[Senate Hearing 112-]
[From the U.S. Government Publishing Office]


 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2013 

                              ----------                              


                       WEDNESDAY, MARCH 28, 2012

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Pryor, Mikulski, Brown, Shelby, 
Cochran, and Moran.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        GRIFFIN P. RODGERS, M.D., M.A.C.P., DIRECTOR, NATIONAL 
            INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
        HAROLD VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
        RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        THOMAS R. INSEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL 
            HEALTH, ACTING DIRECTOR, NATIONAL CENTER FOR ADVANCING 
            TRANSLATIONAL SCIENCES


                opening statement of senator tom harkin


    Senator Harkin. The Senate Appropriations Subcommittee on 
Labor, Health and Human Services, Education, and Related 
Agencies will come to order.
    Dr. Collins, welcome back to the subcommittee. Welcome 
also, Dr. Harold Varmus, Director of the National Cancer 
Institute (NCI); Dr. Tony Fauci, Director of the National 
Institute of Allergy and Infectious Diseases (NIAID); Dr. 
Griffin Rodgers, Director of the National Institute of Diabetes 
and Digestive and Kidney Diseases (NIDDK); Dr. Richard Hodes--
again, good to see you again--Director of the National 
Institute on Aging (NIA); and Dr. Thomas Insel, both the 
Director of the National Institute of Mental Health and the 
Acting Director now of the new National Center for Advancing 
Translational Sciences (NCATS).
    Again, my personal and professional thanks to all of you 
and the hundreds of thousands of people who are supported by 
National Institutes of Health (NIH) funding. Because of all of 
you, America is the world leader in biomedical research.
    But how long America can maintain that status is a matter 
of growing concern. The threat of sequestration looms large. 
The Congressional Budget Office (CBO) has estimated that most 
nondefense discretionary programs, such as NIH, will be cut by 
about 7.8 percent next January if the Congress does not enact a 
plan before that time.
    The budget plan proposed by the House Budget Committee 
chairman, which the House will vote on this week, is even more 
worrisome. In fiscal year 2013, the Ryan plan would cut 
nondefense spending by 5 percent. The following year, the plan 
will cut nondefense spending by 19 percent.
    If that cut were applied equally across the Government, the 
number of new NIH grants for promising research projects would 
shrink by more than 1,600 in 2014 and by more than 16,000 
during the next decade. That means 16,000 fewer opportunities 
to gain insights and possibly find cures for cancer and 
Alzheimer's and diabetes, and any number of other diseases.
    Such a cut would be devastating not only for medical 
research but also for our economy. A study released last week 
by United for Medical Research concluded that, in 2011, NIH 
funding supported more than 430,000 jobs across the country. 
The link for this report follows: http://
www.unitedformedicalresearch.com/wp-content/uploads/2012/07/
NIHs-Role-in-Sustaining-the-US-Economy-2011.pdf.
    Again, it always amazes me how most people think that all 
of that money goes to Bethesda, Maryland, and that is not so. 
Most is awarded to researchers at academic institutions all 
across the United States.
    This same research also found that NIH research generated 
$62 billion in new economic activity last year. So now imagine 
cutting NIH funding by 19 percent in 2014.
    Again, a classic case of pennywise and pound-foolish 
thinking, especially when China, India, and Europe are spending 
more, not less, on medical research.
    But even under the best-case scenario, the budget for NIH 
is likely to remain tight for the immediate future, so we must 
do everything we can to ensure that NIH makes the most 
effective use of the money that is available.
    That was part of the thinking behind the new NCATS, which 
this subcommittee created in last year's appropriations bill.
    NCATS brings together, under one roof, translational 
activities that were already being funded but scattered 
throughout the NIH. For virtually no additional money, NIH now 
has an opportunity to address translational sciences in ways 
that we've never done before.
    So, I look forward to hearing more about NCATS and other 
topics from our witnesses. And again, I just thank all of you 
for your great leadership of one of the great institutions of 
this country, the NIH.
    And with that, I will yield to Senator Shelby for his 
opening statement.


                 statement of senator richard c. shelby


    Senator Shelby. Thank you, Mr. Chairman.
    I want to thank, at this time, Dr. Collins and the Center 
Directors who've joined us today to discuss the important role 
the NIH plays in every American's life.
    For the millions of Americans suffering from a serious 
illness, biomedical research is the beginning of hope. NIH-
funded research investigates ways to prevent disease, 
understand its causes, and develop more effective treatments.
    A continued commitment to NIH is essential to addressing 
our Nation's growing health concerns and to spur medical 
innovation for the next generation of treatment and cures.
    Unfortunately, the NIH budget request for the year 2013 
abandons that commitment. The proposed budget for NIH is $30.86 
billion, which is claimed to be level funding from fiscal year 
2012. However, this amount does not take into account the 
additional funding the Department of Health and Human Services 
(HHS) requested for Departmentwide evaluation activities.
    If this so-called evaluation tap is agreed to, it will 
reduce the NIH budget by $215 million, bringing the budget 
request below the 2012 level.
    Further, the administration's request does not keep pace 
with biomedical research inflation, and as a result, in 
inflationary adjusted dollars, the NIH is 17 percent--that's 
right, 17 percent--below where they were 10 years ago.
    Without sustained support for the NIH, the translation of 
discoveries from bench to bedside will be dramatically slowed, 
and the United States will surrender its role as a world leader 
in scientific research.
    I do not agree with the funding level proposed by the 
administration for the NIH. I believe that the NIH funding 
should be a priority and that its benefits extend well beyond 
its research discoveries.
    In 2011, NIH research funding supported 432,000 jobs 
nationwide. The research carried out by the NIH in this network 
of 325,000 researchers at 3,000 institutions across the country 
serves this Nation with the goal of improving human health.
    However, Dr. Collins, I understand that your request 
attempts to live within the confines of a difficult budget 
environment. That said, I'm concerned about several of the 
proposed changes to awarding grant funding.
    For example, you proposed capping the grant amount that a 
principle investigator can receive at $1.5 million. This 
proposal discourages success by limiting awards to some of the 
most successful scientists who accordingly receive the most 
grant funding.
    NIH awards grants through a highly competitive, two-tiered, 
independent, peer-review process that ensures support of the 
most promising science and the most productive scientists. By 
limiting grant award amounts, you're changing the system from 
one that grants awards based on science, merit, and good ideas, 
to one based on whether an investigator has previously received 
a grant.
    I'm also troubled with the proposals to cap inflationary 
cost and reduce the average award of competing research project 
grants below the fiscal year 2012 level. While I recognize that 
you're trying to keep your success rate high and fund as many 
grants as possible, I question whether this is the right 
approach. We do not want the only results of this change to be 
scientists spending more time chasing grants than making 
discoveries, and I don't believe you do either.
    I understand that constrained budgets lead to tough 
decisions. However, it is critical that the NIH not lose sight 
of its goal to fund the best science in the hope of reducing 
the burden of illness.
    A fundamental part of the NIH success over the years has 
been that scientific need and opportunity have always dictated 
NIH funding priorities.
    Dr. Collins, I would caution you on opening the door to 
targeting particular diseases for funding as proposed in the 
fiscal year 2013 budget. The last thing I imagine you want is 
the President deciding what specific diseases deserve NIH 
research.
    Finally, as we continue to operate in a tough budget 
environment, I think we need more out-of-the-box thinking to 
stimulate the research community in imaginative ways. In 
particular, I want to highlight such an approach at the NCI.
    Dr. Varmus has started a new program to answer the 
provocative questions in cancer research. This project focuses 
scientists on 24 unanswered, perhaps nonobvious, questions as 
defined by the research community.
    With more than 750 research teams submitting proposals, 
this project shows there are innovative ways to energize the 
research community, even when budgets are constrained.
    And as the Congress faces unprecedented challenges to 
reduce Government spending, we must all face the consequences 
of tough choices. Certainly, these are difficult times, but I 
believe biomedical research is a necessary and worthy 
investment in the health of our people and the vitality of our 
communities.


                          prepared statements


    Funding for the NIH lays the foundation for drug and device 
discoveries over the next 10 years. Biomedical research is an 
answer to lowering, I believe, our Nation's healthcare costs. 
This is not the time to abandon our commitment to the health of 
all Americans and to the NIH.
            Prepared Statement of Senator Richard C. Shelby
    Thank you, Mr. Chairman. I want to thank Dr. Collins and the Center 
Directors who joined us today to discuss the important role the 
National Institutes of Health (NIH) plays in every American's life.
    For the millions of Americans suffering from a serious illness, 
biomedical research is the beginning of hope. NIH-funded research 
investigates ways to prevent disease, understand its causes, and 
develop more effective treatments.
    A continued commitment to NIH is essential to address our Nation's 
growing health concerns and to spur medical innovation for the next 
generation of treatments and cures. Unfortunately, the NIH budget 
request for fiscal year 2013 abandons that commitment.
    The proposed budget for NIH is $30.86 billion, which is claimed to 
be level funding from fiscal year 2012. However, this amount does not 
take into account the additional funding the Department of Health and 
Human Services requested for Departmentwide evaluation activities.
    If this so-called ``evaluation tap'' is agreed to, it will reduce 
the NIH budget by $215 million, bringing the budget request below the 
fiscal year 2012 level.
    Further, the administration's request does not keep pace with 
biomedical research inflation. As a result, in inflationary adjusted 
dollars, the NIH is 17 percent less than where they were 10 years ago. 
Without sustained support for the NIH, the translation of discoveries 
from ``bench to bedside'' will be dramatically slowed and the United 
States will surrender its role as the world leader in scientific 
research.
    I do not agree with the funding level proposed by the 
administration for the NIH. I believe that NIH funding should be a 
priority and that its benefits extend well beyond its research 
discoveries.
    In 2011, NIH research funding supported 432,092 jobs Nationwide. 
Research carried out by the NIH and its network of 325,000 researchers 
at 3,000 institutions across the country serves the Nation with the 
goal of improving human health.
    However, Dr. Collins, I understand that your request attempts to 
live within the confines of the difficult budget environment.
    That said, I am concerned about several of the proposed changes to 
awarding grant funding.
    For example, you propose capping the grant amount that a principle 
investigator can receive at $1.5 million. This proposal discourages 
success by limiting awards to some of the most successful scientists 
who, accordingly, receive the most grant funding.
    NIH awards grants through a highly competitive, two-tiered 
independent peer-review process that ensures support of the most 
promising science and the most productive scientists.
    By limiting grant award amounts, you are changing the system from 
one that grants awards based on science, merit, and good ideas to one 
based on whether an investigator has previously received a grant.
    I am also troubled with the proposals to cap inflationary costs and 
reduce the average award of competing research project grants below the 
fiscal year 2012 level. While I recognize that you are trying to keep 
the success rate high and fund as many grants as possible, I question 
whether this is the right approach. We do not want the only result of 
this change to be scientists spending more time chasing grants than 
making discoveries.
    I understand that constrained budgets lead to tough decisions. 
However, it is critical that the NIH not lose sight of its goal to fund 
the best science in the hope of reducing the burden of illness.
    A fundamental part of the NIH's success over the years has been 
that scientific need and opportunity have always dictated NIH funding 
priorities. Dr. Collins, I caution you on opening the door to targeting 
particular diseases for funding as proposed in the fiscal year 2013 
budget. The last thing I imagine you want is the President deciding 
what specific diseases deserve NIH research dollars.
    Finally, as we continue to operate in a tough budget environment, I 
think we need more out-of-the-box thinking to stimulate the research 
community in imaginative ways. In particular, I want to highlight such 
an approach at the National Cancer Institute.
    Dr. Varmus has started a new program to answer the ``provocative 
questions'' in cancer research. This project focuses scientists on 24 
unanswered, perhaps nonobvious, questions as defined by the research 
community. With more than 750 research teams submitting proposals, this 
project shows that there are innovative ways to energize the research 
community, even when budgets are constrained.
    As the Congress faces unprecedented challenges to reduce government 
spending, we must all face the consequences of tough choices.
    Certainly these are difficult times, but I believe biomedical 
research is a necessary and worthy investment in the health of our 
people and the vitality of our communities.
    Funding for the NIH lays the foundation for drug and device 
discoveries over the next decade. Biomedical research is the answer to 
lowering our Nation's healthcare costs. This is not the time to abandon 
our commitment to the health of all Americans and the NIH.

    Senator Shelby. Thank you, Mr. Chairman.
    Senator Harkin. Thank you very much, Senator Shelby.
    Senator Inouye regrets that the could not be present but 
has a statement to be included in the record.
    [The statement follows:]
             Prepared Statement of Senator Daniel K. Inouye
    Mr. Chairman, thank you for chairing this hearing to review the 
President's fiscal year 2013 budget for the National Institutes of 
Health.
    Mahalo (thank you), Dr. Collins, for joining us today. In this 
challenging fiscal environment, I will do my best to support the 
continued progress of science and U.S. competitiveness.

    Senator Harkin. Now we'll turn to Dr. Francis Collins, the 
16th Director of the National Institutes of Health, a 
physician-geneticist noted for discoveries of disease genes 
and, of course, his leadership of the Human Genome Project.
    Prior to becoming Director, he served as a Director of the 
National Human Genome Research Institute (NHGRI) at NIH.
    Dr. Collins received his B.S. from the University of 
Virginia; M.D. from University of North Carolina at Chapel 
Hill; and Ph.D. from Yale University.
    Dr. Collins, you're no stranger to this subcommittee. We 
welcome all of you here. Your statement of course, as usual, 
will be made part of the record in its entirety.
    And I ask you to please proceed as you so desire. I won't 
put any clock time on it, so take whatever time you desire. If 
it starts going more than 10 minutes, however, we will get a 
little nervous, okay?
    Welcome back. Please proceed.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Thank you and good morning, Mr. Chairman and 
members of the subcommittee. I'm pleased to be here with my 
colleagues to present the President's budget request for the 
NIH for fiscal year 2013.
    And I must begin by thanking you, Mr. Chairman, and the 
subcommittee members, for the ultimate fiscal year 2012 
appropriation, which maintained NIH's budget at the fiscal year 
2011 level. And we're also very grateful for your leadership in 
creating the new National Center for Advancing Translational 
Sciences (NCATS).
    I do want to express my concern, since we're here in front 
of the subcommittee, about the health of Senator Kirk, and 
convey best wishes for a speedy recovery from all of us in the 
NIH community.
    In the next few minutes, I want to offer some details 
associated with our budget request, to discuss the health and 
economic benefits of biomedical research, as you have done in 
your opening statements, and talk about the promise that lies 
at the intersection of the life sciences and technology.
    As you can see here, and I'm going to show you some 
visuals, the President's fiscal year 2013 budget request for 
NIH is $30.86 billion, the same overall program level as in 
fiscal year 2012. This proposed appropriation will enable us to 
invest in areas with extraordinary promise for medical science.
    We will also use these resources wisely to encourage a 
vigorous workforce prepared to tackle major scientific and 
health challenges.
    As in the past, we will continue to support a wide array of 
research mechanisms, from investigator-initiated research to 
larger and more complex team and center efforts.
    In fiscal year 2013, NIH expects to support an estimated 
9,415 new and competing Research Project Grants (RPGs). That's 
an increase of 672 more than the estimate for fiscal year 2012, 
with an average cost of about $431,000. For fiscal year 2013, 
total RPGs are expected to number around 35,888.
    And also, to nurture early career scientists, we will 
continue our efforts to ensure that the success rates for 
investigators submitting new applications are the same, whether 
the applicant is first-time or more experienced.
    To maximize funding for investigator-initiated grants and 
to continue our support of first-time researchers, we've had to 
make some tough choices.
    For example, we propose to reduce budgets for noncompeting 
RPGs by 1 percent from the fiscal year 2012 level and to 
restrain growth in the average size of new awards. In addition, 
we will no longer assume out-year inflationary increases for 
new and continuing grants.
    Other highlights of the fiscal year 2013 request include a 
$40 million ramp up of the Cures Acceleration Network (CAN) and 
additional support for Alzheimer's disease research, $80 
million coming as part of an HHS-wide initiative.
    NIH-funded research has prevented untold human suffering by 
enabling Americans to live longer, healthier, and more 
productive lives, and let me mention a few examples.
    Life expectancy: A child born today can look forward to an 
average lifespan of almost 79 years. That's nearly three 
decades longer than one born in 1900.
    Cardiovascular disease: During the last half-century, our 
Nation's death rates for heart disease and stroke have fallen 
by 70 percent.
    Infant mortality: We've achieved an impressive 40-percent 
reduction in this vital area over the last two decades.
    In cancer, the just released 2012 annual report to the 
Nation on the status of cancer shows a continuing decline in 
death rates for most cancers, along with a drop in the overall 
rate of new cancer diagnoses.
    And today's biomedical research holds much, much more 
promise. For example, I want to show you this picture of a 
recent publication of research on Alzheimer's disease, and this 
represents a new opportunity in translational research through 
what we would call drug repurposing.
    Recently, a team of researchers, some supported by NIH, 
found that a drug called bexarotene, a drug originally 
developed for treating a type of skin cancer, can clear beta-
amyloid, as you see in the before and after picture, in mouse 
models of Alzheimer's disease in just 72 hours.
    In people with Alzheimer's, beta-amyloid accumulates in the 
brain like this, eventually leading to the death of neurons. 
Hope for bexarotene has gone particularly high because it has 
already been studied in humans, providing a wealth of 
information about dose and toxicity, and providing the 
opportunity to initiate clinical trials.
    And that's not all. Here's a list, Senator and members of 
the subcommittee, of just a few of the many recent examples of 
progress in biomedical research, scrolling by here. I wish I 
could tell you the details of each one, but this opening 
statement would then go on for most of the day.
    I would like, however, to talk something about the U.S. 
economy, as you have touched on, both of you, in your opening 
statements.
    As our Nation struggles to recover from a difficult period, 
it's worth pointing out that Government investments in 
biomedical research are a terrific way to spur economic growth. 
A recent analysis estimated that every $1 of NIH support 
returns $2.21 in goods and services to the local economy in 
just 1 year. And on average, every NIH grant creates seven 
high-quality jobs.
    Furthermore, NIH serves as the foundation for the entire 
U.S. medical innovation sector, a sector that employs 1.42 
million directly and supports an additional 6.6 million jobs in 
the United States, resulting in a total employment impact of 
more than 8 million jobs, generating $84 billion in wages and 
salaries, and exporting $90 billion in goods and services.
    Already referred to, the latest figures from the United for 
Medical Research report paint a similar picture. According to 
their update, NIH recently, directly and indirectly, supported 
more than 432,000 American jobs, spurring more than $62 billion 
in economic activity.
    And here's another thing to consider: NIH funding is the 
foundation for long-term U.S. global competitiveness in 
industries such as biotech, drug development, and medical 
devices. Around the world, many nations are following America's 
success story and ramping up their investments in the life 
sciences.
    Global research and development (R&D) spending across the 
world is expected to grow by about 5.2 percent to more than 
$1.4 trillion in 2012. India has posted double-digit percentage 
increases in R&D for several years. Europe plans to increase 
research spending by 40 percent over the next 7 years. China 
has just announced that it will increase its investment in 
basic research by 26 percent in 2012. And Vladimir Putin has 
voiced his intention to increase support for research in Russia 
by 65 percent during the next 5 years.
    Let me now turn to a few areas that are driving medical 
research. No less a futurist than Steve Jobs once predicted, 
``I think the biggest innovations of the 21st century will be 
the intersection of biology and technology.'' And he was spot 
on.
    One striking example is the cost of sequencing a human 
genome. Eleven years ago, it cost $100 million. Five years ago, 
$10 million. Today, less than $8,000 and heading down.
    Within the next year or two, in fact, a couple of U.S. 
companies plan to sell machines that can sequence a genome in a 
single day for $1,000 or less, using devices like the one I'm 
holding up here, the size of a postage stamp. That's a 
sequencing machine. It used to be as big as a phone booth or 
bigger. This is a new model.
    This will revolutionize how doctors diagnose and treat 
diseases and will allow researchers to pursue previously 
unimaginable scientific questions.
    So this kind of advance in technology empowers both basic 
and applied research, and NIH is a leading supporter of basic 
biomedical research in the world.
    Slightly more than one-half of NIH's budget is being 
invested to support this kind of fundamental research. In our 
view, there is no competition between basic and applied 
research. They're synergistic. And our support of basic 
research makes possible a wide range of new biological 
discoveries.
    Take the example of induced pluripotent stem cells, stem 
cells derived from patients' own skill cells. This technology 
is now being used to develop exciting new models of disease, 
so-called ``diseases in a dish,'' that are expanding our 
understanding of human biology, as well as opening the door to 
new treatment possibilities.
    But let's be honest. There's much work yet to be done. 
Despite phenomenal progress in basic science, we still lack 
effective treatments for far too many diseases.
    And the translational pipeline is long; 14 years on the 
average. And it's terribly leaky.
    A recent article in the Journal Nature Reviews Drug 
Discovery found that despite huge R&D investments, the number 
of new drugs approved per $1 billion, as you see here, has 
fallen steadily since 1950. Bottlenecks continue to vex this 
process, resulting in long development times, high failure 
rates, and steep costs.
    We need to re-engineer this pipeline, and that's why our 
new center, NCATS, is already working with industry to develop 
innovative ways to speed the flow of new therapies to patients.
    Mr. Chairman, I've described the administration's fiscal 
year 2013 request for NIH, the health and economic benefits of 
biomedical research, and the synergy between basic and 
translational research at NIH that's made possible by today's 
technological advances. But I'd like to close with a story that 
ties these points together.
    As toddlers, the twins Alexis and Noah Beery were diagnosed 
with a rare and devastating movement disorder called dystonia. 
Although they initially responded to standard treatment, their 
symptoms reappeared and worsened.
    Noah developed severe tremors in his hands. And Alexis 
encountered even greater difficulties. As you can see in this 
heartbreaking video clip, she began falling frequently and had 
frightening episodes where she could not breathe.
    Desperate for answers, doctors at Baylor College of 
Medicine sequenced the twins' genomes. The result was the 
discovery of a never-before described genetic mutation 
affecting neurotransmitters in the brain. After being put on a 
new treatment regimen tailored to their unique genetic profile, 
the twins' symptoms began to improve within just 2 weeks.
    In fact, Alexis' breathing is so much better today that she 
has joined the school's track team.
    Tonight in a NOVA special on advances in genetic medicine, 
PBS viewers will be able to witness the twins' progress. And 
here's a sneak peak. That's Noah and Alexis, healthy, happy, 
and enjoying themselves on a trampoline.

                          PREPARED STATEMENTS

    While this study centers on teens with a rare disease, the 
outcome carries a message of hope for all of us. It points 
directly to the promise that NIH research offers the patients 
of today and tomorrow.
    So thank you for this opportunity, Mr. Chairman and members 
of the subcommittee. And my colleagues and I will be glad to 
answer your questions.
    [The statements follow:]
         Prepared Statement of Francis S. Collins, M.D., Ph.D.
                national institutes of health's mission
    Good morning, Mr. Chairman and distinguished members of the 
subcommittee. I am Francis S. Collins, M.D., Ph.D., and I am the 
Director of the National Institutes of Health (NIH). I have with me 
Anthony S. Fauci, M.D., Director of the National Institute of Allergy 
and Infectious Disease (NIAID); Richard J. Hodes, M.D., Director of the 
National Institute on Aging (NIA); Thomas R. Insel, M.D., Director of 
the National Institute of Mental Health (NIMH), and the Acting Director 
of the new National Center for Advancing Translational Sciences 
(NCATS); Griffin P. Rodgers, M.D., Director of the National Institute 
of Diabetes and Digestive and Kidney Diseases (NIDDK); and Harold E. 
Varmus, M.D., Director of the National Cancer Institute (NCI).
    It is a great honor to appear before you today to present the 
administration's fiscal year 2013 budget request for the NIH.
    First, I would like to thank each of you for your continued support 
of NIH's mission to seek fundamental knowledge about the nature of 
living systems and to apply it in ways that enhance human health, 
lengthen life, and reduce suffering from illness and disability. In 
particular, I want to thank the subcommittee for your support during 
the fiscal year 2012 appropriations process, for the ultimate 
appropriation of $30.62 billion for NIH, and for the provisions that 
established NCATS.
    As the largest supporter of biomedical research in the world, NIH 
has been a driving force behind decades of advances that have improved 
the health of people across the United States and around the world.
    NIH basic research and translational advances have prompted a 
revolution in the diagnosis, treatment, and prevention of disease. 
Biomedical research funded by NIH has prevented immeasurable human 
suffering and has yielded economic benefits as well, thanks to U.S. 
citizens living longer, healthier, and more productive lives. These 
benefits include:
  --nearly 70-percent reduction in the death rate for coronary disease 
        and stroke in the last half century;
  --effective interventions for HIV/AIDS prevention and treatment, such 
        that an AIDS-free generation may be within our grasp;
  --nearly 30-percent decline during the last three decades in the age-
        standardized prevalence of chronic disability among American 
        seniors;
  --40-percent decline in infant mortality during 20 years and better 
        treatments for premature and low-weight births that result in 
        increased infant survival, the prevention of cerebral palsy, 
        and better developmental outcomes; and
  --more than 150 U.S. Food and Drug Administration (FDA)-approved 
        drugs and vaccines, or new uses of existing drugs.\1\
---------------------------------------------------------------------------
    \1\ Stevens, A.J., et al., The Role of Public-Sector Research in 
the Discovery of Drugs and Vaccines. N. Engl. J. Med., 364: 535-41, 
2011.
---------------------------------------------------------------------------
    The administration's fiscal year 2013 budget request for NIH is 
$30.86 billion, which is the same overall program level as fiscal year 
2012. This proposed appropriation will enable us to spark innovation 
and invest in areas of extraordinary promise for medical science. We 
will also invest these resources wisely to encourage a vigorous 
workforce that is prepared to tackle major scientific and health 
challenges.
    Within the administration's fiscal year 2013 budget, we will 
continue to protect and increase Research Project Grants (RPGs), NIH's 
fundamental funding mechanism for investigator-initiated research. NIH 
expects to support an estimated 9,415 new and competing RPGs in fiscal 
year 2013, an increase of 672 more than the estimate for fiscal year 
2012, with an average cost of about $431,000. For fiscal year 2013, 
total RPGs are expected to number around 35,888.
    To maximize funding for investigator-initiated grants, and to 
continue our support of first-time researchers, we propose to reduce 
budgets for noncompeting RPGs by 1 percent from the fiscal year 2012 
level and to restrain growth in the average size of new awards. We will 
also no longer assume out-year inflationary increases for new and 
continuing grants. To nurture early career scientists, we will continue 
our efforts to ensure that the success rates for investigators 
submitting new R01 applications are the same whether the applicant is 
first-time or more experienced.
    In fiscal year 2013, we will also conduct an additional review of 
proposed awards to any principal investigator (PI) who already has NIH 
funding of $1.5 million or more in total annual costs, approximately 6 
percent of PIs. This review will be conducted by each institute's 
advisory council. This is similar to a policy the National Institute of 
General Medical Sciences (NIGMS) has had since 1998, which will serve 
as a model for NIH. We recognize that some types of research, notably 
large complex clinical trials, routinely will trigger this review. We 
also know that some of our most productive investigators are leading 
significant research teams that require more than $1.5 million to be 
sustained. This extra level of review will not be viewed as a cut-off 
point but as an opportunity to apply additional scrutiny to be sure any 
added resources are justified by exceptional scientific promise.
    Another significant change in the fiscal year 2013 request is an 
11-percent increase in the NCATS budget. The proposed budget includes 
an increase of $39.6 million for the Cures Acceleration Network (CAN), 
which received $10 million for start-up funding in fiscal year 2012. As 
you know, Mr. Chairman, CAN will fund initiatives to address scientific 
and technical challenges that impede translational research, and to 
advance the development of ``high-need cures'' by accelerating the pace 
and reducing the time between research discovery and therapeutic 
treatment. In total, nearly one-half of the increase requested for 
NCATS will be used to transition programs from the Common Fund, 
allowing the Common Fund to support additional cross-cutting, trans-NIH 
programs.
    I would also note that the fiscal year 2013 NIGMS budget would 
decrease by $48.3 million (after comparability adjustments), primarily 
due to not continuing the 21 percent increase that the Congress 
provided in fiscal year 2012 for the Institutional Development Awards 
(IDeA) program. The budget of the Office of the Director is also cut by 
1.9 percent from fiscal year 2012 enacted level, reflecting a reduced 
request for the National Children's Study (NCS); we will implement 
alternative sampling approaches that will reduce costs and still 
achieve the ambitious objectives of the study.
    In fiscal year 2013, the President is also proposing to spend $80 
million from the Prevention and Public Health Fund to provide 
additional support for Alzheimer's research as part of the national 
plan to address Alzheimer's disease. As many as 5.1 million Americans 
currently suffer from Alzheimer's disease, more than 280,000 more 
Americans will be diagnosed with the disease this year, and nearly 800 
of our fellow citizens are diagnosed every day. By the year 2030, the 
last baby boomer will turn 65 and 7.7 million Americans older than the 
age of 65 will have Alzheimer's disease.\2\ Today, Alzheimer's and 
other dementias cost the United States economy more than $180 billion a 
year and if no cures and therapies are found, will cost the United 
States $1.1 trillion annually by 2050. The $80 million of new funding 
will support research with a strong focus on the prevention of 
Alzheimer's disease, including research to identify genes that cause 
this disease, to develop tests for high-risk individuals, and to 
identify possible targets for therapeutic development.
---------------------------------------------------------------------------
    \ 2\ Alzheimer's Association, 2011 Alzheimer's Disease Facts and 
Figures, Alzheimer's & Dementia, Volume 7, Issue 2.
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      investing in basic science, applying knowledge to therapies
    NIH's commitment to basic research provides the foundation for 
understanding the underlying causes of diseases which is essential to 
the development of promising treatments and cures for some of our 
Nation's most debilitating diseases and conditions. Apple Computer 
founder, Steve Jobs, has been quoted as saying: ``I think the biggest 
innovations of the 21st century will be the intersection of biology and 
technology.'' \3\ Jobs was absolutely right: today technological 
advances are driving science. We need look no further than the cost of 
DNA sequencing to see this dynamic at work. The cost curve for 
sequencing is dropping at a breathtaking rate; sequencing speed has 
increased even faster than computer processing speed. What's more, the 
average cost of sequencing an entire genome has fallen from about $3 
billion 12 years ago, to $10 million 5 years ago, to about $7,700 
today. Two U.S. companies have recently announced that they are 
manufacturing machines that will sequence an individual's genome in 1 
day for approximately $1,000, and that the first such instruments will 
go on sale before year's end. Lower sequencing costs will likely 
revolutionize how clinicians diagnose and treat diseases and enable the 
research community to pursue previously unimaginable scientific 
questions.
---------------------------------------------------------------------------
    \3\  Isaakson, Walter, Steve Jobs (New York: Simon & Schuster, 
2011) 539.
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    NIH is the leading supporter of basic biomedical research in the 
world. Put plainly, if we don't fund basic research, most of this work 
would not get done, and it would be only a matter of time before this 
wellspring of new understanding and new therapies would dry up. NIH's 
funding for basic research is slightly more than one-half (54 percent) 
of research funding, and this balance between basic and applied 
research has remained fairly constant over the past decade.
    I also would like to address what may be a misconception about a 
competitive tension between basic and applied research at NIH. As our 
support of basic research has enabled new discoveries, NIH-funded 
scientists have always worked to turn the most compelling of them into 
medical advances. Basic discovery and the development of therapies go 
hand-in-hand at NIH. The two types of research have--and always will--
exist together in a continuum. Today, I would like to highlight just a 
few areas in which basic research advances are opening up new 
translational opportunities.
    Human Microbiome Project.--One fascinating area of basic research 
is the Human Microbiome Project, an initiative supported through the 
NIH common fund. This project is giving us wonderful insights into the 
sweeping range of bacteria that live on and in each of us, and is 
expanding our knowledge about the role of these microbial communities 
in health and disease. Recent scientific evidence suggests that changes 
in the composition and activity of the human microbiome may contribute 
to obesity, which may provide us with new ways of addressing this 
serious threat to our Nation's health.
    Undiagnosed Diseases Program.--Another recent example emphasizes 
the ``virtuous cycle'' between basic and clinical research. The NIH 
clinical center has recently established a groundbreaking program that 
seeks to identify the cause of illnesses that have remained unsolved by 
other medical practitioners. Since the program started in 2008 some 
1,700 people with undiagnosed conditions have been referred to Dr. 
William Gahl, and more than 300 have been accepted for an initial week 
of consultations and testing. In the 15 to 20 percent of cases that we 
have successfully diagnosed, it has taken from a week to as long as 2 
years to resolve. For example, a pair of sisters from Kentucky suffered 
from joint pain and mysterious calcification of the arteries in their 
extremities. Full evaluation and DNA sequencing led to the discovery of 
an entirely new genetic condition, where a previously unknown enzyme 
pathway in their arteries was blocked. This has led to a dramatic new 
understanding of how the large arteries in all of us maintain their 
normal health, with immediate research spinoffs in the basic and 
clinical arenas.
    Alzheimer's Disease.--NIH-supported investigators are expanding our 
understanding of Alzheimer's disease in ways that may open doors to new 
therapies. Using mice genetically engineered to make the abnormal human 
tau protein--a protein already identified in the brains of Alzheimer's 
patients--scientists found that Alzheimer's disease appears to spread 
through the brain in much the same way that an infection or cancer 
moves through the body. The abnormal tau protein started in one area of 
the brain in the mice and, over time, spread from cell to cell to other 
areas of the brain in a pattern very similar to the earliest stages of 
human Alzheimer's disease. The discovery of the tau pathway could 
influence the direction of future research and give investigators a 
target for drug development that might arrest Alzheimer's disease 
progression at very early stages when the disease is most amenable to 
treatment.\4\
---------------------------------------------------------------------------
    \4 \ Liu L, Drouet V, Wu JW, Witter MP, Small SA, et al. (2012) 
Trans-Synaptic Spread of Tau Pathology In Vivo. PLoS ONE 7(2): e31302. 
doi:10.1371/journal.pone.0031302
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    Alzheimer's disease also stands to benefit from translational 
research by way of drug rescuing and repurposing. Recently, a team that 
included NIH-supported investigators reported that bexarotene, a drug 
compound originally developed for treating T-cell lymphoma (a type of 
skin cancer), was capable of clearing the protein beta-amyloid quickly 
and efficiently after only a short exposure to the compound in 
Alzheimer's disease mouse models. Beta-amyloid accumulates in the brain 
of Alzheimer's patients due to an impaired ability to clear the 
protein, leading to a build-up of beta-amyloid plaques and ultimately 
neuronal death. These findings are exciting because, in time, they 
could benefit patients with Alzheimer's disease. Hopes are particularly 
high because the drug used in the study has already been studied in 
humans, providing a wealth of information about dosage and toxicity.\5\
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    \5\ Cramer PE, Cirrito JR, Wesson DW, Lee CYD, Karlo JC, et al. 
(2012) ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse 
Deficits in AD Mouse Models. http://www.sciencemag.org/content/early/
2012/02/08/science.1217697.full.pdf
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    Cystic Fibrosis.--In a step towards personal medicine, the FDA in 
January approved Kalydeco, the first drug to treat an underlying cause 
of cystic fibrosis (CF). Twenty-three years ago, I co-led the team that 
discovered the gene responsible for CF. Mutations in this gene cause a 
protein to malfunction, resulting in a sticky buildup of mucus in the 
lungs and digestive tract that eventually causes fatal health problems. 
Kalydeco, which was developed by Vertex Pharmaceuticals, counters one 
of these mutations, which affects about 4 percent of people with CF. 
Vertex is now testing the drug in combination with another new compound 
to target a more common mutation found in 90 percent of CF patients.
clinical research: national center for advancing translational sciences
    The translation of basic biological discoveries into clinical 
applications is a complex process that involves a series of intricate 
steps. These steps range from the discovery of basic information about 
the causes of disease, an assessment of whether that information has 
the potential to lead to a clinical advance, the development and 
optimization of therapeutics to test in human trials, and ultimately, 
the application of the approved therapy, device, or diagnostic in the 
real world. Drugs exist for only about 250 of the more than 4,400 
conditions with defined molecular causes.\6\ And it takes far too long 
and far too much money to get a new drug into our medicine cabinets. 
This is an old problem that cries out for new and creative solutions.
---------------------------------------------------------------------------
    \6 \ Braun, et al., ``Emergence of orphan drugs in the United 
States: a quantitative assessment of the first 25 years.'' Nature Rev. 
Drug Discov. 9(521), 2010; Online Mendelian Inheritance in Man, http://
www.ncbi.nlm.nih.gov/omim/.
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    In the past, drug development was based on a short list of a few 
hundred targets, but with advances in technology, we are now able to 
identify thousands of new potential drug targets.\7\ We can also study 
whole pathways, organ systems, or even entire organisms rather than 
limiting the research to a single aspect of cell biology or physiology. 
Technologies such as large-scale sequencing, robotic high-throughput 
screening, and real-time imaging modalities uncover massive amounts of 
data that may one day lead to new therapies to prevent, treat, and 
possibly cure diseases. Many of the NIH institutes are deeply engaged 
in these efforts. But we face serious engineering challenges. To put it 
simply, the current translational science framework pursued in both the 
public and private sectors, largely focused on individual projects on 
specific diseases, has not been fully able to utilize recent scientific 
advances to address the bottlenecks that lead to long development 
times, high failure rates, and high costs. This month's issue of Nature 
Reviews Drug Discovery includes a review that demonstrates that, 
despite huge investments in biomedical science and technology, the 
number of new drugs approved per billion R&D dollars spent has been cut 
in one-half every 9 years since 1950.\8\ NCATS is the catalyst we need 
to reengineer the discovery and development process.
---------------------------------------------------------------------------
    \7 \ Collins, F.S., ``Reengineering Translational Science: The Time 
is Right.'' Sci. Transl. Med., 3(90):90cm17, 2011.
    \8 \  Scannell JW, Blanckley A, Boldon H, & Warrington B. (2012). 
Diagnosing the decline in pharmaceutical R&D efficiency. Nature Reviews 
Drug Discovery 11, 191-200. doi:10.1038/nrd3681.
---------------------------------------------------------------------------
    To tackle this problem in a science-driven way, NIH proposed the 
creation of NCATS with the goal to develop and test innovative tools, 
technologies, and approaches that will enhance the development of drugs 
and diagnostics for application in all human diseases. NIH has the 
expertise and enthusiasm to tackle this as a scientific problem. By 
focusing on the development of innovative new methods for conducting 
translational science, as opposed to developing therapeutics 
themselves, NCATS can enable others to bring new medical products to 
patients in a highly efficient, cost-effective manner. In the 4 months 
since it was established, NCATS has already developed three new 
initiatives in partnership with industry, academia, and other 
government agencies.
    In the first initiative, NIH is working closely with several 
pharmaceutical companies to develop model agreements for a new pilot 
program to rescue failed drugs. Pharmaceutical companies have access to 
promising compounds that have been shown to be safe in humans, but that 
did not prove effective in treating the condition for which they were 
intended. Researchers are now learning that a compound that is a 
failure for one condition may help to treat another. To capitalize on 
this, NCATS is developing a pilot program in partnership with industry 
that will seek to crowd source some of the most promising of these 
compounds to the brightest minds in science, an unprecedented 
opportunity for NIH-funded researchers, and a new way to bridge 
academic science with industrial expertise.
    Second, NCATS is partnering with the Defense Advanced Research 
Projects Agency (DARPA) to develop a chip that will mimic how humans 
respond to a drug. Scientists funded by NIH and DARPA will spend 5 
years working closely with each other to place 10 diverse human tissues 
on a chip so that they will interact with drugs the same way that they 
do in living patients. By providing a better model to predict drug 
safety and efficacy, the most promising drug candidates can be 
identified more quickly and moved forward into development. FDA will be 
heavily involved in an advisory capacity to ensure this research aligns 
with regulatory requirements.
    In the third initiative, NCATS is working closely with industry to 
develop systematic ways to identify the most promising drug targets 
from the troves of data pouring out of basic research labs. To turn 
these discoveries into therapies, scientists in academia and industry 
need to be able to sift quickly and accurately through these data to 
identify the best targets. NCATS, along with industry partners, is 
taking the lead on developing a consortium that will strive to come up 
with the most streamlined ways to conduct target validation.
    I want to emphasize that these and other initiatives within NCATS 
will provide resources and expertise to assist the basic research 
community in moving their discoveries to the next phase, as well as 
stimulate the basic research enterprise. For example, the Molecular 
Libraries and Imaging Program, originally implemented through the NIH 
Common Fund, has been successful in the development of chemical probes 
for basic and translational research. Many of these new probes have 
been, or are being, modified for use in the clinic, resulting in patent 
applications, licenses to pharmaceutical companies, and new therapeutic 
strategies.
    In the months before NCATS was created by this subcommittee, NIH 
engaged in an unprecedented outreach campaign to make sure that all 
stakeholders--including industry--had an opportunity to comment on the 
proposed Center. In addition to NIH's scientific management review 
board and advisory council to the director, NIH consulted with the 
boards of the Pharmaceutical Research and Manufacturers of America and 
the Biotechnology Industry Association, the R&D heads of pharmaceutical 
and biotechnology companies, and the investment banking and venture 
capital communities. In addition, NIH held a series of workshops with 
pharmaceutical and biotech firms to discuss drug rescue and repurposing 
and target validation.
    It is important to note that NCATS' work will assist all of NIH's 
Institutes and Centers in their translational and drug development 
efforts. NCATS will provide NIH Institutes and Centers the tools, 
methodology, and infrastructure necessary to speed new approaches to 
therapeutic treatments. The new Center also will work with other NIH 
Institutes and Centers to convene workshops with industry, nonprofits, 
and other government agencies to explore critical translational areas 
and innovative public-private sector partnerships.
    With the fiscal year 2013 budget, NIH will pursue efforts to 
streamline and shorten the pathway from discovery to health through 
several new and ongoing initiatives and programs.
              economic returns and global competitiveness
    In our knowledge-based world economy, innovation in medical 
research has been able to generate growth, high-quality jobs, better 
health, and better quality of life for all Americans. Investment in NIH 
continues to bring new ways to cure disease, alleviate suffering, and 
prevent illness. Furthermore, it generates new economic activity and 
employment in the communities that receive its funds. One study 
estimates that every $1 of NIH support returns $2.21 in goods and 
services in just 1 year, and that on average, every NIH grant creates 
seven high-quality jobs.
    Investments in the biomedical infrastructure, in scientists' ideas, 
and in workforce training are essential to drive the innovation that 
will spur America's economic recovery and future growth. NIH serves as 
the foundation for the entire U.S. medical innovation sector that 
employs 1 million United States citizens, generates $84 billion in 
wages and salaries, and exports $90 billion in goods and services.\9\ 
United for Medical Research has just released an updated version of 
their report ``An Economic Engine: NIH Research, Employment, and the 
Future of the Medical Innovation Sector.'' According to UMR data, the 
$23.7 billion NIH spent extramurally in the U.S. in 2011 directly and 
indirectly supported 432,092 jobs, enabling 16 States to experience job 
growth of 10,000 jobs or more, and propelling $62.135 billion in new 
economic activity.
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    \9 \ Ehrlich, Dr. Everett, An Economic Engine: NIH Research, 
Employment and the Future of the Medical Innovation Sector, 8, United 
for Medical Research (May 2011).
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    Thanks in large part to NIH-funded medical research, Americans are 
living longer, healthier, more rewarding lives. A child born today can 
look forward to an average life span of almost 79 years, an increase of 
nearly three decades over life expectancy in 1900. The economic value 
of these gains in average life expectancy in the United States has been 
estimated at $95 trillion for the period from 1970-2000.\10\
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    \10\  Murphy, K.M., & Topel, R.H. (2006). ``The value of health and 
longevity''. Journal of Political Economy, 114(5), 871-904.
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    NIH funding is the foundation for long-term U.S. global 
competitiveness in industries such as biotechnology, medical devices, 
and pharmaceutical development. Around the world, many nations are 
following suit and beginning to ramp up their own investment in the 
life sciences. Global R&D spending is expected to grow by about 5.2 
percent to more than $1.4 trillion in 2012.\11\ India has posted 
double-digit increases for several years, and Europe plans to increase 
research spending by 40 percent over the next 7 years. Even Vladimir 
Putin has announced the intention to increase support for research in 
Russia by 65 percent over the next 5 years. China has just announced 
that it will increase its investment in basic research by 26 percent in 
2012.\12\ To be sure, the scale of China's effort does not match ours. 
However, Chinese scientists are second only to the United States in the 
number of scientific manuscripts published annually, and China's 
intention to compete with us is obvious.
---------------------------------------------------------------------------
    \11\  Grueber, Martin, 2012 Global R&D Funding Forecast, 3, Batelle 
and R&D Magazine (December 2011).
    \12 \  Hvistendahl M. (2012). ``A Bumper Year for Chinese 
Science.'' Science Vol. 335, No. 6073 p.1156. doi: 10.1126/
science.335.6073.1156.
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    The United States must compete in training America's next 
generation to make tomorrow's health discoveries and ensure continued 
scientific leadership.
                            a patient story
    Mr. Chairman, this morning I've described the promise that 
inexpensive whole-genome sequencing holds for future medical practice, 
the synergy between basic and translational research at NIH, and the 
need for NCATS. I'd like to close my testimony by telling you a story--
a story about real patients--that ties my three points together.
    As toddlers, twins Alexis and Noah Beery were diagnosed with a rare 
and devastating movement disorder, called dystonia. Although they 
initially responded to empirical treatment, their symptoms reappeared 
and worsened as they entered their teenage years. Noah developed severe 
tremors in his hands. Even worse, his sister Alexis began falling 
frequently and had frightening episodes where she couldn't breathe.
    Desperate for answers, doctors at Baylor College of Medicine 
sequenced the twins' genomes. The result? Discovery of a never-before 
described genetic mutation affecting neurotransmitters in the brain. 
After being put on a new treatment regimen tailored to their unique 
genetic profile, the twins' symptoms began to improve within just 2 
weeks. I recently saw a video of the two of them doing tricks on a 
trampoline. In fact, Alexis' breathing is so much better today that 
she's joined her school's track team. While this story centers on two 
teens with a rare disease, the outcome carries a message of hope for 
all of us. It points directly to the promise that NIH research offers 
the patients of today and tomorrow.\13\
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    \13\ Bainbridge MN, et al. (2011). Whole-Genome Sequencing for 
Optimized Patient Management. Science Translational Medicine 3, 87re3. 
doi: 10.1126/scitranslmed.3002243.
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    In conclusion, we have never witnessed a time of greater promise 
for advances in medicine than right now. NIH is prepared to continue 
our long tradition of leading the world in the public support of 
biomedical research. Successful development of prevention strategies, 
diagnostics, and therapeutics will require bold investments in research 
across the spectrum from basic science to clinical trials, as well as 
new partnerships between the public and private sectors. With your 
support, we can promise continuing advances in medicine, creation of 
new economic opportunities, and stimulation of American global 
competitiveness in science, technology, and innovation.
                                 ______
                                 
   Prepared Statement of Anthony S. Fauci, M.D., Director, National 
              Institute of Allergy and Infectious Diseases
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2013 budget request for the 
National Institute of Allergy and Infectious Diseases (NIAID) of the 
National Institutes of Health (NIH). The fiscal year 2013 NIAID budget 
of $4,495,307,000 includes an increase of $10,210,000 more than the 
comparable fiscal year 2012 level of $4,485,097,000.
    NIAID conducts and supports biomedical research to understand, 
treat, and prevent infectious and immune-mediated diseases, including 
HIV/AIDS, tuberculosis, malaria, influenza, emerging and re-emerging 
infectious diseases, asthma and allergic diseases, autoimmune diseases, 
and the rejection of transplanted organs. I appreciate the opportunity 
to highlight our recent scientific advances and to describe some of our 
most promising research aimed at improving public health and quality of 
life.
                      infectious diseases research
    HIV/AIDS.--In the 30 years since AIDS was first recognized in the 
United States, the substantial NIAID investment in basic, 
translational, and clinical HIV/AIDS research supported consistently by 
this subcommittee has resulted in many groundbreaking discoveries. With 
this commitment, we have made significant progress, including 
strengthening HIV prevention efforts and developing nearly 30 
antiretroviral drugs to suppress HIV. Thirty years ago, HIV/AIDS was 
for the most part a death sentence. Today, if a young person enters the 
clinic with early HIV disease and begins appropriate therapy, he or she 
can expect to live a near-normal lifespan, a milestone unimaginable at 
the start of the HIV/AIDS pandemic.
    I am pleased to report landmark advances and opportunities in HIV/
AIDS research this year. In December 2011, the journal Science named an 
NIAID-funded international HIV prevention study its breakthrough of the 
year, reinforcing that the investment in NIH research continues to pay 
extraordinary dividends for public health. This study, known as HPTN 
052, demonstrated that HIV-infected heterosexual individuals who began 
taking antiretroviral medicines when their immune systems were still 
relatively healthy, rather than later, were 96 percent less likely to 
transmit the virus to their uninfected sexual partners. This study 
convincingly demonstrates that antiretrovirals not only can be life-
saving to people infected with HIV but also can prevent transmission of 
the virus to their uninfected sexual partners. Other studies have shown 
that medically supervised adult male circumcision has proven to be 
highly effective and durable in preventing the acquisition of HIV 
infection. In addition, pre-exposure prophylaxis of at-risk uninfected 
individuals may be an important means of preventing HIV infection.
    HIV vaccines still represent the best long-term hope for ending the 
HIV pandemic. Building on the promising results of the United States 
Army-NIAID RV144 HIV vaccine clinical trial, which found a ``prime-
boost'' vaccine candidate to be safe and modestly effective at 
preventing acquisition of HIV, NIAID is working to understand the 
immune mechanisms that explain these results, to optimize the 
protective immune responses elicited by the vaccine candidate, and to 
develop and evaluate new vaccine candidates. We also are encouraged by 
the discovery by NIAID-supported scientists of human antibodies that 
can block a wide range of HIV strains. We are expanding clinical 
testing in this area, and insights gained from these studies will guide 
future HIV vaccine research.
    These research advances taken together with the implementation of 
other evidence-based HIV prevention and treatment strategies make the 
possibility of an ``AIDS-free generation'' in the foreseeable future 
eminently feasible. This July, we will consider strategies to implement 
these important findings during the International AIDS Society 
Conference in Washington, DC.
    Tuberculosis and Malaria.--NIAID continues to invest in basic and 
clinical research and collaborate with global partners, including the 
World Health Organization's Stop Tuberculosis (TB) Partnership, to 
combat the co-infections that often accompany HIV infection, including 
TB and malaria. Building on these efforts, we now have a substantial 
development pipeline of TB treatments and vaccines. NIAID has developed 
a Strategic Blueprint for TB Vaccines that proposes new research 
pathways for achieving a licensed TB vaccine. For malaria, NIAID 
supported early-stage basic research that ultimately led to the 
development by others of the first moderately successful malaria 
vaccine candidate aimed particularly for children, RTS,S/AS01, a 
science runner-up breakthrough of the year in 2011. In addition, the 
NIAID Vaccine Research Center is partnering with a biotechnology firm 
to undertake clinical studies of a novel malaria vaccine candidate, 
PfSPZ. NIAID also plays a leading role in the international Malaria 
Eradication Research Agenda initiative.
    Other Infectious Diseases of Domestic and Global Health 
Importance.--NIAID's longstanding investments in basic and clinical 
research have led to many successes in vaccine development for diseases 
of worldwide public health concern, including gastroenteritis caused by 
rotavirus, pneumonia, hepatitis A, and deadly meningitis caused by 
Haemophilus influenzae type b. These are among the vaccines now being 
delivered to countries around the world; where they have been deployed, 
substantial reductions in morbidity and mortality have been observed. 
NIAID has assumed a major leadership role in the ``Decade of Vaccines'' 
initiative, a 10-year collaborative effort coordinated by the Bill & 
Melinda Gates Foundation, to develop and deliver vaccines to the 
world's poorest countries. NIAID will continue research on other 
urgently needed vaccines, including vaccines for Group B streptococci, 
Epstein-Barr virus, and hepatitis C virus.
    Seasonal and pandemic influenzas remain critical global health and 
economic threats. NIAID has made significant progress in the 
development and testing of vaccines to protect people from influenza, 
including the elderly, young children, and those with asthma. Recently, 
NIAID researchers demonstrated that a ``prime-boost'' gene-based 
vaccination strategy could activate the immune system and lead to 
broadly neutralizing antibody responses against influenza viruses. This 
finding and those from other researchers signal that we are closer to 
developing a ``universal'' vaccine that could protect against multiple 
strains of seasonal and pandemic influenza viruses.
    This year, in response to the growing public health issue of 
antimicrobial resistance, NIAID will expand our clinical trials 
networks developed originally for HIV/AIDS to investigate this 
important concern. In addition, NIAID will support research to 
determine how to preserve the effectiveness of current antibiotics.
    NIAID's biodefense research has yielded numerous scientific 
advances as we have moved from a ``one bug-one drug'' approach to a 
more flexible, broad-based product development strategy that utilizes 
sophisticated genomic and proteomic platforms to address infectious 
disease outbreaks, whether they are deliberately introduced or 
naturally occurring. As part of this effort, NIAID has awarded 
contracts for the development of broad-spectrum therapeutics against 
emerging infectious disease and biodefense agents.
          research on immunology and immune-mediated disorders
    NIAID was highly gratified that the 2011 Nobel Prize in Physiology 
or Medicine was awarded to three NIAID grantees:
  --Bruce A. Beutler;
  --Jules A. Hoffmann; and
  --the late Ralph M. Steinman.
    Their research has been pivotal in understanding the human immune 
response, and it is helping to inform the development of new vaccines 
and vaccine adjuvants that may provide better protection against 
infectious diseases.
    NIAID's commitment to basic immunology research has led to advances 
in the treatment of immunological conditions such as the rejection of 
transplanted organs. In 2011, the Journal of the American Medical 
Association published an NIAID Immune Tolerance Network study 
demonstrating that children who receive liver transplants may not need 
lifelong anti-rejection therapy to maintain the transplanted organ. 
Other NIAID-supported investigators demonstrated that some kidney 
transplant recipients who also received bone marrow from the kidney 
donor can maintain their kidney grafts without immunosuppressive drugs.
                               conclusion
    NIAID basic and clinical research on infectious and immune-mediated 
diseases will continue to promote the development of vaccines, 
therapeutics, and diagnostics to improve health and save millions of 
lives worldwide. NIAID remains committed to supporting highly 
meritorious research with the goal of translating fundamental 
scientific findings into public health advances.
                                 ______
                                 
  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 subcommittee: I am pleased to 
present the President's fiscal year 2013 budget request for the 
National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK) of the National Institutes of Health (NIH). The fiscal year 
2013 budget includes $1,792,107,000, which is $2,798,000 less than the 
comparable fiscal year 2012 appropriation of $1,794,905,000. 
Complementing these funds is an additional $150 million also available 
in fiscal year 2013 from the special statutory funding program for type 
1 diabetes research. The NIDDK supports research on a wide range of 
common, chronic, costly, and consequential diseases and health problems 
that affect millions of Americans. These include diabetes and other 
endocrine and metabolic diseases; digestive and liver diseases; kidney 
and urologic diseases; blood diseases; obesity; and nutrition 
disorders.
         building new opportunities: basic research discoveries
    From in-depth exploration of fundamental biologic processes, NIDDK-
supported scientists are achieving remarkable advances and building the 
foundation for previously unimaginable strategies to improve health and 
quality of life. Among these advances, recent NIDDK-supported research 
into genetic risk factors for diabetes, inflammatory bowel disease, 
obesity, liver disease, and the kidney disease focal segmental 
glomerular sclerosis, along with other studies are providing insights 
into disease development and whether an individual is likely to respond 
to a given therapy. Investigating the different types of bacteria that 
reside in the intestines, researchers have discovered surprising links 
to obesity, inflammatory bowel disease, fatty liver disease, and other 
health conditions. Scientists supported by our institute are also 
designing novel intervention strategies and testing these in pre-
clinical, laboratory models. For example, pursuing a treatment for 
fecal incontinence, researchers used tissue engineering to build muscle 
implants in mice with promising initial results, providing hope for 
future therapeutic use in people. Other scientists examined a potential 
drug for the rare disease Neimann-Pick type C in experiments with 
isolated human cells, and found encouraging results.
    We will continue support for basic research across the Institute's 
mission, to gain further insights into health and disease and propel 
new ideas for interventions. Examples include research to identify type 
2 diabetes risk genes in minority populations disproportionately 
affected by this disease; to discover environmental factors that 
trigger type 1 diabetes in genetically susceptible individuals; to 
elucidate the causes and consequences of a form of diabetes that can 
strike people with cystic fibrosis; to increase understanding of 
intestinal stem cells, which could benefit a variety of digestive 
diseases; and to augment knowledge of blood cells and hematologic 
diseases.
      preventing and treating disease--in clinics and communities
    Through innovative design and rigorous testing of interventions--
whether in the operating room, doctor's office, or home or community 
settings--NIDDK-supported researchers are improving lives with new 
approaches to prevent, treat, and reverse diseases and disorders. For 
example, investigators previously showed that intensive blood glucose 
control, beginning soon after diagnosis of type 1 diabetes, reduced 
early signs of complications; now, after an average 22-year follow-up, 
the researchers demonstrated that controlling blood glucose reduced the 
risk of developing kidney disease by 50 percent, preserving kidney 
function for decades. The first cystic fibrosis therapy targeting a 
specific molecular defect gained U.S. Food and Drug Administration 
(FDA) approval. This important advance was a culmination of research 
supported in part by NIDDK, from the historic gene discovery (by the 
NIH Director) to clinical trials of the drug. With cutting-edge tissue 
engineering, researchers have successfully generated urethras to 
replace defective tissue and ameliorate urination difficulties in boys. 
A network of investigators found that vitamin E helps reduce fatty 
liver disease in children. In studies that may alert clinicians to 
patients with heightened need for intervention, scientists found that 
elevated levels of the hormone FGF-23 mark increased risk for heart 
disease and death in people with chronic kidney disease, while high 
levels of certain amino acids in the blood signify increased risk for 
type 2 diabetes.
    Looking forward, NIDDK is committed to continuing funding for 
clinical research. Because many diseases within our mission 
disproportionately affect certain populations, we will also continue to 
seek insights and answers to health disparities. As just a few examples 
of our many clinical studies, Institute-supported scientists will 
conduct trials of approaches to prevent or slow the onset of type 1 
diabetes, and they will press forward in developing technology to 
create an artificial pancreas for people with diabetes. In a new 
effort, the Institute is planning a comparative effectiveness study of 
commonly used drugs for type 2 diabetes. We will also continue a 
promising, long-term clinical trial of a lifestyle intervention 
designed to promote weight loss and improve health in obese people with 
type 2 diabetes. Among multifaceted efforts to meet the challenge of 
obesity will be a consortium studying lifestyle interventions for 
overweight and obese pregnant women, to improve the health of both 
mother and child. The Institute will continue to support clinical 
studies for a range of liver diseases; for example, a multicenter 
research network is planning trials of different treatment strategies 
for hepatitis B, including comparative effectiveness research. Multiple 
efforts will pursue approaches to combat chronic kidney disease, 
polycystic kidney disease, primary glomerular disease, and other forms 
of kidney disease and injury. We have also spearheaded an initiative 
encouraging studies to prevent and treat obesity, diabetes, and kidney 
disease in military populations. NIDDK continues to support a multi-
disciplinary study in chronic urologic pelvic pain, and will support a 
new research network to improve measurement of the complex symptoms of 
lower urinary tract dysfunction in men and women and to advance 
clinical studies. To maximize the reach and benefits of interventions 
proven successful in clinical trials, we will sustain support for 
translational research, to implement these in real-world medical 
practice and community settings, cost effectively, for diverse 
populations. For example, an NIDDK-funded research project provided the 
first demonstration that YMCAs, now officially called Ys, can deliver a 
group-based version of the lifestyle intervention shown to reduce type 
2 diabetes in the Diabetes Prevention Program clinical trial.
         supporting an innovative, multidisciplinary workforce
    Research breakthroughs happen only through the efforts of a 
creative, well-trained workforce. Thus, NIDDK will continue programs to 
train and support researchers at all stages of their careers, and to 
ensure that we benefit from the best scientific minds. NIDDK supports 
summer research opportunities for underrepresented high school and 
college students, workshops for minority investigators and new 
investigators, a new initiative for professional societies to promote 
diversity in the research workforce, and other efforts. We will 
continue to support investigator-initiated projects, along with 
solicited research that is guided by input from expert researchers and 
the public.
          integrating science-based information into practice
    We will also continue to support education, outreach, and awareness 
programs. These efforts include materials tailored for diverse 
audiences and span the range of diseases within our mission, to bring 
vital, science-based knowledge to healthcare providers, patients and 
their families, and the general public.
    In closing, NIDDK's future research investments will build upon 
findings from past and ongoing studies, pursue promising new 
opportunities, and tackle critical challenges toward innovative and 
more effective prevention and treatment strategies. Our research will 
be guided by five principles:
  --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.
                                 ______
                                 
        Harold Varmus, M.D., Director, National Cancer Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Cancer 
Institute (NCI) of the National Institutes of Health (NIH). The fiscal 
year 2013 NCI budget of $5,068,864,000 includes an increase of 
$2,717,000 more than the comparable fiscal year 2012 level of 
$5,066,147,000.
    As many of you will read upon its release later today, the 2012 
annual report to the Nation on the status of cancer offers a generally 
encouraging view of cancer trends. The report documents that death 
rates from all cancers combined for men, women, and children in the 
United States continued to decline between 2004 and 2008, the latest 
year for which we have complete analysis. Age-adjusted mortality rates 
for 11 of the 18 most common cancers among men and for 14 of the 16 
most common cancers in women have declined. The overall rate of new 
cancer diagnoses, also known as incidence, among both men and women 
also declined over similar periods, although for women the decline 
leveled off from 2006-2008.
    These continued declines in death rates for most cancers, as well 
as the overall drop in incidence, are powerful evidence that our 
Nation's investment in many fields of cancer research produces life-
saving approaches to cancer control. The breadth of the Nation's cancer 
portfolio and our ability to pursue many different approaches to cancer 
research must match the heterogeneity of cancer itself, which we now 
understand to be literally hundreds of genetically distinct diseases 
with many avenues to prevention, screening, diagnosis, and treatment.
                           basic and science
    A large part of the NCI basic research portfolio uses molecular 
biology and genetics to deepen our knowledge about the origins and 
behavior of cancers and to develop drugs and understand drug 
resistance. For example, decades of basic research culminated in 
development of the molecularly targeted drug Gleevec (imatinib). Since 
the U.S. Food and Drug Administration (FDA) approved the drug in 2001, 
it has been the treatment of choice--and a very effective one--for 
chronic myelogenous leukemia (CML) as well as a few other cancers. 
Targeted drugs usually inhibit enzymes--in this case, kinases--that are 
essential to the survival of cancer cells, rather than broadly killing 
all rapidly dividing cells in the body. In CML, the target is the 
abnormal protein made by fused genes, BCR-ABL, in cancerous blood 
cells, where in its activated or ``on'' state the mutant enzyme pushes 
white blood cells into overdrive, causing disease. Gleevec blocks the 
mutant enzyme, kills cancer cells, and returns the blood system and the 
patient to a normal state.
    But despite Gleevec's generally powerful effects, some CML patients 
relapse when new mutations make the BCR-ABL protein resistant to 
Gleevec, allowing the abnormal enzyme to drive white blood cell growth 
again despite treatment. This phenomenon, drug resistance, is now being 
encountered with the several other targeted therapies more recently 
introduced for lung cancer, melanoma, and other cancers. So it is 
encouraging to report that NCI-supported research has identified a 
number of drugs targeting BCR-ABL proteins even after they acquire 
mutations that confer resistance to Gleevec. Two of these, approved a 
few years ago, did not overcome relatively common resistance mutation. 
But a third generation of drugs is able to do that, in an interesting 
new way, by freezing the target protein in an inactive conformation, so 
that its enzyme cannot work. This example illustrates another important 
point. Many different research streams--from genetics to structural 
biology to pharmacology--were required for these advances in treatment. 
The need to bring together multidisciplinary teams to focus on key 
questions like drug resistance in cancers increasingly defines modern 
biomedical research.
    To strengthen NCI's ability to drive similar discoveries, NCI this 
year consolidated a number of its genomics initiatives--including the 
flagship program The Cancer Genome Atlas (TCGA)--into a single Center 
for Cancer Genomics. TCGA's aim is to characterize comprehensively the 
genomic alterations in hundreds of samples of about 20 known tumor 
types. With the project nearing completion on schedule, the vast influx 
of data promises to dramatically alter our knowledge of the genetic 
changes that drive cancer development. The new center will work with 
other components of NCI to ensure that the findings are applied to 
developing new diagnostics and therapeutics and are integrated swiftly 
into medical practice.
                        screening and prevention
    Early detection of cancer can enhance therapy. Last year I briefed 
this subcommittee on the recently concluded National Lung screening 
trial, which had demonstrated that current and former smokers who were 
screened with low-dose helical computed tomography were 20 percent less 
likely to die of lung cancer compared to others who received standard 
chest xrays.
    Recent findings from another long-term study also point to 
screening as an effective way to cut deaths from another common 
cancer--colorectal adenocarcinoma, which kills about 49,000 Americans 
every year. Clinical studies, several funded by NCI, have consistently 
demonstrated that tests for fecal blood and direct observation of the 
colon with endoscopy can effectively reduce the mortality rates 
associated with colorectal cancer--by up to 50 percent, according to 
one recent estimate. NCI also is investing in studies to understand 
behavioral and economic barriers to screening to increase screening 
rates, especially among minority populations.
                        diagnosis and treatment
    One of the most critical aspects of cancer is its remarkable 
heterogeneity--cancer is actually a collection of hundreds of 
genetically distinct diseases, each with its unique vulnerabilities. 
Lung adenocarcinomas, for instance, develop through a variety of 
genetic changes, and each pattern of changes requires a different 
therapeutic approach. Just a few years ago, it was recognized that up 
to 7 percent of lung adenocarcinomas contain a fused chromosome that 
activates the protein made by a gene called ALK to cause cancerous 
growth. FDA last fall approved crizotinib to treat patients with the 
abnormal ALK gene. Crizotinib blocks the activity of the enzyme, again 
a kinase, produced by the fused ALK gene, similar to the action of 
Gleevec in CML. This oral drug has been approved by the FDA and must be 
used with a companion molecular test to make sure it is used to treat 
only tumors with the abnormal ALK gene.
    Another potential treatment recently emerged from academic research 
laboratories, this one for metastatic prostate cancer. MDV-3100 is a 
so-called anti-androgen therapy that prevents male hormones from 
stimulating the growth of prostate cancer cells through androgen 
receptors--preventing testosterone from binding to androgen receptors 
and preventing the androgen receptor from initiating the production of 
proteins that induce tumor growth. Current anti-androgen drugs suppress 
the growth of prostate cancer cells temporarily, but in most patients, 
the cancer ultimately develops resistance to these drugs by increasing 
the amount of receptors. MDV-3100, by contrast, binds so tightly to the 
androgen receptors that it prevents them from functioning even when the 
receptor numbers are very high. The new drug performed so well that the 
clinical trials were halted early, and the drug now awaits approval at 
FDA.
                         provocative questions
    During the past 14 months, NCI has brought together researchers to 
propose, craft, and debate what they consider to be the critical 
questions in cancer research that may fall outside our current sphere 
of focus, but that could lead to important discoveries about the causes 
and behaviors of cancers. NCI convened 17 workshops across the country 
that identified some 24 provocative questions, and NCI has set aside an 
initial $15 million from its fiscal year 2012 budget to fund some of 
the more than 750 applications received under this program. While this 
initiative does not replace NCI's longtime and essential emphasis on 
funding investigator-initiated research, it represents a useful new 
approach to making the greatest impact with our research dollars.
    The Congress's past investments in cancer research are the reason 
we are able to report promising scientific findings each year, and why 
the report to the Nation continues to show steady progress against a 
wide range of cancers. We are now able to define genetic changes that 
cause cancer, use them to control cancer with more precise tools, and 
thereby reduce the Nation's cancer burden. The President's budget for 
2013 for the NCI will provide the support for discoveries in basic 
science, cancer control and prevention, for early detection and 
diagnosis, and for methods to prevent, treat, and in some instances, 
cure cancers.
                                 ______
                                 
   Prepared Statement of Richard J. Hodes, M.D., Director, National 
                           Institute on Aging
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2013 budget request for the 
National Institute on Aging (NIA) of the National Institutes of Health 
(NIH). The fiscal year 2013 budget includes $1,102,650,000, which is 
$522,000 more than the comparable fiscal year 2012 level of 
$1,102,128,000.
    More than 40 million people age 65 and older live in the United 
States, and data from the Federal Interagency Forum on Aging-Related 
Statistics indicate that their numbers will double by 2040. In less 
than 50 years, the number of ``oldest old''--people ages 85 and older--
may quadruple. As record numbers of Americans reach retirement age and 
beyond, profound changes will occur in our economic, healthcare, and 
social systems.
    NIA leads the national effort to understand aging and to identify 
and develop interventions that will help older adults enjoy robust 
health and independence, remain physically active, and continue to make 
positive contributions to their families and communities. We support 
genetic, biological, clinical, behavioral, and social research related 
to the aging process, healthy aging, and diseases and conditions that 
often increase with age. We also carry out the crucial task of training 
the next generation of researchers who specialize in understanding and 
addressing the issues of aging and old age.
       building momentum in the fight against alzheimer's disease
    Estimates of how many people in the United States currently have 
Alzheimer's disease (AD) range from 2.7 to 5.1 million, depending on 
how AD dementia is defined and measured. However, scientists agree that 
unless the disease can be effectively treated or prevented, the numbers 
will increase significantly if current population trends continue.
    At the same time, there has never been greater cause for optimism. 
In recent years, we have expanded our understanding of how the disease 
takes hold and progresses, identified promising targets for 
intervention, and developed new models to speed discovery. For example, 
researchers have developed a mouse model that expresses human tau, one 
of AD's pathological hallmarks, and discovered that tau pathology is 
transmitted from cell to cell, beginning in the brain's entorhinal 
cortex and spreading from one brain region to the next. This discovery 
provides insight into AD's earliest development and offers a model for 
testing mechanisms and functional outcomes associated with disease 
progression. In another study, investigators ``reprogrammed'' human 
skin cells into induced pluripotent stem cells, which then 
differentiated into working neurons; this breakthrough will facilitate 
the study of AD in human neurons and provide important insight into the 
etiology of the disease.
    Advances in imaging technology, most notably through the NIH-
supported Alzheimer's Disease Neuroimaging Initiative (ADNI), have 
expanded our ability to understand the underlying pathology of AD, 
diagnose the disease, track the progress of interventions, and even 
identify individuals at risk. ADNI data were also used last year to 
develop new, more comprehensive diagnostic guidelines at both the 
clinical and pathological levels.
    NIH currently supports more than 35 clinical trials, including both 
pilot and large-scale trials, of a wide range of interventions to 
prevent, slow, or treat AD and/or cognitive decline; more than 40 
compounds are in preclinical development through the AD Translational 
Initiative. NIA also participates in the NIH Neuroscience Blueprint 
under which investigators developing new compounds will have access to 
drug development services not typically available to the academic 
research community.
    Investigators are also ``re-purposing'' treatments for other 
diseases as treatments for AD, with encouraging results. For example, a 
pilot clinical trial recently demonstrated that a nasal-spray form of 
insulin was able to delay memory loss and preserve cognition in people 
with cognitive deficits ranging from mild cognitive impairment (often a 
precursor condition to AD) to moderate AD. In a separate study, the 
skin cancer drug bexarotene promoted clearance of amyloid-beta and 
reversed cognitive deficits in mice. These preliminary findings offer 
new and exciting possibilities for the effective prevention and 
treatment of AD.
    NIA has been an active participant in the implementation of the 
National Alzheimer's Project Act, including the development of a 
national plan to address AD. A new Presidential initiative to boost 
support for AD research, which will provide an additional $50 million 
in fiscal year 2012 and $80 million in fiscal year 2013 for the 
disease, will stimulate and support important groundbreaking work in a 
number of areas, including AD-extensive whole genome sequencing to 
identify genetic risk and protective factors for AD. Our activities 
will be informed by input from expert advisors participating in the May 
2012 Alzheimer's Disease Research Summit.
              understanding aging at the most basic level
    NIA initiatives on the molecular mechanisms of aging, from in-depth 
study of single cells to the broad study of organisms at the systems 
level, continue to advance our understanding of the basic underpinnings 
of the aging process. For example, investigators recently found that it 
was possible to delay onset of age-related changes in the skeletal 
muscle, fat, and eye tissues in mice by removing senescent cells--i.e., 
cells that are alive but no longer functional. The study also found a 
slowing of progression of age-related disorders in the mice. These 
results suggest that cell senescence may be a fundamental mechanism 
that drives aging.
         improving the health and well-being of older americans
    As the American population continues to age, it is imperative that 
we identify the optimal means to address the unique health needs of 
older individuals. For example, the Centers for Disease Control and 
Prevention reports that fully one-half of older Americans have at least 
two chronic health conditions that compromise quality of life. NIA is 
participating in a trans-NIH initiative to develop interventions to 
modify behavior and improve health outcomes among individuals with or 
more chronic conditions.
    Increased adherence to recommended medication regimens promises 
substantial improvements in public health as well as savings in 
healthcare costs. NIA-supported investigators found that simply 
encouraging people to write down the time and date when they plan to 
receive a flu vaccination can significantly increase vaccination rates. 
NIA also participates in an NIH-wide initiative to identify practical 
interventions to improve medication adherence in the primary care 
setting.
    Studies have shown that regular physical activity can improve 
physical performance in older people, but definitive evidence that 
physical activity can prevent mobility disability is lacking. NIA 
supports the Lifestyle Interventions and Independence for Elders Study 
to assess the effects of a structured physical activity program in 
1,600 sedentary older individuals. With the U.S. Surgeon General, NIA 
has also launched its nationwide Go4Life campaign to motivate older 
Americans to engage in physical activity and exercise.
    In the past year, preliminary results were released from the 
``Oregon Lottery'' study, in which randomly selected low-income Oregon 
residents were able to enroll in the State's Medicaid program. Compared 
to a control group, the new Medicaid enrollees reported improved health 
and well-being, as well as reduced financial strain. Use of important 
types of healthcare services such as preventive care also increased.
          empowering the next generation of aging researchers
    The need for healthcare professionals who specialize in the unique 
needs of older individuals is becoming ever more urgent. We must not 
only increase the number of practicing physicians trained in geriatrics 
and in subspecialty fields related to the health problems of elders but 
also foster the development of the next generation of physician-
scientists whose clinical research will lead to improved care and more 
effective treatment options for older patients with complex medical 
conditions. Recently, NIA established the Grants for Early Medical/
Surgical Subspecialists' Transition to Aging Research (GEMSSTAR) 
program to promote future leaders in clinical aging research through 
support of physicians who seek to become clinician-scientists in 
geriatric aspects of their subspecialty. NIA has also established a 
program targeting undergraduate students from diverse backgrounds in 
order to advance their interest in and knowledge of aging issues.
                                 ______
                                 
 Thomas R. Insel, M.D., Acting Director, National Center for Advancing 
                         Translational Sciences
    Mr. Chairman and members of the subcommittee: It is a privilege to 
present to you the President's budget request for the newly established 
National Center for Advancing Translational Sciences (NCATS) for fiscal 
year 2013. The fiscal year 2013 budget of $639,033,000 includes 
$64,320,000 more than the comparable fiscal year 2012 level of 
$574,713,000. We are thankful for your support for this new Center and 
look forward to sharing progress with you as the Center evolves.
    Our mission is to catalyze the generation of innovative methods and 
technologies that enhance the development, testing, and implementation 
of diagnostics and therapeutics across a wide range of human diseases 
and conditions. As such, NCATS will focus on addressing scientific and 
technical challenges in order to reduce, remove, or bypass significant 
hurdles across the continuum of translational research. These advances 
will enable others in both the public and private sectors to develop 
drugs and diagnostics more efficiently for any number of human 
diseases--ultimately accelerating the pace in which new therapeutics 
are delivered to the patients who need them.
                         fulfilling our mission
    In achieving its aims, NCATS activities will be guided by three 
important principles:
  --facilitate--not duplicate--other translational research activities 
        supported by NIH;
  --complement--not compete with--efforts already underway in the 
        private sector; and
  --reinforce--not reduce--NIH's commitment to basic research.
    These guiding principles underscore the role of NCATS as a 
catalytic hub for evidence-based research on the process of translating 
scientific discoveries into new diagnostics and therapeutics.
    Key to the success of the NCATS mission is identifying, studying, 
and reducing significant bottlenecks in the process of translation, 
which will require extensive consultation with experts across 
disciplines and sectors. NIH held numerous workshops for stakeholders 
to solicit ideas for the NCATS research agenda. A working group of 
several NIH Institute and Center directors, including those most 
involved in translational research, clarified the need for a new effort 
focused on the discipline of translation, providing tools and resources 
that could facilitate research across NIH. A working group of the NIH 
advisory committee to the Director, comprised of experts from industry, 
private equity firms, nonprofits, and academia identified the need for 
NCATS to catalyze, invigorate and streamline translational sciences 
nationally and globally. Many areas of priority were identified, 
including research on biomarkers, predictive toxicity, target 
validation, regulatory science and de-risking the pipeline. The 
perspectives of both of these working groups are reflected in several 
of the NCATS initiatives being pursued, ensuring that NCATS is not 
duplicating other efforts at NIH or competing with efforts in industry.
    NCATS is currently assembling an advisory structure comprising both 
the NCATS advisory council and the Cures Acceleration Network (CAN) 
review board. These individuals will span many sectors, from patient 
advocacy organizations to pharmaceutical industry and private equity 
firms, along with renowned experts in translational science and 
regulatory review.
               catalyzing innovation in clinical research
    Re-engineering and accelerating the clinical research enterprise is 
a major priority for NCATS. The Clinical and Translational Science 
Awards (CTSAs), which represent nearly three quarters of the proposed 
NCATS budget, will lead our efforts to re-engineer and accelerate 
clinical research. Across the Nation, CTSA institutions have been 
supporting first-in human trials for rare and common diseases; 
developing and testing innovative trial designs; and developing 
postmarketing clinical research. Since the first awards in 2006, the 
CTSAs have transformed clinical research in academic medical centers, 
creating new homes for translational science, integrating communities 
into the research process, and training a new generation of 
interdisciplinary clinical researchers. An external evaluation of the 
CTSA program has been conducted and offers constructive recommendations 
for ensuring that this highly valuable program is optimally leveraged 
and aligned with NCATS as we move forward.
    To accelerate research, the CTSAs have developed innovative 
informatics tools, such as REDcap, a freely available tool for clinical 
study management and capture, and ResearchMatch, a free, secure, Web-
based registry which now has more than 20,000 volunteers for research 
studies and enables researchers to find the ``right match'' to 
participate in studies.
    In 2013, we will be launching CTSA 2.0, the next phase of this 
program building on the successes of the past 6 years. While CTSA 1.0 
established homes for translational research, CTSA 2.0 can create 
neighborhoods, networks of centers with shared resources to accelerate 
research on rare diseases and new therapeutics. Going forward, the 
CTSAs can have an even broader role on translational science, 
supporting the entire pipeline of development from bench to bedside, 
bedside to practice, and beyond practice to public health policy.
                 catalyzing innovation in therapeutics
    Drug development is expensive, slow, and failure prone. 
Approximately 90 percent of compounds that advance to clinical testing 
fail to reach the market. While NCATS will not create an industrial 
drug development pipeline, it can experiment on the process, 
identifying solutions for specific problems in drug development.
    For instance, of the most common concerns we heard from industry, 
patient groups, and the Food and Drug Administration (FDA), was the 
need for detecting toxicity early in the drug development process. 
Roughly one-third of the failures of new medications can be attributed 
to toxicity not predicted from preclinical (animal or in vitro) 
studies. NCATS is working with the Defense Advanced Research Project 
Agency (DARPA) and the FDA to design a chip composed of diverse human 
cells and tissues with read outs that can detect toxicity. This 
``tissue chip'' should make drug safety assessments more accurate and 
even make them possible earlier in the translational pipeline. DARPA 
and NIH have committed approximately $70 million each over 5 years and 
FDA will provide guidance. The first applications were received in late 
January 2012 and will be funded this year with partial support from the 
NIH common fund.
    Aside from predicting toxicity, NCATS will be working on another 
innovation to speed medication development. Repositioning drugs that 
have not been approved (drug rescue) and drugs that are already 
approved (drug repurposing) are probably the most rapid and cost 
effective approaches to new therapies. As industry holds many of the 
assets and data required for efficient rescue and repurposing, many 
institutes at NIH have been interested in working with companies to 
access specific compounds. Rather than creating 26 different 
approaches, NCATS is working with industry to provide a single, 
comprehensive mechanism with several companies for drug rescuing. This 
will permit investigators and small businesses to apply for NIH funding 
to conduct research on new indications using compounds from industry-
provided drug collections.
    NCATS is also innovating the process of drug repurposing. Through 
the NCATS Pharmaceutical Collection, we have developed a comprehensive 
database of 3,800 approved and investigational drugs to permit NCATS to 
screen all existing medications for novel effects that might be 
therapeutic for a new indication. With this approach, we discovered 
that a drug approved for rheumatoid arthritis could be a novel 
treatment for leukemia. Rather than requiring 6-8 years for the usual 
preclinical research and development, we moved this approved compound 
into a leukemia trial (in a CTSA institution) within 9 months. 
Continued funding of this program in fiscal year 2013 will contribute 
to the NIH effort of decreasing the time, cost, and attrition rate in 
therapeutic development, to bring more promising new therapies to the 
public.
                support for rare and neglected diseases
    There are more than 6,000 rare diseases, affecting an estimated 25 
million Americans. Fewer than 250 of these rare diseases have 
treatments, according to data from the Online Inheritance in Man 
Database, Orphanet, and FDA. It is clear that efforts need to be 
directed to increasing the number of treatments either through new or 
repurposed drugs. The Therapeutics for Rare and Neglected Diseases 
(TRND) program within NCATS develops treatments for rare diseases, with 
20 projects currently underway. But TRND is not a typical drug 
development effort--the projects are selected as experiments on the 
pipeline of drug development. That is, each project is an attempt to 
re-engineer the process in addition to addressing a medical need. For 
instance, a project on sickle cell disease has introduced a new class 
of molecules not previously considered as medications for any disease. 
Moreover, the study of rare diseases, including many single gene 
disorders (Niemann-Pick Type C and Hereditary Inclusion Body Myopathy), 
is also giving us new insights into fundamental biology. This process, 
sometimes called reverse translation because it moves from ``bedside to 
bench,'' is one of the ways that NCATS is reinforcing rather than 
reducing NIH's commitment to basic research.
                          investing in people
    NCATS fosters the training of clinicians and researchers in an 
environment of innovation and collaboration, encouraging the next 
generation of leaders in translational sciences. For example, the CTSAs 
are currently supporting more than 900 trainees across a wide array of 
disciplines. NCATS will promote novel training mechanisms, such as drug 
development apprenticeships for early-stage investigators, and explore 
cross-training of physicians and scientists between industry and 
academia.
                               conclusion
    The creation of NCATS offers an exciting new opportunity for 
accelerating the development of new and more effective therapeutics and 
diagnostics; namely by approaching the process of translation as a 
scientific challenge. By encouraging biomedical researchers across the 
Nation to experiment with new and innovative ways of improving these 
processes, our best and brightest can meet today's challenges head on. 
Moreover, the development of new tools and methodologies enable all 
sectors to participate in this arena, maximizing the likelihood of 
ensuring much needed products are actually available to those who need 
it the most--patients.
                                 ______
                                 
  Prepared Statement of James F. Battey, Jr., M.D., Ph.D., Director, 
    National Institute on Deafness and Other Communication Disorders
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute on 
Deafness and Other Communication Disorders (NIDCD) of the National 
Institutes of Health (NIH). The fiscal year 2013 NIDCD budget of 
$417,297,000 includes an increase of $1,519,000 over the comparable 
fiscal year 2012 level of $415,778,000.
    The NIDCD conducts and supports research and research training in 
the normal and disordered processes of hearing, balance, smell, taste, 
voice, speech, and language. Our Institute focuses on disorders that 
affect the quality of life of millions of Americans in their homes, 
workplaces, and communities. The physical, emotional, and economic 
impact for individuals living with these disorders is tremendous. NIDCD 
continues to make investments to improve our understanding of the 
underlying causes of communication disorders, as well as their 
treatment and prevention. It is a time of extraordinary promise, and I 
am excited to be able to share with you some of NIDCD's ongoing 
research and planned activities addressing communication disorders.
                early experience shapes salt preference
    Even though we know that too much salt is bad for our health, many 
of us still consume too much of it. In a typical diet, a lot of salt 
comes from starchy foods, such as breads and cereals. Too much salt can 
cause high blood pressure, or hypertension. Although hypertension 
itself usually has no symptoms, it can cause serious health problems 
such as stroke, heart failure, heart attack, and kidney failure. NIDCD-
supported scientists determined that babies whose diets contain 
starchy, salty foods will develop a preference for salty taste by as 
early as 6 months of age, as compared to babies who have not been given 
salty foods. During a preference test, the babies accustomed to saltier 
diets consumed 55 percent more salt than their unexposed peers. Salt 
preference endures into the preschool years, when children exposed to a 
salty diet as babies are more likely to consume plain salt. This 
research identifies a potential role for early dietary experiences in 
shaping taste preferences that could influence salt consumption in our 
adult years. If these results can be repeated in a larger study 
population, it suggests that we may be able to reduce salt consumption 
in future generations by encouraging parents to restrict salt in their 
babies' early diets. Reducing salt consumption will also reduce the 
incidence of hypertension, thus reducing healthcare costs due to 
hypertension and the serious health problems it can cause.
          identification of major proteins involved in hearing
    According to NIDCD statistics, 2 to 3 out of 1,000 children in the 
United States are born deaf or hard of hearing, with changes in genes 
being a major cause of hearing impairment. NIDCD-supported scientists 
have shown that mutations in the TMC1 and TMC2 genes cause hereditary 
deafness in humans and mice. Further, they discovered that the proteins 
encoded by TMC1 and TMC2 genes may be key components of the long-sought 
after mechanotransduction channel in the inner ear--the place where 
mechanical stimulation of sound waves is transformed into electrical 
signals recognized by the brain as sound. Using mice without the TMC1 
and TMC2 genes, the scientists discovered the mice had a deficit in the 
mechanotransduction channels in their sterocilia, the sound-sensing 
organelles of the inner ear, while the rest of the auditory hair cell's 
structure and function was normal. These genes and the proteins they 
regulate are the strongest candidates yet in the search for the 
transduction channel. If these genes do indeed encode the transduction 
channel, they will be useful tools to screen for drugs or molecules 
that bind to or pass through the channel and could be used to prevent 
damage to hair cells.
                      keep noise down on the farm
    Farming is loud work. Squealing pigs, grinding combines, whirring 
power tools, and roaring vehicles can add up to a lot of noise. 
Prevention and treatment of noise-induced hearing loss (NIHL) is a 
priority for the NIDCD. NIDCD's campaign ``It's a Noisy Planet. Protect 
their Hearing'' promotes early education of elementary and middle-
school children about NIHL and how to prevent it. The NIDCD has 
introduced new materials for parents of children who live and work on a 
farm to help them develop healthy hearing habits and protect their 
hearing for life. The NIDCD hopes that these materials will help 
protect individuals who live and work on a farm from developing NIHL. 
Preventing NIHL will improve quality of life for the millions exposed 
to noise, and decrease overall healthcare costs.
   saliva is effective in screening for cytomegalovirus infection in 
                                newborns
    In June, NIDCD-supported scientists reported that swabbing a 
newborn's mouth for saliva can be used to quickly and effectively 
screen for cytomegalovirus (CMV) infection, a leading cause of 
progressive hearing loss in children. Scientists at the University of 
Alabama at Birmingham (UAB) determined that saliva correctly identified 
every baby born with the infection when liquid samples were used, and 
97.4 percent of babies when the samples were dried. Most babies 
infected with CMV don't show symptoms at birth. NIDCD has placed a high 
priority on developing diagnostic tools to screen babies for congenital 
CMV infection, so that those who test positive can be monitored for 
possible hearing loss. These children can be provided with appropriate 
intervention as soon as possible. Because of this research, we know 
that testing saliva is an effective way to identify children at risk 
for hearing loss due to CMV.
          hiv-exposed children at high risk of language delay
    Children who do not use language well may not do well in school and 
may also have difficulty communicating with their peers and 
establishing friendships. A recent study funded by the NIDCD and seven 
other NIH Institutes found that 35 percent of a group of school-age 
children born to women with an HIV infection during pregnancy have 
difficulty understanding spoken words and expressing themselves 
verbally. These data should encourage those caring for children exposed 
to HIV in the womb to provide early treatment for language impairments.
                                 ______
                                 
   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 subcommittee: I am pleased to 
present the President's budget request for the National Institute of 
Environmental Health Sciences (NIEHS) of the National Institutes of 
Health (NIH). The fiscal year 2013 NIEHS budget of $684,030,000 
includes a decrease of $725,000 less than the comparable fiscal year 
2012 level of $684,755,000.
                              introduction
    As the Dutch philosopher Desiderius Erasmus so succinctly put it: 
Prevention is better than cure. In most instances, disease is a result 
of a combination of age, genetics, and environment. But unlike age and 
genetics, environment is something that we can affect in order to 
prevent illness. As an environmental public health institute, the NIEHS 
is entrusted with the mission to prevent human suffering and illness by 
creating and sharing the knowledge necessary for understanding the role 
of the environment in disease, and thereby enable people to lead 
healthier lives. NIEHS continually strives to lead public health 
prevention efforts by providing research science and translation to 
inform decisions and policies at the individual, community, national, 
and global levels that prevent hazardous environmental exposures and 
thus reduce disease and disability. Many of the most challenging 
diseases--and most costly in terms of both human suffering and economic 
resources--are being shown to have strong environmental components. 
Diseases such as cardiovascular disease and stroke, that cause 1 in 3 
deaths in America each year, have been associated with exposure to 
environmental agents such as air pollution and secondhand smoke. An 
estimated nearly 70 percent of Americans older than the age of 20 are 
overweight or obese; for children the figure is more than 30 percent. 
New research, including studies funded by the NIEHS, shows that obesity 
and its common companion diabetes are complex disorders that are 
affected not just by food consumption and physical exertion but also by 
environmental factors including exposures to environmental contaminants 
during early life. Greater understanding of the role of such exposures 
and concomitant efforts to prevent them could dramatically change the 
trend of this increasing public health epidemic. And the list goes on. 
Strong associations have been shown between exposure of pregnant 
mothers to chemicals, including polybrominated diphenyl ethers added to 
products as flame retardants, and a range of neurodevelopmental 
disorders, learning disabilities, and behavioral effects in their 
children. NIEHS continues to commit significant efforts to increasing 
our understanding of these health effects and how they might be 
prevented. On a global level, the problem of respiratory illnesses 
resulting from exposure to indoor air pollution represents an area ripe 
for intervention. Toxic smoke from burning biofuels in cookstoves kills 
nearly 2 million people each year, largely women and children, 
according to the World Health Organization. NIEHS is part of the Global 
Alliance for Clean Cookstoves, a public-private initiative working to 
eliminate exposure to harmful cookstove smoke. This is a tractable 
prevention problem with a potentially huge payoff in public health.
 national institute of environmental health sciences strategic planning
    Looking at this long list of environmentally related diseases 
raises the question, ``How can one Institute have an impact on research 
and disease prevention in all these areas?'' To answer this question, 
NIEHS is striving to maximize its impact and leadership in the 
environmental health sciences through a comprehensive and inclusive 
strategic planning process focused on identifying key strategic goals 
for the next 5 years. Through this process, NIEHS hopes to achieve its 
vision of providing a catalyst for leading the field of environmental 
health sciences in applying state-of-the-art biomedical research to the 
most important issues surrounding environmental impacts on health.
    Six broad-based themes of this plan have been established, through 
ongoing dialogue with research scientists and stakeholder groups. 
``Fundamental Research'' investigates basic biological pathways of how 
our bodies function, to set the stage for asking more in-depth 
questions about the effects of the environment on biological systems. 
``Exposure Research'' focuses on the study of environmental exposures 
themselves, internal and external to the body. And since NIEHS 
recognizes that information is only effective if it can be translated 
into sound decisions, ``Translational Science'' is identified as a key 
theme covering research that moves a basic science observation into a 
public health or medical application. NIEHS also affirms its commitment 
to ``Health Disparities and Global Environmental Health'' in 
recognition of the fact that individuals and communities that are 
socioeconomically disadvantaged also tend to suffer inequalities in 
both health and environmental burdens. Through ``Training and 
Education,'' NIEHS recognizes the need to develop the next generation 
of top-notch, innovative, and dedicated environmental health scientists 
and professionals. Finally, to fulfill its mission and statutory 
mandate to disseminate information, NIEHS is committed to developing a 
full range of research translation and communication tools and creative 
stakeholder partnerships. This ``Communications and Engagement'' theme 
is vital for realizing the Institute's mission to promote public health 
and prevent environmentally related disease and disability. Two 
crosscutting themes, ``Collaborative and Integrative Approaches'' and 
``Knowledge Management'' will be implemented across the other themes to 
ensure the success of the goals throughout the strategic plan.
                         recent accomplishments
    The NIEHS strategic plan highlights areas of leadership that will 
build on an impressive list of recent research accomplishments. For 
example, NIEHS-funded researchers recently published the first study 
documenting how exposure to perfluorinated compounds (PFCs), widely 
used in manufactured products such as nonstick cookware, was associated 
with lowered immune response to vaccinations in children. Other recent 
research funded by NIEHS has shown that even moderate air pollution, at 
levels generally considered safe under current Federal regulations, 
increases the risk of stroke by 34 percent.
    NIEHS is also committed to helping those impacted by environmental 
exposures. In the aftermath of the Deepwater Horizon disaster, many 
questions remain about the long-term impact on the health of gulf coast 
residents and communities. NIEHS is leading a trans-NIH effort to 
create a network of community and university partnerships that seeks to 
identify personal and community health effects stemming from the 
Deepwater Horizon oil spill and to enhance community resiliency to 
potential disasters. The 5-year, $25.2 million program will support 
population-based and laboratory research, which will ultimately develop 
the scientific evidence base needed to promote health and well-being 
for people living along the gulf coast who are at greatest risk for 
potential adverse physical, psychological, and behavioral health 
effects. In addition, research will seek to develop new strategies to 
enhance capacity to respond to future disasters and prevent or minimize 
adverse health effects arising from them. Once completed, research 
findings from the Deepwater Horizon Research Consortia should 
contribute to the evidence base needed to improve preparedness and 
response aimed at minimizing disaster-related health impacts.
    Ultimately, NIEHS remains committed to its overall mission to 
discover how the environment affects people's health, in order to 
promote healthier lives.
                                 ______
                                 
  Prepared Statement of Josephine P. Briggs, M.D., Director, National 
           Center for Complementary and Alternative Medicine
    Mr. Chairman and members of the subcommittee: As the Director of 
the National Center for Complementary and Alternative Medicine (NCCAM) 
of the National Institutes of Health (NIH), I am pleased to present the 
President's fiscal year 2013 budget request for NCCAM. The fiscal year 
2013 budget includes $127,930,000, which is $26,000 more than the 
comparable fiscal year 2012 level of $127,904,000.
    The landscape of our healthcare system is changing in many 
important ways. Among them is a clear trend toward incorporation of 
complementary health practices, which often have origins outside of 
conventional medicine, into integrative approaches to care. There are a 
number of factors--including consumer demand and emerging scientific 
evidence--driving these changes. Nonetheless, there are compelling 
needs of the public, healthcare providers, and policymakers for good 
scientific evidence on the safety and potential benefit of these 
complementary and integrative approaches. Using the highest standards 
of scientific rigor, NCCAM is committed to developing evidence about 
practices that are being integrated into healthcare. We are 
particularly interested in those cases where there is scientific 
opportunity and/or important public health need.
           trends in complementary and integrative healthcare
    National surveys conducted by the National Center for Health 
Statistics (NCHS) at the Centers for Disease Control and Prevention 
show that nearly 40 percent of Americans report using one or more 
practices such as acupuncture, massage, yoga, meditation, spinal 
manipulation, dietary supplements, or herbal medicines to help manage 
their health and wellness. Similarly, data show that healthcare systems 
and providers are incorporating such interventions. For example, an 
American Hospital Association survey conducted in 2007 showed that 37 
percent of hospitals offered complementary modalities; and a national 
study reported last year by the NCHS reported widespread availability 
of complementary approaches in hospice settings. Other data from the 
Departments of Defense (DOD) and Veterans Affairs (VA) show increasing 
use of complementary modalities in their populations. According to the 
VA, 89 percent of their facilities offered complementary therapies in 
2011. Both the DOD and VA have integrated complementary modalities into 
the care of patients with post-traumatic stress and sleep disorders, 
and to improve treatment of pain.
             reducing pain and improving symptom management
    One area of urgent public health need is better strategies for 
managing chronic pain. According to the Institute of Medicine, chronic 
pain affects an estimated 116 million Americans, and costs the Nation 
approximately $635 billion each year. Chronic pain is the most 
frequently cited reason for which Americans use complementary health 
practices. For many individuals suffering from chronic pain, 
conventional approaches provide incomplete relief. Furthermore, 
pharmacological treatment with opioids or anti-inflammatory drugs can 
have significant adverse effects. There is now emerging evidence, much 
of it from NCCAM-supported studies, that some nonpharmacological 
interventions, such as massage, spinal manipulation, yoga, meditation, 
and acupuncture, may be helpful in treating chronic pain. Additional 
scientific evidence is needed to better understand these findings, and 
the optimal use and safety of these integrative approaches.
    To this end, NCCAM is supporting a growing portfolio of studies on 
the use of nonpharmacological interventions for the management of 
chronic pain, including back and neck pain and pain associated with 
osteoarthritis, fibromyalgia, and headaches. In addition, we are 
supporting research to better understand the biological mechanisms by 
which complementary modalities may contribute to management of pain and 
other symptoms. For example, we recently funded Centers of Excellence 
for Research on Complementary and Alternative Medicine that use 
advanced functional and structural neuroimaging technologies to study 
pain. NCCAM is also providing leadership to a working group within the 
trans-NIH Pain Consortium to develop standards for research on chronic 
low back pain. Finally, in the next year, NCCAM plans to focus its 
intramural research program on understanding the role of the brain in 
chronic pain syndromes. The program will be highly collaborative with 
other intramural neuroscience programs on the NIH campus.
                 advancing research on natural products
    NCCAM remains strongly committed to developing better evidence and 
information resources on the safety and efficacy of commonly used 
natural products. The Center is targeting investment in research in 
this arena on understanding the biological mechanisms of these 
products, thus creating the translational foundation for subsequent 
human studies.
    In addition, research examining issues of safety is of great public 
health importance, given the widespread availability and use of these 
products by the public. In this regard, one area of specific need is 
rigorous scientific information about interactions of these products 
with drugs or with other natural products. This spring, NCCAM will lead 
a workshop, cosponsored by the NIH Office of Dietary Supplements and 
the National Cancer Institute, with researchers from a variety of 
fields to discuss ways to improve the methodologies needed to study 
herb-drug interactions. Workshop recommendations will help guide 
NCCAM's research agenda.
              building and disseminating rigorous evidence
    Researchers studying the effectiveness and safety of healthcare 
approaches already in widespread use face methodological challenges, 
challenges that are not unique to NCCAM's mission. To develop better 
methods of studying health outcomes in real-world settings, NCCAM is 
leading an NIH Common Fund Initiative, the Health Care Systems Research 
Collaboratory. The Collaboratory will develop innovative research 
partnerships with healthcare delivery organizations to maximize the 
potential use of electronic health information. NCCAM is also exploring 
possible collaborations with the DOD and the VA, aiming to leverage the 
data being gathered on the use of complementary and integrative 
practices in their healthcare systems. Additionally, NCCAM is providing 
leadership and support to the trans-NIH Patient-Reported Outcomes 
Measurement Information System (PROMIS), which will provide clinicians 
and researchers with more efficient and reliable means for gathering 
data on a variety of patient-reported measures of health and well-
being.
    NCCAM continues to provide reliable, objective, and evidence-based 
information on the usefulness and safety of complementary health 
practices to the public and healthcare providers. For example, NCCAM 
publishes the Clinical Digest (nccam.nih.gov/health/providers/digest), 
a monthly e-newsletter that summarizes the state of the science on 
complementary health practices and clinical guidelines. Additionally, 
NCCAM provides an online resource (nccam.nih.gov/health/providers) that 
enables healthcare providers to make informed recommendations.
                               conclusion
    Strong consumer use of complementary health practices, and growing 
integration of these practices into a variety of conventional 
healthcare settings are important trends in U.S. healthcare. While 
there is emerging evidence of promise for some, there are many 
important unanswered questions about effectiveness and safety. NCCAM 
remains committed to building the scientific evidence needed by 
consumers, providers, and health policy makers to make informed 
decisions about the use of complementary and integrative health 
practices.
                                 ______
                                 
 Prepared Statement of Roger I. Glass, M.D., Ph.D., Director, Fogarty 
                          International Center
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the Fogarty International 
Center (FIC) of the National Institutes of Health (NIH). The fiscal 
year 2013 FIC budget of $69,758,000 includes an increase of $219,000 
more than the comparable fiscal year 2012 level of $69,539,000.
    These are exciting times for global health. New HIV prevention 
strategies and the use of mobile technologies to extend the reach of 
health interventions are just two examples of research into emerging 
opportunities that can transform our efforts to improve health around 
the world. These are also examples of advances that can make a 
significant impact on health here at home as well as abroad. As 
populations in both the developed and developing world are vulnerable 
to existing and emerging infectious agents, as well as the growing 
noncommunicable disease (NCD) epidemic, there is no longer a ``them'' 
in global health, only an ``us'' (Global Health Council).
    To most effectively address this shared burden of disease, U.S. 
scientists can only benefit from the unique insights and collaboration 
of skilled research partners around the world. At the NIH and within 
the U.S. Government, FIC plays a unique role by supporting the 
development of global health research expertise in the United States 
and abroad, and by fostering the international partnerships that extend 
the frontiers of science, accelerate discovery, and enable the United 
States to continue to lead in addressing the world's most pressing 
health challenges.
              strengthening sustainable research capacity
    For over two decades, Fogarty has supported the long-term training 
of thousands of scientists worldwide. These scientists provide unique 
insights and perspectives on how to best combat global health 
challenges, and often contribute to groundbreaking research advances in 
collaboration with U.S. partners.
    As the largest international commitment by any one country to fight 
a specific disease, the President's Emergency Plan for AIDS Relief 
(PEPFAR) relies on trained scientists to provide an evidence base for 
the new and effective strategies that have enabled PEPFAR programs and 
policies to make significant contributions to the progress toward an 
AIDS-free generation. For example, with support from Fogarty's 
longstanding HIV/AIDS research training program, Fogarty-supported 
researchers have provided evidence that a new, simpler, and shorter 
treatment regimen of antibiotics can prevent those infected with the 
tuberculosis (TB) bacterium--particularly those who also have HIV--from 
developing full-blown TB. In addition, Fogarty-supported researchers 
and trainees have also helped demonstrate: the effectiveness of anti-
retroviral therapies in stopping mother-to-child transmission of the 
HIV virus; that male circumcision reduces HIV transmission to HIV-
negative female partners; and a reduction in HIV transmission among 
women using microbicides that incorporate anti-retrovirals.
    In response to the increased global burden of NCDs, Fogarty's NCD-
Lifespan research training program supports partnerships between U.S. 
and low- and middle-income country (LMIC) institutions to build NCDs 
research capacity. By focusing on early childhood exposures and the 
genetic, environmental, and lifestyle risk factors that can contribute 
to later onset of disease, NCD-Lifespan projects are creating a cadre 
of investigators and institutions able to conduct research relevant to 
local and global epidemics in areas such as cancer, stroke, mental 
illness, and metabolic disorders. In Ghana, for example, Fogarty is 
supporting the development of a Cardiovascular Research Training 
Institute as a partnership between New York University and the 
University of Ghana, to train investigators to conduct research on 
preventing and treating hypertension, diabetes, stroke, and chronic 
kidney disease. The resulting cadre of investigators will contribute 
research and expertise to the global effort to reduce cardiovascular 
disease morbidity and mortality.
    With respect to identification of innovative, sustainable, and 
cost-effective strategies to fulfill its mission, Fogarty recognizes 
that information and communication technologies, mobile technologies, 
and distance learning can transform the way in which health and health 
research training can be conducted in the 21st century--particularly in 
resource-poor and remote settings. More than 50 Fogarty-supported 
projects have incorporated distance learning activities, which provide 
an innovative and cost-effective way to connect health research 
students in the developing world with state-of the-art content on the 
other side of the globe.
                      new investigators, new ideas
    Over the last decade, American university campuses have seen a 
soaring interest in global health among students and faculty from 
diverse fields, placing U.S. universities in an excellent position to 
help generate solutions to complex global health challenges. Fogarty's 
International Clinical Research Scholars and Fellows program and 
International Research Scientist Development Awards capitalize on this 
groundswell of interest to invest in future American leaders in global 
health research. These programs are investing in the next generation of 
talented American scientists, who will develop the skills and 
sensitivities to conduct research in international settings, and engage 
talented local researchers who can help to address complex health 
challenges that affect populations in the United States and abroad. 
Former Scholars and Fellows have developed innovative solutions to 
concrete global health problems. For example, in Zambia, Dr. Krista 
Pfaendler developed and implemented an effective and low-cost cervical 
cancer screening program using digital cameras for cervical photography 
and acetic acid (vinegar) for visual inspection.
    In 2010, Fogarty piloted a 1-year program to support postdoctoral 
investigators in U.S. universities to carry out innovative, 
multidisciplinary team research in global health. With support from 
this program, scientists developed point-of-care telemedicine units 
built with $2 microscopes that can be attached to a cell phone, 
enabling diagnosis of infectious diseases, such as malaria and HIV, in 
remote settings. Because of their ease of use, effectiveness, cost-
effectiveness, and the ability for quick diagnosis, these microscopes 
have the potential to revolutionize care in resource-poor settings. The 
next generation of this program, Framework Innovations, will support 
U.S. and developing country institutions as they develop 
interdisciplinary postdoctoral research training programs in global 
health and enable young investigators to develop and test concrete and 
innovative health products, processes, and policies that respond 
practically and cost-effectively to critical health needs.
                    advancing translational science
    Innovative strategies are needed to translate biomedical 
discoveries into new therapies, diagnostics, and prevention tools. 
Supported by Fogarty's International Cooperative Biodiversity Groups 
Program, United States and international scientists conduct discovery 
research on potential health applications of molecules--from plants, 
animals, and micro-organisms--and initiate partnerships with companies 
interested in developing these molecules for potential new drugs or 
diagnostics. This public-private partnership model has led to four 
active patents in the areas of cancer, parasitic diseases, and malaria.
                               conclusion
    As the world continues to become more interdependent, international 
scientific partnerships will play a critical role in building bridges 
between countries and scientists in the interest of advancing the 
health of our country and our globe. Fogarty invests in the best and 
brightest minds and catalyzes long-term, productive research 
collaborations. Working in partnership with the rest of the NIH, 
Fogarty's unique programs will continue to push the frontiers of 
science and enable scientists in the United States and abroad to work 
together to successfully tackle the world's most pressing and complex 
health challenges.
                                 ______
                                 
  Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN, Director, 
                 National Institute of Nursing Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2013 budget request for the 
National Institute of Nursing Research (NINR) of the National 
Institutes of Health (NIH). The fiscal year 2013 NINR budget of 
$144,153,000, includes a decrease of $444,000 less than the comparable 
fiscal year 2012 level of $144,597,000.
                              introduction
    I appreciate the opportunity to share with you a brief summary of 
some of the recent activities and future scientific directions of NINR. 
NINR supports clinical and basic research to build the scientific 
foundation for clinical practice, prevent disease and disability, 
manage and eliminate symptoms caused by illness, enhance palliative and 
end-of-life care, and train the next generation of scientists. In doing 
so, NINR promotes and improves the health of individuals, families, and 
communities across the lifespan, in a variety of clinical settings and 
within diverse populations. NINR's emphasis on clinical research and 
training places NINR in a position to make major contributions to 
developing the evidence base for science-driven practice through 
innovative treatment and behavioral research.
    Over the past year, we have commemorated NINR's 25th anniversary at 
NIH through a series of scientific outreach events that culminated in 
October 2011 with the release of NINR's new Strategic Plan: Bringing 
Science to Life. As NINR looks ahead to the next 25 years, the 
Institute is well-positioned to continue to advance rigorous science, 
develop and support evidence-based science-driven interventions across 
the lifespan, develop future leaders in nursing science, and contribute 
to improving the Nation's health and national healthcare system.
           advancing the quality of life: symptom management
    With the aging of a major sector of the Nation and advances in 
treatment of formerly fatal diseases, we are faced with a population 
that is living with multiple chronic conditions. The challenge of 
treating and managing these multiple conditions and their associated 
symptoms is one that confronts nearly all health practitioners, 
especially nurses involved with chronic illness management. NINR has 
invested deeply in the area of symptom management, from funding basic 
research on pain in our Intramural Research Program (IRP) to our 
extramural support for psychosocial and nutritional interventions to 
improve symptoms of chronic heart failure. Further, recognizing that 
chronic illness strikes across the lifespan, NINR also supports 
research aimed at helping children and adolescents manage their own 
chronic conditions and their symptoms more effectively to improve their 
quality of life. Finally, NINR initiated a call for research on the 
interconnections of diabetes and asthma, both on the rise in the United 
States; this research is focused on early life exposures that are 
associated with both conditions, as well as interventions that target 
the management of each disease and their synergisms.
                health promotion and disease prevention
    NINR is also heavily committed to health promotion and disease 
prevention. Nurses are often in unique positions as the health 
providers with the most frequent interactions with individuals and 
their support networks, and are therefore well-poised to help develop 
interventions that promote health and prevent disease. In one example, 
NINR currently supports an innovative community-based program in urban 
Pennsylvania that trains male Latino lay health advisors who provide 
their peers information on community support resources, including 
healthcare resources. NINR also is leading a funding opportunity 
focused on developing healthy habits in children and adolescents that 
lead to lifelong sustainable healthy behaviors that prevent disease and 
disability. Finally, in line with our focus on health promotion and 
disease prevention across the lifespan, NINR supported a research 
project that developed a successful program to guide mothers of very 
preterm infants in correctly feeding their vulnerable infants.
                     investing in nurse scientists
    NINR is strongly committed to the development of future health 
scientists, with a specific focus on the training of nurse scientists. 
Along with extramural research grants and fellowships that support pre- 
and postdoctoral students and junior and senior researchers, NINR 
offers a number of intramural training opportunities to develop nurse 
scientists. This year, we are proud to once again offer the NINR Summer 
Genetics Institute, a month-long, intensive course in genetics for 
nurse scientists at all career levels. The course is designed to 
increase research in genetics among graduate students and faculty in 
nursing, and expand the knowledge base among clinicians for genetics in 
clinical practice. NINR also sponsors the Methodologies Boot Camp, a 1-
week intensive research training course at NIH that focuses on applying 
state-of-the-art methodologies to studies of symptom management, 
including pain, fatigue, and sleep.
                    end of life and palliative care
    With advances in treatment for chronic diseases and the aging of 
our population, we as a society are facing new challenges in 
understanding the complexities of decisionmaking issues surrounding 
palliative and end-of-life care for those with advanced illness. As the 
lead NIH Institute for end-of-life research, NINR is committed to 
supporting research that leads to science-driven practices in 
palliative care that assists individuals, families, caregivers, and 
healthcare professionals in alleviating symptoms and planning for end-
of-life decisions. In August 2011, NINR convened a 3-day National 
Summit on, ``The Science of Compassion: Future Directions in End-of-
Life and Palliative Care.'' The Summit, co-sponsored by partners across 
NIH, examined the state of research and clinical practice in end-of-
life and palliative care and, with almost 1,000 registrants, provided 
an opportunity for scientists, healthcare professionals, and public 
advocates to come together to catalyze and shape the future research 
agenda for this critical scientific area. NINR also supports, along 
with the NIH Office of the Director, a palliative care research 
cooperative to develop an enhanced evidence base for palliative care by 
facilitating multi-site research studies and clinical trials.
                        investing in innovation
    NINR supports innovations that advance patient care, help lower the 
cost of healthcare, and take advantage of the advances in real-time 
personalized information on patients that guide healthcare today. For 
example, NINR supported two critical phases of the development of a 
novel ``lab-on-a-chip'' device for rapidly detecting HIV. The technique 
has proved highly successful, and the research team has gone on to 
refine and clinically test this microfluid-based lab-on-a-chip--or 
mCHIP--in real-life settings, with studies demonstrating that the mCHIP 
can accurately, rapidly, and cost-effectively detect clinically 
relevant infectious diseases in resource-limited settings. Other NINR-
supported researchers have developed a novel, automated medication 
dispenser that reminds patients when to take medication, monitors 
dosage, and reduces treatment errors. The new dispenser will be the 
first on the market that can deliver not only all common forms of drugs 
but also biologically derived injectables.
                               conclusion
    Nursing science has a central role in developing the evidence-base 
for science-driven practices in healthcare. NINR's research agenda has 
guided and will continue to guide the advances in this field of health 
research through the implementation of our new Strategic Plan. NINR 
looks forward to continuing its support of innovative nursing science 
focused on some of the most important health and healthcare related 
issues of today.
                                 ______
                                 
 Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National 
                    Human Genome Research Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Human Genome 
Research Institute (NHGRI) of the National Institutes of Health (NIH). 
The fiscal year 2013 NHGRI budget of $511,370,000 includes a decrease 
of $893,000 less than the comparable fiscal year 2012 level of 
$512,263,000.
    It is an extraordinary time for the field of genomics. Through 
recent scientific advances and technological developments, we are 
gaining a deeper understanding for how the human genome plays a central 
role in health and disease, enabling investigators across the 
biomedical research spectrum to pursue new avenues for translating this 
knowledge into clinical applications. NHGRI, guided by an ambitious 
vision for genomics research that the Institute published in February 
2011, is poised to lead a research agenda in fiscal year 2013 that will 
focus not only on basic genome biology and the genomic underpinnings of 
disease but will also seek to develop strategies for applying genomics 
to advance medical science and, ultimately, to improve the 
effectiveness of healthcare.
                      ensuring a strong foundation
    The unprecedented decreases in the cost of DNA sequencing--
resulting from NHGRI-stimulated technology development coupled with 
myriad innovations by the NHGRI Large-Scale Genome Sequencing Centers--
have fundamentally changed how genomic data is now generated as part of 
biomedical research. Whereas sequencing that first human genome during 
the Human Genome Project cost upwards of a $1 billion, sequencing a 
human genome using recently developed technologies will soon cost 
$1,000 (or less).
    The recent renewal of the program supporting the NHGRI Large-Scale 
Genome Sequencing Centers ensures the productive continuation of 
flagship initiatives such as The Cancer Genome Atlas (TCGA) in addition 
to special projects with specialists focusing on specific disorders, 
such as Alzheimer's disease. These centers will continue to develop 
innovative methodologies and information management systems, which will 
inevitably lead to further reductions in the cost of genome sequencing. 
With such reductions will come the opportunity to sequence the tens of 
thousands of individual genomes required to understand the small 
genetic differences that cumulatively confer risk for common diseases, 
such as diabetes and heart disease. Furthermore, the accessibility of 
low-cost DNA sequencing technologies will be essential for making 
genome sequencing a routine part of clinical care.
    To facilitate the utilization of genomic tools and information for 
exploring biological questions and ultimately improving clinical care, 
the NHGRI Centers of Excellence in Genomic Science will conduct 
interdisciplinary research and training initiatives focused on the 
production, analysis, and utilization of genomic data. From these 
efforts, new insights into the complexity of human genome function are 
emerging, and these in turn are benefiting the research community at 
large. Similarly, the human-centric ENCyclopedia of DNA Elements 
(ENCODE) project and the companion model organism ENCODE project 
(modENCODE) will continue to build a ``knowledge base'' that details 
the functional genomic elements underlying biological processes in 
humans as well as organisms that serve as important models for studying 
human biology.
    To complement the requisite understanding of normal genome function 
established by these projects, tools for defining the genetic 
contributions to human disease are being developed. NHGRI continues to 
lead efforts within the international 1000 Genomes project to build a 
deep catalog of genomic variants among different human populations; in 
turn, this information will be used to identify the subsets of rare and 
common variants that confer risk for (or protection from) specific 
diseases or adverse drug responses. Fiscal year 2013 will also see the 
key maturation of the Human Heredity and Health in Africa (H3Africa) 
initiative, an NIH Common Fund project managed by NHGRI. The increased 
knowledge generated about genomic variation and the complex 
interactions between environmental and genetic factors in African 
populations will enhance understanding of disease predispositions and 
drug responses for all human populations.
    If genomics is to be a powerful contributor to studies being 
performed across the biomedical research community, researchers must be 
able to process and analyze the massive amounts of genomic data that 
they can now readily produce. NHGRI will pursue the establishment of 
pioneering approaches for data management and analysis via the 
development and refinement of bioinformatic tools, resources, and 
standards.
                       translating the potential
    The Genome Sequencing Program continues to be a prominent and 
vibrant part of the Institute's research portfolio. Looking ahead, it 
will play an increased role in translating genomic-based capabilities 
to understand disease biology. The Program's renewal in fiscal year 
2012 included not only continued support for medical sequencing 
projects but also a charge to conduct collaborative research projects 
with other investigators to broaden the application of genome 
sequencing as a tool for unraveling the genomic basis of human disease. 
The prototype for the latter is TCGA, a collaboration with the National 
Cancer Institute to identify the genomic basis of many different forms 
of human cancer.
    The renewal of NHGRI's Genome Sequencing Program also included 
establishment of new Mendelian Disorders Genome Centers focused on 
rare, single-gene (called Mendelian) diseases. These new centers will 
seek to establish the genetic basis for thousands of rare disorders 
(affecting millions of Americans) for which the genetic defects remain 
unknown. Recent advances in genome sequencing offer the hope that the 
genetic underpinnings for most of these rare diseases can be identified 
through focused research efforts that were not possible or affordable 
with previous genome sequencing technologies.
                     preparing for genomic medicine
    To capitalize on its growing foundation of basic and translational 
research, NHGRI recently launched the Clinical Sequencing Exploratory 
Research projects, a new component of the Institute's Genome Sequencing 
Program. The new projects will investigate how to utilize genomic 
knowledge in medical settings and begin to explore how healthcare 
professionals can routinely use genome sequence information for patient 
care. A related effort, the Electronic Medical Records and Genomics 
(eMERGE) Network, is pursuing how patients' genomic information can be 
linked to disease characteristics and symptoms in their electronic 
medical records, providing the ability to explore associations with 
disease pathologies and eventually to improve patient care.
    Key to the ultimate success in all of these endeavors will be 
continued attention to the societal implications of advancing genomic 
technologies and understanding. Deliberate, ongoing engagement by 
laboratory, clinical, and social scientists and scholars in ethics, 
law, and philosophy with the public must remain a priority.
    Through its portfolio of basic and translational research, the 
Institute is pushing forward the boundaries of our knowledge and 
defining the issues that must be addressed before genomics is routinely 
deployed as a standard element in medical care. NHGRI is leading this 
charge by funding ambitious research programs to understand the 
structure and function of genomes more fully, to use genomics as a 
central tool for understanding the biology of disease, and to establish 
the path for the implementation of genomic medicine. In all of these 
pursuits, the Institute maintains a laser-like focus on its ultimate 
mission--to improve human health through genomics research.
                                 ______
                                 
  Prepared Statement of Judith H. Greenberg, Ph.D., Acting Director, 
             National Institute of General Medical Sciences
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget for the National Institute of General 
Medical Sciences (NIGMS) of the National Institutes of Health (NIH). 
The fiscal year 2013 budget of $2,378,835,000 includes a decrease of 
$48,354,000 less than the comparable fiscal year 2012 level of 
$2,427,189,000.
    This year, in 2012, the National Institute of General Medical 
Sciences (NIGMS) celebrates its 50-year anniversary as NIH's ``basic 
research institute.'' Since 1962, NIGMS has continuously supported 
highly creative people committed to building a broad and deep 
foundation of discovery. The findings are used and applied by 
scientists everywhere, leading to new diagnostics, new therapies, and 
new ways to prevent a wide range of diseases.
                 model systems illuminate human health
    Laboratory-animal versions of disease are a staple of basic 
biomedical and behavioral research. Because fruit flies, worms, mice, 
and other animals are easy and relatively inexpensive to work with--and 
have most of the same genes and many of the same behaviors as we do--
they are valuable tools for biomedical discovery. Sometimes, though, 
results with animal models do not hold up in human studies, in part 
because organisms studied in the laboratory lack the genetic diversity 
of people. NIGMS has addressed this problem through its support of the 
Collaborative Cross, a large-scale mouse-breeding project that 
significantly expands the genetic diversity of mice. This project has 
made its resources widely available to scientists everywhere--helping 
to fast-track important discoveries about genetics and human disease.
    Other recent studies with model systems, in this case worms, have 
pointed to new information about a group of neurological diseases that 
have a common molecular defect: the inability of normal cellular 
proteins to fold themselves into their proper three-dimensional shapes. 
Misfolded proteins are implicated in Alzheimer's, Parkinson's, and 
Huntington's diseases, amyotrophic lateral sclerosis, cancer, cystic 
fibrosis, and type 2 diabetes. The recent work identified new genes and 
signaling pathways that keep proteins folded properly and prevent toxic 
clumping. The researchers also extended their findings by identifying 
small molecules that appear to repair misfolded proteins.
                             all systems go
    While animal models offer key clues to understanding human disease, 
other studies that investigate large, interacting systems are an 
essential avenue for learning about health and disease. Systems biology 
approaches, which promote a more thorough grasp of the intricate and 
dynamic workings of how molecular and cellular parts interact to make a 
whole, is a robust area of NIGMS-funded biomedical research.
    Human behavior is one example of an enormously complicated system--
not just for an individual but also between individuals and within and 
between populations. Systems biology research employing mathematical 
models can draw connections among a vast number of inputs, uncovering 
new connections and making new predictions. NIGMS has joined forces 
with the NIH Office of Behavioral and Social Sciences Research to 
identify opportunities, challenges, and gaps in knowledge needed to 
develop useful models of social behavior. This past fall, NIGMS issued 
a call for funding research that models social behavior. The new 
program has generated substantial interest in the research community, 
and the Institute is looking forward to the results that are likely to 
have broad application.
    Another scientific area of great complexity, even though the 
subject of study is microscopic, is the interactions between viruses 
and their hosts. For many years, NIGMS has funded the AIDS-Related 
Structural Biology Program to obtain the three-dimensional structures 
of HIV proteins. Representing the culmination of hundreds of studies, 
researchers have just published a map of nearly 500 physical 
interactions between components of HIV and those in human cells. The 
research provides a gold mine for further studies into new drugs and 
vaccines against HIV.
                   accelerating the pace of discovery
    As our world has flattened due to increased human travel and 
expanded commercial trade among many international partners, a number 
of new diseases have emerged and infected people around the world. To 
help the Nation and the world understand and prepare for contagious 
outbreaks, NIGMS funds the Models of Infectious Disease Agent Study 
(MIDAS). This international effort continues to add new research 
expertise to increase its capacity to simulate disease spread, evaluate 
different intervention strategies, and help inform public health 
officials and policymakers. In 2011, MIDAS scientists used whole-genome 
sequencing to trace the path of the E. coli outbreak that made 
thousands of people ill and killed more than 50 people in Germany and 
France. The project demonstrates the power of modeling and is one of 
the first uses of genetic detective work to study the dynamics of a 
food-borne outbreak.
    The NIGMS investment accelerates the pace of discovery through its 
support of chemistry projects that enable biologists to study cells and 
organisms using state-of-the-art chemical tools; help clarify the 
chemical reactions that underlie human metabolism; and provide new 
strategies for drug development. NIGMS-supported chemists recently made 
two new discoveries that should enhance the manufacture of key drugs. 
In the first study, scientists made significant progress toward a 
simpler, more efficient way to synthesize Taxol, an important cancer 
drug used routinely to treat ovarian, breast, lung, liver, and other 
cancers. In a second study, NIGMS-funded chemists unveiled the working 
parts of the commonly used anti-fungal medicine amphotericin B, 
nicknamed by physicians ``ampho-terrible'' for its harsh side effects. 
The new work opens up possibilities for designing similar anti-fungal 
medicines that are just as effective but easier on the body.
                  investing in the future of discovery
    The Institute believes that a strong biomedical research workforce 
is essential for the tandem goals of improving health and maintaining 
global competitiveness. In 2011, NIGMS published ``Investing in the 
Future: the NIGMS Strategic Plan for Biomedical and Behavioral Research 
Training.'' Implementation of this plan is now in full swing. Going 
forward, NIGMS has articulated clearly that research training is a 
partnership between the NIH and the academic community and continues to 
engage actively with its full range of stakeholders. Key foci include 
the importance of excellent mentoring, a continuing emphasis on 
diversity, and the need to recognize a full menu of career options 
beyond academic research for newly trained scientists.
    NIGMS has also recently established a new organizational component, 
the Division of Training, Workforce Development, and Diversity, which 
integrates training, diversity, and capacity-building activities across 
Institute programs. This new component also oversees the Institutional 
Development Award (IDeA) program that broadens the geographic 
distribution of NIH funding. A new component of this effort is the IDeA 
Program Infrastructure for Clinical and Translational Research 
initiative, which encourages applications from IDeA States to develop 
infrastructure and capacity to conduct clinical and translational 
research on diseases that affect medically underserved populations and/
or diseases prevalent in these 23 States and territories traditionally 
underfunded by the NIH.
                 extending the reach of basic research
    Within the clinical realm, NIGMS continues to support the NIH 
Pharmacogenetics Research Network (PGRN), now in its 12th year of 
funding. This endeavor has yielded a bounty of medically relevant 
knowledge, including how genetic information can help predict how heart 
drugs, cancer medicines, nicotine patches, and a range of other 
treatments are likely to work in a particular person. One PGRN project 
is now partnering with the Electronic Medical Records and Genomics 
(eMERGE) Consortium to test samples from people whose electronic 
medical records are also available to the researchers. The goal is to 
demonstrate that DNA differences can be useful for decisionmaking about 
drug type and dosage, and ultimately to improve medication safety and 
efficacy.
                                 ______
                                 
   Prepared Statement of Alan E. Guttmacher, M.D., Director, Eunice 
     Kennedy Shriver National Institute of Child Health and Human 
                              Development
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the fiscal year 2013 President's budget request for the Eunice 
Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD) of $1,320,600,000. This reflects an increase of 
$775,000 more than the comparable fiscal year 2012 level of 
$1,319,825,000.
                  50 years of contributions to health
    This year marks the 50th anniversary of the founding of the NICHD. 
Thanks to continuing congressional support and the unwavering 
dedication of our scientists and stakeholders, NICHD research has 
changed the lives of women, children, families, and those individuals 
with disabilities worldwide. Since the NICHD was established in the 
early 1960s, research supported by the Institute contributed to a 50 
percent drop in sudden infant death syndrome (SIDS), and a 70-percent 
drop in respiratory distress syndrome, both leading causes of the 
Nation's infant mortality rate. Transmission of HIV from infected 
mother to fetus dropped from 25 percent to less than 1 percent in the 
past 15 years. Discovery of an early biological marker of pregnancy led 
to the development of what is now the standard pregnancy test. The 
incidence of Haemophilus influenzae type b (Hib) meningitis, once the 
leading cause of acquired intellectual disability, has dropped more 
than 90 percent with the development of the Hib vaccine by NICHD 
scientists. Beyond these past contributions to public health, our 
anniversary presents a unique opportunity to catalyze scientific 
advances.
                   new advances continue the momentum
    The NICHD's basic research, conducted on the NIH campus and 
supported at academic institutions nationwide, adds to scientific 
knowledge and enables clinical researchers to develop and test new 
treatments. For example, in type 1 diabetes, the immune system destroys 
the body's insulin-producing cells that help control blood glucose 
levels. Infertility researchers funded by the NICHD found a way to 
convert endometrial stem cells into insulin-producing cells and 
transplant them into mice to control diabetes. These findings suggest 
that ultimately, a woman's own, readily available, endometrial stem 
cells could be used to develop insulin-producing islet cells, 
minimizing the chance of rejection posed by using tissues or cells from 
another person.
    Research shows promise for developing new treatments for uterine 
fibroids. These noncancerous tumors, 3 to 4 times more common in 
African American than white women, are often associated with chronic 
pain, infertility, and preterm labor. Currently, few treatment options 
exist except surgical removal of the uterus (hysterectomy). A recent 
NICHD-sponsored analysis concluded that the economic costs of the poor 
health outcomes, treatment, and management of fibroids in the U.S. may 
reach $34 billion annually. Other NICHD-supported researchers found 
that treatment with vitamin D reduced the size of uterine fibroids in 
laboratory rats predisposed to developing the tumors, suggesting that 
differential rates of vitamin D deficiency could help explain the 
health disparities in fibroid formation. Another approach, using a drug 
to shrink the tumors, has shown promise in preliminary clinical 
studies.
    New technologies and tools are allowing the research community to 
move science along faster than ever. For example, a NICHD-supported 
physiatrist is combining bioengineering with a technique called 
``targeted muscle reinnervation,'' using nerves that remain after 
amputation to control assistive devices; this has enabled researchers 
to link an individual's brain impulses to a computer in a prosthesis 
that directs motors to move the limb. The NICHD Small Business 
Innovation Research (SBIR) program has supported development of 
emerging technologies to address mounting concerns about the effects of 
concussions. Scientists have created a device mounted inside a football 
helmet to measure the impact of a collision. This new tool has already 
helped to quantify the impact of concussions for college football 
players, determine how head injuries may differ for football players at 
different positions, and can be used to design more protective helmets.
    Scientists at the NIH's Autism Centers of Excellence are taking 
advantage of new insights into brain structure and function in their 
Infant Brain Imaging Study. Using a special imaging technique, they 
tracked the brain development of infants and toddlers who have an older 
sibling with an autism spectrum disorder (ASD), and thus, are at 
increased risk of developing ASD themselves. The researchers found 
distinctly different patterns of brain development in the younger 
siblings who were later diagnosed with ASD compared to those who 
weren't. These findings represent the earliest age (6 to 24 months) at 
which such biomarkers for ASD have been identified.
    It is especially gratifying when scientific advances like these are 
put into practice. Last year, I reported on a major new study supported 
by the NICHD demonstrating that fetal surgery to correct 
myelomeningocele (spina bifida) greatly reduced the risk of death and 
doubled the chances of children being able to walk, compared to the 
standard practice of postnatal surgery. Over the past year, the NICHD 
has convened a series of meetings with numerous leading professional 
societies to ensure sufficient and consistent training and guidelines 
for performing this highly complex procedure as it becomes available in 
various sites around the country.
    In late 2011, an NICHD-supported analysis of more than 5 million 
medical records showed that pregnant women assaulted by an intimate 
partner are at increased risk of giving birth to infants at lower birth 
weights. Babies born at low birth weights are at higher risk for SIDS, 
heart and breathing problems, and learning disabilities. The American 
College of Obstetricians and Gynecologists used this information in 
developing physician training materials for screening patients for 
intimate partner violence.
    Since 2002, the NICHD has led the NIH's implementation of the Best 
Pharmaceuticals for Children Act, supporting pharmacokinetic research 
and new clinical trials on drugs not previously tested for pediatric 
use. Due in large part to the NICHD's Pediatric Trials Network, data on 
pediatric safety, dosing, and efficacy for several common drugs were 
sent to the Food and Drug Administration this year so that the drugs' 
labels can be changed, and the children potentially benefiting from 
these therapeutics can be treated appropriately.
                  looking ahead: scientific visioning
    As exciting as these advances are, we know that the promise of 
improving the Nation's health depends on enlightened management of the 
research enterprise. The NICHD has just concluded a ``visioning'' 
process to help us focus over the next 10 years on the best ways to 
achieve scientific goals, enhance prevention, and continue to improve 
the Nation's health. After in-depth consultation with more than 700 
experts from around the country, white papers covering nine major areas 
of our science were made available online (http://www.nichd.nih.gov/
vision), and a scientific commentary summarizing NICHD's overall vision 
will appear in a major medical journal later this year. Now the NICHD 
looks to the future, where we will work with our research partners to 
detail how genes, the environment, and behaviors interact, starting 
before birth, to affect health outcomes. We plan to determine all the 
causes of preterm birth, devise new treatments to maximize gynecologic 
health, and improve the health and functioning of individuals with 
intellectual, developmental, or physical differences. Collaborative 
efforts to strengthen transdisciplinary research and enhance the ways 
that we conduct science will be essential to this future.
                               conclusion
    Whether they work at the NIH or receive grants at academic 
institutions across the country, NICHD-supported scientists are an 
invaluable national resource. In the past year alone, two long-time 
NICHD grantees were among only seven researchers named by President 
Obama as recipients of the National Medal of Science. And, to honor her 
work encouraging young women from the inner city to engage in 
scientific research careers, a third NICHD grantee was recently awarded 
the Presidential Award for Excellence in Science, Mathematics, and 
Engineering Mentoring. It is with the help of exceptional individuals 
such as these, and your support, that we will embark on the next 50 
years of the NICHD's ``Research for a Lifetime.''
                                 ______
                                 
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 subcommittee: I am pleased to 
present the President's budget request for the National Institute of 
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National 
Institutes of Health (NIH). The fiscal year 2013 NIAMS budget of 
$535,610,000 includes an increase of $462,000 more than the comparable 
fiscal year 2012 level of $535,148,000.
                              introduction
    As the primary Federal agency for supporting medical research on 
diseases of the bones, joints, muscles, and skin, NIAMS touches the 
lives of nearly every American. Training the basic and clinical 
scientists who carry out this research, and disseminating information 
on research progress in these diseases, are two other important 
components of the NIAMS mission.
              using science to inform healthcare decisions
    Over the past two decades, the NIH Study of Osteoporotic Fractures 
(SOF) has provided information that healthcare providers are using to 
assess people's bone health. SOF's finding that bone mineral density 
(BMD) relates closely to fracture risk, for example, contributed to 
Medicare's decision to pay for numerous people to get their BMD 
measured every 2 years. Many started taking bone-preserving drugs 
because of their results, and the rate of hip fractures dropped nearly 
25 percent among female beneficiaries. New, longer-term data from SOF 
could refine the screening guidance: women at the highest risk of 
osteoporosis might benefit from annual exams, while frequent 
measurements may be unnecessary for others. In fact, women with the 
lowest risk could be tested much less frequently unless other aspects 
of their health change.
    As multiple treatments become available for various conditions, 
research is needed to help clinicians decide which options are best for 
their patients. Studies of adults who have rheumatoid arthritis (RA) 
suggest that aggressive treatment is more beneficial than waiting until 
the disease progresses. A group of rheumatologists tested whether a 
similar approach would reduce the disability and healthcare costs of 
juvenile idiopathic arthritis (JIA). They compared two therapies and 
determined that early treatment with either strategy increased the 
likelihood that the joint-destroying processes would stop.
    Many diseases within the NIAMS mission involve pain, fatigue, and 
other difficult-to-measure symptoms. The ability to quantify changes in 
these parameters could enhance clinical outcomes research and, 
ultimately, clinical practice. NIAMS is one of several NIH components 
engaged in the Patient-Reported Outcomes Measurement Information System 
(PROMIS) Initiative to develop such a tool. In addition to managing 
PROMIS on behalf of NIH, NIAMS is encouraging researchers to use the 
resource in ongoing clinical studies of rheumatic, musculoskeletal, and 
skin diseases.
    For the past decade, researchers have been monitoring the health of 
people who have low back pain due to intervertebral disk herniation, 
lumbar spinal stenosis, or degenerative spondylolisthesis. Early 
findings showed that, in general, most surgical patients fared better 
than patients who received nonoperative care, although many patients 
got better without surgery. Recent data show that the cost-
effectiveness of surgery for low back pain due to these disorders--4 
years after an operation--is comparable to that of other common 
treatments for nonmusculoskeletal conditions.
    Community engagement is a key component for translating 
interventions into healthcare and integrating lifestyle changes into 
daily living. To address the well-documented disparities in medical 
knowledge and research participation, NIAMS will continue its 
Multicultural Outreach Initiative to improve access to health 
information for underserved minority populations. Fiscal year 2013 
plans include field testing program materials and creating an 
electronic toolkit to facilitate their dissemination.
                      investing in basic research
    Itch is an often difficult and sometimes debilitating symptom of 
many skin diseases and other disorders within the NIAMS mission. Poor 
knowledge of the mechanisms underlying chronic itch has hampered the 
development of pharmacologic treatments. In fiscal year 2013, NIAMS 
will encourage basic and translational studies in this area.
    NIAMS maintains a considerable investment into the genetic and 
cellular basis of osteoarthritis (OA), with the goal of identifying 
potential targets for therapies that halt tissue degeneration. Even 
after researchers develop treatments to stop or reverse OA progression, 
however, some patients will require total joint replacement. With 
support from the American Recovery and Reinvestment Act of 2009, 
researchers made a surprising discovery about the lubricating layer 
that forms around metal-on-metal hip implants. Instead of cell-based 
fluid made by the patient, the lubricant is a synthetic material 
produced through friction. This finding could lead to longer-lasting 
materials which, in turn, could improve the surgeries' success and 
reduce their long-term costs.
    With the advent of new laboratory and data mining tools, 
investigators are making connections among biologic processes and organ 
systems that previously were viewed independently. For example, 
researchers are learning that inflammation, which plays an important 
role in RA and other autoimmune joint diseases, is involved in OA onset 
and osteoarthritic joint degeneration. Others are exploring how 
normally harmless microorganisms can lead to RA by causing the immune 
system to attack healthy tissue.
    The technologic advances related to genome-wide analyses have 
enabled investigators to identify a genetic mutation that causes a rare 
childhood disease characterized predominantly by inflammation and fat 
loss. The disorder, named chronic atypical neutrophilic dermatosis with 
lipodystrophy and elevated temperature (CANDLE), may actually represent 
a spectrum of diseases that have been described in the literature under 
a variety of names. More importantly, since no treatment for this 
disease exists, the findings may have uncovered a possible target for 
future therapies.
                    advancing translational sciences
    NIAMS supports several large programs to encourage teams of 
translational researchers. In fiscal year 2013, it again will partner 
with other NIH Institutes to fund applications for the Wellstone 
Muscular Dystrophy Cooperative Research Centers program. The Centers 
have facilitated numerous basic discoveries and animal tests since 
their establishment in 2003. A group of investigators that includes 
Wellstone researchers recently published preclinical data about small 
molecules that target the defective RNA that causes myotonic dystrophy 
type 1. The cell-culture and mouse-model findings have the potential to 
benefit people who have myotonic dystrophy type 1; their promise also 
extends to other conditions that might be amenable to RNA-targeted 
therapies.
    NIAMS strengthened its Small Business Innovation Research (SBIR) 
program in recent years by inviting eligible companies to propose 
studies on specific topics that complement the Institute's other 
grants. Results from the targeted efforts include a cell-derived human 
skin substitute for use in consumer product testing, drug discovery, 
and toxicity screening. NIAMS will continue to look for opportunities 
that could benefit from an SBIR focus and will solicit applications as 
areas are identified.
                               conclusion
    The advances described above are just a few of the contributions 
that NIAMS-funded investigators have made to save and improve millions 
of American lives. Collectively, the Institute's research, training, 
and health information programs have significantly advanced our 
understanding of how to treat or prevent many common, chronic, costly 
diseases. Looking forward, this progress will serve as a strong 
foundation for the future, as the burden that these conditions place on 
individuals and society is reduced and, over time, eliminated.
                                 ______
                                 
   Prepared Statement of Story C. Landis, Ph.D., Director, National 
             Institute of Neurological Disorders and Stroke
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute of 
Neurological Disorders and Stroke (NINDS) of the National Institutes of 
Health (NIH). The fiscal year 2013 NINDS budget of $1,624,707,000 
includes an increase of $278,000 more than the comparable fiscal year 
2012 level of $1,624,429,000. The NINDS mission is to reduce the burden 
of neurological diseases through research. NIH research has improved 
the lives of many people with neurological disorders directly and by 
providing the foundation for private sector research. The American 
Heart Association (AHA) reported that the stroke death rate decreased 
by 34.8 percent from 1998 to 2008. Better treatments are available for 
multiple sclerosis, epilepsy, Parkinson's, and other diseases, and 
genetics research has led to tests that significantly reduce the time 
to obtain the correct diagnosis for many rare disorders. Moreover, 
basic science is driving remarkable opportunities for progress. 
Paradoxically, however, industry is significantly reducing their 
investment in research on brain disorders because of the challenges 
brain diseases present. NINDS supports a spectrum of basic, 
translational, and clinical research to complement and encourage 
private sector efforts. Because gaps in basic understanding of the 
normal brain or disease are most often the cause when progress against 
neurological disease is not forthcoming, the Institute continues to 
invest more than one-half of its resources in basic research, for which 
the NIH role is especially crucial.
                         accelerating discovery
    Last year, for the first time, researchers provided a molecular 
diagnosis for a family's inherited disease using whole genome 
sequencing (WGS). The disease was a type of Charcot Marie Tooth 
disease, a disorder that affects the body's nerves. This year WGS 
provided not only a molecular diagnosis but also immediate therapeutic 
benefit. In this study, twin children had been diagnosed with dopa-
responsive dystonia, a movement disorder that reflects a deficiency of 
the neurotransmitter dopamine. The children's health problems persisted 
despite treatment with the drug l-dopa, which replenishes dopamine and 
is usually effective. Once WGS identified the specific gene defect, it 
became apparent that the neurotransmitter serotonin was also deficient. 
Boosting serotonin with a readily available drug dramatically improved 
the children's health. Dozens of studies are now underway using these 
``next generation'' sequencing methods in common and rare neurological 
diseases. A new ``Center without Walls,'' for example, is bringing the 
best researchers together, regardless of geography, to apply the new 
genetics technologies to epilepsy.
    Next-generation sequencing is just one of several technologies that 
are transforming basic and clinical neuroscience. Optogenetics allows 
precise control of nerve cells' activity by light. Induced pluripotent 
stem cell (iPSC) methods derive nerve cells from skin cells of patients 
affected by disease, to enable studies of disease and screening of 
drugs in a culture dish. NINDS supports extensive iPSC research, 
including consortia in ALS, Parkinson's, and Huntington's disease. 
Brain imaging now reveals structure, activity, and chemistry of the 
living brain in health and disease. Recently, for example, brain 
imaging provided insights about traumatic brain injuries (TBI) in the 
military, the lingering effects of concussions in young athletes and 
new understanding of autism . The NIH Human Connectome Project is an 
ambitious imaging effort to map the wiring diagram of the entire human 
brain. NIH encourages sharing of data from the Connectome project, gene 
studies, iPSC methods, and other research that is producing 
extraordinary amounts of useful information. A notable recent effort to 
promote data sharing is a TBI database created jointly by the NIH and 
the Department of Defense.
                    translating discovery to health
    NINDS has a long history of translating scientific advances into 
better medicine. Rare disease studies, bold new therapeutic strategies, 
and technology development are examples of translational research in 
which NINDS plays a key role. Several NINDS programs support 
translational research. The Anticonvulsant Screening Program (ASP) has 
contributed to the development of eight epilepsy drugs now on the 
market. Following an external review completed this year, the ASP will 
refocus on what most concerns the epilepsy community today--drugs to 
address treatment-resistant epilepsy and to modify the course and 
development of the underlying disease. Recent activities in the NINDS 
Neural Prosthesis Program, which pioneered this entire field, include 
collaboration with Defense Advanced Research Projects Agency (DARPA) to 
enhance brain control of an advanced prosthetic arm, and development of 
an ultrathin flexible brain implant that could one day be used to treat 
epileptic seizures and other disorders. To exploit opportunities across 
all neurological disorders, the Cooperative Program in Translational 
Research, begun in 2002, supports teams of academic and small business 
investigators to carry out preclinical therapy development. NINDS is 
now funding two Phase II clinical trials of therapies developed in this 
program. NINDS is also leading an NIH Blueprint Grant Challenge to 
develop truly novel drugs that will transform the treatment of nervous 
system diseases.
    Because candidate therapies for many disorders are emerging, in 
2011 NINDS launched the NeuroNext clinical network at 25 sites across 
the United States. NeuroNext will remove roadblocks to the crucial 
early stage clinical testing of novel therapies and reduce from years 
to months the time to move new therapies into testing in patients. 
NeuroNext will test biomarkers for spinal muscular atrophy (SMA) in its 
first clinical study to prepare for trials of candidate therapies for 
SMA.
    NINDS phase III, multi-center clinical trials continue to advance 
public health. The Neurological Emergency Treatment Trials (NETT) 
network completed the Rapid Anticonvulsant Medication Prior to Arrival 
(RAMPART) trial well ahead of schedule, showing that paramedics in the 
field can safely deliver the drug midazolam into muscle using an 
autoinjector (like an EpiPen) and stop continuous seizures faster than 
the usual intravenous treatment. These results inform responses to 
common continuous seizures and seizures caused by industrial accidents 
or nerve agents. NETT trials of stroke and TBI emergency treatments are 
underway. Also this year, the Stenting vs. Aggressive Medical 
Management for Preventing Recurrent Stroke in Intracranial Stenosis 
(SAMPRISS) clinical trial showed that patients at high risk for a 
second stroke who received intensive medical treatment had fewer 
strokes and deaths than patients who received a stent in blood vessels 
that supply the brain in addition to the medical treatment. Follow up 
is continuing to compare longer-term benefits.
    With the concern about dementia as our population ages, it is worth 
noting that stroke is a major contributor to dementia, highlighting the 
complex relationships among various types of dementia. Not only do the 
7 million U.S. stroke survivors have an increased likelihood of 
cognitive problems, and perhaps also 13 million who have had ``silent 
strokes'' but also vascular problems that cause stroke are also 
associated with Alzheimer's disease. Signs that a stroke has occurred 
are often found in the brains of Alzheimer's patients, and beta-
amyloid, a key protein in Alzheimer's pathology, may stimulate the 
formation of blood clots, which can cause stroke. Furthermore, last 
year the Reasons for Geographic and Racial Differences in Stroke 
(REGARDS) study, which is following more than 30,000 people, reported 
that high blood pressure and other known risk factors for stroke 
increase the risk of cognitive problems, even among people who have 
never had a stroke. Research suggests that there is a dementia spectrum 
from pure vascular dementia to pure Alzheimer's disease, with most 
patients having contributions from both. Recognition of intersections 
not only between Alzheimer's disease and stroke but also Alzheimer's 
disease with TBI, Parkinson's, frontotemporal dementia, and other 
disorders may provide leads toward better prevention and treatment of 
all dementias.
    Hundreds of neurological disorders affect patients, families, and 
society. The aging population, concern about the long lasting effects 
of TBI, and reduced private sector investment are among several factors 
that underscore the importance of NINDS funded research. Although 
neurological disorders present enormous challenges, progress in 
neuroscience and other areas of research provides exceptional 
opportunities for the future.
                                 ______
                                 
 Prepared Statement of Donald A.B. Lindberg, M.D., Director, National 
                          Library of Medicine
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Library of 
Medicine (NLM) of the National Institutes of Health (NIH). The fiscal 
year 2013 NLM budget of $372,651,000 includes an increase of $7,608,000 
more than the comparable fiscal year 2012 level of $365,043,000. Funds 
have been included to allow the National Center for Biotechnology 
Information (NCBI) to meet the challenges of collecting, organizing, 
analyzing, and disseminating the deluge of data emanating from research 
in molecular biology and genomics.
    As the world's largest biomedical library and the producer of 
internationally trusted electronic information services, NLM delivers 
trillions of bytes of scientific data and health information to 
millions of users every day. Many searches that begin in Google or a 
mobile ``app'' actually retrieve information from an NLM Web site. 
After 175 years, NLM is a key link in the chain that makes biomedical 
research results--DNA sequences, clinical trials data, toxicology and 
environmental health data, published articles, and consumer health 
information--readily available to scientists, health professionals, and 
the public. A leader in biomedical informatics and information 
technology, NLM also conducts and supports leading-edge research and 
development in electronic health records, clinical decision support, 
information retrieval, imaging, computational biology, 
telecommunications, and disaster response.
    NLM's programs and services directly support NIH's four key 
initiatives in basic research, technology, translational science, and 
research training. The Library organizes and provides access to the 
published medical literature and massive amounts of scientific data 
from high throughput sequencing; assembles data about small molecules 
to support research and therapeutic discovery; provides the world's 
largest clinical trials registry and results database; and is the 
definitive source of published evidence for healthcare decisions. 
Research supported or conducted by NLM underpins today's electronic 
health record systems. The Library has been the principal funder of 
university-based informatics research training for 40 years, supporting 
the development of today's leaders in informatics research and health 
information technology. NLM's databases and its partnership with the 
Nation's health sciences libraries deliver research results wherever 
they can fuel discovery and support health decisionmaking.
                     research information resources
    NLM's PubMed/MEDLINE database is the world's gateway to research 
results published in the biomedical literature, linking to full-text 
articles in PubMed Central, including those deposited under the NIH 
Public Access Policy, and on publishers' Web sites, as well as 
connecting to vast collections of scientific data. Through its NCBI, 
NLM is a hub for the international exchange and use of molecular 
biology and genomic information, with many databases fundamental to the 
identification of important associations between genes and disease and 
to the translation of new knowledge into better diagnoses and 
treatments. Resources such as dbGaP, the Genetic Testing Registry (GTR) 
and the ClinVar database create a bridge between basic research and 
clinical applications.
    NLM also stands at the center of international exchange of data 
about clinical research studies. NLM's Lister Hill National Center for 
Biomedical Communications builds ClinicalTrials.gov, the world's most 
comprehensive clinical trials database, including registration data for 
more than 117,000 clinical studies with sites in 178 countries. 
ClinicalTrials.gov has novel and flexible mechanisms that enable 
submission of summary results data for clinical trials subject to the 
Food and Drug Administration Amendments Act of 2007. To date, summary 
results are available for more than 5,000 completed trials of FDA-
approved drugs, biological products, and devices--providing a new and 
growing source of evidence on efficacy and comparative effectiveness. 
NLM is a primary source for results of comparative effectiveness 
research, providing access to evidence on best practices to improve 
patient safety and healthcare quality. In 2011, the Library greatly 
expanded its collection of full-text guidelines, evidence summaries, 
and systematic reviews from authoritative agencies and organizations 
around the world.
          health data standards and electronic health records
    Electronic health records (EHRs) with advanced decision-support 
capabilities and connections to relevant health information will be 
essential to achieving precision medicine and helping Americans manage 
their own health. For 40 years, NLM has supported seminal research on 
electronic patient records, clinical decision support, and health 
information exchange, including concepts and methods now reflected in 
EHR products and personal health record tools, such as Microsoft Health 
Vault. As the HHS coordinating body for clinical terminology standards, 
NLM works closely with the Office of the National Coordinator for 
Health Information Technology to facilitate adoption and ``meaningful 
use'' of EHRs. NLM supports, develops, and disseminates several key 
data standards now required for U.S. health information exchange. While 
actively engaged in research on Next Generation EHRs, NLM also produces 
tools, frequently used subsets of large terminologies, and mappings to 
help EHR developers and users implement health data standards right 
now. NLM's MedlinePlus Connect is used in multiple EHR products to 
provide high quality health information relevant to a patient's 
specific health conditions, medications, and tests, as present in his 
or her EHR.
                  information services for the public
    This EHR connection builds upon NLM's extensive information 
services for patients, families and the public. The Library's 
MedlinePlus Web site provides integrated access to high quality 
consumer health information produced by all NIH components and HHS 
agencies, other Federal departments, and authoritative private 
organizations. It serves as a gateway to specialized NLM information 
sources for consumers, such as the Genetic Home Reference and the 
Household Products Database. Available in English and Spanish, with 
selected information in 40 other languages, MedlinePlus averages well 
over 750,000 visits per day. Mobile MedlinePlus, also in both English 
and Spanish, reaches the large and rapidly growing mobile Internet 
audience.
    The NIH MedlinePlus magazine, in English and Spanish, is an 
outreach effort made possible with support from many parts of NIH and 
the Friends of the NLM. Distributed free to the public via physician 
offices, community health centers, libraries and other locations, the 
magazine reaches a readership of up to 5 million nationwide. Each issue 
focuses on the latest research results, clinical trials and guidelines 
from the 27 NIH Institutes and Centers.
    To be of greatest use to the widest audience, NLM's information 
services must be known and readily accessible. The Library's outreach 
program, with a special emphasis on reaching underserved populations, 
relies heavily on the more than 6,300-member National Network of 
Libraries of Medicine (NN/LM). The NN/LM is a network of academic 
health sciences libraries, hospital libraries, public libraries and 
community-based organizations working to bring the message about NLM's 
free, high-quality health information resources to communities across 
the Nation.
                    disaster information management
    Through its Disaster Information Management Resource Center, NLM 
builds on proven emergency backup and response mechanisms within the 
NN/LM to promote effective use of libraries and information specialists 
in disaster preparedness and response. NLM conducts research on new 
methods for sharing health information in emergencies as its 
contribution to the Bethesda Hospital Emergency Preparedness 
Partnership, a model of private-public hospital collaboration for 
coordinated disaster planning. NLM works with the Pan American Health 
Organization (PAHO) and the Latin American Network for Disaster and 
Health Information to promote capacity-building in disaster information 
management. In addition, NLM responds to specific disasters worldwide 
with specialized information resources appropriate to the need, 
including a recently launched Disaster Information Apps and Mobile Web 
Sites page.
    In summary, NLM's information services and research programs serve 
the Nation and the world by supporting scientific discovery, clinical 
research, education, healthcare delivery, public health response, and 
the empowerment of people to improve personal health. The Library is 
committed to the innovative use of computing and communications to 
enhance public access to the results of biomedical research.
                                 ______
                                 
  Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D., Director, 
      National Institute of Biomedical Imaging and Bioengineering
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute of 
Biomedical Imaging and Bioengineering (NIBIB) of the National 
Institutes of Health. The fiscal year 2013 NIBIB budget of $336,896,000 
is $1,058,000 less than the comparable fiscal year 2012 level of 
$337,954,000.
    The mission of NIBIB is to improve human health by leading the 
development and accelerating the application of biomedical 
technologies. NIBIB invests resources in scientific and technological 
research opportunities at the convergence of the physical, quantitative 
and life sciences, and in training the next generation of researchers. 
The Institute is at the forefront of translating scientific advances 
into engineered medical solutions. Ultimately, NIBIB seeks to realize 
innovations that address healthcare challenges, reduce disease 
mortality and morbidity, and enhance quality of life. To accomplish 
this goal, NIBIB continues to fund bold and far-reaching projects that 
facilitate discovery and translate basic science into better 
healthcare.
         discovery science and technologies to empower patients
    Neurostimulation Research in Paraplegics: Recovery of Voluntary 
Motion, Bladder, and Sexual Function.--Through the NIBIB Rehabilitation 
Engineering program, researchers from the University of California, Los 
Angeles, have developed a high-density electrode array technology for 
epidural stimulation of the spinal cord. The first patient, the victim 
of a car accident that left him completely paralyzed from the chest 
down, received electrical stimulator implants in his lower back. Over a 
1-year period, he received daily electrode stimulating sessions with 
specific tasks and movements being performed, which is known as 
locomotor training. The procedure resulted in independent standing, 
some voluntary leg control, and regained bladder, bowel, and sexual 
function. It is believed that the epidural stimulation and locomotor 
training have two distinct roles. The stimulation appears to switch on 
intact circuits in the spinal cord, while the training relays specific 
information about body and limb positions. The investigators have 
applied this technology to three patients with complete spinal cord 
injury. All patients are able to stand and voluntarily control both 
legs in the presence of epidural stimulation.
    Wireless Tongue Drive System Could Provide Independence to 
Paralyzed Patients.--Assistive technologies (ATs) have been available 
to control devices used for daily living such as powered wheelchairs 
and computers. However, many of these devices have limited commands, 
cause rapid muscle fatigue, or interfere with the user's basic 
functions. NIBIB-funded researchers from the Georgia Institute of 
Technology have developed a tongue-operated AT called the Tongue Drive 
System (TDS) that is unobtrusive, wearable, wireless, and can 
substitute for many arm and hand functions. The core TDS technology 
exploits the fact that even a person with severe paralysis that impairs 
breathing and speech can still move their tongue and therefore, can 
fully utilize this extraordinary system. The device consists of a 
headset, a compact computer, and a tiny magnet attached to the tongue. 
Tongue movements change the magnetic field around the mouth. These 
changes are detected by magnetic sensors in the headset, relayed to the 
computer, and translated into the commands of the user. The system 
allows users to control various devices and perform numerous tasks such 
as drive their wheelchairs, operate their computers, and generally 
control their environment in an independent fashion. The TDS can be 
linked to currently available technologies such as a smart phone, to 
control household appliances, lights, locks, heating/air conditioning, 
as well as prosthetic arms or legs. This remarkable technology could 
offer paralyzed individuals an unprecedented level of independence for 
leading active, productive lives.
          technologies to accelerate therapeutics development
    Multi-Layered Nanoparticles for Specific Delivery of Drugs to 
Tumors.--An important area of investigation supported by NIBIB is 
targeted drug delivery, e.g., to cancer cells and not the surrounding 
normal tissue. One group of investigators has created multilayered 
nanoparticles that can be delivered systemically (by venous injection) 
but act only at the site of the tumor due to the specific chemical 
properties of each layer and their interaction with the specific 
biochemistry of tumor cells. The properties of the outer surface layer 
were designed to provide a surface that promotes distribution of 
particles throughout the body and shields the drug while preventing 
binding to healthy tissues. This outer ``stealth'' layer is also pH-
sensitive and is shed in the acidic environment of tumors exposing the 
toxic load of the nanoparticle. At the site of a tumor, the shed 
surface layer reveals a charged nanoparticle layer, which contains the 
anti-cancer agent and is readily taken up by tumor cells. The 
investigators have demonstrated that this concept for tumor targeting 
is applicable to a broad range of cancers and compatible with various 
therapies designed to be triggered by acidic tumor tissue. Because 
particles can be designed with layers that can be shed in specific 
environments, the cancer drug can be exposed and delivered directly to 
the tumor, which makes this emerging technology an extremely promising 
cancer drug delivery technique.
    Nanoscale Theranostics: Delivering Treatment and Monitoring 
Efficacy Simultaneously.--Recent advances in nanoscience have spurred 
new developments in the field of theranostics (the combination of both 
therapeutic and diagnostic functions in a single system). These 
integrated systems have been shown to selectively transport therapeutic 
agents to target tissues while simultaneously monitoring biological 
responses to the delivered therapy. The current challenge is to develop 
systems or ``platforms'' that allow the optimization of the function of 
each of the combined molecular components that target the disease site, 
deliver the therapy, and allow for imaging of the results immediately. 
Researchers recently developed a nanoscale delivery platform known as 
polymer-caged nanobins (PCNs). The surface of PCNs can be chemically 
modified to attach a variety of molecules in order to target specific 
cells or tissues. The platform is liposome based, which allows for a 
simplified loading and encapsulation of a range of therapeutic drugs. 
To allow monitoring of the response to therapy, the PCN shell contains 
magnetic resonance imaging (MRI) contrast agents, which provide images 
of the drug targets as well as real time images of the response to the 
drug, e.g., reduction in tumor size. This type of theranostic can make 
the treatment of numerous diseases safer and more successful because 
the prescribed regimens can be adjusted in real time during treatment.
           accelerating early diagnosis at the point-of-care
    Handheld Nuclear Magnetic Resonance for Rapid Point-of-Care 
Diagnostics.--One of the major challenges in medicine is the rapid and 
accurate measurement of proteins that are biomarkers of a specific 
disease, or pathogens in biological samples. Magnetic particles which 
target biomarkers are attractive candidates for such biosensing 
applications because most biological samples do not have any background 
magnetization that would interfere with detection. A handheld micro-
nuclear magnetic resonance (NMR) device, which can detect such 
particles, has recently been developed for rapid approximately one-half 
hour analysis of a variety of biologics, from bacteria identification 
in small fluid samples to protein markers of cancer. The device employs 
magnetic particles that bind to targets of interest, creating a signal 
detectable by the micro-NMR. Also known as diagnostic magnetic 
resonance (DMR), this powerful biosensor technology offers unique 
advantages, such as robust signal amplification, broad applicability to 
profile different types of targets (DNA, proteins, metabolites, and 
cells), minimal sample preparation, ability to perform measurements in 
turbid media, and high-throughput capacity. Importantly, the low cost 
and ability to use the device at the point-of-care could make important 
contributions to the battle against serious public health issues such 
as tuberculosis and HIV in underserved populations. In an early study 
of patients with unknown solid masses, the diagnosis of cancer was made 
at the bedside in approximately one-half hour and with higher accuracy 
than with the traditional method of tissue biopsy which requires two 
days for final results.
                      new investigators, new ideas
    NIBIB Design by Biomedical Undergraduate Teams Challenge.--The 
Design by Biomedical Undergraduate Teams (DEBUT) challenge is a new 
NIBIB program opened to teams of undergraduate students working on 
projects that develop innovative solutions to unmet health and clinical 
problems. The main goals of the challenge are:
  --to provide undergraduate students experience in working in teams to 
        identify unmet clinical needs, and design, build and debug 
        solutions for open-ended problems;
  --to generate novel, innovative tools to improve healthcare, 
        consistent with NIBIB's mission; and
  --to highlight and acknowledge the contributions and accomplishments 
        of undergraduate students.
    Entries have been solicited in three categories:
  --Diagnostic Devices and Methods;
  --Therapeutic Devices and Methods; and
  --Technologies to Aid Underserved Populations and Individuals with 
        Disabilities.
    The winning student team in each category will receive a $10,000 
prize at the NIBIB DEBUT Award Ceremony during the annual conference of 
the Biomedical Engineering Society.
                                 ______
                                 
Prepared Statement of John Ruffin, Ph.D., Director, National Institute 
               on Minority Health and Health Disparities
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute on 
Minority Health and Health Disparities (NIMHD) of the National 
Institutes of Health. The fiscal year 2013 NIMHD budget of $279,389,000 
includes an increase of $3,278,000 more than the comparable fiscal year 
2012 level of $276,111,000.
                              introduction
    Millions of Americans from racial and ethnic minority, rural and 
low-income populations continue to be burdened by disparities in health 
status and healthcare, despite recent scientific and medical advances 
to improve the quality of health in this nation. Evidence-based 
research has shown that these disparities result from the interaction 
of multiple chronic influences, such as social, environmental, 
behavioral, and biological factors. Traditionally, research emphasis 
has been on examining the biology of health disparities. In recent 
years, the impact of social factors has become more evident in having a 
strong causal linkage to health disparities. For example, the role of 
the social and physical environment, the effect of poor housing 
circumstances, and the difficulties of accessing transportation to 
obtain timely needed medical care, are all important factors. 
Therefore, the elimination of health disparities requires a coordinated 
and integrated approach across multiple disciplines to understand and 
solve the underlying biological and nonbiological evolution of health 
disparities. NIMHD has been at the forefront leading scientific 
research and building bridges to eliminate health disparities while 
working with public and private sector partners.
                         innovation in research
    NIMHD administers a portfolio of programs aimed at approaching 
health disparities from many angles, embodied in the principal goals of 
research, research capacity building, and outreach. Through research, 
the NIMHD seeks to understand the development and progression of 
diseases and conditions disproportionately affecting underserved 
populations, and to develop evidence-based strategies to improve 
prevention, diagnosis, and treatment methods. The Centers of Excellence 
(CoE) Program continues to be a powerful force for encouraging large-
scale, transdisciplinary research. CoE researchers have analyzed 
associations between insulin resistance and other markers of disease in 
a sample of Mexican-American adolescents from a severely disadvantaged 
community on the Texas-Mexico border. This study found that 
approximately 50 percent of their sample (mean age, 16 years old) were 
overweight or obese, and more participants were obese than overweight. 
Participants (27 percent) in this sample had insulin resistance, a 
strong predictor of diabetes, and two biomarkers, low high-density 
lipoprotein cholesterol and high waist circumference, were strongly 
linked to insulin resistance. These findings emphasize the need to 
address insulin resistance at least as early as adolescence to prevent 
adverse economic, social, and health consequences. Another group found 
evidence that supports the hypothesis that the loss of function of a 
molecule that promotes cell adhesion contributes to the development of 
the aggressive breast cancer commonly found in African-American women. 
NIMHD COE researchers have also discovered that moral beliefs and lack 
of awareness contribute to low rates of cervical cancer screening in 
young Asian-American women.
                   toward diversity in the workforce
    Building the capacity of individuals, institutions, and communities 
to conduct research and undertake training, with the goal of 
strengthening the diversity of the science and medical workforce, are 
crucial to improving the quality of healthcare of America's underserved 
populations. The Research Endowment, Research Centers in Minority 
Institutions (RCMI), and the Building Research Infrastructure and 
Capacity (BRIC) Programs are the pillar of the NIMHD support for 
building a national enterprise of academic institutions with the 
physical and intellectual capability to be leaders in health 
disparities research. At the University of Texas Brownsville, NIMHD 
funding has helped to leverage resources for the creation of a new 
college, the College of Biomedical Sciences and Health Professions, and 
establish a new degree program in biomedical sciences.
    NIMHD continues to recruit an average of 250 new candidates into 
its Loan Repayment Program annually, adding to the diversity of 
individuals from health disparity populations in the science and health 
professions workforce. Many of these scholars are engaged in 
behavioral, social sciences, prevention, health services, and 
community-oriented research exploring the various social determinants 
of health. Some of the innovative research projects include studying 
text messaging to improve depression treatment adherence in low-income 
patients, creating web-based treatment programs for substance use in 
American Indian and Alaska Natives, and examining how perceived 
discrimination and health system distrust affect behavior and 
decisionmaking related to cervical cancer prevention in rural and 
minority women.
                          engaging communities
    Harnessing the power and insights of diverse communities is another 
important factor because health disparity populations often encounter 
cultural or environmental barriers to improved health. Outreach efforts 
remain at the core of the NIMHD's commitment to engage communities in 
the research process, and equally important, to translate research 
findings into culturally and linguistically appropriate tools and 
programs to educate and empower affected communities and their 
healthcare providers. The Community-Based Participatory Research (CBPR) 
Initiative supports research that engages communities in the research 
process as equal partners with scientists. This engagement is valuable 
in helping communities sustain healthy behaviors over the long-term. 
For example, one project at Wake Forest University trained members of 
Latino soccer teams in North Carolina to discuss HIV-prevention 
behaviors with fellow players. After 18 months, men in the intervention 
group were significantly more likely to report consistent condom use 
and HIV testing than those in a control group. Grantees at Saint Louis 
University are increasing fruit and vegetable consumption by local 
black men by producing community gardens. These plots have provided 
more than 1,800 pounds of fresh produce to 150 families, and residents 
showed decreases in hypertension and body mass index.
                   a future of sustainable commitment
    NIMHD seeks to ensure that the investment and progress that has 
been made toward eliminating health disparities is not lost. It will 
continue to identify opportunities to sustain effective programs and 
initiatives by forging and strengthening partnerships across all 
sectors, while accelerating the pace of research, policy, practice, and 
community interventions to address pervasive barriers and emerging 
issues impeding the elimination of health disparities. It will also be 
imperative to establish an effective system of coordination for these 
inter and intra-agency activities. Enhanced understanding of the social 
determinants of health and how where we live, work, and play influence 
health outcomes are among the priorities that must be aggressively 
advanced through innovative approaches. While the issues are many, 
NIMHD is confident that the infrastructure it has built throughout the 
Nation is up to the challenge, and it is poised to support and create 
sustainable interventions that will move the country closer to 
eliminating health disparities. Ensuring that all Americans have an 
equal chance at healthy life is not an option. NIMHD remains committed 
to achieving health equity for underserved communities.
                                 ______
                                 
Prepared Statement of Susan B. Shurin, M.D., Acting Director, National 
                    Heart, Lung, and Blood Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Heart, Lung, 
and Blood Institute (NHLBI) of the National Institutes of Health (NIH). 
The fiscal year 2013 NHLBI budget of $3,076,067,000 includes an 
increase of $709,000 more than the comparable fiscal year 2012 level of 
$3,075,358,000.
    The NHLBI leads research and education programs to discover and 
apply knowledge to improve health by preventing and treating heart, 
lung, and blood diseases. I appreciate the opportunity to highlight 
just a few examples of our success in doing so and some of our most 
promising research programs that will enable further advances.
                     chronic disease risk reduction
    Cardiovascular diseases (CVD) and pulmonary conditions are among 
the leading causes of disability and death around the world. Although 
their prevention and treatment have improved dramatically, without 
further progress they will continue to impose an increasing health 
burden as our population ages. A recent meta-analysis of lifetime risk 
for CVD underscored the availability of lifelong opportunities for CVD 
prevention. The Institute is funding a clinical trial to examine diet 
and exercise interventions to improve neurocognition in patients with 
CVD risk factors who have cognitive impairment. Effective ways to help 
people lose weight and sustain weight loss were identified in an NHLBI-
supported study reported in November 2011; multiple ongoing projects 
are addressing ways to help children and adults in a wide range of 
circumstances improve their health through weight control and physical 
activity.
    The NHLBI continues to focus upon understanding CVD risk in 
vulnerable populations. The Jackson Heart Study is addressing the 
biological, behavioral, and psychosocial factors that account for the 
high burden of CVD in African Americans. The Hispanic Community Health 
Study--Study of Latinos is addressing the factors involved in the 
prevalence and development of CVD in Hispanic populations in the United 
States. Both studies are expected to be renewed in fiscal year 2013. A 
new program planned for fiscal year 2013 will foster development of 
effective and sustainable public health interventions to reduce CVD 
morbidity and mortality in high-risk rural populations.
          interpreting the human genome in health and disease
    Data from the NHLBI's substantial investment in whole exome 
sequencing of participants in its long-term cohort studies is paying 
off: data are now being deposited in dbGaP, the informatics resource at 
the National Library of Medicine, for use by investigators around the 
world. The return on this investment will provide valuable new 
diagnostics and treatments for the next decade.
    The NHLBI has led multiple global consortia in sharing data and 
encouraging analysis of large genomic data sets linked to phenotype. 
One such consortium identified 16 genetic loci important for control of 
blood pressure that are now being explored by other NHLBI-supported 
investigators as new approaches to control blood pressure. Still other 
NHLBI-supported studies are revealing the genetic and environmental 
causes of chronic obstructive pulmonary disease (COPD), asthma, 
abnormalities of heart rhythm, and factors that affect the severity of 
hemoglobin disorders such as sickle cell disease.
           new therapies for heart, lung, and blood disorders
    The NHLBI supports development of improved therapies for heart 
disease through resources such as the Cardiac Translational Research 
Implementation Program (C-TRIP) and their assessment in clinical trials 
through Institute-initiated programs such as the Pediatric Heart 
Network (now completing a trial in Marfan's syndrome and multiple 
studies of genetics and clinical management of congenital heart 
disease), the Heart Failure Network (conducting studies of cellular and 
drug therapies of heart failure), and the Cardiothoracic Surgical 
Trials Network (conducting comparative studies of surgical approaches).
    Several NHLBI programs are advancing translation of basic 
scientific knowledge into new therapies. The Centers for Advanced 
Diagnostics and Experimental Therapeutics in Lung Diseases (CADET) will 
accelerate the development of agents for diagnosing and treating lung 
diseases. Investigators are partnering with other NIH programs such as 
Therapeutics for Rare and Neglected Diseases (TRND) to do early-stage 
translational work that will be followed by NHLBI-supported clinical 
trials.
                      gene and cellular therapies
    NHLBI-supported scientists recently reported success in treating 
hemophilia B, an inherited bleeding disorder, in several patients with 
a single infusion of a gene therapy that durably boosted the production 
of the missing clotting factor. If confirmed in other patients, this 
approach may allow patients to minimize or discontinue expensive 
treatment with replacement clotting factor.
    Encouraging results from studies that use gene therapies in animal 
models for other diseases offer promise for the treatment of human 
disease. For example, a unique genetic approach of replacing the single 
mutated amino acid in mice cured their sickle cell disease. A new form 
of gene therapy for heart failure improved heart function in pigs 
without apparent toxicity.
    Bone marrow transplantation has been standard clinical therapy for 
certain diseases since the 1960s. The NHLBI is the primary Institute 
supporting the Bone Marrow Transplant (BMT) Clinical Trials Network 
(CTN), with strong support from the NCI. A BMT CTN finding that use of 
mobilized peripheral blood stem cells rather than bone marrow 
substantially lowers the risk of graft-versus-host disease (an often 
fatal complication of BMT) has already affected practice and should 
lessen complications of BMT.
    The NHLBI is supporting resources such as the Production Assistance 
for Cellular Therapies program to facilitate laboratory and clinical 
studies of cellular therapies to enhance healing after tissue damage 
caused by myocardial infarction and some forms of lung disease. Use of 
mesenchymal stem cells to repair tissue without scarring is being 
tested in early-stage human trials, with some very encouraging results.
                             rare diseases
    The NHLBI supports infrastructures--registries, clinical trial 
networks, and biorepositories--to enable research on rare diseases and 
on risk factors for more common diseases. For example, both sporadic 
and Marfan-associated thoracic aortic disease may have a common 
pathway, and a genetic cause of aortic aneurysms may be more prevalent 
than previously thought. The NHLBI is a leader in conducting clinical 
trials in pulmonary hypertension and idiopathic pulmonary fibrosis. 
Linkage of genetic and clinical data with a biorepository is enabling 
identification of factors influencing the development of congenital 
heart disease.
    Following promising studies in mice, the NHLBI is now completing a 
study of losartan, an FDA-approved antihypertensive drug, in Marfan 
syndrome. The NHLBI supported a clinical trial that showed rapamycin 
(Sirolimus) stabilized lung function, reduced symptoms, and improved 
quality of life in patients with lymphangioleiomyomatosis (LAM), a 
progressive cystic lung disease in women. NHLBI partnerships with 
patient advocacy organizations in the conduct of both trials 
facilitated their rapid enrollment and completion.
    Sickle cell disease remains an area of intensive focus for the 
NHLBI. A trial recently demonstrated that hydroxyurea, known to be an 
effective treatment for adults, is also safe and effective in very 
young children. In fiscal year 2013, the NHLBI plans to initiate 
Excellence in Hemoglobinopathy Research Awards to promote 
multidisciplinary basic and translational research and facilitate 
collaboration with clinical hematologists. The NHLBI has played a major 
role in a Department of Health and Human Services (HHS)-wide initiative 
to coordinate the research and healthcare delivery efforts of six HHS 
components to reduce the health burdens of hemoglobinopathies (sickle 
cell disease and thalassemia). The NHLBI is developing clinical 
practice guidelines to ensure that providers know the components of 
high-quality, evidence-based care for sickle cell disease.
                             hemovigilance
    The NHLBI supports multiple studies, and works closely with the 
FDA, to ensure appropriate monitoring of the blood supply against 
potential threats. In 2010 and 2011, an NHLBI-led interagency group 
demonstrated that a xenotropic murine retrovirus (XMRV), which had been 
reported to be associated with chronic fatigue syndrome in some 
patients, did not pose a risk to the safety of the blood supply. NHLBI 
leadership ensured that this and other important health questions were 
quickly resolved.
                                 ______
                                 
Prepared Statement of Paul A. Sieving, M.D., Ph.D., Director, National 
                             Eye Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Eye Institute 
(NEI) of the National Institutes of Health (NIH). The fiscal year 2013 
NEI budget of $693,015,000 includes a decrease of $8,861,000 less than 
the comparable fiscal year 2012 level of $701,876,000. As the Director 
of the NEI, it is my privilege to report on the many research 
opportunities that exist to reduce the burden of eye disease.
                    clinical/translational research
    Gene Therapy.--In 2008, NEI-supported investigators reported 
results from a landmark phase I clinical trial of gene therapy in three 
patients with a blinding, early onset retinal disease, Leber congenital 
amaurosis (LCA), which is caused by a defect of the RPE65 gene. 
Treatment, consisting of injecting a viral vector to deliver normal 
copies of the RPE65 gene, was well tolerated, and there was objective 
evidence of modest visual improvement in all three study subjects. To 
date, 15 participants have been treated and all have experienced visual 
improvements. Recently published clinical trial results find that 
increasing the dose with a second injection safely expands the area of 
retina exposed to the treatment (RPE65-AAV). Responsiveness of light-
sensitive photoreceptor cells near injection sites increased after 
treatment. Younger participants, when compared to older participants, 
did not experience greater visual improvements. In fact, the two 
participants with the greatest visual acuity gains were among the 
oldest in the study. The researchers speculated that the number and 
health of remaining photoreceptors matter more than patient age, as the 
rate of photoreceptor loss varies considerably among people with RPE65-
deficient LCA. The finding suggests that careful evaluation of 
photoreceptor cell health is important in determining potential 
clinical trial participants. Because safety was the primary outcome of 
this trial, a conservative approach was taken that limited treatment to 
the eye with poorer vision. In the future, the researchers plan to seek 
further visual gains by administering three injections of RPE65-AAV and 
treating the better eye.
    A team of NEI investigators restored vision in a canine model of X-
linked retinitis pigmentosa (XLRP) using a new gene therapy vector 
capable of transfecting both rod and cone cells. XLRP is a severe 
retinal disease that affects both rod and cone photoreceptor cells. 
Patients with XLRP experience night blindness as children and become 
blind by middle age. A common form of XLRP results from mutations in 
the retinitis pigmentosa GTPase regulator (RPGR) gene. Treatment 
restored lost photoreceptor cell structure and repaired photoreceptor 
cell connections to other retinal neurons that send visual signals to 
the brain. This study provides a clearer path to clinical trials for 
XLRP. In addition, gene therapy trials for age-related macular 
degeneration (AMD), choroideremia, Leber's hereditary optic neuropathy, 
Stargardt macular dystrophy (SMD), and Usher syndrome were launched 
this past year. Clinical trials for juvenile retinoschisis, 
achromatopsia, and retinitis pigmentosa are also planned. All of these 
trials were made possible by sustained NEI support to develop and 
refine gene therapy techniques.
    Stem Cell Therapies.--In January 2012 Advanced Cell Technologies 
published preliminary results of the first-ever clinical trials of a 
product derived from human embryonic stem cells (hESCs). These landmark 
clinical trials are evaluating hESC-derived retinal pigment epithelium 
(RPE) cells for the treatment of Stargardt's macular dystrophy (SMD) 
and age-related macular degeneration (AMD). In the two treated 
patients, there were no adverse events and both had modest but 
objective improvements in vision. The RPE is a highly specialized layer 
of cells adjoining the retina that support photoreceptor cell function. 
SMD and AMD are known to result from a diseased RPE.
                                genetics
    NEI created the International AMD Genetics Consortium in 2010 to 
identify the remaining genetic risk variants for AMD. To increase the 
statistical power needed to identify genes that have small, yet 
significant contributions to AMD, the consortium is conducting a meta-
analysis on 15 Genome Wide Association Studies (GWAS) representing more 
than 8,000 patients with AMD and 50,000 controls. In addition to 
verifying known genes, the consortium identified 19 new gene variants. 
The genes identified in these studies function in the immune system, 
cholesterol transport and metabolism, and formation and maintenance of 
connective tissue. This study provides a nearly complete picture of 
genetic heritability for AMD. NEI's effort to unite the international 
research community to share GWAS data sets made it possible to solve a 
common goal in our understanding of this blinding disease.
    In 2009, NEI established the NEI Glaucoma Human Genetics 
Collaboration (NEIGHBOR), a consortium of clinicians and geneticists at 
12 institutions throughout the United States dedicated to identifying 
the genetics of glaucoma. NEIGHBOR collected and sequenced 6,000 DNA 
samples and is the largest genetics study of glaucoma. Thus far, 
NEIGHBOR investigators identified a risk variant in the gene CDKNB2. 
This gene is thought to play a role in the development of the optic 
nerve head, where retinal ganglion cell axons, which degenerate in 
glaucoma, converge to form the optic nerve. NEI will make GWAS data 
from NEIGHBOR available to the vision research community for further 
evaluation in 2012.
                              neuroscience
    In 2011, NEI awarded a grant to support Project Prakash, which 
combines an extraordinary scientific opportunity with a humanitarian 
mission. Understanding how the human brain learns to perceive objects 
remains a fundamental challenge in neuroscience. Project Prakash seeks 
to treat older children born with congenital cataracts and other eye 
disorders and then study how their visual function develops. Visual 
development normally takes place during infancy before children acquire 
language and can communicate what they are seeing. By treating older 
children who can fully communicate, Project Prakash will permit 
scientists to more directly address the nature of neuroplasticity and 
visual development. This study will also provide important clinical 
insights to inform visual rehabilitation. India accounts for nearly 30 
percent of the world's blindness. Many are poor children with treatable 
congenital eye disorders, but most never receive medical attention 
because they live in rural areas far from urban medical centers. 
Tragically, it is estimated that 60 percent of India's blind children 
die before reaching adulthood. Project Prakash is a unique opportunity 
to offer humanitarian medical aid while advancing the field of 
neuroscience.
                                 ______
                                 
    Prepared Statement of Martha J. Somerman, DDS, Ph.D., Director, 
         National Institute of Dental and Craniofacial Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute of 
Dental and Craniofacial Research (NIDCR) of the National Institutes of 
Health (NIH). The fiscal year 2013 NIDCR budget of $408,212,000 
includes a decrease of $2,010,000 less than the comparable fiscal year 
2012 level of $410,222,000.
    Science long has served as one of the Nation's most essential 
economic engines. From the Human Genome Project to the Internet, 
scientists started with basic research questions that later propelled 
American entrepreneurship into creating previously unimaginable new 
markets. So what types of research now are advancing in the Nation's 
laboratories and clinics that might one day propel American industry 
and public health to new heights? Today, I offer a brief overview of 
NIDCR's investment and progress in a few key areas, and suggest their 
potential to enhance the dental, oral, and craniofacial health of 
millions of Americans.
                          chronic inflammation
    A great place to start is with a promising therapeutic approach 
that mimics the body's own signals to control inflammation and 
inflammatory pain. Inflammation is part of the immune system's normal 
response to infections and tissue injury. Without it, tissues would not 
heal. At some pre-programmed point, when the threat subsides, the 
response turns off and inflammation is resolved. For millions of 
people, however, the immune system's signals get crossed and 
inflammation is dangerously prolonged.
    An NIDCR grantee has developed promising candidate compounds based 
on the body's own inflammation-resolving molecules. The compounds have 
proven potent at reducing inflammation and inflammatory pain in animals 
without the adverse side effects of available analgesics. The plan is 
to move into human studies within the next year to evaluate their 
safety and efficacy in turning off the destructive inflammation 
occurring in periodontal disease. The hope is these compounds one day 
will provide a more effective approach to managing this widespread oral 
condition and, possibly, other chronic inflammatory conditions 
elsewhere in the body.
                              chronic pain
    The Institute of Medicine reported in 2011 that more than 116 
million Americans suffer from chronic pain, with annual costs of 
approximately $600 million. The profound complexity of the body's 
processes for perceiving and responding to pain is a key factor 
contributing to the current inadequacies of chronic pain control and 
interventions to prevent the transition from acute to chronic pain. For 
the most part, chronic pain conditions and their molecular 
underpinnings remain poorly understood. This is changing. In late 2005, 
NIDCR began supporting the first-ever, large longitudinal clinical 
study of a chronic pain condition. It focuses on temporomandibular 
joint and muscle disorders (TMJDs), a common group of conditions that 
affect the area in and around the jaw joint and often overlap with 
other chronic pain conditions. Preliminary findings, reported in 
December 2011, identified mutations in genes linked to chronic TMJD, 
including genes associated with stress, psychological well-being, and 
inflammation. Building on this work, NIDCR places a high priority on 
supporting research on the genetics of chronic orofacial pain, with a 
focus on identifying gene variants that influence pain perception, 
their interactions with environmental triggers, and behavioral 
responses to pain.
    In other work, NIDCR-supported behavioral scientists are providing 
insight into factors influencing providers' treatment decisions for 
chronic pain. They found that decisions tend to be influenced by 
individual characteristics of patients, such as gender and race or 
ethnicity, which are extraneous to the pain condition itself. These 
results are leading to new ways of training providers, helping to focus 
treatment decisions on more clinically relevant factors.
                              oral cancer
    Personalized healthcare offers tremendous promise for improving the 
lives of people diagnosed with cancer, as well as other diseases. Among 
new cancer occurrences, oral and pharyngeal cancer (OPC) is the eighth 
most common among U.S. men and seventh among African-American men, 
affecting more than 30,000 people each year. Since 2009, NIDCR has 
invested in the Oral Cancer Genome Project, which aims to define the 
genetic changes driving development of oral and pharyngeal tumors. As 
part of this project, NIDCR-supported researchers employed next-
generation sequencing technology to yield one of the most comprehensive 
analyses yet of the genetics underlying head and neck squamous cell 
carcinoma (HNSCC), the most common of OPCs. The genomics data provide 
evidence that HNSCC involves dozens of distinct molecular conditions, 
each driven by a unique pattern of gene alterations. NIDCR will support 
work to validate the research findings, which could help identify and 
reclassify these tumors based on their individual specific molecular 
characteristics--a key first step in establishing personalized 
therapies.
    Another important result from the Oral Cancer Genome Project was 
the confirmation that head and neck tumors associated with human 
papillomavirus (HPV) infection have their own distinct genetic profile. 
HPV is associated with a subset of OPCs that increased by 225 percent 
from 1998 to 2004. NIDCR supports research to understand the natural 
history of this growing public health issue.
    The Institute also supports research to improve the survival rate 
for HNSCC. In a significant advance, scientists in NIDCR's laboratories 
demonstrated that metformin, a widely used anti-diabetes drug, prevents 
development and progression of oral squamous cell carcinomas in mice. 
NIDCR is initiating clinical studies to determine its effectiveness in 
humans, opening a new approach to treating this deadly cancer.
                        craniofacial development
    Cleft lip and cleft palate (CLP) are among the most common of all 
birth defects, occurring in 1 of 700 live births in the United States, 
or 7,000 babies per year. Treatment is expensive and difficult, 
requiring multiple surgeries, orthodontics, and speech therapy over a 
period of years. NIDCR takes a multi-pronged approach to these 
devastating conditions, incorporating basic research with prevention, 
treatment, and post-treatment research. The goal is fewer children born 
with CLP, better outcomes for those afflicted with the disorders, and 
less cost and stress for families.
    Through genome-wide studies, NIDCR-supported investigators defined 
several genetic and environmental CLP risk factors. This work set the 
stage for a researcher co-funded by NIDCR and NICHD to develop a mouse 
model that closely mimics CLP. The same researcher demonstrated that 
restoring function in one molecule resulted in complete correction of a 
cleft lip defect in mouse embryos still developing in utero.
    NIDCR-funded investigators have found that many children born with 
CLP have impaired cognitive functioning that goes undetected until the 
child is older and remediation is more difficult. Early screening for 
cognitive deficits in children with CLP may help them reach their full 
potential through timely, tailored instruction. Research on early 
screening technologies is underway. In addition, NIDCR continues to 
fund research to optimize care for children with clefting disorders, 
including clinical studies comparing the cost and effectiveness of 
intervention procedures.
    NIDCR's investment in small business innovation research (SBIR) and 
small business technology transfer (STTR) programs is sparking economic 
activity and improving outcomes for people with craniofacial defects 
such as CLP. An NIDCR grantee developed surgical simulation software to 
help clinicians plan and optimize craniofacial surgery and provide a 3D 
prediction of patients' outcomes. Another grantee leveraged SBIR/STTR 
investments to patent a minimally invasive surgical instrument system 
to aid periodontal surgery, often needed by people with CLP.
                          evidence-based care
    NIDCR efforts to strengthen the knowledge base for dental practice 
will accelerate in April 2012 with the establishment of a National 
Dental Practice-Based Research Network. Building on the success of 
precursor regional networks, the national network will leverage the 
power of large numbers of practitioners to propose and perform clinical 
studies on topics important to dentistry. Because the research is 
conducted in the real-world environment of dental practice, dentists 
are more likely to accept and adopt the findings. The expected result 
is nothing short of a transformation of dental practice--one that will 
result in more individualized and evidence-based treatment and 
prevention, to the benefit of millions of Americans.
                                 ______
                                 
   Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal 
             Deputy Director, National Institutes of Health
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the Office of the Director 
(OD) of the National Institutes of Health (NIH). The fiscal year 2013 
OD budget of $1,429,161,000 includes a decrease of $28,220,000 less 
than the comparable fiscal year 2012 level of $1,457,381,000.
    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 the Institutes and 
Centers through the activities of several cross-cutting program 
offices. The OD also develops policies in response to emerging 
scientific opportunities employing ethical and legal considerations; 
provides oversight of peer review policies; coordinates information 
technology across the agency; and, coordinates the communication of 
health information to the public and scientific communities.
    The fiscal year 2013 request will also support activities managed 
by the OD's operational offices. 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
    Division of Program Coordination, Planning, and Strategic 
Initiatives (DPCPSI) is the home for cross-cutting offices that support 
research in areas of emerging scientific opportunity, rising public 
health challenges, or knowledge gaps that deserve special emphasis. 
DPCPSI's scope expanded in fiscal year 2012 with the creation of a new 
Office of Research Infrastructure Programs (ORIP) which supports 
research resources that serve grantees across the NIH. In addition to 
ORIP, there are five offices that are described. The fiscal year 2013 
budget for DPCPSI, Office of the Director and the Office of Strategic 
Coordination is $8,116,000.
               office of research infrastructure programs
    Office of Research Infrastructure Programs (ORIP) supports research 
infrastructure, research-related programs, and NIH's science education 
efforts. Within ORIP, the Division of Comparative Medicine provides 
scientists with essential resources--including specialized disease-
model laboratory animals, research facilities, training, and other 
tools--that enable research funded by all NIH ICs. The Shared and High 
End Instrumentation programs provide support for the purchase of 
research equipment, ranging in cost from $100,000 to $2,000,000. The 
Animal Facilities Improvement program provides funds to modernize 
animal facilities that support biomedical and behavioral research. ORIP 
also currently monitors more than 350 construction awards that have not 
yet reached their 20-year milestone and 147 ARRA awards for 10 years. 
The ORIP budget for fiscal year 2013 is $283,698,000. The Science 
Education Partnership Awards (SEPA) program encourages pre K-12 
projects that support diversity in the research workforce as well as 
museum exhibits for students, teachers, and the public. In fiscal year 
2013, the budget for SEPAs is $20,282,000. The Office of Science 
Education (OSE) develops science education programs, instructional 
materials, and career resources that serve our Nation's science 
teachers, their students, and the public. The fiscal year 2013 budget 
for OSE is $3,980,000.
                      the office of aids research
    The Office of AIDS Research (OAR) plays a unique role at NIH, 
establishing a plan for the AIDS research program. OAR coordinates the 
scientific, budgetary, legislative, and policy elements of the NIH AIDS 
research program. OAR's response to the AIDS epidemic requires a unique 
and complex multi-Institute, multidisciplinary, global research 
program. This diverse research portfolio demands an unprecedented level 
of scientific coordination and management of research funds to identify 
the highest priority areas of scientific opportunity, enhance 
collaboration, minimize duplication, and ensure that precious research 
dollars are invested effectively and efficiently, allowing NIH to 
pursue a united research front against the global AIDS epidemic. The 
fiscal year 2013 budget for OAR is $63,802,000.
         the office of behavioral and social sciences research
    The Office of Behavioral and Social Sciences Research (OBSSR) was 
established by the Congress to stimulate behavioral and social science 
research at NIH and to integrate it more fully into the NIH research 
enterprise. To address the contribution of behavior to health and 
disease, OBSSR supports the activities of the NIH Basic Behavioral and 
Social Science Opportunity Network, a trans-NIH initiative to expand 
the agency's funding of basic behavioral and social sciences research. 
The fiscal year 2013 budget for OBSSR is $27,001,000.
                the office of research on women's health
    The mission of the Office of Research on Women's Health (ORWH) is 
to advance NIH research on women's health. This is accomplished by 
catalyzing innovative research addressing the gaps in knowledge 
regarding diseases and conditions that affect women and in partnership 
with the ICs through the implementation of the NIH strategic plan for 
women's health and sex differences research which serves as a framework 
for interdisciplinary scientific approaches. ORWH promotes the 
recruitment, retention, reentry, and sustained advancement of women in 
biomedical careers and continues to lead efforts to ensure adherence to 
policies for the inclusion of women and minorities in NIH clinical 
research. The fiscal year 2013 budget for ORWH is $42,324,000.
                    the office of disease prevention
    The mission of the Office of Disease Prevention (ODP) is to foster, 
coordinate, and assess research in disease prevention and health 
promotion at the NIH. ODP collaborates with other Federal and 
international organizations, academic institutions, and the private 
sector in formulating new research initiatives and policies to improve 
public health. The fiscal year 2013 budget for ODP is $6,065,000. The 
Office of Dietary Supplements (ODS) is within the ODP organizational 
structure. ODS strengthens knowledge and understanding of dietary 
supplements by evaluating scientific information, stimulating and 
supporting research, disseminating research results, and educating the 
public. The fiscal year 2013 budget for ODS is $27,717,000.
        the office of strategic coordination and the common fund
    Office of Strategic Coordination (OSC) leads strategic planning for 
and centrally manages Common Fund (CF)-supported programs. OSC works 
with staff across the NIH in CF program development and implementation. 
The NIH 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 
NIH ICs or would otherwise benefit from strategic planning and 
coordination. The 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. The fiscal year 2013 budget for the Common 
Fund is $544,930,000.
           intramural loan repayment and scholarship programs
    The NIH Intramural Loan Repayment and Scholarship Programs (ILRSP) 
seek to recruit and retain highly qualified physicians, dentists, and 
other health professionals with doctoral-level degrees. These programs 
offer financial incentives and other benefits to attract highly 
qualified physicians, nurses, and scientists into careers in 
biomedical, behavioral, and clinical research as employees of the NIH. 
The Undergraduate Scholarship Programs (UGSP) offers competitive 
scholarships to exceptional college students from disadvantaged 
backgrounds that are committed to biomedical, behavioral, and social 
science health-related research careers at the NIH. The fiscal year 
2013 budget for ILRSP is $7,393,000.
                                 ______
                                 
    Prepared Statement of Nora D. Volkow, M.D., Director, National 
                        Institute on Drug Abuse
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute on 
Drug Abuse (NIDA) of the National Institutes of Health (NIH). The 
fiscal year 2013 NIDA budget of $1,054,001,000 includes an increase of 
$1,887,000 more than the comparable fiscal year 2012 level of 
$1,052,114,000.
    The President's budget for fiscal year 2013, which has just been 
released, offers a timely opportunity to review NIDA's research 
priorities for bringing the power of science to bear on drug abuse and 
addiction and reducing their burden on the public's health.
                       a technological revolution
    The technologies of biomedical research are advancing at 
unprecedented rates ushering in scientific breakthroughs that are 
providing a deeper understanding of human genetics, chemistry, and 
brain circuitry. The emerging picture has the potential to transform 
how we prevent and treat drug abuse and addiction and its health 
consequences, and involves new techniques for capturing and analyzing 
vast and diverse datasets on everything from genetics to neuroimaging 
to social networks.
    NIDA is poised to harness complete genome and ``deep'' sequencing 
tools and a growing portfolio of epigenetic initiatives to elucidate 
how biological processes and environmental factors like chronic stress 
and drug exposure can alter the expression of genes that influence 
brain organization and function and the expression (or not) of 
substance use disorders. For example, the recent finding in an animal 
model that nicotine can trigger epigenetic processes that make the 
brain more susceptible to the effects of cocaine could have important 
policy and practice implications, if it occurs also in humans.
    Epigenetic research is also shedding critical new light into the 
mechanisms that govern the disease progression of HIV, the spread of 
which is closely intertwined with injection and noninjection drug-use 
behaviors. A cure for HIV has been elusive because the virus is able to 
``hide'' in a latent form in resting CD4-T cells. This allows HIV to 
persist for years, even with prolonged exposure to antiretroviral 
drugs. Understanding this ``latency'' effect could enable researchers 
to reactivate the virus and use current or future therapies to rid the 
body of it altogether.
    The overlaying of neuroimaging data will further accelerate 
discovery by linking molecular and cellular data with human behavior. 
For example, a new functional magnetic resonance imaging (fMRI)-based 
approach can probe the resting brain (i.e., one not performing any 
specific task) to illuminate circuit-level functions that may prompt 
behavioral responses, including those related to diseased states or 
vulnerability. Individual differences found in these images could 
provide useful biomarkers (neural signatures) of illness risk, course, 
and treatment response.
    The amount and diversity of data being generated by genetic, 
epigenetic, and imaging studies call for harmonization standards that 
will allow data integration across laboratories. Thus, our continuing 
efforts to train the next generation of addiction researchers must now 
take into account the urgent need for a new cadre of interdisciplinary 
scientists capable of developing modern analytical tools for 
integrating and managing large pooled data sets and for modeling and 
analyzing complexity.
                        therapeutics development
    To help those already suffering from addiction, we need to expand 
the tools available to treat substance use disorders and their health 
consequences. To this end, NIDA will continue to invest in the 
development of addiction medications and to seek public-private 
partnerships with pharmaceutical companies still reluctant to play an 
active role due to perceived stigma and financial disincentives. 
Success demands both adaptable and novel approaches.
    Among the ``low-hanging fruit'' are already-approved drugs, which 
NIDA is seeking to repurpose for addiction indications, saving enormous 
amounts of research and development time and cost. Notable in this 
category are: buspirone, which blocks action at the dopamine (D3) 
receptor (among its other effects) and may be useful in treating 
stimulant addiction, based on well-established findings in the animal 
literature; and cytisine, which acts on nicotinic receptors and has 
recently been shown to be about 3.5 times more effective than placebo 
in a smoking cessation trial.
    NIDA also continues to support research to increase the 
effectiveness of various vaccines being tested against nicotine, 
cocaine, heroin, and methamphetamine. Efforts aim to increase these 
vaccines' immunogenicity--that is, their ability to stimulate the 
production of antibodies capable of blocking a drug's entry into the 
brain.
    Finally, NIDA is actively pursuing a strategy that involves the use 
of medication combinations, an approach that has proven effective for 
treating many diseases (e.g., HIV, cancer) and one starting to show 
success with addiction. For example, the combination of lofexidine (a 
hypertension medication) and marinol (a synthetic form of marijuana's 
THC) has shown promise in treating withdrawal symptoms (which can 
trigger relapse) among marijuana-addicted individuals.
         improving public healthcare: delivery and performance
    NIDA will harness every opportunity to translate scientific 
knowledge to improve strategies for combating drug abuse and addiction. 
This commitment includes engaging physicians as ``frontline'' 
responders and providing them with tested tools, including a Web-based 
screening tool that generates specific clinical recommendations. The 
broad availability of these resources is an important step toward 
integrating substance abuse screening, brief intervention, and referral 
to treatment (SBIRT) into routine medical care, which will enable 
better healthcare decisions and outcomes.
    NIDA will also capitalize on the Affordable Care Act to study how 
innovations in service delivery, organization, and financing can 
improve access to and use of effective prevention and treatment 
interventions. Because so few people access treatment, coupled with the 
more than $600 billion that drug abuse and addiction cost society each 
year, even a marginal increase in treatment use and retention could 
have a sizeable public health impact--for individuals, families, and 
society as a whole.
    To help get evidence-based treatments to providers in a variety of 
settings, NIDA uses collaborative research infrastructures designed to 
deploy proven strategies rapidly and effectively. For example, NIDA's 
Criminal Justice-Drug Abuse Treatment Studies (CJ-DATS) network 
promotes multilevel collaborations to test proven treatment models in 
the criminal justice system, disproportionately affected by both drug 
abuse and HIV. One example, called ``Seek, Test, Treat, and Retain,'' 
expands access to HIV testing and treatment, ultimately reducing HIV 
spread.
                       staying ahead of the curve
    NIDA continues to monitor drug abuse trends across different 
populations. Particularly worrisome are the trends pertaining to 
marijuana use, on the rise after about a decade of decline; the 
emergence of an ever-evolving array of synthetic drugs (e.g., spice and 
bath salts) that are sending users to emergency rooms nationwide; and 
the continued high rates of prescription drug abuse, which have 
resulted in a quadrupling in unintentional overdose deaths in this 
country since 1999. NIDA is addressing all these problems through both 
broad-based prevention efforts and targeted initiatives.
    Prescription drug abuse is one such targeted area that demands a 
multifaceted approach. NIDA's long-term strategy to help reverse this 
trend includes:
  --research to understand the factors that influence an individual's 
        risk, treat those already addicted, and develop pain 
        medications with reduced abuse potential;
  --physician education to improve pain treatment while minimizing 
        prescription drug abuse; and
  --community engagement exemplified by NIDA's leadership of a 
        multiagency effort to create a Surgeon General Call to Action 
        to reduce prescription drug abuse among youth.
    In closing, NIDA pledges to continue to tackle the emerging and 
significant public health needs related to drug abuse and addiction, 
taking advantage of unprecedented scientific opportunities to close the 
gaps in our knowledge and develop and disseminate more effective 
strategies to prevent and treat drug abuse and addiction.
                                 ______
                                 
   Prepared Statement of Kenneth R. Warren, Ph.D., Acting Director, 
           National Institute on Alcohol Abuse and Alcoholism
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Institute on 
Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of 
Health (NIH). The fiscal year 2013 NIAAA budget of $457,104,000 for the 
NIAAA reflects a decrease of $1,868,000 less than the comparable fiscal 
year 2012 level of $458,972,000.
                          scope of the problem
    The Centers for Disease Control and Prevention (CDC) ranks alcohol 
as the third leading cause of preventable death in the United States, 
and the World Health Organization lists alcohol as one of the top 10 
causes of Disability Adjusted Life Years in the United States. And, 
according to a new study by the CDC, the cost of excessive alcohol 
consumption in the United States reached $223.5 billion in 2006.
    On a more personal level, I would venture that each of you knows 
someone who has experienced an alcohol-related problem. It could be a 
child who has difficulty in school as a result of prenatal alcohol 
exposure. Perhaps you have a relative or colleague who is one of the 
almost 18 million people who suffer from alcohol abuse or dependence. 
Alternatively, your son or daughter may be one of the more than 40 
percent of college students who binge drink, many of whom experience 
blackouts, not remembering where they were, what they did, or with 
whom. You may know one of the 97,000 college students to experience 
alcohol-related sexual assault or heard the frustration of a college 
student trying to study while the alcohol-fueled party raged in the 
room next door. Many of us also have friends that grew up in a 
household where alcohol was a problem; in fact, 1 in 10 children in the 
United States grow up under such circumstances. Clearly, alcohol 
related problems are not reserved for the middle-aged, nor are they 
only experienced by those who drink.
                                research
    NIAAA supported research is advancing our understanding of alcohol-
related problems across the lifespan. By translating this research into 
new and better prevention and treatment approaches we have the ability 
to enhance the well-being of individuals, their families, and society-
at-large.
    Much of what we have learned about alcohol use and alcohol use 
disorders in the U.S. population comes from analyses of NIAAA's 
National Epidemiologic Survey on Alcohol and Related Conditions 
(NESARC). Beginning in 2012, the third wave of NESARC will collect DNA 
samples in addition to detailed information on alcohol use, alcohol use 
disorders, and related physical and mental disabilities from an 
estimated 46,000 participants. This rich resource of genetic and other 
data will enable future studies comparing whole genome sequences to 
identify interactions between environmental and genetic risk factors 
that are associated with harmful alcohol use patterns and their 
associated disabilities. Survey data on the distribution of alcohol-
related problems and treatment utilization will inform treatment 
delivery systems to better help those in need of services.
    Research on individuals at different stages of life and at 
different points in the trajectory of their alcohol use and related 
problems underscores the importance of early identification and 
intervention in reducing future health problems. This is true for:
  --children exposed to alcohol in utero;
  --children and adolescents using alcohol and/or at high risk for 
        alcohol-related problems; and
  --individuals who exceed the low risk drinking guidelines, including 
        those with alcohol dependence.
    One of the barriers to intervening early with children with fetal 
alcohol spectrum disorders is identification of affected children given 
the wide range of physical, behavioral, and cognitive effects that may 
result from prenatal alcohol exposure. Ongoing studies are 
demonstrating the utility of fetal ultrasound and 3D facial image 
analysis for earlier and improved recognition of affected children. 
Alcohol has also been implicated in sudden infant death syndrome and 
stillbirth. In collaboration with National Institute of Child Health 
and Human Development and NIDCD, NIAAA is supporting studies to 
investigate this association and the role other environmental and 
maternal factors may play.
    Children and adolescents who drink are also vulnerable to a number 
of adverse outcomes. These range from immediate consequences such as 
academic and social problems, injuries, and death, to longer-term 
consequences including increased risk for alcohol dependence. 
Nevertheless, alcohol use increases dramatically during adolescence. 
Given the range and severity of consequences associated with underage 
drinking and the prevalence of drinking and binge drinking, routine 
screening and intervention for alcohol use in young people is critical. 
Yet many pediatricians and family practitioners cite a lack of time, a 
lack of familiarity with screening tools, and a lack of confidence in 
their alcohol management skills as barriers to screening. NIAAA 
designed Alcohol Screening and Brief Intervention for Youth: A 
Practitioner's Guide to help clinicians conduct fast, effective alcohol 
screens and brief interventions. The guide contains a new two-question 
screen and presents the first youth alcohol risk estimator chart, which 
combines information about a patient's age and drinking frequency to 
give a clinician a broad indication of the patient's chances for having 
alcohol-related problems. Coupled with what a clinician already knows 
about a patient, the risk estimator can help determine the depth and 
content of the clinician's response. The guide outlines different 
levels of intervention and presents an overview of brief motivational 
interviewing, an interactive, youth-friendly intervention that is 
considered to have the best potential effectiveness for the adolescent 
population. Importantly, the guide has been endorsed and promoted by 
the American Academy of Pediatrics.
    In addition to the acute consequences of underage drinking, there 
is increasing evidence that alcohol use during adolescence may result 
in enduring functional and structural changes in the brain. Studies to 
date, however, cannot differentiate between anomalies which resulted 
from adolescent alcohol exposure and those which predated it. NIAAA is 
embarking on a new multi-site initiative enlisting children and young 
adolescents before they begin to use alcohol and following them through 
adolescence. These studies will use advanced neuroimaging technology as 
well as neuropsychological and behavioral measures to assess alcohol's 
effects on brain development and associated cognitive, affective, and 
behavioral processes. NIAAA will continue to support complementary 
basic animal research on the effects of adolescent alcohol exposure on 
subsequent brain function and behavior into adulthood. Collectively 
these studies will provide a more complete picture of alcohol's effects 
on the developing brain and potentially provide insight into the 
association between early alcohol use and later alcohol dependence at 
the molecular and structural levels.
    NIAAA continues to promote screening and brief intervention for 
adults and encourages inclusion of it in electronic health records. The 
primary goal is to identify and address high-risk drinking behavior 
early, including advising individuals who do not meet criteria for 
alcohol dependence. By intervening early, providers are able to offer 
their patients more appealing, accessible options to address their 
alcohol problems, options that are less resource intensive and less 
expensive.
    For those who continue to drink excessively, especially long term, 
the risk of alcoholic liver disease becomes a significant concern. In 
fact, 40 percent of patients with severe alcoholic hepatitis, a serious 
and potentially treatable form of alcoholic liver disease, die within 6 
months of the onset of the clinical syndrome. NIAAA has launched a new 
initiative to foster close collaboration between basic scientists and 
clinicians expediting the translation of emerging findings into more 
effective treatment strategies. Of particular interest is the 
connection between the gut, liver, and brain and how perturbations to 
one organ may aggravate the disease state in another. NIAAA is 
supporting the integration of research to better understand the basic 
biological mechanisms that underlie the disease and the individual 
factors that contribute to disease susceptibility in clinical studies 
that will test new and improved strategies. The goal is to decrease the 
high mortality and morbidity associated with alcoholic hepatitis.
    Developing effective treatments for alcohol dependence remains a 
high priority for NIAAA. Preliminary studies suggest that the smoking 
cessation drug varenicline (Chantix) could reduce drinking in alcohol-
dependent smokers. NIAAA is currently conducting a larger clinical 
trial with alcohol dependent smokers and nonsmokers to assess safety 
and determine if varenicline reduces drinking in either group.
                                 ______
                                 
  Prepared Statement of Jack Whitescarver, Ph.D., Director, Office of 
                             AIDS Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the fiscal year 2013 President's budget request for the trans-
National Institutes of Health (NIH) AIDS research program, which is 
$3,074,921,000. This amount is the same as the fiscal year 2012 enacted 
level. It includes the total trans-NIH support for intramural and 
extramural research for basic, clinical, behavioral, social science, 
and translational research on HIV/AIDS and the wide spectrum of AIDS-
associated malignancies, opportunistic infections, co-infections, and 
clinical complications; as well as research management support; 
research centers; and training.
    Within the total, the Office of AIDS Research (OAR) has provided 
increases to high-priority prevention research in the areas of 
microbicides, vaccines, behavioral and social science, and treatment as 
prevention research, as well as to etiology and pathogenesis research 
that provides the essential basic science foundation not only for AIDS-
related research but for other related diseases and conditions as well. 
In order to provide those increases, OAR has reduced and redirected 
funds from other areas, including natural history and epidemiology, 
therapeutics, and training and infrastructure support.
                           the aids pandemic
    The HIV/AIDS epidemic continues to expand. UNAIDS estimates that in 
2010, more than 34 million people were living with HIV/AIDS; 2.7 
million were newly infected; and 1.8 million people died of AIDS-
related illnesses. In the United States, the Centers for Disease 
Control and Prevention (CDC) estimates that more than 1.2 million 
people are HIV-infected; and someone is infected with HIV every 9\1/2\ 
minutes. AIDS disproportionately affects racial and ethnic populations, 
women of color, young adults, and men who have sex with men. The number 
of individuals aged 50 years and older living with HIV/AIDS is 
increasing, due in part to antiretroviral therapy, which has made it 
possible for many HIV-infected persons to live longer but also due to 
new infections in individuals older than the age of 50. The AIDS 
pandemic has devastating consequences around the world in virtually 
every sector of society. Further research to improve prevention and 
treatment is urgently needed. Advances in prevention and treatment also 
will have extensive economic benefits.
 30 years of extraordinary national institutes of health aids research 
                            accomplishments
    HIV, the virus that causes AIDS, is one of the most complex 
pathogens to affect human health and challenge biomedical research. In 
the three decades since AIDS was first recognized, NIH has established 
the world's leading AIDS research program. This investment in HIV 
research has transformed the disease from a mysterious and uniformly 
fatal infection into one that can be accurately diagnosed and 
effectively managed with appropriate treatment. A recent study 
estimated that 14.4 million life-years have been gained among adults 
around the world since 1995 as a result of AIDS therapies developed 
through NIH-funded research.
    NIH research has resulted in landmark advances that have led to:
  --the co-discovery of HIV, the virus that causes AIDS;
  --development of the first blood test for the disease, which has 
        allowed diagnosis of infection as well as ensured the safety of 
        the blood supply;
  --the critical discovery of key targets to develop Antiretroviral 
        Therapies (ART) and multi-drug regimens that have resulted in 
        improved life expectancy for those with access to and who can 
        tolerate these drugs;
  --the development of treatments for many HIV-associated coinfections, 
        comorbidities, malignancies, and clinical manifestations, with 
        benefits for patients also suffering from those other diseases;
  --groundbreaking strategies for the prevention of mother-to-child 
        transmission, which have resulted in dramatic decreases in 
        perinatal HIV in the United States;
  --demonstration that the use of male circumcision can reduce the risk 
        of HIV acquisition;
  --the first step in proving the concept that a vaccine to prevent HIV 
        infection is feasible; and discovery of two potent human 
        antibodies that can stop more than 90 percent of known global 
        HIV strains from infecting human cells in the laboratory;
  --demonstration of the first proof of concept for the feasibility of 
        a microbicide gel capable of preventing HIV transmission;
  --demonstration that the use of therapy by infected individuals can 
        dramatically reduce transmission to an uninfected partner;
  --groundbreaking research regarding Pre-Exposure Prophylaxis (PrEP), 
        examining whether the use of antiretroviral treatment regimens 
        by some groups of high-risk uninfected individuals could reduce 
        the risk of HIV acquisition;
  --discovery that genetic variants may play a role in protecting some 
        individuals, known as ``elite controllers,'' who have been 
        exposed to HIV over an extended period, from developing 
        symptoms and enabling them to control the infection without 
        therapy;
  --critical basic science discoveries that continue to provide the 
        foundation for novel research; and
  --progress in both basic and treatment research efforts aimed at 
        eliminating viral reservoirs in the body, which is, for the 
        first time, leading scientists to design and conduct research 
        aimed at a cure.
            extraordinary opportunities for fiscal year 2013
    Advances made by NIH investigators have opened doors for new and 
exciting research opportunities to answer key scientific questions that 
remain in the search for strategies to prevent and treat HIV infection 
both in the United States and around the world, and represent the 
building blocks for the development of the OAR Trans-NIH AIDS research 
budget:
      Investing in Basic Research.--OAR will increase support for basic 
        research that will underpin further development of critically 
        needed vaccines and microbicides.
      Encouraging New Investigators and New Ideas.--OAR will provide 
        additional support for innovative multi-disciplinary research 
        and international collaborations to develop novel approaches 
        and strategies to eliminate viral reservoirs that could lead 
        toward a cure for HIV.
      Accelerating Discovery Through Technology.--OAR will increase 
        funds to support critical studies in the area of therapeutics 
        as a method to prevent infection, including treatment to 
        prevent HIV infection after exposure; Pre-Exposure Prophylaxis 
        (PrEP); a potential prevention strategy known as ``test and 
        treat,'' to determine whether a community-wide testing program 
        with treatment can decrease the overall rate of new HIV 
        infections; and improved strategies to prevent mother-to-child 
        transmission. A key priority is to evaluate prevention 
        interventions that can be used in combination in different 
        populations, including adolescents and older individuals.
      Improving Disease Outcomes.--OAR will target funding for NIH 
        research focused on developing better, less toxic treatments 
        and investigating how genetic determinants, sex, gender, race, 
        age, nutritional status, treatment during pregnancy, and other 
        factors interact to affect treatment success or failure and/or 
        disease progression. Studies will address the increased 
        incidence of malignancies, cardiovascular and metabolic 
        complications, and premature aging associated with long-term 
        HIV disease and ART.
      Advancing Translational Sciences.--OAR will ensure adequate 
        resources for research on the feasibility, effectiveness, and 
        sustainability required to scale-up interventions from a 
        structured behavioral or clinical study to a broader ``real 
        world'' setting.
      global impact of national institutes of health aids research
    Research to address the global pandemic is essential. AIDS research 
represents the largest component of the total NIH global research 
investment. Since the early days of the epidemic, NIH has maintained a 
strong international AIDS research portfolio that has grown to include 
projects in approximately 100 countries around the world. NIH AIDS 
research studies are designed so that the results are relevant for both 
the host nation and the United States. These research programs also 
enhance research infrastructure, and training of in-country scientists 
and healthcare providers. New collaborations have been designed to 
improve both medical and nursing education as a mechanism to build a 
cadre of global health leaders. Most of these grants and contracts are 
awarded to U.S.-based investigators to conduct research in 
collaboration with in-country scientists; some are awarded directly to 
investigators in international scientific or medical institutions.
              benefits of aids research to other diseases
    It is essential to point out that AIDS research also pays extensive 
dividends in many other areas of biomedical research, including in the 
prevention, diagnosis and treatment of many other diseases. It deepens 
our understanding of immunology, virology, microbiology, molecular 
biology, and genetics. AIDS research is helping to unravel the 
mysteries surrounding so many other diseases because of the pace of 
discovery and because of the unique nature of HIV, i.e., the way the 
virus enters a cell, causes infection, affects every organ system, and 
unleashes a myriad of opportunistic infections, co-morbidities, 
cancers, and other complications. AIDS research continues to make 
discoveries that can be applied to other infectious, malignant, 
neurologic, autoimmune, and metabolic diseases, as well as complex 
issues of aging and dementia, AIDS treatment research has led to more 
effective drugs for multiple bacterial, mycobacterial, and fungal 
diseases and fostered significant improvements in drug design 
technologies. AIDS research has led to the development of new models to 
test treatments for other diseases in faster, more efficient and more 
inclusive clinical trials. Drugs developed to prevent and treat AIDS-
associated opportunistic infections also now benefit patients 
undergoing cancer chemotherapy and patients receiving anti-transplant 
rejection therapy. AIDS research also has advanced understanding of the 
relationship between viruses and cancer. New investments in AIDS 
research will continue to fuel biomedical advances and breakthroughs 
that will have profound benefits far beyond the AIDS pandemic.
                                summary
    Despite these advances, however, AIDS is not over, and serious 
challenges lie ahead. The HIV/AIDS pandemic will remain the most 
serious public health crisis of our time until better, more effective, 
and affordable prevention and treatment regimens are developed and 
universally available. NIH will continue to search for solutions to 
prevent, treat, and eventually cure AIDS.

    Senator Harkin. Thank you very much again, Dr. Collins, for 
a very provocative statement. I mean ``provocative'' in a good 
way, provoking thinking.

                        IMPACT OF SEQUESTRATION

    Senator Harkin. We'll start a round of 5-minute questions 
now.
    First, Dr. Collins, I'd like to start by asking about the 
threat of sequestration.
    Under the Budget Control Act of 2011, funding for virtually 
all Federal programs face a possible across-the-board cut in 
January. So we could approve our appropriations bill later this 
year, and then find that virtually every program will be cut in 
January 2013.
    Now CBO has estimated, as I said in my opening statement, a 
7.8-percent cut. Other observers, such as the Center on Budget 
and Policy Priorities, think the cuts could be even larger, 9.1 
percent. But for the sake of discussion, we'll go with CBO's 
numbers.
    Could you just give us a thumbnail sketch of what that 
would mean for NIH? I mentioned earlier, I think in my 
statement, about the number of cuts that would come because of 
that it was estimated that the number of grants would shrink by 
more than 1,600 in 2014, by more than 16,000 over a decade.
    Just gives us an idea of what that would mean in terms of 
overall NIH performance.
    Dr. Collins. Senator, I appreciate the question. It is a 
very serious one.
    We also heard this estimate from the CBO, that if the 
sequesters were to kick in on January 2013, that NIH would 
expect to lose 7.8 percent of the budget, about $2.4 billion. 
That would, of course, happen with the fiscal year already 3 
months along. The estimate that has been put forward by an 
analysis would result in roughly 2,300 grants that we would not 
be able to award in fiscal year 2013 that we otherwise would've 
expected to.
    That represents almost a quarter of our new and competing 
grants. That would result in success rates for applicants who 
come in with new applications or competing ones falling to 
historically low levels, and it would be devastating for many 
investigators who are seeking to continue programs that they 
have had funded in the past and are back for their competing 
renewal or who are starting things that are entirely new.
    And I think the burden would hit particularly heavily upon 
first-time investigators who are seeking to get their programs 
up and going. And upon learning of something of this sort, what 
is already a considerable sense of anxiety in that cohort, who 
are our future, would only go up.
    This would have across-the-board implications in terms of 
both basic and clinical science. We would, of course, attempt 
to try to prioritize those things that are most critical. But 
there's no question that such things as an influenza vaccine, 
which Dr. Fauci can tell you much more about, in terms of a 
universal vaccine, would be slowed down; that efforts in cancer 
research would be slowed down; that the common fund, also a 
component of the NIH budget where we have a lot of our venture 
capital space, we would not be able to start new programs, such 
as one focused on how to bring together cellphone technology 
and prevention in health, which is a very exciting new area.
    All of those things would be put at great risk by this kind 
of outcome.

              NATIONAL CANCER INSTITUTE BUDGET RESTRAINTS

    Senator Harkin. Thank you, Dr. Collins.
    And, Dr. Varmus, even if we can avoid sequestration, the 
budget is likely to remain tight. You've been managing the NCI 
with small or no increase since your return.
    What strategies have you found or do you plan that will 
allow you to continue to make progress against cancer with 
these tight budgets?
    Dr. Varmus. Thank you, Senator.
    Well, we've done several things to try to cope with the 
tight budgets. I can't print money, so that would be the ideal 
solution. But we have been, for example, looking very carefully 
at grants that get lower-priority scores, to see if there are 
grants that meet certain high-priority topics to make sure 
those get funded. We've been reorganizing our clinical trials 
cooperative groups to be sure they operate effectively and are 
answering deep scientific questions.
    As you've heard in Mr. Shelby's opening statement, we have 
started a new program that emphasizes the bringing together of 
the scientific community to help define the great unanswered 
questions in cancer research, the so-called provocative 
questions, the initiative that solicited more than 750 
applications to study these deeper questions and empower the 
scientific community to help us define what needs to be 
answered in the future.
    We have the ability to act on our new conception of what 
the genetic underpinnings of cancer are through the 
collaborative project we undertake with the Genome Institute on 
the cancer genome atlas.
    All of these things are helping us, but, of course, these 
strategies don't solve the underlying problem of having 
adequate resources to support science, which costs real money.
    Senator Harkin. Sure.
    Well, I am about out. Senator Shelby, I want to make sure 
everybody gets at least one round of questions.
    Senator Shelby.

                            OBESITY EPIDEMIC

    Senator Shelby. Thank you, Mr. Chairman.
    More than one-third of U.S. adults, as everybody at the 
table knows, are obese. The Deep South, my area of the country, 
has the highest obesity rate in the country with 6 out of 7 
States having an obese population higher than 30 percent.
    Obesity is most prevalent in racial and ethnic minorities, 
low-income populations, and those who live in rural areas. 
Currently, there's a limited number of the most high-risk 
population involved in clinical trials and other NIH-funded 
research.
    My question to you, Dr. Collins, is how can the NIH ensure 
the involvement of the communities most affected by obesity?
    Dr. Collins. A very appropriate question, Senator, and one 
that we are quite concerned about as we look at those curves 
showing increasing longevity for our population. We worry that 
they might flatten out and actually go the wrong way, if we're 
not able to get control of this epidemic of obesity and 
diabetes.
    NIH is deeply engaged in this effort, and I'm going to ask 
my colleague, Dr. Griffin Rodgers, who codirects the effort in 
obesity research across all of the NIH Institutes, to tell you 
something about that plan.
    Senator Shelby. Thank you, Dr. Rodgers.
    Dr. Rodgers. Thank you, Senator.
    NIH supports really a broad array of activities and basic 
translational and clinical research related to the issue of 
obesity. As you point out, this is really a complex problem, 
and a problem that one solution will clearly not be the issue.
    As a result of this, the NIH engaged in a strategic 
planning exercise and just published, about a year ago, a 
strategic plan directed to obesity, aiming at prevention in 
local communities, the hardest affected. You mentioned the 
disparities in racial and ethnic groups, and physicians' 
offices, bringing into the fold a whole lot of people who were 
previously not--including urban planners and others.
    We've enlisted a number of behaviorists to work on this 
problem, and we have some really healthy relationships both in 
the private sector as well as with foundations to tackle this 
major problem.
    Senator Shelby. How do you get people, and I'm one of them, 
I'm sure, to eat an apple instead of a cheeseburger?
    A cheeseburger, sometimes we crave that. We might not crave 
the apple. But we all know the apple is much healthier for us. 
Is that correct?
    Dr. Rodgers. You're absolutely right. And you raised an 
interesting point, something that people have described as 
``nudge.''
    Sometimes if you make the default value something that is 
healthy, you can achieve your objective. So instead of, ``Would 
you like fries with that?'' could it be ``Would you like an 
apple with that?''
    And I'm pleased to say that many in the food industry are 
beginning to consider these types of approaches.

              INSTITUTIONAL DEVELOPMENT AWARDS ELIGIBILITY

    Senator Shelby. Institutional Development Awards (IDeA), in 
its entirety, my State of Alabama is a significant recipient of 
NIH funding, mainly due to research grants received by one 
institution, the University of Alabama (UAB), of course.
    While their success provides significant benefits to both 
the State and the Nation through medical breakthroughs and 
economic investment, I'm concerned that its success puts other 
institutions in Alabama at a competitive disadvantage to 
similar schools in the IDeA area.
    The goal there, I understand, is to broaden the geographic 
distribution of the NIH funding to institutions that have a 
historically low success rate. However, many institutions that 
could benefit are unable to compete for this funding, because 
the State they reside in is ineligible due to the success of 
just one institution.
    The fiscal year 2012 bill included report language in 
support of revising current eligibility criteria. No update was 
provided in the congressional justification for fiscal year 
2013.
    Dr. Collins, my question to you, can you discuss the 
progress you've made in response to this language, if you have 
one?
    Dr. Collins. Senator, I appreciate the question, and we are 
very much supportive of the IDeA program, and you've correctly 
cited it's an effort to try to make sure that institutions that 
are in States that don't have particularly heavy research 
investments are still able to compete for funds to be able to 
do good science.
    As I understand it, Senator, the way in which the IDeA 
program is defined, in terms of which States are eligible, is 
not something that NIH has control over, but that in fact is 
something which is in the hands of the Congress.
    We recognize that the IDeA program is not entirely in sync 
with the Experimental Program to Stimulate Competitive Research 
(EPSCoR) that the National Science Foundation (NSF) supports, 
which has a similar intention but a slightly different 
definition.
    We are happy to continue to explore this, but we are unable 
to do so all on our own.
    Senator Shelby. Thank you.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Shelby.
    Let's see, this will be Senator Brown.

                   STATEMENT OF SENATOR SHERROD BROWN

    Senator Brown. Thank you, Mr. Chairman.
    Thank you all for being here and for your public service. 
All six of you are part of the reason that life expectancy is 
30 years longer than it was a century ago, so thank you for 
that.
    My first question is for Dr. Collins, and then a question 
for Dr. Fauci.

                       NATIONAL CHILDREN'S STUDY

    The National Children's Study (NCS), what you're doing is 
impressive, following children from birth to age 21. In 2008, 
Case Western Reserve University School of Medicine in 
Cleveland, where Dr. Collins recently visited, was awarded two 
study center contracts to research children in Lorain and 
Cuyahoga counties, two urban, industrial counties that have a 
pretty diverse population and pretty widespread poverty.
    Case Western Reserve University has worked with community 
partners, such as Battelle Memorial Institute, the Cuyahoga 
County Board of Health--that's Cleveland--and the Lorain County 
General Health District. They employed some 60 people for 
research and data collectors.
    It's been brought to my attention that NIH found that the 
study's geographic approach is too expensive. It seems to back 
off that, and my understanding is that the seven original sites 
conducting this research are opposed to making that change.
    It seems you're missing a whole cohort of children that are 
coming to the office rather than going to the community.
    Can you explain to me what are your thoughts in reversing 
that direction, that decision?
    Dr. Collins. Certainly, Senator, and thank you for the 
question.
    We are very much invested in the success of the NCS as a 
critical way of assessing environmental and genetic risk 
factors for many disorders that affect individuals, with the 
goal then of ascertaining and following 100,000 kids from even 
prior to pregnancy, through the pregnancy, and on to age 21.
    We've conducted over the last 3 or 4 years a series of 
Vanguard studies to try to assess what is the best way to 
ascertain such a large number of individuals. And what we've 
learned through that process, as well as the evolution of the 
way in which science is being conducted and the way in which 
healthcare is now possible to deliver, is that there may be 
ways to do this study which are actually at least as effective 
and considerably more efficient.
    And as a result of that, and what we've learned from the 
Vanguard study, there is consideration underway that main study 
might be focused in a different way than knocking on doors, 
which had been the original plan.
    Knocking on doors turns out to be very expensive, and it 
turns out also to be quite difficult to ascertain a sufficient 
number of cases, whereas working through providers--and again, 
geographically distributed providers--provides us a better 
opportunity to do this in a fashion which can actually save 
taxpayers' dollars.
    But we're very sensitive to the issues you raise. This 
needs to be a study of children in this Nation that does not 
leave out those who, at the present time, don't have much in 
the way of health coverage.
    And so the main study, which is still in the process of 
having its design worked out, will have some serious attention 
paid to that issue, so that we have a representative group of 
children, not necessarily ascertained in the original way, in 
terms of door-knocking but which does in fact give us the 
information we need to know about genetics, about environment 
in multiple different groups across socioeconomic status.
    And I guess I would just encourage those who are concerned 
about the change to be part of the process that's going forward 
now, including a major meeting in the advisory group next 
month, to be sure that we're getting all the input we need to 
design a study that is going to give the answer that the Nation 
needs.

           TUBERCULOSIS: PREVENTION, DETECTION, AND TREATMENT

    Senator Brown. Thank you.
    One other question, Mr. Chairman.
    Dr. Fauci, thank you for your work on infectious disease. 
As you know, March 24, this last Saturday, was World 
Tuberculosis Day, commemorating the day in 1882 when the cause 
of tuberculosis was discovered, as you know.
    It's not much of a problem in this country. It's still a 
problem, obviously. It's not expensive to cure, as long as 
people take their medicines. You know all of that of course.
    One million children will die of tuberculosis (TB) in the 
next 5 years around the country, as you also know, and more 
than 10 million children were orphaned just, I believe, last 
year alone because of TB.
    Most alarming is the spread of multidrug-resistant (MDR) 
and now extensively drug-resistant TB (XDR-TB). The cures for 
MDR are there. The cure for XDR is significantly more 
difficult.
    What are we doing? What is your Institute doing to foster 
the development of diagnostic drugs? What are we doing, 
especially to prevent, detect, and treat TB? And how do we 
manage the pockets, especially of XDR-TB, around the world and 
particularly in India and in sub-Saharan Africa?
    Dr. Fauci. Thank you for that question, Senator Brown.
    This is truly a very important problem that has slipped off 
the radar screen, because of the victims of our success in the 
developed world, as you mentioned. But there are 1.8 million 
deaths with TB worldwide with an increasing percentage being 
MDR and XDR TB.
    To your question, what we have been doing over the past 
several years, most intensively over the past 5 to 10 years at 
NIH, has been to try and bring the science of tuberculosis into 
the 21st century. All of the advances in molecular biology, in 
sequencing and drug targeting, have really not been applied as 
robustly as it should have been to tuberculosis.
    So, we are engaging in rather intense partnerships, with 
industry and public-private partnerships, for the screening and 
development of drugs for what we call point-of-care 
diagnostics. One of the real tragedies about tuberculosis is 
we're using the same diagnostic test that was used a century 
ago, namely looking into the microscope to look for, in a very 
insensitive way, the tubercle bacillus without even knowing 
just by looking at it whether it's sensitive or resistant to 
the common drugs.
    We've now been involved in developing point-of-care 
diagnosis that can tell you within a couple of hours, for 
example, not only is it TB but is it going to be MDR TB.
    We are now on the way to developing a vaccine. It's curious 
that we have a vaccine for TB that's been around again for a 
century that doesn't work on respiratory TB at all, which is 
the most common form of spread.
    So, these are all the kinds of things that we've 
accelerated intensively over the last several years in both the 
control and, hopefully, it sounds maybe pie in the sky but 
people are starting to think about it now, is major control and 
in some countries even elimination of TB.
    So we're very excited about the efforts, and we will 
continue to make them a high priority.
    Senator Brown. Thank you.
    Thanks, Mr. Chairman.
    Senator Harkin. Senator Moran.
    Senator Moran. Chairman, thank you very much.
    Doctors, welcome. One of the first visits that I made after 
becoming a member of the United States Senate was to the 
University of Kansas, where I saw research, basic research in 
pharmacology, pharmaceutical drugs being developed. And this 
research seems to me to be so beneficial.
    And, particularly, I would highlight an example of 
collaboration between the University of Kansas, NCI, and the 
Leukemia and Lymphoma Society. And it seems to me, if we're 
going to get the best opportunities out of our investment, it 
is this public-private collaboration that's going to make a 
significant difference.

     NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES ROLE AND 
                             RESPONSIBILITY

    And I want to talk, at least in this round of questions, 
about the National Center for Advancing Translational Science 
(NCATS).
    How do we turn medical discoveries into life-saving 
treatments and cures? And my assumption is that's the goal of 
this new center. Is there a problem? Does that not occur 
adequately today in the absence of NCATS? So in other words, 
what role will NCATS play in improving the circumstance, if 
there is a problem to overcome?
    What are the impediments toward getting that basic research 
and pharmacology into those drugs that save and cure and treat? 
And is there any incompatibility with what the private sector, 
what drug companies are doing, and with what NCATS is 
attempting to accomplish?
    And then finally, perhaps this is for Dr. Varmus, but what 
will be the relationship between NCI and NCATS in this process?
    Dr. Collins. Thank you, Senator Moran, for a very 
interesting set of questions, and one that is very much on the 
minds of many of us as we try to make sure the deluge of basic 
science discoveries that are pouring out of laboratories move 
as quickly as possible into their translational and clinical 
benefits.
    You mentioned this relationship between Kansas and NCATS, 
and the Leukemia and Lymphoma Society.
    Senator Moran. I did it to give you a heads up as to my 
question, so you could anticipate it.
    Dr. Collins. We're very excited about this particular 
program, because it's already now enrolling patients into a 
clinical trial.
    I'm going to ask Dr. Insel, who is now the Acting Director 
of NCATS, to address some of the questions you've posed about 
what we aim to accomplish with this newest part of NIH.
    Dr. Insel. Thank you. It's an honor to be able to tell you 
a little bit about this.
    I think the first thing to be clear about is that all 27 
Institutes and Centers at the NIH have an investment in this 
kind of translation going from fundamental discoveries to 
making changes in health. That's what we do.
    What this new entity will do, and as the chairman said 
before, this new entity is essentially just putting under one 
roof many programs that were already there.
    But this is an attempt to develop the tools and to develop 
some new procedures that make it easier for the other 26 
Institutes and Centers to succeed.
    So this is a great example. This is a case in which we were 
interested in taking a compound that was already available in 
the pharmaceutical industry but not being used very much, one 
that was developed for rheumatoid arthritis, and developing a 
process by which we could screen all of the drugs that were out 
there, to see whether they might hit new targets that might be 
helpful for a disease that no one had ever considered before.
    In this case, a drug for rheumatoid arthritis turned out to 
be very helpful for a particular form of leukemia. And then we 
could go to our colleagues in Kansas, who have one of the NCATS 
centers, the Clinical and Translational Science Awards, and get 
them to begin to develop this, working with the Leukemia and 
Lymphoma Society to have this partnership to potentially 
develop a new treatment for this form of leukemia.
    Senator Moran. I appreciate that story very much. It was 
very impressive, again, for me to see in the laboratory.
    Why does that research not take place elsewhere? Why is NIH 
such an important component in bringing these, as you say, in 
this case, a drug that existed but not, I assume, thought of to 
be used for another purpose?
    Is it the NCI that is necessary to get us to move in the 
directions of this new thought, these new opportunities?
    Dr. Insel. Well again, I would want to make clear that I 
think the NCI and many other Institutes have a stake in doing 
just this. The question is whether you want to do it 26 times 
or you want to do it once.
    So in the case of developing, for instance, a procedure to 
move compounds from the pharmaceutical industry into academic 
settings, we all do that at all the Institutes to some extent. 
It's a bit of an impediment. It gets complicated.
    There are templates that can be developed that will make 
that much easier doing it once instead of doing it multiple 
times. And there are tools that we need.
    In this case, this was a particular repository that was 
developed by the folks at NCATS that collected in one place all 
the medications that were out there, so we could do a single 
screen instead of having to break it up into many different 
attempts.
    So NCATS is really an enabler, essentially. We sometimes 
call it a catalyst for innovation. It's a way of putting under 
one roof many of the tools that all of us need to get things 
done faster.
    Senator Moran. Thank you very much, Doctor. Thank you.
    Dr. Varmus.
    Dr. Varmus. Well, let me just add one or two words here.
    As you pointed out, Senator, the categorical institutes 
have a deep investment in translational research activities, 
and the NCI is no exception to that, with well more than $1 
billion a year being invested in these topics.
    In the case of chronic lymphocytic leukemia, we have a 
major program to look at the basic genetics. It's a disease 
that is a smoldering disease which becomes acute, and we have 
very few treatments when the disease enters its acute phase.
    The intramural program of the NCI came to the chemical 
genome screening center to help find drugs that might be 
repurposed, drugs that the company might have little interest 
in, because it's off-patent, and we were fortunate to have this 
drug turn up.
    Now this trial we see as emblematic of what NCI might be 
involved in, in working with NCATS. In this case, as you've 
heard, the trial is being sponsored by the Leukemia and 
Lymphoma Society. But I think this is a good example of how the 
interaction between the NCATS and individual institutes like 
ours might be very beneficial.
    Senator Moran. Thank you all very much.
    Senator Harkin. Thank you, Senator Moran.
    Senator Pryor.
    Senator Pryor. Thank you, Mr. Chairman and Ranking Member. 
Thank you for holding this hearing today, and I want to thank 
the panel for being here.
    I'm going to focus my questions with Dr. Collins and Dr. 
Varmus.
    I'm a cancer survivor. I survived clear-cell sarcoma about 
15 years ago. Thank you for all your work and all you do in the 
cancer area, and every other area, for that matter.

                           PANCREATIC CANCER

    I want to ask about pancreatic cancer. As I understand it, 
it's the most lethal of the common cancers. It's the fourth-
leading cause of cancer death. This year, more than 43,000 
Americans will be diagnosed with pancreatic cancer, most of 
whom will die within 1 year of their diagnosis, because the 
disease is usually too far advanced by the time it's 
discovered.
    And I know in this subcommittee, we're careful to avoid 
trying to tie the hands of scientists by directing too 
precisely the appropriated money, on how it should be spent. 
But I'm troubled that while survival rates of many cancers are 
steadily improving, one of the most lethal forms of cancer, 
pancreatic cancer, remains at about 6 percent.
    And I look at the model for breast cancer. I'm not sure 
that's the best model, but I do look at that model and some of 
the focus there. I'm wondering if NIH would consider using that 
breast-cancer model to try to go after pancreatic cancer.
    Dr. Varmus. Thank you for that, Senator.
    As someone who has lost several friends to this disease 
over the last decade and who has worked in my own laboratory on 
this disease, I appreciate the devastation the disease causes 
and the difficulty of trying to make headway against it.
    Indeed, of the cancers that we work on, I'd say progress 
has been relatively small in the clinical arena, as you point 
out.
    But there is a great deal of reason for optimism in this 
domain.
    First of all, we have a much larger number of investigators 
working on the disease, and we have some scientific 
opportunities that are very dramatic that I'd like to outline 
for you very briefly. As a result of both factors over the 
course of the last decade, the amount of money that the NCI 
spends on this disease, despite the flattening of our budget, 
has gone up 300 percent.
    The model that you alluded to of breast cancer is useful, 
because one of the things that's been a factor in increasing 
our attention and increasing our spending on this disease has 
been the role of advocacy groups, such as the Lustgarten 
Foundation and several others, that have helped to incentivize 
NCI-supported investigators to work on this very difficult 
problem.
    There's been a number of dramatic changes in our view of 
this disease in the last few years, one as a result of being 
able to take DNA from tumors and examine the underlying damage 
in the genomes of those cells, to try to understand the disease 
more profoundly.
    One of the consequences of that analysis has been to 
perceive that pancreatic cancer does not arise in a matter of 
months. It rises over the course of one or two decades. And 
that's an important fact, because we know now that there is 
quite a large window of opportunity for detecting the disease 
earlier than we have seen heretofore. And that's, of course, a 
major factor in this disease, the symptoms appear very late 
when the disease has often spread. And unlike certain other 
cancers that manifest themselves on the skin or with symptoms 
at an early stage, it's been difficult to diagnose this disease 
at an early phase.
    Second, we've been able to understand the relationship 
between the tumor itself and the cells that surround it that 
make the disease somewhat impermeable to some of the therapies 
that have been used for other cancers. And there are new ways 
to try to make the surrounding material more permeable to 
cancers.
    Furthermore, there's been a number of mouse models of the 
disease that were previously difficult to create that are now 
being used to try to understand the physiology of the disease 
and to test treatments in animal models.
    All those things give me considerable optimism for the 
future.

                      PRIORITIZING CANCER FUNDING

    Senator Pryor. Well, does that mean, though, that you're 
going to prioritize it in terms of funding and try to invest 
more there?
    Dr. Varmus. It is prioritized, Senator. And I mentioned 
earlier that, in this period of budgetary constraint, the NCI 
has been paying special attention to grants that might in the 
past have been unfunded because they fell below what we used to 
call a pay line. And now we examine quite a number of grants 
that get priority scores that are perhaps less high and look at 
them for the diseases that fall in certain categories where we 
made less progress in therapeutics, neuroblastoma, lung cancer, 
pancreatic cancer, ovarian cancer, and others. And we 
frequently fund grants that scores may have been a little less 
than others but nevertheless represent high-priority areas for 
us.
    Senator Pryor. Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Pryor.
    Senator Cochran.

            INSTITUTIONAL DEVELOPMENT AWARD PROGRAM FUNDING

    Senator Cochran. Mr. Chairman, thank you very much.
    Let me ask about a program that is designed to help ensure 
a broader base of financial support to research institutions 
and those who are in university settings, and who are engaged 
in research that has unique applications and importance to the 
medical community and the life of the citizens of our country.
    This is done through a program called the Institutional 
Development Award (IDeA), and the whole point is to broaden the 
geographic distribution of NIH funding in biomedical and 
behavioral research programs.
    In my State, we have seen some very important strides made 
in these programs. There are 23 other States in the same boat 
as my State of Mississippi.
    The bill that we have provided funding in directed that 
certain areas be undertaken for research and review. The 
Centers of Biomedical Research Excellence (COBRE), which is a 
Competitive Grant Program, received an increase of $45.9 
million through this program. But NIH said that they're not 
going to be able to use the funds, and so this year's bill 
reduces funding by about $50 million.
    I'm asking, what do we need to do, use different wording, 
put a star by the provision in the bill that these are funds 
that are intended to be used and for the purposes that the 
Congress stated? Who wants to take that on and explain what's 
going on to me?
    Dr. Collins. Senator, I appreciate that question and 
clearly the IDeA program is one that NIH is proud of. And 
before you came in, Senator Shelby was asking whether Alabama 
could be added to the club, because, clearly, the 23 States 
that are eligible for this program depend on the opportunity to 
be able to compete for NIH dollars, and lots of good science 
gets done as a result.
    I want to reassure you that the dollars that were allocated 
to the IDeA program in fiscal year 2012, the year that we're 
currently in, are going to be utilized and are going to be 
utilized, I think, quite effectively. We are going to follow 
the Congress's instructions here in terms of how to make the 
most of this additional allocate of almost $50 million, which 
for the IDeA programs represents a 22-percent increase in that 
program in fiscal year 2012 compared to fiscal year 2011.
    So, we will be funding both COBRE program that you referred 
to. Also, as we were asked to do, the new Center for Clinical 
and Translational Science is part of the IDeA program, and that 
process is already very much underway, and we will make sure 
that we do everything you would want us to, in terms of 
reviewing and choosing the very most competitive programs to 
award those dollars to.
    Going forward in fiscal year 2013, you will notice that the 
dollars do not stay at that same level. We are certainly very 
enthusiastic about IDeA, but at the same time, we have so many 
pressures on so many other parts of the program that the 
President's budget reflects that, in terms of decisions that 
were made in putting together that fiscal year 2013 budget.
    But again, I do want to reassure you, as far as fiscal year 
2012, we are going to spend those dollars in a very, I think, 
aggressively innovative way and to the benefit of the IDeA 
States.
    Senator Cochran. Thank you very much.
    And thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Cochran.
    I just might add on that IDeA program, I was not one of 
those States either. But I'm not clamoring for Iowa to be one, 
because while I understand the interest of States to find 
funding for a lot of different things, I think Senator Shelby 
said it in his opening statement: We want the best science 
rewarded.
    If it's not in Iowa, then it's someplace else. But it's got 
to be the best science.
    We're not in the business of just spreading money around. 
We're in the business of trying to take the limited budget that 
we have and reward the best science that's out there. And we 
count of all of you and your advisory boards and others to tell 
us what that best science is. I just want to make that 
statement.
    Senator Cochran. Could I have the opportunity of asking the 
witness whether they think this is wisely invested money or 
not? I think the suggestion of the question that the chairman 
has asked suggests that they may be funding in this program 
just because a Senator on this subcommittee, vice chairman of 
the full committee, asked for it.
    Senator Harkin. No, I just want to----
    Senator Cochran. That's not the purpose of the question. 
The question was on the merits of the program, if it was 
justified and if the funding level and the language and all was 
consistent with what the department and the witnesses here 
thought would be an appropriate investment.

                             H5N1 RESEARCH

    Senator Harkin. Well, I sure hope so. I hope that is what 
they will do.
    Dr. Fauci, over the past few months, there has been quite a 
controversy regarding NIH-funded researched related to H5N1 flu 
virus. You remember, you've been here before in the past on 
this?
    Dr. Fauci. Yes.
    Senator Harkin. A great flare up a few years ago from 
Southeast Asia, concerned about what was going to happen when 
it got here.
    Fortunately, we found out that it wasn't very transmissible 
to humans. But recent research has shown that it's possible to 
genetically alter the virus so that it could spread from human 
to human.
    In December, the National Science Advisory Board on 
Biosecurity said that this research was a ``grave concern to 
public health.'' It asked two journals, Nature and Science, to 
withhold some parts of the research results to reduce the risk 
that bioterrorists and others could misuse this information.
    On the other side, however, many leading flu researchers 
disagree and believe the full results should be published.
    As of now, a final decision on publication is still 
pending. There's also a voluntary moratorium among flu experts 
on some of the research.
    You have said that you support this research. I want to 
know why, and what did NIH hope to learn? Is it worth the 
danger that a lab-made virus could be released into the world, 
either intentionally or by accident? And do you think the full 
results of this research should be published?
    Dr. Fauci. Okay. Thank you for that question, Mr. Chairman.
    First of all, the issue of H5N1 and why we do the research, 
there is no question that influenza, in general, the potential 
for pandemic influenza and, in this case, specifically, the 
H5N1, is a clear and present danger because we still have 
smoldering infections with major outbreaks in chickenpox and, 
occasionally, a jump from a chicken species to the human 
species.
    As you said correctly, this is not easily transmissible 
from human to human, and certainly not transmissible easily 
from chicken to human. The problem is that, as you look in the 
wild, you see that viruses, as they always do, evolve. And the 
critical question that really spurs this research is what are 
those factors that go into the evolution of a virus to what we 
call ``species adapt.'' In this case, adapt to the human in a 
way that would make it transmissible. This is an absolutely, 
unequivocal, critically important question to ask.
    So in that case, the research is really very important. We 
have a major program for decades that studies what we call 
transmissibility in species adaptability that has made us much 
better prepared from year to year and on the rare occasion 
where you get a pandemic to be able to predict and be prepared 
for, to respond to a pandemic. That's issue number one.
    The papers in question, we're doing something that is an 
important approach toward understanding this phenomenon that is 
a real and present danger in the wild. And what they did is 
that they tried to characterize exactly how a virus would look 
if it did develop the capability of, in this case, mammal.
    You use the words human transmissibility. I want to 
underscore that this was transmissibility from ferret-to-
ferret, which is a good but imperfect model for human 
influenza. So there is a misperception there that this is now 
transmissible in human.
    There was also a misperception in the information that was 
given out to the public that when you made a virus 
transmissible from a ferret to a ferret by aerosol 
transmission, which is the way humans transmit virus from one 
to another, that actually those ferrets died with high degree 
of mortality. And that turns out to be not the case.
    So where we are now, today, is that we had a determination. 
We are very careful about the balance between the scientific 
need to know for the public health good and safety and 
security. We take that very, very seriously.
    When it became clear that this could be what we dual-use 
research of concern that could possibly be used for nefarious 
purposes, we put it before an advisory committee that made the 
recommendation on the basis of the information that they had 
that the research was important to perform, but that perhaps 
parts of it, the details, might not be readily available to 
everyone.
    WHO called a meeting, and when they looked at the data and 
some additional data, and some clarification, they came to a 
conclusion that was a little bit different. They said, in the 
big picture of things, the real and present danger of this 
happening in the wild really outweighs the possible risks of 
there being bioterrorists.
    So, we have a disparity now of recommendations.
    Tomorrow, the NIH/HHS is reconvening the National Science 
Advisory Board for Biosecurity, which is a nongovernment, 
outside group that would advise the Government, and we are the 
ones that originally said that we should hold back.
    So we're looking forward to tomorrow and Friday when this 
group will reconvene and look at additional data, because there 
has been considerably more information that has been gathered 
since the original determination to hold back some of the data.
    Senator Harkin. Well, I'll look forward to that, too. In 
the next couple of days?
    Link for Recommendations follows: http://oba.od.nih.gov/
oba/biosecurity/PDF/03302012_NSABB _Recommendations.pdf.
    Dr. Fauci. Yes, Sir.
    Senator Harkin. That's very timely.
    I have a follow-up on that, on H5N1, in my next round, but 
my time is up.
    Senator Shelby.

                             DOWN SYNDROME

    Senator Shelby. In the area Down syndrome, Dr. Collins, I 
support the goal of the NCATS to invest in research that moves 
a potential therapy from development to market as you do. As 
you continue to develop aspects of the new center, this may be 
an opportunity to focus on conditions where comorbidities are 
so pervasive that research will help both the population in 
question and those suffering from such comorbidities.
    For example, 50 percent of those born with Down syndrome, 
also are born with a congenital heart defect, and more than 50 
percent of those with Down syndrome will suffer from the early 
onset of Alzheimer's disease. Yet it's extremely rare for a 
person with Down syndrome to suffer from a solid tumor cancer, 
heart attack, or stroke.
    Can you discuss how NCATS will focus on diseases, such as 
Down syndrome, whose research could benefit many in 
populations?
    Dr. Collins. Thank you for the question, Senator. I'm 
trained as a medical geneticist, and so Down syndrome is 
certainly one of the conditions that, in my clinical years, I 
spent a lot of time wrestling with, in terms of trying to give 
the best advice to children and their parents about this 
disorder.
    As you know, this is caused by an extra copy of an entire 
chromosome, chromosome 21, which means that genes that are 
normally present in two copies are present in three. Even 
though it's one of the smaller chromosomes, there's still a lot 
of genes on that chromosome.
    And it's been a big question for research to figure out 
which of those are the ones that are so dose-sensitive, because 
most of the time, if you have 50 percent more of something, 
it's not going to cause a lot of trouble. But, apparently, on 
that chromosome are some genes that do have that potential.
    It's the National Institute of Child Health and Human 
Development (NICHD), whose Director, Dr. Alan Guttmacher, is 
here, who has the lead in Down syndrome research. They have put 
together a research protocol and a plan over the course of the 
last few years, and now formed a consortium bringing together 
NIH and other organizations to be sure we are looking at what 
the opportunities and gaps are.
    There is some exciting research going on in terms of the 
mouse model of Down syndrome and even some therapeutic 
interventions using neuropeptides that seem to show promise in 
that mouse model.
    In terms of the role of NCATS, again, as you heard from Dr. 
Insel, NCATS does not have as its goal to focus on specific 
disorders. That's the role of the other 26 Institutes.
    NCATS aims to provide resources and to attack those 
bottlenecks that are slowing down everybody, and to try to see 
whether we could do better in terms of, when you have an idea 
about a therapeutic, how do you get it to the point of a 
clinical approval in less than 14 years and with a failure rate 
that's less than 99 percent? That's really what NCATS is all 
about.
    So, NCATS should be an important addition to the landscape. 
But again, I think the lead efforts in Down syndrome will 
continue to be at NICHD.

             INTERAGENCY COLLABORATIONS AND CYSTIC FIBROSIS

    Senator Shelby. Thank you.
    Dr. Collins, this is a very important time, as you said, in 
the history of drug development. We continue to see the 
benefits from mapping the human genome when specific treatments 
for genetic diseases are being developed to target smaller and 
smaller populations.
    This aspect of personalized medicine holds promise to treat 
or to cure rare diseases that plague millions of Americans.
    In January, the Food and Drug Administration (FDA) approved 
a groundbreaking new drug for cystic fibrosis. This drug treats 
the underlying genetic cause of cystic fibrosis in the 1,200 
people who are affected by a particular genetic mutation. This 
breakthrough treatment has led to tremendous health gains for 
those who take the drug, and may lead to the development of an 
innovative new class of drugs for a much larger portion of the 
cystic fibrosis population.
    Collaboration between the NIH and the FDA has the 
potential, I believe, to move genetic breakthroughs more 
quickly through the development process and into the hands of 
patients by ensuring that the FDA has the tools it needs to 
review and to regulate the genetic treatment.
    What are your thoughts on this?
    Dr. Collins. Well, Senator, I think what you've pointed to 
is a really exciting development for cystic fibrosis but also a 
very important point you're making about the need for close 
collaboration between NIH and FDA, the private sector, and 
advocacy organizations, such as the Cystic Fibrosis Foundation, 
who played a big role in this recent advance in cystic 
fibrosis.
    And if you'll permit me, I will tell you what a personal 
delight it was, having been part of the team that discovered 
that gene in 1989, to see at this point the use of that 
information coming forward with the drug Kalydeco.
    Senator Shelby. What can that mean to the people with 
cystic fibrosis?
    Dr. Collins. So for the roughly 1,300 individuals in the 
country who have this specific mutation in the cystic fibrosis 
gene called G551D, which is unfortunately only about 4 percent 
of cystic fibrosis sufferers, this drug causes that defective 
protein to rev itself up. And the clinical results, as 
published in the New England Journal last year, are truly 
dramatic in terms of improvement in lung function, gain in 
weight, because cystic fibrosis is often associated with weight 
loss. And also, you can see the biomarker for cystic fibrosis, 
the sweat chloride, returning to normal in kids who are taking 
this drug.
    Again, this special this evening that NOVA is putting on 
will give you a couple of examples of how that has played out.
    So that is really gratifying. But you're right. We need to 
be sure that we can replicate that many times over.
    Dr. Margaret A. Hamburg, the Commissioner of the FDA, and I 
have formed a joint leadership council between our senior 
leaders, and many of the NIH representatives who are sitting 
here at the table are on that council. She has also brought her 
Center Directors into that same place.
    We have resolved together to identify the areas that are 
most in need of this kind of collaboration and are working 
quite intensively to try to do that.
    Senator Harkin. Thank you very much, Senator Shelby.
    Senator Mikulski.
    Senator Mikulski. Good morning, everybody. I'm so sorry I 
couldn't be here for all of your testimony. I was at the DOD on 
military medicine, and of course, as you know, a lot of that is 
right across the street from NIH, and we won't talk about the 
traffic jam.
    Senator Harkin. But thank you for helping with that, too.

                NATIONAL INSTITUTES OF HEALTH PRIORITIES

    Senator Mikulski. And I was effusive with Senator Inouye.
    But, Dr. Collins, and to all of you, I've known you for so 
many years, and I just want to welcome you and let you know how 
glad I am to see you and how much you are appreciated. We ask 
you to do a lot. We hope that we have the adequate resources, 
and at the same time, we are deeply troubled that, as Federal 
employees are under attack, they seem to forget that you are 
the Federal employees we need and we turn to in the national 
interest.
    I'll come back to that, because I wonder how all of that 
harassment, hazing, the cute one-liners in town hall meetings 
against Federal employees are affecting morale, recruitment, 
and retention, because, I think, from what I hear, standing in 
a bagel line or something, or a broccoli line, in Rockville, 
that I hear it.
    But let me get right to my question. Many of you we have 
turned to at a time of national emergency, and I think of Dr. 
Fauci, when an obscure virus was beginning to kill young men in 
our community and escalated in our country and even into a 
global crisis, AIDS; when we had the anthrax scare here, et 
cetera.
    We came together, and we really moved on a national agenda, 
and this then goes to, picking up on Senator Shelby, the 
acceleration of drugs.
    Now, Dr. Varmus, you and I have talked about these things. 
We don't want industrial policy visits at NIH. We don't want to 
pick winners and losers, et cetera.
    But we have compelling needs. We have the orphan drug, you 
know, the rare disease constellation and then we have those 
areas that relate to chronic illness or the impending or 
arriving epidemic of Alzheimer's.
    And my question to you is looking at both your Center for 
Translational Medicine and so on, how can we look at what are 
compelling national needs, those that we know will impact 
significant parts of our population, use a significant amount 
of our cost for the treatment of these, some so long range, 
like Alzheimer's, some immediate, like diabetes, Dr. Rodgers?
    One, do you think it is a valid thing to do? How can we 
work with you to do that? What are the right resources? And how 
do we avoid the industrial policy syndrome, which we certainly 
don't want to get into, because you do need lots of latitude 
for discovery.
    Dr. Collins. Well, thank you, Senator, and by the way, 
congratulations to the Senator from NIH on this recent 
milestone of recently being recognized as the longest-serving 
woman in Congress. We were all cheering for that.
    Senator Mikulski. Thank you. It was moving from the bagel 
line to the broccoli line.
    Dr. Collins. Your question is a very important one. How do 
we in fact decide how to set priorities is what I think you're 
asking, and of course that's not only----
    Senator Mikulski. And also how to accelerate?
    Dr. Collins. And how do we speed up the process of going 
from basic science to therapeutics?
    Maybe just as an example, because it is timely, I would 
mention what you just mentioned, the situation with Alzheimer's 
disease. So talk about a public health circumstance of enormous 
concern. Here we have a diagram showing the prevalence of 
Alzheimer's disease currently at 5.1 million, expected to rise 
almost to 12 million over the course of the next few years, if 
nothing is done about it, and with the cost going through the 
roof. So here is an area of potential, very serious 
significance.
    And also, I'm happy to say, a situation where the science 
of Alzheimer's disease has come across quite quickly in just 
the last year or two, putting us in a position to be able to 
push that therapeutic agenda harder. And yet for many 
companies, diseases affecting the CNS are not seen at the 
present time as being particularly commercially attractive.
    Senator Mikulski. Do you want to say what CNS means?
    Dr. Collins. CNS, central nervous system. I'm sorry. Brain 
diseases.
    I'm going to ask Dr. Hodes, who is the head of the National 
Institute of Aging, to just say a word about the science that 
propels us to be particularly excited about Alzheimer's, again 
as an example of the exhortation you're providing us about what 
we need to pay attention to.
    Dr. Hodes. Thank you. I'd be happy to do so.
    As we've seen emphasized, the byproduct of the extended 
longevity in the American and world population has really been 
the increased threat posed by diseases of late life, and 
Alzheimer's is certainly prominent among them.
    So there's no question, as there has been for a number of 
years, about the public health importance and imperative. As 
Dr. Collins notes, what is most exciting to us all is the 
advance in science that really creates an opportunity, 
justification for optimism, that didn't exist before.
    Earlier, Dr. Collins presented an example of a drug through 
repurposing, in this case Bexarotene, a drug that had been used 
to treat a kind of skin cancer, which when tested for its 
effect on some of the underlying processes of Alzheimer's 
disease in a mouse model showed absolutely dramatic effects.
    Another kind of advance that has been featured, just in the 
past few months, has been the use of induced pluripotent stem 
cells and particularly the translation from a skin fibroblast 
from an individual with or without Alzheimer's disease into 
neuronal cells in a tissue culture dish, which reflect many of 
the underlying biochemical abnormalities of Alzheimer's 
disease.
    The potential here for screening now in cells and tissue 
culture tens, hundreds, thousands of compounds, to see whether 
they will have an effect that provides a suggestion of which 
might ultimately be translated, is just one of the many 
examples that we are poised to capitalize upon at this time.
    Senator Mikulski. Dr. Hodes, if I could jump in?
    This is so exciting to hear. But I held a hearing 3 years 
ago on the issues of Alzheimer's, with my colleague Senator 
Bond, who was tremendously interested in this as well as 
arthritis. And we heard then, 3 years ago, well, we are on the 
brink of big breakthroughs.
    So I had a legislative framework to take a look at that. I 
was stymied in this institution, okay? I was stymied in this 
institution on taking a look at this. And I won't go through my 
legislation. This is not about me. It's about people, which is 
why we're all in this.
    And my question is, 3 years later, I've given up on 
legislation. I mean, I'm going to move my legislation. Maybe 
it'll happen; maybe it won't.
    But I'm asking, administratively, and through the executive 
branch, where we have a body of knowledge and a variety of 
studies that are breakthrough possibilities that meet 
compelling human need and big budget busters, how can we move 
these through this process and get them into the hands of 
clinicians?
    I've now heard about promising science, and I'm going to 
continue to support it, but the promise of science needs to 
have deliverables.
    Dr. Hodes. If I may, Mr. Chairman? I know we're over time.
    Senator Mikulski. Do you mind, Mr. Chairman?
    Senator Harkin. We're over time, but go ahead and respond, 
please.
    Dr. Hodes. So with regard to Alzheimer's, recognizing the 
exceptional scientific opportunity and public health need, in 
the fiscal year 2013 budget, the President's budget proposes an 
additional $80 million for Alzheimer's disease research, over 
and above the regular NIH appropriation, as a recognition of 
that exceptional opportunity.
    But I think your question is broader than that.
    Senator Mikulski. It's much broader.
    Dr. Hodes. And that is how do we, at a time where resources 
are in fact constrained, make decisions about how to set the 
priorities to the way that benefits the public in the greatest 
way? That is our toughest challenge. That's what we sit around 
the table with the Institute Directors on Thursdays and try to 
wrestle it. That's what all 27 of the Institute and Center 
Directors are charged with, in terms of surveying the 
landscape, trying to see where the gaps are. What we don't want 
to do is be overly top down.
    Senator Mikulski. You haven't answered my question.
    Dr. Hodes. I thought I was getting there, but maybe I----
    Senator Mikulski. I feel the pressures of time, Doctor. And 
I don't mean to be interruptive or whatever. But I know you're 
working hard on it. But do you have an answer to my question?
    And if not, it's not a hostile or aggressive question. I 
just feel the demands of time on our population, the 
frustrations that families and patients have. You meet with 
advocacy groups. You're well-known for your accessibility.
    Do you have an answer on how we can do this without 
industrial policy?
    Dr. Hodes. Senator, I share your frustration and your 
passion, believe me. The reason I went into research was 
because of the concerns that we weren't going fast enough in 
finding answers for people who need them desperately.
    I think what NIH is trying to do, in answer to your 
question, is to be sure we are looking at every possible means 
of promoting science rapidly. We are trying to figure out how 
to work with the private sector in circumstances where we can 
do things together.
    But for circumstances where clearly things are hung up, 
like the bottlenecks we're now trying to tackle with this new 
NCATS, we are jumping out there in a fairly aggressive way, in 
fact, in a way that some have said was too aggressive.
    But we accept that concern, because of our impatience, just 
like yours, to take this science that's happening right now and 
turn it into treatments and cures for those millions of people 
who are waiting for those hopes to come true.
    Senator Mikulski. I know my time is up. Well, I want to 
thank you for your science. I want to thank you for your 
dedication and for your compassion and your humanitarianism.
    Senator Harkin. Thank you.

                           NEW INVESTIGATORS

    Senator Moran.
    Senator Moran. Mr. Chairman, thank you. Doctors, let me 
just join, perhaps, the Senator from Maryland, and I was 
thinking about the--I think most of us spend our lives trying 
to create hope for other people. I hope that you take great 
satisfaction in the noble calling that you're pursuing in your 
lives and know that you are providing hope. In my view, it's 
the mission of the NIH to provide hope for Americans and really 
for people around the world that we find cures and treatments.
    And so I commend you for choosing a profession, a career, a 
path, that I think matters so much in changing the world.
    Somewhat in that regard, obviously bringing new talent and 
professionalism, scientists, researchers, and medical 
practitioners to the arena to provide that hope, I've said 
numerous times that one of the problems with reduced funding at 
NIH, or flat-funding that results in less actual money 
available for research, one of the reasons that that's so 
troublesome to me is that we're sending a message to the next 
generation, the potential researchers, scientists, physicians, 
that the certainty of their career path or the value of what 
they do is not recognized.
    And while I say that, I don't have any basis other than 
perhaps common sense to say that that would be the case, and I 
would be interested in knowing if you can, either anecdotally 
or scientifically, tell me that that's a valid point to make to 
the American taxpayer, the merit of making certain that funding 
continues in a stable manner.
    And one perhaps less philosophical question, I would like 
to hear, Dr. Insel, if there is a--this is a question that 
comes to me just knowing of your center. What's going on that 
will be helpful to our returning veterans related to mental 
health? And is there a relationship between what you do and the 
Department of Veterans Affairs (VA)?
    Dr. Collins. I'll take the first part of your question, and 
then ask Dr. Insel to jump right in.
    Certainly, for a new investigator who has recently gone 
through extensive research training and is now starting up 
their own independent research program in one of our Nation's 
great universities or institutes, this is a somewhat scary 
time. They can see what's happened in terms of the likelihood 
of being funded if you send your best ideas to NIH, which 
traditionally during the last 40 years has been in the range of 
25 to 35 percent, and which last year, the last year we have 
full numbers for, fell to 17 percent.
    That means that an awful lot of that effort comes away 
without support. And, therefore, those investigators spend even 
more of their time writing, revising, resubmitting, hoping that 
they will actually make that cut and be able to get started.
    And certainly, if I had to pick one thing that I would say 
would be most healthy for the American biomedical research 
future, it would be stability. The feast or famine just doesn't 
work in this circumstance. You want to give investigators the 
confidence that if they have good ideas, and if they work hard, 
and if they produce publications that change the direction of a 
particular field, they make insights, they make breakthroughs, 
they take risks, that there is a career there. And it's 
difficult when things are bouncing around, as they currently 
are, for particularly early stage investigators to have the 
confidence that there's a pathway for them.
    That trickles down, and others who are sort of earlier in 
their decisionmaking hear about it and begin to wonder whether 
this is a career that they want to invest themselves in.
    That's not happening in other countries, but that's 
happening, certainly, in the United States.

                       RECRUITMENT OF SCIENTISTS

    Senator Moran. Is there an opportunity for that talent that 
we're trying to retain in the United States? Is there a 
movement abroad? Would research scientists in the United States 
conduct their research elsewhere or pursue--are we competing, I 
guess is the word, in a global economy, for the best talent?
    Dr. Collins. We are, and, of course, we have greatly 
benefited over the years in being able to recruit talent from 
other countries, and we continue to.
    In many instances, those individuals would come and be 
trained in our country and then would stay and become part of 
this remarkable innovative community.
    It is less likely now that those individuals will stay. 
It's easier, in many ways, to go back to their countries, where 
there's more support now plus perhaps they see the environment 
here as not as friendly.
    So, yes, that dynamics have certainly changed.

                     POST-TRAUMATIC STRESS DISORDER

    Dr. Insel. So very quickly, with my day job hat on, from 
NIMH, we're particularly concerned about the needs of returning 
veterans. Estimates are somewhere north of 300,000 who will 
develop post-traumatic stress disorder (PTSD) or a related 
disorder that will require some kind of care in the community 
or potentially through the VA.
    We work closely with the VA, but our largest single project 
currently is actually with the DOD, working with the Pentagon 
on a massive project now with more than 30,000 soldiers 
involved, to look at soldiers, with active-duty soldiers, and 
following them through their service to figure out what we can 
do to make sure that they don't develop PTSD, traumatic brain 
injury, or other problems.
    That was really generated by the increase in suicide that 
was reported by the Army, and we've been charged with trying to 
turn those numbers around.
    Senator Harkin. Thank you, Senator Moran.
    Dr. Fauci, I said I have a follow up on H5N1, and that's 
not true. I have a follow-up question but not necessarily on 
H5N1, except to say I just wonder if we've been kind of lulled 
into a state of complacency on this. And we know viruses mutate 
all the time. If this does mutate into a form that is 
transmissible, it could be devastating.
    Dr. Fauci. Right.
    Senator Harkin. And hopefully, we're prepared for that.
    Dr. Fauci. Right.

                       IMMUNOTHERAPY ADVANCEMENTS

    Senator Harkin. But what I want to ask you about was a 
question that you've responded to previously before this 
subcommittee and it has to do with food allergies. We talked 
about this a lot in the past.
    I've been told that small trials involving immunotherapy 
have been very encouraging in treating children who have 
peanut, egg, and/or milk allergies. As I understand what 
happens, these kids are given small amounts, and then larger 
and larger amounts.
    Again, I guess for some children with very severe cases, 
this isn't enough, so they're given both that plus a drug.
    From what I understand, what's needed now are phase II 
trials for these treatments, as well as studies that could 
explain how they're working.
    So, again, what's happening in this area? Why does 
immunotherapy work for some and not for others? And how are you 
proceeding with the phase II trials?
    Dr. Fauci. Okay. Thank you for that question.
    We have, as I've told you and this subcommittee before, 
over the last several years, dramatically increased the 
resources that we have put in on food allergy. Having said 
that, we started off at a low number. So at a time when the NIH 
budget has been flat, we have been progressively increasing by 
a considerable number of factors.
    We still are not where we want to be, but within that 
realm, answer to one of your specific questions, it is unclear 
at present why some people respond to this early 
desensitization by giving small amounts of what would 
ultimately be desensitizing antigen--in this case, it would be 
peanut or chocolate or something like that.
    Phase II trials are, as you know, the next stage after you 
show that a particular intervention is safe in a phase I to go 
in and get more information from a phase II. We are very much 
right now involved in making that next step to go to phase II 
trials and some of those interventions. But it is not in a 
situation where we are having a large enough trial to 
definitively answer the questions, but that is the next stage 
that we're going.
    So we're right at the point and we are working with a 
number of the societies. In fact, I just met less than 2 weeks 
ago with our food allergy constituency groups to discuss how we 
might continue in an arena of constrained resources to push 
this agenda, particularly in the arena of clinical trials.
    Senator Harkin. If you don't have the figure now, maybe you 
could just transmit it to us later on, just how much is this 
going to cost.
    Dr. Fauci. Right. Okay. I don't have the exact number now, 
but clinical trials in general, particularly when you get to 
phase II and phase IIB, which involves several hundreds of 
people, it costs a considerable amount of money.
    And that's really been one of the constraints that we have, 
because the total budget for food allergy, although it's 
accelerated greatly over the last few years, is still, 
relatively speaking, when you compare it to other things, 
rather small, which we're trying to do something about.

                          ALZHEIMER'S RESEARCH

    Senator Harkin. Thank you, Dr. Fauci.
    I still have a minute and a half. I want to get Dr. Hodes 
into this area of Alzheimer's research. The President, as Dr. 
Collins has said a couple of times in his opening statement, 
again, has proposed $80 million for NIH research specific on 
Alzheimer's.
    And where he's getting the money? He's taking it from the 
Prevention and Public Health Fund (PPHF), Senator, that we put 
into the Affordable Care Act.
    I just, again, in a friendly atmosphere, want you to know 
that that won't happen. That is not going to happen. I will 
make absolutely certain that not one more nickel is taken out 
of the PPHF for anything outside than what it was intended for. 
Just as I will not go after NIH to get money for the PPHF, 
we're not going to take money out of that fund and put it into 
NIH.
    Now, again, if you're wondering why I'm so upset about 
this, it's because this President put in his budget to take 
$4.5 billion out of that fund. And the Congress, in extending 
the unemployment insurance to the end of the year and that tax 
cut on Social Security, while they pay for it, they took the 
money out of the PPHF.
    So I'm very upset about that. I'm very upset with the 
President and his people at the Office of Management and Budget 
(OMB) for what they did on that, and then to come and say, now 
we're going to take another $80 million. I know that sounds 
like a small amount but, still, after you've taken $5 billion 
out, and now they're just going to start nickel and diming us?
    So, I just want you to know, I'm a strong supporter of 
Alzheimer's research, but this $80 million isn't happening. NIH 
has the flexibility to direct a larger share of its funding to 
Alzheimer's research within its own budget, assuming two 
things. One, there are enough scientific opportunities to 
warrant an increase, and, second, researchers submit enough 
high-quality applications.
    So, again, I know all of the data and statistics on what's 
happening on Alzheimer's in the future. It's something we have 
to pay more attention to. We need more research into that area. 
How much more, I don't know. That's up to you. You're the 
experts in this area.
    But this subcommittee will be more than supportive of 
efforts by the NIH to focus more on this, given those two 
conditions that I mentioned, into Alzheimer's research.
    And I don't know if you have a response to that, Dr. Hodes 
or not, I'm not asking for a response. I just want you to know 
what's happening here.
    Senator Shelby.

            NATIONAL INSTITUTES OF HEALTH MERITOCRACY MODEL

    Senator Shelby. Thank you, Senator Harkin.
    The NIH has a highly competitive, two-tiered, independent 
peer-review process that ensures support of the most promising 
science and the most productive scientists. The fiscal year 
2013 budget proposes to alter this system by capping the amount 
of awards one principle investigator can receive at $1.5 
million.
    And while I suspect you will state this proposal will only 
scrutinize large guarantees and not mandate a strict dollar-
level cap, I'm concerned that there's a larger issue with this 
proposal; that is, a disincentive to success.
    This proposal limits the amount of rewards one investigator 
can receive through the peer-review process and does not let 
science dictate funding decisions.
    Dr. Collins, what will make a researcher strive for the 
next discovery when they're limited in the awards that they can 
receive? Could you explain?
    Dr. Collins. Senator, I appreciate the question very much, 
and we are, at NIH, proud of being what we would call ourselves 
a meritocracy; that is, you get supported by NIH because of the 
strength of your science.
    Senator Shelby. Right. Well, that's a strength of NIH, 
isn't it?
    Dr. Collins. It is. And we aim to maintain that.
    This circumstance is born of the particularly difficult 
constraints that we now see in front of us, where there is no 
magical solution to the several pressures.
    I mentioned earlier that the ability of early stage 
investigators who are just getting started to get funded is 
clearly putting them under considerable stress.
    We debated over many months whether in fact there were 
levers that NIH might be willing to try to pull in this 
circumstance to be sure that we were supporting the best 
science in a way that might require a little bit more scrutiny 
in certain circumstances.
    And you're right in your comment. What we are not proposing 
is a cap on an individual investigator's support at $1.5 
million, not at all. It is just that if an investigator has 
already achieved that amount of funding and comes in asking for 
more, that particular grant is going to get a little bit more 
scrutiny to be sure that this is in fact the best use of the 
taxpayers' dollars.
    That's what we're aiming to try to do. This has been, in 
some ways, piloted by National Institute of General Medical 
Sciences (NIGMS). They have been doing this already for several 
years, and even at a lower cap, at $750,000.
    And most of the time, when they look at the application, 
they said, this is great science, we should fund it. We've 
looked at it a little bit more closely now. We want to be sure 
that this investigator can actually manage three or four 
projects as opposed to one, and we think they can, and let's go 
ahead and see what they can do.
    Senator Shelby. So you're not saying you're going to cap 
it?
    Dr. Collins. No.
    Senator Shelby. You're going to measure it and see what 
happens.
    Dr. Collins. We're going to look at it a little more 
closely and see what happens.
    Now only about 6 percent of our investigators are at that 
level, so this is not going to clog the system. And it will be 
the decision of our advisory councils, who are themselves very 
invested in the meritocracy model, who will decide whether, in 
fact, this is the right place to go.

                          REPLICATING RESULTS

    Senator Shelby. In December, the Wall Street Journal ran a 
front-page article entitled, ``Scientists' Elusive Goal: 
Reproducing Study Results.'' I'm sure you saw that.
    The article described a phenomenon in which most biomedical 
study results, including those funded by the NIH, that appear 
in top peer-reviewed journals cannot be reproduced or 
replicated.
    The article cited a Bayer study, describing how it had 
halted 64 percent of its early drug target projects because in-
house experiments failed to match claims made in the 
publications.
    This is a great concern, Dr. Collins. I don't want to ever 
discourage scientific inquiry, and I know you don't, or basic 
biomedical research. But I think we on this subcommittee, we 
need to know why so many published results in peer-reviewed 
publications are unable to be successfully reproduced.
    When the NIH requests $30 billion or more in taxpayer 
dollars for biomedical research, which I think is not enough, 
shouldn't reproducibility, replication of these studies, be a 
part of the foundation by which the research is judged? And how 
can NIH address this problem? Is that a concern to you?
    Dr. Collins. It certainly is, Senator. And that Wall Street 
Journal article also I think raised many ripples of concern, 
because of the numbers that Bayer was citing.
    Well, first of all, we know that investigators who are 
doing cutting-edge science are working in areas where you're at 
the edge of what's possible.
    Senator Shelby. We know you're experimenting and you're 
hoping. I understand.
    Dr. Collins. Exactly. And so it is not surprising that in 
that circumstance you may come up occasionally with results 
that others can't seem to replicate but----
    Senator Shelby. What about that kind of percentage?
    Dr. Collins. Well, the percentages quoted by Bayer were 
certainly deeply troubling.
    Senator Shelby. What about at NIH? What kind of percentages 
do you have there?
    Dr. Collins. I think it would depend on exactly how the 
question was phrased. So certainly----
    Senator Shelby. What do you mean by that?
    Dr. Collins. Well, when somebody is publishing a paper 
saying that we have determined that it is exactly 24.3 percent 
of individuals who have a particular problem when it turns out 
it's really 31 percent or 17 percent. Well, was that a 
confirmation or not? You see the issue in terms of the 
precision.
    Bayer as a company is trying to make drugs. They want to 
tolerate no imprecision before they invest hundreds of millions 
of dollars. So, some of this is along those lines.
    Senator Shelby. Okay.
    Dr. Collins. Some of it is, frankly, the fact that when you 
try to repeat an experiment, you may not do it exactly the same 
way. And both answers could be right, the original investigator 
and the person who tries to reproduce it, but they actually 
didn't quite do the same experiment. And that is always a 
possibility when you look at a conflict of this sort.
    But you know what the good news is? It's that science is 
self-correcting, that over the course of time, any result that 
matters is going to be looked at by other investigators, in the 
private sector, in the public sector. And if it is not correct, 
you will discover that relatively soon. And if it is correct, 
others will know that and will build upon it.
    So despite the concerns here, which I think are quite real, 
I think we can be confident that our overall scientific 
foundation is strong.
    Senator Shelby. Thank you. Thank you, Mr. Chairman.
    Senator Harkin. Great response.
    Senator Mikulski.

              FEDERAL EMPLOYEES: RECRUITMENT AND RETENTION

    Senator Mikulski. I know the hour is growing late, and I 
want to note Senator Harkin's concern about prevention.
    And when we did the Affordable Care Act, this was going to 
be one of the lynchpins of our bill, both prevention and 
quality initiatives, so that we can both save lives, improve 
lives, as well as save money.
    That is why we looked at chronic conditions. That is why 
you'll hear me talk so much about them. The epidemic that we 
know is a chronic condition. Hopefully, one day we can manage 
Alzheimer's the way we manage diabetes, that we know that it is 
there, but we can handle it.
    Unfortunately, the prevention money has been used as a bank 
to fund other things, and this is what has Senator Harkin so 
concerned and, quite frankly, myself.
    And I think we need to look at the Alzheimer's funding. We 
need to talk about where else we can look to that, because it 
would be a sad day in our country where one important need and 
one important paradigm shift and focus is pitted against each 
other. So we look forward to working together to solve this 
problem and to move ahead.
    But I want to talk about Federal employees in your NIH. Of 
course, I am deeply concerned about the continual attack. Not 
only do we have to look at how we are going to fund Federal 
employees, their pay, their pensions, the pay freeze but also 
this ongoing hazing, harassment, snarky comments, throwaway 
one-liners, and so on.
    Now that's how I feel. Could you tell me, Dr. Collins, how 
that impacts your recruitment and retention? Or have I just got 
a soft heart towards Federal employees?
    Dr. Collins. We thank you for your soft heart, Senator. It 
means a lot.
    But this is a very serious issue in terms of morale. For 
individuals like the 18,000 who work at NIH, to read about 
themselves in the comments of individuals who've never met 
anybody who works at NIH and who talk about these being 
employees who are simply overpaid and contributing little is 
deeply hurtful.
    I am so proud to stand at the helm of an organization with 
such incredibly dedicated people, some of whom you see here at 
this table with me, and all of those, in terms of senior 
scientific positions, who could easily be employed at much 
better financial rates in other parts of the public and private 
sectors, and who are doing this work because of their hopes of 
making a difference, because of their public spirit, because of 
their determination to make the world a better place.
    To have that kind of dedication characterized in the way 
that seems to be done in a sweeping way by people talking about 
Federal employees as if they are somehow a parasite upon the 
public is really deeply hurtful.
    And of course, that is translated into decisions in terms 
of ways in which Federal employees are being treated in terms 
of financial aspects, which I think our employees are ready to 
actually tighten their belts and take whatever needs to be done 
in an honorable fair-minded way, as far as helping out with the 
difficulties our Government faces.
    But why gang up on them? Why try to single them out?
    Senator Mikulski. Here is my question in line with that. 
Since all of the activities that have been going on, 
particularly around pensions, extended pay freezes, and so on, 
do you see an upsurge in requests for retirement?
    Dr. Collins. I don't know if I have statistics on exactly--
--
    Senator Mikulski. I am not only talking about the Ph.D.'s, 
but we're talking about the lab people, the ones who run that 
fire department. I mean, there is a lot of support staff that 
goes on to enable the scientist to be the scientist.
    Dr. Collins. Indeed. And we depend on those people 
critically or we couldn't do our work. I don't know whether 
there is an actual statistical indication of an upsurge in 
retirements, but certainly as an indicator of general morale, I 
would not be surprised if that is the case.
    And when it comes to your other question about hiring 
people, the kinds of hires that I am trying to be involved in 
generally are the high-level senior scientists, and this 
question comes up, ``Is this a good time to come and work for 
the Federal Government? All the things we are reading about in 
the paper makes it sounds as if we're not going to be 
considered as the leaders we hoped to be.'' It is a serious 
issue.
    Senator Mikulski. So my colleague from the other side asked 
excellent questions about, you know, the issues about the 
availability of scientists, are they going elsewhere to do 
research, should we change our immigration policy, give every 
new Ph.D. a green card? Those are subjects of debate. But we 
are losing out on ourselves, aren't we?
    Dr. Collins. We are. Even for the people that grew up here 
and want to stay here. They are not necessarily being well-
received, as they should be for their dedicated service.
    Senator Mikulski. Right. And as I look at the table, I note 
the longevity and the incredible service, Dr. Hodes, we've 
known. Dr. Fauci I have known from more than 25 years--20 
years.
    Dr. Collins. I bet its 25 or 30 years.
    Senator Mikulski. I bet that.
    And Dr. Varmus was at NIH, left for Memorial Sloan-
Kettering Cancer Center, came back to head a new Institute. 
This says something about mission-driven. But I think we need 
to correct it.
    Now, I want to be clear, I don't have my coat on as 
symbolic defiance of the pay freeze.
    But I think we need to not only look at how we can manage 
our Government in a more frugal way, but I think we need to 
stop this bashing of our Federal employees, and, like you said, 
take note of what we ask them to do. Everybody is against the 
Federal employees until they want them and need them.
    Dr. Collins. Thank you, Senator.
    Senator Mikulski. Thank you very much.

                 NATIONAL INSTITUTES OF HEALTH FUNDING

    Senator Harkin. Thank you, Senator Mikulski.
    I just want to clear up--maybe I misspoke or I may have 
left a wrong impression when I said that we won't take money 
from the prevention fund for NIH; we won't take from the NIH 
for the prevention fund.
    That is not necessarily true. It depends on what it is 
being used for.
    For example, Dr. Rodgers, we have the NIH fund for the 
diabetes prevention program. In fact, I included $10 million 
from the PPHF for that, because that is a proven intervention. 
It has been proven to prevent and to delay the onset of type 2 
diabetes.
    The research for that, however, was funded both by NIH and 
CDC collaboratively. So once they have funded the adequate 
research, and they have proven interventions, that is where 
we're more than willing--I am more than happy to get money out 
for the prevention aspects of that.
    What I was talking about on Alzheimer's is that the 
research for Alzheimer's should not come from the PPHF. If your 
research leads to some proven preventative measures, which we 
hope it does, then that is the point at which then we step in 
with the PPHF. Do you see what I'm saying?
    So I just want to kind of clear that up. That's why the $80 
million is not going to happen from us. If you've got a proven 
prevention strategy that has been proven through research, 
fine. That's what the Prevention and Public Health Fund is for. 
I just want to clear that up.

                            BIOLOGY OF AGING

    But one other question, Dr. Hodes, on Alzheimer's. As to 
the question about the biology of aging, when we think of 
Alzheimer's, cancer, congestive heart failure as distinct 
diseases, one thing they have in common, it comes with aging. 
And so if we can learn more about the aging process, we think 
that might give us more insight into this.
    The NIA took the lead in establishing a group to coordinate 
efforts across the NIH on understanding the role aging plays in 
susceptibility to age-related diseases.
    Can you just tell us a little bit more about the current 
activities of this interest group and why is it important?
    Dr. Hodes. Thank you for that question, and I would be 
happy to.
    Just as you described, aging is clearly a risk factor for 
many of the changes, diseases, conditions that occur as the 
years go by. And there is increasing evidence that there are 
identifiable, underlying biological processes that occur with 
aging that may be of interest not only in their own purely 
scientific right, but because they give clues as to points of 
intervention to affect many of the conditions with aging.
    With this in mind, with increasing evidence, exciting 
studies such as a recent demonstration that in experimental 
animals, small numbers of cells which can be identified as 
senescent--they behave abnormally; they secrete abnormal 
proteins; but they are in very small numbers--went through very 
ingenious genetic manipulations. They are removed from a live 
animal, a mouse model. The mouse does better. The mouse has 
reversed many of the conditions that occur with aging, as an 
example of the way that intervening at this basic level may 
have broad implications.
    Based on this kind of conviction, there has been over the 
past several months discussions beginning with a number of us 
at the table here as Institute Directors, a support of an 
interest group that brings together those who may have primary 
affiliations with various disease organ-centered Institutes and 
Centers, but in common have reason to believe that the 
underlying aging process is relevant to all of us.
    This interest group now has sponsored and will continue a 
series of lectures, of journal clubs. But most importantly, it 
creates a new forum for looking at ways in which common support 
from across the NIH toward problems that are appropriately 
targeted for the benefit of all us based on the condition of 
aging will benefit--and it is truly an exciting time and a 
revolutionary kind of expansion in the way this consciousness 
now has progressed across NIH.
    So we're very excited by it. We think it has great promise 
for making our research more efficient, more targeted to serve 
all.
    Senator Harkin. Very good.
    I have agreed to permit this room to be used by the 
National Alliance on Aging after this hearing for a press 
conference on that subject.
    There was one other thing I wanted to bring up here. I have 
a lot of things I would like to bring up here, as a matter of 
fact.
     I am down to 15 seconds. Do you have another question that 
you want to ask?
    Senator Mikulski.
    Senator Mikulski. I think that's it.
    Senator Harkin. Do you want anything else?
    I'll tell you what, I'll submit it in writing. It is a 
longer question. I'll submit it in writing. We're getting close 
to the noon hour anyway. It has to do with the tension between 
more grants for less money, fewer grants for more money. We 
kind of touched on that in the beginning. I would like to delve 
into that a little bit more, and I'll do it with a written 
question, just how you're looking at that tension that is going 
on, because we want to increase the grants but decreasing the 
amount of money, what does that do?
    Anyway, I am conflicted by it. I don't know what the right 
answer is. So I'll write it to you.
    Anything else that anybody wanted to bring up for the 
record that we not have asked or you wanted to follow up for 
any clarification purposes or anything like that? Anyone at 
all?

                     ADDITIONAL COMMITTEE QUESTIONS

    Well, listen, our thanks to all of you for your great 
leadership at the NIH, and we're going to do our best to make 
sure that our budget is not only not decreased, but we 
hopefully increase it a little bit, but things are tight around 
here, as you know.
    Senator Shelby. Especially in the area of biomedical 
research.
    [The following questions were not asked at the hearing but 
were submitted to the Department for response subsequent to the 
hearing:]
               Questions Submitted by Senator Tom Harkin
                          number of new grants
    Question. Dr. Collins, you noted in your opening statement that the 
number of new and competing research grants in the President's budget 
would rise from 8,743 in fiscal year 2012 to 9,415 in fiscal year 2013, 
an increase of 672. That's encouraging. But to achieve this increase, 
the value of individual grants would drop slightly. As you explained, 
noncompeting grants would be cut by 1 percent.
    This raises a fundamental dilemma for National Institutes of Health 
(NIH), one that is likely to persist as long as budgets remain tight. 
And that is: Is it better to award more grants for less money or fewer 
grants for the same (or more) money?
    The President's budget seems to have opted for the former approach. 
More grants mean a higher success rate, plus more opportunities for 
young researchers to win their first award. But of course there are 
also disadvantages when the average value of each grant drops. Some 
argue that it makes more sense to simply fund the best science, and if 
that means fewer grants, then so be it.
    Please comment on this tension and why the President's budget puts 
an emphasis on increasing the number of grants.
    Answer. NIH uses its Research Project Grants (RPG) to support the 
most meritorious research applications identified by a rigorous peer-
review process to have the highest potential for advancing biomedical 
knowledge and public health. The total number of competing RPG 
estimated in the President's fiscal year 2013 budget request is 
expected to increase to 9,415 compared to the 8,743 funded by the 
fiscal year 2012 enacted level. A tight budget environment prompts a 
delicate balancing of needs to fund adequately new individual projects, 
support the maximum number of new research opportunities, and sustain 
existing grants. In order to maximize resources for investigator-
initiated grants, NIH plans to follow grants management policies in 
fiscal year 2013 that discontinue outyear inflationary allowances for 
most grants. In the short term, NIH plans to reduce noncompeting 
continuation grants by 1 percent less than the fiscal year 2012 level, 
and negotiate the budgets of competing grants to avoid growth in the 
average award size. In the future, sound fiscal management requires 
that we continue to carefully consider the number, cost, and duration 
of new RPGs in order to minimize negative impact on existing programs.
    Accompanying these policies for maximizing resources in fiscal year 
2013 for new investigator-initiated grants is our continued commitment 
to award grants to new investigators at rates equal to those of 
established investigators. Also, NIH will establish a new process for 
additional scrutiny of awards to any principal investigator with 
existing grants of $1.5 million or more in total costs by an Institute 
or Center's Advisory Council. The purpose of this policy is to promote 
the award of NIH research grants to as many distinct principal 
investigators as possible.
    These policies will work in concert to ensure that pursuit of new 
research questions, the lifeblood for cutting-edge science, is 
maintained. Science advancement includes both the production of new 
knowledge and new scientists. New scientists, however, must have a 
reasonable expectation that they will be able to successfully compete 
for their own research grants at the end of their prolonged period of 
training if they are to be retained as members of the biomedical 
research workforce. NIH has strategically chosen in fiscal year 2013 to 
support a larger number of new research project grants by sustaining 
support for noncompeting continuations at 99 percent of their competing 
levels. This approach balances NIH's commitment to its ongoing research 
portfolio with the need to stimulate new research ideas and priorities 
in this time of limited resources.
                       national children's study
    Question. Dr. Collins, NIH, Centers for Disease Control and the 
Environmental Protection Agency spent a combined $54.7 million on the 
National Children's Study (NCS) from fiscal year 2000 through fiscal 
year 2006. From fiscal year 2007 through fiscal year 2012, the Congress 
appropriated another $937 million for the NCS, bringing the total to 
almost $1 billion. What has this nearly $1 billion achieved so far?
    Answer. NIH has shown the feasibility of performing an NCS by 
designing and testing varied scientific approaches and demonstrating 
how to conduct a study of this size and scientific and logistical 
complexity in a fiscally sound manner.
    In addition to comparing different enrollment strategies to develop 
a scientifically valid and fiscally responsible methodology to enroll 
100,000 children in the Main Study, the NCS has enrolled more than 
3,000 children to date in the Vanguard Study. In addition, we have 
developed innovative approaches to research methodology and developed 
broadly useful research tools.
    Examples include:
  --New informatics approaches including:
    --The capacity to capture systematically the operational, 
            logistical, and cost data for an ongoing study;
    --A comprehensive approach to harmonize the terminology for 
            neonatal medicine, including the deposition of hundreds of 
            terms that researchers around the world can use into the 
            National Cancer Institute Enterprise Vocabulary Services;
    --Development of nonproprietary data collection, case management, 
            and data archiving tools that conform to international data 
            standards and can be used in many types of research;
    --Development of a system of tagging data to allow rapid analysis 
            and data pooling for research data;
    --Simulation strategies for comparing complex recruitment 
            strategies; and
    --New methods for implementing and analyzing recruitment in large 
            studies and an analytic approach to examine rates, 
            kinetics, and efficiencies to allow selection of optimal 
            recruitment strategies;
  --A research portfolio of approximately 300 individual studies, most 
        of which were multicenter, to establish and validate methods to 
        support the Study;
  --In conjunction with the U.S. Department of Health and Human 
        Services Office for Human Research Protections, a national 
        network of Institutional Review Boards using a Federated Model 
        that covers all 36 National Children's Study Centers, which 
        saves time and costs for administrative review for human 
        research protections;
  --A biobank repository for human biological specimens and 
        environmental samples that is modular and scalable. The 
        repository has collected about 125,000 specimens and has 
        already distributed thousands of specimens for analysis and 
        additional scientific projects;
  --A research workflow process in 40 locations that is flexible and 
        cost effective that can be used by many other types of 
        research, as well as the NCS. For example, the Clinical and 
        Translational Science Awards (CTSA) Consortium is adapting the 
        same processes in many of the 28 NCS locations that are also 
        CTSA locations;
  --Collaborations with longitudinal birth cohort studies around the 
        globe to harmonize practices and leverage resources; and
  --In collaboration with other statistical agencies, new statistical 
        methods for analysis for combining data from multiple types of 
        research.
    Question. The President's budget for fiscal year 2013 would add 
another $165 million. What do you estimate the cost of the NCS will be 
in fiscal year 2014, when recruitment is expected to begin?
    Answer. Pilot testing conducted through the NCS Vanguard sites 
showed that a study design based on recruiting participants through 
healthcare providers was most efficient. Other large Federal studies 
have also effectively employed this provider-based approach. Also, 
while the revised approach may use healthcare provider networks as the 
primary source for recruitment, the NCS could see additional 
participants through secondary sources (such as title V clinics, Indian 
Health Service clinics, or contract research organizations) to assure 
inclusion of all appropriate population groups. The President's budget 
request for fiscal year 2013, which shows a reduction of approximately 
15 percent to $165 million for the NCS, appropriately reflects these 
proposed design changes. While future funding needs for the outyears 
will be determined by early data gathered by the Main Study, we 
anticipate that the budget for fiscal year 2014 will be the same as for 
fiscal year 2013.
    Question. How long will the recruitment phase take, and do you 
expect the annual cost will remain fairly constant during that period?
    Answer. We expect to issue the Request for Proposals for the Main 
Study in the fall of 2012, with awards made in 2013 and recruitment 
beginning in 2014. The recruitment phase is expected to continue for 
approximately 3 to 3\1/2\ years. We anticipate annual costs will remain 
flat in unadjusted dollars during the recruitment phase.
    The NCS is able to reduce overhead costs through greater 
operational efficiencies and redistribution of tasks and 
responsibilities. Examples include the use of nonproprietary software 
to eliminate license fees and proprietary support; use of a federated 
model for human subject protection to reduce redundancy and speed 
approvals through elimination of duplicate administrative resources; 
use of the NCS Program Office as a coordinating center to develop study 
instruments and protocol documents, to perform data analysis, and to 
manage field operations and general consolidation of overlapping field 
operations.
    With the reduction in overhead, we anticipate that for fiscal year 
2013 we need approximately $35 million for support services and $130 
million for ongoing Vanguard operations and Main Study initiation. Main 
Study initiation includes:
  --community outreach and advertising;
  --memoranda of understanding with cooperating facilities;
  --establishment and testing of informatics platforms, including data 
        security and regulatory compliance;
  --establishment and testing of biospecimen and environmental sample 
        collection and shipping from study locations;
  --training of field personnel;
  --regulatory approvals for information collection from participants; 
        and
  --establishment of data collection and transmission quality assurance 
        and quality control processes.
    Question. Is the annual cost expected to rise or decline after the 
recruitment phase? If so, by approximately how much (e.g., 25 percent)?
    Answer. Once the more labor-intensive recruitment phase has been 
completed, funding requirements for the NCS over the life of the study 
are expected to remain stable. While the number of participant visits 
each year may decrease to once per year, some subgroups in the Study 
may receive additional questionnaires on specific topics. In addition, 
as the number of biospecimens and other data collected from Study 
participants increases, the fiscal needs of the biobank and data 
warehouse rise, as these data and samples are both stored and made 
ready for analysis by other scientists.
    Question. Do you expect the annual cost will remain fairly constant 
during the Main Study, once recruitment has been completed?
    Answer. Annual unadjusted costs are expected to remain constant in 
unadjusted dollars following the recruitment phase of the Main Study. 
The prenatal and infant development phases are of critical importance 
because of the potentially long-term effects of various environmental 
exposures; consequently, the NCS plans to ``frontload'' the Study, 
conducting more participant visits and sample collections in those 
years. However, as the frequency and intensity of study visits 
decreases, the costs associated with biospecimen and environmental 
sample processing, storage, and analysis and with data processing, 
storage, analysis, and security will increase.
                             pain research
    Question. Dr. Collins, I understand that National Institute of 
Neurological Disorders and Stroke plans to establish a new trans-NIH 
working group on overlapping chronic pain conditions. Please provide 
some more details on this effort and what it is intended to accomplish.
    In addition, what mechanisms will the NIH employ to:
  --expedite scientific understanding of the factors that predispose, 
        trigger, and perpetuate chronic pain;
  --advance our knowledge of the diverse underlying mechanisms 
        responsible for chronic pain (including individual differences 
        and sensitivity to pain);
  --identify promising effective therapeutic drugs (and other 
        approaches) for pain control; and
  --expedite the translation of these findings to those suffering, 
        especially the most at-risk populations such as women?
    Answer. In 2011, NIH hosted a number of meetings and workshops 
focusing on overlapping chronic pain conditions that disproportionately 
affect women. These workshops included discussions of possible common 
pathways underlying these conditions as well as the need for improved 
research diagnostic criteria for overlapping pain conditions. To 
address these issues further, a new trans-NIH overlapping chronic pain 
conditions working group was formed in fall 2011. The group is led by 
the National Institute of Neurological Disorders and Stroke (NINDS) and 
the National Institute of Dental and Craniofacial Research and brings 
together staff from 13 Institutes and Centers involved in pain research 
as well as a representative from the patient advocacy community. The 
working group will help coordinate research efforts across the NIH on 
overlapping chronic pain conditions and is planning a trans-NIH 
conference in August 2012 that aims to:
  --evaluate and summarize current knowledge on the causes and 
        progression of overlapping pain conditions;
  --identify critical research needs, such as improved research 
        diagnostic criteria for this group of conditions; and
  --enhance interdisciplinary collaboration and cooperation in this 
        area of research.
    NIH utilizes a number of mechanisms to fund research on 
understanding the factors that predispose, trigger, and perpetuate 
chronic pain and the underlying mechanisms responsible for individual 
differences and sensitivity to pain. Sixteen NIH Institutes and offices 
supported the NIH Blueprint for Neuroscience Grand Challenge on Pain, 
whose goal was to facilitate highly collaborative, multidisciplinary 
research to better understand the mechanisms that underlie the 
transition from acute to chronic pain. Research supported by this 
initiative aims to understand the important role of neuroplasticity--or 
changes in the nervous system--in transitioning to chronic pain and the 
need to reverse these maladaptive changes, to allow recovery. Other 
projects funded through this initiative are focused on the 
identification and modulation of genetic changes that predispose 
individuals to and contribute to the onset of chronic pain. NIH 
continues to accept competitive revisions that propose a collaborative, 
1-year pilot study or new specific aim associated with an active NIH 
grant as part of this initiative. The Mechanisms, Models, Measurement 
and Management in Pain Research Initiative supported by 11 NIH 
Institutes is another example of a trans-NIH solicitation that 
encourages a wide range of basic, translational, and clinical research 
on pain including sex differences in the pain experience and genetic 
contributions to individual variability and response to treatment.
    The pain portfolios at a number of NIH Institutes include research 
focused on risk factors for chronic pain and individual differences in 
pain perception. For instance, brain imaging studies (fMRI and resting 
state fMRI) supported by NIH have compared structural and functional 
brain changes with pain states, supporting the notion that central 
nervous plasticity is a characteristic of chronic pain. A cutting-edge 
study used cortical imaging to detect changes in the brain to 
distinguish which patients transition from acute to chronic back pain 
and which recover. Extensive use of imaging tools have also shown that 
differences in patient reported pain sensitivity are correlated to 
activation of brain regions associated with pain and are linked to sex, 
race, genetic makeup, and environmental stress levels. Environmental 
factors such as hormones and stress have been shown to contribute to 
differences in pain sensitivity and analgesic response, while genetic 
variants determine individual sensitivity to certain analgesics, 
ability to sense pain, and risk for chronic pain. Preliminary results 
from the NIH-supported Orofacial Pain: Prospective Evaluation and Risk 
Assessment (OPPERA) study have helped identify several genetic markers 
associated with risk for orofacial pain and related to different 
patterns of self-reported pain. NIH is also funding the ongoing 
Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) 
studies to study pain characteristics that contribute to risk for 
transition to chronic pelvic pain and a 10-year study on overlapping 
pain conditions that disproportionately affect women, including 
episodic migraines.
    In addition to funding basic research on underlying mechanisms and 
causes for chronic pain, NIH supports a number of activities to advance 
the development of therapies to control and alleviate pain, including 
multiple activities in partnership with the FDA. Members of the NIH 
Pain Consortium--a joint undertaking across 25 NIH Institutes, Centers, 
and offices that facilitates collaborative pain research--currently 
participate in an advisory committee for the Analgesic Clinical Trial 
Translations, Innovations, Opportunities, and Networks (ACTTION) 
Initiative, a public-private partnership program sponsored by FDA to 
streamline the discovery and development of analgesics. In May 2012, 
NIH and the Federal Drug Administration plan to hold a state of the 
science workshop on assessing opioid efficacy and analgesic treatment 
in conjunction with the seventh annual NIH Pain Consortium Symposium 
focusing on advancing pain therapies. More broadly, senior leadership 
from the NIH and FDA are involved in an NIH-FDA leadership council that 
is exploring better coordination of NIH and FDA efforts to improve 
regulatory science and overcome hurdles in the drug development 
pipeline for common and rare diseases.
    The NIH Small Business Innovation Research (SBIR)/Small Business 
Technology Transfer (STTR) program supports research on developing pain 
therapies including projects focused on:
  --the development of small molecules as anti-inflammatory, analgesic 
        agents;
  --neural stimulation to relieve phantom limb pain;
  --Internet tools for self-management as an adjunct to chronic pain 
        care;
  --improved opioid formulations with fewer side effects; and
  --selectively targeting pain nerve fibers for gene delivery.
    NIH continues to encourage applications through the SBIR program, 
Institute-specific translational programs, and other mechanisms 
including trans-NIH initiatives. For example, the NIH Blueprint for 
Neuroscience Research currently supports a Grand Challenge for 
Neurotherapeutics to address the lack of effective treatments for 
disorders of the nervous system, including chronic pain. Additionally, 
the newly established National Center for Advancing Translational 
Sciences (NCATS) at NIH will catalyze the generation of innovative 
methods and technologies to enhance therapy development for a wide 
range of human diseases and conditions.
    NIH is currently involved in diverse dissemination efforts to 
inform the public about pain research findings. NIH is a member of the 
new Interagency Pain Research Coordinating Committee (IPRCC) which was 
recently created under the Affordable Care Act to enhance pain research 
efforts and promote collaboration across the government, with the 
ultimate goals of advancing fundamental understanding of pain and 
improving pain-related treatment strategies.
    The subcommittee has been specifically charged with making 
recommendations on how to best disseminate information on pain care, 
and NIH is working together with other member Federal agencies to 
collect information on current dissemination efforts in order to inform 
these recommendations.
    The NIH Pain Consortium is encouraging medical, dental, nursing, 
and pharmacy schools to respond to a new funding opportunity to develop 
Centers of Excellence in Pain Education (CoEPEs). The CoEPEs will act 
as hubs to develop and disseminate pain management curriculum resources 
for healthcare professionals and provide leadership for change in pain 
management education. Additionally, NIH provides online informational 
material on numerous chronic pain disorders that specifically reference 
overlapping pain conditions, and funds grants testing methods to teach 
patients how to access high-quality web-based health information for 
self-management of pain.
                             food allergies
    Question. Dr. Fauci, life-threatening food allergy conditions 
affect millions of America's children. Trials in a small number of 
patients have demonstrated that oral immunotherapy (OIT) is safe and 
effective in a significant percentage of patients. Many researchers 
believe the next step is to determine the most effective dosage and 
timeframe for treatment through larger and more complex clinical 
trials. As we both know, however, these trials are expensive. While 
there are indications of substantial private philanthropic support, 
Federal money will also be required. One private research group has 
estimated that the cost of phase II trials for the eight major food 
allergens (peanut, tree nut, milk, egg, soy, wheat, fish, and 
shellfish), along with mechanism and longitudinal studies, would total 
about $90 million over 6 years.
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) is conducting Phase I and II clinical trials to evaluate OIT or 
sublingual immunotherapy (SLIT) to treat or prevent food allergy. These 
clinical trials include studies of various immunologic parameters to 
understand factors that relate to the development or natural resolution 
of food allergy and/or response to therapy. Recent and ongoing NIAID-
sponsored OIT and SLIT trials include:
  --phase II clinical trial that showed that egg OIT is safe and 
        effective in children 5 to 18 years old with egg allergy (in 
        press, New England Journal of Medicine);
  --phase I/II clinical trial to determine whether peanut extract 
        placed under the tongue (SLIT) is a safe and effective 
        treatment for adolescents and adults with peanut allergy;
  --phase II clinical trial of milk OIT combined with anti-
        immunoglobulin E (omalizumab) for the treatment of children 
        with milk allergy;
  --phase II clinical trial to determine if regular consumption of 
        baked foods containing milk will enable children with milk 
        allergy to drink milk and consume milk-containing foods; and
  --phase I/II prevention trial in which infants and young children at 
        high risk for peanut allergy regularly consume peanut-
        containing snacks to determine if this will prevent the 
        development of peanut allergy by age 5-6 years.
    Several OIT trials also are in development for children (1-4 years 
of age) and adults with peanut allergy.
    A few additional studies, conducted without NIH sponsorship, have 
recently been published. Similar in size to the NIH-sponsored studies, 
these phase I/II clinical trials (typically 20-60 children per study) 
have focused on milk, egg, and peanut and lead to similar conclusions, 
i.e., approximately 60-90 percent of those subjects who remain on OIT 
for 1-2 years can tolerate modest amounts of the food.
    Question. Are you in general agreement that the scientific studies 
already completed on OIT indicate that moving ahead with larger trials 
on key allergens is appropriate at this time?
    Answer. NIAID is enthusiastic about recent results of OIT for milk, 
egg, and peanut and agree that it will be important to proceed with 
larger phase II trials for these and other food allergens. While we 
anticipate many similarities in study design, the most promising 
approaches will likely differ based on the particular allergen and 
study populations (e.g., children vs. adults; mild vs. severe disease; 
treatment vs. prevention design; and single vs. multiple food 
sensitivities).
    Although OIT is currently the most promising approach for treating 
food allergy, a small number of patients appear not to respond to OIT 
and others (10-20 percent) are unable to tolerate OIT because of 
recurrent allergic reactions. Furthermore, patients with a history of 
severe anaphylaxis, who are most in need of new treatment strategies, 
have not been enrolled in these early-stage OIT clinical trials due to 
safety concerns. Further research is necessary to develop and test 
treatment strategies that will benefit these patients. Novel treatment 
strategies may also provide improved safety and efficacy for food 
allergic individuals in general. For example, the addition to OIT of an 
anti-immunoglobulin E or similar molecule may reduce adverse effects of 
OIT and allow for larger doses of OIT that might be more effective. 
Other routes of allergen administration, e.g., via a cutaneous patch, 
should also be explored.
    Question. What is your professional judgment as to the cost and 
appropriate timing of such a system of trials?
    Answer. For OIT that involves administration of a food alone (e.g., 
milk, egg, and peanut), large phase II studies may be sufficient to 
change clinical practice (foods are not licensed by the FDA as 
therapeutics). Nonetheless, many such studies would be comparable in 
scope, complexity and cost to modest size phase III clinical trials 
required for drug licensure. In contrast, full phase III licensure 
studies will be required if OIT is combined with pharmaceuticals or 
allergen immunotherapy is administered through devices such as a 
cutaneous patch.
    In our professional judgment, a prioritized set of clinical trials 
would include:
  --a series of larger phase II studies to confirm the promising 
        results of the studies on egg, milk, and peanut outlined 
        previously (estimated cohort sizes of 100-300 subjects);
  --phase II/III studies of OIT for the same allergens with the 
        addition of pharmaceuticals (e.g., anti-immunoglobulin E) to 
        diminish adverse events in OIT and improve efficacy of OIT;
  --phase I-III studies of peanut (and perhaps other food allergens) 
        delivered by cutaneous patch;
  --phase I/II pilot studies exploring OIT for the other major food 
        allergens (tree nut, soy, wheat, fish, and shellfish) followed 
        by larger phase II studies (100-300 subjects) to confirm any 
        promising results; and
  --various food allergy prevention trials in high-risk infants and 
        young children. We anticipate that the minimum duration of most 
        phase II-III trials would be 3-4 years and most prevention 
        trials would take 6-7 years.
    To ensure that the highest-priority studies are conducted 
ethically, rigorously, and safely, such studies should be phased in 
over a period of years. A phased process will allow knowledge gained 
from the initial studies to inform the design of future studies, 
improve safety, and enable cost efficiencies.
    Factors that contribute to total costs include cohort size, study 
duration, complexity of treatment regimens and clinical outcomes, the 
number of protocol-required blinded food challenges, costs of allergen 
preparation and distribution under Good Manufacturing Practices, costs 
of additional pharmaceuticals (e.g., biologics, such as monoclonal 
anti-immunoglobulin E or cutaneous patch delivery devices), and the 
type and number of immunologic parameters to be studied. Thus, in our 
professional judgment, an integrated set of a prioritized set of 
clinical trials could cost $150-$250 million over many years. 
Additional constraints on implementation of such a highly ambitious set 
of clinical trials include the limited capacity of academic research 
centers and the relatively small existing cadre of highly trained and 
experienced adult and pediatric specialists in food allergy research.
    Question. How much money would be required in the first year to 
initiate a full set of OIT trials?
    Answer. NIAID would recommend that a full prioritized set of OIT 
clinical trials as outlined above not be initiated in a single year. We 
estimate a first-year total cost of $20-$25 million to fund four of the 
highest priority OIT clinical trials for peanut, egg, and/or milk 
allergens.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye
             institutional development award (idea) program
    Question. Over the past 13 years, the Congress has supported the 
National Institutes of Health (NIH) Institutional Development Award 
(IDeA) program. In IDeA States like Hawaii, our biomedical communities 
have seen great improvement in our scientists' ability to garner NIH 
support as well as our capacity to recruit and retain biomedical 
scientists, physician-scientists, teachers, graduate students, and 
postdoctoral fellows. With the dissolution of the National Center for 
Research Resources (NCRR), which administered IDeA, and the proposed 
budget reduction of IDeA by $50 million (representing an 18-percent 
cut), there is concern that NIH is not fully committed to the IDeA 
program even though the Congress has been supplementing the IDeA budget 
for the purpose of expanding clinical translation research efforts in 
IDeA States. What assurances can you provide that NIH supports the IDeA 
program and will continue to sustain research infrastructure support 
targeting the chronically underfunded IDeA States?
    Answer. Following the dissolution of NCRR, the IDeA program was 
transferred to the National Institute of General Medical Sciences 
(NIGMS), a logical home in view of NIGMS' long-standing commitment to 
research training and capacity building. Nearly all the NCRR staff who 
managed the IDeA program also moved to NIGMS, enabling the 
administration of the IDeA grants to proceed seamlessly.
    NIGMS is strongly supportive of the IDeA program. NIGMS appreciates 
its value to States that do not receive high levels of support from 
NIH's traditional grant mechanisms, as well as its importance in 
enabling excellent research, training, and career development that 
benefit the entire Nation. NIGMS intends to essentially maintain the 
level of support for the Centers of Biomedical Research Excellence 
(COBRE) and IDeA Networks of Biomedical Research Excellence (INBRE) 
programs and the new Clinical and Translational Research program.
                           health disparities
    Question. Given the continuing disparities in health outcomes and 
NIH's acknowledgement of the low numbers of underrepresented minority 
researchers, please describe efforts to address disparities in health 
outcomes and the representation of minority investigators in NIH 
support research programs.
    Answer. While the overall health of the U.S. population has 
improved, certain populations continue to have a higher risk of adverse 
health outcomes. These health disparities are the result of 
multifactorial biologic and nonbiologic influences. The NIH Health 
Disparities Strategic Research Plan and Budget, a 5-year plan, provides 
a blueprint for addressing health disparities and fostering access of 
racial/ethnic minorities to the clinical benefits of NIH research. The 
Plan focuses on three major goals each NIH Institute and Center must 
strive to achieve:
  --conduct and support research on the factors underlying health 
        disparities;
  --expand and enhance research capacity to create a culturally 
        competent workforce; and
  --engage in proactive community outreach, information dissemination, 
        and public health education.
    The pace of translation is a recognized barrier to racial/ethnic 
minorities reaping the benefits of clinical research. NIH is committed 
to accelerating the pace of research translation by reducing the time 
it takes for scientific discoveries to reach patients in the form of 
treatments or health information. Several ongoing research programs and 
studies contribute to the NIH efforts to translate research findings to 
racial/ethnic communities and increase their access to the benefits of 
NIH-funded research, including the following:
Development and Translation of Medical Technologies That Reduce Health 
        Disparities Initiative
    National Institute on Minority Health and Health Disparities 
(NIMHD) and the National Institute of Biomedical Imaging and 
Bioengineering established a partnership through the Small Business 
Innovation Research program to support the development and translation 
of medical technologies aimed at reducing disparities in healthcare 
access and health outcomes. Potential technologies targeted are 
telehealth for remote diagnosis and monitoring, sensors for point-of-
care diagnosis, devices for in-home monitoring, mobile, portable 
diagnostic and therapeutic systems, devices which integrate diagnosis 
and treatment, diagnostics or treatments that do not require special 
training, devices that can operate in low-resource environments, non-
invasive technologies for diagnosis and treatment, and integrated, 
automated system to assess or monitor a specific condition.
National Institute on Minority Health and Health Disparities Community-
        Based Participatory Research Initiative
    This 11-year initiative is designed to facilitate the translation 
of scientific discoveries arising from laboratory, clinical, or 
population studies into clinical applications to reduce health 
disparities and to disseminate scientific information. These Community-
Based Participatory Research (CBPR)-supported intervention studies are 
expected to enhance clinical practice and improve the health of racial/
ethnic populations by actively engaging the community in all phases of 
research including design, implementation, and dissemination of the 
research results.
National Institute on Minority Health and Health Disparities Centers of 
        Excellence Program
    The Centers of Excellence (COE) program advances scientific 
knowledge on the biological and nonbiological factors contributing to 
health disparities and develops interventions to address some of the 
most prevalent diseases, and health conditions that disproportionately 
affect racial/ethnic minority populations. Since 2002, NIMHD has 
supported 91 COE sites in 35 States, the District of Columbia, Puerto 
Rico, and the U.S. Virgin Islands. Awardees represent all types of 
institutions including Historically Black Colleges and Universities, 
Hispanic Serving Institutions, Tribal Colleges and Universities, and 
Alaska Native and Native Hawaiian Serving Institutions.
    Although NIH recognizes a unique and compelling need to promote 
diversity in the biomedical, clinical, behavioral, and social sciences 
research workforce; sufficient representation has been to date elusive. 
Advancing diversity through NIH training support is expected to produce 
a number of tangible and overlapping benefits including:
  --enhancing the overall capacity to address health disparities;
  --improving patient satisfaction in ways that enhance participation 
        in clinical research setting; and
  --creating and preparing a culturally competent workforce that 
        enhances communication.
Research Supplements To Promote Diversity in Health-Related Research
    This NIH-wide program provides supplemental support to existing 
NIH-funded institutions to encourage the participation of individuals 
from groups currently underrepresented in biomedical, clinical, 
behavioral, and social sciences throughout the continuum from high 
school to the faculty level. There is some evidence that individuals 
who have participated in the NIH administrative supplement program 
preferentially conduct research in areas related to minority health or 
health disparities.
National Institute on Minority Health and Health Disparities Extramural 
        Loan Repayment Program for Health Disparities Research
    The Loan Repayment Program for Health Disparities Research (LRP-
HDR) recruits, trains, and retains highly qualified health 
professionals through repayment of educational loans in exchange for 
conducting minority health or health disparities research. More than 60 
percent of LRP-HDR scholars are from racial/ethnic minority 
populations. Since its inception, more than 2,200 awards to individuals 
representing multiple disciplines including internal medicine, mental 
health, behavioral science, anthropology, pharmacology, cardiology, 
epidemiology, health sciences, oncology, psychology, and 
gastroenterology have been made through this program.
    Question. Does the Research Center in Minority Institutions (RCMI) 
plan to dedicate funding that would further enhance research 
infrastructure and training opportunities at RCMI institutions that 
have been dedicated to addressing these concerns? Also, given the 
importance of science networking within minority serving institutions, 
are there plans for the RCMI Clinical Translational Research program to 
work with the RCMI Translational Research Network to promote more 
multi-site clinical trials to address health disparities in minority/
underserved communities?
    Answer. An environment that is conducive to health-related research 
at academic institutions, including minority institutions, is a 
priority for the NIH. The NIMHD RCMI program supports the basic 
underpinning of research to further, biomedical, clinical, behavioral, 
and social sciences research activities. Enhancement of infrastructure 
and research capacity includes renovation/alteration of new research 
facilities, creating shared resources that result in economies of scale 
for research projects, and developing a diverse scientific workforce. 
This investment has been instrumental in the engagement of racial/
ethnic minority populations in research and in the translation of 
research advances into culturally competent, measurable, and sustained 
improvements in health outcomes.
    The RCMI Infrastructure for Clinical and Translational Research 
(RCTR) awards support the development of infrastructure required to 
conduct clinical and translational science in RCMI institutions. This 
infrastructure enhancement may include outpatient clinical research 
resources, biostatistical support, core laboratories, or facilities to 
support patient-oriented investigations such as community-based 
research. Multi-site investigations on those diseases that 
disproportionately impact health disparity populations are an integral 
component of the RCTR program. As the Data and Technology Coordinating 
Center for RCMI, the RCMI Translational Research Network will continue 
working with RCTR to promote scientifically sound, clinical trials 
involving multiple academic institutions, clinical sites, and community 
health providers.
                                 ______
                                 
                Questions Submitted by Senator Herb Kohl
                       national children's study
    Question. The National Institutes of Health (NIH) has announced a 
change in the National Children's Study (NCS) Vanguard contracts from 
academic centers to a national research firm. How do these changes in 
contracts affect the scientific integrity of the study?
    Answer. The change in Vanguard Study operations, to have primary 
data collection performed by another contractor, affects 7 of the 40 
Vanguard locations for a period of 6 months, from July to December 
2012. That contractor, Research Triangle Institute, was selected 
through a full and open competition in 2010 for the purpose of 
providing additional data collection capacity for the Vanguard Study. 
During this 6-month period, the seven locations will participate in a 
pilot project to optimize the transition process and maintain the 
scientific quality and integrity of the Study.
    Prior to July 2012, new funding opportunities to provide data 
collection for all of the Vanguard locations will be announced. These 
new contracts will also be awarded through a full and open competition. 
All current contractors are eligible to compete for these new 
contracts. Following award of those contracts, all Vanguard Study 
centers, including the seven locations in the transition pilot, will 
transition to the new contractors.
    Question. What is NIH's plan for transitioning from a 
decentralized, academic center based recruitment strategy to a 
recruitment strategy with a centralized, national research firm?
    Answer. The NIH is currently planning recruitment for the NCS Main 
Study, which is a separate activity from the Vanguard Study. Based on 
data from the Vanguard Study and consultation with the NCS Federal 
Advisory Committee and other experts, primary recruitment for the Main 
Study will be conducted through healthcare providers. We are currently 
asking for input and gathering additional data on implementation of a 
healthcare provider approach. New solicitations for recruitment and 
data collection for the Main Study will be made through a full and open 
competition. We anticipate that multiple contracts will be awarded. We 
also intend to award new contracts for supplemental recruitment to 
target populations that, on the basis of demographics or potential 
environmental exposures, may be under-represented if one used only a 
provider based approach.
    Question. What is NIH's plan, if any, to collaborate with the 
current Vanguard centers to maintain those children who have already 
enrolled in the studies? What are the logistical challenges to this 
transition?
    Answer. Current NCS Vanguard Study contracts expire over the next 
17 months; new contracts will be awarded following full and open 
competitions. The NCS is working with current contractors to ensure the 
orderly transition of data collection services and of relationships 
with participants, communities, and other local institutions. As is 
usual with longitudinal studies that extend across many years, 
individual contractors may continue to change during the course of the 
study, and it is important for the NCS to have procedures in place to 
ensure smooth transitions that may occur in the future.
    The Vanguard Study will continue to pilot study methods in its 
current 40 locations, several years in advance of the Main Study, 
following the children already recruited by the Vanguard Study until 
they turn 21. In this follow-up phase, it will use a smaller number of 
contractors than in its earlier recruitment phase, thus following 
recommendations in the Institute of Medicine report from 2008 and 
realizing cost savings, while improving scientific quality by achieving 
greater consistency in data and specimen collection among study sites.
    Question. What, if any, role will the current Vanguard sites have 
within the NCS after the NIH ends their contracts?
    Answer. The Vanguard Study will continue in the same sites for the 
next two decades, although it may not be carried out by the same 
contractors. All Requests for Proposals for both the Vanguard and Main 
Studies will have full and open competitions. All current contractors 
can offer proposals for new contracts and also have other options to 
participate in the NCS, including partnering with a primary data 
collector, conducting ancillary studies using NCS infrastructure, and 
doing their own research analyses using NCS data as they become 
available.
                                 ______
                                 
            Questions Submitted by Senator Mary L. Landrieu
 national institutes of health institutional development award program
    Question. The National Center for Research Resources (NCRR), an 
Institute within the National Institutes of Health (NIH), houses a 
program called the Institutional Development Award (IDeA program). The 
IDeA program funds research in States that are traditionally 
underrepresented within the NIH, including Louisiana.
    In the fiscal year 2012 U.S. Department of Health and Human 
Services budget, the Congress increased the funding for the IDeA 
program by $46 million. However, for the fiscal year 2013 budget year, 
the President proposes a $48 million decrease. It appears that this 
money is being taken away in order to help fund the new National Center 
for Advancing Translational Sciences (NCATS).
    At a time when NIH budgets are flat, and when the most heavily 
funded States will continue to be funded as they always have, why would 
the administration propose reducing the one pot of money that is 
specifically designed for States that have traditionally been 
underfunded?
    Answer. For fiscal year 2012, the IDeA program was provided with a 
21-percent increase in the congressional appropriation, or 
approximately $50 million, in funding over fiscal year 2011, while most 
other NIH programs were held relatively flat. For fiscal year 2013, the 
budget proposes $225 million for the IDeA program, about the same as 
the fiscal year 2011 level, and approximately $50 million below fiscal 
year 2012. The IDeA program is valued by NIH and gives many 
investigators at less research-intensive institutions an opportunity to 
contribute to biomedical research. Within a constrained budget 
environment, NIH believes that the IDeA program should not be treated 
differently than most other programs in the fiscal year 2013 NIH budget 
which are flat with fiscal year 2011. With regard to NCATS, the fiscal 
year 2013 budget requests an increase because of the need for 
innovative solutions to the bottlenecks currently in the development 
pipeline that hinder the movement of basic research findings into new 
diagnostics and therapeutics for patients. The request for IDeA is made 
in the context of the total NIH budget and not as a particular offset 
to any one program or line item.
   national institute of diabetes and digestive and kidney diseases 
                             funding levels
    Question. The National Institute of Diabetes and Digestive and 
Kidney Diseases (NIDDK) continues to conduct and support innovative 
diabetes research that will move the Nation forward in treatment, 
enhanced detection, and prevention of diabetes.
    In the proposed fiscal year 2013 HHS budget, the NIDDK received a 
slight decrease in funding of $2 million compared with the fiscal year 
2012 funding level. I am concerned that this decrease in funding will 
affect NIDDK's ability to continue to make progress on promising 
diabetes research.
    Would you please share with us the percentage of grants that NIDDK 
has been able to fund over the past 2 years and how this cut will 
affect grants/research going forward?
    Answer. In fiscal year 2010 and fiscal year 2011, the success rates 
for NIDDK-funded Research Project Grants (RPGs) were 26 percent and 21 
percent, respectively; the estimate for fiscal year 2012 is 20 percent. 
In the fiscal year 2013 President's budget request, there is an overall 
reduction of 1 percent in the average cost of both competing and 
noncompeting RPGs. NIDDK also expects to have fewer non-competing 
grants that require funding in fiscal year 2013. As a result, the 
number of new or competing RPGs would increase by 43, resulting in an 
estimated success rate of 21 percent in fiscal year 2013. The slight 
net decrease in funding of $2.798 million, or -0.1 percent, in the 
President's budget request, compared with the fiscal year 2012 funding 
level, is due primarily to a reduction in NIDDK HIV/AIDS research that 
results from $30.951 to $27.635 million or $3.316 million in AIDS 
research. The AIDS reduction is a result of the annual AIDS priority 
level review of all expiring grants in fiscal year 2012 that would be 
competitively submitted for funding in fiscal year 2013. These projects 
are no longer considered to be aligned with the fiscal year 2013 
priorities for trans-NIH AIDS research. The overall non-AIDS total is 
increased by $518,000 resulting from the increased funding in R&D 
Contracts and National Research Service Award Research Training. The 
AIDS reduction plus a non-AIDS increase results in a $2.798 million 
reduction in the total NIDDK.
                          gestational diabetes
    Question. Currently, gestational diabetes is a disease affecting up 
to 18 percent of all pregnant women. Long-term health consequences face 
women and children who have gestational diabetes, such as 
susceptibility to type 2 diabetes.
    Would you please provide a list of the specific research 
initiatives or projects NIDDK or other Institutes at NIH are currently 
funding to address this issue?
    Answer. The NIDDK and National Institute of Child Health and Human 
Development are vigorously supporting research and other efforts to 
address gestational diabetes mellitus (GDM) and its immediate and long-
term health consequences for women and their children. While complete 
data for fiscal year 2012 are not yet available, we are pleased to 
provide examples of a number of current efforts. The NIDDK, under its 
``Healthy Pregnancy Program,'' is supporting three major GDM-related 
initiatives:
  --A multi-center research consortium testing interventions in diverse 
        groups of overweight and obese pregnant women to improve weight 
        and metabolic outcomes in both the women and their offspring. 
        This effort is co-supported by NICHD, National Heart, Lung, and 
        Blood Institute (NHLBI), and the NIH Office of Research on 
        Women's Health.
  --The Hyperglycemia and Adverse Pregnancy Outcomes Follow-up Study, 
        which will examine whether elevated blood sugar levels less 
        severe than GDM carry similar long-term health risks for women 
        and their offspring.
  --An educational component, led by the National Diabetes Education 
        Program (NDEP), that targets women with a history of GDM, their 
        families, and their healthcare providers to raise awareness of 
        health risks and the steps that women and their children can 
        take to avert health problems. The NDEP is a joint program of 
        the NIDDK and the Centers for Disease Control and Prevention 
        (CDC).
    NIDDK and NICHD also support basic and clinical research to better 
understand GDM, as well as to identify ways to prevent or treat it and 
its long-term health risks. For example, several studies focus on 
understanding how maternal diet and metabolism affect fetal development 
and incur long-term risks for obesity and other health problems. 
Researchers are also continuing to study women at risk for type 2 
diabetes due to GDM history who participated in NIH's landmark Diabetes 
Prevention Program clinical trial. Researchers are also:
  --following a large population of women with a history of GDM to 
        understand how the frequency and duration of their 
        breastfeeding may prevent their later development of type 2 
        diabetes;
  --screening women for GDM in the first months of pregnancy, to 
        understand whether early-emerging and later-emerging forms of 
        GDM differentially affect maternal and child outcomes. Other 
        goals of the research are to refine GDM tests and to determine, 
        at a systems level, whether routine screening for early GDM in 
        obese women improves outcomes in the women and their children;
  --searching for abnormalities in fetal development of heart function 
        and other factors that could eventually cause adult heart 
        disease in offspring of pregnant laboratory animals with GDM; 
        and
  --analyzing post-partum maternal and infant cord blood samples to 
        determine whether specialized types of human fat and immune 
        cells could be novel biochemical markers to help predict future 
        GDM.
                national cancer institute funding level
    Question. The funding for NIH, and in turn, National Cancer 
Institute (NCI), has eroded since fiscal year 2010, not only due to 
lost purchasing power as a result of biomedical inflation but also due 
to outright cuts in fiscal year 2011.
    How has the eroded funding affected the Institute in terms of the 
number of new grants funded and harm to existing grants? What decisions 
have you had to make as a result? If we could restore funding to fiscal 
year 2010 levels, or even better, increase funding above those levels, 
what could you do with the new money?
    Answer. As a result of the decrease to the NCI budget in fiscal 
year 2011, we funded 1,106 competing grants, 147 fewer than in 2010. 
For the 3,769 existing grants that received continuation funding in 
2011, the amount was reduced by 3 percent from the fiscal year 2010 
level. Principal investigators could have used a number of strategies 
to accommodate lower funding levels, including reducing staff, 
deferring the purchase of equipment or supplies, or scaling back their 
projects in some way.
    In fiscal year 2011, NCI applied reductions of 2 to 5 percent in 
most budgets for our many activities--including the intramural 
programs, contracts at NCI-Frederick and elsewhere, the NCI-designated 
cancer centers, and the operating budgets of all NCI components. NCI's 
leadership made choices to achieve the necessary savings while 
preserving core elements needed to sustain the pace of discovery. NCI 
leadership has carefully assessed the overall research portfolio and 
determined the areas where, in our professional judgment, increased 
funding could have additional impact over time in reducing cancer 
incidence and mortality. Any increase in funding would be used in part 
to increase support for new research grants, especially grants to new 
investigators to support new ideas. Other critical areas that could 
receive additional support include cancer genomics and transformation 
of NCI's clinical trials to increase efficiency and reflect the state 
of the science. An increase to our appropriation could also allow NCI 
to fund additional grants through the new Provocative Questions project 
by augmenting the $15 million that was dedicated to the project. 
Additional resources could support more research toward solving some of 
the enduring paradoxes in cancer research.
               national cancer institute--drug resistance
    Question. We've heard reports of some targeted treatments achieving 
incredible results, but then cancers stop responding to those drugs. 
What is the NCI doing to understand and overcome this drug resistance?
    Answer. One of the most disappointing features of the development 
of new targeted therapeutics is how routinely drug resistance emerges 
and the disease begins to progress. Resistance to treatment with 
anticancer drugs results from a number of factors--every cancer 
expresses a different array of drug-resistance genes, and various 
mechanisms have evolved as protection from toxic agents. As therapy has 
become more effective, acquired resistance has become common. NCI is 
aggressively pursuing research to gain an understanding of the 
mechanisms that lead to drug resistance and is looking for agents that 
overcome these mechanisms. NCI is supporting studies of combination 
therapies for patients whose disease has become resistant to therapy, 
as well as exploring alternative approaches through the Provocative 
Questions Initiative to determine if controlling rather than killing 
cancer cells can avoid the development of drug resistance.
    One example of the development of resistance following dramatic 
response is the clinical experience with the targeted drug vemurafenib 
(Zelboraf), a BRAF inhibitor that has been shown to nearly double the 
survival of patients with advanced melanoma. Because nearly one-half of 
all cases of metastatic melanoma--about 4,000 patients per year--have 
the BRAF mutation, vemurafenib represents a significant breakthrough in 
treatment. Unfortunately, after an average of 8 months of treatment, 
many patients become resistant to the drug and their disease begins to 
progress. However, with NCI support, researchers are making headway in 
understanding vemurafenib resistance. Recent data from Memorial Sloan 
Kettering, for example, demonstrated that some resistant BRAF-mutated 
melanoma cells produce a shortened version of the mutated BRAF protein 
that remains active even in the presence of vemurafenib. Strategies to 
overcome the resistance include finding ways to increase potency of the 
therapy, disrupting the activity of the altered form, or combining 
therapies. Other leads have come from researchers at the Moffitt Cancer 
Center, who identified a new approach utilizing a small molecule 
inhibitor called XL-888 to target a family of proteins known as Heat 
Shock Proteins 90 (Hsp90). The Moffitt researchers reported preclinical 
data that XL-888 overcame six different models of vemurafenib 
resistance, demonstrating its therapeutic potential. This work was made 
possible by early NCI research on Hsp90 as an anticancer agent.
    Melanoma is just one example of a disease in which drug resistance 
is driving creative approaches in cancer research. The drug imatinib 
(Gleevec), for example, is widely recognized for its success in 
treating chronic myeloid leukemia by targeting a protein known as BCR-
ABL. However, some CML patients relapse when new mutations make the 
BCR-ABL protein resistant to Gleevec, preventing it from binding to its 
target and allowing the abnormal enzyme to drive white blood cell 
growth, again despite treatment. It is encouraging to report that NCI-
supported research has identified a number of drugs that can target 
BCR-ABL proteins even after they acquire mutations that confer 
resistance to Gleevec. Although two of these, approved a few years ago, 
could not overcome a relatively common resistance mutation, a third 
generation of drugs has a new way to attack the mutation, freezing the 
target protein and rendering it inactive. This example illustrates 
another important point: many different research fields--from genetics 
to structural biology to pharmacology--were required for these advances 
in treatment. The need for multidisciplinary teams to address key 
questions like drug resistance in cancers increasingly defines modern 
biomedical research.
                       national children's study
    Question. NIH wants to cut 15 percent from National Children's 
Study's (NCS) current $193 million budget in fiscal year 2013 by 
shifting away from the sampling plan put forth by the Institute of 
Medicine in 2008 to an health maintenance organization (HMO)-based 
sample.
    New Orleans was selected as one of the sites for national sampling 
and this is particularly important because, as Louisiana is near the 
bottom of every health outcome ranking and near the top in indicators 
of poverty, this new knowledge could prove invaluable to improving 
both. The gulf region has a number of health disparity issues and a 
large number of uninsured mothers who do not participate in an HMO.
    How do you plan on maintaining the scientific integrity of the NCS 
study so that it reflects a national sample, including unique 
populations such as those in the gulf region?
    Answer. The change in the NCS Study design is being considered 
primarily for scientific reasons but also with awareness of our need to 
be fiscally responsible. It is based on data generated during the 
ongoing Vanguard, or pilot phase, of the NCS. As currently envisioned, 
the NCS Main Study would use a provider-based participant selection and 
recruitment strategy that the NIH and the Agency for Healthcare 
Research and Quality have both employed effectively in other studies. 
This approach uses research-ready healthcare provider networks as the 
primary source for recruitment. The NCS would gain additional 
participants through the award of contracts for supplemental 
recruitment from secondary sources (such as title V clinics, Indian 
Health Service clinics, or contract research organizations) to assure 
inclusion of appropriate population groups, specifically those with 
health disparities. The use of these two coordinated selection and 
recruitment strategies would improve the quality of the Main Study and 
allow analyses not feasible with either approach alone.
    If adopted, this revised approach would offer several advantages, 
including:
  --greater recruitment efficiency;
  --leveraging access to consenting participants' electronic health 
        records, thus improving the amount and consistency of data 
        collected while lowering costs;
  --the potential to leverage the existing infrastructure of networks 
        of healthcare providers, again improving the quality of data 
        and lowering costs;
  --allowing built-in continuity for participants who move but remain 
        within the provider network (many provider networks have 
        statewide or regional coverage) or join another provider 
        network affiliated with the Main Study.
    Current Vanguard Study contracts are due to expire over the next 17 
months. New contracts are required to continue into the next phase of 
the Vanguard Study, and the NCS has issued a pre-solicitation to 
request preliminary information on the services available to meet the 
study's evolving needs. (Please see https://www.fbo.gov/
index?s=opportunity&mode=form&id=674a4f3a690d6584870fc84c9cb2b
511&tab=core&-cview=0.) All new Requests for Proposals for both the NCS 
Vanguard and Main Studies will have full and open competitions. Whoever 
is awarded the new contracts, the NCS plans to remain in the Vanguard 
locations and to following current Vanguard participants until the last 
enrolled child turns 21 years old.
    Question. On a related topic, Tulane University, in New Orleans, 
was one of the sites selected for national sampling. The New Orleans 
Study Location represents a strong collaboration among major healthcare 
providers and universities, including Tulane, LSU, and Ochsner, and 
employs many full-time and part-time professionals.
    Termination of the contract would be a very significant loss both 
to the universities, the local community and damage the capacity that 
has been built.
    How will this new system account for the loss of expertise and jobs 
at study sites throughout the Nation?
    Answer. To date, the NCS Vanguard Study has accomplished what it 
set out to do, provide data on recruitment and early retention into the 
Study. We will continue to follow all children born into the Vanguard 
Study, until age 21. We have no intention to lose NCS participants from 
the Vanguard Study; instead, we are developing and field testing a 
proactive plan that includes personal contacts, special events for 
participants, linkages to local health resources through other Health 
and Human Services programs, returning results of Study assessments, 
and soliciting feedback about the Study experience. In addition, 
participants that might have been lost under the original Study design 
because they moved out of a particular geographic area might still be 
included in a health provider network involved in the Study.
    Current NCS Vanguard Study contracts expire over the next 17 
months, but none are expected to be prematurely terminated. The NCS is 
working to standardize the transition process so that if a new 
contractor replaces a current contractor at an NCS location, the data, 
the knowledge, the relationships and the continuity can be maintained. 
We are targeting a minimum 90-day overlap in contracts, to allow for an 
orderly and systematic transfer.
    All new Requests for Proposals for both the Vanguard and Main 
Studies will have full and open competitions. Academic institutions can 
offer proposals for new Study contracts for primary data collection, 
and have other options as well, including partnering with a primary 
data collector, conducting ancillary studies using NCS infrastructure, 
or doing their own research analyses using NCS data as they become 
available. Finally, contractors that complied with NCS specifications 
for field operations will have established a platform that is flexible 
and adaptable to multiple uses, so they can leverage that investment 
for additional projects.
     national institutes of health investigator-initiated research
    Question. Will the investigator-initiated research be able to grow 
in the area of translational science, and will basic science be a part 
of it?
    Answer. Within the administration's fiscal year 2013 budget request 
for NIH of $30.86 billion, the same overall program level as in fiscal 
year 2012, we plan to continue to maintain funding emphasis and 
increase the overall number of Research Project Grants (RPGs). RPGs are 
NIH's fundamental funding mechanism for investigator-initiated 
research. The NIH budget request will support an estimated 9,415 new 
and competing RPGs in fiscal year 2013, an increase of 672 more than 
fiscal year 2012. The total number of RPGs funded for fiscal year 2013 
is expected to be around 35,888, or approximately the same as the 
35,944 estimated for fiscal year 2012.
    In pursuit of its mission to alleviate the burden of illness, NIH 
supports a continuum of research, from understanding basic causes and 
mechanisms of health and disease to translating that understanding into 
new ways of identifying and intervening upon disease processes, and in 
turn translating those new interventions into clinical practice. As the 
leading supporter of basic biomedical research in the world, NIH 
commits slightly more than one-half its annual budget to better 
understand the basics of how life works.
    Yet, the path from basic research to clinical practice is not 
always linear; each step in the process may inform any other step. For 
example, clinical research can inform basic research. This is 
exemplified by a recent clinical finding made by NIH scientists in the 
intramural program's Undiagnosed Diseases Program that has led to a 
dramatic new understanding of basic functioning. These scientists 
studied a pair of sisters from Kentucky who suffered from joint pain 
and a mysterious calcification of the arteries in their extremities. 
Their research uncovered a novel genetic condition that affected a 
previously unknown enzyme pathway, resulting in blocked arteries. The 
discovery provides a dramatically new understanding of how large 
arteries maintain normal functioning, and it has opened the door to 
many other lines of inquiry across both basic and clinical arenas.
    The proposed increase in RPGs provides the framework for NIH to 
prospectively expand investigator-initiated research across the 
continuum of biomedical and behavioral science. Each new finding in one 
arena will inform and lead to new investigations in other areas of 
basic, translational, and clinical research.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
                        congenital heart disease
    Question. Congenital Heart Disease (CHD) is one of the most 
prevalent birth defects in the United States and a leading cause of 
birth defect-associated infant mortality. Due to medical advancements 
more individuals with congenital heart defects are living into 
adulthood. Please provide an update of research within National 
Institutes of Health (NIH), particularly the National Heart, Lung, and 
Blood Institute (NHLBI) related to congenital heart defects across the 
life-span.
    The healthcare reform law included a provision, which I authored, 
that authorizes the Centers for Disease Control and Prevention (CDC) to 
expand surveillance and track the epidemiology of CHD across the life-
course, with an emphasis on adults. The Consolidated Appropriations Act 
of 2012 provided the CDC with $2 million in new funding for enhanced 
CHD surveillance. Please describe how NIH is working with CDC to 
enhance CHD surveillance across the life-course. CDC is using a portion 
of the newly appropriated funds to convene a congenital heart defects 
experts meeting. Please summarize NIH's role at the expert meeting and 
in shaping the meeting's research agenda.
    Answer. NHLBI continues to make an extensive investment in research 
related to congenital heart defects across the life-span. The Institute 
is working in conjunction with the CDC on a number of activities to 
expand surveillance of CHD and improve our understanding of its 
epidemiology, including the following:
      Newborn Screening for Critical Congenital Heart Diseases.--In 
        September 2011, Secretary Sebelius recommended that screening 
        for Critical Congenital Heart Diseases (CCHD) be added to 
        routine newborn screening and called for research to address 
        evidence gaps that are presently constraining implementation of 
        screening programs. In response, the NHLBI, the National 
        Institute of Child Health and Human Development (NICHD), the 
        CDC, and other Federal partners involved in newborn screening 
        have set up regular calls and meetings to determine how best to 
        proceed. As an example, the CDC and NHLBI have been discussing 
        details of a common nomenclature to be used in screening for 
        cardiovascular malformations and the potential for combining 
        the efforts of the CDC's robust birth defects case-
        ascertainment and research programs with the NHLBI-funded 
        Pediatric Heart Network and the Pediatric Cardiac Genomics 
        Program to answer research questions about approaches to and 
        effectiveness of screening for CCHD.
      Data Set on Sudden Cardiac Death in the Young.--Development of 
        effective screening and prevention strategies for Sudden 
        Cardiac Death in the Young (SCDY) is limited by a lack of 
        prospectively defined epidemiological data, including incidence 
        rates and etiology. NHLBI is planning an innovative program to 
        address this knowledge gap. Its initial phase, in coordination 
        with the CDC and others, would be to develop a surveillance 
        system and registry that broadens and enhances the activities 
        of the National Center for Child Death Review and the Sudden 
        Unexpected Infant Death Registry. This phase would result in 
        the first prospective, population-based U.S. data set on SCDY; 
        it would include data from death certificates, medical records, 
        death-scene investigations, and pathology reports and also 
        include serum samples for DNA extraction. It would be followed 
        by a second phase that would support scientific research using 
        the data set.
      Congenital Heart Public Health Consortium.--NHLBI and the CDC 
        were founding Federal advisors to the Congenital Heart Public 
        Health Consortium (CHPHC), a group formed in 2008 to address 
        the public health burden of CHD. The CHPHC has united a variety 
        of organizations, including Federal agencies, patient advocacy 
        groups, and physician associations that have a strong interest 
        in CHD. Its approach includes strong emphasis on enhanced 
        surveillance via monitoring CHD throughout the lifespan, as 
        well as assessment of the needs of patients and families for 
        chronic disease management and age-appropriate preventive care. 
        Representatives from NHLBI and the CDC currently serve as 
        advisors to the Consortium Steering Committee.
    NHLBI is working closely with the CDC to organize the upcoming 
congenital heart defects experts meeting which will occur September 10-
11, 2012. Its goal is to determine priorities for public health 
research on congenital heart disease across the life course in the 
United States. The planning committee consists of representatives from 
the CDC and the NHLBI and pediatric cardiologists from academia. The 
meeting agenda will focus on three main areas of public health concern 
for congenital heart disease--epidemiology, long-term health outcomes 
(both medical and nonmedical), and health services research (including 
access to care, employability, and economics). Invitations have been 
sent to a variety of experts, including pediatric cardiologists, adult 
congenital heart specialists, adult cardiologists with expertise in 
epidemiology, epidemiologists, cardiac surgeons, health services/
outcomes researchers, patient advocates, health economists, and other 
Federal partners.
                        antimicrobial resistance
    Question. NIH is part of an Interagency Task Force on Antimicrobial 
Resistance (ITFAR) that was created in 1999. What is the status of the 
subcommittee's recommendations to address the complex issue of 
antimicrobial resistance?
    Answer. In 2001, the ITFAR published a Public Health Action Plan to 
Combat Antimicrobial Resistance (the Public Health Action Plan). This 
plan was updated, with stakeholder input, in 2011 and lays out specific 
action items in the areas of Surveillance, Prevention and Control, 
Research, and Product Development to address the complex issue of 
antimicrobial resistance. The updated plan is posted here: http://
www.cdc.gov/drugresistance/pdf/public-health-action-plan-combat-
antimicrobial-resistance.pdf.
    Progress toward the implementation of Action Items under each of 
the goals in the Public Health Action Plan is reported annually by all 
participating agencies and documented at this link: http://www.cdc.gov/
drugresistance/annualReports.html.
    At NIH the National Institute of Allergy and Infectious Diseases 
(NIAID) is the lead institute responsible for research on antimicrobial 
resistance. NIAID supports basic, translational, and clinical research 
to understand and combat the problem of antimicrobial resistance. NIH, 
with support from NIAID, co-chairs the ITFAR and conducts research 
addressing several of the goals of the Public Health Action Plan, 
including goals supporting basic, applied, and clinical research on 
antimicrobial resistance. For example, NIAID is supporting a robust 
response to Action Items under Goal 7.2: Design and implement studies 
focused on optimizing the dose and duration of antibacterial agents 
prescribed for treatment of community-acquired pneumonia, urinary tract 
infections, skin and soft-tissue infections, and other infectious 
illnesses. To address this goal, NIAID is supporting clinical trials to 
inform the rational use of existing antimicrobial drugs to help limit 
the development of antimicrobial resistance, and is also supporting a 
clinical study to optimize the use of colistin, an antibiotic approved 
in the late 1950s that is increasingly being used today to treat multi-
drug resistant Gram-negative infections. NIAID-supported clinical 
trials evaluating the effectiveness of different drug combinations in 
treating influenza, HIV, and malaria are also ongoing.
    In addition, NIAID supports basic research to identify new 
antimicrobial targets and translational research on strategies to 
combat antimicrobial-resistant infections. NIAID supports the 
development of effective diagnostics, drugs, and vaccines to identify, 
treat, and prevent infectious diseases. As part of this effort, NIAID 
provides a broad array of preclinical and clinical research resources 
to researchers in academia and industry designed to facilitate the 
movement of a product from bench to bedside. By providing these 
critical services to the research community, NIAID can help to bridge 
gaps in the product development pipeline and lower the financial risks 
incurred by industry to develop novel antimicrobials. For example, 
NIAID supports the preclinical development of new antibacterial agents 
through directed contracts to companies involved in novel drug design 
and synthesis. These contracts were solicited through a Broad Agency 
Announcement entitled ``Development of Therapeutics for BioDefense.'' 
To foster clinical research on antimicrobial resistance, in January 
2012, NIAID released a request for applications to support a new 
leadership group for an antibacterial resistance clinical trial network 
similar to the existing HIV/AIDS clinical research networks (http://
grants.nih.gov/grants/guide/rfa-files/RFA-AI-12-019.html). The 
antibacterial resistance leadership group would develop and implement a 
comprehensive clinical research agenda to address the pressing problem 
of antibacterial resistance.
    The research described above represents only a small portion of 
NIAID's significant investment in research addressing the problem of 
antimicrobial resistance. For more information, please visit the ITFAR 
annual report linked above as well as the NIAID Web page at: http://
www.niaid.nih.gov/topics/antimicrobialresistance/Pages/default.aspx.
                      diabetes prevention program
    Question. Diabetes Prevention Program (DPP) was a clinical research 
study investigating the impact of lifestyle and drug interventions on 
diabetes prevention. Two new NIH initiatives have taken advantage of 
DDP's findings and are building on the discoveries. Please summarize 
the two new programs and explain how they are different from DPP.
    Answer. NIH's landmark DPP clinical trial proved that an intensive 
lifestyle intervention reduced rates of diabetes incidence by 58 
percent among an at-risk population. The lifestyle intervention was 
effective in all ethnic groups, and was particularly effective in those 
older than age 60 at the beginning of the trial, among whom it reduced 
diabetes incidence by 71 percent. The trial also found that the safe, 
well-tolerated, inexpensive, generic diabetes drug metformin reduced 
diabetes incidence by 31 percent, and was most effective in younger 
participants, and women with a history of gestational diabetes, who 
otherwise develop type 2 diabetes at particularly high rates.
    NIH has built on these major findings in several ways. First, most 
of the DPP participants elected to enroll in a follow-on study, the DPP 
Outcomes Study (DPPOS). Phase 1 of this study showed that both 
interventions are durable, and continue to provide significant diabetes 
prevention benefit for at least a decade. Moreover, participants in the 
lifestyle arm of the study had dramatically better quality of life and 
a reduced need for medications to control blood pressure and 
cholesterol. Both lifestyle and metformin were also found to be highly 
cost effective, and metformin was actually found to be cost saving. 
Phase 2 of DPPOS will assess the long-term impact of the interventions 
on diabetes complications. The National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK) is also currently working with 
National Cancer Institute (NCI) to determine the feasibility of 
detecting potential effects of the interventions on later development 
of cancer.
    To develop ways to make diabetes prevention more practical and 
affordable, the NIH-funded research to translate the DPP lifestyle 
intervention into widespread practice. Some particularly promising 
projects have focused on research to reduce costs, while maintaining 
efficacy, by delivering the intervention in a group-based form. Strong 
preliminary results from one such ongoing study led to creation of the 
``National'' DPP (NDPP) by the Centers for Disease Control and 
Prevention, which is working to train and credential a cadre of group 
lifestyle intervention providers for diabetes prevention. Many of the 
providers trained so far work at YMCAs, which now provide access to 
these services to people with prediabetes at more than 50 locations 
(http://www.ymca.net/diabetes-prevention/participating-ys.html). 
Additional work to help realize the potential of the DPP and other 
diabetes studies is being conducted through the Diabetes Translational 
Research Centers program.
    Detailed DPP genetic analyses have shown that the lifestyle 
intervention helps prevent diabetes even among those at greatest 
genetic risk. Interestingly, a gene was identified that substantially 
reduces the efficacy of metformin in about 1 in 3 people. NIH is 
supporting a June 7 conference on metformin pharmacogenetics to explore 
this and related issues.
    Question. Although the long-term outlook for children with type 1 
diabetes has improved, the rates of diagnoses continue to rise. Please 
provide an update on research efforts within NIH related to type I 
diabetes and how additional innovations in research could prevent 
children from developing this disease.
    Answer. NIH-supported research has shown that people with type 1 
diabetes are living longer and healthier lives than ever before. 
However, research has also shown that rates of type 1 diabetes are 
rising, especially in children under 4 years of age. One approach to 
curb the rising rates of type 1 diabetes is to identify a disease 
prevention strategy. Toward this goal, the NIDDK has undertaken a bold, 
long-term initiative--called The Environmental Determinants of Diabetes 
in the Young (TEDDY) study--to identify the environmental triggers that 
intersect with genetic risk and lead to the development of type 1 
diabetes. More than 8,600 newborns are enrolled in the study--after 
screening more than 420,000 newborns--and researchers are collecting 
biological samples, as well as information about the children's diet, 
illnesses, vaccinations, and allergies, until the children are 15 years 
of age. Knowledge gained from the TEDDY study can revolutionize our 
ability to prevent type 1 diabetes. For example, the discovery of a 
viral cause could lead to development of a vaccine to prevent the 
disease. Identification of a dietary factor as a cause could lead to 
changes in feeding practices.
    NIH-supported researchers are also conducting clinical trials 
testing promising prevention therapies in people at high genetic risk 
of developing type 1 diabetes. For example, the NIDDK's Type 1 Diabetes 
TrialNet is conducting two clinical trials testing agents to prevent 
the disease in relatives of people with type 1 diabetes. The NICHD's 
Trial to Reduce IDDM (insulin-dependent diabetes mellitus) in the 
Genetically At-Risk, or TRIGR, is testing whether hydrolyzed infant 
formula compared to cow's milk-based formula decreases the risk of 
developing type 1 diabetes in at-risk children.
                       national children's study
    Question. The National Children's Study (NCS) will examine 
environmental influences on the health and development of a cohort of 
U.S. children from birth until age 21. Field work for the study ended 
in March 2012, which provided data about recruitment processes and 
costs associated with the study. How are these data being used to 
inform the cost-effectiveness of the main study?
    Answer. Data generated during the ongoing Vanguard, or pilot, phase 
of the NCS showed that a study design based on recruiting through 
healthcare providers was more efficient than recruitment through door-
to-door contact or direct outreach to the public. Other large Federal 
studies have also effectively employed provider-based approaches.
    More specifically, the NCS uses several methods to analyze costs 
and cost effectiveness. We maintain our own internal data base of 
contract invoices and analyze the invoice data for costs and level of 
effort based on activity. In addition, operational data elements that 
record the activities, logistics and costs of all aspects of the 
Vanguard Study have been embedded into the protocol data collection. 
These operational data elements are the primary outcome measures for 
the Vanguard Study goals of testing feasibility, acceptability, and 
cost-of-study operations. These data are captured in a central data 
repository and analyzed every 2 weeks to guide operations and assess 
overall data quality. In a third approach, two contractors, one a 
consulting firm and the other an academic institution, have been 
engaged to project operational resources and potential costs based on 
data from the field.
    Question. A recent restructuring of the field operations will 
centralize some data collection to a single subcontractor. Please 
explain the rationale and cost-effectiveness of this restructuring.
    Answer. The change in Vanguard Study operations, to have primary 
data collection performed by another contractor, affects 7 of the 40 
Vanguard locations for a period of 6 months, from July to December 
2012. That contractor, Research Triangle Institute, was selected 
through a full and open competition in 2010 for the purpose of 
providing additional data collection capacity for the Vanguard Study. 
During this 6-month period, the seven locations will participate in a 
pilot project to optimize the transition process and maintain the 
scientific quality and integrity of the Study.
    Prior to July 2012, new funding opportunities to provide data 
collection for all of the Vanguard locations will be announced. These 
new contracts will also be awarded through a full and open competition. 
All current contractors are eligible to compete for these new 
contracts. Following award of those contracts, all Vanguard Study 
centers, including the seven locations in the transition pilot, will 
transition to the new contractors.
    Question. The NIH/NICHD has suggested an alternative sampling 
strategy that uses health plans or health providers to identify and 
recruit pregnant women. How can the proposed strategy ensure the sample 
represents all U.S. children, particularly uninsured, minority, 
immigrants, and low-income children?
    Answer. As currently envisioned, the NCS Main Study would use a 
provider-based participant selection and recruitment strategy that the 
NIH and the Agency for Healthcare Research and Quality have both 
employed effectively in other studies. This approach uses research 
ready healthcare provider networks as the primary source for 
recruitment. The NCS would gain additional participants through the 
award of contracts for supplemental recruitment from secondary sources 
(such as title V clinics, Indian Health Service clinics, or contract 
research organizations) to assure inclusion of appropriate population 
groups, specifically those with health disparities. The use of these 
two coordinated selection and recruitment strategies would improve the 
quality of the Main Study and allow analyses not feasible with either 
approach alone.
                                 ______
                                 
                Questions Submitted by Senator Jack Reed
                       national children's study
    Question. You mentioned during the hearing that the proposed re-
design of the National Children's Study (NCS) will be as effective and 
more efficient in enrolling study participants. However, you didn't 
mention the scientific basis for this re-design. Did you consult the 
national panel of experts--the Institute of Medicine (IOM), and the 
National Children's Study Federal Advisory Committee that informed the 
original design of the study with this new re-design? If these 
individuals and entities have already been consulted, do you plan to 
make those comments available to the public? If they have not already 
been consulted, do you intend to consult these groups and make those 
comments public?
    Answer. The change in NCS design is being considered primarily for 
scientific reasons but also with awareness of our need to be fiscally 
responsible. It is based on data generated during the ongoing Vanguard, 
or pilot phase, of the NCS. The Vanguard data showed that the proposed 
study design would not enroll sufficient numbers of families within a 
scientifically acceptable timeframe or within a fiscally sound budget. 
Pilot testing conducted through the Vanguard sites showed that a study 
design based primarily on recruiting participants through healthcare 
providers was most efficient and could offer scientific advantages that 
would more than offset its scientific compromises. This provider-based 
approach also has been employed effectively in other large Federal 
studies. The President's fiscal year 2013 budget request, which shows a 
reduction of approximately 15 percent, to $165 million annually, for 
the NCS, appropriately reflects these proposed design changes.
    As currently envisioned, the NCS Main Study would use a provider-
based participant selection and recruitment strategy that the NIH and 
the Agency for Healthcare Research and Quality have both employed 
effectively in other studies. This approach uses research ready 
healthcare provider networks as the primary source for recruitment. The 
NCS would gain additional participants through the award of contracts 
for supplemental recruitment from secondary sources (such as title V 
clinics, Indian Health Service clinics, or contract research 
organizations) to assure inclusion of appropriate population groups, 
specifically those with health disparities. The use of these two 
coordinated selection and recruitment strategies would improve the 
quality of the Main Study and allow analyses not feasible with either 
approach alone.
    If adopted, this revised approach would offer several advantages, 
including:
  --greater recruitment efficiency;
  --leveraging access to consenting participants' electronic health 
        records, thus improving the amount and consistency of data 
        collected while lowering costs;
  --the potential to leverage the existing infrastructure of networks 
        of healthcare providers, again improving the quality of data 
        and lowering costs; and
  --allowing built-in continuity for participants who move but remain 
        within the provider network (many provider networks have 
        statewide or regional coverage) or join another provider 
        network affiliated with the Main Study.
    NCS continues to refer to the IOM report that was written by a 
panel of experts convened to review the original study design. Many of 
the changes recommended in the report have already been addressed, 
including the need for an ongoing Vanguard Study to test the study 
protocol and scientific methodology. The report also noted that the 
large number of field contractors was a weakness of the Study design, 
and the NCS is moving to correct this weakness.
    The NCS Study Advisory Committee meets at least four times a year; 
the April 24, 2012 meeting was the 32d meeting of the subcommittee. 
These meetings are open to the public, and a public comment period is 
provided. Presentations to the Advisory Committee also are posted on 
the NCS Web site. As they have become available, data from the Vanguard 
Study have been presented at each of the subcommittee's meetings. The 
topic of a provider-based approach to Study recruitment was discussed 
twice in the last year with the Advisory Committee, first in April 2011 
and then again in July 2011, before being the focus of the entire April 
24, 2012 meeting. The NCS Study Director holds weekly national 
conference calls for Vanguard Study contractors to update them on 
recent developments and to receive their input. The investigators also 
provide expertise and comments through a monthly Executive Steering 
Committee meeting, through 2-day, face-to-face meetings every 6 months, 
through circulation of all study instruments and protocol changes to 
all investigators for comment, and through a mailbox account dedicated 
to contractors.
    Question. I am also concerned that the re-design will jeopardize 70 
high-quality jobs in Rhode Island, including 20 full-time positions 
that would have otherwise been created for the Main Study. How will 
this proposal impact the work of researchers and practitioners already 
participating in the study and the potential for job growth in my 
State? Does NIH plan to abandon its commitment to the 105 counties that 
have been selected to participate in the study?
    Answer. To date, the NCS Vanguard Study has accomplished what it 
set out to do, provide data on recruitment and early retention into the 
Study. We will continue to follow all children born into the Vanguard 
Study, until age 21. We have no intention to lose NCS participants from 
the Vanguard Study; instead, we are developing and field testing a 
proactive plan that includes personal contacts, special events for 
participants, linkages to local health resources through other Health 
and Human Service programs, returning results of Study assessments, and 
soliciting feedback about the Study experience. In addition, 
participants that might have been lost under the original Study design 
because they moved out of a particular geographic area might still be 
included in a health provider network involved in the Study.
    Current NCS Vanguard Study contracts expire over the next 17 
months. All Requests for Proposals for both the Vanguard and Main 
Studies will have full and open competitions. Academic institutions can 
offer proposals for new Study contracts for primary data collection, 
and have other options as well, including partnering with a primary 
data collector, conducting ancillary studies using NCS infrastructure, 
or doing their own research analyses using NCS data as they become 
available. Finally, contractors that complied with NCS specifications 
for field operations will have established a platform that is flexible 
and adaptable to multiple uses, so they can leverage that investment 
for additional projects.
    As indicated above, the change in study design is based on data 
generated during the ongoing Vanguard pilot phase of the NCS, which 
showed that the previously proposed study design would not enroll 
sufficient numbers of families within a scientifically acceptable 
timeframe or within a fiscally sound budget. Pilot testing conducted 
through the Vanguard sites showed that a study design based primarily 
on recruiting participants through healthcare providers was most 
efficient and could offer scientific advantages that would more than 
offset its scientific compromises.
                       pediatric cancer research
    Question. Dr. Varmus, last year you and Dr. Collins provided me 
with a detailed explanation of NIH efforts to address pediatric 
cancers, including late-term effects. However, I am still concerned 
that a mere 4 percent--just $200 million--of NCI funding is allocated 
to cancer research specifically for this population. I am concerned 
that this funding level remains stagnant because the peer-review 
process doesn't recognize the importance of pediatric cancer research 
in terms of years of life lost and poor quality of life for many 
survivors. How could a Pediatric Cancer Study Section improve the 
funding devoted to pediatric cancer research?
    Answer. Over the past year, the National Cancer Institute (NCI) has 
worked with members of the Congressional Childhood Cancer Caucus to 
discuss this very question, and to explore how pediatric cancer 
research proposals fare in comparison to other proposals under the 
current peer-review process, with a goal of determining whether or not 
pediatric cancer grant applications are competitive in the peer-review 
process. NCI performed this analysis, which showed that pediatric 
cancer grant applications actually have success rates (number of grants 
awarded/number of grants received) that are equal to--and in some cases 
higher than--grant applications focusing on adult cancers. NCI further 
focused on R01 (individual investigator initiated) grant applications 
to exclude large program grants (such as cancer center support grants, 
for example) that have little competition. And again the data showed 
that pediatric cancer-focused R01 grant applications are quite 
competitive in the peer-review process.
    The NIH Center for Scientific Review (CSR), which oversees the NIH 
peer-review process, considers a number of criteria when it establishes 
study sections. These criteria were developed by an external blue 
ribbon panel set up to systematically assess and reorganize CSR's 
review groups. For example, these guiding principles indicate that 
applications pertaining to a given disease/organ system are best 
reviewed in the context of the biological question being addressed. 
They provide that study section boundaries should not be too broad or 
too narrow, and that sufficient overlap should exist between other 
study sections inside and outside their integrated review groups 
(IRGs--clusters of study sections based on scientific discipline).
    Therefore, the NIH has no standing study sections that review 
applications relevant to specific diseases, groups of diseases, or 
organ sites; rather, study sections are formed around scientific 
disciplines, e.g., epidemiology, genomics, therapeutics development, 
populations, behavior, etc., and are populated by productive 
investigators with expertise in those areas.
    Within the category of pediatric cancer research, applications 
under consideration for funding pose an extremely diverse set of 
biological questions, as evidenced by the array of standing study 
sections that are called upon to review grant applications relevant to 
pediatric cancer. Because pediatric cancers are so heterogeneous, it 
makes sense scientifically to distribute review of these applications 
among multiple study sections.
    Data analyzed from fiscal year 2008 through fiscal year 2010 
indicate that the NCI supports pediatric cancer research applications 
via numerous mechanisms, and that support of pediatric cancer research 
grants has increased during that time period. As previously noted, 
success rates were in line with--and in many cases exceeded--those for 
other cancer types. This evidence suggests that pediatric cancer 
applications are very competitive within NIH's scientific review 
process.
    Additionally, although disease-specific funding estimates can be 
useful indicators of some focused work, they do not reflect the full 
level of NCI's investment (approximately $1.9 billion) into research 
exploring cancer biology and cancer causation--broad areas of inquiry 
applicable to all types of cancers, including pediatric cancers. It is 
important to consider NCI's full cancer research portfolio, and to also 
recognize that investments in one area of cancer research can, and 
often do, contribute to advances in others. For example, identifying 
the clinical value of crizotinib in the treatment of adults affected by 
lung cancer with abnormalities of the Alk gene has led to the current 
clinical testing children with neuroblastoma whose tumors have Alk 
abnormalities.
                                 ______
                                 
               Questions Submitted by Senator Mark Pryor
                       pancreatic cancer research
    Question. Dr. Varmus, during the hearing you testified that 
research for pancreatic cancer is being prioritized by National Cancer 
Institute (NCI) and that the Institute currently has flexibility to 
fund grant applications that fall below what used to be called the 
``pay line'' in cases where therapeutic progress in relation to a 
disease has been low. Are there examples you can describe of grants in 
relations to pancreatic cancer where the Institute exercised this 
flexibility?
    Answer. Pancreatic cancer is a high priority for the NCI, and we 
are supporting a wide range of research projects to rapidly develop the 
tools needed to diagnose pancreatic tumors as early as possible, to 
characterize tumors genetically, and to find new ways to treat this 
disease. NCI has been paying special attention to grants that might not 
be funded because they fell below what used to be considered a 
``payline,'' a percentile score derived from the results of peer 
review. Beginning in fiscal year 2011, NCI scientific program leaders 
have been performing additional evaluations of grant applications to 
ensure a balanced grant portfolio and to recognize the value of 
research proposals that are highly original or address important 
scientific priorities, such as research on pancreatic cancer, even 
though they might not have received percentile scores that fall within 
a pre-determined payline. Of the applications that were focused 
exclusively on pancreatic cancer and were funded in fiscal year 2011, 
more than one-third were selected as a result of this programmatic 
review, rather than on the basis of receiving exceptionally high 
scores.
    Examples of pancreatic cancer projects approved by this process 
include:
  --a case-control study aimed at characterizing a select group of 
        biomarker candidates in pancreatic juice that may enable 
        earlier detection;
  --a study to develop a multifunctional nanoparticle platform with 
        both imaging and drug delivery capabilities;
  --a study of corcetin (a carotenoid molecule isolated from saffron) 
        that has been shown to have anticancer effects as a potential 
        therapy for pancreatic cancer; and
  --a study focused on identifying vulnerable areas of pancreatic 
        tumors and overcoming the tough ``stromal barrier'' of 
        pancreatic tumors that limits the delivery and diffusion of 
        drugs.
                            long-term goals
    Question. In the past, this subcommittee has urged NCI to develop a 
long-range plan for research in the area of pancreatic cancer research. 
Research advocates have been disappointed with the plan and view it 
more as a summary of research that's already underway. Would it be 
possible for NCI to lay out more of a long-term research strategy--
something that sets out concrete goals and objectives for the future 
that moves beyond current practice?
    Answer. Pancreatic cancer is distinct from other cancers due to its 
complex biology, late manifestation of symptoms, and the lack of early 
screening tools. In addition, there are a large number of genetic 
mutations involved, which complicates the development of effective 
targeted therapies to disable the growth of cancer cells and arrest 
progression of the disease. These factors explain the poor outcomes for 
most pancreatic cancer patients. However, there is great opportunity to 
change these outcomes. Recent NCI-supported research has demonstrated 
that there is a long time period--more than 11 years--between the first 
cancer-related mutation in a pancreatic cell and the development of a 
mature pancreatic tumor. This means that with the right tools for 
detection and targeted treatments, pancreatic cancer could be diagnosed 
while it is surgically curable.
    Both NCI's research portfolio and the fiscal year 2011 strategic 
plan for pancreatic cancer reflect several specific goals, including:
  --in-depth gene sequencing of pancreatic tumors to develop tools for 
        detection and treatment;
  --identification of genetic factors, environmental exposures, and 
        gene-environment interactions that contribute to the 
        development of this cancer;
  --identification and development of biomarkers to allow early 
        detection;
  --improvement in our ability to detect tumors when they are much 
        smaller than those currently able to be detected with our 
        imagining capabilities; and
  --development of effective targeted therapies.
    To accomplish these goals, NCI is supporting a breadth of research 
across its portfolio that applies to the scientific underpinnings of 
all of these goals, including in-depth sequencing of pancreatic tumors 
through The Cancer Genome Atlas. But it is also important to note that 
advances in oncology that have great benefit for a particular type of 
cancer do not necessarily flow from research specifically on that 
cancer type. For example, investment in a rare disease, retinoblastoma, 
was critical for the discovery of tumor suppressor genes, a class of 
genes that is altered in essentially every cancer. Similarly, work on 
an animal model of neuroblastoma led to the discovery of an oncogene, 
HER2, which is targeted by antibodies now widely used in the treatment 
of breast cancer. Thus, while it is crucial for the NCI to give full 
attention to the clinical consequences of every cancer type, we must 
also be responsive to opportunities and ideas that seem likely to offer 
the best chances of making discoveries that bring us closer to 
understanding all cancers, as well as individual cancer types.
                                 ______
                                 
           Questions Submitted by Senator Barbara A. Mikulski
                          cancer genome atlas
    Question. Dr. Varmus, please provide an update on how The Cancer 
Genome Atlas (TCGA) is proceeding and how it is contributing to 
reaching the goal of precision medicine that was described in the 2011 
Institute of Medicine report, ``Toward Precision Medicine: Building a 
Knowledge Network for Biomedical Research and a New Taxonomy of 
Disease.''
    Answer. TCGA, a joint effort of the National Cancer Institute (NCI) 
and the National Human Genome Research Institute (NHGRI), is the 
largest and most comprehensive analysis of the molecular basis of 
cancer ever undertaken. Through the application of genome analysis 
technologies, including large-scale genome sequencing, TCGA is 
beginning to provide a comprehensive foundation of the abnormalities 
associated with the tumor types under study, the degree to which tumors 
within each type are similar and distinct, and the degree of overlap 
between tumor types. This foundation has the potential of improving our 
ability to diagnose, treat, and prevent cancer, providing an important 
element in reaching the goal of precision medicine.
    TCGA began as a pilot project in 2006, studying cancers of the 
lung, brain (glioblastoma) and ovary, and it has been expanded over 
time to include additional tumor types. Currently in the third year of 
its post-pilot phase, TCGA has begun the comprehensive analysis of 16 
additional cancers including breast, colorectal, kidney, lung, 
endometrial, and pancreatic cancers, among others. Of these projects, 
one-quarter are published or in manuscript form; one-quarter are in 
late-stage analysis; and the remaining one-half are still being 
collected and studied, with TCGA on track to conclude this phase in 
2014. TCGA has also initiated a small project on rare tumors, with 
plans to complete initial discovery by the end of this year.
    TCGA's efforts to advance the understanding of the molecular basis 
of cancer are already providing the biological insights considered 
critical by the 2011 report, ``Toward Precision Medicine: Building a 
Knowledge Network for Biomedical Research and a New Taxonomy of 
Disease,'' to reaching the goal of precision medicine. The report, 
produced by the National Research Council of the National Academy of 
Sciences, and sponsored by the National Institutes of Health, 
identifies a ``knowledge network of disease'' as necessary to enable a 
new taxonomy of disease that integrates molecular and clinical data, as 
well as health outcomes. TCGA's findings, as well as other work 
supported by the NCI's Center for Cancer Genomics, are poised to 
contribute directly to this network. The NCI is taking a leadership 
role in advancing precision medicine in cancer, and in April 2012 
hosted a workshop that brought together NCI scientists and colleagues 
from across the cancer community to consider ways in which NCI can 
support the acceleration of precision medicine to cancer research and 
treatment.
                           angiogenic levels
    Question. Dr. Collins, what work is NIH conducting to help 
establish baseline angiogenic levels in healthy individuals and those 
with disease? How will this work impact NIH's ability to measure the 
effects of diet on blood vessel development?
    Answer. NCI funds angiogenesis-related research that includes 
examination of cancer-related angiogenesis and exploration of therapies 
targeting this process, as well as research on diet, angiogenesis, and 
cancer prevention. Research is also underway to investigate the effect 
of moderate intensity exercise on blood vessels. Angiogenesis, and 
specifically research measuring the effects of diet on blood vessel 
development, is an area of research the NCI continues to support. Two 
examples of ongoing NCI research related to angiogenesis include:
  --An examination of the underlying mechanisms for the association 
        between increased physical exercise and decreased risk of 
        several types of cancer and the effects of exercise on 
        angiogenesis-related biomarkers in serum.
  --A diagnostic imaging study examining baseline tissue angiogenic 
        markers and the outcomes of chemotherapy delivered directly to 
        liver tumors via a catheter (transarterial chemo embolization 
        therapy).
                       strategic scientific plan
    Question. Dr. Collins, NIH has published a Request for Information 
seeking comments on the Strategic Scientific Plan for the proposed new 
Substance Use and Addiction Disorders Institute. Does NIH intend to 
provide access to these comments to the scientific community and the 
general public? Will NIH make all of the responses available to the 
public as they are received?
    Answer. The Request for Information seeking input into the 
Scientific Strategic Plan is open through May 11, 2012. NIH will 
provide access to all of the responses after the comment period closes. 
NIH will also provide a summary of the comments after completing an 
analysis of the responses.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby
                       national children's study
    Question. Dr. Collins, I am hearing serious concerns from the 
research community regarding proposed changes to the National 
Children's Study (NCS). The study was originally designed around a 
representative door-to-door sampling of the U.S. population and now the 
sampling strategy has been significantly changed to be based on 
provider locations instead.
    How much input did you receive from the scientific community and in 
particular the principal investigators participating in the study and 
your advisory committee, on the changes being made to the sampling 
strategy?
    Answer. The change in the NCS Study design is being considered 
primarily for scientific reasons but also with awareness of our need to 
be fiscally responsible. It is based on data generated during the 
ongoing Vanguard, or pilot phase, of the NCS. The Vanguard data showed 
that the proposed study design would not enroll sufficient numbers of 
families within a scientifically acceptable timeframe or within a 
fiscally sound budget. Pilot testing conducted through the Vanguard 
sites showed that a study design based primarily on recruiting 
participants through healthcare providers was most efficient and could 
offer scientific advantages that would more than offset its scientific 
compromises. This provider-based approach also has been employed 
effectively in other large Federal studies. The President's fiscal year 
2013 budget request, which shows a reduction of approximately 15 
percent, to $165 million annually, for the NCS, appropriately reflects 
these proposed design changes.
    As currently envisioned, the NCS Main Study would use a provider-
based participant selection and recruitment strategy that the National 
Institutes of Health (NIH) and the Agency for Healthcare Research and 
Quality have both employed effectively in other studies. This approach 
uses research ready healthcare provider networks as the primary source 
for recruitment. The NCS would gain additional participants through the 
award of contracts for supplemental recruitment from secondary sources 
(such as title V clinics, Indian Health Service clinics, or contract 
research organizations) to assure inclusion of appropriate population 
groups, specifically those with health disparities. The use of these 
two coordinated selection and recruitment strategies would improve the 
quality of the Main Study and allow analyses not feasible with either 
approach alone.
    If adopted, this revised approach would offer several advantages, 
including:
  --greater recruitment efficiency;
  --leveraging access to consenting participants' electronic health 
        records, thus improving the amount and consistency of data 
        collected while lowering costs;
  --the potential to leverage the existing infrastructure of networks 
        of healthcare providers, again improving the quality of data 
        and lowering costs; and
  --allowing built-in continuity for participants who move but remain 
        within the provider network (many provider networks have 
        statewide or regional coverage) or join another provider 
        network affiliated with the Main Study.
    NCS continues to refer to the Institute of Medicine (IOM) report 
that was written by a panel of experts convened to review the original 
study design. Many of the changes recommended in the report have 
already been addressed, including the need for an ongoing Vanguard 
Study to test the study protocol and scientific methodology. The report 
also noted that the large number of field contractors was a weakness of 
the Study design, and the NCS is moving to correct this weakness.
    The National Children's Study Advisory Committee meets at least 
four times a year; the April 24, 2012 meeting was the 32d meeting of 
the committee. These meetings are open to the public, and a public 
comment period is provided. Presentations to the Advisory Committee 
also are posted on the NCS Web site. As they have become available, 
data from the Vanguard Study have been presented at each of the 
committee's meetings. The topic of a provider based approach to Study 
recruitment was discussed twice in the last year with the Advisory 
Committee, first in April 2011 and then again in July 2011, before 
being the focus of the entire April 24, 2012 meeting. The NCS Study 
Director holds weekly national conference calls for Vanguard Study 
contractors to update them on recent developments and to receive their 
input. The investigators also provide expertise and comments through a 
monthly Executive Steering Committee meeting, through 2-day face-to-
face meetings every 6 months, through circulation of all study 
instruments and protocol changes to all investigators for comment, and 
through a mailbox account dedicated to contractors.
    Question. How will the academic community be involved going 
forward?
    Answer. Current NCS Vanguard Study contracts expire over the next 
17 months. All Requests for Proposals for both the Vanguard and Main 
Studies will have full and open competitions. Academic institutions can 
offer proposals for new Study contracts for primary data collection, 
and have other options as well, including partnering with a primary 
data collector, conducting ancillary studies using NCS infrastructure, 
or doing their own research analyses using NCS data as they become 
available.
    In addition, the NCS holds workshops and conferences several times 
a year and holds open Advisory Committee meetings on a quarterly basis 
to which the academic community is welcome. NCS also meets with 
professional societies and other organizations on an ongoing basis and 
NCS personnel plan and attend academic meetings throughout the year.
    Question. In 2010, the committee was informed by NIH that the 
approximate cost of the entire NCS program would double--from $3.1 to 
$6 billion. Now, you are cutting the request by 15 percent. The budget 
justification provides no details on how you arrived at the request 
amount for fiscal year 2013. Can you lay out, specifically, how the 
$165 million request was reached?
    Answer. NCS is able to reduce overhead costs through greater 
operational efficiencies and redistribution of tasks and 
responsibilities. Examples include the use of nonproprietary software 
to eliminate license fees and proprietary support; use of a federated 
model for human subject protection to reduce redundancy and speed 
approvals through elimination of duplicate administrative resources; 
use of the NCS program office as a coordinating center to develop study 
instruments and protocol documents, to perform data analysis, and to 
manage field operations and general consolidation of overlapping field 
operations.
    With the reduction in overhead, we anticipate that for fiscal year 
2013 we need about $35 million for support services and about $130 
million for ongoing Vanguard operations and Main Study initiation.
    Question. Why are there no longer any study hypotheses which 
address the congressional concerns for the NCS put forth in the 
Children's Health Act of 2000?
    Answer. As directed by the Children's Health Act of 2000, the NCS 
is a longitudinal birth cohort study with the overall goal of examining 
the role that environmental influences (including physical, chemical, 
biological, and psychosocial) have on children's health and 
development. Hypotheses about what factors affect children's health and 
development will inform the questions asked and the data collected for 
the Study, but the NCS will not be hypothesis-driven. Children's 
environments are likely to change substantially over the next two 
decades, and our goal is to create the richest possible data, 
biospecimen, and environmental specimen resource to answer important 
questions about health and development as they arise.
    Question. It is my understanding that the new proposal will move 
the sampling scope from a door-to-door model to a health maintenance 
organization-based model. By design, this would exclude involvement of 
the uninsured and likely the involvement of rural and minority 
populations. These populations are a critical component to achieving 
scientifically valid findings. How will you address this issue?
    Answer. As currently envisioned, the NCS Main Study would use a 
provider-based participant selection and recruitment strategy that the 
NIH and the Agency for Healthcare Research and Quality (AHRQ) have both 
employed effectively in other studies. This approach uses research 
ready healthcare provider networks as the primary source for 
recruitment. The NCS would gain additional participants through the 
award of contracts for supplemental recruitment from secondary sources 
(such as title V clinics, Indian Health Service clinics, or contract 
research organizations) to assure inclusion of appropriate population 
groups, specifically those with health disparities. The use of these 
two coordinated selection and recruitment strategies would improve the 
quality of the Main Study and allow analyses not feasible with either 
approach alone.
    Question. The Vanguard Centers have created nearly a decade's worth 
of research infrastructure including costly ``build outs'' of field 
office space composed of laboratories for processing biological and 
environmental specimens, and call centers. These facilities were built 
to detailed specifications provided by the NCS program office. Other 
NCS research infrastructure include the hiring, certifying and training 
of staff, development of a Federated Institutional Review Board, and 
establishment of a Federal Information Security Management Act 
compliant environment. In addition, the Vanguard Centers have spent 
years developing cooperative agreements and memoranda of understanding 
with countless delivery hospitals to ensure that NCS participant 
biological and medical data can be obtained at the time of birth. Given 
the newly proposed design of the NCS, it appears as though this 
infrastructure could go to waste without utilizing the resources of the 
existing Vanguard Centers. What assurances can you provide that these 
Vanguard Centers will be eligible to compete for continued 
participation in the NCS and be afforded a reasonable, full, and fair 
opportunity to do so?
    Answer. The Vanguard Study will continue to pilot study methods in 
its current 40 locations, several years in advance of the Main Study, 
following the children already recruited by the Vanguard Study until 
they turn 21. In this follow-up phase, it will use a smaller number of 
contractors than in its earlier recruitment phase, thus following 
recommendations in the IOM report from 2008 and realizing cost savings, 
while improving scientific quality by achieving greater consistency in 
data and specimen collection among study sites.
    Current NCS Vanguard Study contracts expire over the next 17 
months; new contracts will be awarded following full and open 
competitions. The NCS is working with current contractors to ensure the 
orderly transition of data collection services and of relationships 
with participants, communities, and other local institutions. As is 
usual with longitudinal studies that extend across many years, 
individual contractors may continue to change during the course of the 
study, and it is important for the NCS to have procedures in place to 
ensure smooth transitions that may occur in the future.
    All Requests for Proposals for both the Vanguard and Main Studies 
will have full and open competitions. Academic institutions can offer 
proposals for new Study contracts for primary data collection, and have 
other options as well, including partnering with a primary data 
collector, conducting ancillary studies using NCS infrastructure, or 
doing their own research analyses using NCS data as they become 
available. Finally, contractors that complied with NCS specifications 
for field operations will have established a platform that is flexible 
and adaptable to multiple uses, so they can leverage that investment 
for additional projects.
                      drug rescue and repurposing
    Question. Dr. Collins, at the NIH hearing last year, we discussed 
drug rescue and repurposing--that is, leveraging existing compounds to 
develop new, novel treatments for patients. In January, NIH released a 
concept for a program called the Drug Rescue Program to fund research 
to identify new therapeutic uses of proprietary investigational drugs 
and biologics. I am pleased to see NIH moving forward on this issue 
since it is an ideal opportunity for academia to team with industry to 
bring treatments to patients faster. However, repurposing compounds 
brings up a number of challenges, including concerns regarding 
intellectual property rights and liability. In particular, will 
pharmaceutical companies be interested in repurposing drugs they 
currently make money on if a new patient population could open them up 
to new lawsuits? How will you address these concerns?
    Answer. In early May, National Center for Advancing Translational 
Sciences (NCATS) expects to establish a pilot collaborative drug rescue 
program, Discovering New Therapeutic Uses for Existing Molecules, to 
match researchers with a selection of industry-developed molecular 
compounds in an attempt to identify a therapeutic use. These compounds 
are currently not approved for any use and are not being pursued by the 
pharmaceutical company. The program will incorporate innovative 
template agreements designed to streamline the legal and administrative 
process for participation by multiple organizations. These templates 
will reduce time, cost, and effort, as well as enable greater 
participation than traditional partnerships. The templates also provide 
a roadmap for handling intellectual property used in or developed 
through the program. Participating industry partners will retain the 
ownership of their compounds, while academic research partners will own 
any intellectual property they discover through the research project 
with the right to publish the results of their work.
    This pilot program will focus on drug rescuing only. It does not 
include drug repurposing, which is an attempt to find a new use for a 
drug that is already approved for another therapeutic use. NCATS is 
considering how best to structure initiatives which enable drug 
repurposing, with the understanding that repurposed drugs would undergo 
the same Federal Drug Administration (FDA) requirements and clinical 
development investments as newly developed compounds and will need to 
meet FDA patient safety and efficacy requirements.
                            health economics
    Question. Dr. Collins, the President's budget requests $13 million 
from the Common Fund for health economics research. Diverting 
biomedical research funds to pay for health economics research is not 
only a significant departure from traditional NIH research funding but 
also duplicative of AHRQ health economics research and the Center for 
Disease Control and Prevention research on the economics of prevention. 
For example, one of the programs four major initiatives in the budget 
request is for a program entitled: ``The Science of Structure, 
Organization, and Practice Design in the Efficient Delivery of 
Healthcare.'' This initiative appears directly duplicative of AHRQ's 
existing program, the Patient-Centered Health Research/Effective Health 
Care, that seeks to conduct research around the same areas on 
healthcare delivery and efficiency. Since AHRQ's mission seems more 
appropriately suited toward researching the economics and efficiency of 
healthcare delivery, why should we be taking money away from valuable 
investments in biomedical research, when much of this work appears to 
be in progress within other Health and Human Services Operating 
Divisions?
    Answer. We are working with AHRQ and other agencies to collaborate 
on this critical issue to ensure that NIH research does not conflict 
with their efforts and missions. NIH's mission is ``to seek fundamental 
knowledge about the nature and behavior of living systems and the 
application of that knowledge to enhance health, lengthen life, and 
reduce the burdens of illness and disability.'' We initiated this 
Common Fund program in Health Economics as a way to measure the success 
of the translation of the benefits of our research into enhanced health 
of the U.S. population.
    Much of the NIH research enterprise generates optimism that a new 
era of personalized medicine (meaning both prevention and treatment) 
will lead to improved outcomes while keeping cost growth under control. 
For this promise to be realized, we will need to understand the reasons 
organizations and individuals adopt new approaches.
                                 ______
                                 
             Questions Submitted by Senator Lamar Alexander
               clinical and translational science awards
    Question. The largest single Federal grant at Vanderbilt University 
is a clinical and translational science award (CTSA) for approximately 
$50 million. Vanderbilt is also the national coordinating center for 
all of the CTSA's. How do you see the interactions between the CTSAs 
and the rest of the National Center for Advancing Translational Science 
(NCATS) developing, and what is being done to support a high level of 
interaction?
    Because of the shortage of products in the drug pipeline, do you 
see NCATS as more focused on drug development, or will the CTSAs also 
continue to be able to build on the programs of training, career 
development for young investigators, research informatics, community 
engagement, and clinical research infrastructure? All of these are 
still important for biomedical research.
    Answer. With the creation of NCATS on December 23, 2011, the 
administration of the CTSA program moved into a new home. Within NCATS, 
the program will continue to support the highest quality translational 
research. Now as part of a new division, the Division of Clinical 
Innovation (DCI), the CTSA program is benefiting from adjacency to the 
new Division of Preclinical Innovation (DPI). DPI includes programs 
that focus on re-engineering the early phases of translation (including 
assay development, high-throughput screening, lead optimization, and 
predictive toxicology) as well as the Therapeutics for Rare and 
Neglected Diseases program. A fully integrated program will be put in 
place so that the DPI and the DCI are truly a single effort guided by a 
shared mission.
    One of the great successes of the CTSA program has been its 
development of training programs for clinical researchers and allied 
professionals in the many aspects of translational science. As the CTSA 
program incorporates the mission of NCATS, this emphasis on training 
will be sustained and expanded to build in specific areas of need, such 
as informatics and pharmacology. We anticipate that the CTSAs will have 
an important role in facilitating first-in-human trials for new 
therapies, promoting innovation in research methods, and re-engineering 
the processes for clinical research. We expect that they will continue 
to provide a home for community outreach and education at institutions 
across the country. The CTSA program will continue to support the 
entire spectrum of translational research, evolving to meet the most 
pressing scientific needs and opportunities. NCATS is not a drug 
development center; its broader mission is to enhance the development, 
testing, and implementation of diagnostics and therapeutics across a 
wide range of diseases and conditions.
                         personalized medicine
    Question. The physicians and researchers at Vanderbilt are 
investing a great deal in the science of personalized medicine. Can you 
tell us what the term ``personalized medicine'' means to you, and what 
role you see for National Institutes of Health (NIH)?
    Answer. Personalized medicine, or more precisely ``genomic 
medicine,'' is the medical application of genomics for the purposes of 
disease prevention, diagnosis, and treatment. It is sometimes referred 
to as ``precision medicine'' or ``individualized medicine.'' Through 
genomic medicine, we will anticipate and often pre-empt the onset of 
disease, diagnose disease more quickly and accurately, and tailor the 
choice of medications according to an individual's genomic information.
    This vision for improved healthcare tools and options was a key 
driving force behind the Human Genome Project (HGP; http://
www.genome.gov/10001772)--a major international project led by the NIH. 
Scientists recognized that, in order to realize genomic medicine, we 
would first need much more detailed knowledge of the human genome. 
Through the HGP, scientists were able to determine the full molecular 
sequence of the human genome and its genes.
    NIH, led by the National Human Genome Research Institute (NHGRI), 
is now building on the success of the HGP. In 2011, NHGRI published a 
new strategic vision describing the research path necessary for genomic 
medicine to become reality (http://www.genome.gov/sp2011/). The plan 
emphasizes that a deeper understanding of the basic biology of the 
genome, such as identifying all its functional elements and how genomes 
vary from person to person is needed. It also highlights the need to 
investigate how genome variation influences health and disease and the 
work to be accomplished to explore the clinical applications of 
genomics. NIH is now leading this research through cutting-edge 
programs and research initiatives.
    For instance, NHGRI and the National Cancer Institute 
collaboratively lead ``The Cancer Genome Atlas'' to better understand 
the molecular basis of cancer. NHGRI also is funding research to detect 
the genetic underpinnings of thousands of rare diseases for which there 
is no known cause, as well as undertaking a major project to 
investigate the genetic causes of Alzheimer's disease. While it will be 
many years before genomics is fully incorporated into patient care, 
NHGRI-funded researchers are investigating the clinical use of genomics 
in patients at risk for many diseases, including those with mysterious 
conditions that have long eluded diagnosis. Institutes and Centers 
(ICs) across NIH are conducting genomic research to elucidate the 
genomic causes of disease and how the genome influences the 
effectiveness of treatment.
    Though sometimes envisioned as a phenomenon of the future, genomic 
medicine is already having an impact on how patients are treated. This 
is especially true in the field of pharmacogenomics, where drug 
selection and administration increasingly is assisted by prior genetic 
testing. The Food and Drug Administration now lists approximately 100 
approved drugs with pharmacogenomic information on their labels. These 
include abacavir, now the standard of care for HIV-infected patients, 
as well as drugs for the treatment of cancers, clopidogrel for treating 
cardiovascular disease, and warfarin for preventing blood clotting.
    Genomics is also being used to help patients who do not respond to 
conventional treatment. An example of this was described by NIH 
Director Francis Collins, M.D., Ph.D. during his testimony before the 
subcommittee during the NIH hearing on March 28. Dr Collins told the 
story of twins Alexis and Noah Beery, who suffered from a rare and 
devastating movement disorder called dystonia. The causative mutation 
was identified through sequencing of their genomes, after which their 
treatment was changed and their health improved remarkably.
    Genomics promises to advance healthcare over the next several 
decades. NIH will continue to lead the way toward genomic medicine 
through funding and conducting the pioneering science that will be 
necessary to realize the full potential of genomic medicine.
                                diabetes
    Question. Diabetes continues to be a costly and growing epidemic 
for Tennessee and the United States. Dr. Collins and Dr. Rodgers, can 
you tell us how NIH, and National Institute of Diabetes and Digestive 
and Kidney Diseases (NIDDK) in particular, are addressing this 
epidemic?
    Answer. NIH and NIDDK are working to develop and test prevention 
and treatment strategies for type 1 and type 2 diabetes through a 
robust research program that supports basic, clinical, and 
translational research, as well as research training. Future research 
will be guided by a strategic plan for diabetes research that was 
recently released by the NIDDK (http://www2.niddk.nih.gov/AboutNIDDK/
ReportsAndStrategicPlanning/DiabetesPlan/PlanPosting.htm). Landmark 
clinical research supported by the NIH has included the Diabetes 
Control and Complications Trial and the United Kingdom Prospective 
Diabetes Study, which established the value of tight blood glucose 
control in reducing complications in type 1 and type 2 diabetes 
respectively; and the Diabetes Prevention Program, which proved that 
type 2 diabetes can be prevented or delayed through delivery of an 
intensive lifestyle intervention, or, to a lesser degree, with the 
generic drug metformin. Knowledge from NIH diabetes research is 
communicated to patients, health professionals, and the public through 
the National Diabetes Information Clearinghouse and the National 
Diabetes Education Program.
    In 2011, NIDDK completed the first major trial of type 2 diabetes 
management in children and adolescents, a newly emerging problem, and 
demonstrated that intensive glucose control in people with type 1 
diabetes can reduce rates of chronic kidney disease and end-stage renal 
disease by 50 percent 22 years later. NIDDK supported planning grants 
for a comparative effectiveness clinical trial testing different 
medications, in combination with metformin, for type 2 diabetes 
treatment, and for a clinical trial testing vitamin D in prevention of 
type 2 diabetes based on a promising pilot study. Other clinical trials 
include Action for Health in Diabetes (Look AHEAD), to determine the 
value of a lifestyle intervention for improving diabetes outcomes, and 
investigation of bariatric surgery as treatment for diabetes, 
complemented by studies in animal models.
    New initiatives are fostering research toward preserving function 
of insulin-producing beta cells early in the course of type 2 diabetes, 
and a new consortium was launched to study approaches to prevent 
gestational diabetes. The Beta Cell Biology Consortium identified a 
potential new strategy to induce beta cell regeneration to replace lost 
beta cells and reverse aging-associated decline in beta cell growth. 
NIDDK is also working to understand and ameliorate disparities in 
diabetes with research to identify gene regions conferring type 2 
diabetes risk in multiple ethnic groups, translational research to 
bring scientific discoveries to all who can benefit, and a clinical 
trial of type 2 diabetes management including minority youth and 
adolescents.
                 minority health and health disparities
    Question. Dr. Collins, the healthcare reform law clarified the role 
of the National Institute on Minority Health and Health Disparities 
(NIMDH) at NIH as it pertains to coordinating health disparities 
research. How are you and the IC Directors going to work together to 
make the newly elevated NIMHD the coordinating body at NIH on health 
disparities?
    Answer. The law clearly identifies the NIMHD as the coordinating 
body for minority health and health disparities at NIH. The NIH 
Institutes and Centers will continue to administer their programs on 
minority health and health disparities and work with the NIMHD as 
required in its coordinating role.
    Question. Where does the NIH stand in terms of funding that is 
allotted to minority health and health disparities? In the last 
strategic plan, there was $2.5 billion being spent on minority health 
and health disparities at various ICs. What is that amount now, and how 
are you going to work with the new health reform law so that the NIMHD 
is the coordinating entity at NIH for these issues?
    Answer. The overall NIH fiscal year 2011 funding for health 
disparities was $2.7 billion. NIMHD recently hired a Deputy Director 
for strategic scientific planning and program coordination, who will 
lead the NIMHD coordination of minority health and health disparities 
working with the Institutes and Centers.
    Question. Considering last year's NIH study, which showed possible 
bias against African Americans with the awarding of NIH R01 grants, 
will you work with Meharry Medical College and the Association of 
Minority Health Professions Schools to ensure their annual health 
profession pipeline symposium, exposing hundreds of students to the 
health professions, receives adequate funding?
    Answer. A working group of the National Advisory Council (ACD) has 
been working on this vexing problem and is scheduled to report its 
recommendations at the June 14 meeting of ACD. The president of Meharry 
Medical College, Dr. Wayne Riley, is a member of this working group. As 
part of this deliberative process, outreach efforts have included many 
of the institutions represented by the Association of Minority Health 
Professions Schools (AMHPS). Meharry Medical College and the AMHPS have 
successfully competed in the past for NIH funding to support the annual 
health professions symposium, and are encouraged to continue applying 
for NIH funding. Several of the NIH Institutes and Centers have 
contributed funds to support the symposium.
    Question. The NIH has issued two strategic plans and budgets to 
reduce and eliminate health disparities since the Congress enacted the 
legislation requiring it. What is the status of the next strategic 
plan?
    Answer. The NIH Health Disparities Strategic Plan and Budget fiscal 
year 2009-2013 has been approved and is available on the NIMHD Web site 
at http://www.nimhd.nih.gov/about_ncmhd/index2.asp.
    Question. Can you provide detailed funding information for minority 
health and health disparities activities at the NIH broken out 
programmatically by Institute and Center?
    Answer. The NIH Health Disparities Strategic Plan and Budget fiscal 
year 2009-2013 provides information on programs/activities by 
Institutes and Centers with associated budgets for each goal by IC and 
is available on the NIMHD Web site at http://www.nimhd.nih.gov/
about_ncmhd/index2.asp.
                                 ______
                                 
               Questions Submitted by Senator Jerry Moran
   intersection of national cancer institute and national center for 
                    advancing translational science
    Question. We have heard Dr. Collins and others discuss the value to 
National Institutes of Health (NIH) of the newly created National 
Center for Advancing Translational Science, or (NCATS). NCATS is being 
positioned to become a resource that will support the translational 
research work across all of NIH's Institutes and Centers.
    Could you clarify how the National Cancer Institute (NCI) will work 
with NCATS to optimize the investments that will be made in NCATS and 
the knowledge that will be developed in this new center?
    Answer. Translational research supported by NCI transforms 
scientific discoveries arising from laboratory, clinical, or population 
studies into clinical applications to reduce cancer incidence, 
morbidity, and mortality--it is a critical piece of the NCI's research 
portfolio and encompasses numerous programs and funding mechanisms.
    For example, researchers working in NCI's Specialized Programs of 
Research Excellence (SPOREs) and investigator initiated Program Project 
(P01) grants at NCI-supported research institutions across the country, 
conduct promising translational research. The NCI Drug Discovery and 
Development Program, run through the Frederick National Laboratory for 
Cancer Research, has successfully guided drug candidates through the 
final steps of development to first-in-human studies. The Cancer Genome 
Atlas (TCGA) and Therapeutically Applicable Research to Generate 
Effective Treatment (TARGET) programs are generating data on the 
genomic foundations of cancer, and the Cancer Target Discovery and 
Development (CTDD) Network is accelerating the transition of molecular 
data from initiatives like TARGET and TCGA to new treatments through 
gene validation studies as well as high-throughput screening of small 
molecules.
    NCATS will complement these efforts, particularly by providing 
resources and infrastructure to assist the basic research community in 
moving their discoveries to the next phase. NCATS will work to improve 
the methodology of translational research, and will also collaborate 
with and utilize NCI programs in the process. There will be points 
where NCI and NCATS intersect to share knowledge and technology. For 
example, Clinical and Translational Science Awards (CTSA) are an 
initiative funded principally by NCATS. Most academic institutions that 
have an NCI-designated Cancer Center also have a CTSA and many 
collaborative projects have emerged from these synergies.
                        value of cancer centers
    Question. I have had the opportunity to visit a cancer center in my 
home State--The University of Kansas Cancer Center. I have seen basic 
research at work in impressive labs. In particular, at the University 
of Kansas (KU) I have seen how this research is being translated into 
the development of early phase drugs--in one case through a ground-
breaking collaboration between the University of Kansas Cancer Center, 
NIH, and the Leukemia Lymphoma Society. I believe that collaborations 
such as this that bring public and private resources and expertise 
together are important if we are to maximize the return on the 
investments of our Federal dollars. And last but definitely not least, 
I have seen patients coming to KU with the ability to participate in 
clinical trials, with the hope and real potential that the delivery of 
cutting-edge research into their care may change the course of their 
disease for the better.
    What are the programs at NCI that make this cycle of innovation and 
translation possible?
    Specifically, do you see a specific role for the Cancer Centers 
program in making sure that this cycle of translation of basic research 
findings into clinic application continues to take place?
    Answer. NCI engages in multiple collaborations along the research 
continuum, including funding a variety of innovative biotechnology 
companies via its Small Business Innovation Research program.
    The NCI's 66 Designated Cancer Centers, which are distributed in 
all regions of the United States, play a crucial role in the Nation's 
cancer research effort and are the primary source of new discoveries 
about cancer prevention, diagnosis, and treatment. The Cancer Centers 
deliver state-of-the-art care to patients and their families, inform 
healthcare professionals and the general public, and often work through 
partnerships with other healthcare organizations to reach underserved 
populations. Clinical application--providing prevention, diagnosis, and 
therapies for patients--is the ultimate goal for all cancer research, 
and NCI-designated Cancer Centers have a proud history of leadership in 
clinical trials, many of which have led to changes in the standard of 
care for cancer patients. Along with the many other NCI-funded research 
and academic institutions, and NCI's intramural program, they are a 
major source of new discoveries into cancer's causes, prevention, 
diagnosis, and treatment.
    The NCI-Designated Cancer Centers are required to facilitate the 
rapid transfer of clinical observations to laboratory experiments, and 
promising lab-based discoveries to innovative applications in the 
prevention, detection, diagnosis, treatment, and survivorship of 
cancer. The Cancer Centers are required to work together and with the 
NCI to facilitate the translation of fundamental discoveries into 
tangible patient benefit. For example, researchers at the University of 
California San Francisco Cancer Center have shown that a molecular test 
measuring the activity of 14 genes in cancerous lung tissue can improve 
the accuracy of prognosis and guide treatment options for patients with 
the most common form of lung cancer. Other recent developments include 
identification of the first major genetic mutation associated with 
inherited prostate cancer by researchers from the Johns Hopkins Cancer 
Center, with implications for the development of genetic tests to 
identify the mutation and screening practices for men with a family 
history of prostate cancer. And at the Koch Institute for Integrative 
Cancer Research at MIT, cancer researchers and engineers are working 
together to develop more effective drug delivery systems such as 
nanoparticle ``smart bombs'' that deliver high concentrations of drugs 
directly to the cancer cells, a technology currently being studied in a 
phase I clinical trial.
            update on national cancer institute initiatives
    Question. When I read stories about the development of cutting-edge 
treatments, particularly those that use the body's own immune system to 
fight cancer and other diseases, I know that we are doing something 
right to save lives and lower healthcare costs. Can you explain some of 
the most promising cancer research opportunities and discoveries that 
the NCI is currently pursuing?
    Answer. NCI supports a diverse research portfolio aimed at 
increasing our understanding of the genomic foundations of cancer, 
improving screening technologies, advancing effective treatments 
including immunotherapies, and developing new approaches for overcoming 
drug resistance.
      Genomic Foundations of Cancer.--Using genomics to match drugs to 
        the patients most likely to benefit from them, and conversely 
        sparing patients courses of treatment from which they will not 
        benefit, promises to be among the new modalities for 
        successfully managing cancer. Understanding the genomic 
        underpinnings of cancer allows for the development of 
        molecularly targeted agents that may be effective against 
        several cancer types, and can often be used in combination with 
        other therapies. NCI's Center for Cancer Genomics, with a 
        mission of developing and applying genome science to better 
        treat cancer patients, coordinates this research area across 
        the NCI.
      Screening Technologies.--Tools that can accurately detect and 
        diagnose tumors have potential to markedly improve outcomes for 
        cancer patients since these tools often detect cancer early, 
        before it has spread throughout the body and when treatment is 
        more likely to be curative. Last year, NCI released results 
        from the National Lung Screening Trial indicating that 
        screening with low-dose-computed tomography results in 20 
        percent fewer lung-cancer deaths among current and former heavy 
        smokers compared with screening with chest xray. This 
        development marks the first time that a screening test has been 
        found to reduce mortality from lung cancer, the most common 
        cause of cancer deaths in the United States and the world. 
        Other initiatives and projects, including a large portfolio of 
        grants, are pursuing biomarkers and imaging techniques with 
        potential to aid in early detection and diagnosis of several 
        types of cancers.
      Immunotherapies.--The pace of research advances to stimulate the 
        body's immune system to fight cancer has quickened in recent 
        years, with clinical trials of different therapies showing 
        positive results for several different cancer types. In 2010, 
        data from a large clinical trial established a monoclonal 
        antibody called ipilimumab as the first immunotherapeutic agent 
        to show an increase in survival for patients with advanced 
        melanoma. The drug stimulates the immune system to attack 
        melanoma cells by binding to and inhibiting a molecule called 
        CTLA-4 that is found on the surface of immune cells.
      In March 2011, the Food and Drug Administration (FDA) approved 
        the antibody (marketed as Yervoy) to treat late-stage melanoma. 
        NCI-supported research has validated CTLA-4 as a target and has 
        paved the way for studies of the drug for prostate, lung, and 
        renal cancers. Other potentially promising immunotherapy 
        approaches include ``adoptive cell transfer,'' in which T-cells 
        are taken from a patient's tumor, stimulated and reproduced, 
        then put back into the body; and the targeting of ``tumor 
        initiating cells'' (thought to be the chief cause of cancer 
        recurrences) as well as normal cells that cooperate with cancer 
        cells to help them survive and spread.
      Drug Resistance.--One of the most disappointing features of the 
        development of new targeted therapeutics is how routinely drug 
        resistance emerges and the disease begins to progress. 
        Resistance to treatment with anticancer drugs results from a 
        number of factors--every cancer expresses a different array of 
        drug-resistance genes, and various mechanisms have evolved as 
        protection from toxic agents. As therapy has become more 
        effective, acquired resistance has become common. NCI is 
        aggressively pursuing research to gain an understanding of the 
        mechanisms that lead to drug resistance and is looking for 
        agents that overcome these mechanisms. NCI is supporting 
        studies of combination therapies for patients whose disease has 
        become resistant to therapy, as well as exploring alternative 
        approaches through the Provocative Questions Initiative to 
        determine if controlling rather than killing cancer cells can 
        avoid the development of drug resistance.
    Question. Also, since NIH's work has been managed over the past few 
years with flat and decreased funding when you account for inflation, 
what innovative strategies have you found, or do you plan, that will 
allow NIH to continue making research progress in this challenging 
budgetary environment?
    Answer. NCI is employing a number of innovative strategies to 
ensure efficient stewardship of the Nation's investment in cancer 
research, particularly in the face of stagnant budgets. As mentioned at 
the recent subcommittee hearing, the Provocative Questions (PQ) project 
is one creative approach that contributes to this goal. The project is 
assembling a list of important but nonobvious questions that will 
stimulate the NCI's research communities to use laboratory, clinical, 
and population sciences in especially effective and imaginative ways. 
While this initiative does not replace the NCI's longtime and essential 
emphasis on funding investigator-initiated research, it represents a 
useful new approach to making the greatest impact with our research 
dollars. Reductions in funding tend to prompt all parts of the research 
community to become more conservative, often converging on similar 
subjects, narrowing research portfolios. By pooling the imaginations of 
the research community to address understudied areas, an initiative 
such as PQ provides a venue for innovative approaches even in times of 
fiscal constraint.
    Another area where NCI is making strategic changes is its Clinical 
Trials Cooperative Groups program. Clinical trials are a critical step 
in moving potential therapies into clinical practice, and the 
Cooperative Groups are an essential part of this process. The groups 
are now being reorganized, consolidating nine adult groups into four, 
with the Children's Oncology Group remaining a separate group. The 
consolidation is an effort to streamline the development and execution 
of trials, while continuing to select and prioritize trials through 
stringent peer review, and to fund the most promising and innovative 
studies. This process will reduce redundancy and improve the 
effectiveness and efficiency of trials; and will also result in 
simplified and better harmonized operations centers, data management 
centers, and tumor banks. The streamlined framework will also foster a 
more collaborative approach to selecting the most important trials to 
perform.
    NCI is also changing the way it conducts early phase clinical 
research. Over the last several years, NCI has developed the ability to 
do ``proof of mechanism'' studies, which allow the research community 
to understand early on whether a drug hits its target. This work 
defines patient populations that are most likely to benefit from 
targeted therapies as early in the process as possible. Continued 
progress in this area will lead to clinical research models that are 
not only more efficient, but more effective in identifying the 
appropriate treatment approach for specific patient populations. These 
are just a few examples that demonstrate NCI's strategic approaches to 
continue to make progress in a challenging budgetary environment.
    Question. The Cancer Genome Atlas (TCGA) is one of NIH's most 
prominent examples of research growing out of the HGP and is the basis 
for much of the work taking place today that explores the genomic 
foundations of cancer. Researchers are working to increase our 
understanding of the genetic basis of various forms of cancer and how 
to best capitalize on these genomic breakthroughs. Can you provide an 
update on how TCGA is proceeding and how this project is contributing 
to advancements in precision medicine?
    Answer. TCGA, a joint effort of the NCI and the National Human 
Genome Research Institute (NHGRI), is the largest and most 
comprehensive analysis of the molecular basis of cancer ever 
undertaken. Through the application of genome analysis technologies, 
including large-scale genome sequencing, TCGA is beginning to provide a 
comprehensive foundation of the abnormalities associated with the tumor 
types under study, the degree to which tumors within each type are 
similar and distinct, and the degree of overlap between tumor types. 
This foundation has the potential of improving our ability to diagnose, 
treat, and prevent cancer, providing an important element in reaching 
the goal of precision medicine.
    TCGA began as a pilot project in 2006, studying cancers of the 
lung, brain (glioblastoma) and ovary, and it has been expanded over 
time to include additional tumor types. Currently in the third year of 
its post pilot phase, TCGA has begun the comprehensive analysis of 16 
additional cancers including breast, colorectal, kidney, lung, 
endometrial and pancreatic cancers, among others. Of these projects, 
one quarter are published or in manuscript form; one quarter are in 
late-stage analysis; and the remaining one-half are still being 
collected and studied, with TCGA on track to conclude this phase in 
2014. TCGA has also initiated a small project on rare tumors, with 
plans to complete initial discovery by the end of this year.
    TCGA's efforts to advance the understanding of the molecular basis 
of cancer are already providing biological insights considered critical 
to reaching the goal of precision medicine. The work supported by NCI's 
Center for Cancer Genomics, including not only TCGA but also CTDD and 
Therapeutically Applicable Research to Generate Effective Treatments 
(TARGET), will contribute to the advancement of precision medicine.
    Question. Last year, the Journal of Oncology published an article 
entitled ``Tumor Angiogenesis as a Target for Dietary Cancer 
Prevention'' examining the suppression of tumor growth by controlling 
blood vessel growth through diet. I understand that promoting healthy 
blood vessel growth may have applications in not only fighting cancer 
but also Alzheimer's disease, arthritis, and cardiovascular disease. I 
also understand that evaluating baseline angiogeneic levels in healthy 
individuals and those with disease are critical to measuring the 
effects of diet on blood vessel development. What work is NIH 
conducting to help establish baseline angiogenic levels?
    Answer. NCI funds angiogenesis-related research that includes 
examination of cancer-related angiogenesis and exploration of therapies 
targeting this process, as well as research on diet, angiogenesis, and 
cancer prevention. Research is also underway to investigate the effect 
of moderate intensity exercise on blood vessels. Angiogenesis, and 
specifically research measuring the effects of diet on blood vessel 
development, is an area of research the NCI continues to support. NCI's 
Division of Cancer Prevention is considering hosting a workshop to 
bring together experts in angiogenesis and nutrition to explore current 
science regarding angiogenesis modification, diet, and cancer. Two 
examples of ongoing NCI research related to angiogenesis include:
  --an examination of the underlying mechanisms for the association 
        between increased physical exercise and decreased risk of 
        several types of cancer and the effects of exercise on 
        angiogenesis-related biomarkers in serum; and
  --a diagnostic imaging study examining baseline tissue angiogenic 
        markers and the outcomes of chemotherapy delivered directly to 
        liver tumors via a catheter (transarterial chemo embolization 
        therapy).

                          SUBCOMMITTEE RECESS

    Senator Harkin. Thank you all very much.
    [Whereupon, at 11:54 a.m., Wednesday, March 28, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]
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