Research Informatics System (FITBIR) and the
Center for Neuroscience and Regenerative Medicine (CNRM), for example,
are among the many ways NIH and the Department of Defense cooperate on
TBI. NINDS relies heavily on investigator-initiated research, which
harnesses the insight and ingenuity of the U.S. research community,
because of its track record of stimulating breakthroughs. When gaps are
compelling, NINDS targets resources to unmet mission-critical
scientific opportunities and public health needs. Among the many
examples are the NeuroNext clinical network, which carries out early
phase clinical trials of therapies from the academic or private sector,
and centers or consortia in epilepsy, Parkinson's disease, autism,
muscular dystrophy, and TBI. Policies and resources, such as brain
banks, data centers, and gene and tissue repositories, enhance the
research possible for individual researchers and promote sharing. To
maximize research value, NINDS is among the leaders in advocating
transparency of reporting and reproducibility of research, engaging
researchers, peer reviewers, journal editors, trainees, and NIH staff.
Because the private sector is often reluctant to tackle
neurological disorders, NINDS supports preclinical therapy development.
These programs have recently, for example, developed candidate drugs,
gene therapy, or biologics for ALS, muscular dystrophy, brain tumor,
and stroke to readiness for clinical testing. From its inception, NINDS
has played an indispensable role in rare disease research. Programs now
bring academic disease experts together with drug development resources
and knowhow. A current project, for example, is developing drugs for
familial dysautonomia. It reflects a 23-year journey that identified
the genetic cause, developed a screen for at-risk populations,
engineered a mouse model, and screened for drugs that reverse symptoms
in mice. The first drug for this disease is now in clinical trials. As
the first therapies for several rare disorders are moving to clinical
testing, NINDS is promoting clinical trials readiness, and NeuroNext is
poised to expedite early phase trials.
Physicians and scientists in the public and private sector agree
that basic research is essential for progress against neurological
disorders, but without government support, basic neuroscience would
scarcely exist. Some shift toward more applied research is appropriate
given the remarkable opportunities arising from basic research.
However, an extensive NINDS analysis revealed a decline over several
years in the number of grant applications for fundamental research on
the healthy brain. The Institute is holding the line against that
trend, including targeted support with set-aside funds. The BRAIN
Initiative reinforces NINDS emphasis on basic research and innovation.
In fiscal year 2016, NINDS also launched the Research Program Award
(RPA) to spur innovation, especially in basic research. The RPA
application, review criteria, and award duration accentuate the
investigators' promise and the long term significance of the proposed
research program, rather than the details of proposed experiments.
Finally, NINDS must recruit and develop the best scientists and
physicians from the full breadth of the Nation's talent pool. NINDS
supports an array of training and career development opportunities to
attract a vibrant and diverse scientific workforce. The inherent allure
of understanding the brain attracts many of the brightest students, as
do the prospects for progress against neurological disorders, which
have never been so encouraging. Whether people will embark on training
for scientific careers depends on their perception of the Nation's
commitment to supporting research in the future.
______
Prepared Statement of Richard J. Hodes, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute on Aging (NIA) of the National Institutes of Health (NIH).
Census data indicate that the number of Americans ages 65 and
older, currently estimated at over 43 million strong, will likely
double by 2040. Because aging remains the single most important risk
factor for most chronic diseases and degenerative conditions in adults,
it is imperative that we pursue a comprehensive national effort to
understand aging and to develop interventions that will help older
adults enjoy robust health and independence, enabling active engagement
with their families and communities.
NIA leads this effort in support genetic, biological, clinical,
behavioral, and social research related to the aging process, healthy
aging, and diseases and conditions that increase with age. We also
support training of the next generation of researchers. In addition, we
are the lead Federal agency supporting research on Alzheimer's disease
(AD).
research on alzheimer's disease
Data from several recent studies suggest that the rate of dementia,
including AD, is actually decreasing. For example, researchers with the
long-running Framingham Heart Study found that there was a progressive
decline in incidence of dementia at a given age, with an average
reduction of 20 percent per decade since the 1970s. The decline was
more pronounced with a subtype of dementia caused by vascular diseases,
such as stroke, and was observed only in persons with high school
education and above. These results are consistent with findings from
other recent studies in the United States and Canada, and it is our
hope that as we identify factors that contribute to this unprecedented
decline, we will also identify potential preventive strategies or even
clarify the disease process itself.
Despite this promising trend, however, it is estimated that as many
as 5.2 million Americans currently have the most common form of
dementia--Alzheimer's disease. Scientists agree that unless the disease
can be effectively treated or prevented, the numbers of people affected
will increase significantly if current population trends continue. And
in addition to the severe medical and psychological costs to patients
and their families, AD and related forms of dementia impose significant
societal and individual economic costs. One recent NIA-funded study
found in the last 5 years of life, total healthcare spending for people
with dementia was more than a quarter-million dollars per person, some
57 percent greater than costs associated with death from other
diseases, including cancer and heart disease.
As the Federal lead on Goal 1 of the National Action Plan to
Address Alzheimer's Disease--Prevent and Effectively Treat Alzheimer's
Disease by 2025--NIA continues to move forward on a number of fronts,
informed by input from researchers and advocates worldwide from the
February 2015 Alzheimer's Disease Research Summit, the 2013 Summit on
Alzheimer's-Related Dementias, and other key scientific conferences and
emerging research findings. Additional funds directed to Alzheimer's in
recent years are being used to accelerate research identifying new risk
and protective genes; development of new cellular models of the disease
to enable rapid screens of hundreds of thousands of molecules for
potential as therapeutic agents; establishment of translational centers
that will develop and apply cutting-edge approaches to drug
development; population studies of trends in the incidence and
prevalence of dementia; development of novel interventions to support
dementia caregivers; and trials of therapies in people at the highest
risk of disease.
Other researchers are repurposing existing compounds for use in AD.
For example, investigators funded by NIA and the National Center for
Advancing Translational Sciences found that AZD0530, a compound that
has been used experimentally to treat some solid tumors, reversed
memory loss and pathology characteristic of AD in a mouse model and is
a promising candidate to test in humans with the disease.
Notably, in September/October 2015, NIA released a series of 10
Program Announcements (PAs) soliciting funding applications across the
spectrum of AD research. These requests for applications offer
opportunities for investigators in virtually every aspect of AD
research--from basic biological studies to epidemiology to caregiving
to clinical trials. The initial response to these PAs was extremely
robust, and initial awards are anticipated for late fiscal year 2016.
Alzheimer's is also a primary focus of NIH's Accelerating Medicines
Partnership (AMP), a joint public-private partnership to transform the
current model for developing new diagnostics and treatments by jointly
identifying and validating promising biological targets of disease. In
March 2015, AMP-AD launched its Alzheimer's Big Data Portal and
concomitantly released the first wave of data through this new
resource, facilitating sharing and analyses of large and complex
biomedical datasets. This approach will enable the development of
predictive models of AD and the selection of novel targets that drive
the changes in molecular networks leading to the clinical signs and
symptoms of the disease.
NIH's plans, priorities, and recent accomplishments for Alzheimer's
research are presented in our first Bypass Budget for Alzheimer's
Disease and Related Dementias, in response to a Congressional
directive.\3\ This comprehensive professional judgment proposal for
fiscal year 2017, which was developed without taking into account the
full range of resource constraints and competing priorities that the
President's Budget must consider, was released in July 2015 and will be
updated annually, informed by expert input from several key sources.
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\3\ Https://www.nia.nih.gov/alzheimers/bypass-budget-fy2017.
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advances in aging research
NIH supports research aimed at improving our understanding of the
changes seen with aging at the physical, cognitive, behavioral, and
social levels, as well as development of interventions to prevent or
ameliorate age-related disease and dysfunction. For example, NIA-
supported investigators recently found that naturally-occurring
senescent cells that accumulate in the body shorten lifespan in mice,
and that removing those cells delays age-related organ dysfunction.
This finding aligns with previous research and provides additional
support for the hypothesis that removal of senescent cells may be an
effective approach to extending healthy lifespan.
NIA coordinates the NIH GeroScience Interest Group (GSIG), which
was established in 2012 to accelerate and coordinate efforts to promote
further discoveries on the mechanisms that link aging biology to the
etiology of multiple chronic diseases and conditions, by developing a
collaborative framework that includes multiple NIH Institutes. In
October 2013, the GSIG and several private-sector partners convened a
national Summit entitled ``Advances in Geroscience: Impact on
Healthspan and Chronic Disease.'' This meeting drew over 500 expert
participants from around the world and led to the publication of a
position paper in Cell, one of the world's leading journals on basic
research, in 2014. A second Geroscience Summit is planned for April
2016 in collaboration with the New York Academy of Sciences and others.
NIA also continues to support its flagship studies on aging. As it
approaches its sixtieth anniversary, the groundbreaking Baltimore
Longitudinal Study of Aging (BLSA) continues its work toward
identifying the longitudinal physical and cognitive changes that define
aging; identifying the factors that affect the rate of age-related
change; and understanding the relationship between aging and chronic
disease. BLSA investigators are particularly interested in
``exceptional agers''--those rare individuals who live well into their
eighties with few health problems. In addition, this year the Health
and Retirement Study (HRS) will complete 25 years of data collection
and will implement several enhancements: addition of respondents
representing the ``Late Baby Boom'' born 1960-1965; deployment of an
improved approach to assessing cognitive impairment and dementia; and
expansion of collection of objective health measures, including blood-
based assays capturing the aging of the immune system and related
molecular and cellular age-related changes. This and other future work
also has the potential to reveal the biological pathways through which
differences between social and demographic groups affect health.
NIA-supported investigators are looking at better ways to translate
what we know into clinical practice that will help improve the health
and well-being of older Americans. For example, a recent clinical trial
identified several interventions directed at primary care clinicians
that reduced the number of inappropriate prescriptions for antibiotics
for acute viral respiratory tract conditions, an important cause of
population-level antibiotic resistance. These interventions--which
involved prompting a clinician to record a justification for
prescribing antibiotics or comparing the clinician's performance to
others in their region--may be useful tools to improve quality of care.
In another recent study, the Systolic Blood Pressure Intervention
Trial (SPRINT), reducing systolic blood pressure to less than 120 mm
Hg, as compared with less than the current standard target of 140 mm
Hg, resulted in lower rates of major cardiovascular events and death
from any cause among patients at high risk for cardiovascular events
but without diabetes. Of particular note is the age of the SPRINT
participants: all were over 50, and 28 percent were over 75. SPRINT was
supported by NIA and several other NIH Institutes.
Serious injuries from falls, such as broken bones or traumatic
brain injury, are a major reason for the loss of independence among
older people. In 2014, the NIA partnered with the Patient-Centered
Outcomes Research Institute (PCORI) to support a large, multi-center
clinical trial to test individually tailored interventions to prevent
fall-related injuries. The study, which is scheduled to conclude in
2019, is ongoing and involves the NIA-funded Claude D. Pepper Older
Americans Independence Centers.
Finally, NIA has continued to grow its award-winning Go4Life
exercise and physical activity campaign. This effort centers on an
interactive website, which features an evidence-based exercise guide in
both English and Spanish, exercise videos, ``virtual'' coaches, and
more. Over 350 partners at both the local and national levels use these
resources in their community activities with seniors. September 2015
was designated national Go4Life Month. Partners sponsored over 600
activities in communities across the United States, culminating in a
Capitol Walk in Washington, D.C., in which a corps of older adults
joined Dr. Hodes, U.S. Surgeon General VADM Vivek H. Murthy, M.D.,
M.B.A., fitness expert Donna Richardson, and leaders from a number of
agencies and organizations for a walk around the National Mall.
empowering the next generation of scientists
As the number of older Americans continues to grow, we must not
only increase the number of practicing physicians trained in geriatrics
and relevant subspecialties but also foster the development of the next
generation of scientists whose research will lead to improved care and
more effective treatment for older patients with complex medical
conditions. To encourage emerging scientists, NIA supports an advantage
in pay line for new and early-stage investigators. The Paul Beeson
Career Development Awards in Aging Research program, sponsored by the
NIA, the National Institute of Neurological Disorders and Stroke, and
private partners, continues to produce leaders in the fields of aging
and geriatrics research. A recent Funding Opportunity Announcement
solicited applications for new training programs for joint M.D.-Ph.D.s
in the social sciences relevant to aging. Finally, the Butler-Williams
Scholars Program (formerly the NIA Summer Institute) remains a vibrant
and vital institution at NIA.
______
Prepared Statement of Christopher P. Austin, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National Center
for Advancing Translational Sciences (NCATS) of the National Institutes
of Health (NIH).
translation
NCATS defines translation as the process of turning observations in
the laboratory, clinic and community into interventions that improve
the health of individuals and the public--from diagnostics and
therapeutics to medical procedures and behavioral changes. An
overarching need to translate research discoveries more efficiently and
effectively led to the creation of NCATS. NCATS is advancing the
relatively new field of translational science, through which
investigators seek to understand the scientific and operational
principles underlying each step of the translational process. These
efforts serve as a basis for system-wide improvements in translational
efficiency and effectiveness to ultimately get more treatments to more
patients more quickly.
Following are examples of NCATS programs directed at overcoming
major scientific and operational bottlenecks in the translational
research process.
transforming the nation's clinical research network capacity
NIH's Institutes, Centers and Offices have a long, distinguished
history of funding landmark clinical trials including those for
coronary bypass surgery, treatments for breast cancer, and anti-
retroviral drugs for people at high risk for HIV/AIDS infection. NCATS
is addressing issues common to all clinical trials including approval
and oversight of research protocols and timely participant recruitment,
which have often resulted in high cost burdens for studies and frequent
delays in implementation. These problems have led some investigators
and companies to conduct their research outside of the United States,
and this threatens our Nation's innovative capacity and
competitiveness, reduces economic opportunities, and deprives patients
of the option to participate in research. In addition, when clinical
investigators set up a clinical trial, they often create agreements and
processes from scratch and abandon those tools at the end of the study,
rather than making use of the existing structure and agreements for any
future studies.
To address these pitfalls and inefficiencies, through its Clinical
and Translational Science Award (CTSA) Program, NCATS has launched
several initiatives designed to work together to strengthen and
streamline our Nation's network capacity to conduct clinical research.
There are more than 50 CTSA Program medical research institutions
across the country that serve as clinical and translational research
hubs. Hub investigators collaborate to support high-quality clinical
and translational research locally, regionally and nationally,
fostering innovation in training, patient involvement and new
methodologies.
NCATS is expanding the networking capacity of the CTSA Program with
the addition of Trial Innovation Centers (TICs) and Recruitment
Innovation Centers (RICs) that address key roadblocks to high-quality,
harmonized, accelerated, efficient and effective multisite clinical
trials. Through TICs, investigators will explore innovative approaches
in streamlining trial implementation and disseminate best practices.
RICs are intended to improve participant recruitment into clinical
trials by using innovative means to assess the availability of
potential participants and to enroll them in a timely manner. NCATS
will make TIC and RIC awards later in fiscal year 2016. When fully
implemented, these centers will be crucial resources for NCATS' CTSA
Program clinical trial innovation network. By making the clinical trial
network available to any investigator or organization wishing to
conduct a clinical trial, the CTSA Program will benefit all clinical
research, including that of other NIH Institutes and Centers (ICs), as
well as other government, industry, academic, and patient advocacy
group sponsors.
innovation to advance pre-clinical translational science
Too often, the laboratory tests that scientists conduct during the
pre-clinical phases of the translational process--research on a drug or
other intervention conducted prior to testing in humans--fails to
predict the safety and effectiveness of a treatment in humans. NCATS is
studying, and developing solutions to overcome, the scientific and
operational roadblocks in this part of the translational research
spectrum as well.
An example is the Tissue Chip for Drug Screening program, which
supports the creation of bioengineered devices to improve the process
of predicting whether drugs will be safe and effective in humans. NCATS
collaborates with the Defense Advanced Research Projects Agency (DARPA)
and FDA to support the development of these three dimensional (3-D)
platforms, sometimes called tissue chips or organs-on-chips, engineered
to mimic the structure and function of living human tissues. Since the
program's inception in 2012, scientists have developed more than 10
different types of individual organ chips. The program is now focused
on integration of organ chips, making it possible to model the
complexity of organ-to-organ interactions in response to drugs. One
such success was the creation of EVATARTM, a miniaturized 3-D
representation of the female reproductive tract and liver on a
handheld, interconnected platform. This advance required a team effort
of scientists from Northwestern University, Charles Stark Draper
Laboratory and the University of Illinois at Chicago (UIC)
collaborating to design the model for use in drug testing and to study
the basic biology of female reproduction. The current success of the
Tissue Chip is indicating future directions for the NCATS program, with
some investigators already using the technology to develop disease
models on chips to both understand the basis for diseases and identify
treatments for them.
In a complementary program, NCATS is developing 3-D bioprinted
human tissues to be used in the earliest stages of drug discovery. This
initiative has the potential to accelerate the drug discovery process,
enabling treatments to be developed faster and at a lower cost by
bridging the predictability gap between the lab test and the test in
humans. The manufacturing technique used to build live tissue
structures results in a product that mimics natural live tissue. Live
cells are harvested and dispensed into spatially-controlled patterns,
layer-by-layer, to generate 3-D arrangements. These structures undergo
further biological treatment until they form tissue-like structures.
The ability to develop 3-D tissue structures on demand will enable the
generation of data that are more relevant to the whole body response
than traditional means, which use two-dimensional, single-layer cell
cultures grown on plastic plates.
Of all translational tools, the most enabling is information, so
NCATS also is developing a variety of informatics resources to collate
and disseminate data that will help advance translational research. For
example, using the flexible funding mechanisms available through NCATS'
Cures Acceleration Network (CAN), NCATS is developing a breakthrough
translational informatics ``matrix'' that will incorporate data about
all diseases, including signs, symptoms, signaling pathways, genes and
treatments. This effort will help empower the generation of new disease
hypotheses and connections, as well as testable predictions of
potential treatments. This is an unprecedented assembly of disparate
data types into a multi-dimensional relational informatics platform and
will be usable by doctors, researchers and non-experts. As such, it
will require extensive and complex teamwork among the scientific,
healthcare and patient communities, and we anticipate the need to use
our CAN Other Transactions Authority. We expect the NCATS' matrix
project to spur innovation in methods, techniques, prevention and
treatments, and to help move from the ``one disease at a time, one
organ at a time'' therapeutic model toward a far more efficient
approach of studying diseases and potential interventions, including
generating new hypotheses that could be tested across related diseases.
conclusion
These projects are just a few examples of the exciting activities
planned or already underway at NCATS. Though NCATS is still relatively
new, we operate following the NCATS 3Ds: developing new approaches,
technologies, resources, and models; demonstrating their usefulness;
and disseminating the data, analysis and methodologies to the
community. Our early successes demonstrate how this approach can help
solve some of the most challenging problems in translational science. I
look forward to sharing more of our achievements with you as NCATS
continues to evolve.
______
Prepared Statement of Dr. Nora Volkow, M.D.
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute on Drug Abuse (NIDA) of the National Institutes of Health
(NIH).
drug use and addiction research priorities
As a part of NIH, the Nation's premier biomedical research agency,
NIDA's mission is to advance science on the causes and consequences of
drug use and addiction and to apply that knowledge to improve
individual and public health. Over the last four decades, NIDA-
supported research has revolutionized our understanding of drug use and
addiction, transforming our understanding of the biological, social,
and environmental factors that contribute to substance use disorders
(SUD), and driving the development of improved strategies to prevent
and treat SUDs.
Drug use and addiction represent major public health challenges in
our Nation. In 2014 alone, over 47,000 Americans died as a result of an
unintentional drug overdose, and the past few years have seen rapid
increases in babies born with neonatal abstinence syndrome (NAS), an
unprecedented local outbreak of HIV, an increasing prevalence of
hepatitis C (HCV), and new synthetic drugs flooding the market. Despite
these challenges, this is a time of great opportunities for addiction
research. The last few years have seen tremendous advances in
technologies with research applications--from gene sequencing and
manipulation, to higher resolution brain imaging technologies, to
mobile health tools and electronic health records. In 2015, NIDA
released an updated strategic plan focused on leveraging these recent
scientific and technological advances to re-envision what research can
accomplish over the next 5 years.
The NIDA Strategic Plan for 2016-2020 outlines our broad goals
across basic science, prevention, treatment, and public health and
identifies four priority focus areas that we believe present unique
opportunities to be leveraged over the next 5 years including: \4\
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plan.
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1. Understanding the complex interactions of biological,
behavioral, and environmental factors influencing drug use
trajectories. Capitalizing on emerging technologies and
discoveries to facilitate integration and analysis of diverse
data sources, including genomic, behavioral, neurobiological,
environmental, and other data associated with drug use and
addiction.
2. Accelerating the development of treatments for SUDs.
Translating basic knowledge of the molecular pathways and brain
circuits involved in SUDs to develop new therapeutics for SUDs
and leveraging existing safety profiles and pharmacology data
to lower development costs and shorten the timeline for
obtaining FDA approval.
3. Addressing real-world complexities including comorbidities and
poly-drug use. Conducting research to better understand the
barriers to successful and sustainable implementation of
evidence-based practices and developing implementation
strategies that effectively overcome these barriers to ensure
that all populations benefit from the Nation's investments in
scientific discoveries.
4. Advancing bi-directional translation from basic to clinical and
applied research. Fostering stronger collaborations across
basic and clinical researchers to integrate and coordinate
human and animal research on addiction across the trajectory
from initiation to recovery.
current research highlights
Within the strategic priorities discussed above, NIDA research is
addressing ongoing national public health priorities including the
epidemic of opioid overdoses, the impact of adolescent drug use on
brain development, and the impact of tobacco use on health.
Addressing the Opioid Overdose Epidemic.--In 2015, both President
Obama and the Secretary of the Department of Health and Human Services
launched initiatives to address the complex problem of prescription
opioid and heroin abuse in this country. Both initiatives are focused
on improving opioid prescribing practices, expanding dissemination of
the opioid overdose reversal drug naloxone, and increasing access to
medication assisted treatment (MAT) to treat opioid use disorders.
NIDA-supported research contributes to both opioid initiatives through
support for research on alternative treatments for pain with reduced
potential for abuse; treatment of opioid use disorder; and development
of lay-friendly naloxone formulations.
Development of alternative pain treatments with reduced abuse
potential. While many strategies are currently being utilized to
reverse the opioid overdose epidemic, there remains a pressing need to
develop more effective treatments for chronic pain with reduced abuse
potential. NIDA, in partnership with the NIH Pain Consortium, funds
research to foster development of new pain treatments with reduced
potential for abuse. Funded grants range from neurobiology, genetics/
epigenetics, and molecular biology research that drives early stage
drug target discovery, to therapeutics development including
preclinical safety and efficacy testing and early phase human trials,
to health services research. For example, NIDA research is supporting:
--Testing of new compounds that exhibit novel properties as a result
of their combined activity on two different opioid receptors
(i.e., mu and delta). Preclinical animal studies show that
these compounds can induce strong analgesia without producing
tolerance or dependence.
--Development of new non-opioid medications for severe pain including
compounds that work through the endocannabinoid system and
others that modulate members of the transient receptor
potential (TRP) ion channel family.
--Exploration of combinatorial approaches that utilize both opioid
and non-opioid systems to minimize the dose of opioids needed
for pain control.
--Development of non-pharmacological strategies for pain treatment
including transcranial magnetic and direct current stimulation
of the brain, electrical deep brain stimulation, peripheral
nerve stimulation, stem cell transplants, and integrative
health approaches that consider the biopsychosocial nature of
pain.
Improving Treatment of Opioid Use Disorders.--An estimated 1.9
million people in the United States suffered from SUDs related to
prescription opioid pain medicines in 2014, and 586,000 suffered from a
heroin use disorder. Despite the availability of evidence-based
pharmacotherapies for opioid use disorders, including methadone,
buprenorphine, and extended-release naltrexone, we have a significant
and ongoing treatment gap in our Nation with more than a million
persons unable to access care and less than 40 percent of those being
treated for opioid addiction receiving these medications. NIDA supports
a broad portfolio of research to improve treatments for opioid use
disorders (OUDs) ranging from basic research to identify novel targets
for new therapeutics to preclinical and early clinical trials of new or
improved therapeutics; to implementation science to improve the
dissemination and effective use of evidence based practices.
For example, NIDA research supported the development of a
buprenorphine implant (Probuphine), a novel formulation that provides
stable round-the-clock dosing for 6 months. Buprenorphine is one of
three FDA approved medications that has been shown to be a safe and
highly effective treatment for opioid addiction. This new formulation
delivers a steady dose of buprenorphine for 6 months, an innovation
that improves the efficacy and acceptance of buprenorphine maintenance
treatment by: 1) removing the need to take a daily pill, promoting
continuous patient adherence; 2) preventing diversion of the drug; and
3) eliminating the risk of accidental ingestion by children. FDA
accepted a resubmission of the Probuphine New Drug Application (NDA)
that includes results from a Phase III double-blind clinical study in
September of 2015. Agency action is expected by May 27, 2016.
Development of Lay-Friendly Formulations of Naloxone.--The opioid
overdose-reversal drug naloxone can rapidly restore normal respiration
to a person who has stopped breathing as a result of overdose from
heroin or prescription opioids. Naloxone is widely used by emergency
medical personnel and some first responders and a growing number of
communities have established overdose education and naloxone
distribution programs that issue naloxone directly to opioid users and
potential bystanders. As of 2014, more than 152,000 naloxone kits had
been distributed to laypersons, and more than 26,000 overdoses had been
reversed since 1996.
In late 2015, FDA approved a user-friendly intranasal formulation
that was developed through a NIDA partnership with Lightlake
Therapeutics, Inc. (a partner of Adapt Pharma Limited). This
formulation can easily be used by potential bystanders (laypeople) and
is an important advance beyond the improvised nasal devices (consisting
of a syringe of injectable naloxone attached to an atomizer) that have
been used in recent years.
NIDA also continues to support implementation science to develop
strategies to improve the dissemination and sustainable implementation
of naloxone distribution programs; to increase co-prescribing of
naloxone to patients receiving opioid medications; to test strategies
for teaching high risk individuals strategies for managing overdose and
mitigating risk; and to test the efficacy of pharmacy based naloxone
access polices.
Basic Research on Brain Development and Drug Use Trajectories.--
NIDA supports a robust portfolio of basic research to understand the
mechanisms that underlie the transition from drug use to addiction and
the brain changes that characterize SUDs. One illustrative example of
this type of research is the Adolescent Brain Cognitive Development
(ABCD) study, a landmark study led by NIDA in partnership with NIAAA,
NCI, and other NIH partners that officially got underway in September
2015 with 13 grants. Researchers will recruit approximately 10,000
children at age 9 or 10--before initiation of drug use--and collect
detailed neuroimaging, genetic, behavioral, environmental, and other
health data at periodic intervals over the course of a decade. This
study will examine how biology and environment (including drug use)
interact and relate to developmental outcomes such as physical health,
mental health, and life achievements including academic success. This
study will allow us to answer questions such as how does marihuana use
during adolescence affect the development of the human brain and how
does this subsequently influence behavior. Such information is crucial
to guide prevention efforts.
Research on Tobacco Use and Health.--Smoking is the leading
preventable cause of disease, disability, and death in the United
States. Over 480,000 Americans die each year from smoking and second
hand smoke exposure. NIDA partners with FDA's Center for Tobacco
Products on the Tobacco Regulatory Science Program (TRSP) to support
research on the impact of tobacco-related policies on population health
and on the Population Assessment of Tobacco and Health (PATH) Study, a
national longitudinal study of tobacco use and how it affects the
health of people in the United States. One recent study evaluated the
effects of smoking cigarettes that contained different levels of
nicotine among current smokers and found that the average number of
cigarettes smoked per day was lower after six-weeks in participants
randomly assigned to cigarettes containing lower amounts of nicotine.
Compared with the normal (control) cigarettes, the cigarettes with
lower levels of nicotine decreased exposure to and dependence on
nicotine and also reduced craving during abstinence from smoking.
Ongoing studies are examining how low-nicotine cigarettes affect
smoking behavior in vulnerable populations including women of
childbearing age or pregnant women, individuals with comorbid SUDs, and
individuals with comorbid serious mental illness. Each of these
populations is at increased risk for tobacco use and dependence or
tobacco related adverse health outcomes. Yet despite these serious
vulnerabilities, these populations have not typically been included in
tobacco regulatory studies.
conclusion
Drug use and addiction are complex conditions. The fiscal year 2017
budget request will allow NIDA to support cutting-edge research that
leverages the most powerful technologies and latest emerging
opportunities to expand our understanding of drug use and addiction to
advance prevention and treatment and improve public health.
______
Senator Blunt. Thank you, Dr. Collins. We're on a pretty
tight 5-minute clock here on questions. If anybody wants to
stay--I'm sure there will be a time for it--and can stay, there
will be time for a second round of questions.
RESEARCH BUDGET CUTS
Dr. Collins, what would happen if we cut your research
budget by $1 billion, as the administration's request asked us
to do?
Dr. Collins. Losing $1 billion for medical research at the
present time would be devastating. We would have to cut the
number of new and competing grants that we give by a very
substantial number. Great ideas that scientists are putting
forward would go unsupported. Momentum that has been started
thanks to your efforts in fiscal year 2016 would be severely
damaged as a result.
MANDATORY FUNDING
Senator Blunt. Do you know something I don't know that
would suggest that the mandatory funding at a level that
exceeds that is likely?
Dr. Collins. Well, Senator, I have to say when it comes to
the discussions about discretionary budgets versus mandatory
budgets, I think all of us at NIH are a little puzzled by
exactly what the consequences of those particular options might
be. Our concern is to try to see, by some means, an increase in
the support for biomedical research at a time of such great
opportunity. So I'm not sure I can weigh the balance, but it
would certainly be, as a bottom line, deeply unfortunate if
these kinds of conversations resulted in an overall decrease in
the resources that we have when we have been hoping very much,
as you and others have projected, that perhaps we are finally
turning a corner after 10 years of lost resources into a
positive space, as happened in 2016 and as we very much hope
can continue in 2017.
YOUNG RESEARCHERS
Senator Blunt. And one of the things we had hoped we would
achieve from conversations we've had with all of you in the
past would be encouragement of young researchers. I know you
just now have this 6.6 percent increase, the $2 billion
increase. It may be too early to project, but do you want to
create a sense for us of what you're seeing in the research
community generally and young researchers specifically?
Dr. Collins. Thanks for that question because it's looking
certainly much more encouraging than if you had asked me that
question 2 or 3 years ago. Just a couple days ago, I was at a
major meeting of the basic scientists called ASBMB in San
Diego, and I spent a lot of time talking to young researchers.
A couple of years ago, those conversations were pretty
difficult, our young researchers wondering if they had a career
path, wondering if there was going to be support for their
ideas. It feels different this year. They have gotten the sense
that there is a path here for their careers, that they can try
innovative ideas and expect that there is going to be a
possibility of living out those kinds of career dreams.
And we're all about supporting them, and we have taken a
number of measures to try to achieve that kind of support. For
instance, early-stage investigators, who are not as experienced
as the more seasoned ones, compete against each other instead
of against the seasoned investigators in our peer review, and
that gives them a bit of a boost.
We started a whole new program that I am personally very
attached to, which allows the most talented graduate students
to skip the postdoc all together and go straight into an
independent position because we know that a lot of the great
ideas that scientists have don't happen when you're 50 or 60,
they happen at a little earlier stage than that, and yet we
have oftentimes kept people in less than fully independent
positions for a long time.
Something that's recently been floated, and I think may
very well come through in terms of a way of attracting more
physicians particularly into science is our loan repayment
program, where we try to counter what is otherwise a major
financial hit for those who have big medical school debts and
want to go into research. And you have recently proposed in the
authorizing side of this an increase of the loan repayment
program to a higher cap of $50,000 instead of $35,000 and that
will improve, I think, our opportunity to recruit those much
needed researchers into our workforce.
So many different points here we're trying to push
simultaneously. The most important thing, though, is for the
overall tide to raise and lift all those boats, many of them
with young investigators in them with their dreams of doing
great things, but dependent upon a confidence that we're on a
stable, positive trajectory for research that will go over many
years and not have a feast or a famine.
Senator Blunt. In this budget year we're in right now, if I
understood this right, you hope to set aside a certain amount
of research dollars for young researchers specifically and then
they would be competing against other young researchers. Do you
have a sense of how big that amount of money might be?
Dr. Collins. So we're dependent on, of course, what comes
in as far as applications. What we are making sure is that
those new and early-stage investigators have a chance to
compete against each other, and that gives them a boost in the
priority scores. And, in fact, in recent years, something like
35 percent, if I remember correctly, of our grant funds go to
new and early-stage investigators. They're not all young
scientists. Some of them are scientists who have been working
in other fields like engineering or physics or mathematics who
now see biology as a place that they would like to come and do
their work, but we want them, too, and we want to be sure they
have a fair shake at getting started on their careers in our
particular community.
Senator Blunt. Now, we may come back to engineers later and
something that I saw the other day at the Thompson Center for
Autism at the University of Missouri, but I'm going to try to
keep my time with everybody else's.
Senator Murray.
COLLABORATION IN ALZHEIMER'S RESEARCH
Senator Murray. Thank you very much.
The Vice President's Moonshot Initiative has actually
increased awareness about some of the barriers to sharing data
among cancer researchers, and I understand there's been some
success at fostering greater sharing of research data among
those focused on Alzheimer's disease with a range of formal
public, private, State, and Federal international cooperation.
Can you share with us a little bit about how NIH has been able
to foster this better collaboration and the effect it is having
on our efforts to develop treatments and ultimately a cure for
Alzheimer's and related dementia?
Dr. Collins. So I appreciate the question because this is
something we're very intensely focused on, is the idea of data
sharing. And NIH is pulling all the levers that we have and are
happy for others that maybe get granted to us to be able to
insist upon that. Let me ask Dr. Hodes, who is overseeing this
for Alzheimer's, to respond to your question.
Dr. Hodes. The microphone is on? Yes. Thank you very much
for the question, and it touches upon a very important aspect
of progress to success that I think reflects the understanding
from public--or private sector about common purpose and the
advantage of working together to ultimately accomplish the
common goals of finding diagnostic and therapeutic
interventions.
So to be specific, I can cite one of those, which Francis
Collins initiated NIH-wide, the AMP, or Accelerating Medicines
Partnership. It's a great example. One of the diseases being
approached in this sense is Alzheimer's disease. It brings
together contributions from pharma, from biotech, from advocacy
and philanthropies, along with NIH dollars, and in this case,
for example, in two general areas. One of them supporting in
clinical trials the use of new biomarkers; the other, looking
at the grand progress in ``omics,'' proteomics, genomics,
metabolomics, looking at the differences in the brains of
people affected by Alzheimer's and those not. These data now
are integrated in near real time through a common database.
It's a new culture among investigators in the academic sense,
as well as with industry to make the data, the products of
research, available as quickly as possible to the community, as
posted, and we'll have enormous repercussions, I think, in
accelerating the progress of research. And again this idea
reflects a common purpose in understanding that it would
benefit everyone, ultimately product development, and there's a
way to achieve that, expansion in basic science and knowledge.
So it has been an enormous success. I think it's a culture
change that will perpetuate.
ALZHEIMER'S DISEASE FOR AT-RISK POPULATIONS
Senator Murray. Good. And I think part of that, from what
I'm hearing, is that instead of waiting till someone is older
and in further stages of Alzheimer's, you're looking at ways to
have new trials with participants who are at risk of the
disease rather than already being diagnosed?
Dr. Hodes. Exactly true. One of the advances we've seen, by
understanding of genetic determination of those at risk and by
biomarkers, notably neuroimaging, is the ability to detect
early stages of Alzheimer's, related dementias, long before the
appearance of symptoms, and now to design treatments to
intervene and allow us to monitor these biomarkers to see if
we're engaging the right targets, having signs of progress, and
therefore identify successes, and for that matter, failures
more quickly and have an opportunity to test more candidate
interventions.
BIG DATA TO KNOWLEDGE
Senator Murray. Okay. Very good. We hear a lot about big
data challenges facing researchers, and perhaps nowhere is that
more relevant than with the massive amounts of data that the
BRAIN Initiative is now generating, a challenge that's only
going to increase, I assume, as we learn more. I know some of
your team has been really focused on this, and I wanted to ask
you about the challenge of opening and integrating an
accessible data warehouse on a massive scale and maybe some of
the examples you've seen that you've learned from.
Dr. Collins. So we do in fact have major investments in the
space of big data. I just showed up on this screen, there are
all kinds of data types that are being generated now in very
rapid phase and produce very large datasets of terabytes. And
you mentioned the BRAIN Initiative as an example. Genomics is
certainly in there as well as imaging.
And now with electronic health records becoming accessible
for research purposes, NIH recognizing this was going to be a
major need and a potential threat if not attended to, put
together a plan which has now resulted in $100 million of
spending on a program called BD2K, Big Data To Knowledge, which
aims to try to take all these large datasets, develop the
appropriate ways to have standards so that they can be properly
compared and integrated, and develop new kinds of software to
mine the nuggets of information out of these very complicated
sets. This supports a number of centers of excellence in data
science around the country and also it is the major source now
of training for the next generation of data scientists, who we
are going to need to be able to handle what is clearly a
growing area of scientific opportunity and responsibility.
Senator Murray. Okay. Thank you.
Senator Blunt. I would normally go to Chairman Cochran, but
he says he was a little late getting across the street, so he
didn't want to get in front of anybody who was already here.
And Senator Alexander, you're the first person who was
here.
Senator Alexander. Thank you, Senator Blunt.
Senator Cochran, thank you.
Welcome, Dr. Collins, and your team. I want to first
express my appreciation to Senator Blunt and Senator Murray for
their leadership last year on the significant increase in
funding for the National Institutes of Health, which I am glad
to support. I don't think there's anybody here who doesn't hope
that we can find ways to make the increase that happened last
year a pattern this year and in the future. So I thank Senators
Blunt and Murray for their leadership on that in this
committee.
Second, thank you for mentioning the work that our
authorization committee has done. Senator Murray is ranking on
that. We finished our work in the committee. We've done the
things that you have asked us to do. You said the ability to
recruit top talent was very important for you. We've made many
of the changes you suggested. Electronic medical records are
absolutely essential to the Precision Medicine Initiative you
described. We've done a number of things there.
The Vice President is talking about making researchers who
use NIH funds share their data. You've talked about that.
That's in the bill that we passed yesterday.
Dr. Collins. Thank you.
Senator Alexander. We gave you more flexibility to make
alliances like the Google-Vanderbilt alliance that the
President announced not long ago. We reduced a number of really
pretty silly provisions that create a lot of unnecessary
paperwork. So we asked you, what could we do to create an
environment where you could succeed? And we tried to do that.
Now, the major thing remaining is what I would describe as
an NIH innovation project fund and how to pay for it. The House
of Representatives has already passed its 21st Century Cures
Act. They appropriated $8.8 billion in mandatory funding. I've
tried to come up with a way to do that in the Senate. We can
reduce existing mandatory spending to pay for the NIH
innovation projects fund, we would make sure that we have
appropriate oversight, and it would not replace increases in
annual discretionary funding.
MANDATORY FUNDING FLEXIBILITY
So let me ask you in the remaining time to comment on that.
Are the priorities that I suggested earlier, launching
Precision Medicine, Cancer Moonshot, the BRAIN Initiative, 650
American young investigator corps, big BioThink awards, are
those still priorities? Can you do those without creating
funding cliffs? Would mandatory funding somehow give you more
flexibility to ramp spending up and then down? And what would
you do about oversight in terms of a strategic plan for each of
those five areas?
Dr. Collins. Well, thank you for that question and your
leadership, Senator. We are enormously excited about the five
areas that you just enumerated, the focus, for instance, on
young investigators trying to create an even more vigorous
pathway for their recruitment and support, which is one of
those five; the big BioThink, which you mentioned, which is an
opportunity for all of the 27 Institutes to have a chance to
put a challenge out there to their community about what are the
really big ideas that could go forward in the next few years.
And, of course, Precision Medicine and the Cancer Moonshot and
the BRAIN, all very high priorities for us.
While I totally agree with what you said about the
importance of not having this kind of mandatory funds displace
regular discretionary support, because that would be a very
unfortunate outcome, we do believe that for those five areas,
we could, in the space of a few years, identify components that
could be nicely supported through this mechanism and would not
result in a cliff, and which would, if we were given
appropriate flexibility, be something that we could put forward
in terms of what those timetables would look like and what
those envelopes might look like as far as specific dollar
figures.
And I certainly agree that we would expect to have
appropriate oversight about how those dollars would be spent.
We would be happy, in fact, to submit a work plan and then be
held accountable for that over the course of the coming years
to make it very clear that we do understand this is a big
responsibility that you, through the congressional process and
speaking for the taxpayers, expect us to use and----
Senator Alexander. So you do believe that in those five
areas those are still priorities that you've identified----
Dr. Collins. Absolutely.
Senator Alexander [continuing]. And, second, that you could
identify elements of them that would be discrete, have a
beginning and an end, do them without creating a cliff, and
perhaps even the mandatory funding would provide us a way to
give the NIH funding in a way that you didn't have to spend it
all at once and you could ramp up and ramp down according to
the real needs of the project.
Dr. Collins. That's exactly right. Yes, I do believe these
are major priorities. We could design things that way, and I
appreciate what you said at the end about the flexibility that
would help us a lot in terms of designing the exact funding
envelope that would make the most sense for each of those five
programs.
Senator Alexander. Thank you, Mr. Chairman.
Senator Blunt. Thank you, Senator Alexander.
Senator Durbin.
NIH MARCH-IN RIGHTS
Senator Durbin. Thanks very much, Mr. Chairman.
And thank you, Dr. Collins, for being here with your team.
It's a moment of satisfaction and pride that we look at this
year's budget and contemplate next year's budget. Though I am a
strong supporter of my President, I do disagree with their
budget request and believe that we can do better. The
encouraging thing is that gathered at this table on this side
are men and women who have proven that in this fiscal year and
can prove it again. It's going to take some good luck, but we
have some exceptional leadership here, not only in terms of
Senator Blunt and Senator Murray on this subcommittee, but
Senator Alexander and Senator Murray working on the authorizing
committee, and not to overlook at all my close friend and
colleague, Senator Cochran, who has overall responsibility for
the Appropriations Committee. So among us is the opportunity
and the potential to meet this year's challenge and next year's
budget, and I hope that we can do it.
I would like, if I can, to move to an area separate, but I
think very important, when it comes to the medical health of
America. A recent Reuters report found that the prices of four
of our Nation's top 10 drugs have increased more than 100
percent since 2011; 6 others went up 50 percent. The price for
arthritis drug Humira went up 126 percent; multiple sclerosis
drug Copaxone, 118 percent; asthma drug Advair, 67 percent. The
list goes on and on.
What makes this so worrisome is not only it limits
accessibility for the American people, but it also is
objectionable because many of these drugs were developed at the
expense of taxpayers, taxpayers funding the National Institutes
of Health. These taxpayers have paid to develop drugs that they
now cannot afford, while drug companies make record profits.
The National Institutes of Health has historically been
reluctant to exercise march-in rights, an existing authority
that was created by the Bayh-Dole Act that allows the NIH to
grant a license for others to use drugs developed with NIH
dollars which are inaccessible to those in need. I agree that
we need to be especially careful in this area of intellectual
property protection and that march-in rights have to be used
sparingly, if at all. But when we take a look at the staggering
prices of drugs, the dramatic increases for drugs, many of
which have been on the market for years before these increases
took place, I ask you, have you considered, would you consider,
using your statutory authority under the Bayh-Dole Act for
march-in rights to protect the consumers of America from abuse
by overpricing by pharmaceutical companies?
Dr. Collins. Senator, I share your concern about the way in
which individuals who need access to medical treatment may be
prevented from readily achieving that on the basis of the costs
involved, and certainly, as a physician, I would never want to
see a circumstance where an effective drug was not available to
somebody who needed it and would benefit from it. But I'm not
sure that NIH is in a great position here in terms of the
levers that need to be pulled to try to do something about what
everybody agrees is a difficult situation with drug pricing.
The Bayh-Dole Act, which I recently went back and looked at
in terms of those march-in rights and what they were intended
for, does not appear to have really been designed to be
utilized in a fashion where the price is the obstacle, it seems
more to be a circumstance where the product was simply not
available because it was not being commercialized, and then NIH
had the authority to step in and take over. And, of course, it
only applies if NIH has some connection to the intellectual
property, which is true for many drugs, but certainly not all.
We are certainly looking at the situations on a case-by-
case basis. We have a recent letter from a few Senators about
something called Xtandi, which we're studying at the moment,
and I am not saying in any way that we're not going to take
this potential responsibility seriously, but I am concerned the
negatives that may be flowing forward. If we begin to use
march-in in a very broad way about drug pricing, it may in fact
be substantial in terms of a loss of interest then in terms of
industry participation in discoveries that NIH has supported.
ACCESSIBILITY OF DRUGS
Senator Durbin. Let me just, because my time is up here,
let me just say first, accessibility I think goes beyond
physical accessibility. If a drug is overpriced, it is not
accessible to a consumer. And, secondly, I accept your premise
that you don't want to abuse this right, but if you cannot find
one egregious example where you can apply this, I would be
surprised. And applying it even in one case sends at least the
message to the pharmaceutical companies across America that
patients need to have access to drugs that were developed with
taxpayers' expense and the research that went into it. I think
doing nothing sends the opposite message, that it's fair game,
open season, for whatever price increases they wish.
Senator Blunt. Senator Cassidy, and after that it will be
Senator Mikulski.
Senator Cassidy.
Senator Cassidy. Thank you. Dr. Collins, all of you, thank
you very much. Thank you for your service to our country.
Dr. Collins, first I want to thank you. We've spoken in the
past. You know, I've kind of made it my jihad to get NIH to
redirect dollars to more pressing current biomedical needs.
You've initiated that, and I thank you for that, and I look
forward to seeing the fruits of that, because I look up and
down the panel, you all have got a lot of work to do, and we
thank you, too.
PRECISION MEDICINE INITIATIVE RECRUITMENT
Secondly, I've been thinking about your Precision Medicine
Initiative. What is the business plan? There's a million people
that you wish to recruit, it supposed to reflect the diversity
of our country. I've done clinical research, nothing like you
all, but significant, and my patient population was lower
income, more transient lifestyles. We successfully recruited,
but this would be for a 6-month or a year study, nothing such
as ongoing for the rest of their life.
Dr. Collins. Right.
Senator Cassidy. So in your business plan, I have several
questions. You have an ambitious effort to recruit a million
people from all socioeconomic groups. How do you plan to do so?
Secondly, it's longitudinal. There is going to be significant
expense. So to what degree do private entities, say, Pfizer, do
they have to pay to access that data? If not, why not? Because
there are going to be significant benefits.
And, thirdly, if I am someone who has agreed for the rest
of my life to contribute hair and rectal swabs and nasal swabs
and everything, because you've spoken of our biome being
included as well as our genome, am I going to get to share
that? If there are a billion dollars that come in, in revenue,
a certain portion ideally would be used to maintain the
program, does some of it flow back to one of those million? We
think of that HeLa strain, the woman who donated her cervical
cancer, so much benefit, but her family has not benefited
directly.
Dr. Collins. Not directly.
Senator Cassidy. In this contractual process, will those
who contribute their data, will they be able to benefit as
well?
So it's three questions, if you will.
Dr. Collins. Well, thanks for the question and also for
your initial comment about strategic planning. I hope everybody
at the dais there has seen the strategic plan that NIH put
forward, published in December, very much a response to your
request to have a clear sense of how we set priorities, and I
hope you've had a chance to look at that, and if not, please
do, and let us know if there are things you would like to
discuss further about it.
How are we going to enroll a million people and have that
be generalizable as far as the population in the United States?
Something we've thought about a great deal. Many of the
participants are in fact going to be those who are currently
involved in health provider organizations who have recently
come forward and applied to be part of this, but, of course,
that's not going to be fully diverse in terms of socioeconomic
and ethnicity of the country.
We will also have an outreach which is, I think, going to
be pretty interesting to the community health centers, the
federally Qualified Health Centers that are supported by HRSA
(Health Resources Services Administration), to try to enroll
those individuals who get their care in those settings, who
tend to be fairly stable in terms of their geographic location,
despite what people might think. And actually I have
interesting research based on polls, but haven't generally been
asked.
We also will have this open to any American, so anybody can
volunteer to take part in this, and that opportunity will
appear at approximately August or September. So maybe all of
you all would like to join in. It would be great to have you as
members of this million-strong cohort.
Yes, it is intended to be a longitudinal cohort. It will
collect a great deal of data. We do intend to make that data
available to any qualified researcher who adheres to certain
principles about protecting the privacy and confidentiality.
I hear what you're saying about pharma therefore being able
to use this as well, and yet I don't see a great alternative.
Basically, pharma will have the opportunity to learn from this.
It will be very pre-competitive, early-stage data, the kind
that we traditionally do make available in publications, and it
would be hard to put up a barrier here, I think, in this case,
without slowing down the progress of research overall.
Finally, your question about whether the participants
should receive some of the financial benefits that may come out
of this, we've certainly talked about that. I think the general
position, though, of bioethicists who look at that question is
that the extremely low likelihood of such actual benefit coming
back because the data that we generate here is not itself
likely to produce much in the way of intellectual property,
it's pre-competitive data, it might actually be a disservice
then to be seen by potential participants as an inducement to
take part in a project which might not really result----
COMPENSATION FOR PMI COHORT PARTICIPANTS
Senator Cassidy. If I may, I know in clinical research,
you're allowed to compensate people for the expense of
participation.
Dr. Collins. Yes.
Senator Cassidy. So it isn't an inducement as in, you know,
stick a nail in your eye; it is, listen, you're going to be
taking your hair, you're going to put it in an envelope, you're
going to mail it to us, you're going to give us access, a lot
of hassle associated with that. It is a compensation for
participation.
Dr. Collins. So we would certainly be willing and have it
planned to compensate people for the time that they have to
spend by taking part in this, if they're going to have an
examination, have a blood sample, have to----
Senator Cassidy. In my remaining seconds, let me interrupt.
Now, the thing that concerns me regarding this data, granted,
it's pre-competitive, but we, as taxpayers, funded for
electronic medical records to collect this data to make it
generalizably available to people doing public health. We heard
when I was in the House on Energy and Commerce, it's not being
used that way. Insurance companies are instead packaging and
selling to big pharma, but $500,000 for a cohort of
information, and if you are a dadgum public health doctor and
you don't throw in $500,000, you don't get the data.
So I guess my concern is the taxpayers investing heavily in
this, but our precedent is, is that the taxpayer is misled in
terms of its generalizable use. For this data, there is going
to be such profit generated, is there really no way that the
person that comes up with a blockbuster drug in any way comes
back to help support the maintenance of this dataset, which is
going to be critical to their development of that blockbuster
drug?
Senator Blunt. Can you respond to that in 30 seconds, Dr.
Collins?
[Laughter.]
Dr. Collins. Sure. I guess, Senator, I see this as not so
different than the way in which our American ecosystem has
flourished, and I would be reluctant to try to impose that kind
of payback provision for pharmaceutical companies to be able to
get access to a very large dataset which is pre-competitive
which may give them ideas about new drug targets they hadn't
thought of, but which is probably not going to result in a
direct intellectual property claim. So I think of this much
more the same way that the Framingham Study has produced all
kinds of insights about heart disease, and nobody has
contemplated that the companies that are selling statins should
now be paying money back to Framingham.
Senator Blunt. Thank you very much. There will be time to
come back to that and other topics, as we all want to as well,
Senator Cassidy.
Senator Mikulski.
Senator Mikulski. Mr. Chairman, thank you.
Senator Murray.
Dr. Collins, it's so good to see you and your team here and
those also who represent institutes and offices at NIH. You
know, this might be your last hearing, but it certainly is my
last hearing at the appropriations for NIH, but I'll be out
there on Monday to be able to talk to you on more detail.
It has been my great joy, one of the greatest joys I've had
being in the Senate, was to be able to represent the National
Institutes of Health, both my work in the House on Energy and
Commerce, where so many of us came from, to now certainly in
the Senate, and to represent both NIH in the Bethesda campus,
our two institutes in Maryland, the one on Aging and on Drug
Abuse, and of course, our extramural work with Johns Hopkins,
the University of Maryland, and multiple campuses, one of your
rival institutes, the Craig Venter, where we watched you and
Dr. Venter do the race to map the human genome. So it has been
a great joy. It will be even more joy if I can help leave you
in pretty solid financial health. We could go through the
numbers about clinical trials and so on, but let me tell you my
principles and then get to my questions.
Number one, do no harm. So either for this year or next
year, that through our own self-inflicted wounds, we're ready
to budget processes of sequester or shutdown, we don't go in
that direction. I really want to compliment Senator Cochran and
Senator McConnell and say we're going to follow regular order
and do our job. So one, do no harm.
Second, capitalize existing programs. So those that are
already on their way, that we help sustain so that the
researchers, both senior researchers and the new ones we hope,
and so on, have predictability.
And then third, go for the big ideas.
BASELINE FOR FUTURE YEAR BUDGETS
So let me then get to my question, which goes to we have an
agreement here to do no harm, and I really look forward to
working with my colleagues on my side of the aisle to move our
process forward.
But let's go to the money. You answered Senator Alexander
in terms of mandatory funding. I'm squeamish about mandatory
funding. I am concerned that it is a hope and a promise. It
rests on new revenue. Well, maybe. I'm coming back to actual
discretionary funding, so no matter what, you, as the
administrator and the director of the Institutes, because we
don't earmark, we've never earmarked at NIH, though there's
been a tendency, yet discretionary.
So you have a request for here it's $33 billion, but in
terms of real discretionary money, what is it that NIH needs to
be able to be and do the job it wants for the next fiscal year
and make sure we have the baseline to build on it, you know, on
future years? Because you, research, researchers, need
predictability over multiple years.
Dr. Collins. Senator, I can't say enough how much I've
appreciated your support over these years, just a remarkable
leader, and we look forward to celebrating you next Monday when
you come out to NIH.
Senator Mikulski. The golden Petri dish, I guess.
[Laughter.]
Dr. Collins. So in terms of your question, and I assume
you're asking for my professional judgment, which I'm always
happy to be asked about.
Senator Mikulski. Yes.
Dr. Collins. We have, of course, seen over the course of
the last 12 years a pretty tough period for NIH until this
year, fiscal year 2016. I've often thought it was useful to
show this graphically, and if you look at the screen----
[The graphic follows:]
Senator Mikulski. I need a short answer so I can get to
other questions.
Dr. Collins. Okay.
Senator Mikulski. Okay?
Dr. Collins. You can see the white line. That's what's
happened to our resources over the course of the last 20 years,
and we have made some progress this year, but we need----
Senator Mikulski. The number now. This is not a colloquium;
it's a hearing, please. How much do you need?
Dr. Collins. A stable trajectory of inflation plus 5
percent for multiple years in a row would be a wonderful way to
support medical research in the way that it needs to be.
Senator Mikulski. So if we made that percentage--now,
wouldn't that be over a 5-year period, wouldn't we get to
almost doubling NIH?
Dr. Collins. You would get to doubling by about I think 7
years or maybe 8. I would have to go back and do the
compounding again, but about that.
Senator Mikulski. Well, first of all, I'm so pleased last
year at the splendid bipartisan way we worked together, and I
want to compliment Senators Blunt and Murray in doing that. I
think we need to really be serious about thinking about that as
a model to be able to have the predictability, again not a
guarantee, we don't know what lies ahead in some instances for
our country, but I think that type of commitment, along with
maybe the hope and promise of mandatory funding, would be the
way to go.
Dr. Collins. Okay.
RESEARCH IN EXISTING PROGRAMS
Senator Mikulski. Now, let's go to what we would buy for
the money, what we would get for the money. First of all, I
support these new ideas, and you know, Precision Medicine, the
BRAIN Initiative, and all of this promise, but where do you see
in terms of existing programs where you see some of the
greatest promise? Yes, we're working at the BRAIN, et cetera,
but what about things where people are often the sickest the
most with awful consequences, diabetes and heart disease?
Dr. Collins. Great promise in diabetes, heart disease.
Cancer is at a unique moment. Conditions like autism coming
forward. Vaccines, the opportunity to prevent diseases that we
desperately need to get on top of, like Zika and others. But,
you know, the good news is if you look across the entire
landscape of NIH research, there's not really a sort of place
where things are in a cul-de-sac. All of those areas, and that
includes the basic science agenda that undergirds it all, are
poised for dramatic advances. So it's almost hard for me to
pick one or two.
I do have to mention Alzheimer's. I think we are at a
inflection point for that condition, and I know that's one
you've had major leadership in trying to draw to people's
attention. The ability now to be able to identify who's at high
risk and conduct these trials to reduce their likelihood of
developing the disease is looking more promising than ever.
Senator Mikulski. Well, my time is up, but in the area of
Alzheimer's, I remember when Senator Bond and I had a hearing
and we were in the poise of breakthroughs. So that was like 5
years ago. So we're always poised during the breakthrough, and
I'm ready for the breakthrough.
[Laughter.]
Dr. Collins. So are we.
Senator Mikulski. So let's all continue to work together.
Thank you. You were indulgent with the time.
Senator Blunt. Thank you, Senator Mikulski, and thank you
for how well you've represented NIH as a Senator and as their
advocate for a long time now.
Senator Capito.
OPIOID ABUSE
Senator Capito. Thank you, Mr. Chairman. And thank all of
you, and thank the ranking member.
I'd like to talk with Dr. Volkow about the National
Institute on Drug Abuse. As you probably are aware, I represent
the State of West Virginia. We've been particularly hard hit by
the epidemic of opioid abuse in the country. And I just had a
few questions I wanted to ask specific to that.
I understand that you are partnering with the Appalachian
Regional Commission to improve opioid intervention services.
Can you explain and tell me what are the goals of this
collaboration and where you are on that?
Dr. Volkow. We're trying to actually create infrastructure
that will allow us to launch research projects and also to give
us information about the nature of the problems that they
currently have vis-a-vis injection drug abuse and the
associated consequences along with medical infrastructure that
they have that they could deploy. Unfortunately, this
information is currently not available and there are not
integrated groups that would allow us to deploy the type of
implementation research that we would be very much interested
to do in order to contain the injection drug abuse epidemic in
that area.
Senator Capito. Well, I understand there have been issues
with different States on reporting data, causes of death, and
because there are associated issues, it could be a heart
attack, and then not be identified as a drug overdose. Is this
an issue across the country? I'm sure it is.
Dr. Volkow. Yes, it is an issue, and as a result of that,
we don't have clear-cut numbers of the cases that is related to
opioid overdoses, and varies, as you said, by State.
Senator Capito. So I'm sure, as a researcher, you don't
want to speculate, but I would imagine speculation is the
problem. It may be greater than what we really realize
according to the data?
Dr. Volkow. Yeah, there is consensus that we are
underestimating the numbers that's associated with----
Senator Capito. Well, that's a frightening thing I'm sure
for you all and certainly for all of us, every family that's
affected.
DEVELOPING NON-ADDICTIVE PAIN MEDICATION
I was pleased to hear, Dr. Collins, in your opening
remarks, that you talked about the research that's being
developed to find a non-addictive pain medicine. I know
Secretary Burwell has talked about this as well. How far along
are we on that and what can we expect there? If you could just
shine a little light on that.
Dr. Collins. Sure. I might ask Dr. Koroshetz, who directs
the Pain Consortium at NIH, to say something to respond to your
question.
Dr. Koroshetz. Yes. So it's an interesting area to think
about. Pain is something we all have. It's good to know we have
a sense of pain. But the problem that we're facing is we don't
understand too well about what characterizes the transition
from acute to chronic pain. Chronic pain is not helping in any
fashion whatsoever. We think, and all the evidence so far,
suggests that there is a change in the brain circuits that
occurs after someone has been exposed to an acute pain that
leads those circuits to change and develop a chronic pain
disease basically by itself.
So we have pretty good information on some of the
beginnings of how that happens. It starts very peripherally and
moves more centrally over time. And there actually are targets
for therapy that could be pursued by pharmaceutical companies
and by the NIH to try to prevent that transition. So in the
Blueprint for Neuroscience, that was our major challenge, to
develop products that would prevent this acute-to-chronic pain
transition. From talking to the pharmaceutical companies, I
have a lot of leads.
I think the problem that we have to focus more on is how to
improve the testability of those compounds as we go into people
because we're still reliant upon someone's reporting of their
pain, and we don't have objective measures. So we think at NIH
that that should be our major focus. And the drug companies
tell us they have lots of targets, but they need this objective
measure. So that's where our focus was.
Senator Capito. Well, I would hope--I mean, I'm pleased to
hear that. I would like to see it on the fast track. I think
for a business model, you know, there's going to be a lot of
demand for a non-addictive pain medication that works.
Dr. Koroshetz. Right.
Senator Capito. So I don't see how the private sector would
be contrary to this at all, and so I'm pleased to know you're
working together.
NEONATAL ABSTINENCE SYNDROME
The last issue, again, Dr. Volkow, about fetal--let's see,
neonatal abstinence syndrome, that's babies that are born
addicted, and this is an issue, and our State has particularly
high statistics here again. Are you pursuing research in this
area or what kind of partnerships are you doing here to try to
help those very innocent victims of drug abuse?
Dr. Volkow. Indeed, we are pursuing the area of research in
terms of interventions, number one, to prevent neonatal
abstinence syndrome, and number two, in those women that are
opioid--have an opioid use disorder, to determine what are the
best treatments that can be given to them in pregnancy to
minimize the likelihood that those infants will suffer from
neonatal abstinence syndrome. So we are working on prevention
and on treatment.
Senator Capito. Well, thank you very much. We have a place
in West Virginia called Lily's Place that helps to deal with
these babies. And just my final comment would be I noticed in
your report that you're working on a Human Placenta Project.
I'm very interested in that and have a personal connection with
that. So thank you very much.
Senator Blunt. Senator Schatz.
Senator Schatz. Thank you, Mr. Chairman.
Thank you to all of you and everybody who works at the
National Institutes of Health. This is, I think it's fair to
say, among the most inspiring, invigorating hearings that we
have. I'm going to try to get to a couple or maybe three
questions.
FEDERAL PAIN RESEARCH STRATEGY
First, Dr. Volkow, following up on Senator Capito's
question about non-addictive alternatives to the current pain
medication, opioids, acetaminophen, the NSAIDs, where are we
with that in terms of the national--the NIH is working on a
Federal pain research strategy. When will this be completed?
And when will it be launched? And who is going to be point on
this? And I'm not sure if the question should be directed to
Dr. Volkow or Dr. Koroshetz.
Dr. Collins. Koroshetz will answer.
Dr. Koroshetz. It's really complicated. There are a bunch
of different documents out there, but there is a National Pain
Strategy that has been released, and that is basically
directing the country's medical care system on how to improve
pain care in both a safe and effective manner. And then that
process is followed by the Federal Pain Research Strategy,
which is being developed now and will be completed by January
2017, where an expert panel of basic and clinical researchers
will work out the highest research priorities in these
different areas, some of which I mentioned, the acute-to-
chronic pain transition being one. And another what is
determining the best way of treating people who have chronic
pain, depending on what caused it and what type of pain it is.
Senator Schatz. Great. Thank you.
PUBLIC HEALTH STRATEGIES FOR DENGUE/ZIKA
Dr. Collins, as you know, the Hawaii Islands, the State of
Hawaii, but the big Island of Hawaii, is experiencing a dengue
fever outbreak, and the vector for dengue fever is the same as
the vector for the Zika virus. And I would like you to tell the
committee what recent developments there may be in terms of
public health strategies relating to dengue and also to Zika.
Dr. Collins. So with dengue, the National Institute of
Allergy and Infectious Disease just announced a couple of weeks
ago success of a quad--I'm sorry--a tetravalent vaccine, which
was tried out in volunteers and showed complete protection
against dengue infection. And there is also a vaccine that has
been produced by the company Sanofi that is already approved in
a few places like Brazil and Mexico, but not yet in the United
States. I know that Hawaii has had more than 300 cases of
dengue, and there's a great interest in speeding up the process
of getting access to that vaccine, and I would be glad to talk
to you further about that, and Dr. Fauci, who directs that
effort, would also.
In terms of Zika, the Zika vaccine efforts are on the fast
track and we are doing everything we can to speed that up, but
it will be until probably August or September before the first
phase 1 trials can be initiated for human volunteers. And
realistically, because then one has to go to phase 2 and 3
trials, this will not probably be generally available until
2018. We're also working on therapeutics as well as the
vaccine.
CHILDHOOD VACCINATIONS
Senator Schatz. Dr. Collins, a new question. There is
unfortunately a lot of confusion among young parents about the
benefits and efficacy of vaccinating their children, and I
would like for you to say as clearly and concisely and
authoritatively as possible, what's your recommendation to
young parents who may be reading things on the Internet and are
otherwise well informed and certainly care very deeply about
their children, but want to take the right advice?
Dr. Collins. Well, I really appreciate that question
because there still is confusion out there, though I think the
facts are now incredibly clear. There was a suggestion 20 years
ago that there might be some connection with vaccination with
the MMR vaccine and the onset of autistic symptoms. The report
that put that forward ultimately was turned out to have been
falsified. The author of that report has been stripped of his
professional standing, and the paper has been retracted. But it
started a concern, an understandable concern, amongst patients
and parents about whether this might be a real connection.
Multiple studies done over the course of these two decades in
the United States and in other countries, especially Denmark,
have repeatedly failed to show any connection whatsoever
between childhood vaccines and the onset of autism.
Autism is a terrible tragedy when it happens, we need to
understand its causes, we are learning much about those, but
what we can say I think categorically is that vaccines are not
the cause. And, of course, it is very much an unfortunate
circumstance if kids are not getting vaccinated and then fall
ill from treatable diseases, like measles, which can even be
fatal.
Senator Schatz. So your recommendation to parents is?
Dr. Collins. Get your kids vaccinated. Follow the
recommendations from the professional societies like the
American Academy of Pediatrics. Don't worry. This is a good
thing. This will help your kids.
Senator Schatz. Thank you.
Senator Blunt. Thank you, Senator Schatz.
Senator Cochran.
JACKSON HEALTH STUDY AND PMI
Senator Cochran. Mr. Chairman, thank you for this follow-up
hearing. It gives us an opportunity to check in again with the
status of what can be gleaned now from the Jackson Heart Study,
which involved a cohort, a research cohort, of 5,000 men and
women in Jackson, Mississippi, relating to the heart and the
illnesses and consequences of heart disease. As you work to
build a national research cohort, is this study going to be a
part of that initiative in any way?
Dr. Collins. So the Jackson Heart Study, Senator, which
you've been a wonderful leader for, and which you and I got to
visit together 2 or 3 years ago, is a national resource to look
particularly at the factors that play out in terms of
cardiovascular disease in the African American community, where
we know that the risk factors are particularly high. That study
has already taught us a great deal about what those
environmental and genetic and social and behavioral risk
factors are turning out to be, and those 5,300 individuals who
have volunteered to take part in this effort I think are real
national heroes by their willingness to do so.
We are continuing to look for ways to connect up that
effort with other kinds of studies, and I know Dr. Gibbons, who
is the director of the National Heart, Lung, and Blood
Institute, recently visited Mississippi to think a bit more
about that with regard to other kinds of research going on in
your State.
With regard to this Precision Medicine Initiative cohort,
where we aim to enroll a million Americans, we very much open
that door to every volunteer, and my hope would be that those
who have already taken part in research studies would be
particularly interested, and therefore, we might see particular
interest coming forward from those folks who are already part
of the Jackson Heart Study. Certainly, we learn more the more
data that we have, and to be able to do that kind of connection
would be quite useful. But we want everybody to have the
opportunity to decide whether this is the kind of study they
want to take part in.
Again, though, I can't tell you how much from NIH's
perspective it has been valuable to have that already ongoing
study now going on 20 years, or it will be in a couple more
years, to teach us things that you can only learn over the
course of time, and which we also hope to learn from this
cohort, the Precision Medicine cohort, as it gets launched in
the next year or 2 and then moves forward going who knows how
many decades to try to really understand all the factors that
play out in terms of health and disease.
Senator Cochran. Okay. Thank you very much.
Senator Blunt. Senator Shaheen.
Senator Shaheen. Thank you, Mr. Chairman.
Thank you, Dr. Collins, and all of you for being here this
morning and for the work that you do every day.
ARTIFICIAL PANCREAS
So I have three questions, and I want to start with
congratulating and thanking you all for continuing to make the
artificial pancreas a priority. I was pleased to see that both
in your written testimony, and although I didn't hear your
comments, I know that you mentioned it in what you had to say.
It will completely change the lives of people living with type
1 diabetes, like my granddaughter, Elle, who was diagnosed
after her eighth birthday. So can you talk about what you hope
to deliver in the next 5 years with respect to the artificial
pancreas?
Dr. Collins. Thanks for the question. And of course, this
is a very high priority for our National Institute of Diabetes,
Digestive, and Kidney Diseases. The challenge is to come up
with the kind of engineering, both tissue engineering and other
types, that would reliably produce an accurate minute-by-minute
measure of blood glucose and then deliver appropriately and
safely the appropriate dose of insulin to keep those levels in
the right zone. We all know that the current way that this is
done, as your granddaughter no doubt knows every day, involves
the sort of regular opportunity to find out blood levels
oftentimes by a finger stick, and yet you can't do that every
minute, and so there are peaks and valleys that undoubtedly are
less than ideal. And we do know the better the control, the
better likelihood of avoiding those consequences of
cardiovascular and kidney disease and eye disease, which is
very much our goal to try to prevent.
So the challenge here has been, because of the safety
issues, to move this forward in a fashion where we know we are
going to be doing good. There have now been a number of studies
under very closely observed circumstances----
Senator Shaheen. Actually, my granddaughter participated in
one of the initial studies for juveniles.
Dr. Collins. Wonderful. And those have shown very
encouraging results. I think the reason of going cautiously is
that, of course, an overdose of insulin can be extremely
dangerous and even fatal, and so you want to be sure you have a
failsafe system, and that's where a lot of the focus now is.
But as I----
Senator Shaheen. And so--I'm sorry to interrupt, but my
time is running. So do you think--are you optimistic that in
the next 5 years we may have a device that is going to be
available on the market for people?
Dr. Collins. In my opening statement, I said 10. I would
love for it to be 5. I think it could be. It would certainly
require both some good scientific effort and some good support
for that, but also some of the things we don't quite know yet.
If they turn out well, yes, I think that is a feasible kind of
goal, but I wouldn't want to overpromise.
Senator Shaheen. Because Europe is ahead of us on this,
which is disappointing to see. Good for people in Europe, but
we want to catch up with that.
HEROIN AND OPIOID OVERDOSES
Dr. Volkow, I want to follow up on Senator Capito's
questions about the heroin and opioid epidemic because in New
Hampshire, we are experiencing the highest percentage of
overdose deaths of any State in the country. It is not just an
epidemic, I believe, but a pandemic. We talked about this when
you were here before us last year. And you know, I was at a
forum recently where the local hospital CEO said that they can
tell when there's a new batch of heroin on the streets within
an hour because they see about a half a dozen people admitted
into the emergency room. And so that's what we're dealing with.
So can you tell me what resources NIH, the Institute on
Drug Abuse, has that can assist those people on the front
lines? Because I think, as we talked last year when you were
here, I think we have been very slow at the national level to
respond in the way that this epidemic deserves.
Dr. Volkow. Yes. As an institute and the NIH does research,
so the way that we have responded is to provide with products
that allow us to address and prevent the overdoses from
opioids, which, of course, is very tragic, and I am very, very
aware of what's going on in New Hampshire.
Senator Shaheen. I know you are.
Dr. Volkow. One of them very successfully led to a product
that was approved by the FDA last year, which is intranasal
Narcan, that has many advantages, including the fact that it
can deliver very high concentrations to the blood very rapidly,
and that's fundamental to overcome an overdose. And this is
particularly relevant now on selling because we are seeing that
many of these overdoses are due to the fact that they are
combining with Fentanyl----
Senator Shaheen. Yes.
Dr. Volkow [continuing]. Which is very, very potent. So
note that regular Narcan may be as useful as we need stronger
products. This product also is very cheap, it's something like
$37, so it becomes very, very available. That's one.
The second strategy that we've also shown decreases
overdoses is medication-assisted therapy, but it's not being
deployed.
Senator Shaheen. Right.
Dr. Volkow. And sometimes it's not just the issue of
deployment, but the structure is not there for patients to be
able to take advantage of it. Very problematic in rural
communities. So we are developing again with pharma in a
partnership medications that will be easier to comply with and
that will require much less infrastructure to sustain.
But also we are doing research on implementation. How can
we take advantage of the healthcare system so that they are
involved in the deployment of medication-assisted therapy for
individuals with opioid use disorders? Because it has been
shown to prevent overdoses.
Senator Shaheen. We're still hoping that you might be able
to come to New Hampshire and talk about some of these new
developments because I think it's the kind of thing that would
be--is very important, and there was a lot of interest.
Dr. Volkow. I would welcome it, and I think they are
arranging it.
Senator Shaheen. Yes.
Senator Blunt. Thank you, Senator Shaheen.
Senator Moran.
Senator Moran. Mr. Chairman, thank you very much. Thanks to
you and the ranking member for conducting this hearing.
Dr. Collins and others, thank you very much for your
presence here.
SPENDING PRIORITIES
Dr. Collins, this wasn't my intended question, but I
heard--I actually listened to the things you and others said in
the panel this morning, and this is a response to what I heard.
One of the things that you and I have talked about over a long
period of time is how to prioritize spending within NIH, and
you make decisions about what research receives a priority and
what centers are receiving funding. You have appealed to me,
and particularly in my time as the ranking member of this
subcommittee, that we don't want the decisions to be made by
Congress, we want science and medicine to determine, the
researchers to determine, how money is spent at NIH, and you
know, that's against our inclination. We have people who come
to us who ask for help, who make suggestions of how we could
improve their lives, their family members' lives. And I think
all of us want to help, and you'd love to say we'll give NIH
more money to cure or treat this disease. I have believed in
the theory that those decisions are best made by science and
medicine.
Do you have evidence--I mean, one of the things you said
was we ramped up, ``sped up'' I think was your word, research
in regard to Zika. What that would suggest to me, that if you
can ramp up something to do that, do you not have to diminish
something else? And so my question is, when you assure us that
you're making priority decisions based upon science and
medicine, when you increase spending someplace, is there a
corresponding reduction in spending someplace else?
Dr. Collins. It sort of has to be that way, doesn't it? And
this is one of the things that we very much tried to outline in
this NIH Strategic Plan, which is now just 4 months out and
which I think does lay out the difficult situation we face when
we have something that really requires urgent attention, like
Zika, there needs to be a way to pay for it. Now, obviously in
that situation, the administration has proposed an emergency
supplemental lacking so far a response because it's taking
time, just yesterday, now the Department advising that we shift
dollars away from other things to put into that. But already,
if Tony Fauci was here, he would say he was doing that, and by
necessity, to try to accelerate that.
So for all of us, as science managers, we are facing sort
of Sophie's choices every day, especially in the course of the
last decade or more where our success rates for grant
applications have been the lowest in history, below 20 percent.
And so one of the hardest things that each one of us at this
table faces is that almost on a daily basis you have to turn
away a science that you know is exciting, a science that is
well designed, and science that is important for a particular
public health need, but on the scheme of things, when you have
to set priorities, which we're forced to do, it doesn't quite
make that cut, and we know we're giving away opportunity.
Senator Moran. Well, Zika perhaps is an example, but maybe
not the best example, in the sense that----
[Cell phone rings.]
Senator Moran. I didn't know anybody had my phone number.
[Laughter.]
Senator Moran. I thought I was on the no call list.
[Laughter.]
Senator Moran. Dr. Collins, the sense that we would make
medical and scientific decisions, Zika comes as something new,
something relatively new, and so we make choices of allocation
there, but on an ongoing basis, you've indicated, you know,
promising developments in many areas, but I assume when you say
that, that means that if there is a promising development on
the horizon, that means that you're making a decision to put
additional resources, dollars, into that research at the
expense of something less promising. Is that true?
Dr. Collins. That's absolutely true. That's our
responsibility.
ALZHEIMER'S DISEASE AND DOWN SYNDROME
Senator Moran. Okay. Let me ask a question about
Alzheimer's, and particularly the relationship between Down
syndrome and Alzheimer's. We've had this conversation, I don't
know how recently, maybe even a couple years ago, but the beta-
amyloid deposits and the scientific evidence that those appear
in individuals by age 40 who develop Down syndrome, who have
developed Down syndrome, and that often apparently a
correlation between that and Alzheimer's. What's the latest
knowledge that's been gained in regard to the relationship
between Down syndrome and Alzheimer's?
Dr. Collins. Well, it's very clear that individuals with
Down syndrome, who have an extra chromosome number 21, have a
heightened risk of Alzheimer's disease as they get older, and
they may very well develop that both pathologically and in
terms of effect on the brain function by their twenties or
thirties. This is presumably on the basis of the fact that the
Alzheimer's amyloid protein deposits in the brain is on
chromosome 21. So they have an extra copy of that and
presumably, therefore, are making an excess amount of the
protein, and ultimately it deposits.
This is a tragedy for kids who may have been functioning
pretty well and then develop this problem in their twenties and
thirties, but it's research-wise also an opportunity that we
want to take advantage of, knowing that these are individuals
at very high risk who themselves and their families are
interested in interventions.
We are now mounting research studies with some of the new
ideas about Alzheimer's prevention, specifically making those
available to kids with Down syndrome who are in their twenties
to see whether in fact we can show benefit and in the process
learn everything we can about both Down syndrome and
Alzheimer's disease.
Senator Moran. Thank you. Thank you, Mr. Chairman.
Senator Blunt. Thank you.
CHEMOTHERAPY FOR BREAST CANCER PATIENTS
I'm sorry. Dr. Lowy, I was at the Siteman Cancer Center at
Washington University a few months ago and just sitting around
a table talking with doctors there on the topic of breast
cancer. They said their view was that maybe most doctors who
deal with breast cancer are coming to the conclusion that
chemotherapy is usually not needed, but they don't know how to
determine whether it's needed or not, that maybe as many times
as 8 out of 10 times that the chemotherapy that a breast cancer
patient goes through after surgery, it just wasn't necessary.
Comment on that generally and other things like that where
both the patient and the cost could be dramatically impacted if
we just had a little more information and more ways to identify
a group of patients that we can clearly determine, ``You don't
need this, you're in the 2 out of 10 that do,'' ``You do need
it, you're in the 7 or 8 out of 10 that don't.'' Your thoughts
on that would be helpful to me.
Dr. Lowy. Thank you, Senator Blunt.
First I want to thank you, Senator Murray, and your
colleagues for the incredible strong support that you have had
for NCI and all of NIH.
Your question is critically important, and we are
optimistic that the future of predictive oncology has enormous
potential, the question of: How do you deliver the right drug
to the right patient at the right time? And an important aspect
of that is: Who should be treated and who should not be
treated?
We need to do two different kinds of research in order to
establish that on an evidence-based manner. The first is to do
more preclinical studies so that we understand the biological
basis for the different prognosis for different patients with
breast cancer. And the second is to do clinical research
particularly through understanding large datasets that have
been discussed earlier in the hearing to understand the patient
responses and whether patients actually need this through large
databases with genomic analyses, et cetera, that Dr. Collins
referred to earlier. Through this combination, we will get to
the point of being able to tell who is better to give more
treatment to and who less.
Senator Blunt. I think for those of us who are the ultimate
laypeople in part of this discussion, having a few things like
that that we can mention as possibilities make a difference. It
certainly begins to make the case for how this research impacts
individuals, how the research impacts overall healthcare costs,
how the research leads to more opportunity for people and
families, and it's just helpful for us to have.
ALLOCATING ALZHEIMER'S DISEASE FUNDING
Dr. Hodes, if you know, looking at what you're looking at
with Alzheimer's, as an example, how much of a factor is
determined on how you allocate research dollars based on what
you see as a growing problem rather than a more stable problem?
Alzheimer's would be an example of your numbers.
The committee asked you a couple of years ago to do some
forward projections on this. You did. If your projections are
anywhere close to correct, it's an astronomical problem, and I
assume that has impact on how quickly you apply research focus
there, but your thoughts on that would be helpful.
Dr. Hodes. Thank you for the question. You summarized
yourself very well the projections for cost, and of course, the
cost isn't just dollars, but above all, is human suffering
until we are successful. The increased funding that's been
provided is being applied to research, research that's directed
according to a plan very much based on best expert opinion,
which sets up priorities, milestones. What we need to do each
year to achieve with greatest optimism, at least the goal of
the national plan, that is an effective intervention by 2025,
it's an aspirational goal, it's a hope for goal, and so you're
quite right, as we allocate resources in this area, we allocate
across the spectrum, the most basic research to discover new
targets, because we don't know that what we know now is
ultimately what's going to give the best cure. Also, the
translation of our current best targets into clinical trials.
And the great hope we have now, I think, in the field, that by
intervening in a way we couldn't just a few years ago in the
disease process long before there are symptoms, we have an
opportunity to arrest damage before it perhaps occurs
irreversibly with death of brain cells and so on, all of this,
as you say, driven by the suffering of people today as well as
by the demographic projections of how great this problem will
be and even increased magnitude in years to come because of the
success we've had in increasing life expectancy and health span
in so many other respects.
Senator Blunt. Thank you.
Senator Murray.
BIG DATA FUNDING
Senator Murray. Thank you. I want to go back and ask Dr.
Koroshetz a question on the big data. How much of the funding
in your request is going to be dedicated to creating data
centers in the fiscal year 2017 budget?
Dr. Koroshetz. Yes, thanks. We have been thinking about
this for a while. You know, the BRAIN Initiative starts out
primarily developing new technologies, so that's currently in
the space we're in now. So not a lot of big data coming in yet,
but the expectation was that at about 3 years, which is going
to be fiscal year 2017, that we would start moving into actual
experiments that look at brain function in humans as well as
animals, and so we are going to be challenged now with building
the data platforms that will allow this work to happen on a
collaborative basis.
Having been at the Allen Brain Institute, you may have
seen, they have a tremendous, tremendous data platform for the
work that they're doing. And so, we have multiple different
groups, doing different areas of research, and those groups are
actually working out, what is the best data platform for them
at this point. We expect in 2017, we will spend $5 million a
year on data platforms.
Senator Murray. $3 to $5 million. Okay.
And Dr. Collins, let me go back to you. The challenge isn't
unique just to the BRAIN Initiative, it's across NIH. What are
you doing to make sure that we have common standards
established across the entire enterprise to avoid creating
incompatible systems and practices?
DATA SYSTEM STANDARDIZATION
Dr. Collins. That is a very important challenge and
responsibility. And again, as part of this Big Data To
Knowledge, BD2K, program, we are actually funding something
called a Data Discovery Index, which is one of our centers for
data science, and basically this is attempting to come up with
standards where data that's been produced on a wide variety of
research studies, from basic to clinical, can be accessed by
individuals who are looking for it without having to run
through all kinds of incompatibilities. This is a challenge,
but I think one that we're making some significant progress on.
Obviously, it's easier if we do these things prospectively than
trying to retrofit databases after the fact, and so there's a
lot of focus in that space.
What we're dreaming of, and which we have actually some
significant pilot projects underway on, is a data commons where
basically all of this information finds its way into a common
space with standards, with appropriate so-called metadata, so
when you get a data file, you know what it is and how it was
derived and----
Senator Murray. Housed at NIH?
Dr. Collins. Probably in the cloud, but potentially our
investigators contributing to it, and we would need to, as part
of grant funding, supply the resources to make that possible.
DIVERSITY IN MILLION-PERSON COHORT
Senator Murray. Okay. And let me just quickly ask you about
the million-person cohort again. I am concerned about
diversity, and I just wanted to ask you again, how do you make
sure you're doing it and working with experts that you avoid
the risk of bias that could affect the cohort's usefulness if
it isn't a diverse trial?
Dr. Collins. We want very much for this to be a
generalizable cohort, which means we need to have
overrepresentation of groups that are traditionally
underrepresented. So that means minorities, that means
individuals from lower socioeconomic status. We will look
carefully when we open this up to direct volunteers and begin
to try to see how we're doing as far as bringing such
individuals in, and we'd be concerned that they might not be
coming in as large numbers as those who are more in the
majority population.
A big effort is going to be for us, through the community
health centers, to try to see how we could use, in an
unprecedented way, those centers which give care to more than
10 million people, also as an opportunity to carry out
research, recognizing that we want people involved in this
study not to think of themselves as subjects, but as partners,
as full participants, in this effort, and we will approach them
in that way.
Senator Murray. When do you expect to have the details of
that worked out and are going to be willing to share them?
Dr. Collins. So we already put together the overall plan.
It was published last September as far as the design, the
Precision Medicine cohort. We're now trying to figure out how
to implement that. Later this year, by the fall, we'll have a
much better sense of exactly how successful we're going to be
with those various inputs.
Senator Murray. Okay. Thank you. Thank you very much.
Senator Blunt. Thank you, Senator Murray.
Chairman Cochran.
RECENT BREAKTHROUGHS
Senator Cochran. You may have just answered the question I
was going to ask, but I'm going to ask it anyway. Do you have
any recent breakthroughs that you can announce or tell the
committee about as a result of investments that we have funded
through the appropriations process here in Congress?
Dr. Collins. One of the things that's a great privilege for
me is to write every Tuesday and every Thursday a blog, I hope
some of you are reading my blog, but I bet you're not, but I
would encourage you, if you have a couple minutes, to do so.
And as part of that, I survey across the whole landscape of
biomedical research to see what new things have just appeared
in the published literature that are particularly exciting. And
so every time I have the chance to do that, there's a new
story.
Today's story, if you read the blog, which came up, I
guess, about an hour ago, is about a engineer who has developed
the kind of sensor that you could use for measuring all kinds
of body performance properties, including glucose, if you
wanted to use this as part of a artificial pancreas, but the
sensor is designed so that it's not this rigid metal structure,
which probably wouldn't work very well in the body, it's
flexible, and this is an interesting sort of materials issue.
If we are going to come up with ways to monitor all kinds of
ways in which our bodies are performing in health or disease,
we need these kinds of sensors to be very durable and to be
possible to not interfere with function, which means sort of
rigid structures may be not such a great idea. So that's
today's blog, for instance.
But looking across the board, goodness, some of the things
that are happening in cancer right now, I guess I'd have to
point to particularly something I mentioned in the opening
statement that relates to President Carter, the ability to
activate the immune system to tackle cancer cells that you know
the immune system ought to be able to see, but somehow it's
been masked, and we can unmask it with things like checkpoint
inhibitors or actually taking immune cells to school and
teaching them how to go chasing after the cancer that they
haven't noticed, and to figure out how you might take those
advances, which have changed everything for people with
melanoma and leukemia and lymphoma, and figure out, how does it
work for pancreatic cancer and how does it work for brain
cancers, where we are not as successful? That's a big push.
That's one of the reasons for the Cancer Moonshot that the Vice
President is now promoting.
And I guess I should ask Doug Lowy to say another word or
two about why we see this as such an exciting moment and why
there are some breakthroughs already happening, but more to
come.
Dr. Lowy. Senator Cochran, let me give a two-part answer
first to your question and then what Dr. Collins has mentioned.
The excitement in immunotherapy is matched by the fact that
immunotherapy started really with basic research quite a long
time ago with support from NIH specifically at NCI, and what we
are seeing is almost on a monthly basis the surprising finding
that checkpoint inhibitors progressively have beneficial
effects in more and more cancers.
The Vice President's Moonshot Initiative, an important part
of it is to try to understand and utilize combination treatment
so that we use combinations of immunotherapy, combinations of
targeted treatment, and intersection between those so that we
can get better responses and target a much broader percentage
of people who have cancer.
But the Moonshot goes far beyond that, and it looks at
cutting edge research opportunities that have been created as a
result of new understanding, and new understanding of the
dynamics of this, and putting them together so that we can make
accelerated progress in prevention, screening, treatment, and
basic research.
CLINICAL TRANSLATIONAL SCIENCE AWARDS
Dr. Collins. If I may, one of the things I think that the
public is particularly excited about is when we have a clinical
breakthrough, and Dr. Austin has not had a chance to speak, but
I wanted to ask him to say a word about where we are by
building this national clinical research network called the
CTSAs, which is in a phase of coming forward with a number of
ways of accelerating that part of the research enterprise. It's
pretty exciting.
Dr. Austin. Yes. So thank you. As you all know, the current
numbers are, it takes about 15 years to go from a discovery to
a new intervention, a new drug, for instance, and another 15
years before it reaches all the patients that need it. That's
always been a problem, but it's a particularly heartbreaking
problem now given how many opportunities there are. So our
Center is focused on the general issues that prevent that from
happening faster, and our aim is to decrease that time by
tenfold and increase the efficiency by which it happens. That's
our goal, and I think it's achievable.
[The graphic follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Dr. Austin. The biggest part of that, the year, those
years, happens in the time when we're testing in people. There
are many things that can be done through the CTSA program,
which is this unprecedented program that NIH has of academic
medical centers all over the country which have been
previously--oh, so there they are, that's where they are, in
many or most of your States, and they have connections to the--
all the ones that don't have little dots there, connections to
all the States in the Union. And what we've been doing is to
tie these together into a collaborative national network for
translational medicine such that patient clinical studies,
multisite clinical studies, can get started up, recruited,
completed, much more quickly and with much higher quality, and
we've done this through a national network for IR, or
Institutional Review Board standards of subcontracting, a
national way to do recruitment for any clinical trial, it
doesn't matter what the disease is, and novel clinical trial
designs. So those are just some of the things that we're doing
through the program. And I really do want to thank you for your
support in doing that because it's really been critical to us.
Senator Cochran. Thank you very much.
Senator Blunt. Thank you, Chairman.
Senator Shaheen.
NIH/DHS PARTNERSHIP
Senator Shaheen. Thank you, Mr. Chairman. I very much
appreciated getting a copy of this NIH-wide Strategic Plan. I
haven't had a chance to review it completely, but I wanted to
ask a question that puzzles me as I look at the list of your
frequent Federal partners and see many agencies that I would
expect and departments I would expect to be on the list: DOD,
EPA, Veterans Affairs. But what is not on this list is the
Department of Homeland Security, and I found that puzzling
because we had a hearing yesterday before our subcommittee of
Appropriations where we heard from the DHS Office of Health
Affairs, their Domestic Nuclear Detection Office, the Science
and Technology Office, and they talked about some of the things
that they're working with respect to workforce issues for both
mental and physical health. And so I'm just puzzled by whether
that's an omission on this list or whether you don't work with
them regularly, and why that is.
Dr. Collins. That's a great question. We do work with them
in terms of particular topics of shared interests, such as, for
instance, concerns about bioterrorism. I think the list that
you see in the strategic plan is more about agencies where we
share research projects, where we're putting dollars together
into something to try to do a research study and get an answer.
Our work with Homeland Security is really much more about
policies, and we see them quite regularly when it comes to
that, particularly when it comes to concerns about infectious
diseases.
Senator Shaheen. That's helpful. The hearing yesterday
actually was on their R&D efforts, and so there was some
overlap, and I just--I'm always concerned about the silos that
I think too often we work in, in government and the need to
coordinate and cooperate across agency portfolios so that we
get the benefit of what everyone is doing.
Dr. Collins. I appreciate your pointing this out, and it's
something I will personally look into to see whether it could
be in fact we are working with them in an R&D project and I
just didn't know about it and didn't put it in that plan. But I
will follow up on that.
Senator Shaheen. Thank you. I appreciate that.
Thank you, Mr. Chairman.
Senator Blunt. Senator Cassidy.
UNIQUE IDENTIFIERS IN BD2K
Senator Cassidy. Hey, Dr. Collins, a couple other things.
As I look at your BT--your Big Data To Knowledge initiative,
and you speak about having centralized data where people allow
their EHR (Electronic Health Record) information to be
transferred, obviously, some folks will be in multiple EHRs.
That suggests to me that you've some way decided on a unique
identifier, means of identifying. On this panel and this
Senate, there is some concern about unique identifiers, however
they be. So do you want to give an in-depth--if you think it's
too in depth, but if you could point me in the direction
because we are trying to understand the use of unique
identifiers, et cetera.
Dr. Collins. Very important and complex topic. Purely from
a research perspective, it would be wonderful to have unique
identifiers so that we could deal with circumstances where we
have data on the same person coming from multiple directions.
We understand the concerns that many have about the use of such
identifiers, and so we are not counting on that becoming a
reality, and instead, it becomes necessary to use other kinds
of algorithms to try to disaggregate records that appear to be
from the same person, but might not be. And of course,
oftentimes one tries to do that with simple things like birth
dates and middle names and so on, but there will be times where
we don't get that right.
The good news, I guess, is that we're talking about very
large studies where in fact if we are unable to utilize a few
records because we can't be sure of their particular
provenance, we may just have to set those aside.
Senator Cassidy. The answer you just gave suggests that it
won't be a passive process where somebody will designate my
records shall go, but there will be some sort of outreach from
the database searching like a bot, where did Bill Cassidy show
up as you search, and then to pull in there's a Bill Cassidy
that previously consented for his data to be--is that correct?
Dr. Collins. That is correct, because we understand the
sensitivities about not having electronic health records with
personal identifiers being stored in one common dataset where
there might be more of a potential for hacking problems.
STORAGE OF BIOSPECIMENS
Senator Cassidy. Now, in that case, I've looked at it, much
of what your PMI (Precision Medicine Initiative) has done is
said to be centralized, but it sounds as if your EHR aspect
will be federated in that my record will reside in Louisiana,
but nonetheless, here in D.C., my blood sample would be kept,
my hair, my nail clipping, and somehow that has reached out to
where my primary care physician is in Baton Rouge. Is that
fair?
Dr. Collins. With regard to the biospecimens, we anticipate
that in many instances these are people who part of health
provider organizations and there obtain the biospecimens, but
we do intend to have a biobank which is centralized where all
these specimens are stored and kept over many years of time.
So, yeah, you're right, that will be centralized even though
the details of the electronic health record will remain with
the patient.
Senator Cassidy. Now, I've read an article by Keith
Yamamoto and heard a lecture by him. I know he's been on
advisory boards.
Dr. Collins. Yes.
Senator Cassidy. Very impressive, talks about the Google
Map aspect of it. Again, your thinking prepared me for this,
but the genomes, the microbiome, the exposures, behaviors,
clinical tests, and EHR. Now, the expense of that is going to
be enormous. So is your initial PMI going to include all these
layers, or would that be something that we move towards?
Dr. Collins. The latter. It's a very important question.
We're going to start off very simple to both try to save costs
and try to be sure we have this set up in a fashion that is
completely robust. We don't, in fact, even anticipate doing
much DNA analysis on individuals who join just from blood DNA
for the first year or so, and certainly the idea of adding a
microbiome part, which many of us are excited about, would be
downstream. That will help us because the costs of those
analyses are coming down, as you know, quite dramatically.
Right now, we could not afford, with a million people, to do
all the things that we'd like to, but if we stretch that out
over the coming years, the costs will come down, and we think
we can afford to add those things as we go along.
Senator Cassidy. Going back to the business model, though,
I can see where, okay, so gut flora can influence obesity, for
example.
Dr. Collins. Yes.
Senator Cassidy. So we'll be swabbing gut flora. But I
guess I keep on going back to the business model because I can
see this terabytes and terabytes growing, so it not only grows
in terms of terabytes, but in terms of its bite on the NIH
budget, the cost to accumulate, to maintain, longitudinally on
a million people, and from your aspect, you actually want to
grow that million to a larger number.
So I see that California has begun their own Precision
Medicine Initiative. I can imagine other States might as well,
both as an economic driver as well as an aid. I don't know how
far your business model is going down, but I can still see a
federated model of this where instead of everything
centralized, just as you federated the EHR, so you've federated
some of this other.
There's a unique population in Louisiana of young pre-
menopausal black women who have triple negative breast cancer,
and another group of folks of Cajun extraction at high risk for
colon cancer. I have tremendous interest in my State because I
want to address both the needs of these women and these men. It
seems more practical that that would be domiciled, all that
specimen, et cetera, in Louisiana than there; the women are in
an impoverished area of the State, as an example.
So anyway, any thoughts about that, a federated model of
the whole setup as opposed to----
Dr. Collins. I think part of the conversation is
distinguishing between the Precision Medicine Initiative, which
is this explicit now designed cohort of a million people, and
Precision Medicine writ large. I think the concern I would have
is that we not try to have the initiative take on all of the
opportunities that now exist in Precision Medicine. They should
be also going forward supported by all of the NIH Institutes
and other sources as well. And it will serve us well, I think,
best at the present time if the million-strong cohort keeps a
very simple approach and doesn't focus on any specific
diseases, but tries to enroll a generalizable population on
which other studies can then be layered.
Senator Cassidy. A follow-up question, but you may tell me
I should do a QFR unless you're going to give me an allowance
for one more.
[Laughter.]
Senator Cassidy. Forgiveness, not the permission.
[Laughter.]
DUPLICATIVE DATASETS
Senator Cassidy. But that tells me then that we're actually
going to have duplicative efforts because I think I've read
that there are 70 different datasets at NIH, and so logically--
now, I may not have that quite right, but each institute has
its own dataset, and there is some effort to coordinate, but
that means that we're going to have these 70 different datasets
and we're going to have the PMI, the Precision Medicine
Initiative, Ken Mandl has written so well, that really we don't
need to have all these different datasets plus, rather, we need
this to be able to bring in these different datasets.
We're trying to find you funding, but, again, I see this
initiative taking more and more of what Senator Cochran is
going to give you. And if we could integrate, now that you've
thought about this, if we could integrate this, why not, if you
will?
Dr. Collins. Well, maybe I didn't explain this as clearly
as I should have. The Precision Medicine Initiative has had its
budget sort of thought through, and that's in the proposal that
came out in September, and right now for fiscal year 2017,
proposed at $300 million. They need to ramp up to about $500,
but not to go beyond that. But let me be clear, the institutes
at NIH all look at this million-strong cohort and think, wow,
what a great platform on which we could layer all kinds of
other studies. With a million people, there are going to be
tens of thousands who have a particular condition already
consented for research, already with background information.
So a lot of the studies that we have been doing in the
past, by setting them up de novo, which is expensive, and then
running the study and then closing it down, can now be done
much more efficiently by utilizing this platform for whatever
it is that we need more information about. I think ultimately
this saves us a lot of money over what we currently spend in
clinical research.
Senator Cassidy. Okay. Thank you. I yield back.
Senator Blunt. Thank you. Well, Senator Cassidy figured out
how to get his second and third round at the same time.
[Laughter.]
Senator Blunt. You know, on the national children's study
that was done a few years ago, this diversity topic at the end
of that study I think became one of the more questioned parts
of the study, so a lot of these questions I think are helpful.
There will be--the record is going to stay open for a week for
additional questions, but is there anything while we're all
here for another 5 minutes or so that you or any of your
colleagues would like to address?
The written questions are good, and they're particularly
good for people who have submitted them. I'm not sure that very
many people look at the questions they didn't ask in the
written questions. So is there anything here--we almost left
Dr. Austin out. Is there anything here that any--Francis, Dr.
Collins, that any of you want to bring up?
Dr. Collins. Any of you want to volunteer a point that you
didn't get to make that you thought would have been
particularly timely?
Dr. Lowy. Thank you, Senator Blunt. I think that you all
have a copy of the New England Journal of Medicine perspective
that Dr. Collins and I wrote and was published earlier this
week about the Vice President's Moonshot Initiative. Dr.
Collins and I and my colleagues at NCI, as well as many
extramural people, are working closely together to try to
develop what we think are going to be incredible opportunities
for cancer research to benefit patients. This effort really
goes from basic science all the way to implementation, and
thanks to your strong long-term support, we are poised to
accelerate progress thanks to this proposal.
And we have a blue ribbon panel that is going to be
reviewing what we currently propose as well as looking forward
to receiving other potential enormous opportunities. We are not
trying to cover the entire waterfront of cancer research, but
instead, to point to specific opportunities for research that
will be bold, feasible, and have an impact in basic prevention,
screening, and treatment.
Thank you.
Dr. Koroshetz. Yeah, I would just like to talk a little bit
about the question of priorities that came up and just make the
point that if you look at the history of advances, you can't
predict where they were going to come from. And so I think it's
tricky to say, you will get a certain result if you put money
into that I think Zika is a great example. It turns out that
one of the investigators who was working on the BRAIN
Initiative to develop ways of identifying all the different
cell types in the brain is the one who found out how the Zika
virus was getting into the brain. He had nothing to do with
Zika, but that technology turned out to be beneficial, and
there was no way of predicting this.
Our major advance lately was a study using a diabetes drug.
The study was 17 people who had a stroke, and also but didn't
have diabetes had an abnormal glucose metabolism. We treated
them for 5 years with a diabetes drug, and their stroke risk
dropped by 24 percent. So, again, this is something that you
couldn't have predicted, but retrospectively, it kind of makes
sense.
And so I just urge the committee to think about this
importance of the foundational basis of research, which is
critical. Targeted research is risky in the sense that you're
putting your money on one horse. You don't actually know all
the time which horse is going to win.
Senator Blunt. Anything else?
Dr. Collins. I'll just add to what Walter said about the
convergence both of science that comes from unexpected
directions, but also about scientific disciplines that have
increasingly come together. You mentioned your experience of
seeing how engineers are playing a role in biomedical research
in really exciting ways. That's happening all around us, and
the idea that we have to have physics over here and chemistry
over there and biology over there, engineering over there; not
anymore. These are all very much now coming together in an
integrated way.
I guess I would just like to say, because I've now been at
NIH for some 23 years, it was real poignant today walking from
Union Station over here to this hearing, passing by the pink
dogwoods and tulips that are blooming along the sidewalk and
realizing this is probably my last opportunity to appear before
all of you distinguished Senators.
People have asked me since I became NIH director 7 years
ago, ``So what's that part like where you have to interact with
the Congress?'' and I always break into a smile and I say,
``It's one of the favorite things that I get to do because I
get to sit in the room or in a hearing with very substantive
people who are trying to lead our country in the right
direction and talk about medical research, and it's a topic
that everybody is interested in, and it's not partisan, and
it's not political, and everybody wants to do the right
thing.'' And I can't think of a single one of those
interactions that went badly, and I'm happy to say today has
added to that list of things that actually went really well.
And so I just want to thank you, the four of you still
here, and all the others who aren't here, but who I've had the
chance to talk to, hundreds of them, over the course of this
time, for your dedication to our country, for trying to do the
right thing for all the people out there whose hopes and dreams
are rested upon progress in this area, because everybody cares
about health and everybody hopes that there will be something
there for them if they fall ill.
You are doing wonderful work. We are thankful to you for
what you've done and hopeful for what you may be able to do
this year, even in what is undoubtedly a challenging time. So
thank you.
Senator Blunt. Well, thank you, Dr. Collins, and you've
done a great job leading the organization. Every time you
suggest this could be the last time you're doing something, I'm
always here to encourage you not to rush out the door.
[Laughter.]
Senator Blunt. There are plenty of things yet to be done,
and I would be personally pleased if you continue to be a big
part of those things to be done.
Also, I think comments were just made, it's so important to
us to realize that you can't prescribe results, and not to
become overly prescriptive in the work that you do or how you
do it. The Thompson Center I mentioned earlier at the
University of Missouri deals with autism. Somebody from the
engineering department is very engaged in trying to find an
early way to detect autism in very young children with some
equipment looking at eye examinations, no medical background,
but a very important part of that team, and you know, what
Walter mentioned, is discovering things you don't think you're
going to discover, and we don't want to build walls that make
it impossible for you all to have that kind of flexibility and
determination.
ADDITIONAL COMMITTEE QUESTIONS
So thank you for today. The record will stay open for one
week for additional questions.
[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 Roy Blunt
``surge'' funding
Question. NIH received 2 year ``surge'' funding in fiscal year 2009
and fiscal year 2010 as part of emergency funding contained in the
American Recovery and Reinvestment Act of 2009. Dr. Collins, can you
discuss what happened in fiscal year 2011 when this ``surge'' funding
was not maintained and NIH had approximately $5 billion less in funding
than it did the year before?
In particular, as we think about the appropriate upward funding
projection for NIH, would you ever want funding to decrease at a given
point?
And what happens to the research infrastructure the first year
funding is reduced?
Answer. Everyone was aware that the $10.4 billion NIH received
under the American Recovery and Reinvestment Act (ARRA) would be one-
time funding. It was spent in a way that did not create out-year
commitments, either by providing full funding for a multi-year research
project up front, or by making capital investments such as construction
projects. As a result, the return to a more typical funding level in
fiscal year 2011 did not have the same impact as a reduction in annual
funding.
NIH usually awards grants for multiple years, with each year's
funding coming from the current year appropriation. Whenever possible,
an increase in appropriations is used to make more new and competing
grants. Those grants will continue to require a similar level of
funding in the out years, as noncompeting grants. With flat or
decreasing funding the next year, the number of new and competing
grants is likely to decline, as the prior year increase has to be used
for the additional noncompeting grants. The optimal scenario is
increasing funding at a steady rate; that allows the number of new and
competing grants to increase each year.
If it is clear in advance that a funding increase is one-time
rather than recurring, NIH can take steps as it did with ARRA to avoid
a negative impact the following year. A reduction to recurring funding,
especially a large reduction, would be damaging to NIH. For example, in
fiscal year 2013 there was a major reduction in funding due to
sequestration. Compared to fiscal year 2012, the number of new and
competing research project grants (RPGs) declined by more than eight
percent, and noncompeting RPGs had their funding cut by nearly 5
percent on average. The number of National Research Service Award
trainees declined by almost five percent, and approximately 7 percent
fewer new patients were admitted to the NIH Clinical Center.
drug repurposing & clinical and transitional science awards
Question. Dr. Austin, clinical trials are key to developing
treatments for disease, but I often hear that they are quite time
consuming and costly. What is NCATS and its Clinical and Translational
Science Award program doing to improve the clinical trial process?
Answer. NCATS is grateful to the committee for its fiscal year 2016
support of the Clinical and Translational Science Awards (CTSA)
Program. We define translation as the process of turning observations
in the laboratory, clinic, and community into interventions that
improve the health of individuals and the public--from diagnostics and
therapeutics to medical procedures and behavioral changes. Through the
CTSA Program and its extensive network of research institutions
nationwide, NCATS is developing innovative solutions to improve
efficiencies and the quality of clinical and translational research.
Our Center also supports multiple efforts to repurpose existing drugs
and compounds for potential treatments for other diseases and
conditions; however, because these repurposing programs do not directly
relate to the clinical trials process, our response is limited to the
NCATS CTSA Program.
NIH's Institutes, Centers, and Offices have a long, distinguished
history of funding landmark clinical trials including those for
coronary bypass surgery, treatments for breast cancer, and anti-
retroviral drugs for people at high risk for HIV/AIDS infection. NCATS
is addressing issues common to all clinical trials with a focus on
approaches to harmonize and streamline multisite clinical trials, which
are more complicated to initiate because each trial site currently
follows its own business and research practices. This continued work to
improve clinical trials research builds upon our Nation's success as a
leader in biomedical discovery and provides a competitive advantage in
developing, demonstrating, and disseminating innovations that help get
more treatments to more patients more quickly.
One NCATS approach is the development of a more efficient review
and approval process of multisite clinical trial safety using a single
Institutional Review Board (IRB) model. Currently, clinical trial
researchers cannot begin recruiting participants until an IRB performs
an ethical review of studies involving human subjects. IRB review often
slows down a multisite clinical trial because the different sites must
address inconsistencies across the different IRBs. The single IRB model
streamlines IRB review by having sites rely on a single IRB without
compromising ethical principles and protections. Through the CTSA
Program, NCATS has supported demonstration projects of single IRB
models and is moving toward a model that will be used throughout the
CTSA Program network. And, in 2016, NCATS will announce CTSA Program
Trial Innovation Center awards to fund centers that will network with
existing CTSA Program hubs to facilitate multisite clinical trial
implementation, including use of a single IRB model.
Another CTSA Program goal is to support recruitment efforts for
clinical trials. Multisite clinical trials may require substantial
subject sample sizes to credibly test hypotheses, and trials often are
delayed or even fail entirely due to challenges in recruiting
participants. To help combat the challenges, NCATS will issue awards in
2016 for CTSA Program Recruitment Innovation Centers. These will
strengthen the CTSA Program's network capacity by addressing
longstanding issues associated with multisite clinical trial
recruitment, including access to data on the availability of potential
participants; recruitment strategies that employ innovative approaches
from other fields such as communications; and engagement of relevant
stakeholders (e.g., potential participants and referring clinicians)
early in the recruitment process.
precision medicine initiative
Question. As you continue to shape the Precision Medicine
Initiative (PMI), have you considered what projects other countries are
working on to further personalized medicine and whether they are
complementary or competitive? For example, both Great Britain and China
have PMI programs.
Answer. As you are aware, during its planning efforts, the PMI
Working Group of the Advisory Committee to the Director (ACD) engaged
many individuals and organizations across industry, nonprofits, and
academia to ensure that Federal funds dedicated to the PMI Cohort
Program are used to fill gaps and not duplicate effort. The PMI Working
Group, for example, was constituted of nationally and internationally
renowned experts in a variety of precision medicine relevant areas and
represented industry, nonprofits, academia, and the participant
communities, including Sir Rory Collins, who leads the UK Biobank. NIH
continues to interact with industry, nonprofits, and academia with
other efforts and cohorts, including Google's Baseline Study, patient
groups, NIH's own funded cohorts, and Department of Veterans Affairs
efforts like the Million Veteran Program, as well as the growing number
of international research precision medicine-oriented cohorts. NIH's
ongoing interaction with these important organizations will allow
opportunities for appropriate, mutually beneficial coordination to
emerge as the PMI Cohort Program developes.
Question. At the White House PMI Summit event in February 2016, all
of the patients presenting precision medicine success stories
attributed those successes to genome sequencing, specifically. Yet, to
date, no plans have been announced for collecting sequencing data from
PMI participants. Why is that? Are there plans to do so?
Answer. NIH has consistently identified the collection of
biospecimens for laboratory and genomic analyses as a critical
component of the research cohort. The award to establish a biobank to
receive such specimens will be issued this summer. Once the biobank is
established, then the PMI Cohort Program may begin specimen
collections, processing, and storage to be conducted over the next 4
years, during which time the timing and platform for genomic analyses
will be identified and implemented.
Question. How will NIH ensure the full participation of women and
minorities in PMI?
Answer. The PMI Cohort Program intends to enroll one million or
more U.S. volunteers representing all life stages, all health statuses,
and all regions of the country, with a special emphasis on enrolling
those who are historically underserved by biomedicine and
underrepresented in biomedical research. We project that the majority
of the one million volunteers that will be enrolled by the end of 2019
(around 70 percent) will join directly through the healthcare provider
organizations (HPOs, including federally Qualified Health Centers), and
the balance (around 30 percent) will enroll directly into the Cohort
(``direct volunteers''). The enrollments of the Cohort through both
streams will be carefully monitored to ensure that our outreach and
enrollment approaches are reaching a broad range of U.S. participants,
including women and underserved communities that are historically
underrepresented in research.
Question. Is NIH working with the National Center for Health
Statistics or other Federal partners that fund or conduct large,
representative surveys to understand the biases in the PMI million
person cohort?
Answer. The PMI Cohort will not attempt to be a representative
sample of the United States. Rather, the PMI Cohort will build a very
large and very diverse cohort of participants from across the United
States. This will allow the PMI Cohort to establish generalizability
using a different approach: by having a diverse sample, it will have
many subsamples that are composed of members of specific subgroups. By
having a large sample, those subsamples will be large enough to develop
estimates of effect and association for many of those subgroups. That
will allow researchers to judge how similar those estimates of effect
and association are across a variety of subgroups within the PMI
Cohort, and thus to establish the generalizability of their findings.
The development of this approach included extensive consultation and
input from expert advisors through the ACD PMI Working Group process.
enrollment data
Question. The GAO recommended that the NIH Director should make
Institute-level enrollment data available through public means, such as
through NIH's regular biennial report to Congress on the inclusion of
women in research, or though NIH's website. How is NIH moving forward
with this recommendation?
Answer. NIH posted the most recent Institute/Center (IC) biennial
inclusion reports for the fiscal year 2013-2014 biennial reporting
cycle in early May 2016 at a newly created website: https://
report.nih.gov/recovery/inclusion research.aspx.
NIH ICs currently provide their IC-level enrollment information
during open, public sessions of their Advisory Council meetings along
with a written report certifying their compliance with the NIH
inclusion policy, and they will continue to take this action at least
biennially in accordance with NIH procedures for biennial reporting of
inclusion. As noted in NIH's initial response to the GAO report, NIH
had already begun efforts to standardize the reporting format for the
ICs as part of the ongoing NIH Inclusion Re-Engineering Project that
began in 2011.\1\ NIH is continuing efforts to standardize a minimum
set of data tables and graphics for each IC to use for biennial
inclusion reporting, in addition to any additional analyses the IC
would like to provide. The standardized reporting format will be
completed before the fiscal years 2015-2016 Biennial Inclusion Report
is due to be produced and posted in 2017.
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\1\ Http://www.gao.gov/assets/680/673276.pdf.
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tuberculosis
Question. The number of tuberculosis cases in the United States
rose last year for the first time in 23 years according to the Centers
for Disease Control and Prevention. What progress has the NIH made on
developing more effective treatments and vaccines?
Answer. Tuberculosis (TB) research, including the development of
effective therapeutics, vaccines, and diagnostics, is a top priority
for the National Institute of Allergy and Infectious Diseases (NIAID).
NIAID supports a broad range of basic, translational, and clinical
research on TB in the United States and abroad to combat TB, including
the growing threat of multidrug-resistant (MDR) and extensively drug-
resistant (XDR) TB. As TB is the leading cause of death in HIV-infected
individuals worldwide, NIAID also supports TB research through its HIV/
AIDS clinical trials networks to test TB therapeutics in the setting of
HIV co-infection.
NIAID is currently implementing the President's National Action
Plan for Combating MDR-TB. TB research objectives outlined in Goal 3 of
the Action Plan, Accelerate Basic and Applied Research and Development
to Combat MDR-TB, are being addressed by NIAID in collaboration with
partners at CDC and USAID. NIAID is leveraging current and past
investments in biomedical research to inform critical scientific areas
of TB research and to facilitate development of new drugs, vaccines,
and diagnostics to help prevent TB and the emergence of MDR-TB.
As part of its TB research portfolio, NIAID offers preclinical
services to TB researchers in academia and industry to help bridge gaps
in the product development pipeline and advance promising
countermeasures to combat TB. NIAID resources have contributed to two-
thirds of clinical TB therapeutic candidates and approaches currently
in development. NIAID support has helped advance several candidate TB
drugs, including SQ109 developed by Sequella, Inc., and Pretomanid
developed by the Global Alliance for TB Drug Development. NIAID
scientists were instrumental in the development of both of these drugs.
Additionally, an NIAID-supported clinical trial will soon test two new
drugs for MDR-TB, bedaquiline and delaminid, singly and in combination
in patients with and without HIV co-infection. NIAID scientists also
participate in the ``TB Drug Accelerator'' program, an innovative
public-private partnership coordinated by the Bill & Melinda Gates
Foundation that brings drug companies together to share their chemical
libraries with researchers to assist in the identification of novel TB
drug candidates.
NIAID also has made efforts to improve existing therapeutics for
drug-susceptible and drug-resistant TB. Clinical trials are underway to
evaluate novel treatment strategies using existing drugs, such as
rifampin, levofloxacin, and linezolid. In addition, NIAID and other
scientists are evaluating two medical imaging technologies, positron
emission tomography and computed tomography, for their utility in
predicting TB drug treatment outcomes by allowing researchers to
monitor whether bacteria remain in the lungs after therapy. These
technologies could be used in combination to help facilitate and
shorten clinical trials for new drug treatments. Studies to further
develop these technologies are currently underway in South Africa.
In addition to supporting research on TB therapeutics, NIAID is
pursuing TB vaccine development to improve upon existing TB vaccine
options. NIAID-supported research has contributed to ten of the TB
vaccine candidates currently in clinical trials, and NIAID is
supporting preclinical development of additional promising vaccine
candidates. For example, NIAID supported early-stage development of
vaccine candidates H56 and ID93. In addition to protecting against
infection, these TB vaccine candidates may also be effective in
protecting individuals with latent TB infection from developing active
TB disease. These vaccines are currently in clinical development.
Longstanding NIAID investments in TB research and collaboration
with domestic and international partners have advanced the development
of novel therapeutics and vaccine candidates. NIAID remains committed
to combating TB and will continue to support basic, translational, and
clinical research focused on developing new countermeasures for drug-
susceptible and drug-resistant TB.
department of defense brain bank
Question. The Department of Defense and the NIH partnered to create
the world's first human brain tissue repository for military personnel.
However, it is my understanding that NIH researchers are having issues
accessing post-mortem tissues from servicemembers affected by blast
injury. Dr. Koroshetz, are NIH researchers being provided access?
What are the hurdles you are facing to gain access to these
resources?
Answer. It is our understanding that the major hurdle is the
absence of an effective manner to obtain informed consent from a
service member's family that would allow a careful examination of
tissue removed at autopsy by the DOD Medical examiners. DOD currently
classifies a careful examination of brain tissue for the effects of
blast injury as research, which requires informed consent. It is our
understanding that autopsies have been performed at the Office of the
Armed Forces Medical Examiner in Dover, Delaware, and that brain tissue
was removed but is not available for detailed study due to the lack of
a means to obtain consent for study. Although consent is a sensitive
and highly personal decision, we believe many families would recognize
the potential of such examinations to benefit other current and future
service members. DOD has recognized and understood the issues
concerning service member brain donation for research purposes, and is
working to increase the availability of specimens while also complying
with established law and policy governing human subjects research and
respecting the needs of families who have recently lost a loved one.
Based on the examination of the handful of well-studied cases, we
are concerned that blast injury causes a unique type of brain injury.
To know how common these unique findings are requires examination of a
larger number of brains. If these findings can be substantiated it
would shift the focus to brain imaging evaluations of living veterans
who were exposed to blast and would also help to direct valuable
research focused on means to protect future service members from blast-
induced brain injury.
Question. Can you discuss the importance of having access to brains
that have experienced blast injuries?
Answer. Access to brains that have sustained a blast injury is
absolutely essential to understand the effects of blast injury. DOD and
academic laboratories are studying the effects of blast on animals, and
scientists are modeling its effects on the brain with computer
simulations. However, these studies are not informed by what actually
occurs in human brains that have been exposed to blast. The physical
forces from a blast differ in crucial ways from other types of trauma
that have been studied in human brains, and the human brain is unique
in many ways--for example, the much larger size of the human brain, and
especially the cerebral cortex, compared to animals can substantially
change the physical forces on brain tissue from blast injury. The
unique findings seen in the few well-studied cases, if substantiated,
suggest that a change in focus is appropriate.
Question. What do you think researchers will learn if they have
access to brains that have sustained a blast injury?
Answer. Based upon examination of brain tissue from the handful of
cases, we are concerned that blast injury damages the brain in unique
ways, compared to other types of trauma. Understanding the unique
pathology is essential to develop better ways to diagnose and treat
service members exposed to blast injury and to improve protective
measures. For instance, it is an open question as to whether
neuropsychiatric disorders classified as PTSD, or even suicide itself
may be related to chronic effects of neurotrauma. Brain examination is
currently the only means to pursue these questions at this time. The
most urgent question is to understand the incidence and pattern of
blast injury in brain tissue and to link the pathologic findings to the
service members' medical histories.
environmental influences on child health outcomes initiative
Question. ECHO is proposing to use existing cohorts as a critical
aspect of understanding child health and allow researchers to get a
better understanding of the normal trajectory of child development.
Have you selected any cohorts yet? Will the array of cohorts
include broad population samples?
Answer. The Environmental influences on Child Health Outcomes
(ECHO) program will leverage existing resources to investigate the
longitudinal impact of early childhood environmental exposures (e.g.,
physical, chemical, biological, social, behavioral, natural and built
environments) on pediatric development and health outcomes with high
public health impact. One specific component of ECHO--the IDeA States
Pediatric Clinical Trials Network (ISPCTN)--will leverage the
infrastructure at existing IDeA State centers by embedding clinical
trials experts at IDeA State locations, facilitating their partnership
with other academic institutions.\2\ This national pediatric research
network may also help address access gaps for rural and medically
underserved children.
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\2\ Https://www.nigms.nih.gov/Research/CRCB/IDeA.
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NIH recognizes the importance of robust recruitment plans that can
address racial and ethnic minority health issues reflective of the
needs of the U.S. population. When making awards, NIH will strive for a
balance between a robust characterization of environmental factors,
including consideration of geographic diversity, and health-related
endpoints. Additionally, the ECHO program aims to utilize both large
studies to build a repository on the trajectory of healthy development
over childhood (health controls), and small, selective studies to
address interesting targeted questions that are specific to a disease
or have a high-risk population.
Last fall, seven Funding Opportunity Announcements (FOAs) were
released to solicit applications for the ECHO program. The applications
were due on April 15, 2016 and will be reviewed this summer. Awards are
anticipated to be made in September 2016; therefore, no specific
cohorts have been selected for funding as of yet. Any investigator with
an existing relevant cohort, whether it is supported by the NIH or not,
was encouraged to apply.
Question. Are you working with National Center for Health
Statistics to ensure ECHO cohorts include measures that would allow you
to compare subjects to studies such as the National Health and
Nutrition Examination Survey?
Answer. A major feature of the ECHO program is the sharing and
harmonization of data across all of the cohorts. Standardized core data
elements will be addressed across all studies: demographics; typical
early health and development; genetic influences on early childhood
health and development; environmental factors; and Patient/Person
(parent and child) Reported Outcomes (PROs). During the planning phase,
the ECHO Steering Committee, which will be composed of the principal
investigators of the ECHO projects, cores and centers, the ECHO ISPCTN,
and the NIH ECHO Program Director and staff, and the External
Scientific Board, composed of external experts, will develop and
provide valuable input on standardizing the collection of the core data
elements. They will be strongly encouraged to consider how NHANES,
NHIS, and other national surveys can inform the development of these
standardized core data elements, and consider how the ECHO data could
be compared to known national samples. Additionally, the Children's
Health Exposure Analysis Resource (CHEAR) is a network of laboratory
hubs that provides researchers access to comprehensive laboratory and
data analysis services to measure environmental exposures. CHEAR is
expected to become operational in the summer of 2016, and will have the
capability of measuring the majority of targeted analytes CDC measures
for NHANES, as well as others. The ECHO program is leveraging this
existing resource to analyze personal environmental exposures from
existing and prospective ECHO sample collections. Therefore,
researchers should be able to compare much of the data generated from
ECHO with that of other large studies.
______
Questions Submitted by Senator Richard C. Shelby
cancer moonshot
Question. Dr. Collins, I am curious of the role that the
President's cancer ``moonshot'' initiative will play in the research
specifically for childhood cancer. Currently, childhood cancer is the
number one disease killer of children under 15 years old and the
incidence of childhood cancer has increased each year for the past 25
years. In addition, over the past 8 years, less than 4 percent of the
National Cancer Institute's (NCI) annual appropriations have been
allocated towards pediatric cancer. I understand the budget
constraint's many of the institutes are under, however, can you explain
why the NCI is not allocating more of its current resources towards
childhood cancer initiatives given the statistics?
Answer. The National Cancer Moonshot Initiative is an important
opportunity to speed progress on childhood cancers. Not only is
childhood cancer research one of the seven core elements within the
initiative, several other elements are also important to advancing
progress for children with cancer. Other Moonshot elements that are
particularly relevant include:
--extending early successes in immunotherapy for cancer treatment
(for adults and children)
--building an even greater understanding of cancer genomics--the
genetic changes that occur within the cancer cell and in
surrounding and immune cells responding to the cancer
--building expanded data sharing systems to speed discovery and
verify treatment response for children and adults.
Cancer in children poses unique challenges. Childhood cancers
generally possess many fewer mutations than adult cancers and are less
likely to have activation of enzymes known as kinases, which are the
most frequent targets of cancer drugs for adult tumors. The molecular
changes that drive many childhood cancers arise in transcription
factors and other cellular targets that are often considered
``undruggable.'' However, new technologies, built upon advances in
chemistry that allow the preparation of libraries of small chemical
molecules with a much more complex arrangement of molecular shapes,
offer the promise of identifying therapies with the potential to target
the unique molecular changes found in pediatric cancers. The National
Cancer Moonshot Initiative aims to support research such as this to
deliver advances and new treatments for pediatric cancers.
As part of the fiscal year 2017 Moonshot initiative, NCI will also
intensify efforts to collect and analyze tumor specimens from the
rarest childhood cancers, and NCI will enlist the pediatric oncology
community to join in this effort. NCI also expects to build a clinical
database focused on the course of rare pediatric cancers that will be
widely accessible and will support further productive research that can
lead to new cancer treatments.
The National Cancer Moonshot Initiative's Blue Ribbon Panel and its
working groups will continue to identify specific promising research
opportunities for each element of the initiative, including childhood
cancer research. The Blue Ribbon Panel includes a number of cancer
researchers with pediatric cancer expertise, such as Dr. James Downing,
President and CEO, St. Jude Children's Research Hospital, and Dr. Peter
Adamson, Director of Experimental Therapeutics in Oncology at the
Children's Hospital of Philadelphia. Dr. Adamson is also Chair of the
NCI-supported Children's Oncology Group, and a member of the National
Cancer Advisory Board.
In addition to the Blue Ribbon Panel and its working groups, the
initiative is also seeking feedback from across the cancer research and
advocacy communities regarding all areas of research focus, including
childhood cancer research.\3\ Additional information about the National
Cancer Moonshot Initiative, including childhood cancer research within
the initiative, can be found at the NCI website.\4\
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\3\ The public and research communities are invited to submit ideas
at this website: https://cancerresearchideas.cancer.gov/.
\4\ Http://www.cancer.gov/research/key-initiatives/moonshot-cancer-
initiative.
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New Childhood Cancer Research Initiatives
NCI is also supporting new research opportunities specific to
childhood cancer, including a Pediatric Provocative Questions
Initiative and the Pediatric MATCH precision medicine trial. NCI is
eager to accelerate progress in cancer research by attempting to define
potentially game-changing scientific questions that could influence the
directions taken by NCI-sponsored research in the future. The NCI
Provocative Questions Initiative is designed to encourage research
around some of the most challenging scientific questions while engaging
the scientific community in serious debate in an effort to identify
compelling research opportunities.
NCI held two childhood cancer Provocative Questions workshops in
2015 to identify questions that address gaps in the pediatric oncology
research field. NCI plans to release the pediatric oncology provocative
questions this spring through program announcements designed to
generate innovative approaches to address childhood cancer research
challenges.
The Pediatric MATCH precision medicine trial will provide a
tremendous opportunity to test molecularly targeted therapies in
children with advanced cancers who have few other treatment options.
With the genomic data captured in the trial, it will also produce an
invaluable resource for studying the genetic basis for why some
pediatric cancers progress or recur while others do not. As in the
adult NCI-MATCH trial, DNA sequencing will be used to identify children
whose tumors have a genetic abnormality for which either an approved or
investigational targeted therapy exists. Pediatric MATCH, which will be
led by the NCI-funded Children's Oncology Group, is under development
and is expected to launch in late 2016.
Other NCI Support for Childhood Cancer Research
NCI has prioritized the development of new treatments for pediatric
cancer in the NCI Experimental Therapeutics (NExT) Program.\5\ This
program focuses on advancing breakthrough discoveries in basic and
clinical research into new therapies, and several new inhibitors with
potential to treat pediatric cancer are being studied for this purpose.
There are currently nine agents from the NExT program being studied in
pediatric clinical trials. Two examples of these include the
investigational agent ganitumab for Ewing sarcoma and the FDA-approved
dinutuximab (ch14.18) therapy for high-risk neuroblastoma.
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\5\ Http://next.cancer.gov/about/mission.htm.
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NCI's active role in developing these agents is what has made these
trials possible. The development of ganitumab was halted by the
pharmaceutical industry after negative results in studies for adult
cancers, and NCI acquired the agent from the industry sponsor to
continue development for therapy for Ewing sarcoma. Similarly, NCI
supported the development of dinutuximab for high-risk neuroblastoma
for decades, from early funding for investigator-initiated research, to
manufacturing and sponsoring the Phase III trial that led to
dinutuximab's approval by FDA, and finally to the NCI Cooperative
Research and Development Agreement (CRADA) with United Therapeutics
that brought this drug to market for patients.
As noted above, childhood cancers pose unique scientific challenges
and opportunities. NCI is supporting research to address these
challenges in ways that can lead to better outcomes for children with
cancer. This is a high priority research area for NCI, and we are
urging the oncology community to submit creative research proposals
focused on childhood cancers. NCI continues to support the best
research opportunities to identify promising new therapies, improve the
outlook for cancer survivors, and to support the foundation of basic
research needed to achieve these goals.
The funding figures cited in your question reflect only research
projects identified as specifically focused on childhood cancer in a
given fiscal year, such as the research data reported in the NIH
Research, Condition, and Disease Categorization (RCDC) database.\6\
While RCDC is a useful tool, it does not provide the complete picture
of NIH and NCI investments that are critical to advancing childhood
cancer research. For example, approximately half of the NCI budget--and
half of the overall NIH budget--supports basic research that may not be
specific to one type of cancer. By its nature, basic research cuts
across many disease areas and makes important contributions to our
knowledge of the underlying biology of cancer. This knowledge supports
the ability of the research community to make advances against many
cancer types.
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\6\ Https://report.nih.gov/categorical_spending.aspx.
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Over the years, research in childhood cancers has led to important
advances for adults with cancer. Similarly, research focused on adult
cancers has led to progress for children with cancer. We have also
demonstrated that research focusing on a particular type of cancer has
led to advances across many cancer types. For these reasons, the
funding levels reported in RCDC and other systems do not definitively
capture all research relevant to a given category.
In addition to soliciting applications in areas of scientific
focus, NCI also remains committed to supporting a number of key
research efforts focused specifically on childhood cancers. NCI has
been renewing many of these programs for numerous 5-year funding
periods. Examples of these critical long-term investments in childhood
cancer research include:
--The Children's Oncology Group (COG), which is part of NCI's
National Clinical Trials Network (NCTN), develops and
coordinates pediatric cancer clinical trials that are available
at more than 200 member institutions, including cancer centers
throughout the United States and Canada.\7\ In addition to
conducting traditional late-phase clinical trials, the COG has
established a Phase 1 and Pilot Consortium that is separately
funded by NCI to conduct early-phase trials and pilot studies
so new anticancer agents can be rapidly and efficiently
introduced into pediatric cancer care.\8\
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\7\ Https://www.childrensoncologygroup.org/.
\8\ Https://www.childrensoncologygroup.org/index.php/phase-1-home.
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--The Pediatric Preclinical Testing Consortium (PPTC) systematically
evaluates new agents in genomically characterized childhood
cancer solid tumor and leukemia in vivo models.\9\ The primary
goal of the PPTC is to develop high-quality preclinical data to
help pediatric oncology researchers identify agents that are
most likely to show significant anticancer activity when tested
in the clinic against selected childhood cancers.
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\9\ Http://ctep.cancer.gov/MajorInitiatives/
Pediatric_Preclinical_Testing_Program.htm.
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--The Childhood Cancer Survivor Study (CCSS) is studying the long-
term effects of cancer and cancer therapy on approximately
35,000 survivors of childhood cancer who were diagnosed between
1970 and 1999.\10\ NCI has supported CCSS since its launch in
1994. NCI has also recently supported a complementary effort,
the St. Jude Lifetime Cohort Study, which will allow for
replication of findings from genomic studies and the
development of collaborative projects to refine risk-based
follow-up guidelines and improve outcomes among childhood
cancer survivors.\11\
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\10\ Http://www.cancer.gov/cancertopics/types/childhoodcancers/
ccss.
\11\ Https://www.stjude.org/research/clinical-trials/sjlife-long-
term-effects.html?vgnextoid=1c4303fb30c23110VgnVCM1000001e0215acRCRD.
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--The Pediatric Brain Tumor Consortium was formed by NCI in 1999 as a
multidisciplinary cooperative research organization devoted to
identifying superior treatment strategies for children with
primary brain tumors.\12\ The participating academic centers
and children's hospitals are responsible for the diagnosis and
treatment of the majority of children with primary brain tumors
in the United States. PBTC has a direct working relationship
with the Children's Oncology Group (COG) to ensure that results
from Phase I and II trials can be confirmed through additional
Phase II and multi-agent Phase III clinical trials in the COG.
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\12\ Https://www.pbtc.org/.
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--The Pediatric Oncology Branch (POB) in NCI's Center for Cancer
Research, part of NCI's intramural research program, conducts
high-risk, high-impact basic, translational, and clinical
research dedicated to the study and treatment of childhood
cancers.\13\
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\13\ Https://ccr.cancer.gov/pediatric-oncology-branch.
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______
Questions Submitted by Senator Thad Cochran
pediatric clinical trials network
Question. I am pleased that the NIH has shown a commitment to
including IDeA States in the Pediatric Clinical Trials Network. It is
my understanding that the network will focus on environmental
influenced diseases like asthma, obesity, and prematurity, all of which
are all too prevalent in my State of Mississippi. The current program
announcement from NIH provides for grans to fund necessary
infrastructure for clinical trials research sites and to promote career
development for pediatric clinical researchers. Please provide me with
more information about how this network will function as it moves
forward. In particular, what studies will the network perform? How will
the studies be chosen, and how will they be funded?
Answer. NIH released a series of funding opportunity announcements
(FOAs) on December 7, 2015 to establish the Environmental Influences on
Child Health Outcomes (ECHO) program. The ECHO program has been
designed to investigate the longitudinal impact of pre-, peri-, and
postnatal environmental exposures on pediatric health outcomes with
high public health impact. The IDeA States Pediatric Clinical Trials
Network (ISPCTN) has been developed as a component of the ECHO program
and includes two FOAs: The Clinical Sites for the IDeA States Pediatric
Clinical Trials Network (RFA-OD-10-001), and the Data Coordinating and
Operations Center for the IDeA States Pediatric Clinical Trials Network
(RFA-OD-16-002). ISPCTN is being established to provide an opportunity
to children in rural and medically underserved locations in IDeA States
to participate in state-of-the-art clinical trials, to enhance
pediatric clinical trial capacity at State and national level, and to
facilitate the implementation of well-designed clinical trials in
pediatric populations.
How will the ISPCTN cooordinate with the ECHO program as a whole?
ISPCTN will study any disease or condition relevant to the pediatric
population, but priority will be given to the four focus areas of the
ECHO program including: upper and lower airway diseases; obesity; pre-,
peri-, and postnatal outcomes; and neurodevelopment. All prospective
data collection will be encouraged to utilize the ECHO program's Core
Elements and standardized research measures. Structurally, there will
be representatives of the ISPCTN on the ECHO Steering Committee and
subcommittees.
How will this network function and move forward? The overall
framework will consist of dedicated pediatric clinical teams at
participating institutions, a professional development component, and a
central Data Coordinating and Operations Center (DCOC). The
institutions that will successfully compete to become IDeA State
Pediatric Clinical Sites will be integrated with the DCOC to form a
Research Network to conduct multicenter studies of pediatric conditions
and disease processes. The proposed activities will provide the
infrastructure and resources needed to initiate and participate in
pediatric clinical trials and enhance the competitiveness of the
investigators to obtain funding for pediatric clinical research.
DCOC will provide comprehensive services across the network. DCOC
will have primary responsibility for resource allocation, data
management and analysis, and data sharing for research conducted
through the network in collaboration with the ISPCTN Steering
Committee, the ECHO Steering Committee, and the NIH Program Staff. DCOC
will facilitate and establish collaborations within the network and
outside of the network, will develop and implement quality control
measures, establish and maintain human subject protections oversight,
develop a central IRB, implement relevant professional development
programs, and organize and implement monitoring activities. ISPCTN will
be directed by a Steering Committee with standing committees and sub-
committees; a Scientific Oversight Board and a Data Safety Monitoring
Board will be constituted as well. ISPCTN will also be guided by the
ECHO Steering Committee and External Scientific Board. Each clinical
site will have a dedicated pediatric clinical trial team including a
board certified Pediatrician as a Principal Investigator (PI), a
Research Nurse Coordinator, and a Data Manager, who will implement the
studies.
How will the studies be chosen? ISPCTN will primarily function to
augment pediatric clinical trials initiated by other entities to
improve access to state-of-the-art pediatric clinical trials to
populations who would otherwise not have access to them. Studies
initiated within the network will also be encouraged. The ECHO Program
Officials and the NIH Project Scientists, one from NICHD and one from
NIGMS, will assist the PI(s) and Program Directors of the Clinical
Sites and the DCOC of ISPCTN to identify research topics of high
priority and provide guidance for the implementation of the protocols
appropriate for the network goals and objectives. Interested
investigators will contact DCOC as a clearing house to determine
feasibility and network interest. Clinical trials to be conducted
through the network will require approval by the ISPCTN Steering
Committee in conjunction with the NIH ECHO Program Officials.
How will the studies be funded? All the studies will be funded by
DCOC. DCOC will receive its entire budget when the award is made, and
will allocate $4.53 million per year for each of the 4 years of the
program budget period in direct costs to pay for services. These costs
will be distributed to the Clinical Sites and for necessary monitoring,
DSMB visits, and Scientific Oversight Board activities.
hiv/aids vaccine
Question. I understand that the NIH is on the path toward
discovering a vaccine for HIV/AIDS. What is the Administration's
position on funding for this effort? How much of the request will be
devoted to HIV/AIDS vaccine discovery? Why do you believe that is
sufficient?
Answer. The fiscal year 2017 President's Budget requested $554
million for HIV vaccine research at NIH. Development of an HIV vaccine
would represent a significant public health achievement and provide
populations around the world with a safe and effective tool for
preventing HIV infection.
The National Institute of Allergy and Infectious Diseases (NIAID)
is the lead NIH Institute for research on HIV/AIDS, including research
to develop an effective vaccine. NIAID oversees a robust portfolio of
basic, translational, and clinical research on HIV/AIDS with the goal
of successfully ending the HIV/AIDS pandemic. While significant
progress has been made in combating HIV/AIDS through the implementation
of prevention and treatment strategies supported by NIAID research, the
development of a safe and effective HIV vaccine is critical to achieve
a durable end to the HIV/AIDS pandemic and thus remains a top priority
for NIAID.
NIAID supports a comprehensive program of extramural and intramural
HIV vaccine research, including at the NIAID Vaccine Research Center
(VRC). Investigators are working at all stages of the vaccine
development pipeline to design, develop, and test vaccine candidates to
prevent HIV infection. To date, NIAID has supported 148 vaccine trials
to evaluate 109 vaccine products and 27 adjuvants--vaccine additives
designed to boost the immune response to vaccination.
HIV vaccine development supported by NIH builds upon basic research
that illuminates the mechanisms of HIV pathogenesis. Studies of viral
and host factors involved in host immune responses to HIV will
contribute knowledge that can help researchers develop novel vaccine
strategies. For example, VRC scientists discovered VRC01, a broadly
neutralizing antibody that is capable of inhibiting a number of HIV
strains. Phase I studies are currently underway to evaluate the safety
and immunogenicity of VRC01. In addition, Phase IIb studies initiated
in March 2016 are evaluating the ability of infusions of VRC01 to
prevent HIV infection. Understanding the preventive properties of
broadly neutralizing antibodies will help scientists design more
effective HIV vaccines that aim to inhibit multiple strains of HIV.
NIAID is collaborating with the Pox-Protein Public-Private
Partnership (P5) to confirm and extend results of the RV144 clinical
trial in Thailand. This trial was the first study to demonstrate
moderate protection against HIV infection in people who received a
candidate HIV vaccine regimen. To build upon the results of the RV144
trial, NIAID launched the HVTN 100 Phase I/II clinical trial in South
Africa. This trial is evaluating an investigational vaccine regimen
that was designed to improve upon the efficacy of the vaccine regimen
used in the RV144 trial. If the vaccine is found to be safe and
adequately immunogenic, NIAID and collaborators anticipate launching a
follow-up randomized controlled trial, HVTN 702, in late 2016 to test
the regimen's protective efficacy.
In addition to HIV vaccine research, NIAID is supporting research
to optimize existing strategies and to develop new strategies for HIV
treatment and prevention, as well as to explore novel approaches to
curing HIV. In partnership with scientific and community stakeholders,
NIAID-supported research is advancing progress toward an AIDS-free
generation, including through critical work to develop an effective HIV
vaccine.
updating research centers in minority institutions guidelines
Question. The Research Centers in Minority Institutions (RCMI)
program has proven important in building biomedical research capacity
at Historically Black Colleges and Universities (HBCUs) nationwide,
including at Jackson State University in my State. I understand the
National Institute on Minority Health and Health Disparities is
preparing updated guidelines for the RCMI program. Where is NIMHD in
that process? How will eligibility for the RCMI program change? For
example, will non-minority institutions become eligible for RCMI
funding, or will institutions that have received ``significant amounts
of Federal funding'' now be allowed to compete? Will the purposes and
uses of the funds change? If yes, how so? It is my hope that this
program will continue to provide important capacity-building funds to
minority-serving institutions like Jackson State.
Answer. Since the transfer of the Research Centers in Minority
Institutions (RCMI) program to the National Institute on Minority
Health and Health Disparities (NIMHD) in 2012 with the dissolution of
the National Center for Research Resources (NCRR), NIMHD has made it a
priority to integrate the RCMI program into the existing NIMHD
portfolio. NIMHD has focused on specific programmatic goals and
objectives in order to minimize overlap and maximize the scientific
benefit of the Federal resources and plans to provide updated guidance
to the extramural research community in the summer of 2016. NIMHD is
committed to keep the intent of the RCMI program and will continue to
engage institutions with a history of supporting students and trainees
underrepresented in biomedical research and to serving diverse
populations.
Consistent with the intent of the RCMI program, the priority
continues to be strengthening the research environment at the
institution. There are multiple ways to accomplish that goal, from
providing specialized expertise such as biostatistics, health
informatics or specific research skills in laboratory science, to
conducting specific research projects in minority health or health
disparities. Individual RCMI institutions have and will continue to be
able to focus on different scientific areas including basic biomedical,
behavioral, and/or clinical research that best align with the strengths
of their institution.
nih ``march-in rights''
Question. What is your position on the use of NIH's ``march-in-
rights'' as a price control measure?
Answer. NIH shares the public's concern about any individuals who
need medical treatments may be prevented access to treatment on the
basis of the cost. Some have suggested that NIH utilize the Bayh-Dole
march-in authority as a means of addressing the difficult situation
with drug pricing. The Bayh-Dole Act, however, does not appear to have
been designed to address situations where the price is the obstacle for
access to products utilizing Government-funded inventions. The Act
seems to address the circumstances where the products are not available
because they are not being commercialized and have not entered the
market. Another case for using march-in may occur when serious public
health needs are not being reasonably met by the owner of the patent or
the company selling the product. In such cases, NIH has the authority
to utilize the march-in authority. NIH reviews each request for the use
of march-in on case by case basis. In previous cases where requests
were based on drug pricing issues, NIH did not find that the march-in
statutory criteria were met.
combatting antibiotic resistant bacteria initiative
Question. Through the Combatting Antibiotic Resistant Bacteria
initiative, the FDA and the CDC have recognized that antibiotic
resistance is a growing public health concern worldwide. As part of
this effort, the White House issued a National Action Plan for
Combatting Antibiotic-Resistant Bacteria in 2015. In January, the NIH
announced that approximately $5 million in funding was granted to
research projects to develop non-traditional therapeutics for bacterial
infections to help address the growing health threat of antibiotic
resistance. Does NIH have adequate resources to address this growing
threat?
Answer. Research to address antibacterial-resistant pathogens is a
top priority for the National Institute of Allergy and Infectious
Diseases (NIAID), the lead NIH Institute for research on infectious
diseases. NIAID plays an important role in the President's National
Strategy for Combating Antibiotic-Resistant Bacteria (CARB) by
investing in basic, translational, and clinical research on
antibacterial resistance. The additional $100 million provided by the
Congress in the fiscal year 2016 Consolidated Appropriations Act to
address antibacterial research and development is both timely and vital
to address the growing problem of antibiotic resistance. This funding
will bolster and expand NIAID's research efforts to better understand
and combat antibacterial resistant infections.
In accordance with the objectives outlined in the National Strategy
for CARB, NIAID is currently sequencing bacterial strains for the
National Database of Resistant Pathogens; optimizing current treatment
strategies to reduce the emergence of drug resistance; and developing
diagnostic platforms capable of detecting multiple resistant pathogens.
NIH is partnering with the Biomedical Advanced Research and Development
Authority, with assistance from FDA and CDC, to incentivize diagnostic
research by designing a prize competition for the development of a
rapid, point-of-care diagnostic test for healthcare providers. NIAID
also is expanding and strengthening its clinical research efforts,
including through the NIAID Antibacterial Resistance Leadership Group
(ARLG), to facilitate high-priority research on antibacterial
resistance. For example, the ARLG is currently investigating the use of
shortened courses of antibiotics in pediatric populations in an effort
to enhance antibiotic stewardship and infection control.
Consistent with the CARB objectives, the NIAID initiative Non-
Traditional Therapeutics that Limit Antibacterial Resistance supports
early-stage, translational research projects focused on discovery and
development of non-traditional therapeutics that provide alternative
treatment strategies for infected patients. In January 2016, NIAID
awarded approximately $5 million in funding for 24 research projects
seeking to develop non-traditional therapeutics for bacterial
infections, including Clostridium difficile, Staphylococcus aureus, and
carbapenem-resistant Enterbacteriaceae (such as Klebsiella pneumoniae).
In addition, NIAID continues to support the discovery and
development of new therapeutics for Gram-negative pathogens, such as
biofilm inhibitors, and anti-virulence, immune-based, and adjunctive
therapies. To that end, in 2016, NIAID will make multiple awards under
several other research initiatives that are designed to advance the
development of new therapeutic products and approaches aimed at
addressing drug resistance. These initiatives include Partnerships for
the Development of Host-Targeted Therapeutics to Limit Antibacterial
Resistance and Systems Biology and Antibacterial Resistance. NIAID also
will fund new contracts to support the development and early clinical
evaluation of promising lead therapeutic candidates and products that
demonstrate broad spectrum therapeutic activity, including activity
against antibiotic-resistant bacteria.
NIAID has provided support for at least 25 percent of antibiotics
currently in clinical development. Currently, NIAID is supporting
several clinical trials evaluating new ways to treat gonorrhea,
including a Phase II trial of an oral antibiotic AZD0914 developed by
AstraZeneca; a Phase I trial assessing the pharmacokinetics of a next-
generation macrolide antibiotic, solithromycin; and a Phase III trial
comparing solithromycin to standard of care treatment for gonorrhea.
NIAID also is supporting trials to determine optimal antibiotic
treatment (e.g., dosage, duration) using existing off-patent
antibiotics for a variety of infections, including community-acquired
methicillin-resistant Staphylococcus aureus (MRSA) infections;
staphylococcal bacteremia; Gram-negative bacteremia; acute otitis
media; urinary tract infections; and hospital-acquired pneumonia.
NIAID remains committed to conducting and supporting research on
antimicrobial resistance, including the development of rapid, point-of-
care diagnostics, improved and innovative therapies, and vaccines to
prevent infections. Utilizing additional resources provided by the
Congress in fiscal year 2016, NIAID will continue to enhance
partnerships with industry, academia, and other Federal Government
agencies to support the goals of the National Strategy for CARB.
animal research
Question. Great strides in medical research and treatment have come
from the study of animal models. Whether a scientist is studying kidney
failure or drug addiction, there is clear value in translating the
lessons learned to the human population. Some in the industry have
suggested that NIH may be backing away from its longstanding commitment
to study certain species of animals due to pressure from activists.
What is your intention related to animal research? How will you ensure
that the humane and scientifically-justified use of animal models is
permitted for those using NIH funds to support their research?
Answer. NIH is committed to funding the most meritorious research
projects, including those involving animal model(s). Research involving
vertebrate animals is key to helping us understand and improve human
health in a multitude of ways, including the development of treatments
and interventions. For ethical reasons, these studies cannot be carried
out in humans and require the use of animal studies to understand
fundamental biological systems. Ultimately, these findings assist
researchers in identifying potential treatments and interventions by
helping to elucidate the mechanisms underlying health and disease.
Figure 1 shows the success rates for new, competing R01 grant
applications over the past 5 fiscal years, broken out by whether the
application proposes only vertebrate animal research, only human
subjects research, both vertebrate animal and human subjects research,
or neither. The R01 grant is NIH's most commonly used funding mechanism
and is used to support a majority of NIH's basic research portfolio.
Success rates for studies involving only vertebrate animals and those
involving both vertebrate animals and human subjects have increased in
fiscal years 2014 and 2015, showing NIH's continued commitment to
funding meritorious research using vertebrate animal models.
Figure 1. Success rates for competing R01 applications, by type of
research proposed, over the past 5 fiscal years.
NIH takes animal welfare seriously, and has numerous policies and
protocols in place to assure the ethical treatment and use of these
invaluable resources. The agency remains confident that the oversight
framework for the use of vertebrate animals in research is robust and
has provided sufficient protections to date. NIH will continue to
support the meritorious research proposals using vertebrate animals, so
long as the research satisfies ethical principles of scientific rigor,
appropriateness of the model, and consideration of animal welfare.
Moreover, NIH has the necessary mechanisms to implement these relevant
policies to ensure the continued responsible use of vertebrate animals
in biomedical and behavioral research.
idea program
Question. I know you are aware of how the IDeA program has helped
build biomedical research capacity across the Nation. The fiscal year
2016 omnibus provided additional funds, reflecting Congress's continued
support for this program. What are your plans for the IDeA programs
going forward? What are some particular success stories that have come
from IDeA investments?
What are your plans for the IDeA programs going forward?
Answer. NIGMS foresees the IDeA Program as a long-term
interventional capacity-building program targeting States and
jurisdictions that have consistently trailed in obtaining significant
NIH support. The intent is to transform institutions with
infrastructure, human resource, and economic challenges to become more
competitive biomedical research enterprises through various distinct
but complementary initiatives.
Currently, institutions in 23 States and Puerto Rico are eligible
for funding from the IDeA Program.\14\ For fiscal year 2017 and in the
foreseeable future, the IDeA program will continue to support
investigators in eligible States through the following initiatives:
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\14\ Alaska, Arkansas, Delaware, Hawaii, Idaho, Kansas, Kentucky,
Louisiana, Maine, Mississippi, Montana, Nebraska, Nevada, New
Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, South
Carolina, South Dakota, Vermont, West Virginia, Wyoming.
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--IDeA Networks of Biomedical Research Excellence (INBRE).--The INBRE
initiative enhances, extends, and strengthens the research
capabilities of biomedical research faculty in IDeA States
through a statewide program that links a research-intensive
institution with primarily undergraduate institutions. INBRE
supports institutional research and infrastructure development;
research by faculty, postdoctoral scientists and students at
participating institutions; and outreach to build science and
technology knowledge in the States' workforces. Only one award
is made per eligible State. Currently (fiscal year 2016), NIGMS
supports 24 INBRE awards. For fiscal year 2017, NIGMS
anticipates continuing support for these 24 INBRE awards.
--Centers of Biomedical Research Excellence (COBRE--Phases I, II, and
III).--The goal of the COBRE initiative is to strengthen
institutional biomedical research capabilities in IDeA States
through three 5-year phases of infrastructure and faculty
development of thematic and multidisciplinary research centers.
In fiscal year 2015, NIGMS supported 107 COBRE awards. For the
current year (fiscal year 2016), 12 new Phase I COBRE grants
will be awarded. In fiscal year 2017, NIGMS will support non-
competing awards and continue to hold open competitions for new
and continuing COBRE awards.
--IDeA Program Infrastructure for Clinical and Translational Research
(IDeA-CTR).--The IDeA-CTR initiative develops network
infrastructure and capacity in eligible States to conduct
clinical and translational research focused on health concerns
that affect medically underserved populations and/or that are
prevalent in IDeA States. IDeA-CTR awards support mentoring and
career development activities in clinical and translational
research. In fiscal year 2015, NIGMS supported 3 IDeA-CTR
awards. In the current year (fiscal year 2016), 4 new IDeA-CTR
awards will be made. In fiscal year 2017, NIGMS will support
non-competing awards and continue to hold open competitions for
new and continuing IDeA-CTR awards.
--Research Co-Funding.--IDeA co-funding is provided to eligible
applications that have already been judged meritorious by NIH
peer-review committees and national advisory councils but are
outside the range of applications under consideration for
funding by the other NIH Institutes and Centers (ICs). In
fiscal year 2015, IDeA co-funded 25 R01/R15 awards to 18 NIH
ICs. For the current year (fiscal year 2016), $9 Million is
allocated for the co-funding initiative. In fiscal year 2017,
NIGMS anticipates to continue soliciting applications from
other ICs for co-funding.
--Administrative Supplements.--Based on continuing evaluation of the
IDeA program, NIGMS will occasionally solicit applications for
administrative supplements from current grantees in order to
address emerging areas for development or enhancement. For the
current year (fiscal year 2016), the Institute published an
administrative supplement solicitation for the optimization
and/or consolidation of core facilities supported by the IDeA
program. The projected budget for this initiative in fiscal
year 2016 is $8 Million.
Additionally, for fiscal year 2017, the IDeA program will provide
continuing support for the non-competing INBRE, COBRE, and IDeA-CTR
awards; these awards constitute the IDeA program budget base. As
indicated above, the rest of the IDeA program budget will support new
competing COBRE and IDeA-CTR awards, and co-funding of meritorious
applications from other ICs.
Question. What are some particular success stories that have come
from IDeA investments?
Answer. Investigators in a COBRE at the University of Mississippi
that is focused on finding natural products that affect neurological
processes (Principal Investigator: Steve Cutler) are developing melt-
cast films for the efficient and prolonged topical delivery of
therapeutic small molecules to the posterior segment of the eyes.
Diseases affecting the posterior segment of the eye such as diabetic
retinopathy, age related macular degeneration, diabetic macular edema
and proliferative vitreo-retinopathy are some of the major causes of
blindness in the United States. Treating posterior segment eye diseases
has always been a great challenge because of the unique physiological
and anatomical barriers of the eye. In a recent publication from this
group, the COBRE investigators demonstrated that melt-cast films based
on polyethylene oxide N10 can serve as a viable platform for sustained
topical delivery of therapeutic agents into tissues in the back of the
eye.
Jennifer Sasser, a COBRE-supported junior investigator at the
University of Mississippi Medical Center, characterized a novel model
of the pregnancy-related disease superimposed preeclampsia. This new
model of the disease in rats provides a powerful tool to gain a greater
understanding of the pathogenesis of preeclampsia. Preeclampsia is a
leading cause of maternal morbidity and mortality worldwide with
currently no effective treatments other than delivery of the placenta.
The new rat model of preeclampsia allows for the analysis of changes
throughout pregnancy in the placenta, vasculature, and kidney, as well
as the discovery of new biomarkers that are present early during
pregnancy and would allow early detection of the condition. Using this
new rat model, Sasser and colleagues found that the phosphodiesterase
inhibitor drug, sildenafil, improves the maternal syndrome of
preeclampsia as well as blood flow to the fetus and placenta, providing
preclinical evidence to support the hypothesis that inhibiting the
enzyme phosphodiesterase type 5 may be a therapeutic strategy for the
treatment of preeclampsia.
The IDeA Program appropriation has been successfully leveraged by
IDeA investigators to provide additional NIH funding to the eligible
jurisdictions. For the 8-year period spanning fiscal years 2007-2014,
the IDeA Program appropriation totaled $1.9 billion. Additional NIH
funding obtained during this period totaled $12 billion, close to a 7-
fold return in investment.
While the number of COBRE-supported investigators increased
modestly during the 8-year period spanning fiscal years 2007-2014, the
productivity of the investigators increased significantly. Whereas the
number of COBRE-supported investigators increased only 9 percent when
comparing fiscal years 2007-2010 (4-year average = 950) to fiscal years
2011-2014 (4-year average = 1,034), the number of COBRE-enabled
publications increased 43 percent in the corresponding period [fiscal
year 2007-2010 (4-year total = 3,951) vs fiscal year 2011-2014 data (4-
year total = 5,651)].
Blake Wiedenheft, a COBRE-supported Assistant Professor at Montana
State, has moved beyond IDeA support and is now funded by an NIGMS R01.
He was recently invited to give the first Annual NIGMS Director's Early
Career Investigator Lecture. Wiedenheft was honored for his
contributions to understanding the three-dimensional structures of key
components of the CRISPR-Cas9 gene editing system. Even though he is
still early in his career, Wiedenheft has already established himself
as one of the international leaders in this field.
In 2014, when Professor Susan Harkema's research at the University
of Louisville in Kentucky was published in the journal Brain, it became
an overnight sensation and was featured prominently in all the major
print and broadcast media outlets. Harkema and her team demonstrated
that modulating the spinal circuitry with epidural stimulation enabled
completely paralyzed individuals to process conceptual, auditory and
visual input to regain relatively fine voluntary control of paralyzed
muscles. Harkema conducted the research as one of the project leaders
in the Kentucky Spinal Cord Injury Research Center, a COBRE funded by
the IDeA program.
A COBRE focused on regeneration medicine based at the Mount Desert
Island Biological Laboratory (MDIBL) in Maine has spun off the first
company in the Laboratory's 115-year history, led by the Principal
Investigator Kevin Strange and junior investigator Voot Yin. The new
company, Novo Biosciences Inc., will look at the therapeutic potential
of drugs that speed tissue healing and stimulate the regeneration of
lost and damaged body parts. Strange and Yin serve as the CEO and Chief
Scientific Officer, respectively, of the new company. Yin, an Assistant
Professor at MDIBL, discovered the tissue regenerative effects of an
experimental drug in a zebrafish model of regeneration using COBRE
funds.
COBRE investigators at the University of Arkansas for Medical
Sciences set up telemedicine (TM) capabilities statewide in an effort
to improve clinical outcomes for very low birth weight (VLBW) neonates.
A prospective study (July 2009 to March 2010) that looked at the
availability of TM consultation capabilities and neonatal interventions
showed decreased deliveries of VLBW neonates in hospitals without NICUs
and was associated with decreased statewide infant mortality.
Telemedicine can be an effective way to translate evidence-based
medicine into clinical care.
A group of researchers at the University of Arkansas for Medical
Sciences (UAMS) have discovered a new molecular ``earmark'' on DNA that
may determine the sex of all mammals. COBRE-supported UAMS biochemist
Alan Tackett, professor of Biochemistry and Molecular Biology in the
College of Medicine, led a team of researchers that uncovered the
earmark, N6-methyladenine, found to regulate access to DNA on the X-
chromosome that ultimately determines the sex of mammals. In addition,
the research has the potential to uncover new targets for therapeutic
development for cancer and other diseases. Their findings were
published in the April 2016 issue of the journal Nature.
Alayna Caffrey, a doctoral student in Montana State University's
Department of Microbiology and Immunology, published important new
findings about how healthy immune systems fight off deadly fungal
infections. She was also one of only 10 people selected to present her
work at an international scientific conference in Galveston, Texas.
Caffrey studies the early immune response against Aspergillus
fumigatus, a common mold that can be found in soil or compost piles.
The mold causes severe lung infections in people with weakened immune
systems, such as individuals with leukemia, chemotherapy or organ
transplants. To help lower the percentage of deaths and understand what
goes wrong in weakened immune systems, Caffrey looked at healthy immune
systems to see how they respond to Aspergillus fumigatus. She
discovered that a molecule called IL-la is critical for recruiting
white blood cells to an infection site. Caffrey conducted the studies
in the lab of Josh Obar, a COBRE-supported investigator. The work
published in PLoS Pathogens was a collaboration between Obar's group
and another COBRE at the Geisel School of Medicine at Dartmouth.
atherosclerosis risk in communities study
Question. The University of Mississippi Medical Center serves as a
field center and conducts research in the NIH's Atherosclerosis Risk in
Communities (ARIC) Study, which examines cardiovascular disease in over
15,000 volunteer participants across the country. This original cohort
of people who participate in this study enrolled in 1987, so they are
well into old age today. What are the NIH's plans for recruiting the
adult children of the current ARIC cohort, in the model of the
Framingham Heart Study, in order to continue this important research?
Answer. The Atherosclerosis Risk in Communities (ARIC) Study has
resulted in outstanding contributions to the understanding of
atherosclerosis and cardiovascular disease (CVD) as evidenced by the
more than 1,700 publications from the study to date. With almost 30
years of follow-up, the ARIC Study is among the longest-running cohort
studies with a large number of African American participants. The ARIC
study data on risk factors and incidence rates shows that African
Americans are at very high CVD risk.
This long-running multi-site cohort study has produced a number of
significant research findings including the following:
--The ARIC Study provided some of the first documentation that
diabetes is associated with accelerated cognitive decline.
--Results from the ARIC Study include some of the first evidence for
lifestyle factors contributing to risk of venous
thromboembolism, offering possible keys to prevention.
--Despite the higher prevalence of hypertension and diabetes in
African Americans, the magnitude of the association of these
two conditions with CVD is similar to the associations in
whites.
--The ARIC Study helped establish that risk of atrial fibrillation is
lower in African Americans than whites and that there is a link
between obesity and atrial fibrillation.
In 2013, the NHLBI Director charged a working group of our National
Heart, Lung, and Blood Advisory Council to consider the future course
for CVD epidemiology studies. Published in 2015 (Roger VL et al. Amer J
Epidemiol 2015), the group's recommendations included ``fostering a
more open, competitive approach to evaluating large-scale longitudinal
epidemiology and population studies.'' NHLBI is developing a process to
fund new and renewed epidemiologic studies that incorporates the
recommendations from this working group. One goal is to solicit from
investigators, innovative research ideas that leverage existing
scientific resources, such as a cohort study of the adult children of
the current ARIC study. Using the Framingham Heart Study, which
includes three generations of participants, as an example, an offspring
cohort of the ARIC study is possible.
alzheimer's research
Question. Last year, this Committee provided a $350 million
increase to funding for Alzheimer's disease research. This additional
funding will help researchers, like those at the Memory Impairment and
Neurodegenerative Dementia (MIND) Center at the University of
Mississippi Medical Center, find a way to alleviate the dreadful
symptoms and realities of this heinous disease. Please give us examples
of any recent breakthroughs that are a result of investment in
Alzheimer's research at the NIH.
Answer. Research on Alzheimer's disease in the United States has
benefited from the provision of additional funds in the past several
years. Many of the studies that the National Institute on Aging (NIA)
and other NIH Institutes supported with these funds are ongoing, and we
look forward to reporting on the results as they become available. Most
notably, the $350 million we received in fiscal year 2015 to support
Alzheimer's research will fund, among other initiatives, research under
10 Program Announcements soliciting funding applications across the
spectrum of Alzheimer's disease research. The initial response to these
Program Announcements was extremely robust, and initial awards are
anticipated for late fiscal year 2016.
Promising new therapeutics currently in clinical testing include:
--LM11A-31, a compound able to enter the brain and prevent the loss
of nerve cells and the connections between them. NIA supported
preclinical testing of this compound, and an industry-supported
Phase I safety trial in young and in elderly normal subjects
showed no significant adverse effects for a wide range of
doses. Further human testing is planned.
--BPN14770, which restores function of damaged synapses in the brain.
NIA, along with the NIH Blueprint Neurotherapeutics Network,
also supported the early development of the compound--which, if
effective, may benefit patients not only with Alzheimer's but
with other brain disorders, such as schizophrenia, as well.
This compound recently entered Phase I clinical trials.
--Allopregnanolone, a neurosteroid that promotes growth of new
neurons and may protect against Alzheimer's pathology. NIA-
supported researchers recently concluded a Phase I clinical
trial and are currently analyzing the results.
Ongoing initiatives include:
--NIH Accelerating Medicines Partnership (AMP), a joint public-
private partnership to identify and validate promising
biomarkers of disease. In March, AMP launched its Alzheimer's
Big Data Portal and concomitantly released the first wave of
data through this new resource.
--Molecular Mechanisms of the Vascular Etiology of Alzheimer's
Disease Consortium, a team-science venture to build a nuanced
model of Alzheimer's disease that more accurately reflects its
many causes and pathways. Scientists from diverse fields using
the latest methodologies will work collaboratively towards
shared goals: to dissect the complex molecular mechanisms by
which vascular risk factors influence Alzheimer's disease and
identify new targets for treatment and prevention.
--MIND Diet Intervention to Prevent Alzheimer Disease: NIA has
recently funded this Phase III randomized controlled trial
designed to test the effects of a 3-year intervention of a
hybrid of the Mediterranean and DASH diets, called MIND, on
cognitive decline among 600 individuals 65+ years without
cognitive impairment who are overweight and have suboptimal
diets that may place them at risk for developing dementia.
--Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study,
led by researchers at the Memory Impairment and
Neurodegenerative Dementia (MIND) Center at the University of
Mississippi Medical Center. Researchers are studying, in a
biracial population, age-related cognitive decline and the
transition from mild cognitive impairment to dementia, with an
emphasis on potentially modifiable vascular risk factors.
Funding for this important study was renewed in 2015.
______
Questions Submitted by Senator Shelly Moore Capito
medication-assisted treatment
Question. Ensuring access to treatment for opioid addiction is
essential to reversing the number of overdose deaths and the overall
opioid epidemic. Medication-Assisted Treatment (MAT) plays an important
role in this treatment. Current treatments such as methadone and
buprenorphine--while effective in many cases--often require continued
use for long periods of time, sometimes years, and daily maintenance.
Is NIDA researching new methods of MATs which would address these
issues?
Answer. MAT, which includes the use of methadone, buprenorphine, or
naltrexone in combination with behavioral therapy and appropriate wrap-
around services, is highly effective for the treatment of opioid use
disorders (OUDs). Like other chronic illnesses (diabetes,
cardiovascular disease), effective treatment for OUD currently requires
ongoing treatment. Abundant scientific data show that long-term use of
maintenance medications successfully reduce illicit drug use, reduce
the risk of relapse and overdose, reduce associated criminal behavior,
and help patients return to a healthy, functional life.\15\
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\15\ The American Society of Addiction Medicine (2013). Advancing
Access to Addiction Medications.
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MAT is the current standard of care for OUD; however, there is a
longstanding misconception that methadone and buprenorphine, which
control opioid craving and withdrawal, merely ``substitute one
addiction for another''. This belief has reinforced scientifically
unsound ``abstinence-only'' philosophies in many treatment centers and
limited the use of these medications. In reality, when properly
prescribed, these medications do not get the patient ``high'', they
restore balance to brain circuits that are impaired by addiction and
allow the patient to return to more normal levels of functioning.
However, these medications require regular dosing and frequent--
sometimes daily--healthcare appointments that can be burdensome for
many patients. NIDA research is exploring ways to improve the treatment
of OUDs including:
Development of non-opioid based medications and treatments:
--Lofexidine is an alpha2A-adrenergic receptor agonist that is
currently being evaluated as an adjunct treatment for cravings
and withdrawal to reduce the doses of buprenorphine or
methadone needed to treat OUD. NIDA, through a public-private
partnership with US WorldMeds LLC, supported a Phase III
Clinical Trial examining the safety and efficacy of Lofexidine
in buprenorphine-maintained patients at 13 sites. If approved,
Lofexidine will be the first non-narcotic medication approved
by the FDA to treat opioid withdrawal.
--NIDA is supporting research examining multiple new targets to treat
OUD, including Doxazosin (alpha1 adrenergic receptor blocker);
Zonisamide (sulfonamide anticonvulsant); Lorcaserin (5HT2C
serotonin agonist); and NT-814 (neurokinin receptor
antagonist).
--Anti-opioid vaccines--NIDA is currently supporting the development
of several vaccines that bind to opioids within the body and
prevent them from entering the brain. Vaccines currently in
development can bind to heroin or prescription opioids or both,
while another targets both opioids and HIV to simultaneously
protect against HIV infection while reducing the rewarding
effects of opioids.
Improving current medications and treatment regimens:
--Probuphine Buprenorphine Implant.--Probuphine provides a new
treatment option for people in recovery who may value the
unique benefits of a six-month implant compared to other forms
of buprenorphine, such as the possibility of improved patient
convenience from not needing to take medication on a daily
basis. A New Drug Application (NDA) that includes results from
a Phase III double-blind clinical study was resubmitted in
September of 2015. FDA action is expected this year.
--Re-Engineering Methadone Treatment.--Ongoing research is testing
strategies to redesign methadone treatment programs to offer
more patient-centered care that improves the counselor-client
relationship, treatment retention, patient outcome, and cost-
efficiency.
--Comparative Effectiveness of MATs.--Methadone, buprenorphine, and
naltrexone are all effective for treating OUD. NIDA is funding
comparative effectiveness studies to determine which
medications work best for specific populations including
opioid-dependent youth and HIV-positive patients.
--Biomarkers for Pain.--NIDA supports imaging studies of pain-altered
brain function as well as molecular markers in order to
identify biomarkers for pain conditions. .
--Partnerships to Improve Service Delivery.--In response to the high
rates of opioid overdose in Appalachia, NIDA has partnered with
the Appalachian Regional Commission to fund research to address
injection opioid use and its consequences in the Appalachian
Region to determine how best to leverage available resources
and programs to address the epidemic, and to improve service
delivery.
--Implementation Science for Improved Medication Assisted Treatment
(MAT) Delivery.--Several NIDA-supported investigators are
developing and testing strategies to facilitate the effective
and sustainable implementation of MAT in settings with high
rates of opioid use disorders including criminal justice
settings, emergency departments, and HIV treatment settings.
--Mobile Health and Telehealth for Improved Delivery of MAT.--NIDA
also funds the development and testing of technology-based
tools to facilitate communication between patients and
providers; improve patient adherence; help providers deliver
more patient-centered care for OUD; and improve client
motivation and build their skills to achieve better outcomes.
______
Questions Submitted by Senator Jeanne Shaheen
institutional development award program
Question. Dr. Collins, I was very pleased Congress provided a
significant increase in funding for NIH in last year's budget. So many
people who are affected by disease look to the NIH for hope that one
day a cure can be found that will help them live longer and healthier
lives. Thank you for your leadership.
I was also very pleased that the NIH Institutional Development
Award program received a significant increase in the fiscal year 2016
omnibus. As you know, New Hampshire is a very active participant in the
program and it has helped us build new research infrastructure and
recruit the new generations of research scientists our Nation needs for
the future. I think New Hampshire has important contributions that we
can make to support NIH's biomedical research mission.
The president's request has an over budget increase for fiscal year
2017. Do you think the budget for the Institutional Development Award
program should grow along with the budget for NIH?
Answer. Funding for the IDeA program was held flat relative to
fiscal year 2016 in the President's fiscal year 2017 Budget Request,
consistent with the overall proposed fiscal year 2017 NIGMS budget and
the proposed budget for other NIH Institutes and Centers excluding
special targeted Presidential initiatives.
______
Questions Submitted by Senator Brian Schatz
opioids
Question. When discussing the urgent need to address the public
health crises of chronic pain and opioid abuse, you stated that ``we
need new alternatives for pain management and the NIH and our partners
will develop them.'' Despite the substantial human and economic burden
of chronic pain on our Nation, according to the NIH Estimates of
Funding for Various Research, Condition, and Disease Categories (RCDC),
the NIH only spent $463 million on pain research in fiscal year 2015,
with a near-flat estimate of $481 million for fiscal year 2016 and
fiscal year 2017 (equal to an investment of less than five cents per
person with chronic pain). Please outline the NIH's specific plan for
fiscal year 2017 to increase the NIH's investment in pain research and
to develop and implement a targeted basic, translational, and clinical
research effort that will: elucidate the underlying biological
mechanisms of chronic pain; develop and discover safe, effective
pharmacologic and non-pharmacologic therapies that can replace the use
of addictive medications in the treatment of chronic pain; and populate
an evidence base that can inform clinical strategies and care. With
which Federal agencies will the NIH partner? Which person,
institute(s), center(s), or office(s) within the NIH will be
responsible for overseeing and implementing this effort across the NIH
and in conjunction with other agencies? Which NIH initiatives hold the
most promise for achieving these goals in a time- and cost-effective
manner (e.g., Advanced Medicines Partnership, public-private
partnerships through NCATS, Precision Medicine Initiative, BRAIN
Initiative)? What is the associated timeline and budget for this
effort?
Answer. The societal and individual benefits derived from improved
pain management are significant, and a continued investment in NIH is
needed to advance research to discover new and effective therapies. NIH
is committed to advancing pain research with the ultimate goal of
reducing the burden of pain and improving safe and effective pain care.
Several principles govern how NIH sets its research priorities:
scientific merit, scientific opportunities, public health needs, and
portfolio balance. NIH funds a broad range of pain research spanning
basic, translational and clinical studies. Through efforts of the NIH
Pain Consortium, funding for pain research has nearly doubled since
2003. In light of the heightened awareness of the opioid and chronic
pain crises and the release of the HHS National Pain Strategy (NPS),
NIH has responded to the need to enhance the pain research agenda and
is acting through several strategies.
NIH, along with Agency for Healthcare Research and Quality (AHRQ),
Centers for Disease Control and Prevention (CDC), Department of Defense
(DOD), Food and Drug Administration (FDA) and Veterans Administration
(VA) currently is engaged in developing a long-term Federal Pain
Research Strategy (FPRS). The effort is coordinated by NIH and the
Interagency Pain Research Coordinating Committee (IPRCC). NIH's Office
of Pain Policy under the direction of Dr. Linda Porter, National
Institute of Neurological Disorders and Stroke (NINDS), is implementing
the effort. The objectives of the strategy are to review the current
state of federally supported pain research, identify gaps and research
needs and prioritize recommendations to advance the Federal research
agenda. A panel of experts will provide recommendations on basic,
translational, and clinical research as it relates to the continuum of
pain from prevention through chronic pain management. The full spectrum
of research will be addressed, from biological mechanisms through
development of novel safe and effective therapies. The timeline for
completion of the strategy is January, 2017.
Pain research is supported by nearly all Institutes across NIH. The
NIH Pain Consortium is a trans-NIH entity that includes members from 25
Institutes and Centers (ICs) and is chaired by Dr. Koroshetz, Director
NINDS. It was established to coordinate pain research efforts across
NIH. It supports many shared funding opportunities that span the
interests of multiple ICs and in some cases those of other Federal
agencies. See: http://painconsortium.nih.gov/Funding Opps/highlighted-
initiatives.html.
The BRAIN initiative provides opportunities to elucidate the
neuronal pain circuitry and dysregulation of neuronal processing
associated with chronic pain and as such is highly relevant to the pain
research agenda. In addition the Precision Medicine Initiative is
creating a large dataset from a cohort of more than a million Americans
that will include information about pain symptoms, analgesic use,
patient characteristics, clinical outcomes, and self-reported
outcomes--providing a resource with tremendous promise for advancing
pain research.
The reliance on opioids for chronic pain management and its
associated harms has heightened the need to develop and promote novel
approaches to integrated pain care that are safe, effective, and not
reliant on opioids. NIH currently funds research that includes
development of non-opioid and non-addictive opioid analgesics, trials
for effectiveness of integrated pain care, development of novel non-
pharmacological treatment approaches, and exploration of new drug
targets. NIH hosted the Pathways to Prevention Workshop on long-term
use of opioids for chronic pain. Follow-up meetings with Federal
partners, focused on research priorities from the workshop and ways
that Federal agencies can coordinate efforts to address the priorities,
including the development of non-opioid pain therapies and
multidisciplinary approaches to care.
One challenge faced by NIH is the small size of the pain research
community, which limits the number of applications and in turn, the
level of NIH funding for pain research. NIH continues its concerted
effort to expand the field by encouraging junior and non-pain
investigators to enter into pain research through funding incentives
that promote early career stage pain researchers, and specifically call
for multidisciplinary pain and non-pain investigators to collaborate
(e.g., http://painconsortium.nih.gov/Funding_Opps/highlighted-
initiatives.html). NIH also regularly provides training workshops at
scientific meetings of pain specialists. Expansion of the research
community is a crucial step toward increasing funding levels for pain
research to ensure that these dollars are directed to high-quality,
innovative research.
NIH hopes that the efforts described here will contribute to a
Department of Health and Human Service (HHS)-wide effort to expand
research needed to address the ongoing opioid crisis and the broad
priorities identified in NPS and in the ongoing FPRS. It is NIH's hope
that once fiscal year 2017 is completed, the full set of pain-related
research applications awarded will lead to a higher amount of funding
than the current fiscal year 2017 estimate indicates.
NIH appreciates the significance of the public health and economic
burden of pain and will continue to develop partnerships across our
institutes and other Federal agencies to enhance and improve our pain
research agenda.
Telehealth
Question. We've spoken before about telehealth and remote patient
monitoring, and how these technologies can improve outcomes and save
money. I know that the NIH has supported a lot of work on mobile
health, or mHealth. Can you please give me an update on the research
currently being funded at NIH on telehealth?
Answer. Telehealth approaches leverage communications technologies
to provide and support healthcare at a distance. NIH is committed to
the development of telehealth approaches that enable people to take
advantage of medical advances, regardless of their circumstances. Many
NIH-sponsored research projects are funded as parts of initiatives
supporting small business innovations. These small businesses are
translating scientific and technological advancements into tools for
the practice of medicine in a diverse range of settings. Other projects
are the result of investigator-initiated exploratory applications that
push the boundaries of how we approach medical treatment and care.
NIH has a history of targeted efforts to stimulate growth in the
telehealth space. As early as 1994, the National Library of Medicine's
High Performance Computing and Communications awards sought out
applicants developing telemedicine and telehealth approaches.\16\ The
National Institute of Biomedical Imaging and Bioengineering (NIBIB) has
also championed the advancement of telemedicine with targeted programs
and general support.\17\ These founder programs established NIH-wide
support of telehealth development. Their impact is evidenced in the
major themes of NIH-funded telehealth research:
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\16\ Advanced Technology Focus of 12 HPCC Health Care Awards.
(1997, April 3). Retrieved April 21, 2016, from https://
www.nlm.nih.gov/archive/20041229/research/telemedhpcc.html.
\17\ Telehealth. (2013, January 22). Retrieved April 21, 2016, from
https://www.nibib.nih.gov/science-education/science-topics/
telehealth#1431.
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--Overcoming Barriers.--Today, there are many barriers for some
patients, including physical and logistical constraints, to
receiving adequate care and treatment in the traditional
medical setting. Telehealth research funded by the NIH aims to
bring the clinic to the patient, and the specialist provider to
the generalist, with tools that allow for healthcare-related
exchanges remotely. For example, investigators on a recently
funded project at the University of Texas, Austin, are piloting
teleconsultation methods that allow low-income, house-bound
seniors to receive mental health counseling.\18\ Other NIH-
funded researchers are investigating the use of extant social
infrastructure, such as community churches, as hubs for the
receipt and distribution of medical care and information
related to obesity and type 2 diabetes.\19\ In addition,
researchers at the University of Washington are harnessing the
reach of telehealth approaches to help manage coordinated care
efforts for women with perinatal depression.\20\
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\18\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8927954.
\19\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8994598.
\20\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9008381.
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--Remote Access to Care.--While the last decade has brought major
technological and intellectual advances to the field of
medicine, these advances are not always readily available at
the myriad points of care upon which people are dependent.
Another focus of NIH-funded telehealth research is building
diagnostic tools that free patients and providers from the
constraints of the hospital or clinic. Along these lines, a
group at Massachusetts General Hospital is pioneering
technology to enable smartphones to be used as confocal
microscopes to help diagnose AIDS-related Kaposi sarcoma, while
scientists at Emory University are leveraging mobile
technologies to create automated web-based methods for early,
remote diagnosis of Alzheimer's disease.\21,22\ NIH funding is
also enabling the development of remote diagnostics for
conditions like traumatic brain injury, HIV, Ebola and other
infectious diseases, and breast cancer.\23,24,25,26,27,28\
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\21\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9018555.
\22\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=8704932.
\23\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8969564.
\24\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8905469.
\25\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9141791.
\26\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9115796&icde=
30006803&ddparam=&ddvalue=& ddsub=&cr=1&csb=default&cs=ASC.
\27\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8891696.
\28\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9133217.
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--Remote Patient Monitoring.--Diagnosis is a first step, but chronic
conditions regularly need frequent monitoring by healthcare
providers. Moreover, it is often critical that emergent, life
threatening events are identified as soon as possible to enable
effective interventions. NIH is funding research that enables
this remote patient monitoring, like efforts by biotechnology
companies to develop a disposable assay to monitor heart
failure at home in at-risk patients and imbedded biosensors to
monitor patients' blood levels of chemotherapy agents in real
time.\29,30\
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\29\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8905933.
\30\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8839582.
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NIH recognizes the promise of telehealth approaches that allow for
delivery of quality healthcare in a range of settings. Not only has NIH
funded discrete research projects that advance the field of telehealth,
the agency has woven telehealth applications development and evaluation
into the fabric of large, trans-NIH and intergovernmental initiatives
like the Precision Medicine
Initiative. As one of its founding principles, NIH is committed to
improving the health and wellbeing of all people, regardless of their
circumstances. As such, NIH will continue to fund cutting edge
research, such as telehealth development, that helps to realize these
principles.
research centers in minority institutions program
Question. The legislation that established the Research Centers in
Minority Institutions (RCMI) program in 1985 was intended to
``strengthen the research environment'' of ``predominantly minority
institutions'' that ``offer degrees in the sciences related to health
but which heretofore have not received significant amounts of research
support.'' NIH moved to accomplish this goal by, as stated in the most
recent Funding Opportunity Announcement (FOA), providing funds to ``(1)
develop and enhance the institutional research infrastructure necessary
for the conduct of biomedical and/or behavioral research; (2) enable
minority institutions to become more successful in obtaining
competitive extramural support for the conduct of biomedical and/or
behavioral research; and (3) enhance the biomedical research
environment at these institutions.'' The RCMI program has benefited
numerous minority institutions, including through the growth of NIH
funding, increased publications and presentations, the recruitment and
retention of excellent faculty, and much more.
I support the intent of the RCMI program as originally enacted.
However, we have been hearing that NIH may be considering changes to
this program. Can you please address the following:
--Will non-minority institutions become eligible for RCMI funding?
--Will institutions that have received ``significant amounts of
Federal funding'' now be allowed to compete?
--Will awardee institutions no longer be allowed to fund pilot
projects within the institution to increase the competitiveness
of their faculty?
--Will it be necessary to distribute RCMI funding across a variety of
disciplines in the awardee institution, i.e., basic biomedical
science, socio-behavioral science, and clinical population
studies, rather than focusing on their institutional strengths
in order to increase competitiveness?
Answer. Eligibility of the RCMI program has historically been tied
to doctoral degree granting institutions of higher education designated
as a ``minority institution'' by the Department of Education. The
National Institute on Minority Health and Health Disparities (NIMHD) is
committed to keep the intent of the RCMI program and will continue to
engage institutions that are less research intensive based on overall
NIH funding and have a history of supporting students and trainees
underrepresented in biomedical research and to serving diverse
populations.
Consistent with the intent of the RCMI program, the priority
continues to be strengthening the research environment at the
institution. There are multiple ways to accomplish that goal, from
providing specialized expertise such as biostatistics, health
informatics or specific research skills in laboratory science, to
conducting specific research projects in minority health or health
disparities. Moreover, NIH recognizes the value of small scale pilot
projects to enhance the expertise and career of junior faculty and
agrees that it is a valuable component of the RCMI program.
Individual RCMI institutions have and will continue to be able to
focus on different scientific areas including basic biomedical,
behavioral, and/or clinical research that best align with the strengths
of their institution.
Since the transfer of the RCMI program to NIMHD in 2012 with the
dissolution of the National Center for Research Resources (NCRR), NIMHD
has made it a priority to integrate the RCMI program into the existing
NIMHD portfolio. NIMHD has focused on specific programmatic goals and
objectives in order to minimize overlap and maximize the scientific
benefit of the Federal resources and plans to provide updated guidance
to the extramural research community in the summer of 2016.
______
Questions Submitted by Senator Tammy Baldwin
ethical issues surrounding non-human primates
Question. Dr. Collins, I understand that NIH has plans to develop a
summer workshop on ethical issues surrounding research with non-human
primates. Can you please share additional background on this workshop?
Which Institutes or Centers are organizing the workshop, and who
will be responsible for choosing the participants?
Is NIH employing a broad range of experts on research with these
animals in order to ensure an open dialog that reflects the significant
scientific investments NIH has in this type of research?
Answer. Research with animals, including non-human primates,
continues to revolutionize our understanding of human health and
disease, and has enabled the development of treatments and cures for a
wide array of devastating diseases and conditions. Non-human primates
are a particularly valuable resource for answering the most complex
questions facing human health, as these animals share similar anatomy,
physiology, and behavior with humans. For instance, scientific and
treatment advances for Parkinson's disease have been a direct result of
research with non-human primates, both in the development of a disease
model and the innovative clinical application of research technologies
such as deep brain stimulation. Also, in response to the 2014-2015
outbreak of Ebola in West Africa, research using non-human primates was
critical in the development of potential new experimental vaccines now
being evaluated in clinical trials.
That being said, the decision to use non-human primates in a
particular study is not taken lightly. Research must satisfy ethical
principles of scientific rigor, appropriateness of the model, and
consideration of animal welfare. Upholding these precepts remains a
steadfast commitment of biomedical research and has been established in
policy since the passage of the Animal Welfare Act in the mid-
1960s.\31\ All NIH-funded research with animals is reviewed to ensure
that the science is highly meritorious and the welfare of the animals
is appropriately protected. NIH has established numerous policies,
procedures, and protocols to ensure all appropriate principles are
followed, including taking animal welfare concerns very seriously. The
Office of Laboratory Animal Welfare ensures this oversight framework is
followed. Its mission is to address humane care and use of animals in
HHS-supported research, testing, and training by guiding researchers
and interpreting the Public Health Service Policy on Humane Care and
Use of Laboratory Animals.\32\
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\31\ Https://awic.nal.usda.gov/government-and-professional-
resources/Federal-laws/animal-welfare-act.
\32\ Https://grants.nih.gov/grants/olaw/references/phspol.htm.
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NIH remains confident that the oversight framework for the use of
non-human primates in research is robust and has provided sufficient
protections to date. However, the Agency acknowledges that a periodic
review of its policies and processes ensures that this framework
evolves in a manner consistent with emerging scientific opportunities
and public health needs.
Toward this end, NIH plans to convene experts in science, policy,
ethics, and animal welfare to discuss the oversight framework governing
the use of non-human primates in NIH-funded biomedical and behavioral
research endeavors. At this workshop, NIH will explore the current
state of science of NIH-supported research involving non-human primates
as research models and discuss how existing regulations and policies
address their continued responsible use in research.
The NIH Office of Science Policy, which is part of the NIH Office
of the Director, is organizing this workshop, which will occur later
this fiscal year. During the planning process, the NIH Office of
Science Policy will consult with NIH Institutes and Centers that fund
research using non-human primates, the Office of Laboratory Animal
Welfare, and the Department of Bioethics to identify a diverse and
knowledgeable group of speakers and panelists for the workshop. The
workshop participants, both internal and external to NIH, will
represent the Agency's significant scientific investment in research
utilizing non-human primates and provide a thorough and productive
dialogue to support the continuation of ethical and responsible
research using nonhuman primates.
SUBCOMMITTEE RECESS
Senator Blunt. And the subcommittee stands in recess.
[Whereupon, at 12:00 p.m., Thursday, April 7, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]
MATERIAL SUBMITTED SUBSEQUENT TO THE HEARING
[Clerk's Note.--The following outside witness testimonies
were received subsequent to the hearing for inclusion in the
record.]
Prepared Statement of Dr. 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 fiscal year 2017 budget request for the
National Institute on Deafness and Other Communication Disorders
(NIDCD) of the National Institutes of Health (NIH).
NIDCD conducts and supports research and research training in the
normal and disordered processes of hearing, balance, taste, smell,
voice, speech, and language. NIDCD 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.
inner ear blueprint may lead to treatment for hearing loss and balance
disorders
Approximately 50 percent of Americans ages 75 and older have a
disabling hearing loss. In addition, more than 1 in 20 children in the
United States between the ages of 3 and 17 have a dizziness or balance
problem. To determine the causes of hearing loss and balance disorders,
it is important to understand how the cells in the inner ear form. To
do this, scientists are identifying gene expression maps of the inner
ear cells. Understanding inner ear cell development could lead to ways
to regenerate lost or damaged cells and restore hearing and balance.
Specialized sensory epithelial cells in the inner ear are
responsible for hearing and balance. These cells, which include hair
cells and supporting cells, are located in the cochlea, the snail-
shaped structure in the inner ear, and work together to detect sound.
Similar types of hair cells and supporting cells are also found in the
utricle, a fluid-filled pouch located near the cochlea, which plays a
critical role in helping us maintain our balance. These cells detect
how we move our heads, how our heads are positioned and whether we are
moving or stationary; this information tells our brain, for example,
whether we are standing or lying down. The utricle is one of several
structures and organs in the body that provide our sense of balance.
Hair cells and supporting cells can be damaged by medications,
infections or disease, injury, exposure to loud noises, or aging,
leading to hearing loss and balance problems. In humans, these cells
cannot naturally repair themselves, so effective treatments are
limited. In addition, there are only a few thousand of these sensory
cells and they are located in a bony channel embedded in the skull,
making them difficult to study.
Using a sensitive new technology called single-cell RNA-seq, NIDCD
intramural scientists have created the first high-resolution gene
expression map of a single cell within the newborn mouse inner ear. By
analyzing the cell's gene activity profiles, the scientists were able
to identify genes that are active at different stages of development.
The findings provide new insights into how epithelial cells in the
inner ear develop and differentiate into the specialized cells that
serve critical functions for hearing and maintaining balance.
Understanding how these important cells form may provide a foundation
for the potential development of cell-based therapies for treating
hearing loss and balance disorders.
mini inner-ear drug delivery device could help common hearing and
balance problems
Approximately 37.5 million American adults report some degree of
hearing loss and almost eight million adults report a chronic problem
with balance. Common examples include middle-ear infections (otitis
media), Meniere's disease, noise-induced hearing loss, tinnitus, age-
related hearing loss, dizziness, and vertigo. Hearing and balance
disorders also decrease quality of life, and they cross all ethnic and
socioeconomic lines.
Developing drug treatments is a long and costly process. One of the
first hurdles is developing drugs that are safe and effective. For drug
therapies to treat hearing loss and balance disorders, a second hurdle
is getting the drugs where they need to go, which is deep inside the
skull to the inner ear. Developing a safe and efficient route to the
inner ear represents a significant technical challenge. Another
challenge is to determine the appropriate concentration or dosage of a
drug to be delivered into the ear.
NIDCD-supported scientists are tackling these hurdles. Using
microfluidic and microelectromechanical systems technologies,
researchers developed a wearable miniaturized pump system that safely
and effectively delivers drugs in various dosages over time to the
inner ear in animal studies. The device can also take samples of the
inner ear fluid, which will aid scientists in drug development and
treatment.
The investigators hope to use this device in preclinical animal
studies. They plan to make the micro-pump and its electronic components
so small that someday the entire system can be implanted in an
individual's mastoid cavity, an opening in the bone behind the ear. The
device would enable programmable, automated, and long-term delivery of
therapeutic compounds to the inner ear. Because it can target inner ear
fluid precisely, the device will serve as a useful tool for
investigating the molecular mechanisms associated with inner ear
diseases and testing new drug treatments for hearing and balance
problems.
Problems with Ability to Taste or Smell are Common in Middle-Aged
and Older Adults People who have a poor ability to taste or smell can
miss important cues to help them avoid dangers such as gas leaks, fire,
and spoiled food. Scientists in the NIDCD Epidemiology and Statistics
Program collaborated with the Centers for Disease Control and
Prevention to conduct the first nationally representative survey about
perceived taste and smell problems in more than 3,600 adults aged 40
and older. About 19 percent of U.S. adults ages 40 and older report
having had a problem with their ability to taste, and approximately 23
percent report having had a problem with their ability to smell. The
likelihood that a person will report a diminished sense of taste and/or
smell increases with age. In adults ages 80 or older, nearly 31 percent
report having had a problem with their sense of smell, and more than 27
percent have had a problem with their sense of taste. This survey was
part of the Healthy People 2020 national objectives for improving the
health of all Americans. The data help us gauge the scope of the
problem. Future data releases will also include results of taste and
smell tests and will give us our first look at prevalence of taste and
smell problems in the United States.
scientists grow vocal fold tissue in the lab
Vocal fold tissue is a complex biological structure that is
responsible for normal voice production. About 7.5 million people in
the United States have trouble using their voices. Voice problems can
cause significant personal and occupational difficulties, loss of
income, and reduced quality of life. People who have sustained injuries
to the larynx or have undergone head and neck surgery can exhibit voice
disorders. These disorders can range in severity from mild to total
voice loss if the surgery was extensive for removal of a malignancy.
NIDCD-supported voice scientists in collaboration with other NIH-
supported researchers have bioengineered vocal fold tissue in the lab
using human cells. Moreover, the tissue had physical qualities that
allowed it to ``behave'' like normal vocal fold tissue. To see if it
could transmit sound, the researchers transplanted the tissue into an
animal model. The bioengineered tissue performed well and was not
rejected by the recipient, which is usually a major obstacle in these
types of surgeries. This proof-of-principle study provides hope that
one day individuals who have lost the use of their voice because of
loss of their laryngeal tissue will have better treatment options.
______
Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S.,
Director, National Institute of Environmental Health Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of Environmental Health Sciences (NIEHS) of the National
Institutes of Health (NIH).
understanding our exposures
An oil rig explodes in the Gulf of Mexico impacting an entire
region's way of life. A manufacturing plant spills thousands of gallons
of toxic chemicals into a river in West Virginia creating unknown risks
to nearby residents. A combination of aging pipes and corrosive water
leaches lead into drinking water in Flint, Michigan, posing
irreversible harm to the city's children. These recent events bring
into stark relief the critical need for strong exposure science--the
first step in responding to an environmental health emergency is to
understand the nature of the threat. But as prominent, tragic, and
increasingly common as such occurrences are, they represent only a
small part of the thousands of potentially harmful chemicals, metals,
and other environmental pollutants our Nation's people are faced with
on a daily basis.
Protecting people's health from the consequences of such encounters
requires knowledge, not only of the nature of the hazard itself, but
just as importantly, of the means, amount, and effects of exposure to
it. And further complicating our ability to determine our risk is the
combination of human response variability and disparate exposures to
environmental health threats. But such knowledge must be obtained if we
are not only to respond to exposures after they occur, but be
successful in the larger goal of avoiding harmful exposures, and
thereby preventing illness and disease from ever occurring. The
recognition of this fundamental scientific need is the basis of the
work of NIEHS and the reason why our Institute has prioritized exposure
science in its Strategic Plan. Although the issue of exposures is
integrated throughout the plan, specific goals call for NIEHS to
``Transform exposure science by enabling consideration of the totality
of human exposures and links to biological pathways, and create a
blueprint for incorporating exposure science into human health
studies,'' and to ``Understand how combined environmental exposures
affect disease pathogenesis.'' I will describe just some of the ways in
which NIEHS has made significant progress toward these goals and toward
ensuring the health of the American people.
connecting exposures to outcomes
Five years after the Deepwater Horizon (DWH) oil rig explosion,
which caused the largest oil spill in U.S. history, NIEHS-supported
researchers continue work in three related areas--a health effects
study of oil spill cleanup workers called the GuLF Study, research
partnerships between Gulf-area universities and community
organizations, and an NIH disaster research response effort. The
research team developed a job-exposure matrix that enabled scientists
to characterize exposures of workers participating in the GuLF Study
and assess possible links between reported health symptoms and the
chemicals each worker was exposed to, and preliminary results are being
analyzed. University-community partnerships are focusing on health
concerns identified by communities after the oil spill, including
pregnancy and birth outcomes, general physical and mental health of
coastal residents, and seafood safety. A study of 2,126 adult women
residing in Southern Louisiana enrolled in the Women and Their
Children's Health (WaTCH) study showed that both physical/environmental
and economic exposure to the oil spill was associated with an increase
in self-reported physical health outcomes. On a positive note, a risk
assessment of exposure to polycyclic aromatic hydrocarbons of
Vietnamese-Americans, a large shrimp-consuming population in the area,
showed no acute health risks or excess cancers, reducing concerns about
shrimp consumption following the DWH spill.
Following the spill of 10,000 gallons of the chemical 4-
Methylcyclohexanemethanol (MCHM) into the Elk River upstream of the
municipal water intake of Charleston, West Virginia, NIEHS researchers
were able to help allay the fears of the community and State officials
through a timely assessment that combined exposure data with a suite of
health effect prediction studies, including computer modeling and
laboratory toxicity studies. Findings of these investigators provided
additional support for the adequacy of the drinking water advisory set
by the Centers for Disease Control and Prevention at the time of the
spill as being protective of health.
In response to the latest public health disaster, the exposure of
the population of Flint, Michigan, to lead in contaminated drinking
water, NIEHS staff and grantees are leading efforts to understand
residents'--especially children's--lead exposures to inform the public
health response, both immediately and over the long-term. A long and
continuing history of support of research on lead enables such efforts.
Recent research by NIEHS grantees in Michigan demonstrated, for the
first time, that lead exposure of pregnant mothers can affect DNA
methylation patterns in their grandchildren, suggesting that a much
longer-term perspective may be needed when considering measures to
protect environmental health in the future. Also, NIEHS-funded research
of lead-poisoned children in China recently established that
measurement of lead in bone (through X-ray fluorescence) is a useful
biomarker of lead exposure in children. Such research illustrates the
kind of knowledge that might be applied to situations like the one in
Flint. It is this kind of useful knowledge that NIEHS hopes to enable
researchers to obtain through its recently established Children's
Health and Exposure Assessment Resource (CHEAR), which will provide a
laboratory network, data repository, and an analysis center to leverage
the public investments of NIH-funded scientists to better understand
environmental exposures and human health.
Public health disasters such as chemical releases, hurricanes,
infectious disease outbreaks, and others comprise unique exposure
scenarios that can offer insights into environmental exposures
encountered, not only by the affected communities and responders, but
also by a broader range of the population. NIEHS, in collaboration with
the National Library of Medicine, has developed the Disaster Research
Response (DR2) program to further our national ability to gather time-
critical exposure and health information to reduce adverse health
effects and improve response, recovery, and preparedness for future
events. At the same time, this program will facilitate discovery
research and generate novel hypotheses that will add to the body of
knowledge underlying exposure related conditions such as cancer,
neurological, and immune diseases and disorders.
Disasters are compelling for both public and research attention,
and deservedly so. But NIEHS efforts to elucidate the broad range of
environmental exposures are far more proactive than responsive, and
consistently generate findings that increase our ability to protect and
improve people's health. For example, an ongoing project is using a
matrix biomarker of tooth development to reconstruct the exposome--the
compilation of multiple chemical exposures--over different life stages.
A better understanding of how and when specific exposures occur will
improve our ability to target interventions, particularly during
critical windows of development. NIEHS-funded investigators also are
working at the cutting edge of research on the microbiome,
investigating interactions between the gut microbiome and exposure to
arsenic, a known human carcinogen, and uncovering the relationship
between obesity and exposure to ozone.
translating science into action
NIEHS efforts are directly supportive of major health initiatives
in the United States including Big Data to Knowledge (BD2K), the
National Cancer Moonshot, and the Precision Medicine Initiative.
NIH's BD2K initiative is focused on developing new strategies to
analyze and leverage the explosion of increasingly complex biomedical
data sets. NIEHS is leading the program's Training and Workforce
Development efforts. These awards support current and future
generations of researchers to specialize in data science fields and in
the use or generation of Big Data. A current awardee is working to
establish new integrative and data-driven methods for building systems
neuroscience models of executive functioning during childhood,
reporting recent advances in improving the specificity of magnetic
resonance imaging (MRI) scans.
The recently announced National Cancer Moonshot aims to bring about
a decade's worth of advances in 5 years, in part by improving our
ability to prevent cancer and detect it at an early stage. Cancer, like
most other non-communicable diseases, is a result of a person's
genetics, age, and environment (including lifestyle), and the World
Health Organization estimates that nearly 20 percent of cancers may
result from toxic chemical exposures. NIEHS-supported researchers
continue to make groundbreaking advances in our understanding of the
complex interactions between these three factors, leading to knowledge
to inform cancer detection and prevention strategies, as well as
treatments and therapies. For example, polycyclic aromatic hydrocarbons
(PAHs) are probable carcinogens found in coal tar, diesel exhaust, and
wildfire, cookstove, and cigarette smoke. People are primarily exposed
to PAHs in mixtures, though current risk assessments focus on
individual components. An NIEHS grantee and colleagues have developed a
faster, more accurate method to assess cancer risk from mixtures of
PAHs by evaluating bioactivity after short-term exposure.
An example of NIEHS contributions to potential cancer therapy lies
in treatment of ovarian cancer. The recurrence rate of ovarian cancer
exceeds 75 percent, and the success of subsequent chemotherapy is
limited because of the progressive development of drug resistance. New
NIEHS findings suggest that a novel mechanism, combined activation of
an early growth factor (EGR1) and microRNA (MIR152), may provide a
useful therapeutic strategy to overcome resistance to the chemotherapy
drug cisplatin, and improve outcomes in ovarian cancer.
NIEHS research spans the spectrum of scientific inquiry from basic
mechanisms to exposure science to clinical research aimed toward
intervention and treatment. Precision medicine is an emerging approach
for disease treatment and prevention that takes into account individual
variability in genes, environment, and lifestyle for each person.
Advances by NIEHS scientists are poised to make great contributions to
the promise of precision medicine. These contributions range from
identifying factors including autoantibodies, clinical factors, and
environmental exposures at illness onset associated with the disease
course of juvenile myositis, a group of rare and life-threatening
autoimmune diseases in children, to developing a method for isolating
certain rare cells of metastatic breast cancers in blood and profiling
their gene expression to provide real-time warnings of emerging
chemotherapy resistance.
conclusion
To conclude, NIEHS continues to be at the forefront of
environmental health: identifying emerging health threats, developing
and implementing new technologies to characterize and analyze our
exposure to the world around us, and leading the generation of
knowledge of how our environment interacts with our genetics to cause
illness and disease. And consistent with our mission, we will continue
to lead these efforts in support of the Nation's initiatives to improve
and ensure the health of the American people.
______
Prepared Statement of Josephine P. Briggs, M.D., Director, National
Center for Complementary and Integrative Health
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National Center
for Complementary and Integrative Health (NCCIH) of the National
Institutes of Health (NIH).
The NCCIH is the lead Federal agency for scientific research on the
usefulness and safety of complementary and integrative health
practices. Complementary health approaches include mind and body
interventions, such as massage, acupuncture, yoga, and meditation, and
natural products, such as dietary supplements and probiotics. To
address the need for objective evidence as to the safety and efficacy
of many of these approaches, NCCIH supports rigorous scientific
investigation to better understand how these interventions work, for
whom, and the optimal method of practice and delivery.
The 2012 National Health Interview Survey (NHIS), conducted by the
Centers for Disease Control and Prevention (CDC) with support from
NCCIH, showed that one-third of U.S. adults use complementary and
integrative health approaches. Many of these individuals seek these
approaches to improve their health and well-being or to manage symptoms
of chronic diseases or the side effects of conventional medicine.
Natural products (dietary supplements other than vitamins and minerals)
are the most commonly used complementary health approach, followed by
deep breathing exercises and yoga.
reducing pain and improving symptom management
Pain is a major public health problem and is the most common reason
Americans turn to complementary and integrative health practices. Data
from the 2012 NHIS found that an estimated 25.3 million adults in the
United States (11.2 percent) experience daily pain. In addition, nearly
40 million adults (17.6 percent) experience severe levels of pain and
are likely to have worse health status than the general public.\1\
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\1\ Nahin RL. Estimates of pain prevalence and severity in adults:
United States, 2012. Journal of Pain. 2015;16(8):769-780.
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CDC has classified fatal overdoses involving opioid analgesics,
medications used to treat pain, as an epidemic. To help address this
crisis, we need improved strategies for pain management so that
healthcare providers are less reliant on prescribing opioids. NCCIH
supports research to better understand pain and to identify effective
nonpharmacologic approaches to reduce the duration and intensity of
pain. For example, our intramural research program studies the role of
the brain in perceiving, modifying, and managing pain. Specifically,
scientists are investigating the role of the brain in pain processing
and how emotion, environment, and genetics affect its perception.
Recent results from NCCIH's extramural research program are
advancing our understanding of the mechanisms of action of mind and
body interventions and helping determine their effectiveness for
treating pain. For example, previous research showed that mindfulness
meditation helps relieve pain, but the mechanism through which
meditation exerts this effect is not well understood. New study
results, funded in part by NCCIH, demonstrate that mindfulness
meditation may work on a different pain pathway in the brain than
opioid pain relievers. Since opioid and non-opioid mechanisms of pain
relief interact synergistically, the results suggest that combining
mindfulness-based and other pain-relieving approaches that rely on
opioid signaling may be particularly effective.
Furthermore, study results published in the Journal of the American
Medical Association expand the evidence base for the effectiveness of
mind and body interventions. In the first randomized clinical trial to
rigorously evaluate mindfulness-based stress reduction (MBSR) for young
and middle-aged adults with chronic low back pain, researchers compared
MBSR with usual care (UC) and cognitive-behavioral therapy (CBT). They
found that individuals with chronic low back pain who received training
in MBSR and CBT, compared with UC, demonstrated greater improvements in
functioning and reductions in chronic low back pain at 6 months and 1
year following treatment. The persistence of these beneficial effects
suggests that MBSR and CBT may provide patients with skills for long-
term management of pain.
NCCIH is also working with other NIH Institutes and Centers, the
Department of Veterans Affairs (VA), and the Department of Defense
(DOD) to test improved pain management strategies. Military personnel,
veterans, and their families often struggle with pain management and
its associated comorbidities including opioid misuse, abuse, and
disorder. NCCIH plans to support a clinical trial coordinating center
to launch a multi-year program to develop and test the efficacy and
effectiveness of nonpharmacologic approaches to pain management and
comorbidities for our military and veteran populations. Additionally,
NCCIH is collaborating on the NIH Brain Research through Advancing
Innovative Neurotechnologies (BRAIN) Initiative to accelerate the
development and application of technologies to study the brain. NCCIH
also is leveraging its resources through the NIH Common Fund's
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program
to better understand the mechanisms of action and the development of
``electroceuticals'' for therapies in which nerves are stimulated to
control organ function.
advancing research on natural products
Nearly one in five U.S. adults use botanical supplements and other
non-vitamin, non-mineral dietary supplements, such as fish oil/omega-3
fatty acids and probiotics, according to the 2012 NHIS. The use of
dietary supplements at times poses risks. For example, adverse events
related to dietary supplements are estimated to contribute to 23,000
emergency department visits in the United States each year.\2\ To
better inform consumers and their healthcare providers, NCCIH supports
research on the biological mechanisms of the benefits and potential
harmful effects of natural products, such as their interaction with
medications and liver toxicity. In fiscal year 2015, NCCIH established
a Center of Excellence for Natural Product-Drug Interaction Research.
The Center is systematically examining methods for studying natural
product-drug interactions; developing standardized protocols to clarify
which interactions have clinical impact; and disseminating its findings
and resources broadly. In essence, the Center is developing a roadmap
for the study of natural product-drug interactions with the ultimate
goal of improving the body of knowledge available to healthcare
providers, patients, and researchers.
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\2\ Geller, AI, et al. Emergency department visits for adverse
events related to dietary supplements. N Engl J Med, 2015;373:1131-40.
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To further enhance NCCIH's natural products portfolio, NCCIH
partnered with NIH's Office of Dietary Supplements (ODS) to fund five
research centers in fiscal year 2015. These research centers focus on
the safety of natural products, how they work within the body, and the
development of innovative research technologies. Specifically, the
three Botanical Dietary Supplements Research Centers will advance the
understanding of the mechanisms through which complex botanical dietary
supplements may affect human health and resilience. The two new Centers
for Advancing Natural Products Innovation and Technology aim to propel
chemical and biological investigation of natural products. Each is
tackling unique research challenges. One center is working to improve
the speed, breadth, and precision of the characterization of natural
products by developing innovative cell-based screening approaches to
uncover bioactive molecules of interest and their corresponding
biological targets. The other center is coordinating and disseminating
research technologies aimed at mining bioanalytical knowledge of
natural products.
Spurring innovation and developing new methodologies may lead to
alternative sources of medically relevant compounds. For example,
researchers, supported in part by NCCIH, created an innovative method
to produce opioid drugs from sugar using genetically modified yeast.
Using genes from a variety of plants, mammals, and microorganisms, they
created yeast cells that can perform the entire process of
manufacturing the opioids thebaine and hydrocodone using sugar as the
starting material--a process that involves more than 20 separate steps.
This innovation opens the door to additional novel approaches to
generating needed medically relevant compounds in diverse settings. The
new technique illustrates the potential value of genetically engineered
yeast as a platform for producing many complex chemicals and materials
and may help lead to better drug development in the future. Given this
advance is moving ahead of regulations and policy, open discussions and
decisions for the use and application of this technology will be
needed.
assessing cardiovascular benefit of chelation therapy in patients with
diabetes
NCCIH is leading a trans-NIH effort (with NHLBI, NIDDK, NIEHS) and
funding a planning phase to replicate the previous NIH-funded Trial to
Assess Chelation Therapy (TACT) in older heart attack patients with
diabetes. ``TACT 2'' will assess if an intravenous solution, which
includes ethylendiaminetetraacetic acid (EDTA)--a chemical used to
treat environmental exposure to heavy metal toxicity such as lead or
cadmium, will reduce cardiovascular events in diabetics. Its use for
treating heart disease was found beneficial in TACT, particularly for
diabetic patients over 50 years of age who had a previous heart attack,
but needs replication before becoming universally accepted. Additional
research to identify the mechanisms by which chelation may affect heavy
metal body burden and cardiovascular disease risk is also being
planned.
inspiring public trust through stewardship
NCCIH works diligently to be an efficient steward of the resources
entrusted to us. Currently, we are undertaking strategic planning
activities focused on prioritizing our future research investments in
complementary and integrative health. Additionally, we are ensuring
that research workforce needs, especially those of clinician-
scientists, are addressed. NCCIH's new strategic plan is expected to be
released this summer.
Due to the self-care nature of these complementary health
approaches, the translation and dissemination of unbiased, evidence-
based information is of great importance to NCCIH. Therefore, helping
consumers, healthcare providers, researchers, and policymakers be
better informed about the safety and effectiveness of complementary
interventions continues to be our primary communication goal. NCCIH
makes research findings available to the public through multiple
platforms, including video, social media, and mobile applications.
conclusion
NCCIH continues to support research and leverage its strategic
partnerships to build the scientific evidence needed by consumers,
healthcare providers, and policymakers regarding the safety and
efficacy of complementary health approaches. By catalyzing innovation,
NCCIH is advancing research on natural products and mind and body
interventions.
______
Prepared Statement of Bruce Cuthbert, Ph.D., Acting Director, National
Institute of Mental Health
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's fiscal year 2017 budget request for the
National Institute of Mental Health (NIMH) of the National Institutes
of Health (NIH).
I am particularly excited to discuss the ways in which NIMH is
working to accelerate scientific progress by supporting research that
will improve our understanding of mental illnesses, fueling the
transformation of care for the greatest public health impact.
public health burden of mental illness
NIMH is vigorously pursuing its mission to transform the
understanding and treatment of mental illnesses through basic and
clinical research, paving the way for prevention, recovery, and cure.
Mental illnesses account for 21.3 percent of all years lived with
disability in the United States, and an estimated 9.8 million American
adults suffer from serious mental illness (SMI) each year, according to
the Substance Abuse and Mental Health Services Administration (SAMHSA).
People with SMI (in which the ability to function in daily life is
significantly impaired) die 8 to 10 years earlier than the general
population. The Centers for Disease Control and Prevention report that
over 42,773 Americans died from suicide in 2014, more than twice the
mortality from homicide or AIDS. Mental illnesses rank as the third
most costly medical conditions in the United States, in terms of
overall healthcare expenditures, behind heart conditions and traumatic
injury.
improving precision in research on mental illnesses
Precision medicine means getting the right treatment at the right
time to the right person. While significant advances in precision
medicine have been made for select cancers, this is still not feasible
for most other disorders, including mental illnesses. NIMH's approach
to precision medicine revolves around the Research Domain Criteria
(RDoC) initiative, which is intended to break mental illnesses down
into fundamental mental processes (e.g., attention) compared across
biological (e.g., genes, brain circuits) and behavioral (e.g.,
wakefulness) measurements.
Results from a recent NIMH-funded study lend support to the RDoC
approach. The Bipolar Schizophrenia Network on Intermediate Phenotypes
(BSNIP) study used ``biomarkers''--or measureable indicators of
disease--to sort patients with psychotic symptoms into ``biotype''
categories. The BNSIP study demonstrated that biotypes outperformed
traditional diagnostic categories of psychotic disorders, such that
sorting individuals with psychotic symptoms into subgroups based on
brain biology can lead to greater precision in diagnosis, and
potentially treatment. In fiscal year 2017, NIMH will continue to
solicit research using RDoC approaches.
The success of RDoC relies heavily on a culture of open science and
rapid data sharing, which NIMH has formalized by creating a set of data
sharing repositories called the NIMH Data Archive (including databases
for RDoC, autism research, and clinical trials). Through these types of
initiatives, NIMH is maximizing the use and impact of a valuable asset:
our shared data.
revolutionizing our understanding of mental illnesses
Together with other NIH Institutes and Centers, NIMH co-supports
two large-scale neuroscience initiatives: The Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the Human
Connectome Project (HCP). The BRAIN Initiative will accelerate the
development and application of innovative technologies to identify how
individual cells and complex neural circuits interact, filling major
gaps in our knowledge about how the human brain functions. HCP is a
collaborative neuroimaging effort to map the neural pathways underlying
human brain function; the primary purpose is to acquire data on the
structural and functional connectivity of the human brain and to
facilitate rapid access to large HCP datasets for secondary data
analyses by other researchers. HCP and the BRAIN Initiative will set
the stage for future studies of abnormal brain circuits, thereby
advancing our understanding of the origins of mental illnesses.
early intervention changes trajectory
NIMH recognizes the vital importance of early diagnosis and rapid
delivery of appropriate and comprehensive treatment for mental
illnesses. Approximately 100,000 adolescents and young adults
experience a first episode of psychosis (FEP) each year in the United
States, and the majority of people with SMI experience significant
delays when seeking care.
To help reduce the duration of untreated psychosis, NIMH is
collaborating with SAMHSA to translate findings from the NIMH Recovery
After an Initial Schizophrenia Episode (RAISE) project into guidance
for States regarding evidence-based approaches to early psychosis
treatment. Utilizing coordinated specialty care (CSC), people
experiencing FEP were connected with specialty care providers at the
earliest stages of illness. RAISE investigators have shown that CSC is
effective and can be implemented in community treatment settings
nationwide. In fact, the Centers for Medicare & Medicaid Services
recently extended Medicaid coverage of evidence-based interventions
such as CSC for individuals experiencing FEP. This fast-paced expansion
in reimbursement practices is rare, but is a promising example of how
NIMH-funded research can be quickly translated into practice.
NIMH will build on the RAISE project with plans to launch the Early
Psychosis Intervention Network (EPINET). EPINET uses a learning
healthcare model to optimize care for youth at high risk to reduce the
incidence of psychosis. With patients' consent, EPINET clinics will
create a database of clinical information to help clinicians and
researchers learn more about the effectiveness of early psychosis
treatment.
In addition to early intervention for FEP, NIMH launched several
major initiatives to intervene early to implement a prioritized
research agenda for suicide prevention. The Emergency Department Screen
for Teens at Risk for Suicide (ED-STARS) study is poised to improve
screening for youth at risk of suicidality following an emergency
department admission; the Suicide Prevention for at Risk Individuals in
Transition (SPIRIT) study, a collaboration with the U.S. Department of
Justice, will evaluate the effectiveness of an evidence-based
intervention among persons recently released from jail or prison; and
the Reducing the Incidence of Suicide in Indigenous Groups--Strengths
United through Networks (RISING SUN) initiative aims to create common
outcome measures for suicide prevention efforts among indigenous
peoples. These efforts represent NIMH's continued commitment to
determining the best methods to prevent suicide, particularly among
high risk populations.
In 2016 and beyond, NIMH will continue to strive toward achieving
the ambitious goals of the NIMH Strategic Plan for Research by
harnessing the potential of the BRAIN initiative, the RDoC and RAISE
projects, and efforts to prevent suicide. These and many other research
endeavors represent NIMH's ongoing commitment to achieving its vision
of a world in which mental illnesses are prevented and cured.
______
Prepared Statement of Anthony S. Fauci, M.D., Director, National
Institute of Allergy and Infectious
diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of Allergy and Infectious Diseases (NIAID) of the National
Institutes of Health (NIH).
NIAID has a dual mandate to not only pursue a robust research
portfolio in the areas of microbiology, infectious diseases,
immunology, and immune-mediated disorders, but also to quickly launch a
research response to newly emerging and reemerging infectious diseases.
This dual mandate has been particularly evident over the past 2 years
as NIAID has accelerated research to address the unprecedented Ebola
and Zika virus outbreaks.
infectious diseases research
NIAID continues to advance research to address emerging and re-
emerging infectious diseases around the world. In recent years we have
faced major threats from diseases that have caused substantial
morbidity and mortality, with Ebola virus disease and Zika virus
disease being perhaps the most notable; however, other diseases such as
dengue and chikungunya also have raised significant concerns. NIAID
research supports progress against these and other emerging and
established infectious disease threats worldwide. Examples of notable
NIAID-supported infectious diseases research are highlighted below.
Zika and other mosquito-borne viruses. The appearance and rapid
spread of Zika virus in the Americas has coincided with new and
concerning presentations of disease. These include reported increases
in the birth defect microcephaly and the immune-mediated neurological
disease Guillain-Barre syndrome. NIAID has rapidly mobilized research
to address the public health threat of Zika by building upon our prior
successes with other flaviviruses, notably West Nile and dengue
viruses. Ongoing NIAID efforts include studies of the natural history,
viral genetics, and pathogenesis of Zika virus, including how infection
may cause the development of microcephaly and other congenital
abnormalities in the fetus. In addition, NIAID is expanding efforts to
develop countermeasures for Zika virus that could help control current
and future outbreaks. NIAID has developed an animal model to test
whether therapeutic compounds with activity against other flaviviruses
also are effective against Zika virus. NIAID-supported researchers are
developing diagnostics that can distinguish Zika virus from other
flaviviruses, as well as investigating unique biosignatures that could
form the basis of rapid, specific, and sensitive Zika diagnostic tests.
The development of safe and effective vaccines against not only Zika
but also several other mosquito-borne viruses is a top priority of
NIAID. The NIAID Vaccine Research Center (VRC) is developing a DNA-
based vaccine for Zika virus that is similar to a West Nile virus
vaccine previously developed by NIAID. Phase I clinical testing of the
West Nile vaccine candidate showed it was safe and generated a robust
immune response, indicating it could be a promising platform for a Zika
vaccine. NIAID scientists also are designing a live-attenuated Zika
vaccine. This effort employs an approach similar to that used for an
NIAID-developed dengue virus vaccine candidate currently in Phase III
clinical trials in Brazil. In addition, NIAID is investigating a Zika
virus vaccine candidate that uses the same platform as an Ebola vaccine
tested in West Africa and is partnering with BARDA to support a whole-
particle inactivated vaccine candidate. We anticipate that one or more
of these Zika virus vaccine candidates will begin clinical testing in
September 2016. NIAID also has supported the development of additional
vaccine candidates for mosquito-borne viruses, notably an NIAID VRC-
developed chikungunya vaccine candidate currently undergoing Phase II
clinical trials in the Caribbean.
Ebola. Longstanding NIAID investments in biodefense research and
collaboration with industry partners enabled the rapid and successful
execution of clinical trials of candidate Ebola countermeasures in
response to the 2014-2016 Ebola outbreak in West Africa. Recently
completed NIAID studies demonstrated that the experimental Ebola
vaccines cAd3-EBOZ and rVSV-ZEBOV are safe and immunogenic. A clinical
trial evaluating ZMapp, a cocktail of three Ebola virus antibodies,
found that treatment with ZMapp likely benefits Ebola virus disease
(EBVD) patients. ZMapp remains the leading Ebola therapeutic candidate
and has been made available to the recent Ebola cases in Guinea.
Finally, ongoing studies in Liberia are enhancing our understanding of
the long-term health consequences in survivors of EBVD. NIAID
researchers and colleagues recently described initial findings
concerning the extent of eye, musculoskeletal, and neurological
problems experienced by EBVD survivors, as well as a possible
persistent risk of sexual transmission of the virus. These NIAID
studies have validated the use of randomized, controlled clinical
trials during an infectious disease outbreak. Our efforts continue to
evaluate improved vaccine strategies to prevent Ebola virus infection
and determine the long-term clinical and public health consequences of
EBVD.
HIV/AIDS. Significant progress has been made in combating HIV/AIDS
through the implementation of treatment and prevention approaches
supported by NIAID research. Despite this progress, continued
investment in the development of a safe and effective HIV vaccine and
cure is needed to achieve a durable end to the HIV/AIDS pandemic.
Research supported by NIAID continues to provide the evidence that
informs the development of improved HIV treatment and prevention tools.
A recent groundbreaking NIAID study conclusively demonstrated the value
of early use of antiretroviral drugs, showing that starting treatment
as soon as possible after HIV diagnosis reduces the risk of developing
AIDS or other serious illnesses. Growing evidence from clinical trials
and real-world implementation supports an approach known as pre-
exposure prophylaxis, or use of antiretroviral drugs by high-risk HIV-
negative individuals to prevent HIV infection. NIAID also is pursuing
research in the development of next-generation interventions, such as
broadly neutralizing antibodies; long-lasting injectable therapeutics;
multipurpose prevention technologies (including microbicides); and a
safe, effective HIV vaccine.
Antimicrobial resistance. NIAID plays an important role in the
President's National Strategy for Combating Antibiotic-Resistant
Bacteria (CARB) in collaboration with partners across the Federal
Government. This year, NIAID will maintain and grow a robust
antimicrobial resistance research portfolio to understand the
mechanisms of resistance and to develop improved countermeasures. Key
NIAID efforts include sequencing bacterial strains for the National
Database of Resistant Pathogens; developing non-traditional
therapeutics; optimizing current treatment strategies to reduce the
emergence of drug resistance; and developing diagnostic platforms
capable of detecting multiple resistant pathogens.
Influenza. NIAID influenza research aims to address the constant
threat of seasonal influenza and the potential for pandemic influenza.
In particular, NIAID is pursuing several promising universal influenza
vaccine candidates that could protect against multiple influenza
strains over multiple influenza seasons. In animal models, NIAID
investigators have shown that two different universal influenza vaccine
candidates can protect against numerous influenza strains. Both of
these vaccine candidates, a nanoparticle vaccine and a virus-like
particle vaccine, will be investigated for further development and
clinical testing.
Malaria. NIAID research support contributed to the early stages of
the development of the RTS,S vaccine, the first vaccine shown to
protect against malaria in young children. In a recent study, NIAID-
supported scientists used advanced genomic sequencing technology to
help explain why the RTS,S vaccine is only partially effective. The
researchers found that children infected with malaria parasites
harboring genetic variants that did not match the protein targeted by
the vaccine were less likely to be protected. These results will inform
pilot implementation of the RTS,S vaccine endorsed by the World Health
Organization as well as future malaria vaccine development strategies.
Tuberculosis (TB). NIAID is playing a critical role in accelerating
basic and applied research to combat multidrug-resistant TB (MDR-TB) as
part of the President's National Action Plan for Combating MDR-TB. With
MDR-TB cases increasing worldwide, there is a need for new diagnostics
to rapidly identify resistance, as well as biomarkers to determine
whether a particular TB drug regimen is effective. NIAID scientists
have identified two medical imaging technologies that may help predict
TB drug treatment outcomes. Positron emission tomography and computed
tomography images allow researchers to monitor the burden of bacteria
remaining in the lungs after therapy. These technologies potentially
could be used in combination to quickly assess effectiveness of drug
treatments and shorten the duration of clinical trials. NIAID also
supports efforts to develop improved TB vaccines. NIAID research has
contributed to more than half of the current clinical pipeline of TB
vaccine candidates, and NIAID is working with product developers to
transition promising candidates to advanced clinical trials.
Respiratory syncytial virus (RSV). RSV is a serious childhood
respiratory infection. Each year in the United States, RSV causes an
average of approximately 55,000 hospitalizations among children younger
than 5 years. NIAID-funded researchers have developed a promising
pediatric RSV vaccine candidate. Early tests in children and--adults
show the vaccine is safe and elicits a stronger immune response than
previously developed RSV vaccines. NIAID has launched an RSV human
challenge model at the NIH Clinical Center to test the efficacy of this
vaccine candidate in adults infected with RSV.
research on immunology and immune-mediated disorders
NIAID remains committed to advancing our understanding of the
immune system and immune-mediated diseases. NIAID scientists and
colleagues have created an extensive database of genetic information to
facilitate research on immune disorders. These researchers used samples
from twins to differentiate approximately 80,000 immune traits that are
likely to be genetically regulated. NIAID has made this open-access
resource available to researchers worldwide who are investigating
diverse immune conditions.
NIAID research also has led to significant progress on treatments
for immune-mediated diseases. NIAID-supported researchers continue to
investigate findings from the groundbreaking Learning Early About
Peanut Allergy (LEAP) food allergy study, which demonstrated that
consumption of peanut-containing foods beginning in infancy decreased
the development of peanut allergy in young children. The recent LEAP-ON
trial demonstrated that tolerance to peanut persisted even after
stopping peanut consumption for 1 year. This result suggests that early
peanut consumption may be a viable long-term strategy for preventing
peanut allergy. NIAID also is supporting research to improve current
treatments for asthma. The Preventive Omalizumab or Step-up Therapy for
Severe Fall Exacerbation (PROSE) clinical trial demonstrated that
treatment with the antibody omalizumab reduced the number of seasonal
asthma attacks experienced by inner-city children with a history of
asthma attacks. Finally, NIAID continues to investigate treatment
options for type 1 diabetes. An NIAID-supported clinical trial of the
immune-suppressing drug alefacept in patients newly diagnosed with type
1 diabetes found that the drug helped preserve the function of insulin-
producing cells in the pancreas. This effect persisted for more than a
year after treatment ended.
conclusion
NIAID continues to confront important historic public health
challenges by supporting an established research portfolio in
infectious and immune-mediated diseases while also responding rapidly
to emerging infectious disease threats. NIAID has assisted
international efforts to combat newly emerging and re-emerging
pathogens, such as the Zika, Ebola, and dengue viruses. Research
supported by NIAID also has advanced progress on persistent infectious
and immune-mediated diseases worldwide. NIAID will continue to pursue
effective medical countermeasures for these diseases in an effort to
improve health globally in collaboration with U.S. and international
government partners, academia, and industry.
______
Prepared Statement of Gary H. Gibbons, M.D., Director, National Heart,
Lung, and Blood Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National Heart,
Lung, and Blood Institute (NHLBI) of the National Institutes of Health
(NIH). NHLBI supports a large and diverse research portfolio including
heart, lung, blood, and sleep (HLBS) disorders.
NHLBI has a proud history of translating Federal research funding
into public health successes. There was a time in our Nation's history
when a heart attack was known as a ``widow-maker'' and a childhood
diagnosis of either sickle cell disease or cystic fibrosis was
considered an early childhood death sentence. Thanks to medical
breakthroughs enabled by NHLBI research investments, there has been a
dramatic reduction in deaths from cardiovascular disease by 70 percent
and children born with sickle cell disease and cystic fibrosis have
extended lifespans well into middle age. NHLBI has recently extended
this legacy of funding major medical advances by conducting the
Systolic Blood Pressure Intervention Trial (SPRINT) in patients with
high blood pressure. This landmark study demonstrated that a more
intensive treatment of high blood pressure prevents heart attacks,
strokes, and heart failure while reducing death rates by 25 percent.
SPRINT is the latest example of NHLBI's approach to turning discovery
into better patient care outcomes. NHLBI's success serves as a
compelling demonstration that a steadfast commitment to America's
biomedical research enterprise yields a tremendous return on investment
that enhances both the health and wealth of our Nation.
building on success to address new health challenges
Our past successes present new and compelling public health
challenges that require strategic and timely investment in and by
NHLBI. NHLBI's track record of success in keeping the Nation's blood
supply safe in the face of the HIV/AIDS epidemic is proving to be a
critically important foundation for building new initiatives that
address the imminent threat to blood safety posed by the Zika virus.
For example, NHLBI-supported investigators are developing ways to
detect new and emerging microbes in donated blood and novel strategies
to ``sterilize'' the blood prior to transfusion.
While we as a Nation must tackle emerging infectious disease
outbreaks, we must remain vigilant in the fight against the greatest
long-term public threat to our Nation's health and wealth--the growing
epidemic and cumulative burden of chronic, age-related conditions such
as cardiovascular disease, lung diseases, and vascular dementia. As we
have reduced death from heart attacks, we must pivot to the emerging
threat of heart failure--a chronic, debilitating, and costly
complication of heart attacks--that millions of heart attack survivors
must now face. While it is true that Americans have benefitted from
high blood pressure treatments to prevent heart attacks and strokes, we
must still address disorders such as vascular dementia--the second most
common form of dementia and a major public health challenge for our
aging population--that can develop as a result of cardiovascular
diseases such as high blood pressure and stroke. To overcome the
emerging health challenges of chronic HLBS disorders, which are major
drivers of Medicare and Medicaid costs, it is critical to fund
biomedical research to elucidate the underlying root causes and
molecular mediators of these chronic conditions long before the
disorder progresses to the end-stage of symptomatic debility and death.
This is a moment of urgency in which investments in biomedical research
could provide enormous return on investment by reducing medical care
expenditures.
NHLBI funded discoveries are challenging the conventional viewpoint
that chronic HLBS disorders are an intrinsic and inevitable consequence
of the aging process. NHLBI is well poised to seize the scientific
opportunities of today to advance research that can preempt or prevent
chronic disease and overcome the economic and health challenges these
disorders pose to millions of Americans. Our goal is to catalyze the
next generation of discoveries and interventions designed to halt
disease progression and promote the remission of chronic HLBS
disorders. Not only do our existing and future research initiatives lay
the foundation for mapping and therapeutically modulating biological
pathways leading to chronic HLBS disorders, but they will help us
understand how normal and diseased HLBS systems affect the health of or
contribute to disease in other body systems.
pioneering precision medicine to preempt, prevent, and predict hlbs
disorders
Continued investment in NHLBI research will allow us to leverage
new scientific discovery to realize personalized care for HLBS
disorders. Scientifically aligned with NIH's Precision Medicine
Initiative, the NHLBI Trans-Omics for Precision Medicine (TOPMed)
program is pioneering a new integrated approach to understanding HLBS
diseases by combining genetic, environmental, imaging, clinical, and
other data from existing NHLBI-supported population-based studies and
disease-based cohorts to create an accessible, communal data resource
for scientific inquiry. The cohorts and studies in TOPMed represent a
broad cross-section of the U.S. population in terms of racial, ethnic,
and cultural backgrounds, as well as medical histories including common
HLBS disorders such as atrial fibrillation, asthma, COPD, high blood
pressure, obesity, and sleep apnea and rare disorders such as sickle
cell disease and pulmonary fibrosis. TOPMed will integrate these
genetic data with other data sets to allow researchers to study and
define health and disease across the lifespan, uncover novel disease
risk factors, and identify subtypes of disease that may be amenable to
personalized treatment. These new discoveries will help reduce the
Nation's disease burden by increasing our capacity to preempt, prevent,
and predict HLBS disorders.
For many HLBS disorders we do not know the molecular cause of
disease, and we lack effective early markers for clinicians to detect
disease in the earliest stages. The complex nature of HLBS disorders
often involves changing dynamics within individual organs and between
multiple body systems and changes across the lifespan due to normal
genetic variation and common environmental exposures. The TOPMed
program provides the opportunity to develop a large normative dataset
to begin defining the transitions from normal to pre-, early-, and
late-disease States.
Chronic Obstructive Pulmonary Disease (COPD) and pulmonary fibrosis
are two diseases for which greater ability to recognize pre-disease
States and early biomarkers can inform interventions to stop or even
reverse early molecular changes, before the body has irreversibly begun
down a path of developing lung disease. Current research through the
TOPMed program and COPD cohorts has shed new light on how people with
COPD respond differently to environmental factors such as tobacco smoke
and has identified developmental and inflammatory pathways at the root
of the different disease experiences. These studies identified lung
function genes that are differentially expressed between control and
COPD patients, which may make possible new COPD drug targets to reverse
genetic signatures in some patients and prevent disease progression.
Expanding research in disease diagnosis, prediction, and refinement
of disease subtypes will inform medical practice and help clinicians
deliver personalized interventions, sometimes based on a patient's
genetic makeup, that have been proven effective for a patient's disease
subtype. For example, NHLBI funded Center for Advanced Diagnostics and
Experimental Therapeutics in Lung Diseases (CADET) found a genetic risk
factor of pulmonary fibrosis that occurs in about 40 percent of
patients with idiopathic pulmonary fibrosis. This discovery is driving
new diagnostic test development to predict who may develop this form of
idiopathic pulmonary fibrosis and drug development to counteract the
effects of this genetic variation.
charting a new vision
NHLBI believes a robust, diverse, and engaged community is
essential to overcoming our future public health challenges. NHLBI also
strive to capitalize on the synergies created and leveraged by patient-
centric care models and patient-driven movements. Over the past year,
NHLBI has spearheaded several broad collaborative partnerships to
connect scientists, policymakers, patients, and healthcare providers,
in person and digitally, to meet people where they are to advance
national public health missions and chart our course for the coming
years.
In June 2015, our Sickle Cell Disease Forum engaged over 400
diverse community partners to understand their greatest needs in the
area of sickle cell disease research. This Forum reviewed the current
knowledge base, some of which NHLBI and our funded Centers of
Excellence in Hemoglobinopathies have helped discover. While our eye is
keenly focused on finding a future cure, possibly through adaptation of
emerging gene editing techniques, the Forum also helped focus our
attention on more immediate ways that NHLBI can significantly reduce
the daily burdens and improve clinical health outcomes for patients
with sickle cell disease. For example, NHLBI is committed to gaining
higher clinical adoption rates of NHLBI's landmark study findings that
hydroxyurea can reduce the risk of strokes in children with sickle cell
disease. The 2014 Transcranial Doppler (TCD) With Transfusions Changing
to Hydroxyurea (TWiTCH) Study confirmed with promising evidence that
hydroxyurea works as well as blood transfusions to lower TCD
velocities, a critical marker of stroke risk in very young children
with sickle cell disease. Helping clinicians move beyond traditional
transfusion-only treatment and increasing the use of hydroxyurea will
allow us to realize a stroke-free generation of children. NHLBI's
Sickle Cell Disease Implementation Consortium is facilitating research
to assess how coordinated interventions that interweave the patient's
home, work, and medical provider environments can improve the health
and well-being of patients with sickle cell disease in the United
States. Lastly, the Forum reinforced NHLBI's view that we are not an
island and our global partnerships to research sickle cell disease in
Sub-Saharan Africa and Brazil are instrumental to refining research and
treatment development for Americans of African and Hispanic descent,
who make up a large proportion of sickle cell disease cases in the
United States.
Our Strategic Visioning Initiative was one of our most notable
engagement successes this year. NHLBI undertook a crowdsourcing effort
to engage patients, investigators, professional societies, and the
broader NHLBI community in an inclusive and iterative process to shape
scientific priorities and guide our funding strategies over the next
decade. During this process, more than 1,000 ideas were submitted and
42,000 votes were cast by 4,000 members of the community from all 50
States and 42 countries around the world. In alignment with NIH's
strategic plan, the resulting NHLBI Strategic Research Priorities will
be published in late spring 2016 and explore four major goal areas:
normal biology and health, pathobiology and disease, clinical and
translation research, and biomedical workforce and training. The
strength of our Strategic Visioning process rests in the collective
input of the entire HLBS community which helps to ensure that the
research NHLBI supports continues to address the most important and
timely scientific and public health questions related to HLBS disorders
and that NHLBI strategically invests in research areas that critically
require our facilitation.
conclusion
NHLBI's portfolio, enhanced by our soon-to-be-released Strategic
Research Priorities, addresses the enormous economic and health burdens
of heart, lung, blood, and sleep disorders. Strategic NHLBI investments
in critical challenges and unanswered research questions over the next
decade will leverage past research and public health gains to help
unlock the potential of precision medicine; strengthen existing and
foster new public-private partnerships for quicker translation of
research findings into new drugs, devices, diagnostics, and cures; and
advance implementation science so existing and cutting-edge science can
be adopted to improve health and reduce health inequities in the
Nation.
______
Prepared Statement of Roger I. Glass, M.D., Director, Fogarty
International Center
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the Fogarty
International Center (FIC) of the National Institutes of Health (NIH).
strengthen and sustain the biomedical workforce
The cutting-edge scientific advances that improve public health are
built on foundations of research capacity and rigorous training for
future scientific leaders. Through its research and research training
programs, FIC is supporting the best science where problems are most
acute, facilitating research collaborations between the United States
and international investigators and institutions, and training the next
generation of scientists to address global health challenges. FIC's
niche of investing in future global health research leaders extends the
reach of research institutions and equips scientists in the United
States and low- and middle-income countries (LMICs) to solve health
problems that affect us all.
Addressing today's complex global health challenges requires a
critical mass of first-class scientists who are well versed in regional
health problems. To this end, FIC continues to support the training of
early-career U.S. scientists at research centers in LMICs. Through
programs like the International Research Scientist Development Award,
FIC and its NIH partners provide experiences that encourage early-
career U.S. investigators to take risks and approach problems
creatively and collaboratively under constraints that may not exist in
high-income settings. For example, Dr. Maria Hyoun Kim of Baylor
College of Medicine is working with mentors in Malawi and the United
States to improve prevention of mother-to-child transmission of HIV in
LMICs. Specifically, her research evaluates Malawi's novel national
Option B+ (B+) program, which offers lifelong antiretroviral treatment
to HIV-infected pregnant and breastfeeding women, and will shed light
on how effective B+ may be for preventing babies from becoming
infected.
In addition, FIC has supported the training of thousands of
scientists in LMICs who, with their intimate knowledge of the local
context, are uniquely poised to make discoveries in global health
research. Many of these investigators have become leaders in academic
institutions and ministries of health in their home countries, and are
involved in national efforts to improve the healthcare of the local
population. For example, FIC's International Collaborative Trauma and
Injury Research Training Program has expanded trauma and injury
research partnerships between U.S. and LMIC scientists, and is
generating data for evidence-based decisionmaking in injury-related
clinical treatment and prevention programs. With support from this
program, the University of California, Los Angeles, School of Medicine
and the University of Cape Town in South Africa are working together to
address the effects of sexual and physical violence during pregnancy on
the growth and development of infants. Their study found that maternal
exposure to physical violence in the year preceding delivery was
significantly associated with lower birth weight in the infants.
Further research is planned to assess relevant underlying mechanisms
and methods in the communities so that effective intervention plans and
health policies can be developed for South Africa and other sub-Saharan
African countries.
Past FIC investments have multiplied the number of foreign
investigators working abroad who serve as change agents within their
institutions, which are then positioned to participate in international
scientific networks. For example, in partnership with the Office of the
Global AIDS Coordinator at the Department of State, FIC administered
the Medical Education Partnership Initiative (MEPI). MEPI provides
medical education and research training for medical students, faculty,
and other health professionals in sub-Saharan Africa. FIC is continuing
to foster the next generation of researchers by providing training and
mentored research opportunities specifically to junior faculty in MEPI-
supported institutions. The MEPI Junior Faculty Program builds on
MEPI's momentum and existing platform to continue expanding research
capacity of junior faculty from MEPI institutions. This second-
generation program is increasing retention of faculty who will focus on
evidence-based clinical teaching as well as strengthen international
research collaboration.
research
Research supported by FIC's programs is generating critical
scientific evidence that can lead to new diagnostics, prevention and
treatment strategies. FIC's Global Brain Disorders Research (Brain)
program has energized a global health research agenda around brain and
nervous system diseases and disorders. In collaboration with several
NIH Institutes and Centers (ICs), Brain has catalyzed innovations
relevant across the lifespan, from fetal and neonatal neuro-development
to neurodegenerative diseases of later life, such as Alzheimer's
disease. For example, scientists at Albert Einstein College of Medicine
are collaborating with colleagues in India to investigate cognitive
decline in older adults. Recent findings report prevalence of motoric
cognitive risk syndrome (MCR)--a newly described predementia syndrome--
and identify MCR in older adults as a strong, early risk factor for
cognitive decline that can be used to identify seniors at high risk for
dementia.
Over the next 5 years, FIC's Global Environmental and Occupational
Health Hub Program will support the establishment of seven regional
research and training hubs. Each hub is based in an LMIC and consists
of a multidisciplinary group of researchers and partner organizations
who will collaborate on common research and training topics that
address environmental and/or occupational health issues. For example,
one hub in Thailand is investigating pesticides commonly used in
agriculture across Southeast Asia, to see if they act as endocrine
disrupters, increasing the risk of metabolic syndrome and associated
diseases such as diabetes, stroke and heart disease. Another hub, in
Peru, aims to build scientific capacity and support research on air
pollution and climate change, with links to the neighboring countries
of Ecuador, Bolivia and Chile.
FIC is stimulating innovation in the development and implementation
of technologies and other locally relevant solutions to address global
health problems. In an effort to understand the impact of mobile
technologies on health, FIC's Mobile Health: Technology and Outcomes in
LMICs (mHealth) program supports research on the use of mobile devices
to generate better health outcomes. One such example is a team of U.S.
and South African scientists that are developing a mobile screening
tool to be used by staff with minimal training to detect neurocognitive
impairment resulting from HIV infection. Pioneering tools like this can
improve care, reduce costs, and have potential relevance for the United
States and worldwide.
FIC's mathematical modelers have been at the forefront of
addressing the recent Zika and Ebola outbreaks. Researchers at FIC are
utilizing a novel methodology to analyze Internet news reports on Ebola
from Africa to describe pathways of transmission. This methodology
provided evidence that news reports can be a useful source of
epidemiologic data. Researchers supported in part by FIC also are
predicting the international spread of Zika virus in Brazil due to the
August 2016 summer Olympic Games; these research findings were recently
published in the Lancet in January 2016.
other
FIC leverages partnerships to maximize the impact of NIH
investments globally. The Global Network for the Study of Malnutrition
and Enteric Disease (MAL-ED) is an international collaboration of
investigators led by FIC and the NIH Foundation. Established in late
2008, the multi-year, multi-site project is supported by the Bill &
Melinda Gates Foundation. The goal of MAL-ED is to investigate the
interactions among exposure, infection, and disease associated with
enteric pathogens; diet and nutritional status; and, socio economic
status in relation to resulting impacts on gut physiology; immune
function and vaccine response; physical growth; and, cognitive
development. A prospective field, clinical, and laboratory based
observational study of cohorts of neonates followed to 24 months has
been established at geographically diverse sites in Asia, Latin
America, and sub-Saharan Africa. The findings of such analyses will be
applied toward improving long-term public health in resource-poor
settings.
Over the last few years, the emerging economies of Brazil, Russia,
India, China and South Africa (BRICS) have built highly capable
biomedical enterprises. NIH and BRICS countries are establishing
innovative partnerships, funding individual teams of experts who work
together sharing expertise to speed discovery. NIH is partnering with
the Brazilian State of Sao Paulo's Science Foundation (FAPESP) to
parallel-fund U.S.-Sao Paulo R01 applications that are meritorious in
standard NIH peer-review. FIC developed and is implementing the
program, which calls for FAPESP to fund the Brazilian institution while
NIH funds the U.S. institution. To date, 22 NIH ICs have signed on,
covering most research areas across NIH. Another example is the United
States-China Program for Biomedical Research Cooperation, a 2010
bilateral agreement that FIC helped draft and facilitate, that
strengthens and develops cooperation in basic biomedical research. In
this program, NIH provides funding to support U.S. scientists involved
in the research collaborations, while the National Natural Science
Foundation of China (NSFC) provides funding to support the Chinese
scientists. So far, there have been a total of 109 awardees, addressing
scientific questions in the areas of cancer, infectious diseases,
neurological diseases, and mental health.
conclusion
FIC will continue to invest in the most promising minds in global
health research, strengthen the capacity of research institutions to be
sustainable platforms for cutting-edge science, and catalyze meaningful
international scientific collaborations in fiscal year 2017 and the
years to come.
______
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 2017 Budget request for the National
Institute of Nursing Research (NINR) of the National Institutes of
Health (NIH).
introduction
The mission of NINR is to promote and improve the health of
individuals, families, and communities. We achieve this mission by
supporting research to: promote health and prevent disease; advance
symptom science to develop personalized health strategies; enhance
self-management of chronic conditions; improve end-of-life and
palliative care; develop new technologies to improve health; and train
nurse scientists. This year, we are pleased to commemorate NINR's 30th
anniversary, which provides an opportunity to reflect on many of the
accomplishments being made every day by nurse scientists across the
Nation. In October 2015, NINR hosted the first in a series of
scientific events to highlight significant contributions of nursing
science for improving health. As we envision the next 30 years, we are
confident that NINR's support of nursing research will continue to
improve the lives of diverse individuals, families, and communities
across the life span. I am grateful for this opportunity to share with
you some examples of the innovative research that NINR supports.
improving the health of children and adolescents
Chronic conditions such as asthma, obesity, and diabetes have the
potential to negatively affect the quality of life of children and
adolescents. NINR-supported scientists are addressing this issue by
developing innovative interventions to increase positive health
outcomes in children. NINR-supported researchers demonstrated the
effectiveness of a school-based healthy lifestyles program for
overweight/obese and depressed teens. Results showed that a year after
completing the program, there was a significant decrease in the
proportion of overweight and obese students, and students who had begun
the program with severely elevated depressive symptoms had
significantly lower depression.
NINR maintains its commitment to support research to improve health
for children from vulnerable groups who are often disproportionately
affected by chronic conditions. One recent NINR-supported study showed
improvements in asthma episode management and prevention behaviors in
medically underserved, inner-city school-age students who received a
school and community based asthma health education and counseling
program. In other ongoing efforts, NINR-supported investigators are
testing a community-based participatory intervention aimed at American
Indian/Alaska Native teens and their mothers to raise awareness of the
risks of gestational diabetes mellitus, promote a healthy lifestyle,
and prevent subsequent development of type 2 diabetes.
maintaining health in older adulthood
In light of our rapidly aging population, it is more important than
ever to support efforts to prevent chronic illness early in life and to
promote active lifestyles, health, and independence as people age. One
promising area of research focuses on developing new technologies to
improve and maintain physical mobility for older adults. For example,
NINR-supported researchers designed an innovative unpowered ankle
exoskeleton that harnesses the power of a person's own muscles to make
walking more efficient. Although scientists are still developing and
testing the exoskeleton, it has the potential to make walking easier
for people recovering from an injury or dealing with normal aging
issues. Another recent NINR-led initiative focuses on development of
technological and biobehavioral interventions to help persons with
dementia or cognitive impairment maintain independence and quality of
life, as well as to reduce stress and burden on caregivers. NINR-
supported researchers are also uncovering complex relationships among
biological, physical, and behavioral factors that may play a role in
depressive symptoms in older adults. A recent study revealed that
mutations in a gene known to be related to depression, as well as pain,
fear of falling, and low physical activity, were all associated with
depressive symptoms in older adults. NINR is also leading an initiative
to support prevention research in mid-life adults, which will inform
efforts to optimize health and wellness as people age.
enhancing end-of-life and palliative care
As the lead NIH Institute for end-of-life research, NINR supports
research to identify the most effective strategies to ease the symptoms
of advanced illness and to assist families in making difficult end-of-
life decisions. In an effort to build the science of end-of-life and
palliative care, we continue to support a palliative care research
cooperative (PCRC), which brings together multidisciplinary researchers
from universities, health systems, hospices, and hospitals across the
United States. Recent findings from research supported by the PCRC
revealed that discontinuing statin medication use in patients with
advanced illness is safe and may increase quality of life, decrease the
use of non-statin medications, and reduce costs. In 2015, NINR launched
the second phase of NINR's Palliative Care: Conversations Matter
initiative, which focuses on children, parents, and families, and
includes a new brochure, in English and Spanish, to help raise
awareness of the benefits of palliative care. NINR also is leading a
new initiative to support research to better understand the unique
perspectives, needs, wishes, and decisionmaking processes of youth
living with serious illnesses and their families, and to enhance their
quality of life.
looking toward the future: nurse scientists
One of NINR's fundamental goals is to develop the next generation
of nurse scientists to address the Nation's most pressing health
issues. NINR offers a variety of training opportunities to nurse
scientists and trainees at all career levels, and recognizes the
importance of supporting new investigators whose success is so critical
to the future of innovative research and high-quality healthcare. In
order to build a scientific workforce that is innovative, diverse, and
ready for the future, NINR's training programs provide nurse scientists
with the skills and tools to support continued advancements in science
and improvements in health. For example, in 2015, NINR sponsored our
second Big Data Research Boot Camp at NIH, a week-long intensive
training that provides a foundation in big data science methodologies
and strategies for incorporating new methods to strengthen research
proposals. NINR's Summer Genetics Institute is an intensive program for
graduate students, faculty, and clinicians designed to provide a
foundation in molecular genetics to improve research and clinical
practice.
conclusion
Thank you for this opportunity to share some of NINR's
accomplishments and the important work being done every day by nurse
scientists across the country. NINR will continue to support innovative
research to improve health now and in the future.
______
Prepared Statement of Eric Green, M.D., Ph.D., Director, National Human
Genome Research Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National Human
Genome Research Institute (NHGRI) of the National Institutes of Health
(NIH).
This past October, the scientific community celebrated a quarter
century since the launch of the Human Genome Project. Now, roughly 13
years since the successful completion of that landmark effort, NHGRI
looks forward to the next quarter century of genomics and its
applications to advance human health. To this end, NHGRI is fostering a
continuum of research from basic studies of the structure and function
of genomes to work that advances medical science and seeks to improve
the effectiveness of healthcare. Research funded by NHGRI, especially
in the area of genomic medicine, has laid the foundation for major
transformational efforts, such as the Precision Medicine Initiative and
the National Cancer Moonshot.
As an example, NHGRI's partnership with the National Cancer
Institute in leading The Cancer Genome Atlas for nearly 12 years has
led to powerful new insights that will fuel the National Cancer
Moonshot. Through the use of new genome-analysis technologies, data
have been generated for over 10,000 tumor specimens, allowing the
assembly of a rich data resource that is now freely available to any
qualified researcher. This body of work is providing new insights about
classifying and treating cancer, fundamental information for the
National Cancer Moonshot.
Another major research program supported by NHGRI, the 1000 Genomes
Project, has now established a powerful data resource with information
about how humans differ with respect to their genomic blueprint. With
its final summary papers published in Nature this past October, this
international effort analyzed the genomes of over 2,500 people from 26
populations around the globe, identifying and cataloguing more than 88
million places in the genome that humans differ. Together, the
generated information accounts for more than 99 percent of the common
genomic variants (or `spelling differences') that exist in the human
population. By producing a global catalog of human genomic variation,
researchers can now focus on which of the identified variants play a
role in health and disease.
Despite the remarkable progress in genomics over the past quarter
century, more powerful and accessible approaches for studying genome
structure and function are needed. To help address this need, the
Centers of Excellence in Genomics (CEGS) program supports multi-
investigator, interdisciplinary teams that develop new approaches and
technologies for using genomics in biomedical research. fiscal year
2017 funds for NHGRI will support CEGS efforts that combine genome-
editing technologies and tissue-engineering methods to develop improved
models of complex tissues such as the brain. The CEGS program
exemplifies how basic research can be applied to specific problems,
yielding solutions that can advance diverse fields of inquiry.
The promise of genomics as a clinical tool for improving patient
care is now coming into focus. A program that vividly highlights this
capability is the Undiagnosed Diseases Network (UDN). An extension of
the Undiagnosed Diseases Program launched within the NIH Intramural
Research Program in 2008 and funded by the NIH Common Fund, the UDN
embodies the promise of genomic and precision medicine. Under NHGRI's
leadership, both programs are helping patients (and their families)
that have faced diagnostic odysseys and are discovering the genomic
bases of extremely rare disorders. The value of UDN is multifaceted,
with some aspects related to the care and support it provides to its
patients and other aspects related to robust approaches being developed
for the study of rare medical conditions. fiscal year 2017 funds for
the program will support an expansion in patient enrollment across the
national network.
NHGRI is further maximizing the potential for public benefit from
the Federal investment in genomics with programs such as UDN by
promoting synergy across research communities. Leveraging leading
experts across national consortia directly stimulates dialog and an
exchange of ideas that can prove mutually beneficial to all groups
involved. An illustration of this can be seen with the collaboration
between UDN and NHGRI's Centers for Mendelian Genomics program, a
large-scale effort that is elucidating the genomic causes of rare human
diseases. Through their synergistic interactions, these consortia are
producing new insights about basic biological pathways that are
relevant to both rare diseases as well as more common ones. Utilizing
the discoveries emanating from rare disease studies should propel
forward basic understanding of common diseases, particularly in the
characterization of disease mechanisms and the establishment of new
treatment options.
NHGRI also recognizes the importance of examining and addressing
the ethical, legal, and social issues associated with moving genomics
initiatives forward and with implementing genomic medicine. In fiscal
year 2017, NHGRI will thus continue to fund research that examines the
increasing accessibility of genomic information and technologies within
society. Such studies will investigate questions related to biobanking,
clinical genome sequencing, and broad data sharing--all issues of great
relevance to the Precision Medicine Initiative. A particular focus will
be placed on how such issues affect studies involving vulnerable or
underrepresented populations. Genomic privacy and genetic
discrimination, as well as the complexities associated with the return
of results from genomics research studies, will also be explored.
Educating providers, patients, and the public about genomics is
also imperative for the successful incorporation of genomics into
healthcare. NHGRI dedicates significant time and attention to outreach
efforts and the education of various stakeholders. The highly
successful Genome: Unlocking Life's Code exhibition, developed in
conjunction with the Smithsonian Institution, has now been seen by more
than four million people as it travels to cities big and small across
the United States.
NHGRI's well-rounded portfolio of basic, translational, and
clinical research programs has the long-term aim of using genomics to
advance the health of all Americans. fiscal year 2017 funds will help
to ensure that NHGRI continues to lead the genomics community, support
the broader biomedical research community, and help realize a future of
remarkable genomics-enabled healthcare innovations.
______
Prepared Statement of Betsy L. Humphreys, Acting Director, National
Library of Medicine
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Library of Medicine (NLM) of the National Institutes of Health (NIH).
overview
NLM, the world's largest medical library, is the most visible face
of NIH across the United States and around the globe. Through its
information systems, a cutting-edge informatics research portfolio,
extensive training programs, and many partnerships, NLM plays an
essential role in catalyzing and supporting the translation of basic
science into new treatments, new products, improved practice, useful
decision support for health professionals and patients, and effective
disaster and emergency preparedness and response. NLM coordinates a
6,400 member National Network of Libraries of Medicine (NN/LM) that
provides a field force for improving access to high-quality health
information in communities nationwide, with an emphasis on populations
with health disparities.
Millions of scientists, health professionals, and members of the
public use NLM's electronic information sources billions of times each
year. The range of information that NLM organizes and disseminates is
enormous, including genetic, genomic, and biochemical data; images;
clinical trials; published and unpublished research results; historical
archives; decision support resources; scientific and health data
standards; informatics tools for system developers; and health
information for the public. Every day, researchers submit 5 terabytes
of data to NLM databases and users download more than 50 terabytes.
Anyone can search or download information directly from an NLM website,
find it via an Internet search engine, or use an ``app'' that provides
value-added access to NLM data. Thousands of commercial and non-profit
system developers regularly use the applications programming interfaces
(APIs) that NLM provides to fuel private sector innovation and to embed
access to NLM information services within electronic health records
(EHRs).
NLM actively conducts and supports basic research in computational
biology and informatics and also funds development of computational
tools and methods for analysis of scientific data, electronic health
records, images, and publications. In fiscal year 2015, NLM intramural
scientists were key members of an international CRISPR-Cas research
team that identified three new naturally occurring systems that show
potential for genome editing.
biomedical and health information services
In fiscal year 2015, NLM greatly expanded the quantity and range of
high-quality information readily available to scientists, health
professionals, and the general public. For example, more than 806,000
new journal articles were indexed for PubMed/MEDLINE, NLM's most
heavily used database, which contains more than 25 million references
to articles in the biomedical and life sciences journals, with links to
related scientific data and full-text articles on publishers' websites
and in NLM's PubMed Central (PMC) repository. PMC now includes more
than 3.6 million full-text research articles, including those submitted
in accordance with the NIH Public Access Policy and similar policies of
the Department of Health and Human Services (HHS) and several other
Federal agencies.
NLM's National Center for Biotechnology Information (NCBI) is a
leader in and a hub for the international exchange of big data utilized
in molecular biology, genomics, and clinical and translational
research. Some of the largest datasets are available in the cloud to
facilitate access and analysis by researchers who have insufficient
bandwidth or computing power. In fiscal year 2015, the database of
Genotypes and Phenotypes (dbGaP), which connects individual-level
genomic data with individual-level clinical information, grew by more
than 20 percent and now contains 600 studies involving more than one
million people. The RefSeq database of curated reference sequences grew
to nearly 15 million genomic records, an 88 percent increase, and more
than 51 million protein records from over 54,000 organisms. Many NLM
databases, including dbGaP, RefSeq, the Genetic Testing Registry, and
ClinVar, are fundamental to the identification of important
associations between genes and disease, and to the translation of new
knowledge into better diagnoses and treatments.
NCBI continues to collaborate with the Food and Drug Administration
(FDA), Centers for Disease Control and Prevention, the Department of
Agriculture, and other groups to maintain a database of whole genome
sequencing (WGS) data for antibiotic-resistant bacteria along with
tools to facilitate analyses of such data. The database provides an
important resource for surveillance and research into the mechanisms
underlying the emergence of antibacterial resistance. This program
builds upon a successful collaborative project among these same
agencies to use WGS to more quickly and accurately identify and
investigate outbreaks of disease caused by foodborne bacteria.
ClinicalTrials.gov, the world's largest clinical trials registry,
now includes more than 200,000 registered studies in 190 countries and
summary results for more than 18,700 trials, including many not
available elsewhere. When finalized, regulations to implement the Food
and Drug Administration Amendments Act of 2007 and a proposed NIH
clinical trial reporting policy are expected to further increase the
amount of information submitted each year to this valuable resource.
NLM's MedlinePlus provides access to high quality consumer health
information produced by NIH and HHS agencies, other Federal agencies,
and authoritative private organizations. It also 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 more than 1.6 million visits per day.
In fiscal year 2015, NLM collaborated with the HHS Assistant
Secretary for Preparedness and Response and the National Institute of
Environmental Health Sciences to develop new information resources for
pre- and post-disaster health issues and disaster research response.
electronic health records and clinical data analysis
For more than 40 years, NLM has supported seminal research in
biomedical informatics, including EHRs, imaging, clinical decision
support, and health information exchange. It has also been the
principal funder of university-based programs that have trained many of
today's leaders in informatics research and health information
technology. As adoption and deployment of EHRs increases, so do
opportunities to mine increasingly large stores of patient data for
research and public health. NLM conducts and supports research to
enable effective use of EHR data in knowledge discovery, public health
surveillance, and healthcare quality improvement. In fiscal year 2015,
NLM intramural scientists took advantage of the Centers for Medicare
and Medicaid Services' (CMS) efforts to streamline research access to
Medicare data to conduct studies about epidemiology of drug-drug
interactions and the potential association between Simvastatin use (a
drug used to lower cholesterol and triglycerides) and dementia/
Alzheimer's disease.
In close collaboration with the HHS Office of the National
Coordinator for Health Information Technology and with assistance from
CMS, Veterans Health Administration, and FDA, NLM develops, funds, and
disseminates the clinical terminologies designated as U.S. standards
for meaningful use of EHRs and health information exchange. NLM
produces a range of tools that help EHR developers and users to
implement these standards and makes them available in multiple formats,
including via APIs. NLM's technical and financial support enables
clinical terminology standards to be updated regularly to reflect new
drugs, tests, devices, and changes in medical knowledge and health
practice--and also allows them to be used free-of-charge in U.S.
healthcare, public health, biomedical research, and product
development.
The inclusion of standard terminology in EHRs enables more
effective clinical decision support by making it easier to use
information in a patient's record to retrieve knowledge relevant to
that record. In fiscal year 2015, NLM's MedlinePlus Connect service
increased its utility to EHR vendors seeking to connect their products
directly to NLM's high quality information relevant to a patient's
conditions, medications, and test results by expanding its links to
standard terminologies and billing codes. Standardized EHRs are also an
increasingly important source of data for cost-effective observational,
clinical, and translational research and will enhance the value of the
Precision Medicine Initiative cohort. NLM continued its work to
facilitate the inclusion of standard clinical terminology in common
data elements and patient assessment instruments used in NIH and HHS-
funded comparative effectiveness and clinical research. NLM's Unified
Medical Language System (UMLS) resources provide essential
infrastructure for advanced clinical decision support by connecting
standard clinical terminologies to billing codes and more than 120
other important biomedical vocabularies, such as those used in
information retrieval and gene annotation. By linking the many
different terms used to represent the same concepts and by providing
associated natural language processing programs, NLM's UMLS resources
help computer programs interpret biomedical text correctly. These
resources are heavily used in NIH-funded research; in commercial
product development; and in many electronic information services,
including those produced by NLM.
reaching the public
NLM has a range of programs to enhance awareness and use of NLM's
information services among biomedical researchers, health
professionals, librarians, patients, and the public. NLM works closely
with more than 6,300 members of the NN/LM--academic health sciences
libraries, hospital libraries, public libraries, and community-based
organizations--and through formal partnerships with historically black
colleges and universities, tribal colleges, and other minority serving
institutions. In fiscal year 2015, dozens of community-based projects
were funded across the country to enhance awareness and access to
health information, including in disaster and emergency situations, and
to address health literacy issues. Use of mobile sites, ``apps,'' APIs,
and responsive design techniques help NLM tailor the delivery of
content to the range of devices employed by its users.
NLM is redesigning many of its web interfaces so that the
information display adjusts automatically to the size of the device,
including smart phones. In fiscal year 2015, the Library released new
``responsive design'' versions of MedlinePlus and MedlinePlus en
espanol. NLM continues to be a leading player in social media amongst
HHS agencies with active Facebook, Twitter, Flickr, Pinterest, and
YouTube accounts; several online newsletters; and its NN/LM, which
covers the U.S. and hosts eight Facebook pages, nine Twitter feeds, and
12 blogs. NLM is consistently ranked among the most liked, most
followed, and most mentioned organizations amongst small government
agencies with social media accounts.
In conclusion, NLM is a trustworthy source of health information
for the public and vital to the practice of 21st Century medicine and
the progress of science. 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. NLM is committed to the development and use of innovative
computing and communications systems to enhance access to the results
of biomedical research.
______
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 2017 budget request for the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of
the National Institutes of Health (NIH).
As the primary Federal agency supporting medical research on
diseases of the bones, joints, muscles, and skin, NIAMS touches the
lives of nearly every American. Arthritis limits the activities of more
than 22.7 million adults in the United States each year (National
Health Interview Survey, 2010-2012); medical care and lost wages
attributable to musculoskeletal conditions cost Americans $874 billion
annually (Agency for Healthcare Research and Quality Medical
Expenditures Panel Survey, 1996-2011); and skin conditions such as
eczema and psoriasis affect more than 12 percent of people worldwide
(Global Burden of Disease Study, 2010). NIAMS is working to enhance
health, lengthen life, and reduce illness and disability by supporting
basic, translational, and clinical research that will make a difference
for patients; fostering innovation to meet current research needs and
to support the next generation of biomedical researchers; and enhancing
stewardship, while reducing administrative burdens on researchers.
basic research leads to new understanding of disease
NIAMS investments in basic research are uncovering the underlying
mechanisms of biological systems and providing new understanding of the
basis of disease. For example, NIAMS intramural researchers, as part of
an international consortium, analyzed DNA from nearly 1,000 children
with systemic juvenile idiopathic arthritis, a severe form of childhood
arthritis. The researchers showed that changes in a section of the
genome related to immune cell function are strongly associated with an
increased risk of developing the condition; when combined with other
knowledge about the gene region involved, the finding suggests that
defects in both how the body immediately reacts to infection, and how
it adapts over time, contribute to the disease.
Long-term investments in data resources to facilitate basic science
discoveries continue to produce results. One such resource, the
Osteoarthritis Initiative, was established a decade ago as a repository
for medical images, clinical data, and biospecimens from people who
were at high risk of developing knee osteoarthritis. Recently,
researchers mining the publicly available database found joint changes
that may predict who will go on to develop osteoarthritis. This
discovery is calling into question long-held beliefs about how
osteoarthritis arises and may open new avenues for halting joint
disease at its earliest stages.
Basic research on fundamental biological processes in healthy
tissues could of regeneration, and currently, we know little about the
signaling pathways that are involved. NIAMS-supported researchers are
beginning to uncover the basic molecular events that underlie recovery
of certain tissues, such as hair follicle regeneration after skin
wounding. Recently, two key regulators of this process were identified
in mouse models. Interestingly, both of the molecules are also involved
in immune system functions, such as protection against viral
infections. By understanding regeneration in this model, scientists may
one day be able to develop methods to stimulate repair of other human
tissues. In fiscal year 2017, NIAMS plans to provide funding for small
businesses to develop novel complex 3-dimensional (3-D) in vitro human
musculoskeletal and skin tissue models. These models will facilitate
the study of human tissue physiology and pathophysiology, and
potentially lead to better interventions that prevent or cure diseases.
biomarkers--a tool for discovery and clincal care
Biomarkers are measurable biological or chemical indicators of
health or disease that are accurate and reproducible. NIAMS research to
identify, validate, and utilize biomarkers across the spectrum from
basic to clinical research is bearing fruit. In a recent study, NIAMS
intramural researchers examined the blood of patients with ANCA-
associated vasculitis (AAV), a systemic autoimmune disease that causes
inflammation in the blood vessels. The researchers found that the
amount of a distinct type of white blood cell in patients with
vasculitis correlated with how they would respond to treatment. Once
validated, this discovery could inform clinicians if a particular
patient is likely to respond to an intervention, helping them to tailor
treatment to the individual.
In addition, biomarkers are important tools in monitoring disease
status. Duchenne muscular dystrophy (DMD) is a genetic disorder
characterized by progressive muscle weakness, and biomarkers that
distinguish among stages of the disease could enable researchers to
rapidly assess how well a novel intervention is working. NIAMS-
supported investigators have identified several different types of
biomarkers for DMD using new techniques to monitor changes in muscle
quality. Recently, other researchers found dozens of proteins in blood
that were significantly different between DMD patients and individuals
without the disease. Several of these proteins also changed during
progression from early disease to its later stages. In the future, this
information may help researchers develop new interventions, identify
appropriate candidates for clinical trials, and more rapidly interpret
trial results.
Other biomarkers are being evaluated as surrogate outcomes when
examining new interventions for diseases. For example, NIAMS-supported
researchers tested a new drug to prevent scarring in patients with
systemic sclerosis, a severe form of the chronic connective tissue
disease scleroderma. The researchers showed that the drug significantly
reduced the amount of two proteins in the skin of patients, and these
reductions correlated with improvement in skin condition assessed via
traditional clinical measures. The study results demonstrate the value
of a biomarker-based approach to measuring treatment response and
confirming clinical data.
helping clinicians better care for patients
While basic research into the underlying mechanisms of disease will
always be an important focus, NIAMS research also helps ensure that
physicians have up-to-date information to facilitate treatment
decisions based on the current state of the science. For example,
children with an abnormal curvature of the spine, called adolescent
idiopathic scoliosis (AIS), often are instructed to wear braces to
prevent worsening of the curve, but the effectiveness of this treatment
had not been rigorously tested. In 2007, NIAMS-supported investigators
launched the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST)
to compare the risk of curve progression in tweens and teens with AIS
who wore a brace versus those who did not. In January 2013, the trial
was stopped early after finding that bracing significantly reduced the
risk of curve progression and the need for surgery, and that more hours
of brace wear were associated with higher success rates. These results
were the primary reason several healthcare provider organizations
recently updated their recommendations regarding scoliosis screening
for adolescents. In addition, the United States Preventive Services
Task Force is currently revisiting its screening recommendations for
AIS.
NIAMS researchers are also leveraging existing data to aid
physicians in everyday practice. Recently, NIAMS intramural scientists
conducted a comprehensive review of clinical studies into the various
treatments available for two major causes of back pain, ankylosing
spondylitis and non-radiographic axial spondyloarthritis. Based on the
systematic review, a series of treatment recommendations were
developed, and they have been endorsed by the American College of
Rheumatology. The recommendations provide clinicians with the current
best-evidence for the treatment of these common conditions, and may
facilitate the effective use of healthcare resources, reduce
inappropriate care, and minimize variation in care.
Looking to the future, NIAMS will capitalize on prior investments
and recent advances in the science of patient-reported outcomes (PROs)
to improve the health and well-being of pediatric patients. The Patient
Reported Outcomes Measurement Information System, or PROMIS, was an
NIH Common Fund project, co-led by NIAMS, to develop a system of highly
reliable, precise measures of patient-reported health status for
physical, mental, and social well-being. The PROMIS tools can give
physicians a clearer understanding of how the patient is feeling and
functioning, and can be used across a wide variety of chronic diseases
and conditions in both research settings and in routine care. In fiscal
year 2015, NIH funded the Validation of Pediatric Patient-Reported
Outcomes in Chronic Diseases (PEPR) Consortium that will expand
existing and new PRO tools for pediatric patients, ultimately improving
the treatment of chronic diseases in children. PEPR is part of a trans-
NIH effort to lay the foundation for a new multi-year initiative called
the Environmental Influences on Child Health Outcomes (ECHO) program
set to begin in fiscal year 2017.
fostering innovation and enhancing stewardship
NIAMS is actively working to enhance and strengthen our scientific
stewardship and encourage innovation. As part of these efforts, NIAMS
is supporting several programs targeting the next generation of
researchers. In fiscal year 2015, NIAMS launched a new program called
the Supplements To Advance Research from Projects to Programs, or STAR,
awards. STAR promotes innovation and exploration of high-risk ideas by
providing flexible funding to early established investigators to expand
upon their currently funded project and facilitate transition from a
single project to a research program. NIAMS made three STAR awards in
fiscal year 2015, and anticipates another group of awards in fiscal
year 2016.
In addition to STAR, NIAMS has implemented several programs to
support clinician researchers, a vital population that faces unique
challenges in pursuing research careers. Since fiscal year 2012, NIAMS
has hosted an annual career development forum for extramural
researchers who have received either a mentored clinical scientist
development (K08) or patient-oriented research (K23) grant. The forum
provides awardees with opportunities to network with each other, as
well as NIAMS leadership and program, review, and grants management
officials; and enhances the Institute's support of early-stage
physician-scientists by encouraging and enabling awardees to continue
performing basic, translational, or patient-oriented research in their
chosen fields. In addition to the forum in fiscal year 2016, NIAMS will
implement a new trans-NIH policy of increased salary support for these
same K awardees, a year earlier than required by NIH. Finally, NIAMS is
planning a new small grant program to assist early-stage clinician
scientists as they pursue research independence through the so-called
K-to-R transition, a particularly vulnerable period for investigators.
Together, these and other training and fellowship programs will help
ensure a robust pipeline of new investigators in the rheumatic,
musculoskeletal, and skin disease mission areas.
NIAMS is also encouraging innovation and stewardship by
collaborating with the research community and other stakeholders to
elaborate on exciting new research opportunities. For example, NIAMS,
on behalf of NIH, led the development of a new Action Plan for Lupus
Research, and also participated in the development of the Action Plan
for the Muscular Dystrophies. Both plans represent a synthesis of NIH
internal input, as well as significant external input from the
scientific, clinician, and patient advocacy communities. They will help
to inform priority-setting processes among all interested
organizations--Federal, private, and non-profit--and may inspire
individual investigators as they develop innovative, independent
research proposals. In addition, NIAMS is leading the Accelerating
Medicines Partnership in Rheumatoid Arthritis and Lupus (AMP RA/Lupus).
This unique public-private partnership with NIH, pharmaceutical
companies, and non-profit organizations aims to transform the model for
identifying and validating promising targets for the development of new
drugs and diagnostics. The AMP RA/Lupus program was funded in late
fiscal year 2014, and researchers and other partners have developed a
research plan with distinct milestones. Substantial progress has
already been made incorporating cutting edge technologies and
establishing standard operating procedures that the broader scientific
community will be able to leverage in the future.
______
Prepared Statement of George F. Koob, Ph.D., Director, National
Institute on Alcohol Abuse and Alcoholism
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's fiscal year 2017 budget request for the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the
National Institutes of Health (NIH).
Alcohol misuse has profound, adverse effects on individuals,
families, and communities. Seventeen million people in the United
States have alcohol use disorder (AUD), and the Centers for Disease
Control and Prevention estimates that excessive alcohol consumption
cost the United States $249 billion in 2010. NIAAA is grateful for the
increase to the NIAAA budget provided in fiscal year 2016. This
additional investment will allow NIAAA to increase support for research
training and career development programs, fund additional cutting-edge
alcohol research projects, and facilitate the translation of alcohol
research into practice.
AUD is a chronically relapsing brain disease. As individuals
progress from initial alcohol use to risky drinking to AUD, changes
occur in the structure and function of their brains. These changes
perpetuate drinking and persist long after a person stops. A major
focus of NIAAA's work is to develop a more thorough understanding of
how these changes contribute to the development and maintenance of AUD.
With the additional funding provided to the agency in fiscal year 2016,
NIAAA is able to pursue several important new areas of inquiry in the
neurobiology of alcohol misuse and AUD, including studies of the
effects of adolescent drinking on brain development, exploration of
neuroimunne function in the development of AUD, and identification of
new AUD treatment targets.
Alcohol consumption during pregnancy can have devastating effects
on the developing embryo and fetus. Fetal alcohol spectrum disorders
(FASD), an umbrella term for a range of developmental, cognitive, and
behavioral problems caused by prenatal alcohol exposure, are the
leading preventable causes of birth defects and developmental
abnormalities in the United States. NIAAA supports research on the
mechanisms through which alcohol disrupts prenatal development, to
develop new biomarkers to improve detection of drinking during
pregnancy, to improve FASD diagnosis and establish more precise
prevalence estimates in the United States, and to develop effective
interventions to mitigate the adverse effects of prenatal alcohol
exposure.
Adolescents are particularly vulnerable to the adverse effects of
alcohol. Drinking during adolescence can impair the development of the
frontal cortex, the region of the brain responsible for executive
function and decisionmaking; compromise short- and long-term cognitive
functioning; and increase risk for alcohol problems later in life.
NIAAA supports a broad portfolio of research to identify the factors
that contribute to adolescent alcohol misuse and the effects of alcohol
on the developing adolescent brain. The NIAAA-funded National
Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), for
example, is a nationally-representative, longitudinal study evaluating
brain structure and function in more than 800 youth before and after
they start to drink. Building on NCANDA, NIAAA, along with other NIH
Institutes and Offices, launched the Adolescent Brain Cognitive
Development (ABCD) Study in September 2015. The study will recruit
approximately 10,000 children ages 9-10, most of whom will not have
initiated substance use, and followed into early adulthood.
Participants' exposure to alcohol and other drugs (alone and in
combination), academic achievement, cognitive skills, mental health,
and brain structure and function will be tracked over a 10-year period.
The findings will enable researchers to better understand the myriad
factors that contribute to brain and cognitive development and how
alcohol and other drugs affect these processes, and they will inform
prevention and treatment interventions and public health strategies.
Like adolescents, young adults are also highly vulnerable to the
adverse effects of alcohol misuse, and binge drinking is a particular
concern within this population. In September 2015, NIAAA released its
College Alcohol Intervention Matrix, CollegeAIM, an evidence-based
decision tool to help college and university administrators select
interventions for addressing alcohol misuse on their campuses.
CollegeAIM rates nearly 60 individual- and environmental-level
intervention strategies based on factors such as effectiveness in
achieving targeted outcomes; estimated cost of adoption, implementation
and maintenance; and barriers to implementation. NIAAA will be working
with its College President's Working Group to hold a series of regional
workshops to introduce CollegeAIM to institutional officials and show
them how it can be used on their campuses. NIAAA also is supporting
research to evaluate the use of alcohol screening and brief
intervention for preventing and reducing alcohol misuse among young
adults in clinical and non-clinical settings.
Alcohol use by older adults is emerging as an important area of
emphasis for NIAAA. Older adults may be more sensitive to alcohol's
effects, more likely to suffer from health problems exacerbated by
heavy drinking, and more likely to experience adverse alcohol-
medication interactions. Additional research is needed to more fully
understand how alcohol differentially affects this population.
Reflecting its increased emphasis on developing new medications to
treat AUD, NIAAA established a Division of Medications Development
(DMD) to coordinate efforts to identify, screen, and evaluate promising
compounds. Through the NIAAA Clinical Investigations Group (NCIG), DMD
is conducting ``fast success/fast fail'' phase II clinical trials of
novel and repurposed compounds in collaboration with the pharmaceutical
industry. NCIG is currently evaluating gabapentin encarbil, an FDA-
approved medication for restless leg syndrome and nerve pain that has
shown promise for reducing heavy drinking and promoting abstinence in
individuals with AUD. NIAAA is also working to bridge the gap between
basic and clinical research through the Small Business Innovation
Research and Small Business Technology Transfer programs. Under these
programs, NIAAA is funding studies intended to result in the submission
of an Investigational New Drug application to FDA for the development
of medications to treat AUD or related conditions.
NIAAA continues to support the development of medications for
alcoholic liver disease, especially alcoholic hepatitis, a serious and
often fatal consequence of alcohol misuse for which there is a dire
need for new treatments. Potential therapies for alcoholic hepatitis
currently being tested include: probiotics; an interleukin inhibitor,
which targets a signaling molecule produced by immune cells; and
immunoglobulin, which binds lipopolysaccharides in the gastrointestinal
tract. Through NIAAA's intramural research program, scientists are
studying the link between endocannabinoids and hepatocellular
carcinoma, a serious form of liver cancer with a high mortality rate
and no adequate treatment. Their research supports a role for
endocannabinoids in tumor promotion and raises the possibility that
compounds that block endocannabinoid action could be used to treat this
form of cancer. NIAAA intramural investigators have also developed and
filed for a patent on compounds that inhibit both peripheral
cannabinoid receptors and inducible nitric oxide synthase. These
inhibitors show promise for treating liver and lung fibrosis in
preclinical studies, and NIH's Office of Technology Transfer is
currently pursuing licensing of these compounds to the private sector
for further development and eventual commercialization.
For individuals undergoing treatment for health conditions
associated with excessive alcohol consumption, monitoring their alcohol
use is important. NIAAA issued the ``Wearable Alcohol Biosensor
Challenge'' to stimulate the development of an unobtrusive, real-time,
continuous alcohol monitoring system. The biosensor is expected to
facilitate alcohol research, enable clinicians to accurately assess
their patients' alcohol intake, and help individuals monitor their own
drinking. NIAAA is currently testing eight biosensor prototypes
submitted in response to the Challenge.
NIAAA participates with other NIH Institutes, the Department of
Defense, the Department of Veterans Affairs, and the Department of
Education to accelerate the discovery of underlying mechanisms of post-
traumatic stress disorder (PTSD). Approximately one-third of
individuals who have had PTSD have had AUD at some point in their
lives, and an estimated 30-60 percent of patients seeking treatment for
AUD meet criteria for PTSD. Both conditions are linked to dysregulation
of brain stress systems, and research suggests that alcohol use may
increase PTSD risk by altering the brain's ability to recover from
traumatic experiences. Scientists in NIAAA's intramural research
program are conducting studies to understand how alcohol and stress
affect the structure and function of brain circuits critical for the
regulation of emotion, cognition, and behavioral control over alcohol
and other drug seeking. NIAAA also supports research to develop
interventions for preventing and treating co-occurring AUD and PTSD
including studies aimed at identifying and overcoming barriers to the
diagnosis and treatment of these conditions.
For more than 45 years, NIAAA has supported a diverse portfolio of
research and related initiatives aimed at understanding the effects of
alcohol on health and wellbeing. Efforts such as the Brain Research
through Advancing Innovative Neurotechnologies (BRAIN) initiative are
expected to spur an explosion of new knowledge about brain structure
and function and yield unprecedented insight into brain diseases
including AUD. To capitalize on these and other opportunities in
alcohol research, it is essential to cultivate a talented and diverse
research workforce. Therefore, NIAAA will continue to support robust,
research training and career development experiences for emerging and
established scientists. NIAAA also will pursue efforts to enhance the
incorporation of addiction medicine into clinical training, thereby
facilitating the translation of alcohol research into practice.
______
Prepared Statement of Jon L. Lorsch, Ph.D., Director, National
Institute of General Medical Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of General Medical Sciences (NIGMS) of the National
Institutes of Health (NIH).
investing strategically in discovery
NIGMS-funded scientists investigate how living systems work at a
range of levels, from molecules and cells to tissues, whole organisms,
and populations. NIGMS believes that, as in finance, a diverse research
investment is wise because it maximizes the opportunity for
breakthroughs. NIGMS supports a diverse population of scientists and a
broad portfolio of science at institutions dispersed across the United
States.
NIGMS has a longstanding commitment to nurturing creative thought
that produces new knowledge. In turn, this knowledge grows into
tangible health solutions. Again this year, two long-time NIGMS
grantees won Nobel prizes in Chemistry for their groundbreaking work
about basic biological processes: in this case, how cells repair
damaged DNA. The work, which has led cancer researchers to develop
useful drugs, explains how cells respond to DNA injuries from
ultraviolet radiation or chemicals like the carcinogens found in
cigarette smoke, as well as how cells fix copy errors in the genetic
code that accumulate naturally during cell division. Another NIGMS
grantee shared the 2015 Albert Lasker Basic Medical Research Award
(``the American Nobel'') for his work on the DNA-damage response--a set
of actions that cells undergo to protect their genomes against a nearly
constant barrage of minor DNA damage. It is clear that seminal
discoveries reflecting decades of careful study of fundamental living
systems can have very practical outcomes in treating deadly conditions
like cancer.
NIGMS values the time-tested practice of supporting investigator-
initiated research grants that unleash the creativity and energy of
investigators across the country to solve important biomedical problems
essential to progress in medicine. Leaving discovery to scientists,
NIGMS nonetheless charts its course guided by its strategic plan that
commits to public service, careful stewardship of taxpayer funds, and a
focus on efficiency and effectiveness.
nigms strategic priority: support investigator-initiated biomedical
research
NIH-funded scientists have faced increased competition to obtain
grant funding over the past several years. As one step in enhancing the
efficiency of this process, NIGMS developed and is currently piloting a
new way to fund scientists. The Maximizing Investigators' Research
Award (MIRA) program provides support for the NIGMS-relevant research
in an investigator's laboratory (via a single, 5-year grant), with the
goal of giving investigators greater stability and flexibility and
enhancing scientific productivity and the chances for important
breakthroughs. The program also aims to help distribute funding more
widely among the Nation's highly talented and promising investigators.
NIGMS extended its first MIRA funding opportunity to established
(experienced) investigators whose grant support would expire this year
or next: approximately 25 percent of the eligible pool applied, using a
streamlined application that outlined a broad vision for their work and
its projected significance. Peer reviewers, the Institute's Advisory
Council and NIGMS staff considered a number of criteria when judging
MIRA proposals in addition to the applicants' research vision,
including their record of scientific productivity and contributions to
training the next generation of researchers. The program, which the
Institute is also testing with a cohort of junior investigators, has
been well-received by the community: ``[MIRA] appears to be more
``organic'' and ``flexible'' than the traditional R01 model, and
intuitively seems more compatible with the manner in which ideas,
hypotheses, and unexpected discoveries emerge from focused and
sustained lines of research,'' said one MIRA applicant. The Institute
is capturing data to evaluate how well program goals are met.
Some areas of biomedical investigation require groups of
investigators to work together to ensure synergistic, interdisciplinary
expertise and a diversity of thought applied to complex problems. In
addition to our programs that support single investigators, NIGMS also
funds larger, team-based scientific research. These programs involve
multiple investigators and can include facilities or cores, and
training and outreach activities. Important areas of team-based
research supported by NIGMS are the specialized Centers for HIV/AIDS-
related structural biology. These Centers tackle difficult problems
such as HIV interactions and viral evolution and mechanism of HIV-virus
fusion dynamics with host cells. Their work has laid the foundation for
the development of new AIDS drugs and possible vaccines. Other areas of
team-based research funded by NIGMS that have had an important
scientific impact include the National Centers for Systems Biology. By
investing in these centers for over a decade, the program has funded
228 group leaders and directly supported 268 graduate students and 278
postdoctoral fellows; with an impact of approximately 2,000 peer
reviewed research papers. As a testament to this program, today many
universities have departments and training programs in systems biology,
home to researchers whose work is now supported by investigator-
initiated R01 grants. Through its strategic plan, the Institute will
explore new models for supporting team science that may be more
efficient ways to promote important collaborations than are current
funding strategies.
nigms strategic priority: build and maintain a diverse research
workforce
Science has changed dramatically over the past three decades, and
the amount of information available about biological systems has grown
exponentially. New methods allow researchers to illuminate and
investigate the inner workings of cells with unprecedented resolution
(see, for example, the discussion below of cryo-EM technology), and to
generate expansive datasets that monitor and measure hundreds to
thousands of molecular entities in a system, in both time and space.
Biomedical research is becoming increasingly interdisciplinary and
collaborative, whilst the questions become ever more complex. NIGMS is
working to catalyze modernization of the education and training of the
next generation of biomedical researchers to meet the rapidly evolving
challenges and opportunities of science and medicine. The Institute
recognizes that teaching and learning are not one-size-fits-all
endeavors, and that institutional context matters. To promote the
necessary shifts, NIGMS is helping colleges and universities test new,
innovative educational models that develop the skills required for
students to become outstanding scientists who conduct rigorous and
reproducible biomedical research. New training paradigms will also
emphasize the essential role of mentoring in career development. The
Institute hopes to promote a culture in the academic community that
continually optimizes training strategies to meet the changing needs of
the scientific enterprise. Toward achieving these goals, in April 2016,
NIGMS is hosting a symposium on the NIH campus to convene stakeholders
from the biomedical graduate education community to continue momentum
for positive change and showcase innovative approaches in Ph.D.
training.
One key element of research excellence is scientific workforce
diversity, because capitalizing on the full spectrum of skills,
talents, and experiences is essential for solving complex human health
challenges. Over the past several decades, the biomedical workforce has
benefited from various NIH programs aimed at enhancing diversity.
NIGMS, in particular, has demonstrated a strong commitment to training
underrepresented individuals through programs supporting all stages of
the career development pathway. The Institute has identified a pressing
need to focus on career inflection points, notably the transition from
trainee to career independence. The Institutional Research and Academic
Career Development Award (IRACDA) program addresses this need by
combining a traditional mentored postdoctoral research experience with
an opportunity to develop academic skills, including teaching, through
workshops and mentored teaching assignments at a partner (typically
underserved) undergraduate institution. NIGMS recently began an
analysis of how well this program is achieving its goals, and the
initial results are very good. IRACDA has sponsored about 400 scholars
who have completed training since the program's 1999 inception. A
substantial number of these alumni (70 percent) hold academic positions
at a variety of educational institutions: 35 percent of academic alumni
are located at research-intensive institutions; 14 percent work at
partner institutions; and the remainder are employed at other
institution types. A particularly promising finding is that IRACDA
scholars are considerably more diverse than either a comparable pool of
NIH-funded postdoctoral fellows or the overall NIH-funded research
workforce.
nigms strategic priority: create and share cutting-edge tools and
resources
In addition to the creativity of the human mind, cutting-edge
technology is a catalyst for innovation. However, technology resources
are often not accessible to investigators because of limited supply,
location, or cost. NIGMS is using a range of approaches to improve the
Nation's research infrastructure, providing investigators better access
to critical, shared research resources and technologies. For the past
few decades, X-ray crystallography has been the method of choice to
allow researchers to take three-dimensional ``pictures'' of proteins
and other molecules important for health and disease. But recently,
advances in another technique, cryo-electron microscopy, or cryo-EM,
have moved it to the forefront of research into the structures of
biological molecules. Unfortunately, despite cryo-EM's advantages over
X-ray crystallography and its great promise for helping scientists
understanding cell function and dysfunction, state-of-the-art cryo-EM
equipment is out of the reach of most of the country's researchers
because of its very high cost. To begin to address this problem, NIGMS
has started a program to support the purchase and maintenance of cryo-
EM technology by regional consortia, giving multiple research groups
and institutions access to the equipment. NIGMS hopes to expand this
consortia model into larger, regional facilities that will produce
significant economies of scale and expand greatly the number of
scientists who can use important, cutting-edge technologies.
Through its Institutional Development Award (IDeA) program, NIGMS
provides targeted support to increase research capacity in States that
historically have had little NIH funding. The IDeA program investment
is catalytic and has been successfully leveraged into additional
investigator-initiated grants to researchers in IDeA States. For the 8-
year period spanning fiscal year 2007 to fiscal year 2014, this
additional funding support was $12 billion, almost a seven-fold return
on investment, according to a recent NIGMS program analysis. The IDeA
Centers of Biomedical Research Excellence (COBRE) program supports
thematic, multidisciplinary centers that expand and develop biomedical
faculty research capability and enhance research infrastructure, in
part through development of core facilities needed to carry out modern
multidisciplinary collaborative research. While the number of COBRE-
supported scientists increased only 9 percent between fiscal year 2007
and fiscal year 2014, the productivity of those investigators in terms
of scientific publications increased much more--an impressive 43
percent--suggesting that resources are integral to priming the
biomedical capabilities of recipient institutions. NIGMS is also
supporting the development of clinical research capacity in IDeA States
through IDeA Infrastructure for Clinical and Translational Research
awards and through joint management, along with the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, of
the new IDeA States Pediatric Clinical Trials Networks.
While the number of scientific publications per scientist is one
metric of success, others include patents and generating interest in
commercialization. The Lexington, Kentucky COBRE, for example, has
launched two start-up companies to further develop potential cancer
treatments identified through NIGMS-funded research. One is pursuing
drug development of a substance that targets molecules that are
overactive in certain colorectal and liver cancers.
In this statement, I have shared just a few examples of the
remarkable types of returns received from NIGMS' investment in
fundamental biomedical research. NIGMS looks forward to the many more
advances that will emerge from laboratories across the Nation.
______
Prepared Statement of Eliseo J. Perez-Stable, M.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 fiscal year 2017 budget request for the National
Institute on Minority Health and Health Disparities (NIMHD) of the
National Institutes of Health (NIH).
advancing health disparities research
Medical and technological advances have afforded individuals with
the potential for longer and healthier lives. However disparities
between racial and ethnic minorities, rural, and disadvantaged
socioeconomic populations continue to persist. NIMHD leads scientific
research that advances understanding of minority health and health
disparities. Understanding the complexity of health disparities
requires examining how health determinants, biological, social,
individual behavior, health system, and environmental factors interact
with race/ethnicity and socioeconomic status (SES) to influence health
outcomes. For example, studies have shown racial and socioeconomic
disparities in pain management, with African American and low SES
patients less likely to receive first-line care. NIMHD currently
supports a project that examines the use of computer-simulated patients
and environments to assess, understand and alleviate pain treatment
disparities that are associated with clinician bias. Findings from the
study indicate that the utilization of virtual patients allows for
greater exposure to racially and socioeconomically diverse patients
than what can be found in traditional training settings. As a result, a
significant decrease was found in decisionmaking bias for how best to
care for the virtual patient.
As the primary Federal agency for guiding and coordinating research
to improve minority health and reduce health disparities, NIMHD has
taking significant steps in setting a transformational agenda for the
field. Recognizing the many factors that drive health disparities and
overall health outcomes in minority health, NIMHD is completing a
scientific visioning process that will establish a standard social-
ecological-biological framework to advance the science of minority
health and health disparities.
collaborative research
A cornerstone of NIMHD's mission is to foster innovative
collaborations and partnerships. In order to effectively address health
disparities, a multidisciplinary approach involving community,
academia, clinicians, service providers, and Federal partners is
necessary. NIMHD has a long standing history of fostering partnerships
both within and outside of NIH. For example, NIMHD supported Georgetown
University, Howard University, and MedStar in their goal to eliminate
breast cancer and stroke disparities by transferring knowledge from
research to practice within a community setting. Advances of this
collaborative effort have led to a community scholars curriculum
designed to provide education in research engagement and capacity for
community partner organizations to develop and maintain their own
research and data systems infrastructure. This partnership also has
strengthened the research workforce by developing a fellows program
that trains, funds, and mentors students and early stage investigators
who are pursuing careers in minority health and health disparities
research. More recently, NIMHD in collaboration with the U.S.
Environmental Protection Agency, National Institute of Environmental
Health Sciences, and the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, supported the establishment of an
indigenous environmental health research center aimed at providing the
Hopi and Navajo communities with the ability to conduct their own
environmental exposure research. A unique approach to the study is the
emphasis on identifying culturally appropriate research methods to be
carried out by a multidisciplinary team involving American Indian
researchers.
An ultimate example of collaboration is the launch of the Precision
Medicine Initiative (PMI). PMI has afforded NIH with the opportunity to
form a strong network among several of its Institutes and Centers.
NIMHD plays a leadership role in the efforts to ensure that the
establishment of the Precision Medicine Cohort includes standard
measures of social determinants of health at baseline and exhibits the
diversity necessary for the outcomes of the study to pertain to all
Americans. Community engagement is vital to the inclusion of all health
disparities populations and therefore, NIMHD has engaged researchers to
conduct studies aimed at identifying biomarkers for disease progression
(e.g., prostate cancer in African Americans) and drug response in
diverse populations (e.g., asthma treatment in Latinos of different
national origin) and to examine facilitators and barriers to
implementing precision medicine findings in disadvantaged populations.
In addition, NIMHD has been at the forefront of ensuring that community
organizations are well-informed about the promises of precision
medicine. Participation in three White House briefings, meetings and
workshops with community organizations, and presentations at national
scientific meetings are examples of NIMHD's commitment to engaging all
communities in the Precision Medicine efforts.
enhancing diversity of the workforce
NIMHD recognizes a unique and compelling need to promote diversity
in the biomedical, behavioral, clinical, and social sciences research
workforce. NIMHD expects that efforts to diversify the workforce will
lead to the recruitment of the most talented researchers from all
groups into research areas relevant to the mission of NIMHD; improve
the quality of the educational and training environment; balance and
broaden the perspective in setting research priorities; improve the
ability to recruit participants from diverse backgrounds into clinical
research protocols; and improve the Nation's capacity to address and
reduce health disparities.
As the U.S. population becomes increasingly diverse, reflection of
that diversity among the biomedical research workforce is vital to the
NIMHD research mission. To develop, maintain, and renew our scientific
talent pool, it is imperative that we create a climate of opportunity
to attract and retain the most talented individuals who can capitalize
on innovation and advance scientific discovery. Research has
demonstrated that a diversity of perspectives leads to better solutions
to complex challenges, including healthcare research and education.
NIMHD's commitment to enhancing the biomedical research workforce is
evident in our continued support of the Loan Repayment Program, an
annual Health Disparities course targeting early career investigators,
Clinical Research Education and Career Development Awards, Research
Centers in Minority Institutions, and our partnership in the NIH
Medical Research Scholars Program. NIMHD's role in all of these
programs has produced marked increase in the number of diverse
scientists entering and persisting within the research arena.
conclusion
Despite medical and scientific advances there continues to be a
disproportionate burden of illness and disease among racial and ethnic
minorities and other health disparities populations. Ameliorating these
disparities in health outcomes is central to NIMHD's mission. NIMHD
envisions an America in which all populations will have an equal
opportunity to live long, healthy, and productive lives. Therefore,
NIMHD remains committed to scientific leadership in coordinating and
supporting highly meritorious research on minority health and health
disparities with the goal of improving public health and promoting
healthier lives.
______
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 2017 budget request for the National
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the
National Institutes of Health (NIH).
The mission of NIBIB is to improve human health by leading the
development of biomedical technologies and accelerating their
application. NIBIB supports research that integrates engineering with
the physical and life sciences to develop emerging technologies that
can be applied to a broad range of biomedical and healthcare problems.
The scope of NIBIB-supported research is vast, from innovations to
address paralysis to novel ways to deliver vaccines.
NIBIB is a leader in bringing together many disciplines to solve
great biomedical challenges, with a mission that spans all diseases. To
achieve that mission, NIBIB supports researchers from every field of
medicine and gathers teams of scientists and engineers from diverse
backgrounds. These researchers work to develop innovative approaches to
advance scientific discovery and address real-world health issues
through new knowledge and new technologies. I am pleased to share a few
highlights from the breadth of NIBIB-funded research efforts that are
working toward our shared goal of improving public health.
delivering a vaccine without a needle or need for refrigeration
NIBIB's Quantum Grants Program is designed to have a profound, or
quantum, impact on a particular healthcare problem. In keeping with
NIBIB's mission, projects in this program take an approach that is
highly collaborative and interdisciplinary with a focused goal that is
achieved through technological innovation. In one Quantum Grant
example, researchers have developed a microneedle patch to deliver
vaccines without the traditional ``shot in the arm.'' This technology
could lead to self-administered vaccines with an easy-to-use, more
widely available device that is about the size of a quarter.
The first targeted application is flu vaccination. Influenza is a
major cause of illness and death worldwide. While vaccines are
effective in preventing infection, access in rural and medically
underserved areas is a challenge. A new microneedle patch addresses
these challenges in that it can be self-administered, does not require
refrigeration, and could be delivered in the mail. The single-use patch
is also painless and research has indicated that all of these benefits
could lead to higher rates of immunization and reduce flu-related
deaths and hospitalizations.
A clinical trial is underway to assess the use of microneedle
patches in vaccinating against influenza. The patches contain very thin
and short microneedles, which are barely visible to the eye. As the
patch is applied to the skin, these microneedles painlessly penetrate
the upper layers of the skin and deliver the vaccine. The study
includes 100 healthy adults and seeks to assess the safety of the
microneedle patch, how the body's immune system responds to the vaccine
delivered through the patch, and participants' opinions about using the
patch. Initial results indicate that influenza vaccination using the
microneedle patch generates immune responses at least as good as
conventional injection, that the microneedle patch has a very good
safety profile, and that study participants strongly prefer vaccination
by the microneedle patch over a traditional flu shot.
using imaging technology to both diagnose and treat disease
For decades, imaging technologies such as magnetic resonance
imaging (MRI), ultrasound, and computed tomography (CT) have provided a
window for a non-invasive look inside the body to locate and assess
tumors or damaged tissue. Increasingly, research in imaging technology
is not only discovering improved ways to see inside the body but also
developing highly integrated systems to provide rapid feedback to guide
treatment.
In another Quantum Grant Program example, researchers are using an
improved imaging technology that combines diagnosis and an intervention
for acute ischemic stroke. Strokes are a major cause of death and
neurological injury. Acute onset of stroke-like symptoms is a medical
emergency and rapid diagnosis and treatment are critical to saving as
many brain cells as possible. This novel method is estimated to save
from one to two hours per patient, and therefore save considerable
brain tissue.
Currently, stroke diagnosis and monitoring is performed with
imaging in dedicated CT or MRI imaging suites separate from where
stroke is treated, requiring the patient to be moved and costing
precious time while brain tissue is damaged through loss of blood
supply. The treatment of stroke caused by blocked blood vessels
involves specialized catheter-based angiography to restore blood supply
to the affected brain area. The breakthrough of this Quantum Grant
award is the integration of angiography with advanced imaging
capabilities into a time-saving and cost-efficient platform that is
housed on a single machine. This is possible through a revolutionary
image acquisition and reconstruction technique that fundamentally
challenges the traditional methods now in use. For the first time, this
new technique produces rapid, high resolution CT images and enables
immediate treatment of strokes caused by blood vessel occlusion
(blockage).
Advances to current imaging technologies such as this could lead to
more rapid and personalized treatment of occlusion stroke, potentially
resulting in better neurological outcomes for patients.
finding rare cells among billions for early detection of cancer
Cancer tumors shed tiny fragments that can enter the blood stream.
Capturing these obscure traces of cancer allows them to be analyzed so
that treatment can be designed specifically for each patient.
Similarly, the technology can be used to monitor treatments for
effectiveness. This individualized approach, which identifies and
targets the specific genetic features in each person, is the hallmark
of the President's Precision Medicine Initiative.
In an initial phase of an ongoing NIBIB Quantum Grant Program,
researchers developed the iChip, a microfluidic device that can capture
one circulating tumor cell (CTC) among one billion red blood cells.
This means that in a small vial of blood there could be from 1--100
CTCs among 80 billion red-blood cells. In one study, human cancer cells
were captured using this technology and analyzed, then tested in animal
models to see which treatment was most effective. Researchers are also
working to make the device so small that it can be used at the point-
of-care to deliver results rapidly. This real-time measurement of CTC
numbers could one day allow doctors to promptly change or stop
ineffective treatments, such as when cancer cells become resistant to a
particular chemotherapy drug.
The technology has also been developed to isolate clusters of CTCs.
Clusters are even rarer than single CTCs, but are 50 times more potent
in producing metastatic spread of cancer. Identifying and capturing CTC
clusters could help identify and study more aggressive cancers.
Building on this research, the investigators are now turning toward
a new phase of development that can capture pieces of DNA shed from
cancer tumors. Researchers are looking at this new use of the
technology as a sensitive method for early identification of prostate
and lung cancer. In both types of cancer, detection is challenging and
cancers are often discovered when tumors are of a significant size, or
the cancer has spread. This technology also has the potential for non-
invasive monitoring to determine if the selected treatment is working.
The new approach integrates the CTC iCHIP technology with known methods
to identify genetic markers for early detection.
using neural stimulation to address paralysis
Each year 12,500 new cases of severe spinal cord injury (SCI) occur
(2015, National SCI Statistical Center). Currently, the approach for
treating this type of injury is to provide rehabilitation therapy to
limit further damage. In these patients, the pathways that send
information about sensation from the legs to the brain and from the
brain to the legs to control movement are disrupted. For years
physicians thought that recovery of function in spinal cord injury was
not possible.
Now, after years of basic research and recent developments in a
very small number of patients, investigators are working to understand
how neurostimulation of the spinal cord might help patients regain
function. Recent studies have shown that it might be possible to
reawaken the neural pathways along the spinal cord after injury. A
small number of patients have received electrical stimulation either
implanted under the skin next to the spine (epidural) or placed on top
of the skin along the spine (transcutaneous) and have regained the
ability for some limb movement and the ability to stand unassisted for
a brief period of time. Patients receiving stimulation also report that
they have regained other functions important for improved quality of
life, such as control of blood pressure, temperature, bladder, bowel,
and sexual function. Further study is aimed at understanding how
electrical stimulation can most effectively lead to restored function
and how stimulation can be customized to work best for individual
patients.
NIBIB is also part of the President's BRAIN Initiative and part of
this effort is to develop tools and technologies that lead to a better
understanding of brain function. Many of the technologies developed for
understanding the brain can be used to understand the spinal cord and
the peripheral nervous system. Understanding these systems will help us
know how to help people overcome these devastating injuries.
conclusion
Advances in technology are catalyzing the development of solutions
to previously intractable disorders and improved approaches to
biomedical research. As these examples illustrate, this type of
research requires many disciplines to work together and this
integration of disciplines is what defines NIBIB's approach. NIBIB is
committed to supporting such convergent teams of researchers to solve
major biomedical challenges that will improve the health of all
Americans.
______
Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P. , Director,
National Institute of Diabetes and Digestive and Kidney Diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the
National Institutes of Health (NIH). NIDDK supports research on many
chronic, consequential, and costly diseases and conditions 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.
discovery research
NIDDK-supported scientific research is expanding knowledge of human
health and disease. Testing novel approaches and hypotheses has led to
new discoveries that continue to build foundations for innovative
strategies to improve health and quality of life. These advances
include researchers revealing a critical role for immune cells in the
development and activity of calorie-burning beige fat, a finding which
could provide new therapeutic targets to treat obesity and metabolic
diseases. Genetic research examining data from hundreds of thousands of
people has more than doubled the number of genetic regions known to be
associated with obesity and body fat distribution patterns.
Additionally, studies have found that a virus in the intestinal tract
could have beneficial effects similar to those granted by gut bacteria,
and research in humans and in mice has shed new light on how genetic
factors shape the composition of the gut microbial community and affect
metabolism. New discoveries could also yield novel, non-antibiotic
approaches to treat or prevent urinary tract infections (UTIs). One
group of scientists discovered a new mechanism by which bacteria such
as E. coli survive and promote UTIs, and another found that in mice,
bacteria that do not cause symptomatic UTIs may be an effective therapy
against ones that do. These and other discovery-based investigations
continue to seek fundamental knowledge about living systems that can
form the basis for new strategies to protect and improve health.
In fiscal year 2017, NIDDK will continue to support pioneering
discovery-based research, including efforts to build integrated human
pancreatic islet and liver tissue chips that can be used to study
metabolism and model human diseases such as diabetes. NIDDK also will
support research to define interactions between the host and the gut
microbiota that can regulate both healthy and disease-related
physiological processes. These projects aim to discover specific human
gut microbiota-derived factors that affect or are affected by the human
host's own physiology and disease and then investigate how these
factors affect the gut and other organs. Harnessing knowledge of normal
kidney development, the NIDKK-funded (Re) Building A Kidney consortium
continues to forge new approaches to treat kidney injury and disease by
enhancing kidney repair and promoting the generation of new kidney
cells. Additionally, the Human Heredity and Health in Africa (H3Africa)
Initiative will continue to support a network of African investigators
to study the interplay between environmental and genetic factors
affecting
the health of African populations. To accomplish this, the H3Africa
Initiative aims to enhance infrastructure and support collaborations to
enable African researchers to carry out large-scale studies on African
populations.
clinical research
Clinical studies are integral to research on the broad spectrum of
diseases for which NIDDK has research responsibility. Through
innovative design and rigorous testing of interventions, NIDDK-
supported researchers are improving lives with new approaches to
prevent, treat, and reverse diseases and disorders. For example,
researchers have developed a potential new method to use examination of
the eye to diagnose diabetes-related nerve complications, a strategy
that could replace the use of skin biopsies to diagnose these problems.
A new research model of the human small intestine was developed by
growing intestinal tissue from human stem cells, resulting in tissue
that can perform digestive functions and be transplanted into mice.
This advance expands scientists' ability to study the intestine under
conditions similar to those in the human body. Researchers found that a
process called ``desensitization'' can alter the immune system of a
person with kidney failure so that their body can accept a kidney
transplant from an incompatible live donor, rather than waiting for a
more compatible cadaveric donor or remaining on dialysis. Another group
found that people who choose to donate one of their kidneys to someone
with kidney failure remain relatively healthy 3 years after their
donation, suggesting that living donor kidney donation can improve the
health of donor recipients without compromising the health of the
donor, at least within the first 3 years after donation. Genetic
studies also found six new genetic regions associated with risk of
developing both inflammatory bowel disease and immunoglobulin A
nephropathy, a major cause of kidney failure worldwide. These findings
may lead to better understanding of the causes of both diseases and,
eventually, to new treatments.
NIDDK-supported clinical research will continue to pursue improved
treatments for diseases and conditions relevant to the Institute's
mission. The Glycemia Reduction Approaches in Diabetes: A Comparative
Effectiveness Study (GRADE) is a major trial that recently began to
compare commonly used diabetes medications, with the goal of
determining which drug--in combination with metformin--is most safe and
effective for patients. NIDDK will also continue its participation in
the Accelerating Medicines Partnership (AMP) Type 2 Diabetes Project--a
public-private partnership between NIH, the Food and Drug
Administration, biopharmaceutical companies, and non-profit
organizations--that seeks to identify and validate the most promising
biological targets for diagnostic and drug development. AMP has
developed and is expanding a Knowledge Portal that consolidates results
from 28 large human genetic studies of type 2 diabetes and supports
analyses that can shed light on possible drug targets. The Predicting
Response to Standardized Pediatric Colitis Therapy (PROTECT) study--
conducted in collaboration with the Crohn's and Colitis Foundation of
America's Pediatric Research Organization for Kids with Intestinal
Inflammatory Diseases (PRO-KIIDS) Network--will continue its efforts to
provide a better understanding of how children newly diagnosed with
ulcerative colitis (UC) respond to corticosteroids, the standard
initial therapies used to treat this disorder. The PROTECT study
results could help predict how children with UC will respond to
treatment and thus lead to more personalized therapies and improved
outcomes. Also, NIDDK-sponsored Multi-Disciplinary Approach to the
Study of Chronic Pelvic Pain (MAPP) Research Network continues to
conduct innovative, collaborative studies of interstitial cystitis/
painful bladder syndrome (IC/PBS) and chronic prostatitis/chronic
pelvic pain syndrome (CP/CPPS). The MAPP Research Network's work can
pave the way to better understanding of what causes these conditions,
improved diagnosis, ways to prevent onset, and more effective
treatments. The Network is also studying the possible relationships
between urologic pelvic pain and other chronic pain disorders, such as
irritable bowel syndrome and fibromyalgia.
New clinical research initiatives include the launch of the
Consortium for the Study of Chronic Pancreatitis, Diabetes and
Pancreatic Cancer. This consortium (co-funded by NCI) will study
chronic pancreatitis (CP) and factors that link CP to other diseases.
The consortium will conduct studies to improve understanding of CP's
disease processes and how these processes are related to outcomes such
as diabetes and development of pancreatic cancer. NIDDK will also
support clinical research into how normal or altered sleep and
circadian rhythms affect metabolism and disease outcomes such as
diabetes. Additionally, through NIH's Common Fund, the ICD-Pieces trial
will test whether a collaborative model of primary and subspecialty
care enhanced by a novel health information technology platform could
result in better care and quality of life for those with multiple
conditions, such as chronic kidney disease, diabetes, and hypertension.
sustaining the biomedical workforce
The future of biomedical research and the continued improvement of
the Nation's health depend critically on maintaining a strong and vital
work force. NIDDK strives to ensure that new investigators can realize
their potential for contributing to biomedical research, and that
today's generation of young scientists will view research as a viable
career. To this end, NIDDK offers a comprehensive set of programs that
support investigators from their initial training as medical and
graduate students through their evolution into established scientists.
In addition to providing institutional and individual grants to support
graduate and post-graduate trainees and physician-scientists, NIDDK
supports one of the largest career development programs at NIH. It
complements this program with a biennial workshop that provides
knowledge and skills necessary to transition to independent research
careers, including career advice and information about the NIDDK's
grant review process. NIDDK also offers career development awardees a
small supplemental grant program to help establish an independent
research program. Early stage independent investigators (ESIs) are
generously supported with priority funding. Recognizing that the first
renewal of an ESI's first grant is typically the final barrier to
becoming an established investigator, NIDDK has targeted ESIs with a
workshop that provides additional guidance, and it has instituted a
pilot program that offers them priority funding when they renew.
To build and sustain a diverse research pipeline, NIDDK has several
programs aimed at facilitating research by and mentorship of
underrepresented groups at various career stages. The Short-Term
Research Experience for Underrepresented Persons (STEP-UP) program
provides hands-on summer research experience for high school and
undergraduate students interested in exploring research careers.
NIDDK's Network of Minority Health Research Investigators fosters
mentoring relationships between senior and early-career scientists, and
NIDDK-supported awards enable mid-career health professionals to
conduct research while acting as mentors to early-stage investigators
from diverse backgrounds underrepresented in biomedical and behavioral
research.
In closing, NIDDK is committed to a vigorous, multi-pronged
research portfolio including both discovery-based and clinical
research. Five principles continue to guide NIDDK's future research
investments: maintain a vigorous investigator-initiated research
portfolio, support pivotal clinical studies and trials, preserve a
stable pool of new investigators, foster research training and
mentoring, and disseminate science-based knowledge through education
and outreach programs.
______
Prepared Statement of Paul Sieving, M.D., Ph.D., Director, National Eye
Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National Eye
Institute (NEI) of the National Institutes of Health. Vision science is
at the leading edge of neuro-regenerative medicine and discovery
science in brain connectivity. I want to share our latest progress and
goals in neuroscience, regenerative medicine, gene discovery, and gene
therapy.
nei audacious goals initiative
The NEI Audacious Goals Initiative (AGI) is a bold, strategic
investment in neuro-regenerative medicine that will enable the
restoration of vision through regeneration of the retina--the light-
sensitive tissue in the back of the eye. AGI focuses on photoreceptor
neurons and retinal ganglion cells. Photoreceptors capture the light
necessary for initiating vision, while retinal ganglion cells transmit
these light-induced signals to the brain and can degenerate in glaucoma
and other optic nerve diseases. Vision scientists have taken the first
steps toward achieving the regeneration of these cells by converting
stem cells into mature retinal cell types and are integrating these
cells into existing retinal circuits. In order for these regenerated
neurons to send signals to the brain, they need to grow long
connections, called axons, and correctly wire themselves to the
appropriate partners in the retina and the brain--a goal that will
require new tools and a better understanding of the underlying
biological processes.
Last year, NEI awarded the first five AGI projects to develop
functional and metabolic imaging technologies that are capable of
visualizing a single live cell. For example, adaptive optics (AO)
technology has been developed to successfully image a single
photoreceptor in patients and track that particular cell in subsequent
patient visits. This powerful tool allows clinicians to non-invasively
monitor the degeneration of the cell and conversely to image its
replacement by healthy stem cells. Prior to this technology, imaging
was severely limited by distortions that bent light waves irregularly.
In addition to AO, advanced magnetic resonance imaging technology is
being developed to assess regeneration of damage to the optic nerve.
These five imaging teams were brought together in a collaborative
consortium to share data, technology, and early results in order to
speed progress toward scientific goals. This consortium also
facilitates input and guidance by NEI program staff as well as by an
external scientific oversight committee. Importantly, the AGI is a
participatory scientific endeavor that actively gathers input from the
vision community and the broader neuroscience community in the form of
expert workshops and town hall meetings.
NEI is currently reviewing applications from a second AGI funding
opportunity to screen cellular and molecular entities critical to the
regeneration of neurons, guiding their axons to targets, and making new
functional connections. NEI anticipates that once the unknown factors
(genes, proteins, signaling molecules, etc.) involved in regenerating
retinal ganglion cells and photoreceptors are discovered, the work will
advance to specific projects to understand the biological mechanisms
through which these factors influence regeneration.
It is noteworthy that AGI has catalyzed the field of neuro-
regenerative medicine, with over 20 investigator-initiated projects
awarded by NEI in fiscal year 2015. While AGI is independent of the
President's BRAIN Initiative, many vision scientists are BRAIN
grantees, and BRAIN research will accelerate AGI efforts to regrow and
regulate retinal neurons and their connections in the eye and brain.
translational research and clinical trials
Proliferative diabetic retinopathy (PDR) is a serious complication
of diabetes, in which vascular endothelial growth factor (VEGF)
secreted by the retina triggers the proliferation of abnormal leaky
blood vessels. Accompanying vitreous hemorrhage and retinal detachment
can lead to permanent vision loss. Since the 1970s, doctors have
treated PDR with a laser therapy, but this treatment can damage night
and side vision, so researchers have sought improved therapies.
Lucentis is one of several drugs that block VEGF and has been shown to
be effective in other eye diseases. Diabetic Retinopathy Clinical
Research Network (DRCR.net) has 400 retina specialists in over 41
States, one third are university based, and the rest are from
community-based practices. A DRCR.net trial found that Lucentis is
highly effective in treating PDR, reversing some vision loss without
affecting side vision. By comparison, laser treatment merely preserves
existing central vision but does not reverse losses. The new research
findings demonstrate the first major therapy advance for PDR in nearly
40 years. The network also conducted a study of three anti-VEGF drugs
for diabetic macular edema: Lucentis, Eylea and Avastin. After 2 years,
patients with mild vision loss at baseline had similar improvements in
visual acuity from all three drugs. However, patients with moderate to
severe vision loss at the start of the trial had slightly better
improvement with Eylea and Lucentis than the less costly drug, Avastin.
From these results, patients and doctors can weigh baseline vision,
expected clinical outcomes, and costs when choosing a personalized
treatment strategy.
For patients who live in rural or urban underserved communities,
telemedicine can be used to remotely screen, monitor and diagnose
disease. DRCR.net just launched a new protocol to explore whether
telemedicine using a new ultra-wide field imaging technology can allow
specialists to remotely identify DR in a patient and to determine what
follow up care is indicated. NEI also has supported telemedicine
technology development through its Small Business Innovation Research
program, e.g., automated retinal scanning technology to detect DR and
monitor images at remote clinical sites.
Using patient-specific induced pluripotent stem cells (iPSCs), NEI
researchers are developing the first personalized therapy for the
``dry'' form of AMD. The retinal pigment epithelium (RPE) is a single
layer of cells that carry out the critical function of nourishing and
supporting the adjacent photoreceptor cells. In dry AMD, RPE cells
start to die, leading to photoreceptor cell loss and visual impairment.
The NEI intramural research team has developed a clinical-grade
manufacturing process to derive iPSCs from AMD patients and convert
them into RPE tissue. The RPE tissue is delivered using a biodegradable
scaffold that helps integrate and maintain proper orientation of the
tissue in the back of the eye. The entire RPE tissue manufacturing
process takes only 142 days after a blood draw from an AMD patient.
Patient-derived tissue has the distinct advantage over donor tissue as
it is less likely to be rejected by the immune system. In preclinical
work to prepare for a human trial, the NEI team demonstrated that
transplanted tissue integrates in the retina and restores lost function
in a pig model of retinal degeneration. Success in the pig model, along
with production of clinical grade iPSC has paved the way toward filing
an application for Investigational New Drug (IND) with FDA in 2017.
iPSC technology is a potentially powerful research tool that
enables scientists to transfer their knowledge of known disease
pathways in particular cells and organs to shed light on the impact of
these same disease mutations in entirely different cell types of other
organs. For example, iPSCs derived from a heart disease patient have a
mutation in the gene STAT3. This mutation impairs blood vessel growth,
and immune and wound-healing responses. The STAT3 gene has also been
suggested to play a role in RPE immune responses and in molecular
signaling that may lead to AMD-like symptoms in patients. The NEI team
is now testing RPE tissue derived from this patient's cells to
understand the role of STAT3 in AMD.
Cataracts are a clouding of the lens caused by misfolding and
aggregation of lens crystallin proteins, and can result from many
causes including side-effects of drugs like steroids, or surgery, or
most commonly from aging. Cataracts occur in over half the population
over age 70 and are a major cause of vision loss in older adults.
Researchers identified a class of molecules that bind to crystallins,
reverse their aggregation and restore lens transparency in mouse models
of cataract. These agents could be delivered via eye drops, potentially
eliminating the need for costly surgical cataract removal.
genetics and gene therapy
In the largest-ever Genome Wide Association Study (GWAS) for AMD,
NEI investigators were part of an international team that studied more
than 12 million gene variants from more than 43,000 participants with
and without AMD. The group identified 52 associated common and rare
gene variants associated with AMD. The success of this study,
particularly for rare variants, was predicated on the extremely large
sample size of participants and bringing together an interdisciplinary
team of clinicians, geneticists, and bioinformatics experts to analyze
``big data.''
Glaucoma is the second leading cause of blindness globally. It is a
group of conditions that damage the optic nerve and have a genetic
predisposition. A consortium called the NEI Glaucoma Human Genetics
Collaboration Heritable Overall Operation Database (NEIGHBORHOOD)
recently identified three new genes that contribute to the most common
form of glaucoma, increasing the total number of such genes to 15. One
new gene is an enzyme that protects cells from oxidative stress.
Another gene had previously been implicated in a rare form of severe
early onset glaucoma. Despite the high heritability of glaucoma,
identifying glaucoma genes has been a challenge and the biological
mechanisms are poorly understood. To address the mechanistic challenge,
NEIGHBORHOOD researchers integrated eight independent GWAS, involving
over 37,000 glaucoma patients and controls to better understand genes
and phenotypes.
A pioneering technology called optogenetics introduces light-
sensing proteins into cells that are not otherwise light sensitive. In
retinitis pigmentosa (RP), the light-sensitive photoreceptor neurons
have died, however many other neurons in the retina are preserved. NEI
investigators have established proof-of-principle with optogenetics
gene therapy in blind mice. By delivering light-sensing proteins
directly to retinal bipolar cells, they effectively bypass the dead
photoreceptor neurons upstream and can elicit a visual response. This
exciting work is being translated into a clinical trial. There are many
gene mutations that cause RP, yet optogenetics is not treating a single
mutation; a single therapy that restores visual responses could have
widespread application.
A major scientific breakthrough in the past few years was the
development of a gene editing tool called CRISPR/Cas9, in which
specific DNA mutations can be changed in specific cells. As a research
tool, this system allows researchers to introduce molecular changes in
cell cultures or animal models to study the function of individual
proteins. The tool also has fundamentally important implications for
clinical therapy in adult tissues. NEI is funding research that is
correcting genetic mutations in stem cells created from patients with
genetic mutations for RP, Usher syndrome, and Best disease. In the
future, these corrected stem cells could be used as a cell therapy. NEI
also is funding research using CRISPR/Cas9 for a wide variety of other
ocular disorders affected by specific gene mutations such as a form of
glaucoma and Fuchs' corneal dystrophy.
retina organoid challenge competition
NEI is preparing to launch a $1.5 million challenge competition to
catalyze therapies for retinal diseases by developing retina organoids.
Organoids are 3D, self-assembling, mini-organs grown in a dish from
human stem cells. They can be used for disease modeling, drug
development, and therapeutic transplantation. On April 4, 2016, NEI
held a technical planning meeting of industry and academic experts to
review progress in organoid engineering of the retina and other organs,
and to help design challenge parameters. The Congress requested a
retina disease challenge in NEI's fiscal year 2016 Appropriations
Report. This competition dovetails with the AGI and will accelerate
retinal therapies since the human tissue-based models will aid in
developing and testing regenerative therapies for retinal neurons.
future directions
The audacious goal to regrow new neurons in the retina and restore
vision builds on a foundation of audacious science that is described
here. In the near terms, we will advance the understanding of
mechanisms that underlie eye disease. The mechanistic knowledge will
propel the drive for clinical applications that help fulfill the
promise of gene and cell therapies that benefit patients.
______
Prepared Statement of Martha J. Somerman, D.D.S., Ph.D., Director,
National Institute of Dental and Craniofacial Research
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the National
Institute of Dental and Craniofacial Research (NIDCR) of the National
Institutes of Health (NIH).
The mission of NIDCR is to improve dental, oral, and craniofacial
health through research, research training, and the dissemination of
health information. In keeping with this mission, NIDCR's research
spans multiple disciplines, scientific approaches, and research
directions. Today, I will highlight selected areas of NIDCR-supported
research that hold particular promise to improve oral health. These
include efforts to understand the role of the oral microbiome, develop
innovative tools and technologies, address emerging public health
challenges, and strategies to cultivate and sustain future oral health
researchers.
foundational discoveries
The community of bacteria and other microbes that live in our
mouths (the oral microbiome) not only has the potential to cause
disease, but also plays a critical role in maintaining our health.
Although we have learned much about the oral microbiome, one of the
most important unexplored questions is how health-promoting and
disease-causing bacterial communities are acquired at birth and how the
balance between the two is developed and maintained over time. To
answer this question, NIDCR-supported researchers are studying the oral
microbiomes of children from birth to adolescence to determine what
happens to bacterial communities during different stages of childhood.
Scientists are using genetic techniques as well as considering specific
environmental factors such as the delivery method at birth, the use of
antibiotics in the hospital, and whether the infant was fed breast milk
or formula. More knowledge about how individuals acquire their own
unique oral microbiome could result in new strategies to help keep our
mouths and bodies healthy.
We have made tremendous progress in developing new approaches to
catalogue the oral microbiome. However, understanding the types of
bacteria present isn't enough. We also need to understand how the
microbiome community in the mouth is organized and how its complex
structure helps to maintain health and contributes to disease. NIDCR-
funded scientists have developed a new imaging technique to visualize
the multiple layers of bacteria that live on each surface of the oral
cavity. They have observed that some microbial communities gather and
form distinctive three-dimensional structures on teeth that look like
spiny hedgehogs and cauliflowers. These structures create the
foundation upon which other bacteria attach and grow and eventually
become the plaque that causes dental caries (tooth decay) and
periodontal disease (an inflammation of the tissues supporting the
teeth). This new imaging technique will also be a valuable tool for
researchers exploring potential drug therapies to change the structure
of the microbial community and treat oral infections.
innovative tools and technologies
Early detection and diagnosis of oral cancer is essential for
successful treatment. Because most people are not diagnosed until after
a tumor has spread to other tissues, the survival rate for people with
oral cancer--especially for African American males--is among the lowest
for the major cancers. The current procedure for detecting oral cancer
starts with inspecting the oral cavity for suspicious lesions. If a
suspicious lesion is identified, a sample of the tissue is typically
removed (i.e., a biopsy) and sent to a lab to check for cancer cells.
To increase the likelihood that oral cancer will be detected earlier
and more accurately, NIDCR-supported researchers have developed a
handheld microscope to screen for oral cancer in the dental office.
Roughly the size of a pen, the microscope uses an innovative technology
called `dual-axis confocal microscopy' to make it easier to
discriminate between healthy and potentially cancerous tissue. Using
this tool, clinicians will be able to make more informed decisions
about whether or not to remove suspicious-looking lesions for
analysis--thus reducing the need for unnecessary invasive procedures.
This novel technology will help meet a critical need for more effective
tools to screen individuals at risk for oral cancer and could also be
used to detect the recurrence of cancer following treatment.
Mobile health, or mHealth, is an exciting technology that
encourages people to make healthy lifestyle changes. For example, many
of us wear wrist bands to count the number of steps we take every day
or we use mobile applications to keep records of what we eat and drink.
NIDCR-supported researchers are taking a lead in developing mHealth
tools to easily and accurately track oral health behaviors, such as
tooth brushing. In collaboration with engineers at Oral-B, NIDCR-
supported researchers have developed an electronic toothbrush with a
built-in sensor that collects precise data about tooth brushing
frequency and duration. By collecting real-time data, this mHealth
sensor is helping investigators bypass the need for research
participants to remember and accurately report their tooth brushing
habits. The objective data gained from this innovative device will
increase our understanding about actual tooth brushing behavior and
potentially lead to new approaches to increase motivation for improved
oral health behavior.
emerging public health concerns
After years of declining cigarette sales in the United States,
spurred in part by awareness of the adverse health effects of tobacco
use, a new form of nicotine delivery has emerged--the electronic
cigarette, commonly called the e-cigarette. The use of e-cigarettes is
increasing dramatically among young adults. In fact, according to the
Centers for Disease Control and Prevention, e-cigarette use by middle
and high school students in the United States tripled between 2013 and
2014. However, very little is known about the chemicals in the aerosol
mixtures released by e-cigarettes or the impact those chemicals might
have on health. NIDCR recently developed an initiative that funded a
number of grants to investigate the effects of e-cigarette chemicals on
oral health. A broad range of studies are being supported that include
human participants, as well as cell and animal model systems. This
research will offer valuable insights into the safety of e-cigarettes
and how they affect the oral microbiome, the immune system, and the
ability of damaged tissues in the oral cavity to heal.
Many people visit their dentist regularly, which puts dental
practitioners in a prime position to address public health issues.
Currently, one particularly pressing public health concern is
prescription opioid abuse. Because dentists prescribe opioids to treat
acute dental and oral pain following dental procedures, it is important
to understand the opioid prescribing practices of dentists. NIDCR
invests in a valuable resource for conducting these types of clinical
studies in real world settings, called the National Dental Practice-
Based Research Network (NDPBRN). The Network consists of more than
6,000 dental practitioners in the United States who see patients on a
regular basis and are interested in conducting research in their
practices. Dental practitioners will participate in a study to assess
dentists' knowledge of opioids and the decisionmaking processes and
behaviors related to opioid prescription. The findings from this NDPBRN
study will increase our understanding about how and why opioids are
prescribed by dentists in order to develop strategies to help halt
opioid abuse in the United States.
recognizing outstanding oral health researchers
NIDCR is proud to support three scientists who have been recognized
for their innovative research. Two of these scientists are recipients
of the Presidential Early Career Award for Scientists and Engineers
(PECASE), the highest honor bestowed by the Federal Government upon
outstanding scientists and engineers beginning their independent
careers. The success of NIDCR-funded scientists in receiving this award
is a testament to our commitment to support research training and
career development. The third scientist is a longtime NIDCR-supported
investigator who recently received recognition as part of the NIH
Common Fund's Gabriella Miller Kids First Research program. The program
is named for a brave girl who raised funds to support research on
childhood illnesses before she died of cancer at age ten. This
investigator is identifying the genetic basis for orofacial clefting
using DNA sequencing to identify common genes in a large cohort of
families. These honors recognize exceptional NIDCR researchers who are
striving to improve the lives of children like Gabriella Miller and the
oral health of all Americans.
______
Prepared Statement of Catherine Y. Spong, M.D., Acting 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 President's fiscal year 2017 budget request for the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD) of the National Institutes of Health (NIH).
Understanding human development, both normative and atypical, is at
the core of NICHD's mission. Unlike many of the other NIH Institutes
and Centers (ICs), NICHD takes a lifespan approach to its work,
supporting research that ranges from efforts to increase our
understanding of basic biological mechanisms to testing health
interventions aimed at improving the lives and health of children,
women, and families, including those with disabilities.
minimizing duplication, maximizing expertise
In this increasingly complex world, highly specific expertise may
be required to ensure that any preventive measures or development and
application of therapies will meet the needs of each affected
population. Because of the breadth of its mission, NICHD can provide a
lifecourse perspective and a depth of expertise to research efforts
related to pregnancy, infants, and the typical or atypical development
of children through young adulthood. This breadth also means that NICHD
works across scientific disciplines and often seeks or is tapped to
lead trans-NIH, collaborative efforts that bring together other ICs'
and non-NIH scientists' knowledge and skills so that the overall
efforts are additive, not duplicative.
Human Placenta Project.--NICHD is leading an initiative known as
the Human Placenta Project that will develop technologies to assess, in
real time, the structure and function of the human placenta. The least
understood human organ, the placenta has substantial implications for
the lifelong health of both mother and child, since so many health
issues can be traced back to the earliest stages of development. The
Project's goals include understanding normal and abnormal placental
development, developing biomarkers to predict adverse pregnancy
outcomes, examining the effects of environmental factors, and
developing interventions to prevent abnormal placental and fetal
development. Each year, NICHD brings together a group of broad thinkers
that includes subject matter experts in various technologies, placental
biologists, and clinicians to generate creative approaches to
developing and applying technologies in new, noninvasive ways to
understand placental function. The impact of the Human Placenta Project
extends beyond enhancing pregnancy to providing additional insights
into health and disease. New knowledge will increase our understanding
of tumor biology and transplant medicine as the placenta mimics tumor
growth and invasion early in gestation and mediates and promotes the
health of two genetically distinct entities.
PregSourceTM.--About 6.5 million pregnancies occur each
year in the United States, and yet we have relatively little scientific
information about what constitutes a normal pregnancy. In the coming
year, NICHD will launch ``PregSourceTM,'' a longitudinal, crowd-
sourced, citizen science approach that will gather information about
pregnancy from the experts--pregnant women. Through web-based
questionnaires or mobile apps, PregSourceTM will expand our knowledge
about what women experience physically and emotionally during pregnancy
and after giving birth, the effects of pregnancy on women's lives, the
special challenges some pregnant women face (such as health issues
related to disability or a chronic health condition), and what features
are common to many pregnancies. Ultimately, this information will help
to fill the large gap in knowledge about medications used by pregnant
women and other issues commonly experienced during pregnancy. In
return, PregSourceTM will provide participants with links to evidence-
based information about pregnancy from 20 trusted national partners,
including several NIH ICs and professional societies. Approved
researchers can view de-identified, amalgamated information that may
suggest fruitful research avenues about pregnancy. This innovative
approach to gathering information was based on the highly successful
DS-Connect: The Down Syndrome Registry, which was launched by NICHD
and its Down Syndrome Consortium partners in 2013. With more than 3,200
registrants across the United States, DS-Connect has facilitated
recruitment into clinical trials on several aspects of Down syndrome.
Birth Defects.--With other NIH ICs and the Common Fund of the NIH
Office of the Director, in fiscal year 2017 NICHD will continue to
provide leadership for extended basic and translational research
efforts related to birth defects. Structural or functional anomalies
affect about 3 percent of births and are the leading cause of infant
death in the United States. Through intramural and extramural programs,
NICHD supports collaborative teams of basic and clinical scientists
studying the developmental biology, epidemiology, and genetics of
structural birth defects. New fiscal year 2017 initiatives in
structural birth defects research will catalyze the development of new
research teams and support data analysis that uses and complements the
genomic sequencing data developed under the Gabriella Miller Kids First
Pediatric Research program, funded by Congress since fiscal year 2014.
Best Pharmaceuticals for Children.--Although progress has been made
in recent years, approximately three-quarters of all medicines marketed
still do not carry Food and Drug Administration (FDA) approved labeling
for use in neonates, infants, children, and adolescents. Although it is
widely recognized that children are not small adults, only five of the
80 drugs most frequently used in newborns and infants are labeled for
pediatric use. For many drugs, developmental, metabolic, and
pharmacokinetics-pharmacodynamic data are needed for their safe and
effective use in children, yet sometimes private pharmaceutical
companies are reluctant to incur the expense of gathering these data.
In the Best Pharmaceuticals for Children Act of 2002, which was
reauthorized in 2007 and 2012, the Congress charged NIH with setting
priorities and funding research on pediatric therapeutic needs, tapping
NICHD to lead this effort. Through an active trans-NIH Working Group,
NICHD has collaborated with other ICs to identify therapeutic gaps in
pediatric diseases, disorders, or conditions for which more complete
knowledge of drugs and biologics would benefit specific pediatric
populations, and develop future clinical trials. Using this approach,
and also consulting with pediatric experts from FDA, academia, and
industry, NICHD regularly publishes a prioritized list of drugs or
indications that require further investigations. Four additional drugs
commonly prescribed for children now have pediatric labeling, with
others pending approval at FDA. Most recently, NICHD staff met with FDA
pediatric leadership in December 2015 to discuss how to further improve
the process for getting drugs labeled for pediatric use.
Rehabilitation Research.--Although NIH was already supporting
multiple lines of research focused on medical rehabilitation for
physical, sensory, and cognitive disability across the lifespan, the
establishment of the National Center for Medical Rehabilitation
Research (NCMRR) by the Congress in 1990 provided a new focus on the
science of medical rehabilitation and how results could be used to meet
the challenges facing individuals with physical disabilities. A
component of NICHD, NCMRR leadership emphasizes the need for medical
rehabilitation across the lifespan, working across the various NIH ICs
that have relevant and complementary missions. NCMRR serves as the
focal point for the coordination and development of policies, plans,
initiatives, and objectives that further rehabilitation research,
convening the NIH Medical Rehabilitation Coordination Committee (MRCC)
on a monthly basis to coordinate ongoing research and training
activities. In addition, MRCC works with other agencies within the
Department of Health and Human Services, the Department of Veterans
Affairs, the Department of Defense, and the National Science Foundation
to develop collaborative projects that serve to enhance and encourage
rehabilitation science. A major conference on rehabilitation research
in May 2016 will bring together scientists from across the
rehabilitation research spectrum, which will serve to inform and
catalyze the research community through a new rehabilitation research
plan, expected in early fiscal year 2017.
Training Opportunities in Endocrinology.--NICHD's intramural
researchers also engage in regular collaborations with scientists from
other ICs. Together with the National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Institute of Dental and
Craniofacial Research, NICHD collaborates on the Inter-Institute
Endocrinology Training Program, an accredited program that provides a
comprehensive training experience for physicians who seek a broad
education in both research and clinical endocrinology. Led by world-
renowned experts in the field, trainees can learn how to manage a wide
variety of common and rare endocrine disorders. For example, the
program provides training in specialized diabetes clinics to teach how
to provide intensive insulin therapy in pediatric patients with severe
diabetes.
IDeA States Pediatric Clinical Trials Network.--Following the
closing of the National Children's Study in late 2014, passage of the
National Pediatric Research Network Act, and after extensive input from
the research and other stakeholder communities about pediatric research
priorities, NIH decided to augment its pediatric research efforts
through the creation of a new national pediatric network, the IDeA
States Pediatric Clinical Trials Network (ISPCTN). The new ISPCTN will
utilize the Institutional Development Awards (IDeA) Program, which was
authorized and funded by the Congress to broaden the geographic
distribution of NIH funding across the United States by enhancing the
ability to compete for funding of institutions located in States in
which the success rate for NIH grant applications historically has been
low. The goal of ISPCTN is to develop a pediatric research
infrastructure and build capacity at academic institutions in IDeA
States for pediatric clinical trials; increase access to clinical
trials for children (some of whom may have rare conditions) in rural
and medically underserved areas who are unable to travel long
distances; and allow researchers across the country who are conducting
pediatric clinical trials to recruit a greater diversity of pediatric
participants in a cost-effective manner. By creating teams of pediatric
clinical trial specialists in IDeA States throughout the country,
children who have never before had realistic access to cutting edge
research will have the opportunity to participate. In addition,
investigators conducting any IRB-approved, funded pediatric clinical
trial (not only those in the IDeA States) may work with the Data
Coordinating and Operations Center to recruit additional pediatric
participants from IDeA State sites for their trials; thus, trials on
rare conditions may be able to complete recruitment within a shorter
period of time, even though there might be a limited number of
individuals in any one geographic area. ISPCTN will be overseen by the
Program Director for the new Environmental influences on Child Health
Outcomes (ECHO) program in the NIH Office of the Director, and managed
by NICHD.
Zika Virus.--The rapid spread of the Zika virus across the Americas
has emerged as a potentially critical public health issue. Although the
virus was initially discovered in 1947, recent reports from Brazil
suggested a possible connection with an increase in severe birth
defects, including microcephaly, which sounded the alarm to the public
health community. NICHD is coordinating with and contributing to the
overall effort by providing expertise in developmental biology,
pregnancy, and preventive measures such as contraception. Efforts
include work to understand how the virus is transmitted and how best to
prevent it; the effects of the virus on the body, especially during
pregnancy and timing of the infection; the impact on the developing
fetus; new assays to test therapeutic candidates, and improved
diagnostics to rapidly identify the virus and distinguish it from
related viruses. Joined by six other NIH ICs, NICHD issued a rapid
funding opportunity announcement to stimulate research on Zika,
particularly on the seminal issue of whether the virus causes fetal
abnormalities and pregnancy complications (fetal loss, stillbirth,
microcephaly, ventriculomegaly, brain anomalies, and ocular
abnormalities). In addition, NICHD is coordinating with the National
Institute of Allergy and Infectious Diseases and sites in several
countries, including Brazil, to conduct a prospective longitudinal
study on Zika-related adverse pregnancy and infant outcomes. Since
evidence of a link between the Zika virus and microcephaly and other
abnormalities is now sufficiently strong, NICHD will again be called
upon to utilize its knowledge base on the long-term consequences of
physical and intellectual disabilities to help children and families
affected by the consequences of the disease.
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Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal
Deputy Director, Office of the Director
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's fiscal year 2017 budget request for the Office
of the Director (OD) of the National Institutes of Health (NIH).
The OD promotes and fosters NIH research and research training
efforts in the prevention and treatment of disease through the policy
oversight of both the extramural grant and contract award functions and
the Intramural Research program. The OD stimulates specific areas of
research to complement the ongoing efforts of NIH Institutes and
Centers (ICs) through the activities of several cross-cutting program
offices. The OD develops policies in response to emerging scientific
opportunities employing ethical and legal considerations; coordinates
the communication of health information to the public and scientific
communities; provides oversight and management of peer review policies;
and coordinates information technology across NIH. The OD also provides
the core administrative and management services, such as budget and
financial management, personnel, property, and procurement services,
ethics oversight, and the administration of equal employment policies
and practices. The fiscal year 2017 budget request also will support
activities managed by the OD's operational offices. The OD Operations
is comprised of several OD Offices that provide advice to the NIH
Director, policy direction and oversight to the NIH research community,
and administer centralized support services essential to the NIH
mission.
The functions and initiatives of the OD's research offices, also
known as Program, Projects, and Activities, are described in detail as
follows:
division of program coordination, planning, and strategic initiatives
DPCPSI (Division of Program Coordination, Planning, and Strategic
Initiatives) provides leadership for identifying, reporting, and
funding trans-NIH research that represents important areas of emerging
scientific opportunities, rising public health challenges, or knowledge
gaps that merit further research and would benefit from collaboration
between two or more ICs, or from strategic coordination and planning.
DPCPSI includes major programmatic offices that coordinate and
support research and activities related to HIV/AIDS, women's health,
behavioral and social sciences, disease prevention, dietary
supplements, research infrastructure, and science education. DPCPSI
serves as a resource for ICs and OD for portfolio analysis by
developing, using, and disseminating data-driven approaches and
computational tools. DPCPSI serves as the focal point for coordinating
research to advance the health and wellbeing of sexual and gender
minorities and for American Indians and Alaska Natives, and
coordinating tribal consultation activities for the NIH.
office of research infrastructure programs
ORIP (Office of Research Infrastructure Programs ) provides support
for research into model systems of human diseases and a variety of
research infrastructure needs. ORIP supports a number of repositories
of animal models, biological materials, genetic information, and human
biospecimens. ORIP also makes grant awards to fund the purchase of
expensive state-of-the-art scientific instruments and to modernize
animal research facilities. ORIP supports training and career
development for veterinarians engaged in biomedical research, and the
diversity of the future biomedical workforce by investing in pre-
kindergarten to grade 12 and museum-based science education programs.
Science Education Partnership Awards
The goal of the Science Education Partnership Awards (SEPA) program
is to invest in educational activities that enhance the early training
of a workforce to meet the Nation's biomedical, behavioral, and
clinical research needs. The SEPA program encourages the development of
innovative educational activities for pre-kindergarten to grade 12 (P-
12), teachers and students from underserved communities with a focus on
Courses for Skills Development, Research Experiences, Mentoring
Activities, Curriculum or Methods Development or Informal Science
Education (ISE) exhibits, and Outreach activities. The SEPA program
will be coordinated with the Department of Education to ensure that
program activities are aligned with ongoing P-12 reform efforts
included in the fiscal year 2017 President's Budget request.
office of aids research
OAR (Office of Aids Research) plays a unique role at NIH by serving
as a model of trans-NIH planning and management, vested with primary
responsibility for overseeing all NIH AIDS-related research. 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.
Office of Behavioral and Social Sciences Research
OBSSR (Office of Behavioral and Social Sciences Research ) furthers
the mission of NIH by emphasizing the critical role that behavioral and
social factors play in health, healthcare, and well-being. OBSSR serves
as a liaison between NIH and the extramural research communities, other
Federal agencies, academic and scientific societies, national voluntary
health agencies, the media, and the general public on matters
pertaining to behavioral and social sciences research. OBSSR's vision
is to bring together the biomedical, behavioral, and social science
communities to work more collaboratively to solve the pressing health
challenges facing our Nation. OBSSR also coordinates and helps support
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.
office of research on women's health
Since its creation in 1990, ORWH (Office of Research on Women's
Health) has worked to ensure the inclusion of women in NIH clinical
research, advance and expand women's health research, and promote
advancement of women in biomedical careers. ORWH is the focal point for
NIH women's health research and works in partnership with ICs to
incorporate a women's health and sex differences research perspective
into the NIH scientific framework. ORWH activities are guided by the
2010 NIH Strategic Plan for Women's Health Research. This strategic
plan outlines six goals to maximize impact of NIH research effort. The
NIH strategic plan for women's health and sex differences research
serves as a framework for interdisciplinary scientific approaches.
office of disease prevention
ODP (Office of Disease Prevention) is responsible for assessing,
facilitating, and stimulating research in disease prevention and health
promotion, and disseminating the results of this research to improve
public health. Research on disease prevention is an important part of
the NIH mission because the knowledge gained from this research leads
to stronger clinical practice, health policy, and community health
programs. In early fiscal year 2014, ODP released its first strategic
plan. This plan outlines the priorities that ODP will focus on over the
next 5 years and highlights ODP's role in advancing prevention research
at NIH. The Office of Dietary Supplements (ODS) is within the ODP
organizational structure. The mission of ODS is to strengthen knowledge
and understanding of dietary supplements by evaluating scientific
information, stimulating and supporting research, disseminating
research results, and educating the public to foster an enhanced
quality of life and health for the U.S. population.
office of strategic coordination and the common fund
OSC (Office of Strategic Coordination) manages the Common Fund
(CF), working with trans-NIH teams for each of the more than 30 CF
programs. These teams ensure that each program meets the criteria of CF
programs to synergize with IC-funded research. CF was created by the
2006 NIH Reform Act, which codified the approach of the NIH Roadmap for
Medical Research to support cross-cutting, trans-NIH programs that
require participation by at least two ICs or would otherwise benefit
from strategic planning and coordination. CF programs tackle major
challenges in biomedical research that affect many diseases or
conditions or that broadly relate to human health. CF provides limited-
term funding for goal-driven, coordinated research networks to generate
data, solve technological problems, and/or pilot resources and tools
that will stimulate the broader research community.
intramural loan repayment and scholarship programs
The mission of ILRSP (Intramural Loan Repayment and Scholarship
Programs) is to develop and manage programs that 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 NIH. There are two education programs
offered: the Intramural Loan Repayment Program (ILRP) and the NIH
Undergraduate Scholarship Program (UGSP).
ILRP repays outstanding eligible educational debt for NIH Full-Time
Equivalent employee postgraduates, and in return, participants must
enter into a contractual agreement to conduct qualified research in the
three statutorily governed targeted ILRPs: (1) the AIDS Research ILRP;
(2) the Clinical Research ILRP for Individuals from Disadvantaged
Backgrounds; and (3) the General Research ILRP.
UGSP offers competitive scholarships to exceptional undergraduate
college students from financially disadvantaged backgrounds. Awardees
must be committed to biomedical, social or behavioral science health-
related research career paths available at NIH. Award recipients also
are obligated to work as employees of the NIH Intramural Research
Program in exchange for each year or partial year of scholarship
funding.
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Prepared Statement of Daniel G. Wheeland, Director, Office of Research
Facilities and Development Operations, Office of the Director
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2017 budget request for the Buildings and
Facilities (B&F) appropriation of the National Institutes of Health
(NIH).
criticality of facilities to the research mission
NIH strives to strike a balance between the infrastructure needs of
tomorrow's research to address a broad spectrum of emerging health
threats and the need for responsible stewardship of our real property
assets supporting the research enterprise. State-of-the art facilities
for scientific research and research support facilities are critical to
the continuing vitality of basic, translational, and clinical research.
The B&F program supports the design, construction, repair, and
improvements of the NIH's portfolio of laboratory, clinical, animal,
administrative, and support facilities at its six campuses in four
States. These facilities house NIH researchers conducting intramural,
basic, translational, and clinical research programs, science
administrators who oversee NIH grant and research contract programs,
the NIH leadership, and various programs that support NIH's operations.
The fiscal year 2017 B&F budget request focuses on the need for
responsible use and stewardship of NIH's past and recent investments in
the ``bricks and mortar'' of the research enterprise. In addition, this
budget seeks to minimize the growing backlog of maintenance and repairs
required to sustain the condition of existing facilities to prevent
further deterioration and, over time, further decreases to the
Condition Index of our existing facilities. To stay abreast of the
changing needs of the NIH programs, it is imperative that we provide
reliable, safe, and secure research support facilities that are
appropriately equipped, operated, and maintained.
The B&F budget request is the product of a comprehensive, corporate
capital facilities planning process. It begins with extensive
consultation across the research community by professional facilities
staff, which results in identifying the most critical NIH facility
needs. We analyze, prioritize, and submit these facility needs to the
Facilities Working Group, an advisory committee to the NIH Steering
Committee, and the HHS Capital Investment Review Board. Through this
process, NIH prioritizes its facilities investments in order to assure
safe, reliable, energy efficient and maintainable facilities to support
current and emerging biomedical research.
The fiscal year 2017 B&F budget request provides funds for specific
repair and improvements projects that resulted from the aforementioned
NIH facilities planning process.