[Senate Hearing 114-160]
[From the U.S. Government Publishing Office]






 
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2017

                              ----------                              


                        THURSDAY, APRIL 7, 2016

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:04 a.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
    Present: Senators Blunt, Moran, Cochran, Alexander, 
Cassidy, Capito, Murray, Durbin, Mikulski, Shaheen, and Schatz.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
        WALTER KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF 
            NEUROLOGICAL DISORDERS AND STROKE
        RICHARD HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        CHRISTOPHER AUSTIN, M.D., DIRECTOR, NATIONAL CENTER FOR 
            ADVANCING TRANSLATIONAL SCIENCES
        NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE


                 opening statement of senator roy blunt


    Senator Blunt. The Appropriations Subcommittee on Labor, 
Health and Human Services, Education, and Related Agencies will 
come to order.
    Thank you all for being here. Thank you, Dr. Collins, for 
bringing your team and the other institute directors you have 
with you for appearing today before the subcommittee. No 
surprise to any of you from comments I've already made that I'm 
troubled by the NIH budget request, a request that reduces 
discretionary funding for medical research by $1 billion. I 
certainly would not think that would be the way we would want 
to follow our effort last year to increase research by $2 
billion, and I'm confident, without asking you this, though I 
may ask it later, if you really want us to fulfill the request 
here, which would cut research by $1 billion.
    The increase we were able to make last year for the year 
you're working in now was really the first significant increase 
in over a decade. During that decade, based on your numbers, 
the real buying power of those research dollars had decreased 
by about 20 percent, and I'm glad we could make a step back in 
the right direction with the work that Senator Murray and I and 
the rest of the committee struggled with and produced what I 
thought was a big step in the right direction last year.
    Certainly, the budget, as it's submitted, leans heavily on 
new mandatory spending proposals that would bypass the current 
spending caps. I think instead of making difficult funding 
choices, the administration here has come up with proposals 
that are unlikely to happen. It's a risky decision. It's a 
decision that I don't support and hope that at the end of this 
process our committee will not look at what the administration 
has asked for, but look at what we would hope to be able to do.
    Mandatory spending largely has been put on autopilot when 
we go in that direction. I think it's a big obstacle to 
addressing debt issues and other issues because we just simply 
don't have to revisit it once we make it a mandatory topic.
    Short-term mandatory funding for NIH, Senator Alexander and 
I have talked about it. A surge, a focus on specific projects 
might be different than that, but anytime you create a 
mandatory cliff, it's possible to go over the cliff, and we've 
seen that happen in these areas before.
    Over the next 10 years, CBO, the Congressional Budget 
Office, estimates that mandatory spending will already increase 
from 13 percent of gross domestic product to 15 percent, and at 
the same time, they anticipate that discretionary spending will 
decrease by 1.3 percent of gross domestic product for our 
entire economy. I think that means it's even more important for 
us to be willing to put a structure together where we look at 
priorities. If everything is a priority, nothing is a priority, 
and the hard work of this committee, with really lots of talent 
on both sides of the aisle, is to figure out what we can do 
about those priorities.
    After last year's significant increase in the National 
Institutes of Health, it's time to again make research funding 
a national priority. You can't develop a pattern, at least you 
can't develop an annual pattern, if you don't do something in 
year 2, and so year 2 becomes increasingly important.
    I believe strongly in the promise of medical research and 
what that medical research does for individuals and families 
and the economy and taxpayers. It represents hope for millions 
of patients who suffer from everything from cancer to kidney 
disease, from Alzheimer's to autism. National Institutes of 
Health (NIH)-funded research has raised life expectancy and 
improved the quality of life for all Americans. It has the 
power to transform the U.S. economy in significant ways as 
well.
    By 2050, according to figures from NIH, the cost to treat 
and care for those suffering from just Alzheimer's alone is 
anticipated to be $1.1 trillion of today's dollars. Now, I 
think most of us have a hard time grasping with what $1.1 
trillion may be. You know, when you hear $10 billion or $100 
billion or $1.1 trillion, my guess is not much happens 
different in anybody's brain to distinguish the difference, but 
to put it in perspective, $1.1 trillion is twice what we 
currently spend to defend the country. So if you're putting 
your mind somewhere, every military base, every ship, every 
plane, every uniform, every paycheck for the Army, Air Force, 
Coast Guard, Marines, the Navy, the Reserves, the National 
Guard, and double all over the world, all over the world, and 
double that, that's what we would be spending on Alzheimer's in 
2050 if research doesn't produce a different way forward.
    I used this statistic in a speech this week where Senator 
Murray and I were being appreciated for what we were able to do 
here last year, and, you know, if with Alzheimer's you can 
delay onset by an average of 5 years, you would reduce that 
number by 42 percent and have great impact on the lives of 
people that would get Alzheimer's and maybe even greater impact 
on the caregivers that are so impacted by what happens with 
that. And that's just one thing. There are numbers that we 
could relate and we ask you to talk to us about on all of these 
issues, but hopefully we'll make a renewed commitment to what 
you're doing, but also we want to keep track of what you're 
doing, and I'm sure that's one of the reasons that you know 
you're here today. We'll have questions about how you're doing, 
what you're doing, and what you plan to do going forward as 
well as what is part of the budget request.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Good morning. Thank you, Dr. Collins and the other Institute 
Directors, for appearing before the Subcommittee today to discuss the 
National Institutes of Health's fiscal year 2017 budget request.
    I am deeply troubled by the National Institutes of Health's budget 
submission to reduce discretionary funding for medical research by $1 
billion. Last year, this Subcommittee made great strides to begin to 
restore the NIH's buying power with a $2 billion increase. This was the 
first significant increase for the National Institutes of Health in the 
Labor/HHS bill in over a decade. Yet the Administration's fiscal year 
2017 request destroys this step forward by proposing a budget that 
reduces annual funding for the National Institutes of Health.
    The Department of Health and Human Services submitted a budget that 
leans heavily on new, mandatory spending proposals to bypass current 
spending caps. Instead of making the difficult funding decisions 
necessary to live within the budget caps agreed to by the 
Administration less than 6 months ago, the Department decided to cut 
programs that receive bipartisan support in the hopes they would 
receive funding outside the annual appropriations process. This was a 
risky decision and one that I do not support.
    The reliance on mandatory spending to supplant discretionary 
funding contributes to exactly what is wrong with our Federal budget. 
Mandatory spending, largely put on autopilot, is the biggest obstacle 
in addressing our national debt. Over the next 10 years, the 
Congressional Budget Office estimates mandatory spending will increase 
from 13 percent of Gross Domestic Product to 15 percent. Conversely, 
discretionary spending is expected to decrease 1.3 percent over the 
next decade. The annual appropriations process allows, and forces, 
Congress to address spending levels every year. It is the responsible 
way to address funding priorities. Further, reducing discretionary 
spending only to increase mandatory spending does nothing but remove 
the accountability of the appropriations process.
    After last year's significant investment in the NIH, this is the 
time to make research funding a national priority. I strongly believe 
in the promise of medical research. It represents hope for millions of 
patients who suffer from conditions ranging from cancer to kidney 
disease. NIH-funded research has raised life expectancy and improved 
the quality of life for all Americans.
    It also has the power to transform the U.S. economy. By 2050, the 
cost to treat and care for those suffering from Alzheimer's disease is 
expected to top $1.1 trillion a year. To put this figure in 
perspective, this is twice what the Federal Government currently spends 
to defend the Nation.
    Last year's funding increase cannot and should not be a one-time 
investment. A pattern is started in a second year, and I believe we 
must seize the opportunity this year to start a pattern of sustained 
increases for the National Institutes of Health. It is time for a long-
term commitment to medical research.
    Thank you for being here today.
    Senator Blunt. And I am pleased to turn to Senator Murray, 
who she and I have had really the first year we've had a chance 
to work closely together, and it's been a significant 
partnership for me.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Well, thank you, Mr. Chairman. It's good to 
work with you as well.
    And, Dr. Collins, thank you for being here. We are so 
grateful for all you've done to champion the critical work of 
the NIH. You have been a great partner, and I really appreciate 
all of your team who is here today, and look forward to hearing 
from all of you.
    The investments that we make here in this subcommittee 
really help keep our families and our communities healthy by 
supporting programs that reduce infant mortality, train doctors 
and nurses, provide care in rural communities, prevent the 
spread of infectious diseases, and so much more. The NIH 
accounts for the largest share of our subcommittee's resources, 
and its work is vital to all these efforts. The basic research 
that it supports leads to discoveries and breakthroughs that 
give hope to those living with chronic and life-threatening 
disease and help drive economic growth and competitiveness.
    Today, the NIH is taking advantage of the achievements made 
in human genetics, neuroscience, and other fields to make major 
advances in our understanding of the human brain, and diseases 
like cancer and Alzheimer's disease. Its Precision Medicine 
Initiative is using the genetics of cancer to find effective 
therapies.
    I recently heard from a woman named Janet in my home State 
of Washington who benefited from this focus on targeted 
treatment. Although she had been in good health, was a non-
smoker, she was diagnosed with stage 3 lung cancer that quickly 
advanced to stage 4. With her treatment options exhausted, she 
learned online about a mutation testing opportunity, and that 
led to a treatment that successfully targeted her cancer 
mutation, and it saved her life. That was 3 years ago, and 
thankfully Janet's illness remains under control.
    NIH's MATCH trial is taking the testing of cancer mutations 
to a national level with the hope that many more patients will 
be helped. The Vice President's Moonshot initiative will 
accelerate these efforts, expand access to clinical trials, and 
improve data sharing, all with the goal of saving more lives.
    I'm really proud that my home State of Washington is home 
to several institutions that are on the cutting edge of this 
field. It includes the Fred Hutchinson Cancer Research Center, 
Seattle Children's Hospital, and the University of Washington, 
which are using Precision Medicine to tackle breast cancer, 
leukemia, and Alzheimer's disease, among others. Nearby, the 
Allen Institute is working with support from the NIH to map and 
unlock the secrets of the human brain. I recently visited 
there, and it is amazing.
    We are on the cusp of major breakthroughs on so many of the 
illnesses that cost lives and hurt families each day, and I 
think we should make sure that our researchers and our 
scientists have all the tools and resources they need.
    I know members on both sides of this aisle agree, so this 
is not a partisan issue. And I'm really pleased that in the 
recent budget deal, Democrats and Republicans were able to come 
together to boost discretionary investments in the NIH. That 
was really an important step forward, and I don't see any 
reason to stop there. That's why I've made very clear in my 
discussions with Chairman Alexander about legislation we're 
working on to advance medical innovation in the HELP Committee, 
that if we really want to get patients safer, more effective 
treatments and cures, we have to take advantage of every 
funding opportunity, including mandatory investments in the 
NIH. It is really a make-or-break priority.
    So I remain hopeful that we'll be able to write a 
bipartisan appropriations bill in this subcommittee for fiscal 
year 2017 and continue strong support for NIH and the many 
other critical investments in this bill.
    I'm also committed to working on a bipartisan agreement on 
our innovations package, my chairman is here on that, to build 
on the progress that we have made in the recent months with 
additional sustained funding.
    Patients and families across the country are waiting and 
hoping for better cures and treatments, and here in Congress, 
we should do our part to deliver. So I really appreciate all 
the bipartisan work on this and look forward to working with 
everyone.
    And, Mr. Chairman, thank you for holding this hearing.
    Senator Blunt. Thank you, Senator Murray.
    Dr. Collins, it's wonderful to have you here, and your 
institute directors. If you would introduce everybody at the 
table with you, I would be pleased for you to do that. And then 
I look forward to your testimony.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Thank you, Mr. Chairman. I'm happy to 
introduce my colleagues, starting to my left, your right.
    Dr. Richard Hodes is the Director of the National Institute 
on Aging.
    Dr. Walter Koroshetz, the Director of the National 
Institute of Neurological Disorders and Stroke.
    Dr. Christopher Austin, the Director of the National Center 
for Advancing Translational Sciences.
    Dr. Douglas Lowy, the Acting Director of the National 
Cancer Institute.
    And Dr. Nora Volkow, who is the Director of the National 
Institute on Drug Abuse.
    It's an honor to appear before you today. And before I 
begin, I want to thank this subcommittee for the recent $2 
billion boost in the fiscal year 2016 omnibus appropriation 
bill. That investment so energized our community and came at an 
unprecedented time of scientific opportunity, and we are truly 
grateful for your leadership.
    Furthermore, I would be remiss not to acknowledge the 
efforts of many on this subcommittee who also serve on our 
authorizing committee, which marked up important and necessary 
new authorities for biomedical research just yesterday. That 
was very much appreciated.
    So in this hearing on the last budget of this 
administration, and potentially my last opportunity to appear 
before you, I hope to reflect more broadly than usual on NIH's 
contribution to the Nation's health, so today I am going to 
break with a more cautious tradition and make some bold 
predictions, 10 areas in which I believe we can make major 
advances in the next 10 years given a sustained commitment of 
resources. So this is 10 for 10. So here we go.
    First, the long arc of scientific discovery must begin with 
basic science. Just last week, all 27 NIH institute and Center 
directors and I published a letter in the Journal of Science to 
underline how essential it is for NIH to invest vigorously in 
basic research. That's how progress happens. Experiments that 
are going on right now in labs all across this Nation contain 
the seeds of breakthrough discoveries that will transform 
medicine. We don't know which ones they are, but we know 
they're there.
    So let's fast-forward to 2026 and the first of our 10 
breakthroughs. Advances in the detailed molecular analysis of 
individual cells. Cells are the unit of life. Cells are for 
biology like atoms are for chemistry. But through most of the 
long history of medical research, we've had very limited 
technical ability to study the intricate life of single cells. 
We've had to deal with millions of cells, sometimes billions. 
That's all changing with new technologies just invented in the 
last couple of years. That's just one example.
    We can now decode the process by which individual immune 
cells attack and destroy healthy tissue in autoimmune 
disorders. We knew the immune system was involved, but now we 
can track each cell and see what it's up to, and then we can 
transform the ways we approach diseases like lupus and 
rheumatoid arthritis and many other conditions.
    On to breakthrough number two. In 10 years' time, tools 
developed through the BRAIN Initiative, which I'm sure we're 
going to talk about this morning, have identified hundreds of 
different types of brain cells, and more than that, major 
circuits that are responsible for motor function, vision, 
memory, emotion, all functioning at the speed of thought. As a 
result, we will be able to diagnose neurological conditions 
earlier and more precisely and we'll have new targets to 
explore for prevention and treatment of conditions like autism, 
traumatic brain injury, prescription drug addiction, 
schizophrenia, and Parkinson's disease.
    Number three. Aided by the BRAIN Initiative's new imaging 
techniques and discoveries made with our private sector 
collaborators, I believe we will be able in the next few years, 
Mr. Chairman, to identify individuals at high risk of 
Alzheimer's disease even before any symptoms appear, and, most 
importantly, provide them with effective therapies aimed at 
slowing or preventing the disease. Personal and family 
tragedies will be delayed or averted, and the economic savings 
from this alone with add up to hundreds of billions of dollars.
    Number four. I predict that 10 years from now, safety 
testing for newly developed drugs, as well as assessment of the 
potential toxicity of numerous environmental exposures, will be 
largely carried out using human biochips that are loaded with 
cells accurately representing heart, liver, kidney, muscle, 
brain, and other tissues. This approach, made possible by the 
dramatic development of induced pluripotent stem cells, iPS 
cells, will mostly replace animal testing for drug toxicity and 
environmental sensing, giving results that are more accurate, 
at lower cost, and with higher throughput.
    Prediction number five. Speaking of iPS cells, hope is also 
on the horizon for heart failure, a major cause of death in 
this country. Early experiments suggest that a patient's heart 
could even be rebuilt using his or her own iPS cells. This 
personalized rebuilt heart would make transplant waiting lists 
and anti-rejection drugs obsolete.
    Number six. We will see the introduction of a safe and 
effective artificial pancreas. For those with diabetes, such a 
device will continually track changes in blood glucose levels 
and provide precise doses of insulin, significantly improving 
the management of their disease and preventing countless 
complications.
    Number seven. New vaccines will be readily available. An 
effective Zika vaccine will have been developed and made widely 
available by 2018. Universal flu vaccines will protect against 
all strains of the virus, preventing that looming next 
worldwide pandemic and saving millions of lives, building on 
research just published last week. I'm also optimistic that an 
effective vaccine for HIV/AIDS will be available at last, 
giving us the opportunity to bring an end to this most 
frightening and costly global epidemic.
    Prediction number eight. Genomics, neuroscience, and 
structural biology will collaborate to unveil entirely new 
targets for the treatment of pain, allowing researchers in the 
public and private sectors to develop highly effective, non-
addictive medications for pain management. Having just attended 
and spoken at the Prescription Drug Abuse Summit last week, I 
can underline the urgency of reversing the alarming trend of 
opioid addiction in America, leading to 28,000 overdose deaths 
in 2014. We need new alternatives for pain management, and NIH 
and our partners will develop them.
    Number nine. Ten years from now, we will have developed and 
broadly applied approaches to medicine that acknowledge not all 
people are the same, thanks in large part to the Precision 
Medicine Initiative and the more than 1 million volunteers that 
will have joined this unprecedented national research cohort. 
The willingness of these participants to share a wide variety 
of their health-related information will ensure that major new 
insights emerge, and Americans from all walks of life will be 
healthier than ever 10 years from now.
    And, finally, for advance number 10, I predict that a 
decade from now, hundreds of thousands of individuals, like 
Janet in Washington, will be thriving, who, without NIH's 
research efforts, would have succumbed to cancer. Powerful new 
prevention strategies and targeted therapies will arise from 
the research described in the just published article which you 
see at your places, all of this accelerated by the Vice 
President's personal leadership of this Cancer Moonshot.
    If that sounds bold, consider what's happening right now. 
Seven months ago, President Jimmy Carter revealed that melanoma 
had spread to his brain and that he was beginning a course of 
therapy to boost his immune system's ability to destroy his 
cancer cells. All of our hearts sank to hear that news. Last 
month, President Carter announced he is cancer-free and no 
longer needs treatment.
    I could tell you a lot more stories like that of President 
Carter, but there are still millions out there waiting and 
hoping for a breakthrough to happen for them. At NIH, we seek 
to turn those hopes into reality. We are the National 
Institutes of Health, but we are also the National Institutes 
of Hope, and hope, wrote Peter Levi, in every sphere of life is 
a privilege that attaches to action. At NIH, we are all about 
action, and supported by this committee, who is also all about 
action, and your sustained efforts, we believe we can implement 
a strong, stable trajectory for NIH research, and the world can 
look forward over the coming decades to a healthier and happier 
future.
    Well, thank you, Mr. Chairman. My colleagues and I welcome 
your questions.
    [The statement follows:]
         Prepared Statement of Francis S. Collins, M.D., Ph.D.
    Good morning, Chairman Blunt, Ranking Member Murray, and 
distinguished Members of the Subcommittee. As you know, I am Francis S. 
Collins, M.D., Ph.D., and I am the Director of the National Institutes 
of Health (NIH). It is an honor to appear before you today to present 
the Administration's fiscal year 2017 budget request for the NIH, and 
provide an overview of our central role in enhancing the Nation's 
health through scientific discovery.
    Before I discuss our diverse investments in biomedical research and 
the exciting scientific opportunities on the horizon, I want to thank 
this Subcommittee for the recent $2 billion boost in the fiscal year 
2016 Omnibus Appropriation bill. This investment comes at a time of 
unprecedented scientific opportunity and we are truly grateful for your 
leadership.
    As the Nation's premier biomedical research agency, NIH's mission 
is to seek fundamental knowledge about the nature and behavior of 
living systems, and to apply that knowledge to enhance human health, 
lengthen life, and reduce illness and disability. I can report to you 
today that NIH leadership, employees, and grantees continue to believe 
passionately in our mission.
    As a Federal research agency, we are acutely aware that in order to 
achieve our mission we must be effective and efficient stewards of the 
resources we have been given by the American public. In December 2015, 
we released the NIH-Wide Strategic Plan, fiscal years 2016-2020: 
Turning Discovery into Health, an overarching, strategic plan that 
reflects the rapid progress in bioscience. This plan ensures our agency 
remains well positioned to capitalize on new opportunities for 
scientific exploration and address new challenges for human health. 
Developed after hearing from hundreds of stakeholders and scientific 
advisers, and in collaboration with leadership and staff of NIH's 
Institutes, Centers, and Offices (ICOs), the plan is designed to 
complement the ICOs' individual strategic plans that are aligned with 
their specific congressionally mandated missions.
    The plan focuses on four essential, interdependent objectives that 
will help guide NIH's priorities over the next 5 years as it pursues 
its mission and optimizes return on public investment. The objectives 
are to:
  --advance opportunities in biomedical research, from basic science to 
        prevention and treatment;
  --use all available information to set NIH priorities nimbly and 
        wisely;
  --enhance stewardship of the resources provided by the American 
        people; and
  --excel as a Federal science agency by managing for results.
    Our strategic plan concludes with a bold vision of advances we will 
strive to deliver over the next 5 years including: enhanced survival of 
cancer patients from applications of precision medicine, critical steps 
toward universal flu and HIV vaccines, and crucial progress on the 
artificial pancreas that will lead to better management of diabetes. 
NIH will pursue these and many other forward-looking measures to 
enhance our role as a visionary steward of the resources entrusted to 
us by the American people. Such actions will ensure that the U.S. 
biomedical research enterprise remains on the pathway to a bright and 
sustainable future.
    Today, I want to share with you a few of the many promising 
opportunities before us that will lead to that healthier future for 
all. First, of all, many recent breakthroughs stem from our Nation's 
commitment to investing in basic science research. Basic science lays 
the foundation for advances in disease diagnosis, treatment, and 
prevention by providing the building blocks for clinical applications. 
Basic science is generally not supported in the private sector, and 
NIH's focus on understanding fundamental biological processes not only 
has led to no less than 145 Nobel Prizes to our grantees, but fosters 
innovation and ultimately leads to effective ways to treat complex 
medical conditions.
    A compelling example of how we are trying to unravel life's 
mysteries through basic science is with the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative, which 
continues to address basic neuroscience questions. We are grateful to 
this subcommittee for its support of this initiative since its launch 
in fiscal year 2014, and we look forward to ramping this up further in 
fiscal year 2017. This bold, multi-agency effort to revolutionize our 
understanding of the human brain will enable the development and use of 
innovative technologies to produce a clearer, more dynamic picture of 
how individual cells and neural circuits interact in both time and 
space. By measuring activity at the scale of neural networks in living 
organisms, we can begin to decode sensory experience and, potentially, 
even memory, emotion, and thought. Ultimately, the technologies 
developed under the BRAIN Initiative may help reveal the underlying 
pathology in a vast array of brain disorders and provide new 
therapeutic avenues to treat, cure, and prevent neurological and 
psychiatric conditions such as Alzheimer's disease, autism, 
schizophrenia, epilepsy, traumatic brain injury, and addiction.
    Scientific advances are also accelerating progress toward a new era 
of personalized medicine. President Obama announced the Precision 
Medicine Initiative (PMI) in January 2015, and we are thrilled to have 
a lead role in this multi-agency effort. As a long-term goal of this 
Initiative, NIH is building a national research cohort of one million 
or more volunteers who will play an active role in how their genetic, 
environmental, and medical information is used for the prevention of 
illness and management of a wide array of chronic diseases. 
Capitalizing on the alignment of scientific opportunities created by 
advances in genomics, the widespread adoption of electronic health 
records, the recent revolution in mobile health technologies, and the 
emergence of computational tools for analyzing large biomedical data 
sets, precision medicine is poised to usher in a new era in how we 
treat and diagnose disease. Ramped up funding in fiscal year 2017 will 
support several activities that are critical to the scope of the PMI 
Cohort Program, including enrolling and consenting participants, core 
phenotyping, expanded informatics, building a biorepository, and 
incorporating the use of wearable sensors.. A cohort of this size will 
capture data on a wide range of diseases and be large enough to detect 
genetic and environmental effects that are difficult to discern from 
research on smaller groups. Scientists will be able to use data from 
this cohort to identify trends and understand health and disease on a 
much larger scale, and that will lead to new ideas for diagnostic 
tests, treatments, and prevention strategies.
    A final area of exceptional scientific opportunity I want to 
highlight today involves one of our Nation's most feared killers: 
cancer. During his 2016 State of the Union Address, President Obama 
announced the establishment of the National Cancer Moonshot--a bold 
initiative to tackle this often life-threatening disease. Too many 
American families know all too well the devastation cancer can bring. 
More than 1.6 million new cases of cancer will be diagnosed and cancer 
will kill an estimated 600,000 Americans in 2016. With passionate and 
principled leadership from Vice President Biden, and in partnership 
with the Food and Drug Administration (FDA) and other Federal agencies, 
NIH's National Cancer Institute (NCI) is launching a bold and promising 
cancer research initiative to accelerate research to prevent, diagnose, 
and treat cancer. In fiscal year 2017, $755 million in mandatory funds 
for new cancer-related activities are proposed at the Department of 
Health and Human Services (HHS). Within NIH, investments of $680 
million will support cutting-edge opportunities, such as prevention and 
cancer vaccine development, early cancer detection, cancer 
immunotherapy, genomic analysis of tumor cells, enhanced data sharing, 
and new approaches to pediatric cancer. Our sister agency, the FDA, 
will develop a virtual Oncology Center of Excellence to expedite the 
development of new diagnostics and therapeutics that will be safe and 
effective. We are at an inflection point in cancer research, and the 
science is ready for the concerted new effort this initiative will 
bring.
    While all of these exciting research efforts and scientific 
opportunities are leading to a much deeper understanding of health and 
human disease, much more work needs to be done.
    To this end, the President's fiscal year 2017 budget request for 
the NIH is $33.136 billion, $825 million or 2.5 percent above the 
enacted fiscal year 2016 level. This budget request reflects the 
President's and the Secretary's commitment to improving the health of 
the Nation and to maintaining our Nation's leadership in the life 
sciences. The request highlights investments in innovative research 
that will advance fundamental knowledge, and speed the development of 
new therapies, diagnostics, and preventive measures to improve public 
health, including an additional $100 million to ramp up the PMI Cohort 
Program to a total of $230 million, an increase of $45 million for the 
BRAIN Initiative, bringing the total to $195 million, and $680 million 
for the National Cancer Moonshot.
    The fiscal year 2017 budget request will enhance NIH's ability to 
support cutting-edge research and training of the scientific workforce. 
Within this budget, we will increase Research Project Grants (RPGs), 
NIH's funding mechanism for investigator-initiated research. NIH 
expects to support 36,440 total RPGs in fiscal year 2017, an increase 
of 600 above the fiscal year 2016 estimate. The budget request 
allocates resources to areas of the most extraordinary promise for 
biomedical research, while maintaining the flexibility to pursue 
unplanned scientific opportunities and address unforeseen public health 
needs.
    I have provided you with examples of how investments in biomedical 
research through NIH are advancing human health, spurring innovations 
in science and technology, stimulating economic growth, and laying the 
groundwork for the future of the United States biomedical research 
enterprise. We have never witnessed a time of greater promise for 
advances in medicine than right now. With your support, the future of 
medicine can be very bright.
    This concludes my testimony, and I look forward to answering your 
questions.
                                 ______
                                 
              Prepared Statement of Douglas R. Lowy, M.D.
    Mr. Chairman and Members of the Committee, I am pleased to present 
the President's fiscal year 2017 budget request for the National Cancer 
Institute (NCI) of the National Institutes of Health (NIH).
                          nci budget overview
    The fiscal year 2016 budget that this subcommittee approved for NCI 
reflects a genuine understanding that this is a transformational moment 
for cancer patients and cancer research, and that the era of precision 
oncology is within reach. The $70 million that you approved to fund the 
precision medicine for oncology initiative will foster a new era of 
medical practice where detailed genetic and other information about a 
patient's cancer is routinely used to deploy effective, patient-
specific remedies to treat it. Other increases for fiscal year 2016 
will allow NCI to broadly advance and successfully integrate the many 
disciplines necessary to improve outcomes for patients with all types 
of cancer.
    For fiscal year 2017, NCI is advancing a new $680 million 
initiative--known as the Cancer Moonshot Initiative--to accelerate 
progress across the entire field of cancer prevention, treatment, and 
discovery. However, in addition to the resources for the Moonshot 
initiative, NCI's $5.9 billion budget supports a range of other 
research that is essential to achieving sustained progress in cancer. 
This includes:
  --basic research, including genetics, cell biology, and cancer 
        pathogenesis;
  --translational and clinical sciences to prevent, screen, and 
        diagnose cancer, and to develop and test drugs, biomarkers, 
        imaging, diagnostics, and radiotherapies; and
  --population studies, including epidemiological, environmental, and 
        behavioral research.
    Cancer Prevention: During fiscal year 2017 and beyond, preventing 
cancer and screening for cancer will remain a central priority for NCI. 
Prevention takes many forms, such as controlling tobacco use, 
vaccinating against cancer-causing infectious agents such as human 
hepatitis B virus and human papillomaviruses, limiting exposure to 
sunlight, and limiting exposure to asbestos and other carcinogens. 
These priorities have contributed to reducing the incidence and 
mortality rates for many cancers. NCI continues to invest heavily in 
cancer screening and prevention because we know that much more progress 
is possible for those at risk of cancer.
    In parallel with our focus on prevention, NCI also will give 
increased attention to cancer health disparities--the differences in 
cancer incidence, prevalence, treatment response, and mortality among 
different population groups. Reducing and eliminating cancer health 
disparities requires a deeper understanding of the complex interplay 
among a range of factors--biological, behavioral, environmental, and 
socioeconomic--that may contribute to the unequal burden of disease.
              vice president's cancer moonshot initiative
    For fiscal year 2017, NCI will launch a bold and promising cancer 
research initiative designed to make broad advances across a range of 
exciting opportunities to prevent, diagnose, and treat cancer. The 
resources supporting this fiscal year 2017 initiative will allow NCI to 
accelerate the pace of discovery in ways that produce tangible benefits 
for patients with all types of cancer, those at risk of cancer, and the 
growing population of cancer survivors.
    The NCI budget justification identifies seven elements that form 
the core of the fiscal year 2017 initiative. These seven elements also 
can be organized into two broad themes: research on cellular analysis 
and research on novel approaches to prevent, diagnose, and treat 
cancer. In addition, some elements of the initiative contribute to both 
of these themes.
    Theme I--Cellular Analysis: Three elements of the fiscal year 2017 
NCI initiative support the cellular analysis theme.
    A. Detecting Cancer Earlier: Even small tumors shed biomarkers into 
fluids of the body, such as the blood, saliva, and urine. Recent 
advances in genomic and proteomic technologies have greatly increased 
the sensitivity of methods to detect biomarkers in fluids, which raises 
the possibility of using such methods to screen for and identify 
cancers earlier. Such minimally invasive methods have recently been 
used for assessing whether cancer has recurred in individuals who were 
previously diagnosed and treated. The exciting new opportunity, for 
which NCI will use the resources in this fiscal year 2017 initiative, 
is to now apply these methods to cancer screening. The goal is to 
detect at a very early stage a range of cancer types for which we do 
not yet have effective screening methods and to improve the detection 
of cancer types for which screening is already established practice.
    B. Research on Mutations: The resources in the fiscal year 2017 
initiative also will allow NCI to support discoveries related to 
mutations and the mechanisms of cancer. Gaining a greater understanding 
of the mutations that occur within the cancer cell, the changes that 
occur within surrounding stromal tissues, and the nature of the immune 
system's response to cancer will serve as a springboard to advance 
immunotherapy and targeted drug therapy.
    Such research also can identify mechanisms used by cancer cells to 
co-opt the vascular tissue and other parts of the micro-environment 
near the cancer. Moreover, this approach can identify what type of 
immune response is already present, but may need a boost to combat the 
cancer. Coupling this information with the clinical response to drug 
therapy and immunotherapy could greatly enhance our understanding of 
the therapeutically relevant interplay between the tumor and the many 
cell types that surround it, leading to an increased ability to improve 
patient responses to treatment.
    C. Speeding Progress on Childhood Cancers: Cancer in children poses 
unique challenges. Childhood cancers generally possess many fewer 
mutations than adult cancers and are less likely to have activation of 
enzymes known as kinases, which are the most frequent targets of cancer 
drugs for adult tumors. Furthermore, characteristic molecular changes 
that drive many childhood cancers arise in transcription factors and 
other cellular targets that are often considered ``undruggable.'' 
However, new technologies, built upon advances in chemistry that allow 
the preparation of libraries of small chemical molecules with a much 
more complex arrangement of molecular shapes, offer the promise of 
identifying inhibitors for the abnormalities found in pediatric 
cancers. The resources in NCI's fiscal year 2017 initiative will 
support research such as this to deliver advances and treatments for 
pediatric cancers.
    Theme II--Novel Approaches to Prevent, Diagnose, and Treat Cancer: 
Two elements of the fiscal year 2017 NCI initiative will advance the 
novel approaches theme.
    A. Cancer Immunotherapy and Combination Therapies: For fiscal year 
2017, NCI will provide increased support to promising research that 
employs the cells of the immune system to attack cancer. Immunotherapy 
is based on the principle that a patient's immune system, when properly 
primed, can often detect and destroy cancer cells.
    However, the challenge of immunotherapy is two-fold: first, tumors 
often effectively blunt anti-tumor immune responses, and second, the 
immune system must be successfully primed to recognize the tumor. 
Despite these challenges, during the past few years there have been 
some remarkable successes in overcoming these problems. NCI is working 
to extend these early successes in cancer immunotherapy to virtually 
all tumor types through improved understanding of the mechanisms that 
enable and limit immunotherapy.
    This element of the initiative will also support advanced research 
on combination therapies. Compared with single agent treatment, 
combinations of drugs that impair the growth and development of tumors 
along multiple molecular pathways are more likely to prevent the 
development of resistance and to produce long-lasting remissions. 
However, to benefit more patients, we urgently need to identify and 
understand the most effective combinations of targeted agents or 
targeted agents used in combination with immune-modulating molecules.
    B. Vaccines to Prevent or Treat Cancer: Vaccines against cancer-
causing infections can prevent certain cancers. The NCI research that 
led to pediatric vaccines to prevent infection with human 
papillomavirus (HPV)--and thereby prevent cervical and some other 
mucosal cancers--represents an important milestone in cancer 
prevention. The most advanced HPV vaccine prevents the infections that 
account for about 90 percent of these cancers. Cancer vaccine 
development will receive increased resources under NCI's fiscal year 
2017 initiative.
    Developing vaccines to treat early stage cancers and pre-malignant 
lesions not related to infections is another exciting opportunity that 
NCI will target with additional resources under the fiscal year 2017 
initiative. Such vaccines can target unique or signature genetic 
changes found in cancers and premalignant lesions. Candidate lesions 
include those found in patients with early prostate cancer, patients 
with premalignant lesions such as ductal carcinoma in situ (DCIS) in 
the breast, and patients with genetic abnormalities that place them at 
high risk of colorectal cancer.
    III--Important Cross-Cutting Elements: Finally, two elements of the 
NCI fiscal year 2017 initiative will broadly contribute to both of the 
themes identified above.
    A. Data Sharing to Speed Discovery and Verify Treatment Response: 
Robust data science--managing enormous sets of molecular and clinical 
data--is essential in modern cancer research. ``Big data'' is a 
critical requirement for work that ranges from cancer genomics to 
research on cell signaling and to clinical trials, using efficient 
collection, storage, retrieval, analysis, and distribution of 
information. Without robust data science and a strong informatics 
infrastructure, the pace and scope of cancer research will be limited.
    Establishing this advanced information technology capability will 
allow NCI to assemble tens of thousands of cases that have been 
carefully annotated with clinical and detailed molecular information. 
These shared bioinformatic resources will greatly increase our 
understanding of cancer and improve our ability to select the most 
appropriate treatment for patients.
    B. Exceptional Opportunities--Funding Other Promising Research: The 
Exceptional Opportunities element of the initiative will allow NCI to 
capitalize on exciting scientific opportunities by awarding research 
funding--prioritized through a competitive process--to pursue 
innovative new ideas that target intractable problems in cancer 
science. NCI will examine novel opportunities in any area of oncology 
research ripe for expansion, from basic science, through translational 
approaches, to clinical trials. NCI will support Exceptional 
Opportunities research at academic sites and through public-private 
partnerships as a means of generating breakthrough results in cancer 
science and treatment.
                            the role of ncab
    The National Cancer Advisory Board (NACB) will provide advice and 
recommendations to NCI on the Moonshot initiative. In addition, on 
April 4, 2016, NCI announced the membership of a Blue Ribbon Panel of 
scientific experts, cancer leaders, and patient advocates as a working 
group of NCAB. The panel will share their insights on the scientific 
direction and goals for all elements of the initiative and offer 
recommendations on other compelling research opportunities. This will 
allow NCI to receive broad scientific counsel about the design and 
implementation of the initiative and its research and resource 
priorities, including the Exceptional Opportunities Fund.
    We are eager to receive recommendations from NCAB and the Blue 
Ribbon Panel about the direction and emphasis for proposed research 
under the fiscal year 2017 initiative.
                               conclusion
    The NCI budget supports core, ongoing biomedical research that will 
advance scientific discovery and continue to reduce the burden of 
cancer in America. Our budget will also fund a compelling new 
initiative that offers the potential to accelerate the rate at which we 
translate discoveries into cancer clinical practice and deliver 
benefits to patients.
    Despite meaningful progress in recent years, too many Americans 
face a cancer diagnosis, and far too many die from the disease. There 
will be more than 1.6 million new cases of cancer in the United States 
during 2016, and more than 600,000 will die from cancer. As these 
statistics demonstrate, much work remains to meet the needs of those 
suffering from cancer, those at risk of cancer, and the growing 
population of cancer survivors. The fiscal year 2017 budget will allow 
NCI to advance our cancer research mission and deliver important 
results for the patients we serve.
                                 ______
                                 
            Prepared Statement of Walter J. Koroshetz, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Neurological Disorders and Stroke (NINDS) of the National 
Institutes of Health (NIH). NINDS supports research to better 
understand the brain and nervous system and to improve the diagnosis, 
treatment, and prevention of nervous system disorders. The burden of 
stroke, traumatic brain injury (TBI), dementia, chronic pain, epilepsy, 
Parkinson's disease, multiple sclerosis, and other all too familiar 
disorders of the nervous system is enormous. Hundreds of rare diseases 
add to the collective impact. The number, variety, and complexity of 
neurological disorders present formidable challenges, and the 
inaccessibility of the brain and its sensitivity to intervention 
compound the difficulty. Nonetheless, NIH research is delivering 
progress, directly and by catalyzing private sector investment. 
Moreover, with increasing recognition of commonalities among underlying 
disease mechanisms, progress against each disorder will spur advances 
against others.
                       stroke, dementia, and tbi
    The United States' age-adjusted stroke death rate fell by 77 
percent from 1969 to 2013, and NIH research is sustaining this 
trend.\1\ In 2015, the Systolic Blood Pressure Intervention Trial 
(SPRINT) showed that, for people with certain common risk factors, more 
stringent than usual blood pressure control lowered the risk of death 
from heart attack or stroke by almost a quarter, and in 2016 the 
Insulin Resistance Intervention after Stroke (IRIS) trial demonstrated 
that pioglitazone, a diabetes drug, prevents many recurring strokes in 
people with insulin resistance. Also last year, decades of public and 
private research led to the most significant advance in acute stroke 
care since NINDS clinical trials of the clot busting drug tPA showed 
that stroke is a treatable emergency. The recent results show that 
intravascular devices can remove an offending clot from a blocked brain 
artery and provide striking benefit when tPA alone does not restore 
blood flow in severe strokes. StrokeNet, a new clinical network, is 
investigating who should receive this intervention, and other stroke 
prevention and treatment trials are underway.
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    \1\ JAMA 314:1731-1739 2015.
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    The National Alzheimer's Project Act recognized the impact of not 
just Alzheimer's disease, the most common dementia, but also 
Alzheimer's disease-related dementias (ADRDs). The National Plan to 
Address Alzheimer's Disease includes research recommendations from a 
2013 NINDS-led summit on ADRDs, implementation has begun, and a follow 
up ADRD Summit in 2016 will continue to guide NIH dementia research. 
ADRD's include, for example, Lewy Body dementia, Parkinson's dementia, 
and frontotemporal dementia (FTD), which is the most common dementia in 
people younger than age 60. The most common ADRD, Vascular Cognitive 
Impairment and Dementia (VCID), like stroke, affects brain blood 
vessels. VCID is so intertwined with Alzheimer's disease that most 
elderly people with dementia have a combination of the two. The new NIH 
Molecular Mechanisms of the Vascular Etiology of Alzheimer's Disease 
(M2OVE-AD) Consortium will investigate how the brain's blood vessels 
contribute to dementias to identify new targets for treatment and 
prevention.
    The growing recognition of intersections among stroke and VCID is 
encouraging in light of the progress in preventing stroke. Although 
increases in dementia loom as our population ages, there are indeed 
hopeful signs. In the Framingham Heart Study, the rate of dementia fell 
by 44 percent from the late 1970s to the early 2010s, and age of 
dementia onset was delayed by 5 years over that period.\2\ What 
accounts for this progress is not fully understood, but converging 
evidence from the Reasons for Geographic and Racial Differences in 
Stroke (REGARDS) study, the Honolulu-Asia Aging study, the 
Atherosclerosis Risk in Communities (ARIC) study, the Northern 
Manhattan study, and other research suggests that controlling blood 
pressure reduces risk for cognitive decline in later life. A new public 
health campaign ``Mind Your Risks'' promotes controlling blood pressure 
for maintaining a healthy brain.
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    \2\ New England Journal of Medicine 374:523-32, 2016.
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    Nearly a century ago, physicians recognized another type of 
dementia, called dementia pugilistica, in boxers. In the modern era, 
neuropathologists are detecting this disorder, now called chronic 
traumatic encephalopathy (CTE), in autopsied brains of professional 
(and a few younger, amateur) athletes from contact sports. This has 
heightened the urgency of understanding the long-term consequences of 
mild TBI, or concussion, for the millions of people who have been 
exposed through sports, military service, or the risks of daily life. 
Despite decades of NIH research, including laboratory studies, brain 
imaging, and helmet impact monitoring in college athletes, many aspects 
of concussion are poorly understood. To augment ongoing research, NINDS 
and the Foundation for NIH's Sports and Health Research Program, which 
was launched with a donation from the National Football League, 
established two multi-institution research consortia on CTE. In 2015, 
these neuropathologists took a major step forward by developing 
criteria that identify CTE and reliably distinguish it from other 
diseases in autopsied brain tissue. Studies applying these criteria on 
brains donated to brain banks for neurological disorders are 
reinforcing the concern that these long-term consequences of TBI may be 
more common than previously thought. The CTE consortia and a multi-site 
longitudinal study funded by NINDS in 2015 are addressing a major 
impediment to progress by testing brain imaging methods to diagnose CTE 
reliably in living people. A brain protein called tau, which 
accumulates abnormally in the brain in CTE, is the focus of a promising 
imaging method. Tau is also implicated in Alzheimer's and other 
neurodegenerative disorders, reflecting the wider theme that abnormal 
protein degradation, accumulation, and propagation are involved in many 
brain diseases.
                 brain connections and brain disorders
    Stroke and TBI are also among the many causes of the epilepsies, 
which are characterized by abnormal brain activity that causes 
seizures, and epilepsy-like brain activity may occur in Alzheimer's 
disease. The epilepsies have many different causes. Hundreds of gene 
mutations cause epilepsy, including many identified by the NINDS Center 
without Walls (CWOW) on epilepsy genetics. Anti-seizure drugs, 
including ten that the NINDS Anticonvulsant Screening Program helped 
develop, can treat epilepsy. However, all epilepsy drugs have 
troublesome side effects, no existing drugmodifies the underlying 
disease, and a third of people who have epilepsy do not respond well to 
any drug. A new CWOW will develop strategies to prevent epilepsy or to 
modify the disease process, rather than suppressing seizures.
    Some diseases, like autism and epilepsy, are fundamentally 
disorders of brain cell activity and circuitry, and others, such as 
TBI, stroke, Parkinson's, and Alzheimer's disease, disrupt brain 
circuits as nerve cells or their connections are compromised. Despite 
our limited understanding of brain circuits and the imprecise 
technologies for altering brain cell activity in people, interventions 
that compensate for malfunctioning brain circuits produce remarkable 
results. Deep brain stimulation (DBS) dramatically reverses some 
symptoms for many people with essential tremor, Parkinson's disease, 
and dystonia, and shows promise for epilepsy, Tourette syndrome, and 
several other disorders. Decades ago the NINDS Neural Interfaces 
Program led development of cochlear implants, which restore useful 
hearing to thousands of people by translating sound into electrical 
signals that brain circuits can interpret. More recently, that program 
pioneered devices that allow paralyzed people to control a robotic arm 
by commands directly monitored from their brains' movement control 
circuits.
    Better understanding of brain circuits and more precise means to 
control them would greatly improve these interventions and likely 
reveal unforeseen therapeutic strategies. Basic neuroscience research 
has made remarkable discoveries at the molecular level about how brain 
cells and synapses operate. And brain imaging, such as The Human 
Connectome Project, has driven advances in understanding how areas of 
the normal brain work together. Until recently, however, researchers 
have had limited tools to map the intricate synapse by synapse 
structure of brain circuits or to monitor or control the activity of 
the large numbers of nerve cells in a working brain circuit. New 
methods are essential to understand precisely how brain circuit 
dysfunction underlies brain diseases. The Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative is providing 
scientists with tools that are transforming understanding of how 
circuits work. Researchers have already, for example, turned on and off 
specific memories in laboratory animals, and found important clues to 
what goes wrong in movement control circuits in Parkinson's disease. 
Public-private partnerships have been facilitated to develop and test 
cutting edge stimulation and recording technologies for patients with 
epilepsy and Parkinson's disease.
                                 people
    NINDS carries out its mission within an ecosystem that includes the 
public, nongovernmental organizations, for profit companies, and the 
academic research community. NINDS engages all stakeholders in 
strategic planning and planning for specific diseases and issues, 
including heath disparities and workforce diversity. NINDS also works 
closely with other parts of NIH and with other Federal agencies. The 
Federal Interagency TBI Research Informatics System (FITBIR) and the 
Center for Neuroscience and Regenerative Medicine (CNRM), for example, 
are among the many ways NIH and the Department of Defense cooperate on 
TBI. NINDS relies heavily on investigator-initiated research, which 
harnesses the insight and ingenuity of the U.S. research community, 
because of its track record of stimulating breakthroughs. When gaps are 
compelling, NINDS targets resources to unmet mission-critical 
scientific opportunities and public health needs. Among the many 
examples are the NeuroNext clinical network, which carries out early 
phase clinical trials of therapies from the academic or private sector, 
and centers or consortia in epilepsy, Parkinson's disease, autism, 
muscular dystrophy, and TBI. Policies and resources, such as brain 
banks, data centers, and gene and tissue repositories, enhance the 
research possible for individual researchers and promote sharing. To 
maximize research value, NINDS is among the leaders in advocating 
transparency of reporting and reproducibility of research, engaging 
researchers, peer reviewers, journal editors, trainees, and NIH staff.
    Because the private sector is often reluctant to tackle 
neurological disorders, NINDS supports preclinical therapy development. 
These programs have recently, for example, developed candidate drugs, 
gene therapy, or biologics for ALS, muscular dystrophy, brain tumor, 
and stroke to readiness for clinical testing. From its inception, NINDS 
has played an indispensable role in rare disease research. Programs now 
bring academic disease experts together with drug development resources 
and knowhow. A current project, for example, is developing drugs for 
familial dysautonomia. It reflects a 23-year journey that identified 
the genetic cause, developed a screen for at-risk populations, 
engineered a mouse model, and screened for drugs that reverse symptoms 
in mice. The first drug for this disease is now in clinical trials. As 
the first therapies for several rare disorders are moving to clinical 
testing, NINDS is promoting clinical trials readiness, and NeuroNext is 
poised to expedite early phase trials.
    Physicians and scientists in the public and private sector agree 
that basic research is essential for progress against neurological 
disorders, but without government support, basic neuroscience would 
scarcely exist. Some shift toward more applied research is appropriate 
given the remarkable opportunities arising from basic research. 
However, an extensive NINDS analysis revealed a decline over several 
years in the number of grant applications for fundamental research on 
the healthy brain. The Institute is holding the line against that 
trend, including targeted support with set-aside funds. The BRAIN 
Initiative reinforces NINDS emphasis on basic research and innovation. 
In fiscal year 2016, NINDS also launched the Research Program Award 
(RPA) to spur innovation, especially in basic research. The RPA 
application, review criteria, and award duration accentuate the 
investigators' promise and the long term significance of the proposed 
research program, rather than the details of proposed experiments.
    Finally, NINDS must recruit and develop the best scientists and 
physicians from the full breadth of the Nation's talent pool. NINDS 
supports an array of training and career development opportunities to 
attract a vibrant and diverse scientific workforce. The inherent allure 
of understanding the brain attracts many of the brightest students, as 
do the prospects for progress against neurological disorders, which 
have never been so encouraging. Whether people will embark on training 
for scientific careers depends on their perception of the Nation's 
commitment to supporting research in the future.
                                 ______
                                 
              Prepared Statement of Richard J. Hodes, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute on Aging (NIA) of the National Institutes of Health (NIH).
    Census data indicate that the number of Americans ages 65 and 
older, currently estimated at over 43 million strong, will likely 
double by 2040. Because aging remains the single most important risk 
factor for most chronic diseases and degenerative conditions in adults, 
it is imperative that we pursue a comprehensive national effort to 
understand aging and to develop interventions that will help older 
adults enjoy robust health and independence, enabling active engagement 
with their families and communities.
    NIA leads this effort in support genetic, biological, clinical, 
behavioral, and social research related to the aging process, healthy 
aging, and diseases and conditions that increase with age. We also 
support training of the next generation of researchers. In addition, we 
are the lead Federal agency supporting research on Alzheimer's disease 
(AD).
                    research on alzheimer's disease
    Data from several recent studies suggest that the rate of dementia, 
including AD, is actually decreasing. For example, researchers with the 
long-running Framingham Heart Study found that there was a progressive 
decline in incidence of dementia at a given age, with an average 
reduction of 20 percent per decade since the 1970s. The decline was 
more pronounced with a subtype of dementia caused by vascular diseases, 
such as stroke, and was observed only in persons with high school 
education and above. These results are consistent with findings from 
other recent studies in the United States and Canada, and it is our 
hope that as we identify factors that contribute to this unprecedented 
decline, we will also identify potential preventive strategies or even 
clarify the disease process itself.
    Despite this promising trend, however, it is estimated that as many 
as 5.2 million Americans currently have the most common form of 
dementia--Alzheimer's disease. Scientists agree that unless the disease 
can be effectively treated or prevented, the numbers of people affected 
will increase significantly if current population trends continue. And 
in addition to the severe medical and psychological costs to patients 
and their families, AD and related forms of dementia impose significant 
societal and individual economic costs. One recent NIA-funded study 
found in the last 5 years of life, total healthcare spending for people 
with dementia was more than a quarter-million dollars per person, some 
57 percent greater than costs associated with death from other 
diseases, including cancer and heart disease.
    As the Federal lead on Goal 1 of the National Action Plan to 
Address Alzheimer's Disease--Prevent and Effectively Treat Alzheimer's 
Disease by 2025--NIA continues to move forward on a number of fronts, 
informed by input from researchers and advocates worldwide from the 
February 2015 Alzheimer's Disease Research Summit, the 2013 Summit on 
Alzheimer's-Related Dementias, and other key scientific conferences and 
emerging research findings. Additional funds directed to Alzheimer's in 
recent years are being used to accelerate research identifying new risk 
and protective genes; development of new cellular models of the disease 
to enable rapid screens of hundreds of thousands of molecules for 
potential as therapeutic agents; establishment of translational centers 
that will develop and apply cutting-edge approaches to drug 
development; population studies of trends in the incidence and 
prevalence of dementia; development of novel interventions to support 
dementia caregivers; and trials of therapies in people at the highest 
risk of disease.
    Other researchers are repurposing existing compounds for use in AD. 
For example, investigators funded by NIA and the National Center for 
Advancing Translational Sciences found that AZD0530, a compound that 
has been used experimentally to treat some solid tumors, reversed 
memory loss and pathology characteristic of AD in a mouse model and is 
a promising candidate to test in humans with the disease.
    Notably, in September/October 2015, NIA released a series of 10 
Program Announcements (PAs) soliciting funding applications across the 
spectrum of AD research. These requests for applications offer 
opportunities for investigators in virtually every aspect of AD 
research--from basic biological studies to epidemiology to caregiving 
to clinical trials. The initial response to these PAs was extremely 
robust, and initial awards are anticipated for late fiscal year 2016.
    Alzheimer's is also a primary focus of NIH's Accelerating Medicines 
Partnership (AMP), a joint public-private partnership to transform the 
current model for developing new diagnostics and treatments by jointly 
identifying and validating promising biological targets of disease. In 
March 2015, AMP-AD launched its Alzheimer's Big Data Portal and 
concomitantly released the first wave of data through this new 
resource, facilitating sharing and analyses of large and complex 
biomedical datasets. This approach will enable the development of 
predictive models of AD and the selection of novel targets that drive 
the changes in molecular networks leading to the clinical signs and 
symptoms of the disease.
    NIH's plans, priorities, and recent accomplishments for Alzheimer's 
research are presented in our first Bypass Budget for Alzheimer's 
Disease and Related Dementias, in response to a Congressional 
directive.\3\ This comprehensive professional judgment proposal for 
fiscal year 2017, which was developed without taking into account the 
full range of resource constraints and competing priorities that the 
President's Budget must consider, was released in July 2015 and will be 
updated annually, informed by expert input from several key sources.
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    \3\ Https://www.nia.nih.gov/alzheimers/bypass-budget-fy2017.
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                       advances in aging research
    NIH supports research aimed at improving our understanding of the 
changes seen with aging at the physical, cognitive, behavioral, and 
social levels, as well as development of interventions to prevent or 
ameliorate age-related disease and dysfunction. For example, NIA-
supported investigators recently found that naturally-occurring 
senescent cells that accumulate in the body shorten lifespan in mice, 
and that removing those cells delays age-related organ dysfunction. 
This finding aligns with previous research and provides additional 
support for the hypothesis that removal of senescent cells may be an 
effective approach to extending healthy lifespan.
    NIA coordinates the NIH GeroScience Interest Group (GSIG), which 
was established in 2012 to accelerate and coordinate efforts to promote 
further discoveries on the mechanisms that link aging biology to the 
etiology of multiple chronic diseases and conditions, by developing a 
collaborative framework that includes multiple NIH Institutes. In 
October 2013, the GSIG and several private-sector partners convened a 
national Summit entitled ``Advances in Geroscience: Impact on 
Healthspan and Chronic Disease.'' This meeting drew over 500 expert 
participants from around the world and led to the publication of a 
position paper in Cell, one of the world's leading journals on basic 
research, in 2014. A second Geroscience Summit is planned for April 
2016 in collaboration with the New York Academy of Sciences and others.
    NIA also continues to support its flagship studies on aging. As it 
approaches its sixtieth anniversary, the groundbreaking Baltimore 
Longitudinal Study of Aging (BLSA) continues its work toward 
identifying the longitudinal physical and cognitive changes that define 
aging; identifying the factors that affect the rate of age-related 
change; and understanding the relationship between aging and chronic 
disease. BLSA investigators are particularly interested in 
``exceptional agers''--those rare individuals who live well into their 
eighties with few health problems. In addition, this year the Health 
and Retirement Study (HRS) will complete 25 years of data collection 
and will implement several enhancements: addition of respondents 
representing the ``Late Baby Boom'' born 1960-1965; deployment of an 
improved approach to assessing cognitive impairment and dementia; and 
expansion of collection of objective health measures, including blood-
based assays capturing the aging of the immune system and related 
molecular and cellular age-related changes. This and other future work 
also has the potential to reveal the biological pathways through which 
differences between social and demographic groups affect health.
    NIA-supported investigators are looking at better ways to translate 
what we know into clinical practice that will help improve the health 
and well-being of older Americans. For example, a recent clinical trial 
identified several interventions directed at primary care clinicians 
that reduced the number of inappropriate prescriptions for antibiotics 
for acute viral respiratory tract conditions, an important cause of 
population-level antibiotic resistance. These interventions--which 
involved prompting a clinician to record a justification for 
prescribing antibiotics or comparing the clinician's performance to 
others in their region--may be useful tools to improve quality of care.
    In another recent study, the Systolic Blood Pressure Intervention 
Trial (SPRINT), reducing systolic blood pressure to less than 120 mm 
Hg, as compared with less than the current standard target of 140 mm 
Hg, resulted in lower rates of major cardiovascular events and death 
from any cause among patients at high risk for cardiovascular events 
but without diabetes. Of particular note is the age of the SPRINT 
participants: all were over 50, and 28 percent were over 75. SPRINT was 
supported by NIA and several other NIH Institutes.
    Serious injuries from falls, such as broken bones or traumatic 
brain injury, are a major reason for the loss of independence among 
older people. In 2014, the NIA partnered with the Patient-Centered 
Outcomes Research Institute (PCORI) to support a large, multi-center 
clinical trial to test individually tailored interventions to prevent 
fall-related injuries. The study, which is scheduled to conclude in 
2019, is ongoing and involves the NIA-funded Claude D. Pepper Older 
Americans Independence Centers.
    Finally, NIA has continued to grow its award-winning Go4Life 
exercise and physical activity campaign. This effort centers on an 
interactive website, which features an evidence-based exercise guide in 
both English and Spanish, exercise videos, ``virtual'' coaches, and 
more. Over 350 partners at both the local and national levels use these 
resources in their community activities with seniors. September 2015 
was designated national Go4Life Month. Partners sponsored over 600 
activities in communities across the United States, culminating in a 
Capitol Walk in Washington, D.C., in which a corps of older adults 
joined Dr. Hodes, U.S. Surgeon General VADM Vivek H. Murthy, M.D., 
M.B.A., fitness expert Donna Richardson, and leaders from a number of 
agencies and organizations for a walk around the National Mall.
              empowering the next generation of scientists
    As the number of older Americans continues to grow, we must not 
only increase the number of practicing physicians trained in geriatrics 
and relevant subspecialties but also foster the development of the next 
generation of scientists whose research will lead to improved care and 
more effective treatment for older patients with complex medical 
conditions. To encourage emerging scientists, NIA supports an advantage 
in pay line for new and early-stage investigators. The Paul Beeson 
Career Development Awards in Aging Research program, sponsored by the 
NIA, the National Institute of Neurological Disorders and Stroke, and 
private partners, continues to produce leaders in the fields of aging 
and geriatrics research. A recent Funding Opportunity Announcement 
solicited applications for new training programs for joint M.D.-Ph.D.s 
in the social sciences relevant to aging. Finally, the Butler-Williams 
Scholars Program (formerly the NIA Summer Institute) remains a vibrant 
and vital institution at NIA.
                                 ______
                                 
           Prepared Statement of Christopher P. Austin, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National Center 
for Advancing Translational Sciences (NCATS) of the National Institutes 
of Health (NIH).
                              translation
    NCATS defines translation as the process of turning observations in 
the laboratory, clinic and community into interventions that improve 
the health of individuals and the public--from diagnostics and 
therapeutics to medical procedures and behavioral changes. An 
overarching need to translate research discoveries more efficiently and 
effectively led to the creation of NCATS. NCATS is advancing the 
relatively new field of translational science, through which 
investigators seek to understand the scientific and operational 
principles underlying each step of the translational process. These 
efforts serve as a basis for system-wide improvements in translational 
efficiency and effectiveness to ultimately get more treatments to more 
patients more quickly.
    Following are examples of NCATS programs directed at overcoming 
major scientific and operational bottlenecks in the translational 
research process.
      transforming the nation's clinical research network capacity
    NIH's Institutes, Centers and Offices have a long, distinguished 
history of funding landmark clinical trials including those for 
coronary bypass surgery, treatments for breast cancer, and anti-
retroviral drugs for people at high risk for HIV/AIDS infection. NCATS 
is addressing issues common to all clinical trials including approval 
and oversight of research protocols and timely participant recruitment, 
which have often resulted in high cost burdens for studies and frequent 
delays in implementation. These problems have led some investigators 
and companies to conduct their research outside of the United States, 
and this threatens our Nation's innovative capacity and 
competitiveness, reduces economic opportunities, and deprives patients 
of the option to participate in research. In addition, when clinical 
investigators set up a clinical trial, they often create agreements and 
processes from scratch and abandon those tools at the end of the study, 
rather than making use of the existing structure and agreements for any 
future studies.
    To address these pitfalls and inefficiencies, through its Clinical 
and Translational Science Award (CTSA) Program, NCATS has launched 
several initiatives designed to work together to strengthen and 
streamline our Nation's network capacity to conduct clinical research. 
There are more than 50 CTSA Program medical research institutions 
across the country that serve as clinical and translational research 
hubs. Hub investigators collaborate to support high-quality clinical 
and translational research locally, regionally and nationally, 
fostering innovation in training, patient involvement and new 
methodologies.
    NCATS is expanding the networking capacity of the CTSA Program with 
the addition of Trial Innovation Centers (TICs) and Recruitment 
Innovation Centers (RICs) that address key roadblocks to high-quality, 
harmonized, accelerated, efficient and effective multisite clinical 
trials. Through TICs, investigators will explore innovative approaches 
in streamlining trial implementation and disseminate best practices. 
RICs are intended to improve participant recruitment into clinical 
trials by using innovative means to assess the availability of 
potential participants and to enroll them in a timely manner. NCATS 
will make TIC and RIC awards later in fiscal year 2016. When fully 
implemented, these centers will be crucial resources for NCATS' CTSA 
Program clinical trial innovation network. By making the clinical trial 
network available to any investigator or organization wishing to 
conduct a clinical trial, the CTSA Program will benefit all clinical 
research, including that of other NIH Institutes and Centers (ICs), as 
well as other government, industry, academic, and patient advocacy 
group sponsors.
        innovation to advance pre-clinical translational science
    Too often, the laboratory tests that scientists conduct during the 
pre-clinical phases of the translational process--research on a drug or 
other intervention conducted prior to testing in humans--fails to 
predict the safety and effectiveness of a treatment in humans. NCATS is 
studying, and developing solutions to overcome, the scientific and 
operational roadblocks in this part of the translational research 
spectrum as well.
    An example is the Tissue Chip for Drug Screening program, which 
supports the creation of bioengineered devices to improve the process 
of predicting whether drugs will be safe and effective in humans. NCATS 
collaborates with the Defense Advanced Research Projects Agency (DARPA) 
and FDA to support the development of these three dimensional (3-D) 
platforms, sometimes called tissue chips or organs-on-chips, engineered 
to mimic the structure and function of living human tissues. Since the 
program's inception in 2012, scientists have developed more than 10 
different types of individual organ chips. The program is now focused 
on integration of organ chips, making it possible to model the 
complexity of organ-to-organ interactions in response to drugs. One 
such success was the creation of EVATARTM, a miniaturized 3-D 
representation of the female reproductive tract and liver on a 
handheld, interconnected platform. This advance required a team effort 
of scientists from Northwestern University, Charles Stark Draper 
Laboratory and the University of Illinois at Chicago (UIC) 
collaborating to design the model for use in drug testing and to study 
the basic biology of female reproduction. The current success of the 
Tissue Chip is indicating future directions for the NCATS program, with 
some investigators already using the technology to develop disease 
models on chips to both understand the basis for diseases and identify 
treatments for them.
    In a complementary program, NCATS is developing 3-D bioprinted 
human tissues to be used in the earliest stages of drug discovery. This 
initiative has the potential to accelerate the drug discovery process, 
enabling treatments to be developed faster and at a lower cost by 
bridging the predictability gap between the lab test and the test in 
humans. The manufacturing technique used to build live tissue 
structures results in a product that mimics natural live tissue. Live 
cells are harvested and dispensed into spatially-controlled patterns, 
layer-by-layer, to generate 3-D arrangements. These structures undergo 
further biological treatment until they form tissue-like structures. 
The ability to develop 3-D tissue structures on demand will enable the 
generation of data that are more relevant to the whole body response 
than traditional means, which use two-dimensional, single-layer cell 
cultures grown on plastic plates.
    Of all translational tools, the most enabling is information, so 
NCATS also is developing a variety of informatics resources to collate 
and disseminate data that will help advance translational research. For 
example, using the flexible funding mechanisms available through NCATS' 
Cures Acceleration Network (CAN), NCATS is developing a breakthrough 
translational informatics ``matrix'' that will incorporate data about 
all diseases, including signs, symptoms, signaling pathways, genes and 
treatments. This effort will help empower the generation of new disease 
hypotheses and connections, as well as testable predictions of 
potential treatments. This is an unprecedented assembly of disparate 
data types into a multi-dimensional relational informatics platform and 
will be usable by doctors, researchers and non-experts. As such, it 
will require extensive and complex teamwork among the scientific, 
healthcare and patient communities, and we anticipate the need to use 
our CAN Other Transactions Authority. We expect the NCATS' matrix 
project to spur innovation in methods, techniques, prevention and 
treatments, and to help move from the ``one disease at a time, one 
organ at a time'' therapeutic model toward a far more efficient 
approach of studying diseases and potential interventions, including 
generating new hypotheses that could be tested across related diseases.
                               conclusion
    These projects are just a few examples of the exciting activities 
planned or already underway at NCATS. Though NCATS is still relatively 
new, we operate following the NCATS 3Ds: developing new approaches, 
technologies, resources, and models; demonstrating their usefulness; 
and disseminating the data, analysis and methodologies to the 
community. Our early successes demonstrate how this approach can help 
solve some of the most challenging problems in translational science. I 
look forward to sharing more of our achievements with you as NCATS 
continues to evolve.
                                 ______
                                 
              Prepared Statement of Dr. Nora Volkow, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute on Drug Abuse (NIDA) of the National Institutes of Health 
(NIH).
               drug use and addiction research priorities
    As a part of NIH, the Nation's premier biomedical research agency, 
NIDA's mission is to advance science on the causes and consequences of 
drug use and addiction and to apply that knowledge to improve 
individual and public health. Over the last four decades, NIDA-
supported research has revolutionized our understanding of drug use and 
addiction, transforming our understanding of the biological, social, 
and environmental factors that contribute to substance use disorders 
(SUD), and driving the development of improved strategies to prevent 
and treat SUDs.
    Drug use and addiction represent major public health challenges in 
our Nation. In 2014 alone, over 47,000 Americans died as a result of an 
unintentional drug overdose, and the past few years have seen rapid 
increases in babies born with neonatal abstinence syndrome (NAS), an 
unprecedented local outbreak of HIV, an increasing prevalence of 
hepatitis C (HCV), and new synthetic drugs flooding the market. Despite 
these challenges, this is a time of great opportunities for addiction 
research. The last few years have seen tremendous advances in 
technologies with research applications--from gene sequencing and 
manipulation, to higher resolution brain imaging technologies, to 
mobile health tools and electronic health records. In 2015, NIDA 
released an updated strategic plan focused on leveraging these recent 
scientific and technological advances to re-envision what research can 
accomplish over the next 5 years.
    The NIDA Strategic Plan for 2016-2020 outlines our broad goals 
across basic science, prevention, treatment, and public health and 
identifies four priority focus areas that we believe present unique 
opportunities to be leveraged over the next 5 years including: \4\
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plan.
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    1.  Understanding the complex interactions of biological, 
        behavioral, and environmental factors influencing drug use 
        trajectories. Capitalizing on emerging technologies and 
        discoveries to facilitate integration and analysis of diverse 
        data sources, including genomic, behavioral, neurobiological, 
        environmental, and other data associated with drug use and 
        addiction.
    2.  Accelerating the development of treatments for SUDs. 
        Translating basic knowledge of the molecular pathways and brain 
        circuits involved in SUDs to develop new therapeutics for SUDs 
        and leveraging existing safety profiles and pharmacology data 
        to lower development costs and shorten the timeline for 
        obtaining FDA approval.
    3.  Addressing real-world complexities including comorbidities and 
        poly-drug use. Conducting research to better understand the 
        barriers to successful and sustainable implementation of 
        evidence-based practices and developing implementation 
        strategies that effectively overcome these barriers to ensure 
        that all populations benefit from the Nation's investments in 
        scientific discoveries.
    4.  Advancing bi-directional translation from basic to clinical and 
        applied research. Fostering stronger collaborations across 
        basic and clinical researchers to integrate and coordinate 
        human and animal research on addiction across the trajectory 
        from initiation to recovery.
                      current research highlights
    Within the strategic priorities discussed above, NIDA research is 
addressing ongoing national public health priorities including the 
epidemic of opioid overdoses, the impact of adolescent drug use on 
brain development, and the impact of tobacco use on health.
    Addressing the Opioid Overdose Epidemic.--In 2015, both President 
Obama and the Secretary of the Department of Health and Human Services 
launched initiatives to address the complex problem of prescription 
opioid and heroin abuse in this country. Both initiatives are focused 
on improving opioid prescribing practices, expanding dissemination of 
the opioid overdose reversal drug naloxone, and increasing access to 
medication assisted treatment (MAT) to treat opioid use disorders. 
NIDA-supported research contributes to both opioid initiatives through 
support for research on alternative treatments for pain with reduced 
potential for abuse; treatment of opioid use disorder; and development 
of lay-friendly naloxone formulations.
    Development of alternative pain treatments with reduced abuse 
potential. While many strategies are currently being utilized to 
reverse the opioid overdose epidemic, there remains a pressing need to 
develop more effective treatments for chronic pain with reduced abuse 
potential. NIDA, in partnership with the NIH Pain Consortium, funds 
research to foster development of new pain treatments with reduced 
potential for abuse. Funded grants range from neurobiology, genetics/
epigenetics, and molecular biology research that drives early stage 
drug target discovery, to therapeutics development including 
preclinical safety and efficacy testing and early phase human trials, 
to health services research. For example, NIDA research is supporting:
  --Testing of new compounds that exhibit novel properties as a result 
        of their combined activity on two different opioid receptors 
        (i.e., mu and delta). Preclinical animal studies show that 
        these compounds can induce strong analgesia without producing 
        tolerance or dependence.
  --Development of new non-opioid medications for severe pain including 
        compounds that work through the endocannabinoid system and 
        others that modulate members of the transient receptor 
        potential (TRP) ion channel family.
  --Exploration of combinatorial approaches that utilize both opioid 
        and non-opioid systems to minimize the dose of opioids needed 
        for pain control.
  --Development of non-pharmacological strategies for pain treatment 
        including transcranial magnetic and direct current stimulation 
        of the brain, electrical deep brain stimulation, peripheral 
        nerve stimulation, stem cell transplants, and integrative 
        health approaches that consider the biopsychosocial nature of 
        pain.
    Improving Treatment of Opioid Use Disorders.--An estimated 1.9 
million people in the United States suffered from SUDs related to 
prescription opioid pain medicines in 2014, and 586,000 suffered from a 
heroin use disorder. Despite the availability of evidence-based 
pharmacotherapies for opioid use disorders, including methadone, 
buprenorphine, and extended-release naltrexone, we have a significant 
and ongoing treatment gap in our Nation with more than a million 
persons unable to access care and less than 40 percent of those being 
treated for opioid addiction receiving these medications. NIDA supports 
a broad portfolio of research to improve treatments for opioid use 
disorders (OUDs) ranging from basic research to identify novel targets 
for new therapeutics to preclinical and early clinical trials of new or 
improved therapeutics; to implementation science to improve the 
dissemination and effective use of evidence based practices.
    For example, NIDA research supported the development of a 
buprenorphine implant (Probuphine), a novel formulation that provides 
stable round-the-clock dosing for 6 months. Buprenorphine is one of 
three FDA approved medications that has been shown to be a safe and 
highly effective treatment for opioid addiction. This new formulation 
delivers a steady dose of buprenorphine for 6 months, an innovation 
that improves the efficacy and acceptance of buprenorphine maintenance 
treatment by: 1) removing the need to take a daily pill, promoting 
continuous patient adherence; 2) preventing diversion of the drug; and 
3) eliminating the risk of accidental ingestion by children. FDA 
accepted a resubmission of the Probuphine New Drug Application (NDA) 
that includes results from a Phase III double-blind clinical study in 
September of 2015. Agency action is expected by May 27, 2016.
    Development of Lay-Friendly Formulations of Naloxone.--The opioid 
overdose-reversal drug naloxone can rapidly restore normal respiration 
to a person who has stopped breathing as a result of overdose from 
heroin or prescription opioids. Naloxone is widely used by emergency 
medical personnel and some first responders and a growing number of 
communities have established overdose education and naloxone 
distribution programs that issue naloxone directly to opioid users and 
potential bystanders. As of 2014, more than 152,000 naloxone kits had 
been distributed to laypersons, and more than 26,000 overdoses had been 
reversed since 1996.
    In late 2015, FDA approved a user-friendly intranasal formulation 
that was developed through a NIDA partnership with Lightlake 
Therapeutics, Inc. (a partner of Adapt Pharma Limited). This 
formulation can easily be used by potential bystanders (laypeople) and 
is an important advance beyond the improvised nasal devices (consisting 
of a syringe of injectable naloxone attached to an atomizer) that have 
been used in recent years.
    NIDA also continues to support implementation science to develop 
strategies to improve the dissemination and sustainable implementation 
of naloxone distribution programs; to increase co-prescribing of 
naloxone to patients receiving opioid medications; to test strategies 
for teaching high risk individuals strategies for managing overdose and 
mitigating risk; and to test the efficacy of pharmacy based naloxone 
access polices.
    Basic Research on Brain Development and Drug Use Trajectories.--
NIDA supports a robust portfolio of basic research to understand the 
mechanisms that underlie the transition from drug use to addiction and 
the brain changes that characterize SUDs. One illustrative example of 
this type of research is the Adolescent Brain Cognitive Development 
(ABCD) study, a landmark study led by NIDA in partnership with NIAAA, 
NCI, and other NIH partners that officially got underway in September 
2015 with 13 grants. Researchers will recruit approximately 10,000 
children at age 9 or 10--before initiation of drug use--and collect 
detailed neuroimaging, genetic, behavioral, environmental, and other 
health data at periodic intervals over the course of a decade. This 
study will examine how biology and environment (including drug use) 
interact and relate to developmental outcomes such as physical health, 
mental health, and life achievements including academic success. This 
study will allow us to answer questions such as how does marihuana use 
during adolescence affect the development of the human brain and how 
does this subsequently influence behavior. Such information is crucial 
to guide prevention efforts.
    Research on Tobacco Use and Health.--Smoking is the leading 
preventable cause of disease, disability, and death in the United 
States. Over 480,000 Americans die each year from smoking and second 
hand smoke exposure. NIDA partners with FDA's Center for Tobacco 
Products on the Tobacco Regulatory Science Program (TRSP) to support 
research on the impact of tobacco-related policies on population health 
and on the Population Assessment of Tobacco and Health (PATH) Study, a 
national longitudinal study of tobacco use and how it affects the 
health of people in the United States. One recent study evaluated the 
effects of smoking cigarettes that contained different levels of 
nicotine among current smokers and found that the average number of 
cigarettes smoked per day was lower after six-weeks in participants 
randomly assigned to cigarettes containing lower amounts of nicotine. 
Compared with the normal (control) cigarettes, the cigarettes with 
lower levels of nicotine decreased exposure to and dependence on 
nicotine and also reduced craving during abstinence from smoking.
    Ongoing studies are examining how low-nicotine cigarettes affect 
smoking behavior in vulnerable populations including women of 
childbearing age or pregnant women, individuals with comorbid SUDs, and 
individuals with comorbid serious mental illness. Each of these 
populations is at increased risk for tobacco use and dependence or 
tobacco related adverse health outcomes. Yet despite these serious 
vulnerabilities, these populations have not typically been included in 
tobacco regulatory studies.
                               conclusion
    Drug use and addiction are complex conditions. The fiscal year 2017 
budget request will allow NIDA to support cutting-edge research that 
leverages the most powerful technologies and latest emerging 
opportunities to expand our understanding of drug use and addiction to 
advance prevention and treatment and improve public health.
                                 ______
                                 

    Senator Blunt. Thank you, Dr. Collins. We're on a pretty 
tight 5-minute clock here on questions. If anybody wants to 
stay--I'm sure there will be a time for it--and can stay, there 
will be time for a second round of questions.

                          RESEARCH BUDGET CUTS

    Dr. Collins, what would happen if we cut your research 
budget by $1 billion, as the administration's request asked us 
to do?
    Dr. Collins. Losing $1 billion for medical research at the 
present time would be devastating. We would have to cut the 
number of new and competing grants that we give by a very 
substantial number. Great ideas that scientists are putting 
forward would go unsupported. Momentum that has been started 
thanks to your efforts in fiscal year 2016 would be severely 
damaged as a result.

                           MANDATORY FUNDING

    Senator Blunt. Do you know something I don't know that 
would suggest that the mandatory funding at a level that 
exceeds that is likely?
    Dr. Collins. Well, Senator, I have to say when it comes to 
the discussions about discretionary budgets versus mandatory 
budgets, I think all of us at NIH are a little puzzled by 
exactly what the consequences of those particular options might 
be. Our concern is to try to see, by some means, an increase in 
the support for biomedical research at a time of such great 
opportunity. So I'm not sure I can weigh the balance, but it 
would certainly be, as a bottom line, deeply unfortunate if 
these kinds of conversations resulted in an overall decrease in 
the resources that we have when we have been hoping very much, 
as you and others have projected, that perhaps we are finally 
turning a corner after 10 years of lost resources into a 
positive space, as happened in 2016 and as we very much hope 
can continue in 2017.

                           YOUNG RESEARCHERS

    Senator Blunt. And one of the things we had hoped we would 
achieve from conversations we've had with all of you in the 
past would be encouragement of young researchers. I know you 
just now have this 6.6 percent increase, the $2 billion 
increase. It may be too early to project, but do you want to 
create a sense for us of what you're seeing in the research 
community generally and young researchers specifically?
    Dr. Collins. Thanks for that question because it's looking 
certainly much more encouraging than if you had asked me that 
question 2 or 3 years ago. Just a couple days ago, I was at a 
major meeting of the basic scientists called ASBMB in San 
Diego, and I spent a lot of time talking to young researchers. 
A couple of years ago, those conversations were pretty 
difficult, our young researchers wondering if they had a career 
path, wondering if there was going to be support for their 
ideas. It feels different this year. They have gotten the sense 
that there is a path here for their careers, that they can try 
innovative ideas and expect that there is going to be a 
possibility of living out those kinds of career dreams.
    And we're all about supporting them, and we have taken a 
number of measures to try to achieve that kind of support. For 
instance, early-stage investigators, who are not as experienced 
as the more seasoned ones, compete against each other instead 
of against the seasoned investigators in our peer review, and 
that gives them a bit of a boost.
    We started a whole new program that I am personally very 
attached to, which allows the most talented graduate students 
to skip the postdoc all together and go straight into an 
independent position because we know that a lot of the great 
ideas that scientists have don't happen when you're 50 or 60, 
they happen at a little earlier stage than that, and yet we 
have oftentimes kept people in less than fully independent 
positions for a long time.
    Something that's recently been floated, and I think may 
very well come through in terms of a way of attracting more 
physicians particularly into science is our loan repayment 
program, where we try to counter what is otherwise a major 
financial hit for those who have big medical school debts and 
want to go into research. And you have recently proposed in the 
authorizing side of this an increase of the loan repayment 
program to a higher cap of $50,000 instead of $35,000 and that 
will improve, I think, our opportunity to recruit those much 
needed researchers into our workforce.
    So many different points here we're trying to push 
simultaneously. The most important thing, though, is for the 
overall tide to raise and lift all those boats, many of them 
with young investigators in them with their dreams of doing 
great things, but dependent upon a confidence that we're on a 
stable, positive trajectory for research that will go over many 
years and not have a feast or a famine.
    Senator Blunt. In this budget year we're in right now, if I 
understood this right, you hope to set aside a certain amount 
of research dollars for young researchers specifically and then 
they would be competing against other young researchers. Do you 
have a sense of how big that amount of money might be?
    Dr. Collins. So we're dependent on, of course, what comes 
in as far as applications. What we are making sure is that 
those new and early-stage investigators have a chance to 
compete against each other, and that gives them a boost in the 
priority scores. And, in fact, in recent years, something like 
35 percent, if I remember correctly, of our grant funds go to 
new and early-stage investigators. They're not all young 
scientists. Some of them are scientists who have been working 
in other fields like engineering or physics or mathematics who 
now see biology as a place that they would like to come and do 
their work, but we want them, too, and we want to be sure they 
have a fair shake at getting started on their careers in our 
particular community.
    Senator Blunt. Now, we may come back to engineers later and 
something that I saw the other day at the Thompson Center for 
Autism at the University of Missouri, but I'm going to try to 
keep my time with everybody else's.
    Senator Murray.

                 COLLABORATION IN ALZHEIMER'S RESEARCH

    Senator Murray. Thank you very much.
    The Vice President's Moonshot Initiative has actually 
increased awareness about some of the barriers to sharing data 
among cancer researchers, and I understand there's been some 
success at fostering greater sharing of research data among 
those focused on Alzheimer's disease with a range of formal 
public, private, State, and Federal international cooperation. 
Can you share with us a little bit about how NIH has been able 
to foster this better collaboration and the effect it is having 
on our efforts to develop treatments and ultimately a cure for 
Alzheimer's and related dementia?
    Dr. Collins. So I appreciate the question because this is 
something we're very intensely focused on, is the idea of data 
sharing. And NIH is pulling all the levers that we have and are 
happy for others that maybe get granted to us to be able to 
insist upon that. Let me ask Dr. Hodes, who is overseeing this 
for Alzheimer's, to respond to your question.
    Dr. Hodes. The microphone is on? Yes. Thank you very much 
for the question, and it touches upon a very important aspect 
of progress to success that I think reflects the understanding 
from public--or private sector about common purpose and the 
advantage of working together to ultimately accomplish the 
common goals of finding diagnostic and therapeutic 
interventions.
    So to be specific, I can cite one of those, which Francis 
Collins initiated NIH-wide, the AMP, or Accelerating Medicines 
Partnership. It's a great example. One of the diseases being 
approached in this sense is Alzheimer's disease. It brings 
together contributions from pharma, from biotech, from advocacy 
and philanthropies, along with NIH dollars, and in this case, 
for example, in two general areas. One of them supporting in 
clinical trials the use of new biomarkers; the other, looking 
at the grand progress in ``omics,'' proteomics, genomics, 
metabolomics, looking at the differences in the brains of 
people affected by Alzheimer's and those not. These data now 
are integrated in near real time through a common database. 
It's a new culture among investigators in the academic sense, 
as well as with industry to make the data, the products of 
research, available as quickly as possible to the community, as 
posted, and we'll have enormous repercussions, I think, in 
accelerating the progress of research. And again this idea 
reflects a common purpose in understanding that it would 
benefit everyone, ultimately product development, and there's a 
way to achieve that, expansion in basic science and knowledge. 
So it has been an enormous success. I think it's a culture 
change that will perpetuate.

              ALZHEIMER'S DISEASE FOR AT-RISK POPULATIONS

    Senator Murray. Good. And I think part of that, from what 
I'm hearing, is that instead of waiting till someone is older 
and in further stages of Alzheimer's, you're looking at ways to 
have new trials with participants who are at risk of the 
disease rather than already being diagnosed?
    Dr. Hodes. Exactly true. One of the advances we've seen, by 
understanding of genetic determination of those at risk and by 
biomarkers, notably neuroimaging, is the ability to detect 
early stages of Alzheimer's, related dementias, long before the 
appearance of symptoms, and now to design treatments to 
intervene and allow us to monitor these biomarkers to see if 
we're engaging the right targets, having signs of progress, and 
therefore identify successes, and for that matter, failures 
more quickly and have an opportunity to test more candidate 
interventions.

                         BIG DATA TO KNOWLEDGE

    Senator Murray. Okay. Very good. We hear a lot about big 
data challenges facing researchers, and perhaps nowhere is that 
more relevant than with the massive amounts of data that the 
BRAIN Initiative is now generating, a challenge that's only 
going to increase, I assume, as we learn more. I know some of 
your team has been really focused on this, and I wanted to ask 
you about the challenge of opening and integrating an 
accessible data warehouse on a massive scale and maybe some of 
the examples you've seen that you've learned from.
    Dr. Collins. So we do in fact have major investments in the 
space of big data. I just showed up on this screen, there are 
all kinds of data types that are being generated now in very 
rapid phase and produce very large datasets of terabytes. And 
you mentioned the BRAIN Initiative as an example. Genomics is 
certainly in there as well as imaging.
    And now with electronic health records becoming accessible 
for research purposes, NIH recognizing this was going to be a 
major need and a potential threat if not attended to, put 
together a plan which has now resulted in $100 million of 
spending on a program called BD2K, Big Data To Knowledge, which 
aims to try to take all these large datasets, develop the 
appropriate ways to have standards so that they can be properly 
compared and integrated, and develop new kinds of software to 
mine the nuggets of information out of these very complicated 
sets. This supports a number of centers of excellence in data 
science around the country and also it is the major source now 
of training for the next generation of data scientists, who we 
are going to need to be able to handle what is clearly a 
growing area of scientific opportunity and responsibility.
    Senator Murray. Okay. Thank you.
    Senator Blunt. I would normally go to Chairman Cochran, but 
he says he was a little late getting across the street, so he 
didn't want to get in front of anybody who was already here.
    And Senator Alexander, you're the first person who was 
here.
    Senator Alexander. Thank you, Senator Blunt.
    Senator Cochran, thank you.
    Welcome, Dr. Collins, and your team. I want to first 
express my appreciation to Senator Blunt and Senator Murray for 
their leadership last year on the significant increase in 
funding for the National Institutes of Health, which I am glad 
to support. I don't think there's anybody here who doesn't hope 
that we can find ways to make the increase that happened last 
year a pattern this year and in the future. So I thank Senators 
Blunt and Murray for their leadership on that in this 
committee.
    Second, thank you for mentioning the work that our 
authorization committee has done. Senator Murray is ranking on 
that. We finished our work in the committee. We've done the 
things that you have asked us to do. You said the ability to 
recruit top talent was very important for you. We've made many 
of the changes you suggested. Electronic medical records are 
absolutely essential to the Precision Medicine Initiative you 
described. We've done a number of things there.
    The Vice President is talking about making researchers who 
use NIH funds share their data. You've talked about that. 
That's in the bill that we passed yesterday.
    Dr. Collins. Thank you.
    Senator Alexander. We gave you more flexibility to make 
alliances like the Google-Vanderbilt alliance that the 
President announced not long ago. We reduced a number of really 
pretty silly provisions that create a lot of unnecessary 
paperwork. So we asked you, what could we do to create an 
environment where you could succeed? And we tried to do that.
    Now, the major thing remaining is what I would describe as 
an NIH innovation project fund and how to pay for it. The House 
of Representatives has already passed its 21st Century Cures 
Act. They appropriated $8.8 billion in mandatory funding. I've 
tried to come up with a way to do that in the Senate. We can 
reduce existing mandatory spending to pay for the NIH 
innovation projects fund, we would make sure that we have 
appropriate oversight, and it would not replace increases in 
annual discretionary funding.

                     MANDATORY FUNDING FLEXIBILITY

    So let me ask you in the remaining time to comment on that. 
Are the priorities that I suggested earlier, launching 
Precision Medicine, Cancer Moonshot, the BRAIN Initiative, 650 
American young investigator corps, big BioThink awards, are 
those still priorities? Can you do those without creating 
funding cliffs? Would mandatory funding somehow give you more 
flexibility to ramp spending up and then down? And what would 
you do about oversight in terms of a strategic plan for each of 
those five areas?
    Dr. Collins. Well, thank you for that question and your 
leadership, Senator. We are enormously excited about the five 
areas that you just enumerated, the focus, for instance, on 
young investigators trying to create an even more vigorous 
pathway for their recruitment and support, which is one of 
those five; the big BioThink, which you mentioned, which is an 
opportunity for all of the 27 Institutes to have a chance to 
put a challenge out there to their community about what are the 
really big ideas that could go forward in the next few years. 
And, of course, Precision Medicine and the Cancer Moonshot and 
the BRAIN, all very high priorities for us.
    While I totally agree with what you said about the 
importance of not having this kind of mandatory funds displace 
regular discretionary support, because that would be a very 
unfortunate outcome, we do believe that for those five areas, 
we could, in the space of a few years, identify components that 
could be nicely supported through this mechanism and would not 
result in a cliff, and which would, if we were given 
appropriate flexibility, be something that we could put forward 
in terms of what those timetables would look like and what 
those envelopes might look like as far as specific dollar 
figures.
    And I certainly agree that we would expect to have 
appropriate oversight about how those dollars would be spent. 
We would be happy, in fact, to submit a work plan and then be 
held accountable for that over the course of the coming years 
to make it very clear that we do understand this is a big 
responsibility that you, through the congressional process and 
speaking for the taxpayers, expect us to use and----
    Senator Alexander. So you do believe that in those five 
areas those are still priorities that you've identified----
    Dr. Collins. Absolutely.
    Senator Alexander [continuing]. And, second, that you could 
identify elements of them that would be discrete, have a 
beginning and an end, do them without creating a cliff, and 
perhaps even the mandatory funding would provide us a way to 
give the NIH funding in a way that you didn't have to spend it 
all at once and you could ramp up and ramp down according to 
the real needs of the project.
    Dr. Collins. That's exactly right. Yes, I do believe these 
are major priorities. We could design things that way, and I 
appreciate what you said at the end about the flexibility that 
would help us a lot in terms of designing the exact funding 
envelope that would make the most sense for each of those five 
programs.
    Senator Alexander. Thank you, Mr. Chairman.
    Senator Blunt. Thank you, Senator Alexander.
    Senator Durbin.

                          NIH MARCH-IN RIGHTS

    Senator Durbin. Thanks very much, Mr. Chairman.
    And thank you, Dr. Collins, for being here with your team. 
It's a moment of satisfaction and pride that we look at this 
year's budget and contemplate next year's budget. Though I am a 
strong supporter of my President, I do disagree with their 
budget request and believe that we can do better. The 
encouraging thing is that gathered at this table on this side 
are men and women who have proven that in this fiscal year and 
can prove it again. It's going to take some good luck, but we 
have some exceptional leadership here, not only in terms of 
Senator Blunt and Senator Murray on this subcommittee, but 
Senator Alexander and Senator Murray working on the authorizing 
committee, and not to overlook at all my close friend and 
colleague, Senator Cochran, who has overall responsibility for 
the Appropriations Committee. So among us is the opportunity 
and the potential to meet this year's challenge and next year's 
budget, and I hope that we can do it.
    I would like, if I can, to move to an area separate, but I 
think very important, when it comes to the medical health of 
America. A recent Reuters report found that the prices of four 
of our Nation's top 10 drugs have increased more than 100 
percent since 2011; 6 others went up 50 percent. The price for 
arthritis drug Humira went up 126 percent; multiple sclerosis 
drug Copaxone, 118 percent; asthma drug Advair, 67 percent. The 
list goes on and on.
    What makes this so worrisome is not only it limits 
accessibility for the American people, but it also is 
objectionable because many of these drugs were developed at the 
expense of taxpayers, taxpayers funding the National Institutes 
of Health. These taxpayers have paid to develop drugs that they 
now cannot afford, while drug companies make record profits.
    The National Institutes of Health has historically been 
reluctant to exercise march-in rights, an existing authority 
that was created by the Bayh-Dole Act that allows the NIH to 
grant a license for others to use drugs developed with NIH 
dollars which are inaccessible to those in need. I agree that 
we need to be especially careful in this area of intellectual 
property protection and that march-in rights have to be used 
sparingly, if at all. But when we take a look at the staggering 
prices of drugs, the dramatic increases for drugs, many of 
which have been on the market for years before these increases 
took place, I ask you, have you considered, would you consider, 
using your statutory authority under the Bayh-Dole Act for 
march-in rights to protect the consumers of America from abuse 
by overpricing by pharmaceutical companies?
    Dr. Collins. Senator, I share your concern about the way in 
which individuals who need access to medical treatment may be 
prevented from readily achieving that on the basis of the costs 
involved, and certainly, as a physician, I would never want to 
see a circumstance where an effective drug was not available to 
somebody who needed it and would benefit from it. But I'm not 
sure that NIH is in a great position here in terms of the 
levers that need to be pulled to try to do something about what 
everybody agrees is a difficult situation with drug pricing.
    The Bayh-Dole Act, which I recently went back and looked at 
in terms of those march-in rights and what they were intended 
for, does not appear to have really been designed to be 
utilized in a fashion where the price is the obstacle, it seems 
more to be a circumstance where the product was simply not 
available because it was not being commercialized, and then NIH 
had the authority to step in and take over. And, of course, it 
only applies if NIH has some connection to the intellectual 
property, which is true for many drugs, but certainly not all.
    We are certainly looking at the situations on a case-by-
case basis. We have a recent letter from a few Senators about 
something called Xtandi, which we're studying at the moment, 
and I am not saying in any way that we're not going to take 
this potential responsibility seriously, but I am concerned the 
negatives that may be flowing forward. If we begin to use 
march-in in a very broad way about drug pricing, it may in fact 
be substantial in terms of a loss of interest then in terms of 
industry participation in discoveries that NIH has supported.

                         ACCESSIBILITY OF DRUGS

    Senator Durbin. Let me just, because my time is up here, 
let me just say first, accessibility I think goes beyond 
physical accessibility. If a drug is overpriced, it is not 
accessible to a consumer. And, secondly, I accept your premise 
that you don't want to abuse this right, but if you cannot find 
one egregious example where you can apply this, I would be 
surprised. And applying it even in one case sends at least the 
message to the pharmaceutical companies across America that 
patients need to have access to drugs that were developed with 
taxpayers' expense and the research that went into it. I think 
doing nothing sends the opposite message, that it's fair game, 
open season, for whatever price increases they wish.
    Senator Blunt. Senator Cassidy, and after that it will be 
Senator Mikulski.
    Senator Cassidy.
    Senator Cassidy. Thank you. Dr. Collins, all of you, thank 
you very much. Thank you for your service to our country.
    Dr. Collins, first I want to thank you. We've spoken in the 
past. You know, I've kind of made it my jihad to get NIH to 
redirect dollars to more pressing current biomedical needs. 
You've initiated that, and I thank you for that, and I look 
forward to seeing the fruits of that, because I look up and 
down the panel, you all have got a lot of work to do, and we 
thank you, too.

               PRECISION MEDICINE INITIATIVE RECRUITMENT

    Secondly, I've been thinking about your Precision Medicine 
Initiative. What is the business plan? There's a million people 
that you wish to recruit, it supposed to reflect the diversity 
of our country. I've done clinical research, nothing like you 
all, but significant, and my patient population was lower 
income, more transient lifestyles. We successfully recruited, 
but this would be for a 6-month or a year study, nothing such 
as ongoing for the rest of their life.
    Dr. Collins. Right.
    Senator Cassidy. So in your business plan, I have several 
questions. You have an ambitious effort to recruit a million 
people from all socioeconomic groups. How do you plan to do so? 
Secondly, it's longitudinal. There is going to be significant 
expense. So to what degree do private entities, say, Pfizer, do 
they have to pay to access that data? If not, why not? Because 
there are going to be significant benefits.
    And, thirdly, if I am someone who has agreed for the rest 
of my life to contribute hair and rectal swabs and nasal swabs 
and everything, because you've spoken of our biome being 
included as well as our genome, am I going to get to share 
that? If there are a billion dollars that come in, in revenue, 
a certain portion ideally would be used to maintain the 
program, does some of it flow back to one of those million? We 
think of that HeLa strain, the woman who donated her cervical 
cancer, so much benefit, but her family has not benefited 
directly.
    Dr. Collins. Not directly.
    Senator Cassidy. In this contractual process, will those 
who contribute their data, will they be able to benefit as 
well?
    So it's three questions, if you will.
    Dr. Collins. Well, thanks for the question and also for 
your initial comment about strategic planning. I hope everybody 
at the dais there has seen the strategic plan that NIH put 
forward, published in December, very much a response to your 
request to have a clear sense of how we set priorities, and I 
hope you've had a chance to look at that, and if not, please 
do, and let us know if there are things you would like to 
discuss further about it.
    How are we going to enroll a million people and have that 
be generalizable as far as the population in the United States? 
Something we've thought about a great deal. Many of the 
participants are in fact going to be those who are currently 
involved in health provider organizations who have recently 
come forward and applied to be part of this, but, of course, 
that's not going to be fully diverse in terms of socioeconomic 
and ethnicity of the country.
    We will also have an outreach which is, I think, going to 
be pretty interesting to the community health centers, the 
federally Qualified Health Centers that are supported by HRSA 
(Health Resources Services Administration), to try to enroll 
those individuals who get their care in those settings, who 
tend to be fairly stable in terms of their geographic location, 
despite what people might think. And actually I have 
interesting research based on polls, but haven't generally been 
asked.
    We also will have this open to any American, so anybody can 
volunteer to take part in this, and that opportunity will 
appear at approximately August or September. So maybe all of 
you all would like to join in. It would be great to have you as 
members of this million-strong cohort.
    Yes, it is intended to be a longitudinal cohort. It will 
collect a great deal of data. We do intend to make that data 
available to any qualified researcher who adheres to certain 
principles about protecting the privacy and confidentiality.
    I hear what you're saying about pharma therefore being able 
to use this as well, and yet I don't see a great alternative. 
Basically, pharma will have the opportunity to learn from this. 
It will be very pre-competitive, early-stage data, the kind 
that we traditionally do make available in publications, and it 
would be hard to put up a barrier here, I think, in this case, 
without slowing down the progress of research overall.
    Finally, your question about whether the participants 
should receive some of the financial benefits that may come out 
of this, we've certainly talked about that. I think the general 
position, though, of bioethicists who look at that question is 
that the extremely low likelihood of such actual benefit coming 
back because the data that we generate here is not itself 
likely to produce much in the way of intellectual property, 
it's pre-competitive data, it might actually be a disservice 
then to be seen by potential participants as an inducement to 
take part in a project which might not really result----

                COMPENSATION FOR PMI COHORT PARTICIPANTS

    Senator Cassidy. If I may, I know in clinical research, 
you're allowed to compensate people for the expense of 
participation.
    Dr. Collins. Yes.
    Senator Cassidy. So it isn't an inducement as in, you know, 
stick a nail in your eye; it is, listen, you're going to be 
taking your hair, you're going to put it in an envelope, you're 
going to mail it to us, you're going to give us access, a lot 
of hassle associated with that. It is a compensation for 
participation.
    Dr. Collins. So we would certainly be willing and have it 
planned to compensate people for the time that they have to 
spend by taking part in this, if they're going to have an 
examination, have a blood sample, have to----
    Senator Cassidy. In my remaining seconds, let me interrupt. 
Now, the thing that concerns me regarding this data, granted, 
it's pre-competitive, but we, as taxpayers, funded for 
electronic medical records to collect this data to make it 
generalizably available to people doing public health. We heard 
when I was in the House on Energy and Commerce, it's not being 
used that way. Insurance companies are instead packaging and 
selling to big pharma, but $500,000 for a cohort of 
information, and if you are a dadgum public health doctor and 
you don't throw in $500,000, you don't get the data.
    So I guess my concern is the taxpayers investing heavily in 
this, but our precedent is, is that the taxpayer is misled in 
terms of its generalizable use. For this data, there is going 
to be such profit generated, is there really no way that the 
person that comes up with a blockbuster drug in any way comes 
back to help support the maintenance of this dataset, which is 
going to be critical to their development of that blockbuster 
drug?
    Senator Blunt. Can you respond to that in 30 seconds, Dr. 
Collins?
    [Laughter.]
    Dr. Collins. Sure. I guess, Senator, I see this as not so 
different than the way in which our American ecosystem has 
flourished, and I would be reluctant to try to impose that kind 
of payback provision for pharmaceutical companies to be able to 
get access to a very large dataset which is pre-competitive 
which may give them ideas about new drug targets they hadn't 
thought of, but which is probably not going to result in a 
direct intellectual property claim. So I think of this much 
more the same way that the Framingham Study has produced all 
kinds of insights about heart disease, and nobody has 
contemplated that the companies that are selling statins should 
now be paying money back to Framingham.
    Senator Blunt. Thank you very much. There will be time to 
come back to that and other topics, as we all want to as well, 
Senator Cassidy.
    Senator Mikulski.
    Senator Mikulski. Mr. Chairman, thank you.
    Senator Murray.
    Dr. Collins, it's so good to see you and your team here and 
those also who represent institutes and offices at NIH. You 
know, this might be your last hearing, but it certainly is my 
last hearing at the appropriations for NIH, but I'll be out 
there on Monday to be able to talk to you on more detail.
    It has been my great joy, one of the greatest joys I've had 
being in the Senate, was to be able to represent the National 
Institutes of Health, both my work in the House on Energy and 
Commerce, where so many of us came from, to now certainly in 
the Senate, and to represent both NIH in the Bethesda campus, 
our two institutes in Maryland, the one on Aging and on Drug 
Abuse, and of course, our extramural work with Johns Hopkins, 
the University of Maryland, and multiple campuses, one of your 
rival institutes, the Craig Venter, where we watched you and 
Dr. Venter do the race to map the human genome. So it has been 
a great joy. It will be even more joy if I can help leave you 
in pretty solid financial health. We could go through the 
numbers about clinical trials and so on, but let me tell you my 
principles and then get to my questions.
    Number one, do no harm. So either for this year or next 
year, that through our own self-inflicted wounds, we're ready 
to budget processes of sequester or shutdown, we don't go in 
that direction. I really want to compliment Senator Cochran and 
Senator McConnell and say we're going to follow regular order 
and do our job. So one, do no harm.
    Second, capitalize existing programs. So those that are 
already on their way, that we help sustain so that the 
researchers, both senior researchers and the new ones we hope, 
and so on, have predictability.
    And then third, go for the big ideas.

                    BASELINE FOR FUTURE YEAR BUDGETS

    So let me then get to my question, which goes to we have an 
agreement here to do no harm, and I really look forward to 
working with my colleagues on my side of the aisle to move our 
process forward.
    But let's go to the money. You answered Senator Alexander 
in terms of mandatory funding. I'm squeamish about mandatory 
funding. I am concerned that it is a hope and a promise. It 
rests on new revenue. Well, maybe. I'm coming back to actual 
discretionary funding, so no matter what, you, as the 
administrator and the director of the Institutes, because we 
don't earmark, we've never earmarked at NIH, though there's 
been a tendency, yet discretionary.
    So you have a request for here it's $33 billion, but in 
terms of real discretionary money, what is it that NIH needs to 
be able to be and do the job it wants for the next fiscal year 
and make sure we have the baseline to build on it, you know, on 
future years? Because you, research, researchers, need 
predictability over multiple years.
    Dr. Collins. Senator, I can't say enough how much I've 
appreciated your support over these years, just a remarkable 
leader, and we look forward to celebrating you next Monday when 
you come out to NIH.
    Senator Mikulski. The golden Petri dish, I guess.
    [Laughter.]
    Dr. Collins. So in terms of your question, and I assume 
you're asking for my professional judgment, which I'm always 
happy to be asked about.
    Senator Mikulski. Yes.
    Dr. Collins. We have, of course, seen over the course of 
the last 12 years a pretty tough period for NIH until this 
year, fiscal year 2016. I've often thought it was useful to 
show this graphically, and if you look at the screen----
    [The graphic follows:]

    
    

    Senator Mikulski. I need a short answer so I can get to 
other questions.
    Dr. Collins. Okay.
    Senator Mikulski. Okay?
    Dr. Collins. You can see the white line. That's what's 
happened to our resources over the course of the last 20 years, 
and we have made some progress this year, but we need----
    Senator Mikulski. The number now. This is not a colloquium; 
it's a hearing, please. How much do you need?
    Dr. Collins. A stable trajectory of inflation plus 5 
percent for multiple years in a row would be a wonderful way to 
support medical research in the way that it needs to be.
    Senator Mikulski. So if we made that percentage--now, 
wouldn't that be over a 5-year period, wouldn't we get to 
almost doubling NIH?
    Dr. Collins. You would get to doubling by about I think 7 
years or maybe 8. I would have to go back and do the 
compounding again, but about that.
    Senator Mikulski. Well, first of all, I'm so pleased last 
year at the splendid bipartisan way we worked together, and I 
want to compliment Senators Blunt and Murray in doing that. I 
think we need to really be serious about thinking about that as 
a model to be able to have the predictability, again not a 
guarantee, we don't know what lies ahead in some instances for 
our country, but I think that type of commitment, along with 
maybe the hope and promise of mandatory funding, would be the 
way to go.
    Dr. Collins. Okay.

                     RESEARCH IN EXISTING PROGRAMS

    Senator Mikulski. Now, let's go to what we would buy for 
the money, what we would get for the money. First of all, I 
support these new ideas, and you know, Precision Medicine, the 
BRAIN Initiative, and all of this promise, but where do you see 
in terms of existing programs where you see some of the 
greatest promise? Yes, we're working at the BRAIN, et cetera, 
but what about things where people are often the sickest the 
most with awful consequences, diabetes and heart disease?
    Dr. Collins. Great promise in diabetes, heart disease. 
Cancer is at a unique moment. Conditions like autism coming 
forward. Vaccines, the opportunity to prevent diseases that we 
desperately need to get on top of, like Zika and others. But, 
you know, the good news is if you look across the entire 
landscape of NIH research, there's not really a sort of place 
where things are in a cul-de-sac. All of those areas, and that 
includes the basic science agenda that undergirds it all, are 
poised for dramatic advances. So it's almost hard for me to 
pick one or two.
    I do have to mention Alzheimer's. I think we are at a 
inflection point for that condition, and I know that's one 
you've had major leadership in trying to draw to people's 
attention. The ability now to be able to identify who's at high 
risk and conduct these trials to reduce their likelihood of 
developing the disease is looking more promising than ever.
    Senator Mikulski. Well, my time is up, but in the area of 
Alzheimer's, I remember when Senator Bond and I had a hearing 
and we were in the poise of breakthroughs. So that was like 5 
years ago. So we're always poised during the breakthrough, and 
I'm ready for the breakthrough.
    [Laughter.]
    Dr. Collins. So are we.
    Senator Mikulski. So let's all continue to work together.
    Thank you. You were indulgent with the time.
    Senator Blunt. Thank you, Senator Mikulski, and thank you 
for how well you've represented NIH as a Senator and as their 
advocate for a long time now.
    Senator Capito.

                              OPIOID ABUSE

    Senator Capito. Thank you, Mr. Chairman. And thank all of 
you, and thank the ranking member.
    I'd like to talk with Dr. Volkow about the National 
Institute on Drug Abuse. As you probably are aware, I represent 
the State of West Virginia. We've been particularly hard hit by 
the epidemic of opioid abuse in the country. And I just had a 
few questions I wanted to ask specific to that.
    I understand that you are partnering with the Appalachian 
Regional Commission to improve opioid intervention services. 
Can you explain and tell me what are the goals of this 
collaboration and where you are on that?
    Dr. Volkow. We're trying to actually create infrastructure 
that will allow us to launch research projects and also to give 
us information about the nature of the problems that they 
currently have vis-a-vis injection drug abuse and the 
associated consequences along with medical infrastructure that 
they have that they could deploy. Unfortunately, this 
information is currently not available and there are not 
integrated groups that would allow us to deploy the type of 
implementation research that we would be very much interested 
to do in order to contain the injection drug abuse epidemic in 
that area.
    Senator Capito. Well, I understand there have been issues 
with different States on reporting data, causes of death, and 
because there are associated issues, it could be a heart 
attack, and then not be identified as a drug overdose. Is this 
an issue across the country? I'm sure it is.
    Dr. Volkow. Yes, it is an issue, and as a result of that, 
we don't have clear-cut numbers of the cases that is related to 
opioid overdoses, and varies, as you said, by State.
    Senator Capito. So I'm sure, as a researcher, you don't 
want to speculate, but I would imagine speculation is the 
problem. It may be greater than what we really realize 
according to the data?
    Dr. Volkow. Yeah, there is consensus that we are 
underestimating the numbers that's associated with----
    Senator Capito. Well, that's a frightening thing I'm sure 
for you all and certainly for all of us, every family that's 
affected.

                DEVELOPING NON-ADDICTIVE PAIN MEDICATION

    I was pleased to hear, Dr. Collins, in your opening 
remarks, that you talked about the research that's being 
developed to find a non-addictive pain medicine. I know 
Secretary Burwell has talked about this as well. How far along 
are we on that and what can we expect there? If you could just 
shine a little light on that.
    Dr. Collins. Sure. I might ask Dr. Koroshetz, who directs 
the Pain Consortium at NIH, to say something to respond to your 
question.
    Dr. Koroshetz. Yes. So it's an interesting area to think 
about. Pain is something we all have. It's good to know we have 
a sense of pain. But the problem that we're facing is we don't 
understand too well about what characterizes the transition 
from acute to chronic pain. Chronic pain is not helping in any 
fashion whatsoever. We think, and all the evidence so far, 
suggests that there is a change in the brain circuits that 
occurs after someone has been exposed to an acute pain that 
leads those circuits to change and develop a chronic pain 
disease basically by itself.
    So we have pretty good information on some of the 
beginnings of how that happens. It starts very peripherally and 
moves more centrally over time. And there actually are targets 
for therapy that could be pursued by pharmaceutical companies 
and by the NIH to try to prevent that transition. So in the 
Blueprint for Neuroscience, that was our major challenge, to 
develop products that would prevent this acute-to-chronic pain 
transition. From talking to the pharmaceutical companies, I 
have a lot of leads.
    I think the problem that we have to focus more on is how to 
improve the testability of those compounds as we go into people 
because we're still reliant upon someone's reporting of their 
pain, and we don't have objective measures. So we think at NIH 
that that should be our major focus. And the drug companies 
tell us they have lots of targets, but they need this objective 
measure. So that's where our focus was.
    Senator Capito. Well, I would hope--I mean, I'm pleased to 
hear that. I would like to see it on the fast track. I think 
for a business model, you know, there's going to be a lot of 
demand for a non-addictive pain medication that works.
    Dr. Koroshetz. Right.
    Senator Capito. So I don't see how the private sector would 
be contrary to this at all, and so I'm pleased to know you're 
working together.

                      NEONATAL ABSTINENCE SYNDROME

    The last issue, again, Dr. Volkow, about fetal--let's see, 
neonatal abstinence syndrome, that's babies that are born 
addicted, and this is an issue, and our State has particularly 
high statistics here again. Are you pursuing research in this 
area or what kind of partnerships are you doing here to try to 
help those very innocent victims of drug abuse?
    Dr. Volkow. Indeed, we are pursuing the area of research in 
terms of interventions, number one, to prevent neonatal 
abstinence syndrome, and number two, in those women that are 
opioid--have an opioid use disorder, to determine what are the 
best treatments that can be given to them in pregnancy to 
minimize the likelihood that those infants will suffer from 
neonatal abstinence syndrome. So we are working on prevention 
and on treatment.
    Senator Capito. Well, thank you very much. We have a place 
in West Virginia called Lily's Place that helps to deal with 
these babies. And just my final comment would be I noticed in 
your report that you're working on a Human Placenta Project. 
I'm very interested in that and have a personal connection with 
that. So thank you very much.
    Senator Blunt. Senator Schatz.
    Senator Schatz. Thank you, Mr. Chairman.
    Thank you to all of you and everybody who works at the 
National Institutes of Health. This is, I think it's fair to 
say, among the most inspiring, invigorating hearings that we 
have. I'm going to try to get to a couple or maybe three 
questions.

                     FEDERAL PAIN RESEARCH STRATEGY

    First, Dr. Volkow, following up on Senator Capito's 
question about non-addictive alternatives to the current pain 
medication, opioids, acetaminophen, the NSAIDs, where are we 
with that in terms of the national--the NIH is working on a 
Federal pain research strategy. When will this be completed? 
And when will it be launched? And who is going to be point on 
this? And I'm not sure if the question should be directed to 
Dr. Volkow or Dr. Koroshetz.
    Dr. Collins. Koroshetz will answer.
    Dr. Koroshetz. It's really complicated. There are a bunch 
of different documents out there, but there is a National Pain 
Strategy that has been released, and that is basically 
directing the country's medical care system on how to improve 
pain care in both a safe and effective manner. And then that 
process is followed by the Federal Pain Research Strategy, 
which is being developed now and will be completed by January 
2017, where an expert panel of basic and clinical researchers 
will work out the highest research priorities in these 
different areas, some of which I mentioned, the acute-to-
chronic pain transition being one. And another what is 
determining the best way of treating people who have chronic 
pain, depending on what caused it and what type of pain it is.
    Senator Schatz. Great. Thank you.

                PUBLIC HEALTH STRATEGIES FOR DENGUE/ZIKA

    Dr. Collins, as you know, the Hawaii Islands, the State of 
Hawaii, but the big Island of Hawaii, is experiencing a dengue 
fever outbreak, and the vector for dengue fever is the same as 
the vector for the Zika virus. And I would like you to tell the 
committee what recent developments there may be in terms of 
public health strategies relating to dengue and also to Zika.
    Dr. Collins. So with dengue, the National Institute of 
Allergy and Infectious Disease just announced a couple of weeks 
ago success of a quad--I'm sorry--a tetravalent vaccine, which 
was tried out in volunteers and showed complete protection 
against dengue infection. And there is also a vaccine that has 
been produced by the company Sanofi that is already approved in 
a few places like Brazil and Mexico, but not yet in the United 
States. I know that Hawaii has had more than 300 cases of 
dengue, and there's a great interest in speeding up the process 
of getting access to that vaccine, and I would be glad to talk 
to you further about that, and Dr. Fauci, who directs that 
effort, would also.
    In terms of Zika, the Zika vaccine efforts are on the fast 
track and we are doing everything we can to speed that up, but 
it will be until probably August or September before the first 
phase 1 trials can be initiated for human volunteers. And 
realistically, because then one has to go to phase 2 and 3 
trials, this will not probably be generally available until 
2018. We're also working on therapeutics as well as the 
vaccine.

                         CHILDHOOD VACCINATIONS

    Senator Schatz. Dr. Collins, a new question. There is 
unfortunately a lot of confusion among young parents about the 
benefits and efficacy of vaccinating their children, and I 
would like for you to say as clearly and concisely and 
authoritatively as possible, what's your recommendation to 
young parents who may be reading things on the Internet and are 
otherwise well informed and certainly care very deeply about 
their children, but want to take the right advice?
    Dr. Collins. Well, I really appreciate that question 
because there still is confusion out there, though I think the 
facts are now incredibly clear. There was a suggestion 20 years 
ago that there might be some connection with vaccination with 
the MMR vaccine and the onset of autistic symptoms. The report 
that put that forward ultimately was turned out to have been 
falsified. The author of that report has been stripped of his 
professional standing, and the paper has been retracted. But it 
started a concern, an understandable concern, amongst patients 
and parents about whether this might be a real connection. 
Multiple studies done over the course of these two decades in 
the United States and in other countries, especially Denmark, 
have repeatedly failed to show any connection whatsoever 
between childhood vaccines and the onset of autism.
    Autism is a terrible tragedy when it happens, we need to 
understand its causes, we are learning much about those, but 
what we can say I think categorically is that vaccines are not 
the cause. And, of course, it is very much an unfortunate 
circumstance if kids are not getting vaccinated and then fall 
ill from treatable diseases, like measles, which can even be 
fatal.
    Senator Schatz. So your recommendation to parents is?
    Dr. Collins. Get your kids vaccinated. Follow the 
recommendations from the professional societies like the 
American Academy of Pediatrics. Don't worry. This is a good 
thing. This will help your kids.
    Senator Schatz. Thank you.
    Senator Blunt. Thank you, Senator Schatz.
    Senator Cochran.

                      JACKSON HEALTH STUDY AND PMI

    Senator Cochran. Mr. Chairman, thank you for this follow-up 
hearing. It gives us an opportunity to check in again with the 
status of what can be gleaned now from the Jackson Heart Study, 
which involved a cohort, a research cohort, of 5,000 men and 
women in Jackson, Mississippi, relating to the heart and the 
illnesses and consequences of heart disease. As you work to 
build a national research cohort, is this study going to be a 
part of that initiative in any way?
    Dr. Collins. So the Jackson Heart Study, Senator, which 
you've been a wonderful leader for, and which you and I got to 
visit together 2 or 3 years ago, is a national resource to look 
particularly at the factors that play out in terms of 
cardiovascular disease in the African American community, where 
we know that the risk factors are particularly high. That study 
has already taught us a great deal about what those 
environmental and genetic and social and behavioral risk 
factors are turning out to be, and those 5,300 individuals who 
have volunteered to take part in this effort I think are real 
national heroes by their willingness to do so.
    We are continuing to look for ways to connect up that 
effort with other kinds of studies, and I know Dr. Gibbons, who 
is the director of the National Heart, Lung, and Blood 
Institute, recently visited Mississippi to think a bit more 
about that with regard to other kinds of research going on in 
your State.
    With regard to this Precision Medicine Initiative cohort, 
where we aim to enroll a million Americans, we very much open 
that door to every volunteer, and my hope would be that those 
who have already taken part in research studies would be 
particularly interested, and therefore, we might see particular 
interest coming forward from those folks who are already part 
of the Jackson Heart Study. Certainly, we learn more the more 
data that we have, and to be able to do that kind of connection 
would be quite useful. But we want everybody to have the 
opportunity to decide whether this is the kind of study they 
want to take part in.
    Again, though, I can't tell you how much from NIH's 
perspective it has been valuable to have that already ongoing 
study now going on 20 years, or it will be in a couple more 
years, to teach us things that you can only learn over the 
course of time, and which we also hope to learn from this 
cohort, the Precision Medicine cohort, as it gets launched in 
the next year or 2 and then moves forward going who knows how 
many decades to try to really understand all the factors that 
play out in terms of health and disease.
    Senator Cochran. Okay. Thank you very much.
    Senator Blunt. Senator Shaheen.
    Senator Shaheen. Thank you, Mr. Chairman.
    Thank you, Dr. Collins, and all of you for being here this 
morning and for the work that you do every day.

                          ARTIFICIAL PANCREAS

    So I have three questions, and I want to start with 
congratulating and thanking you all for continuing to make the 
artificial pancreas a priority. I was pleased to see that both 
in your written testimony, and although I didn't hear your 
comments, I know that you mentioned it in what you had to say. 
It will completely change the lives of people living with type 
1 diabetes, like my granddaughter, Elle, who was diagnosed 
after her eighth birthday. So can you talk about what you hope 
to deliver in the next 5 years with respect to the artificial 
pancreas?
    Dr. Collins. Thanks for the question. And of course, this 
is a very high priority for our National Institute of Diabetes, 
Digestive, and Kidney Diseases. The challenge is to come up 
with the kind of engineering, both tissue engineering and other 
types, that would reliably produce an accurate minute-by-minute 
measure of blood glucose and then deliver appropriately and 
safely the appropriate dose of insulin to keep those levels in 
the right zone. We all know that the current way that this is 
done, as your granddaughter no doubt knows every day, involves 
the sort of regular opportunity to find out blood levels 
oftentimes by a finger stick, and yet you can't do that every 
minute, and so there are peaks and valleys that undoubtedly are 
less than ideal. And we do know the better the control, the 
better likelihood of avoiding those consequences of 
cardiovascular and kidney disease and eye disease, which is 
very much our goal to try to prevent.
    So the challenge here has been, because of the safety 
issues, to move this forward in a fashion where we know we are 
going to be doing good. There have now been a number of studies 
under very closely observed circumstances----
    Senator Shaheen. Actually, my granddaughter participated in 
one of the initial studies for juveniles.
    Dr. Collins. Wonderful. And those have shown very 
encouraging results. I think the reason of going cautiously is 
that, of course, an overdose of insulin can be extremely 
dangerous and even fatal, and so you want to be sure you have a 
failsafe system, and that's where a lot of the focus now is. 
But as I----
    Senator Shaheen. And so--I'm sorry to interrupt, but my 
time is running. So do you think--are you optimistic that in 
the next 5 years we may have a device that is going to be 
available on the market for people?
    Dr. Collins. In my opening statement, I said 10. I would 
love for it to be 5. I think it could be. It would certainly 
require both some good scientific effort and some good support 
for that, but also some of the things we don't quite know yet. 
If they turn out well, yes, I think that is a feasible kind of 
goal, but I wouldn't want to overpromise.
    Senator Shaheen. Because Europe is ahead of us on this, 
which is disappointing to see. Good for people in Europe, but 
we want to catch up with that.

                      HEROIN AND OPIOID OVERDOSES

    Dr. Volkow, I want to follow up on Senator Capito's 
questions about the heroin and opioid epidemic because in New 
Hampshire, we are experiencing the highest percentage of 
overdose deaths of any State in the country. It is not just an 
epidemic, I believe, but a pandemic. We talked about this when 
you were here before us last year. And you know, I was at a 
forum recently where the local hospital CEO said that they can 
tell when there's a new batch of heroin on the streets within 
an hour because they see about a half a dozen people admitted 
into the emergency room. And so that's what we're dealing with.
    So can you tell me what resources NIH, the Institute on 
Drug Abuse, has that can assist those people on the front 
lines? Because I think, as we talked last year when you were 
here, I think we have been very slow at the national level to 
respond in the way that this epidemic deserves.
    Dr. Volkow. Yes. As an institute and the NIH does research, 
so the way that we have responded is to provide with products 
that allow us to address and prevent the overdoses from 
opioids, which, of course, is very tragic, and I am very, very 
aware of what's going on in New Hampshire.
    Senator Shaheen. I know you are.
    Dr. Volkow. One of them very successfully led to a product 
that was approved by the FDA last year, which is intranasal 
Narcan, that has many advantages, including the fact that it 
can deliver very high concentrations to the blood very rapidly, 
and that's fundamental to overcome an overdose. And this is 
particularly relevant now on selling because we are seeing that 
many of these overdoses are due to the fact that they are 
combining with Fentanyl----
    Senator Shaheen. Yes.
    Dr. Volkow [continuing]. Which is very, very potent. So 
note that regular Narcan may be as useful as we need stronger 
products. This product also is very cheap, it's something like 
$37, so it becomes very, very available. That's one.
    The second strategy that we've also shown decreases 
overdoses is medication-assisted therapy, but it's not being 
deployed.
    Senator Shaheen. Right.
    Dr. Volkow. And sometimes it's not just the issue of 
deployment, but the structure is not there for patients to be 
able to take advantage of it. Very problematic in rural 
communities. So we are developing again with pharma in a 
partnership medications that will be easier to comply with and 
that will require much less infrastructure to sustain.
    But also we are doing research on implementation. How can 
we take advantage of the healthcare system so that they are 
involved in the deployment of medication-assisted therapy for 
individuals with opioid use disorders? Because it has been 
shown to prevent overdoses.
    Senator Shaheen. We're still hoping that you might be able 
to come to New Hampshire and talk about some of these new 
developments because I think it's the kind of thing that would 
be--is very important, and there was a lot of interest.
    Dr. Volkow. I would welcome it, and I think they are 
arranging it.
    Senator Shaheen. Yes.
    Senator Blunt. Thank you, Senator Shaheen.
    Senator Moran.
    Senator Moran. Mr. Chairman, thank you very much. Thanks to 
you and the ranking member for conducting this hearing.
    Dr. Collins and others, thank you very much for your 
presence here.

                          SPENDING PRIORITIES

    Dr. Collins, this wasn't my intended question, but I 
heard--I actually listened to the things you and others said in 
the panel this morning, and this is a response to what I heard. 
One of the things that you and I have talked about over a long 
period of time is how to prioritize spending within NIH, and 
you make decisions about what research receives a priority and 
what centers are receiving funding. You have appealed to me, 
and particularly in my time as the ranking member of this 
subcommittee, that we don't want the decisions to be made by 
Congress, we want science and medicine to determine, the 
researchers to determine, how money is spent at NIH, and you 
know, that's against our inclination. We have people who come 
to us who ask for help, who make suggestions of how we could 
improve their lives, their family members' lives. And I think 
all of us want to help, and you'd love to say we'll give NIH 
more money to cure or treat this disease. I have believed in 
the theory that those decisions are best made by science and 
medicine.
    Do you have evidence--I mean, one of the things you said 
was we ramped up, ``sped up'' I think was your word, research 
in regard to Zika. What that would suggest to me, that if you 
can ramp up something to do that, do you not have to diminish 
something else? And so my question is, when you assure us that 
you're making priority decisions based upon science and 
medicine, when you increase spending someplace, is there a 
corresponding reduction in spending someplace else?
    Dr. Collins. It sort of has to be that way, doesn't it? And 
this is one of the things that we very much tried to outline in 
this NIH Strategic Plan, which is now just 4 months out and 
which I think does lay out the difficult situation we face when 
we have something that really requires urgent attention, like 
Zika, there needs to be a way to pay for it. Now, obviously in 
that situation, the administration has proposed an emergency 
supplemental lacking so far a response because it's taking 
time, just yesterday, now the Department advising that we shift 
dollars away from other things to put into that. But already, 
if Tony Fauci was here, he would say he was doing that, and by 
necessity, to try to accelerate that.
    So for all of us, as science managers, we are facing sort 
of Sophie's choices every day, especially in the course of the 
last decade or more where our success rates for grant 
applications have been the lowest in history, below 20 percent. 
And so one of the hardest things that each one of us at this 
table faces is that almost on a daily basis you have to turn 
away a science that you know is exciting, a science that is 
well designed, and science that is important for a particular 
public health need, but on the scheme of things, when you have 
to set priorities, which we're forced to do, it doesn't quite 
make that cut, and we know we're giving away opportunity.
    Senator Moran. Well, Zika perhaps is an example, but maybe 
not the best example, in the sense that----
    [Cell phone rings.]
    Senator Moran. I didn't know anybody had my phone number.
    [Laughter.]
    Senator Moran. I thought I was on the no call list.
    [Laughter.]
    Senator Moran. Dr. Collins, the sense that we would make 
medical and scientific decisions, Zika comes as something new, 
something relatively new, and so we make choices of allocation 
there, but on an ongoing basis, you've indicated, you know, 
promising developments in many areas, but I assume when you say 
that, that means that if there is a promising development on 
the horizon, that means that you're making a decision to put 
additional resources, dollars, into that research at the 
expense of something less promising. Is that true?
    Dr. Collins. That's absolutely true. That's our 
responsibility.

                 ALZHEIMER'S DISEASE AND DOWN SYNDROME

    Senator Moran. Okay. Let me ask a question about 
Alzheimer's, and particularly the relationship between Down 
syndrome and Alzheimer's. We've had this conversation, I don't 
know how recently, maybe even a couple years ago, but the beta-
amyloid deposits and the scientific evidence that those appear 
in individuals by age 40 who develop Down syndrome, who have 
developed Down syndrome, and that often apparently a 
correlation between that and Alzheimer's. What's the latest 
knowledge that's been gained in regard to the relationship 
between Down syndrome and Alzheimer's?
    Dr. Collins. Well, it's very clear that individuals with 
Down syndrome, who have an extra chromosome number 21, have a 
heightened risk of Alzheimer's disease as they get older, and 
they may very well develop that both pathologically and in 
terms of effect on the brain function by their twenties or 
thirties. This is presumably on the basis of the fact that the 
Alzheimer's amyloid protein deposits in the brain is on 
chromosome 21. So they have an extra copy of that and 
presumably, therefore, are making an excess amount of the 
protein, and ultimately it deposits.
    This is a tragedy for kids who may have been functioning 
pretty well and then develop this problem in their twenties and 
thirties, but it's research-wise also an opportunity that we 
want to take advantage of, knowing that these are individuals 
at very high risk who themselves and their families are 
interested in interventions.
    We are now mounting research studies with some of the new 
ideas about Alzheimer's prevention, specifically making those 
available to kids with Down syndrome who are in their twenties 
to see whether in fact we can show benefit and in the process 
learn everything we can about both Down syndrome and 
Alzheimer's disease.
    Senator Moran. Thank you. Thank you, Mr. Chairman.
    Senator Blunt. Thank you.

                CHEMOTHERAPY FOR BREAST CANCER PATIENTS

    I'm sorry. Dr. Lowy, I was at the Siteman Cancer Center at 
Washington University a few months ago and just sitting around 
a table talking with doctors there on the topic of breast 
cancer. They said their view was that maybe most doctors who 
deal with breast cancer are coming to the conclusion that 
chemotherapy is usually not needed, but they don't know how to 
determine whether it's needed or not, that maybe as many times 
as 8 out of 10 times that the chemotherapy that a breast cancer 
patient goes through after surgery, it just wasn't necessary.
    Comment on that generally and other things like that where 
both the patient and the cost could be dramatically impacted if 
we just had a little more information and more ways to identify 
a group of patients that we can clearly determine, ``You don't 
need this, you're in the 2 out of 10 that do,'' ``You do need 
it, you're in the 7 or 8 out of 10 that don't.'' Your thoughts 
on that would be helpful to me.
    Dr. Lowy. Thank you, Senator Blunt.
    First I want to thank you, Senator Murray, and your 
colleagues for the incredible strong support that you have had 
for NCI and all of NIH.
    Your question is critically important, and we are 
optimistic that the future of predictive oncology has enormous 
potential, the question of: How do you deliver the right drug 
to the right patient at the right time? And an important aspect 
of that is: Who should be treated and who should not be 
treated?
    We need to do two different kinds of research in order to 
establish that on an evidence-based manner. The first is to do 
more preclinical studies so that we understand the biological 
basis for the different prognosis for different patients with 
breast cancer. And the second is to do clinical research 
particularly through understanding large datasets that have 
been discussed earlier in the hearing to understand the patient 
responses and whether patients actually need this through large 
databases with genomic analyses, et cetera, that Dr. Collins 
referred to earlier. Through this combination, we will get to 
the point of being able to tell who is better to give more 
treatment to and who less.
    Senator Blunt. I think for those of us who are the ultimate 
laypeople in part of this discussion, having a few things like 
that that we can mention as possibilities make a difference. It 
certainly begins to make the case for how this research impacts 
individuals, how the research impacts overall healthcare costs, 
how the research leads to more opportunity for people and 
families, and it's just helpful for us to have.

                 ALLOCATING ALZHEIMER'S DISEASE FUNDING

    Dr. Hodes, if you know, looking at what you're looking at 
with Alzheimer's, as an example, how much of a factor is 
determined on how you allocate research dollars based on what 
you see as a growing problem rather than a more stable problem? 
Alzheimer's would be an example of your numbers.
    The committee asked you a couple of years ago to do some 
forward projections on this. You did. If your projections are 
anywhere close to correct, it's an astronomical problem, and I 
assume that has impact on how quickly you apply research focus 
there, but your thoughts on that would be helpful.
    Dr. Hodes. Thank you for the question. You summarized 
yourself very well the projections for cost, and of course, the 
cost isn't just dollars, but above all, is human suffering 
until we are successful. The increased funding that's been 
provided is being applied to research, research that's directed 
according to a plan very much based on best expert opinion, 
which sets up priorities, milestones. What we need to do each 
year to achieve with greatest optimism, at least the goal of 
the national plan, that is an effective intervention by 2025, 
it's an aspirational goal, it's a hope for goal, and so you're 
quite right, as we allocate resources in this area, we allocate 
across the spectrum, the most basic research to discover new 
targets, because we don't know that what we know now is 
ultimately what's going to give the best cure. Also, the 
translation of our current best targets into clinical trials. 
And the great hope we have now, I think, in the field, that by 
intervening in a way we couldn't just a few years ago in the 
disease process long before there are symptoms, we have an 
opportunity to arrest damage before it perhaps occurs 
irreversibly with death of brain cells and so on, all of this, 
as you say, driven by the suffering of people today as well as 
by the demographic projections of how great this problem will 
be and even increased magnitude in years to come because of the 
success we've had in increasing life expectancy and health span 
in so many other respects.
    Senator Blunt. Thank you.
    Senator Murray.

                            BIG DATA FUNDING

    Senator Murray. Thank you. I want to go back and ask Dr. 
Koroshetz a question on the big data. How much of the funding 
in your request is going to be dedicated to creating data 
centers in the fiscal year 2017 budget?
    Dr. Koroshetz. Yes, thanks. We have been thinking about 
this for a while. You know, the BRAIN Initiative starts out 
primarily developing new technologies, so that's currently in 
the space we're in now. So not a lot of big data coming in yet, 
but the expectation was that at about 3 years, which is going 
to be fiscal year 2017, that we would start moving into actual 
experiments that look at brain function in humans as well as 
animals, and so we are going to be challenged now with building 
the data platforms that will allow this work to happen on a 
collaborative basis.
    Having been at the Allen Brain Institute, you may have 
seen, they have a tremendous, tremendous data platform for the 
work that they're doing. And so, we have multiple different 
groups, doing different areas of research, and those groups are 
actually working out, what is the best data platform for them 
at this point. We expect in 2017, we will spend $5 million a 
year on data platforms.
    Senator Murray. $3 to $5 million. Okay.
    And Dr. Collins, let me go back to you. The challenge isn't 
unique just to the BRAIN Initiative, it's across NIH. What are 
you doing to make sure that we have common standards 
established across the entire enterprise to avoid creating 
incompatible systems and practices?

                      DATA SYSTEM STANDARDIZATION

    Dr. Collins. That is a very important challenge and 
responsibility. And again, as part of this Big Data To 
Knowledge, BD2K, program, we are actually funding something 
called a Data Discovery Index, which is one of our centers for 
data science, and basically this is attempting to come up with 
standards where data that's been produced on a wide variety of 
research studies, from basic to clinical, can be accessed by 
individuals who are looking for it without having to run 
through all kinds of incompatibilities. This is a challenge, 
but I think one that we're making some significant progress on. 
Obviously, it's easier if we do these things prospectively than 
trying to retrofit databases after the fact, and so there's a 
lot of focus in that space.
    What we're dreaming of, and which we have actually some 
significant pilot projects underway on, is a data commons where 
basically all of this information finds its way into a common 
space with standards, with appropriate so-called metadata, so 
when you get a data file, you know what it is and how it was 
derived and----
    Senator Murray. Housed at NIH?
    Dr. Collins. Probably in the cloud, but potentially our 
investigators contributing to it, and we would need to, as part 
of grant funding, supply the resources to make that possible.

                   DIVERSITY IN MILLION-PERSON COHORT

    Senator Murray. Okay. And let me just quickly ask you about 
the million-person cohort again. I am concerned about 
diversity, and I just wanted to ask you again, how do you make 
sure you're doing it and working with experts that you avoid 
the risk of bias that could affect the cohort's usefulness if 
it isn't a diverse trial?
    Dr. Collins. We want very much for this to be a 
generalizable cohort, which means we need to have 
overrepresentation of groups that are traditionally 
underrepresented. So that means minorities, that means 
individuals from lower socioeconomic status. We will look 
carefully when we open this up to direct volunteers and begin 
to try to see how we're doing as far as bringing such 
individuals in, and we'd be concerned that they might not be 
coming in as large numbers as those who are more in the 
majority population.
    A big effort is going to be for us, through the community 
health centers, to try to see how we could use, in an 
unprecedented way, those centers which give care to more than 
10 million people, also as an opportunity to carry out 
research, recognizing that we want people involved in this 
study not to think of themselves as subjects, but as partners, 
as full participants, in this effort, and we will approach them 
in that way.
    Senator Murray. When do you expect to have the details of 
that worked out and are going to be willing to share them?
    Dr. Collins. So we already put together the overall plan. 
It was published last September as far as the design, the 
Precision Medicine cohort. We're now trying to figure out how 
to implement that. Later this year, by the fall, we'll have a 
much better sense of exactly how successful we're going to be 
with those various inputs.
    Senator Murray. Okay. Thank you. Thank you very much.
    Senator Blunt. Thank you, Senator Murray.
    Chairman Cochran.

                          RECENT BREAKTHROUGHS

    Senator Cochran. You may have just answered the question I 
was going to ask, but I'm going to ask it anyway. Do you have 
any recent breakthroughs that you can announce or tell the 
committee about as a result of investments that we have funded 
through the appropriations process here in Congress?
    Dr. Collins. One of the things that's a great privilege for 
me is to write every Tuesday and every Thursday a blog, I hope 
some of you are reading my blog, but I bet you're not, but I 
would encourage you, if you have a couple minutes, to do so. 
And as part of that, I survey across the whole landscape of 
biomedical research to see what new things have just appeared 
in the published literature that are particularly exciting. And 
so every time I have the chance to do that, there's a new 
story.
    Today's story, if you read the blog, which came up, I 
guess, about an hour ago, is about a engineer who has developed 
the kind of sensor that you could use for measuring all kinds 
of body performance properties, including glucose, if you 
wanted to use this as part of a artificial pancreas, but the 
sensor is designed so that it's not this rigid metal structure, 
which probably wouldn't work very well in the body, it's 
flexible, and this is an interesting sort of materials issue. 
If we are going to come up with ways to monitor all kinds of 
ways in which our bodies are performing in health or disease, 
we need these kinds of sensors to be very durable and to be 
possible to not interfere with function, which means sort of 
rigid structures may be not such a great idea. So that's 
today's blog, for instance.
    But looking across the board, goodness, some of the things 
that are happening in cancer right now, I guess I'd have to 
point to particularly something I mentioned in the opening 
statement that relates to President Carter, the ability to 
activate the immune system to tackle cancer cells that you know 
the immune system ought to be able to see, but somehow it's 
been masked, and we can unmask it with things like checkpoint 
inhibitors or actually taking immune cells to school and 
teaching them how to go chasing after the cancer that they 
haven't noticed, and to figure out how you might take those 
advances, which have changed everything for people with 
melanoma and leukemia and lymphoma, and figure out, how does it 
work for pancreatic cancer and how does it work for brain 
cancers, where we are not as successful? That's a big push. 
That's one of the reasons for the Cancer Moonshot that the Vice 
President is now promoting.
    And I guess I should ask Doug Lowy to say another word or 
two about why we see this as such an exciting moment and why 
there are some breakthroughs already happening, but more to 
come.
    Dr. Lowy. Senator Cochran, let me give a two-part answer 
first to your question and then what Dr. Collins has mentioned.
    The excitement in immunotherapy is matched by the fact that 
immunotherapy started really with basic research quite a long 
time ago with support from NIH specifically at NCI, and what we 
are seeing is almost on a monthly basis the surprising finding 
that checkpoint inhibitors progressively have beneficial 
effects in more and more cancers.
    The Vice President's Moonshot Initiative, an important part 
of it is to try to understand and utilize combination treatment 
so that we use combinations of immunotherapy, combinations of 
targeted treatment, and intersection between those so that we 
can get better responses and target a much broader percentage 
of people who have cancer.
    But the Moonshot goes far beyond that, and it looks at 
cutting edge research opportunities that have been created as a 
result of new understanding, and new understanding of the 
dynamics of this, and putting them together so that we can make 
accelerated progress in prevention, screening, treatment, and 
basic research.

                 CLINICAL TRANSLATIONAL SCIENCE AWARDS

    Dr. Collins. If I may, one of the things I think that the 
public is particularly excited about is when we have a clinical 
breakthrough, and Dr. Austin has not had a chance to speak, but 
I wanted to ask him to say a word about where we are by 
building this national clinical research network called the 
CTSAs, which is in a phase of coming forward with a number of 
ways of accelerating that part of the research enterprise. It's 
pretty exciting.
    Dr. Austin. Yes. So thank you. As you all know, the current 
numbers are, it takes about 15 years to go from a discovery to 
a new intervention, a new drug, for instance, and another 15 
years before it reaches all the patients that need it. That's 
always been a problem, but it's a particularly heartbreaking 
problem now given how many opportunities there are. So our 
Center is focused on the general issues that prevent that from 
happening faster, and our aim is to decrease that time by 
tenfold and increase the efficiency by which it happens. That's 
our goal, and I think it's achievable.
    [The graphic follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
    

    Dr. Austin. The biggest part of that, the year, those 
years, happens in the time when we're testing in people. There 
are many things that can be done through the CTSA program, 
which is this unprecedented program that NIH has of academic 
medical centers all over the country which have been 
previously--oh, so there they are, that's where they are, in 
many or most of your States, and they have connections to the--
all the ones that don't have little dots there, connections to 
all the States in the Union. And what we've been doing is to 
tie these together into a collaborative national network for 
translational medicine such that patient clinical studies, 
multisite clinical studies, can get started up, recruited, 
completed, much more quickly and with much higher quality, and 
we've done this through a national network for IR, or 
Institutional Review Board standards of subcontracting, a 
national way to do recruitment for any clinical trial, it 
doesn't matter what the disease is, and novel clinical trial 
designs. So those are just some of the things that we're doing 
through the program. And I really do want to thank you for your 
support in doing that because it's really been critical to us.
    Senator Cochran. Thank you very much.
    Senator Blunt. Thank you, Chairman.
    Senator Shaheen.

                          NIH/DHS PARTNERSHIP

    Senator Shaheen. Thank you, Mr. Chairman. I very much 
appreciated getting a copy of this NIH-wide Strategic Plan. I 
haven't had a chance to review it completely, but I wanted to 
ask a question that puzzles me as I look at the list of your 
frequent Federal partners and see many agencies that I would 
expect and departments I would expect to be on the list: DOD, 
EPA, Veterans Affairs. But what is not on this list is the 
Department of Homeland Security, and I found that puzzling 
because we had a hearing yesterday before our subcommittee of 
Appropriations where we heard from the DHS Office of Health 
Affairs, their Domestic Nuclear Detection Office, the Science 
and Technology Office, and they talked about some of the things 
that they're working with respect to workforce issues for both 
mental and physical health. And so I'm just puzzled by whether 
that's an omission on this list or whether you don't work with 
them regularly, and why that is.
    Dr. Collins. That's a great question. We do work with them 
in terms of particular topics of shared interests, such as, for 
instance, concerns about bioterrorism. I think the list that 
you see in the strategic plan is more about agencies where we 
share research projects, where we're putting dollars together 
into something to try to do a research study and get an answer. 
Our work with Homeland Security is really much more about 
policies, and we see them quite regularly when it comes to 
that, particularly when it comes to concerns about infectious 
diseases.
    Senator Shaheen. That's helpful. The hearing yesterday 
actually was on their R&D efforts, and so there was some 
overlap, and I just--I'm always concerned about the silos that 
I think too often we work in, in government and the need to 
coordinate and cooperate across agency portfolios so that we 
get the benefit of what everyone is doing.
    Dr. Collins. I appreciate your pointing this out, and it's 
something I will personally look into to see whether it could 
be in fact we are working with them in an R&D project and I 
just didn't know about it and didn't put it in that plan. But I 
will follow up on that.
    Senator Shaheen. Thank you. I appreciate that.
    Thank you, Mr. Chairman.
    Senator Blunt. Senator Cassidy.

                       UNIQUE IDENTIFIERS IN BD2K

    Senator Cassidy. Hey, Dr. Collins, a couple other things. 
As I look at your BT--your Big Data To Knowledge initiative, 
and you speak about having centralized data where people allow 
their EHR (Electronic Health Record) information to be 
transferred, obviously, some folks will be in multiple EHRs. 
That suggests to me that you've some way decided on a unique 
identifier, means of identifying. On this panel and this 
Senate, there is some concern about unique identifiers, however 
they be. So do you want to give an in-depth--if you think it's 
too in depth, but if you could point me in the direction 
because we are trying to understand the use of unique 
identifiers, et cetera.
    Dr. Collins. Very important and complex topic. Purely from 
a research perspective, it would be wonderful to have unique 
identifiers so that we could deal with circumstances where we 
have data on the same person coming from multiple directions. 
We understand the concerns that many have about the use of such 
identifiers, and so we are not counting on that becoming a 
reality, and instead, it becomes necessary to use other kinds 
of algorithms to try to disaggregate records that appear to be 
from the same person, but might not be. And of course, 
oftentimes one tries to do that with simple things like birth 
dates and middle names and so on, but there will be times where 
we don't get that right.
    The good news, I guess, is that we're talking about very 
large studies where in fact if we are unable to utilize a few 
records because we can't be sure of their particular 
provenance, we may just have to set those aside.
    Senator Cassidy. The answer you just gave suggests that it 
won't be a passive process where somebody will designate my 
records shall go, but there will be some sort of outreach from 
the database searching like a bot, where did Bill Cassidy show 
up as you search, and then to pull in there's a Bill Cassidy 
that previously consented for his data to be--is that correct?
    Dr. Collins. That is correct, because we understand the 
sensitivities about not having electronic health records with 
personal identifiers being stored in one common dataset where 
there might be more of a potential for hacking problems.

                        STORAGE OF BIOSPECIMENS

    Senator Cassidy. Now, in that case, I've looked at it, much 
of what your PMI (Precision Medicine Initiative) has done is 
said to be centralized, but it sounds as if your EHR aspect 
will be federated in that my record will reside in Louisiana, 
but nonetheless, here in D.C., my blood sample would be kept, 
my hair, my nail clipping, and somehow that has reached out to 
where my primary care physician is in Baton Rouge. Is that 
fair?
    Dr. Collins. With regard to the biospecimens, we anticipate 
that in many instances these are people who part of health 
provider organizations and there obtain the biospecimens, but 
we do intend to have a biobank which is centralized where all 
these specimens are stored and kept over many years of time. 
So, yeah, you're right, that will be centralized even though 
the details of the electronic health record will remain with 
the patient.
    Senator Cassidy. Now, I've read an article by Keith 
Yamamoto and heard a lecture by him. I know he's been on 
advisory boards.
    Dr. Collins. Yes.
    Senator Cassidy. Very impressive, talks about the Google 
Map aspect of it. Again, your thinking prepared me for this, 
but the genomes, the microbiome, the exposures, behaviors, 
clinical tests, and EHR. Now, the expense of that is going to 
be enormous. So is your initial PMI going to include all these 
layers, or would that be something that we move towards?
    Dr. Collins. The latter. It's a very important question. 
We're going to start off very simple to both try to save costs 
and try to be sure we have this set up in a fashion that is 
completely robust. We don't, in fact, even anticipate doing 
much DNA analysis on individuals who join just from blood DNA 
for the first year or so, and certainly the idea of adding a 
microbiome part, which many of us are excited about, would be 
downstream. That will help us because the costs of those 
analyses are coming down, as you know, quite dramatically. 
Right now, we could not afford, with a million people, to do 
all the things that we'd like to, but if we stretch that out 
over the coming years, the costs will come down, and we think 
we can afford to add those things as we go along.
    Senator Cassidy. Going back to the business model, though, 
I can see where, okay, so gut flora can influence obesity, for 
example.
    Dr. Collins. Yes.
    Senator Cassidy. So we'll be swabbing gut flora. But I 
guess I keep on going back to the business model because I can 
see this terabytes and terabytes growing, so it not only grows 
in terms of terabytes, but in terms of its bite on the NIH 
budget, the cost to accumulate, to maintain, longitudinally on 
a million people, and from your aspect, you actually want to 
grow that million to a larger number.
    So I see that California has begun their own Precision 
Medicine Initiative. I can imagine other States might as well, 
both as an economic driver as well as an aid. I don't know how 
far your business model is going down, but I can still see a 
federated model of this where instead of everything 
centralized, just as you federated the EHR, so you've federated 
some of this other.
    There's a unique population in Louisiana of young pre-
menopausal black women who have triple negative breast cancer, 
and another group of folks of Cajun extraction at high risk for 
colon cancer. I have tremendous interest in my State because I 
want to address both the needs of these women and these men. It 
seems more practical that that would be domiciled, all that 
specimen, et cetera, in Louisiana than there; the women are in 
an impoverished area of the State, as an example.
    So anyway, any thoughts about that, a federated model of 
the whole setup as opposed to----
    Dr. Collins. I think part of the conversation is 
distinguishing between the Precision Medicine Initiative, which 
is this explicit now designed cohort of a million people, and 
Precision Medicine writ large. I think the concern I would have 
is that we not try to have the initiative take on all of the 
opportunities that now exist in Precision Medicine. They should 
be also going forward supported by all of the NIH Institutes 
and other sources as well. And it will serve us well, I think, 
best at the present time if the million-strong cohort keeps a 
very simple approach and doesn't focus on any specific 
diseases, but tries to enroll a generalizable population on 
which other studies can then be layered.
    Senator Cassidy. A follow-up question, but you may tell me 
I should do a QFR unless you're going to give me an allowance 
for one more.
    [Laughter.]
    Senator Cassidy. Forgiveness, not the permission.
    [Laughter.]

                          DUPLICATIVE DATASETS

    Senator Cassidy. But that tells me then that we're actually 
going to have duplicative efforts because I think I've read 
that there are 70 different datasets at NIH, and so logically--
now, I may not have that quite right, but each institute has 
its own dataset, and there is some effort to coordinate, but 
that means that we're going to have these 70 different datasets 
and we're going to have the PMI, the Precision Medicine 
Initiative, Ken Mandl has written so well, that really we don't 
need to have all these different datasets plus, rather, we need 
this to be able to bring in these different datasets.
    We're trying to find you funding, but, again, I see this 
initiative taking more and more of what Senator Cochran is 
going to give you. And if we could integrate, now that you've 
thought about this, if we could integrate this, why not, if you 
will?
    Dr. Collins. Well, maybe I didn't explain this as clearly 
as I should have. The Precision Medicine Initiative has had its 
budget sort of thought through, and that's in the proposal that 
came out in September, and right now for fiscal year 2017, 
proposed at $300 million. They need to ramp up to about $500, 
but not to go beyond that. But let me be clear, the institutes 
at NIH all look at this million-strong cohort and think, wow, 
what a great platform on which we could layer all kinds of 
other studies. With a million people, there are going to be 
tens of thousands who have a particular condition already 
consented for research, already with background information.
    So a lot of the studies that we have been doing in the 
past, by setting them up de novo, which is expensive, and then 
running the study and then closing it down, can now be done 
much more efficiently by utilizing this platform for whatever 
it is that we need more information about. I think ultimately 
this saves us a lot of money over what we currently spend in 
clinical research.
    Senator Cassidy. Okay. Thank you. I yield back.
    Senator Blunt. Thank you. Well, Senator Cassidy figured out 
how to get his second and third round at the same time.
    [Laughter.]
    Senator Blunt. You know, on the national children's study 
that was done a few years ago, this diversity topic at the end 
of that study I think became one of the more questioned parts 
of the study, so a lot of these questions I think are helpful. 
There will be--the record is going to stay open for a week for 
additional questions, but is there anything while we're all 
here for another 5 minutes or so that you or any of your 
colleagues would like to address?
    The written questions are good, and they're particularly 
good for people who have submitted them. I'm not sure that very 
many people look at the questions they didn't ask in the 
written questions. So is there anything here--we almost left 
Dr. Austin out. Is there anything here that any--Francis, Dr. 
Collins, that any of you want to bring up?
    Dr. Collins. Any of you want to volunteer a point that you 
didn't get to make that you thought would have been 
particularly timely?
    Dr. Lowy. Thank you, Senator Blunt. I think that you all 
have a copy of the New England Journal of Medicine perspective 
that Dr. Collins and I wrote and was published earlier this 
week about the Vice President's Moonshot Initiative. Dr. 
Collins and I and my colleagues at NCI, as well as many 
extramural people, are working closely together to try to 
develop what we think are going to be incredible opportunities 
for cancer research to benefit patients. This effort really 
goes from basic science all the way to implementation, and 
thanks to your strong long-term support, we are poised to 
accelerate progress thanks to this proposal.
    And we have a blue ribbon panel that is going to be 
reviewing what we currently propose as well as looking forward 
to receiving other potential enormous opportunities. We are not 
trying to cover the entire waterfront of cancer research, but 
instead, to point to specific opportunities for research that 
will be bold, feasible, and have an impact in basic prevention, 
screening, and treatment.
    Thank you.
    Dr. Koroshetz. Yeah, I would just like to talk a little bit 
about the question of priorities that came up and just make the 
point that if you look at the history of advances, you can't 
predict where they were going to come from. And so I think it's 
tricky to say, you will get a certain result if you put money 
into that I think Zika is a great example. It turns out that 
one of the investigators who was working on the BRAIN 
Initiative to develop ways of identifying all the different 
cell types in the brain is the one who found out how the Zika 
virus was getting into the brain. He had nothing to do with 
Zika, but that technology turned out to be beneficial, and 
there was no way of predicting this.
    Our major advance lately was a study using a diabetes drug. 
The study was 17 people who had a stroke, and also but didn't 
have diabetes had an abnormal glucose metabolism. We treated 
them for 5 years with a diabetes drug, and their stroke risk 
dropped by 24 percent. So, again, this is something that you 
couldn't have predicted, but retrospectively, it kind of makes 
sense.
    And so I just urge the committee to think about this 
importance of the foundational basis of research, which is 
critical. Targeted research is risky in the sense that you're 
putting your money on one horse. You don't actually know all 
the time which horse is going to win.
    Senator Blunt. Anything else?
    Dr. Collins. I'll just add to what Walter said about the 
convergence both of science that comes from unexpected 
directions, but also about scientific disciplines that have 
increasingly come together. You mentioned your experience of 
seeing how engineers are playing a role in biomedical research 
in really exciting ways. That's happening all around us, and 
the idea that we have to have physics over here and chemistry 
over there and biology over there, engineering over there; not 
anymore. These are all very much now coming together in an 
integrated way.
    I guess I would just like to say, because I've now been at 
NIH for some 23 years, it was real poignant today walking from 
Union Station over here to this hearing, passing by the pink 
dogwoods and tulips that are blooming along the sidewalk and 
realizing this is probably my last opportunity to appear before 
all of you distinguished Senators.
    People have asked me since I became NIH director 7 years 
ago, ``So what's that part like where you have to interact with 
the Congress?'' and I always break into a smile and I say, 
``It's one of the favorite things that I get to do because I 
get to sit in the room or in a hearing with very substantive 
people who are trying to lead our country in the right 
direction and talk about medical research, and it's a topic 
that everybody is interested in, and it's not partisan, and 
it's not political, and everybody wants to do the right 
thing.'' And I can't think of a single one of those 
interactions that went badly, and I'm happy to say today has 
added to that list of things that actually went really well.
    And so I just want to thank you, the four of you still 
here, and all the others who aren't here, but who I've had the 
chance to talk to, hundreds of them, over the course of this 
time, for your dedication to our country, for trying to do the 
right thing for all the people out there whose hopes and dreams 
are rested upon progress in this area, because everybody cares 
about health and everybody hopes that there will be something 
there for them if they fall ill.
    You are doing wonderful work. We are thankful to you for 
what you've done and hopeful for what you may be able to do 
this year, even in what is undoubtedly a challenging time. So 
thank you.
    Senator Blunt. Well, thank you, Dr. Collins, and you've 
done a great job leading the organization. Every time you 
suggest this could be the last time you're doing something, I'm 
always here to encourage you not to rush out the door.
    [Laughter.]
    Senator Blunt. There are plenty of things yet to be done, 
and I would be personally pleased if you continue to be a big 
part of those things to be done.
    Also, I think comments were just made, it's so important to 
us to realize that you can't prescribe results, and not to 
become overly prescriptive in the work that you do or how you 
do it. The Thompson Center I mentioned earlier at the 
University of Missouri deals with autism. Somebody from the 
engineering department is very engaged in trying to find an 
early way to detect autism in very young children with some 
equipment looking at eye examinations, no medical background, 
but a very important part of that team, and you know, what 
Walter mentioned, is discovering things you don't think you're 
going to discover, and we don't want to build walls that make 
it impossible for you all to have that kind of flexibility and 
determination.

                     ADDITIONAL COMMITTEE QUESTIONS

    So thank you for today. The record will stay open for one 
week for additional questions.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
                Questions Submitted by Senator Roy Blunt
                           ``surge'' funding
    Question. NIH received 2 year ``surge'' funding in fiscal year 2009 
and fiscal year 2010 as part of emergency funding contained in the 
American Recovery and Reinvestment Act of 2009. Dr. Collins, can you 
discuss what happened in fiscal year 2011 when this ``surge'' funding 
was not maintained and NIH had approximately $5 billion less in funding 
than it did the year before?
    In particular, as we think about the appropriate upward funding 
projection for NIH, would you ever want funding to decrease at a given 
point?
    And what happens to the research infrastructure the first year 
funding is reduced?
    Answer. Everyone was aware that the $10.4 billion NIH received 
under the American Recovery and Reinvestment Act (ARRA) would be one-
time funding. It was spent in a way that did not create out-year 
commitments, either by providing full funding for a multi-year research 
project up front, or by making capital investments such as construction 
projects. As a result, the return to a more typical funding level in 
fiscal year 2011 did not have the same impact as a reduction in annual 
funding.
    NIH usually awards grants for multiple years, with each year's 
funding coming from the current year appropriation. Whenever possible, 
an increase in appropriations is used to make more new and competing 
grants. Those grants will continue to require a similar level of 
funding in the out years, as noncompeting grants. With flat or 
decreasing funding the next year, the number of new and competing 
grants is likely to decline, as the prior year increase has to be used 
for the additional noncompeting grants. The optimal scenario is 
increasing funding at a steady rate; that allows the number of new and 
competing grants to increase each year.
    If it is clear in advance that a funding increase is one-time 
rather than recurring, NIH can take steps as it did with ARRA to avoid 
a negative impact the following year. A reduction to recurring funding, 
especially a large reduction, would be damaging to NIH. For example, in 
fiscal year 2013 there was a major reduction in funding due to 
sequestration. Compared to fiscal year 2012, the number of new and 
competing research project grants (RPGs) declined by more than eight 
percent, and noncompeting RPGs had their funding cut by nearly 5 
percent on average. The number of National Research Service Award 
trainees declined by almost five percent, and approximately 7 percent 
fewer new patients were admitted to the NIH Clinical Center.
      drug repurposing & clinical and transitional science awards
    Question. Dr. Austin, clinical trials are key to developing 
treatments for disease, but I often hear that they are quite time 
consuming and costly. What is NCATS and its Clinical and Translational 
Science Award program doing to improve the clinical trial process?
    Answer. NCATS is grateful to the committee for its fiscal year 2016 
support of the Clinical and Translational Science Awards (CTSA) 
Program. We define translation as the process of turning observations 
in the laboratory, clinic, and community into interventions that 
improve the health of individuals and the public--from diagnostics and 
therapeutics to medical procedures and behavioral changes. Through the 
CTSA Program and its extensive network of research institutions 
nationwide, NCATS is developing innovative solutions to improve 
efficiencies and the quality of clinical and translational research. 
Our Center also supports multiple efforts to repurpose existing drugs 
and compounds for potential treatments for other diseases and 
conditions; however, because these repurposing programs do not directly 
relate to the clinical trials process, our response is limited to the 
NCATS CTSA Program.
    NIH's Institutes, Centers, and Offices have a long, distinguished 
history of funding landmark clinical trials including those for 
coronary bypass surgery, treatments for breast cancer, and anti-
retroviral drugs for people at high risk for HIV/AIDS infection. NCATS 
is addressing issues common to all clinical trials with a focus on 
approaches to harmonize and streamline multisite clinical trials, which 
are more complicated to initiate because each trial site currently 
follows its own business and research practices. This continued work to 
improve clinical trials research builds upon our Nation's success as a 
leader in biomedical discovery and provides a competitive advantage in 
developing, demonstrating, and disseminating innovations that help get 
more treatments to more patients more quickly.
    One NCATS approach is the development of a more efficient review 
and approval process of multisite clinical trial safety using a single 
Institutional Review Board (IRB) model. Currently, clinical trial 
researchers cannot begin recruiting participants until an IRB performs 
an ethical review of studies involving human subjects. IRB review often 
slows down a multisite clinical trial because the different sites must 
address inconsistencies across the different IRBs. The single IRB model 
streamlines IRB review by having sites rely on a single IRB without 
compromising ethical principles and protections. Through the CTSA 
Program, NCATS has supported demonstration projects of single IRB 
models and is moving toward a model that will be used throughout the 
CTSA Program network. And, in 2016, NCATS will announce CTSA Program 
Trial Innovation Center awards to fund centers that will network with 
existing CTSA Program hubs to facilitate multisite clinical trial 
implementation, including use of a single IRB model.
    Another CTSA Program goal is to support recruitment efforts for 
clinical trials. Multisite clinical trials may require substantial 
subject sample sizes to credibly test hypotheses, and trials often are 
delayed or even fail entirely due to challenges in recruiting 
participants. To help combat the challenges, NCATS will issue awards in 
2016 for CTSA Program Recruitment Innovation Centers. These will 
strengthen the CTSA Program's network capacity by addressing 
longstanding issues associated with multisite clinical trial 
recruitment, including access to data on the availability of potential 
participants; recruitment strategies that employ innovative approaches 
from other fields such as communications; and engagement of relevant 
stakeholders (e.g., potential participants and referring clinicians) 
early in the recruitment process.
                     precision medicine initiative
    Question. As you continue to shape the Precision Medicine 
Initiative (PMI), have you considered what projects other countries are 
working on to further personalized medicine and whether they are 
complementary or competitive? For example, both Great Britain and China 
have PMI programs.
    Answer. As you are aware, during its planning efforts, the PMI 
Working Group of the Advisory Committee to the Director (ACD) engaged 
many individuals and organizations across industry, nonprofits, and 
academia to ensure that Federal funds dedicated to the PMI Cohort 
Program are used to fill gaps and not duplicate effort. The PMI Working 
Group, for example, was constituted of nationally and internationally 
renowned experts in a variety of precision medicine relevant areas and 
represented industry, nonprofits, academia, and the participant 
communities, including Sir Rory Collins, who leads the UK Biobank. NIH 
continues to interact with industry, nonprofits, and academia with 
other efforts and cohorts, including Google's Baseline Study, patient 
groups, NIH's own funded cohorts, and Department of Veterans Affairs 
efforts like the Million Veteran Program, as well as the growing number 
of international research precision medicine-oriented cohorts. NIH's 
ongoing interaction with these important organizations will allow 
opportunities for appropriate, mutually beneficial coordination to 
emerge as the PMI Cohort Program developes.
    Question. At the White House PMI Summit event in February 2016, all 
of the patients presenting precision medicine success stories 
attributed those successes to genome sequencing, specifically. Yet, to 
date, no plans have been announced for collecting sequencing data from 
PMI participants. Why is that? Are there plans to do so?
    Answer. NIH has consistently identified the collection of 
biospecimens for laboratory and genomic analyses as a critical 
component of the research cohort. The award to establish a biobank to 
receive such specimens will be issued this summer. Once the biobank is 
established, then the PMI Cohort Program may begin specimen 
collections, processing, and storage to be conducted over the next 4 
years, during which time the timing and platform for genomic analyses 
will be identified and implemented.
    Question. How will NIH ensure the full participation of women and 
minorities in PMI?
    Answer. The PMI Cohort Program intends to enroll one million or 
more U.S. volunteers representing all life stages, all health statuses, 
and all regions of the country, with a special emphasis on enrolling 
those who are historically underserved by biomedicine and 
underrepresented in biomedical research. We project that the majority 
of the one million volunteers that will be enrolled by the end of 2019 
(around 70 percent) will join directly through the healthcare provider 
organizations (HPOs, including federally Qualified Health Centers), and 
the balance (around 30 percent) will enroll directly into the Cohort 
(``direct volunteers''). The enrollments of the Cohort through both 
streams will be carefully monitored to ensure that our outreach and 
enrollment approaches are reaching a broad range of U.S. participants, 
including women and underserved communities that are historically 
underrepresented in research.
    Question. Is NIH working with the National Center for Health 
Statistics or other Federal partners that fund or conduct large, 
representative surveys to understand the biases in the PMI million 
person cohort?
    Answer. The PMI Cohort will not attempt to be a representative 
sample of the United States. Rather, the PMI Cohort will build a very 
large and very diverse cohort of participants from across the United 
States. This will allow the PMI Cohort to establish generalizability 
using a different approach: by having a diverse sample, it will have 
many subsamples that are composed of members of specific subgroups. By 
having a large sample, those subsamples will be large enough to develop 
estimates of effect and association for many of those subgroups. That 
will allow researchers to judge how similar those estimates of effect 
and association are across a variety of subgroups within the PMI 
Cohort, and thus to establish the generalizability of their findings. 
The development of this approach included extensive consultation and 
input from expert advisors through the ACD PMI Working Group process.
                            enrollment data
    Question. The GAO recommended that the NIH Director should make 
Institute-level enrollment data available through public means, such as 
through NIH's regular biennial report to Congress on the inclusion of 
women in research, or though NIH's website. How is NIH moving forward 
with this recommendation?
    Answer. NIH posted the most recent Institute/Center (IC) biennial 
inclusion reports for the fiscal year 2013-2014 biennial reporting 
cycle in early May 2016 at a newly created website: https://
report.nih.gov/recovery/inclusion research.aspx.
    NIH ICs currently provide their IC-level enrollment information 
during open, public sessions of their Advisory Council meetings along 
with a written report certifying their compliance with the NIH 
inclusion policy, and they will continue to take this action at least 
biennially in accordance with NIH procedures for biennial reporting of 
inclusion. As noted in NIH's initial response to the GAO report, NIH 
had already begun efforts to standardize the reporting format for the 
ICs as part of the ongoing NIH Inclusion Re-Engineering Project that 
began in 2011.\1\ NIH is continuing efforts to standardize a minimum 
set of data tables and graphics for each IC to use for biennial 
inclusion reporting, in addition to any additional analyses the IC 
would like to provide. The standardized reporting format will be 
completed before the fiscal years 2015-2016 Biennial Inclusion Report 
is due to be produced and posted in 2017.
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    \1\ Http://www.gao.gov/assets/680/673276.pdf.
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                              tuberculosis
    Question. The number of tuberculosis cases in the United States 
rose last year for the first time in 23 years according to the Centers 
for Disease Control and Prevention. What progress has the NIH made on 
developing more effective treatments and vaccines?
    Answer. Tuberculosis (TB) research, including the development of 
effective therapeutics, vaccines, and diagnostics, is a top priority 
for the National Institute of Allergy and Infectious Diseases (NIAID). 
NIAID supports a broad range of basic, translational, and clinical 
research on TB in the United States and abroad to combat TB, including 
the growing threat of multidrug-resistant (MDR) and extensively drug-
resistant (XDR) TB. As TB is the leading cause of death in HIV-infected 
individuals worldwide, NIAID also supports TB research through its HIV/
AIDS clinical trials networks to test TB therapeutics in the setting of 
HIV co-infection.
    NIAID is currently implementing the President's National Action 
Plan for Combating MDR-TB. TB research objectives outlined in Goal 3 of 
the Action Plan, Accelerate Basic and Applied Research and Development 
to Combat MDR-TB, are being addressed by NIAID in collaboration with 
partners at CDC and USAID. NIAID is leveraging current and past 
investments in biomedical research to inform critical scientific areas 
of TB research and to facilitate development of new drugs, vaccines, 
and diagnostics to help prevent TB and the emergence of MDR-TB.
    As part of its TB research portfolio, NIAID offers preclinical 
services to TB researchers in academia and industry to help bridge gaps 
in the product development pipeline and advance promising 
countermeasures to combat TB. NIAID resources have contributed to two-
thirds of clinical TB therapeutic candidates and approaches currently 
in development. NIAID support has helped advance several candidate TB 
drugs, including SQ109 developed by Sequella, Inc., and Pretomanid 
developed by the Global Alliance for TB Drug Development. NIAID 
scientists were instrumental in the development of both of these drugs. 
Additionally, an NIAID-supported clinical trial will soon test two new 
drugs for MDR-TB, bedaquiline and delaminid, singly and in combination 
in patients with and without HIV co-infection. NIAID scientists also 
participate in the ``TB Drug Accelerator'' program, an innovative 
public-private partnership coordinated by the Bill & Melinda Gates 
Foundation that brings drug companies together to share their chemical 
libraries with researchers to assist in the identification of novel TB 
drug candidates.
    NIAID also has made efforts to improve existing therapeutics for 
drug-susceptible and drug-resistant TB. Clinical trials are underway to 
evaluate novel treatment strategies using existing drugs, such as 
rifampin, levofloxacin, and linezolid. In addition, NIAID and other 
scientists are evaluating two medical imaging technologies, positron 
emission tomography and computed tomography, for their utility in 
predicting TB drug treatment outcomes by allowing researchers to 
monitor whether bacteria remain in the lungs after therapy. These 
technologies could be used in combination to help facilitate and 
shorten clinical trials for new drug treatments. Studies to further 
develop these technologies are currently underway in South Africa.
    In addition to supporting research on TB therapeutics, NIAID is 
pursuing TB vaccine development to improve upon existing TB vaccine 
options. NIAID-supported research has contributed to ten of the TB 
vaccine candidates currently in clinical trials, and NIAID is 
supporting preclinical development of additional promising vaccine 
candidates. For example, NIAID supported early-stage development of 
vaccine candidates H56 and ID93. In addition to protecting against 
infection, these TB vaccine candidates may also be effective in 
protecting individuals with latent TB infection from developing active 
TB disease. These vaccines are currently in clinical development.
    Longstanding NIAID investments in TB research and collaboration 
with domestic and international partners have advanced the development 
of novel therapeutics and vaccine candidates. NIAID remains committed 
to combating TB and will continue to support basic, translational, and 
clinical research focused on developing new countermeasures for drug-
susceptible and drug-resistant TB.
                    department of defense brain bank
    Question. The Department of Defense and the NIH partnered to create 
the world's first human brain tissue repository for military personnel. 
However, it is my understanding that NIH researchers are having issues 
accessing post-mortem tissues from servicemembers affected by blast 
injury. Dr. Koroshetz, are NIH researchers being provided access?
    What are the hurdles you are facing to gain access to these 
resources?
    Answer. It is our understanding that the major hurdle is the 
absence of an effective manner to obtain informed consent from a 
service member's family that would allow a careful examination of 
tissue removed at autopsy by the DOD Medical examiners. DOD currently 
classifies a careful examination of brain tissue for the effects of 
blast injury as research, which requires informed consent. It is our 
understanding that autopsies have been performed at the Office of the 
Armed Forces Medical Examiner in Dover, Delaware, and that brain tissue 
was removed but is not available for detailed study due to the lack of 
a means to obtain consent for study. Although consent is a sensitive 
and highly personal decision, we believe many families would recognize 
the potential of such examinations to benefit other current and future 
service members. DOD has recognized and understood the issues 
concerning service member brain donation for research purposes, and is 
working to increase the availability of specimens while also complying 
with established law and policy governing human subjects research and 
respecting the needs of families who have recently lost a loved one.
    Based on the examination of the handful of well-studied cases, we 
are concerned that blast injury causes a unique type of brain injury. 
To know how common these unique findings are requires examination of a 
larger number of brains. If these findings can be substantiated it 
would shift the focus to brain imaging evaluations of living veterans 
who were exposed to blast and would also help to direct valuable 
research focused on means to protect future service members from blast-
induced brain injury.
    Question. Can you discuss the importance of having access to brains 
that have experienced blast injuries?
    Answer. Access to brains that have sustained a blast injury is 
absolutely essential to understand the effects of blast injury. DOD and 
academic laboratories are studying the effects of blast on animals, and 
scientists are modeling its effects on the brain with computer 
simulations. However, these studies are not informed by what actually 
occurs in human brains that have been exposed to blast. The physical 
forces from a blast differ in crucial ways from other types of trauma 
that have been studied in human brains, and the human brain is unique 
in many ways--for example, the much larger size of the human brain, and 
especially the cerebral cortex, compared to animals can substantially 
change the physical forces on brain tissue from blast injury. The 
unique findings seen in the few well-studied cases, if substantiated, 
suggest that a change in focus is appropriate.
    Question. What do you think researchers will learn if they have 
access to brains that have sustained a blast injury?
    Answer. Based upon examination of brain tissue from the handful of 
cases, we are concerned that blast injury damages the brain in unique 
ways, compared to other types of trauma. Understanding the unique 
pathology is essential to develop better ways to diagnose and treat 
service members exposed to blast injury and to improve protective 
measures. For instance, it is an open question as to whether 
neuropsychiatric disorders classified as PTSD, or even suicide itself 
may be related to chronic effects of neurotrauma. Brain examination is 
currently the only means to pursue these questions at this time. The 
most urgent question is to understand the incidence and pattern of 
blast injury in brain tissue and to link the pathologic findings to the 
service members' medical histories.
      environmental influences on child health outcomes initiative
    Question. ECHO is proposing to use existing cohorts as a critical 
aspect of understanding child health and allow researchers to get a 
better understanding of the normal trajectory of child development.
    Have you selected any cohorts yet? Will the array of cohorts 
include broad population samples?
    Answer. The Environmental influences on Child Health Outcomes 
(ECHO) program will leverage existing resources to investigate the 
longitudinal impact of early childhood environmental exposures (e.g., 
physical, chemical, biological, social, behavioral, natural and built 
environments) on pediatric development and health outcomes with high 
public health impact. One specific component of ECHO--the IDeA States 
Pediatric Clinical Trials Network (ISPCTN)--will leverage the 
infrastructure at existing IDeA State centers by embedding clinical 
trials experts at IDeA State locations, facilitating their partnership 
with other academic institutions.\2\ This national pediatric research 
network may also help address access gaps for rural and medically 
underserved children.
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    \2\ Https://www.nigms.nih.gov/Research/CRCB/IDeA.
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    NIH recognizes the importance of robust recruitment plans that can 
address racial and ethnic minority health issues reflective of the 
needs of the U.S. population. When making awards, NIH will strive for a 
balance between a robust characterization of environmental factors, 
including consideration of geographic diversity, and health-related 
endpoints. Additionally, the ECHO program aims to utilize both large 
studies to build a repository on the trajectory of healthy development 
over childhood (health controls), and small, selective studies to 
address interesting targeted questions that are specific to a disease 
or have a high-risk population.
    Last fall, seven Funding Opportunity Announcements (FOAs) were 
released to solicit applications for the ECHO program. The applications 
were due on April 15, 2016 and will be reviewed this summer. Awards are 
anticipated to be made in September 2016; therefore, no specific 
cohorts have been selected for funding as of yet. Any investigator with 
an existing relevant cohort, whether it is supported by the NIH or not, 
was encouraged to apply.
    Question. Are you working with National Center for Health 
Statistics to ensure ECHO cohorts include measures that would allow you 
to compare subjects to studies such as the National Health and 
Nutrition Examination Survey?
    Answer. A major feature of the ECHO program is the sharing and 
harmonization of data across all of the cohorts. Standardized core data 
elements will be addressed across all studies: demographics; typical 
early health and development; genetic influences on early childhood 
health and development; environmental factors; and Patient/Person 
(parent and child) Reported Outcomes (PROs). During the planning phase, 
the ECHO Steering Committee, which will be composed of the principal 
investigators of the ECHO projects, cores and centers, the ECHO ISPCTN, 
and the NIH ECHO Program Director and staff, and the External 
Scientific Board, composed of external experts, will develop and 
provide valuable input on standardizing the collection of the core data 
elements. They will be strongly encouraged to consider how NHANES, 
NHIS, and other national surveys can inform the development of these 
standardized core data elements, and consider how the ECHO data could 
be compared to known national samples. Additionally, the Children's 
Health Exposure Analysis Resource (CHEAR) is a network of laboratory 
hubs that provides researchers access to comprehensive laboratory and 
data analysis services to measure environmental exposures. CHEAR is 
expected to become operational in the summer of 2016, and will have the 
capability of measuring the majority of targeted analytes CDC measures 
for NHANES, as well as others. The ECHO program is leveraging this 
existing resource to analyze personal environmental exposures from 
existing and prospective ECHO sample collections. Therefore, 
researchers should be able to compare much of the data generated from 
ECHO with that of other large studies.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby
                            cancer moonshot
    Question. Dr. Collins, I am curious of the role that the 
President's cancer ``moonshot'' initiative will play in the research 
specifically for childhood cancer. Currently, childhood cancer is the 
number one disease killer of children under 15 years old and the 
incidence of childhood cancer has increased each year for the past 25 
years. In addition, over the past 8 years, less than 4 percent of the 
National Cancer Institute's (NCI) annual appropriations have been 
allocated towards pediatric cancer. I understand the budget 
constraint's many of the institutes are under, however, can you explain 
why the NCI is not allocating more of its current resources towards 
childhood cancer initiatives given the statistics?
    Answer. The National Cancer Moonshot Initiative is an important 
opportunity to speed progress on childhood cancers. Not only is 
childhood cancer research one of the seven core elements within the 
initiative, several other elements are also important to advancing 
progress for children with cancer. Other Moonshot elements that are 
particularly relevant include:
  --extending early successes in immunotherapy for cancer treatment 
        (for adults and children)
  --building an even greater understanding of cancer genomics--the 
        genetic changes that occur within the cancer cell and in 
        surrounding and immune cells responding to the cancer
  --building expanded data sharing systems to speed discovery and 
        verify treatment response for children and adults.
    Cancer in children poses unique challenges. Childhood cancers 
generally possess many fewer mutations than adult cancers and are less 
likely to have activation of enzymes known as kinases, which are the 
most frequent targets of cancer drugs for adult tumors. The molecular 
changes that drive many childhood cancers arise in transcription 
factors and other cellular targets that are often considered 
``undruggable.'' However, new technologies, built upon advances in 
chemistry that allow the preparation of libraries of small chemical 
molecules with a much more complex arrangement of molecular shapes, 
offer the promise of identifying therapies with the potential to target 
the unique molecular changes found in pediatric cancers. The National 
Cancer Moonshot Initiative aims to support research such as this to 
deliver advances and new treatments for pediatric cancers.
    As part of the fiscal year 2017 Moonshot initiative, NCI will also 
intensify efforts to collect and analyze tumor specimens from the 
rarest childhood cancers, and NCI will enlist the pediatric oncology 
community to join in this effort. NCI also expects to build a clinical 
database focused on the course of rare pediatric cancers that will be 
widely accessible and will support further productive research that can 
lead to new cancer treatments.
    The National Cancer Moonshot Initiative's Blue Ribbon Panel and its 
working groups will continue to identify specific promising research 
opportunities for each element of the initiative, including childhood 
cancer research. The Blue Ribbon Panel includes a number of cancer 
researchers with pediatric cancer expertise, such as Dr. James Downing, 
President and CEO, St. Jude Children's Research Hospital, and Dr. Peter 
Adamson, Director of Experimental Therapeutics in Oncology at the 
Children's Hospital of Philadelphia. Dr. Adamson is also Chair of the 
NCI-supported Children's Oncology Group, and a member of the National 
Cancer Advisory Board.
    In addition to the Blue Ribbon Panel and its working groups, the 
initiative is also seeking feedback from across the cancer research and 
advocacy communities regarding all areas of research focus, including 
childhood cancer research.\3\ Additional information about the National 
Cancer Moonshot Initiative, including childhood cancer research within 
the initiative, can be found at the NCI website.\4\
---------------------------------------------------------------------------
    \3\ The public and research communities are invited to submit ideas 
at this website: https://cancerresearchideas.cancer.gov/.
    \4\ Http://www.cancer.gov/research/key-initiatives/moonshot-cancer-
initiative.
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New Childhood Cancer Research Initiatives
    NCI is also supporting new research opportunities specific to 
childhood cancer, including a Pediatric Provocative Questions 
Initiative and the Pediatric MATCH precision medicine trial. NCI is 
eager to accelerate progress in cancer research by attempting to define 
potentially game-changing scientific questions that could influence the 
directions taken by NCI-sponsored research in the future. The NCI 
Provocative Questions Initiative is designed to encourage research 
around some of the most challenging scientific questions while engaging 
the scientific community in serious debate in an effort to identify 
compelling research opportunities.
    NCI held two childhood cancer Provocative Questions workshops in 
2015 to identify questions that address gaps in the pediatric oncology 
research field. NCI plans to release the pediatric oncology provocative 
questions this spring through program announcements designed to 
generate innovative approaches to address childhood cancer research 
challenges.
    The Pediatric MATCH precision medicine trial will provide a 
tremendous opportunity to test molecularly targeted therapies in 
children with advanced cancers who have few other treatment options. 
With the genomic data captured in the trial, it will also produce an 
invaluable resource for studying the genetic basis for why some 
pediatric cancers progress or recur while others do not. As in the 
adult NCI-MATCH trial, DNA sequencing will be used to identify children 
whose tumors have a genetic abnormality for which either an approved or 
investigational targeted therapy exists. Pediatric MATCH, which will be 
led by the NCI-funded Children's Oncology Group, is under development 
and is expected to launch in late 2016.
Other NCI Support for Childhood Cancer Research
    NCI has prioritized the development of new treatments for pediatric 
cancer in the NCI Experimental Therapeutics (NExT) Program.\5\ This 
program focuses on advancing breakthrough discoveries in basic and 
clinical research into new therapies, and several new inhibitors with 
potential to treat pediatric cancer are being studied for this purpose. 
There are currently nine agents from the NExT program being studied in 
pediatric clinical trials. Two examples of these include the 
investigational agent ganitumab for Ewing sarcoma and the FDA-approved 
dinutuximab (ch14.18) therapy for high-risk neuroblastoma.
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    \5\ Http://next.cancer.gov/about/mission.htm.
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    NCI's active role in developing these agents is what has made these 
trials possible. The development of ganitumab was halted by the 
pharmaceutical industry after negative results in studies for adult 
cancers, and NCI acquired the agent from the industry sponsor to 
continue development for therapy for Ewing sarcoma. Similarly, NCI 
supported the development of dinutuximab for high-risk neuroblastoma 
for decades, from early funding for investigator-initiated research, to 
manufacturing and sponsoring the Phase III trial that led to 
dinutuximab's approval by FDA, and finally to the NCI Cooperative 
Research and Development Agreement (CRADA) with United Therapeutics 
that brought this drug to market for patients.
    As noted above, childhood cancers pose unique scientific challenges 
and opportunities. NCI is supporting research to address these 
challenges in ways that can lead to better outcomes for children with 
cancer. This is a high priority research area for NCI, and we are 
urging the oncology community to submit creative research proposals 
focused on childhood cancers. NCI continues to support the best 
research opportunities to identify promising new therapies, improve the 
outlook for cancer survivors, and to support the foundation of basic 
research needed to achieve these goals.
    The funding figures cited in your question reflect only research 
projects identified as specifically focused on childhood cancer in a 
given fiscal year, such as the research data reported in the NIH 
Research, Condition, and Disease Categorization (RCDC) database.\6\ 
While RCDC is a useful tool, it does not provide the complete picture 
of NIH and NCI investments that are critical to advancing childhood 
cancer research. For example, approximately half of the NCI budget--and 
half of the overall NIH budget--supports basic research that may not be 
specific to one type of cancer. By its nature, basic research cuts 
across many disease areas and makes important contributions to our 
knowledge of the underlying biology of cancer. This knowledge supports 
the ability of the research community to make advances against many 
cancer types.
---------------------------------------------------------------------------
    \6\ Https://report.nih.gov/categorical_spending.aspx.
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    Over the years, research in childhood cancers has led to important 
advances for adults with cancer. Similarly, research focused on adult 
cancers has led to progress for children with cancer. We have also 
demonstrated that research focusing on a particular type of cancer has 
led to advances across many cancer types. For these reasons, the 
funding levels reported in RCDC and other systems do not definitively 
capture all research relevant to a given category.
    In addition to soliciting applications in areas of scientific 
focus, NCI also remains committed to supporting a number of key 
research efforts focused specifically on childhood cancers. NCI has 
been renewing many of these programs for numerous 5-year funding 
periods. Examples of these critical long-term investments in childhood 
cancer research include:
  --The Children's Oncology Group (COG), which is part of NCI's 
        National Clinical Trials Network (NCTN), develops and 
        coordinates pediatric cancer clinical trials that are available 
        at more than 200 member institutions, including cancer centers 
        throughout the United States and Canada.\7\ In addition to 
        conducting traditional late-phase clinical trials, the COG has 
        established a Phase 1 and Pilot Consortium that is separately 
        funded by NCI to conduct early-phase trials and pilot studies 
        so new anticancer agents can be rapidly and efficiently 
        introduced into pediatric cancer care.\8\
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    \7\ Https://www.childrensoncologygroup.org/.
    \8\ Https://www.childrensoncologygroup.org/index.php/phase-1-home.
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  --The Pediatric Preclinical Testing Consortium (PPTC) systematically 
        evaluates new agents in genomically characterized childhood 
        cancer solid tumor and leukemia in vivo models.\9\ The primary 
        goal of the PPTC is to develop high-quality preclinical data to 
        help pediatric oncology researchers identify agents that are 
        most likely to show significant anticancer activity when tested 
        in the clinic against selected childhood cancers.
---------------------------------------------------------------------------
    \9\ Http://ctep.cancer.gov/MajorInitiatives/
Pediatric_Preclinical_Testing_Program.htm.
---------------------------------------------------------------------------
  --The Childhood Cancer Survivor Study (CCSS) is studying the long-
        term effects of cancer and cancer therapy on approximately 
        35,000 survivors of childhood cancer who were diagnosed between 
        1970 and 1999.\10\ NCI has supported CCSS since its launch in 
        1994. NCI has also recently supported a complementary effort, 
        the St. Jude Lifetime Cohort Study, which will allow for 
        replication of findings from genomic studies and the 
        development of collaborative projects to refine risk-based 
        follow-up guidelines and improve outcomes among childhood 
        cancer survivors.\11\
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    \10\ Http://www.cancer.gov/cancertopics/types/childhoodcancers/
ccss.
    \11\ Https://www.stjude.org/research/clinical-trials/sjlife-long-
term-effects.html?vgnextoid=1c4303fb30c23110VgnVCM1000001e0215acRCRD.
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  --The Pediatric Brain Tumor Consortium was formed by NCI in 1999 as a 
        multidisciplinary cooperative research organization devoted to 
        identifying superior treatment strategies for children with 
        primary brain tumors.\12\ The participating academic centers 
        and children's hospitals are responsible for the diagnosis and 
        treatment of the majority of children with primary brain tumors 
        in the United States. PBTC has a direct working relationship 
        with the Children's Oncology Group (COG) to ensure that results 
        from Phase I and II trials can be confirmed through additional 
        Phase II and multi-agent Phase III clinical trials in the COG.
---------------------------------------------------------------------------
    \12\ Https://www.pbtc.org/.
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  --The Pediatric Oncology Branch (POB) in NCI's Center for Cancer 
        Research, part of NCI's intramural research program, conducts 
        high-risk, high-impact basic, translational, and clinical 
        research dedicated to the study and treatment of childhood 
        cancers.\13\
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    \13\ Https://ccr.cancer.gov/pediatric-oncology-branch.
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                                 ______
                                 
              Questions Submitted by Senator Thad Cochran
                   pediatric clinical trials network
    Question. I am pleased that the NIH has shown a commitment to 
including IDeA States in the Pediatric Clinical Trials Network. It is 
my understanding that the network will focus on environmental 
influenced diseases like asthma, obesity, and prematurity, all of which 
are all too prevalent in my State of Mississippi. The current program 
announcement from NIH provides for grans to fund necessary 
infrastructure for clinical trials research sites and to promote career 
development for pediatric clinical researchers. Please provide me with 
more information about how this network will function as it moves 
forward. In particular, what studies will the network perform? How will 
the studies be chosen, and how will they be funded?
    Answer. NIH released a series of funding opportunity announcements 
(FOAs) on December 7, 2015 to establish the Environmental Influences on 
Child Health Outcomes (ECHO) program. The ECHO program has been 
designed to investigate the longitudinal impact of pre-, peri-, and 
postnatal environmental exposures on pediatric health outcomes with 
high public health impact. The IDeA States Pediatric Clinical Trials 
Network (ISPCTN) has been developed as a component of the ECHO program 
and includes two FOAs: The Clinical Sites for the IDeA States Pediatric 
Clinical Trials Network (RFA-OD-10-001), and the Data Coordinating and 
Operations Center for the IDeA States Pediatric Clinical Trials Network 
(RFA-OD-16-002). ISPCTN is being established to provide an opportunity 
to children in rural and medically underserved locations in IDeA States 
to participate in state-of-the-art clinical trials, to enhance 
pediatric clinical trial capacity at State and national level, and to 
facilitate the implementation of well-designed clinical trials in 
pediatric populations.
    How will the ISPCTN cooordinate with the ECHO program as a whole? 
ISPCTN will study any disease or condition relevant to the pediatric 
population, but priority will be given to the four focus areas of the 
ECHO program including: upper and lower airway diseases; obesity; pre-, 
peri-, and postnatal outcomes; and neurodevelopment. All prospective 
data collection will be encouraged to utilize the ECHO program's Core 
Elements and standardized research measures. Structurally, there will 
be representatives of the ISPCTN on the ECHO Steering Committee and 
subcommittees.
    How will this network function and move forward? The overall 
framework will consist of dedicated pediatric clinical teams at 
participating institutions, a professional development component, and a 
central Data Coordinating and Operations Center (DCOC). The 
institutions that will successfully compete to become IDeA State 
Pediatric Clinical Sites will be integrated with the DCOC to form a 
Research Network to conduct multicenter studies of pediatric conditions 
and disease processes. The proposed activities will provide the 
infrastructure and resources needed to initiate and participate in 
pediatric clinical trials and enhance the competitiveness of the 
investigators to obtain funding for pediatric clinical research.
    DCOC will provide comprehensive services across the network. DCOC 
will have primary responsibility for resource allocation, data 
management and analysis, and data sharing for research conducted 
through the network in collaboration with the ISPCTN Steering 
Committee, the ECHO Steering Committee, and the NIH Program Staff. DCOC 
will facilitate and establish collaborations within the network and 
outside of the network, will develop and implement quality control 
measures, establish and maintain human subject protections oversight, 
develop a central IRB, implement relevant professional development 
programs, and organize and implement monitoring activities. ISPCTN will 
be directed by a Steering Committee with standing committees and sub-
committees; a Scientific Oversight Board and a Data Safety Monitoring 
Board will be constituted as well. ISPCTN will also be guided by the 
ECHO Steering Committee and External Scientific Board. Each clinical 
site will have a dedicated pediatric clinical trial team including a 
board certified Pediatrician as a Principal Investigator (PI), a 
Research Nurse Coordinator, and a Data Manager, who will implement the 
studies.
    How will the studies be chosen? ISPCTN will primarily function to 
augment pediatric clinical trials initiated by other entities to 
improve access to state-of-the-art pediatric clinical trials to 
populations who would otherwise not have access to them. Studies 
initiated within the network will also be encouraged. The ECHO Program 
Officials and the NIH Project Scientists, one from NICHD and one from 
NIGMS, will assist the PI(s) and Program Directors of the Clinical 
Sites and the DCOC of ISPCTN to identify research topics of high 
priority and provide guidance for the implementation of the protocols 
appropriate for the network goals and objectives. Interested 
investigators will contact DCOC as a clearing house to determine 
feasibility and network interest. Clinical trials to be conducted 
through the network will require approval by the ISPCTN Steering 
Committee in conjunction with the NIH ECHO Program Officials.
    How will the studies be funded? All the studies will be funded by 
DCOC. DCOC will receive its entire budget when the award is made, and 
will allocate $4.53 million per year for each of the 4 years of the 
program budget period in direct costs to pay for services. These costs 
will be distributed to the Clinical Sites and for necessary monitoring, 
DSMB visits, and Scientific Oversight Board activities.
                            hiv/aids vaccine
    Question. I understand that the NIH is on the path toward 
discovering a vaccine for HIV/AIDS. What is the Administration's 
position on funding for this effort? How much of the request will be 
devoted to HIV/AIDS vaccine discovery? Why do you believe that is 
sufficient?
    Answer. The fiscal year 2017 President's Budget requested $554 
million for HIV vaccine research at NIH. Development of an HIV vaccine 
would represent a significant public health achievement and provide 
populations around the world with a safe and effective tool for 
preventing HIV infection.
    The National Institute of Allergy and Infectious Diseases (NIAID) 
is the lead NIH Institute for research on HIV/AIDS, including research 
to develop an effective vaccine. NIAID oversees a robust portfolio of 
basic, translational, and clinical research on HIV/AIDS with the goal 
of successfully ending the HIV/AIDS pandemic. While significant 
progress has been made in combating HIV/AIDS through the implementation 
of prevention and treatment strategies supported by NIAID research, the 
development of a safe and effective HIV vaccine is critical to achieve 
a durable end to the HIV/AIDS pandemic and thus remains a top priority 
for NIAID.
    NIAID supports a comprehensive program of extramural and intramural 
HIV vaccine research, including at the NIAID Vaccine Research Center 
(VRC). Investigators are working at all stages of the vaccine 
development pipeline to design, develop, and test vaccine candidates to 
prevent HIV infection. To date, NIAID has supported 148 vaccine trials 
to evaluate 109 vaccine products and 27 adjuvants--vaccine additives 
designed to boost the immune response to vaccination.
    HIV vaccine development supported by NIH builds upon basic research 
that illuminates the mechanisms of HIV pathogenesis. Studies of viral 
and host factors involved in host immune responses to HIV will 
contribute knowledge that can help researchers develop novel vaccine 
strategies. For example, VRC scientists discovered VRC01, a broadly 
neutralizing antibody that is capable of inhibiting a number of HIV 
strains. Phase I studies are currently underway to evaluate the safety 
and immunogenicity of VRC01. In addition, Phase IIb studies initiated 
in March 2016 are evaluating the ability of infusions of VRC01 to 
prevent HIV infection. Understanding the preventive properties of 
broadly neutralizing antibodies will help scientists design more 
effective HIV vaccines that aim to inhibit multiple strains of HIV.
    NIAID is collaborating with the Pox-Protein Public-Private 
Partnership (P5) to confirm and extend results of the RV144 clinical 
trial in Thailand. This trial was the first study to demonstrate 
moderate protection against HIV infection in people who received a 
candidate HIV vaccine regimen. To build upon the results of the RV144 
trial, NIAID launched the HVTN 100 Phase I/II clinical trial in South 
Africa. This trial is evaluating an investigational vaccine regimen 
that was designed to improve upon the efficacy of the vaccine regimen 
used in the RV144 trial. If the vaccine is found to be safe and 
adequately immunogenic, NIAID and collaborators anticipate launching a 
follow-up randomized controlled trial, HVTN 702, in late 2016 to test 
the regimen's protective efficacy.
    In addition to HIV vaccine research, NIAID is supporting research 
to optimize existing strategies and to develop new strategies for HIV 
treatment and prevention, as well as to explore novel approaches to 
curing HIV. In partnership with scientific and community stakeholders, 
NIAID-supported research is advancing progress toward an AIDS-free 
generation, including through critical work to develop an effective HIV 
vaccine.
     updating research centers in minority institutions guidelines
    Question. The Research Centers in Minority Institutions (RCMI) 
program has proven important in building biomedical research capacity 
at Historically Black Colleges and Universities (HBCUs) nationwide, 
including at Jackson State University in my State. I understand the 
National Institute on Minority Health and Health Disparities is 
preparing updated guidelines for the RCMI program. Where is NIMHD in 
that process? How will eligibility for the RCMI program change? For 
example, will non-minority institutions become eligible for RCMI 
funding, or will institutions that have received ``significant amounts 
of Federal funding'' now be allowed to compete? Will the purposes and 
uses of the funds change? If yes, how so? It is my hope that this 
program will continue to provide important capacity-building funds to 
minority-serving institutions like Jackson State.
    Answer. Since the transfer of the Research Centers in Minority 
Institutions (RCMI) program to the National Institute on Minority 
Health and Health Disparities (NIMHD) in 2012 with the dissolution of 
the National Center for Research Resources (NCRR), NIMHD has made it a 
priority to integrate the RCMI program into the existing NIMHD 
portfolio. NIMHD has focused on specific programmatic goals and 
objectives in order to minimize overlap and maximize the scientific 
benefit of the Federal resources and plans to provide updated guidance 
to the extramural research community in the summer of 2016. NIMHD is 
committed to keep the intent of the RCMI program and will continue to 
engage institutions with a history of supporting students and trainees 
underrepresented in biomedical research and to serving diverse 
populations.
    Consistent with the intent of the RCMI program, the priority 
continues to be strengthening the research environment at the 
institution. There are multiple ways to accomplish that goal, from 
providing specialized expertise such as biostatistics, health 
informatics or specific research skills in laboratory science, to 
conducting specific research projects in minority health or health 
disparities. Individual RCMI institutions have and will continue to be 
able to focus on different scientific areas including basic biomedical, 
behavioral, and/or clinical research that best align with the strengths 
of their institution.
                        nih ``march-in rights''
    Question. What is your position on the use of NIH's ``march-in-
rights'' as a price control measure?
    Answer. NIH shares the public's concern about any individuals who 
need medical treatments may be prevented access to treatment on the 
basis of the cost. Some have suggested that NIH utilize the Bayh-Dole 
march-in authority as a means of addressing the difficult situation 
with drug pricing. The Bayh-Dole Act, however, does not appear to have 
been designed to address situations where the price is the obstacle for 
access to products utilizing Government-funded inventions. The Act 
seems to address the circumstances where the products are not available 
because they are not being commercialized and have not entered the 
market. Another case for using march-in may occur when serious public 
health needs are not being reasonably met by the owner of the patent or 
the company selling the product. In such cases, NIH has the authority 
to utilize the march-in authority. NIH reviews each request for the use 
of march-in on case by case basis. In previous cases where requests 
were based on drug pricing issues, NIH did not find that the march-in 
statutory criteria were met.
          combatting antibiotic resistant bacteria initiative
    Question. Through the Combatting Antibiotic Resistant Bacteria 
initiative, the FDA and the CDC have recognized that antibiotic 
resistance is a growing public health concern worldwide. As part of 
this effort, the White House issued a National Action Plan for 
Combatting Antibiotic-Resistant Bacteria in 2015. In January, the NIH 
announced that approximately $5 million in funding was granted to 
research projects to develop non-traditional therapeutics for bacterial 
infections to help address the growing health threat of antibiotic 
resistance. Does NIH have adequate resources to address this growing 
threat?
    Answer. Research to address antibacterial-resistant pathogens is a 
top priority for the National Institute of Allergy and Infectious 
Diseases (NIAID), the lead NIH Institute for research on infectious 
diseases. NIAID plays an important role in the President's National 
Strategy for Combating Antibiotic-Resistant Bacteria (CARB) by 
investing in basic, translational, and clinical research on 
antibacterial resistance. The additional $100 million provided by the 
Congress in the fiscal year 2016 Consolidated Appropriations Act to 
address antibacterial research and development is both timely and vital 
to address the growing problem of antibiotic resistance. This funding 
will bolster and expand NIAID's research efforts to better understand 
and combat antibacterial resistant infections.
    In accordance with the objectives outlined in the National Strategy 
for CARB, NIAID is currently sequencing bacterial strains for the 
National Database of Resistant Pathogens; optimizing current treatment 
strategies to reduce the emergence of drug resistance; and developing 
diagnostic platforms capable of detecting multiple resistant pathogens. 
NIH is partnering with the Biomedical Advanced Research and Development 
Authority, with assistance from FDA and CDC, to incentivize diagnostic 
research by designing a prize competition for the development of a 
rapid, point-of-care diagnostic test for healthcare providers. NIAID 
also is expanding and strengthening its clinical research efforts, 
including through the NIAID Antibacterial Resistance Leadership Group 
(ARLG), to facilitate high-priority research on antibacterial 
resistance. For example, the ARLG is currently investigating the use of 
shortened courses of antibiotics in pediatric populations in an effort 
to enhance antibiotic stewardship and infection control.
    Consistent with the CARB objectives, the NIAID initiative Non-
Traditional Therapeutics that Limit Antibacterial Resistance supports 
early-stage, translational research projects focused on discovery and 
development of non-traditional therapeutics that provide alternative 
treatment strategies for infected patients. In January 2016, NIAID 
awarded approximately $5 million in funding for 24 research projects 
seeking to develop non-traditional therapeutics for bacterial 
infections, including Clostridium difficile, Staphylococcus aureus, and 
carbapenem-resistant Enterbacteriaceae (such as Klebsiella pneumoniae).
    In addition, NIAID continues to support the discovery and 
development of new therapeutics for Gram-negative pathogens, such as 
biofilm inhibitors, and anti-virulence, immune-based, and adjunctive 
therapies. To that end, in 2016, NIAID will make multiple awards under 
several other research initiatives that are designed to advance the 
development of new therapeutic products and approaches aimed at 
addressing drug resistance. These initiatives include Partnerships for 
the Development of Host-Targeted Therapeutics to Limit Antibacterial 
Resistance and Systems Biology and Antibacterial Resistance. NIAID also 
will fund new contracts to support the development and early clinical 
evaluation of promising lead therapeutic candidates and products that 
demonstrate broad spectrum therapeutic activity, including activity 
against antibiotic-resistant bacteria.
    NIAID has provided support for at least 25 percent of antibiotics 
currently in clinical development. Currently, NIAID is supporting 
several clinical trials evaluating new ways to treat gonorrhea, 
including a Phase II trial of an oral antibiotic AZD0914 developed by 
AstraZeneca; a Phase I trial assessing the pharmacokinetics of a next-
generation macrolide antibiotic, solithromycin; and a Phase III trial 
comparing solithromycin to standard of care treatment for gonorrhea. 
NIAID also is supporting trials to determine optimal antibiotic 
treatment (e.g., dosage, duration) using existing off-patent 
antibiotics for a variety of infections, including community-acquired 
methicillin-resistant Staphylococcus aureus (MRSA) infections; 
staphylococcal bacteremia; Gram-negative bacteremia; acute otitis 
media; urinary tract infections; and hospital-acquired pneumonia.
    NIAID remains committed to conducting and supporting research on 
antimicrobial resistance, including the development of rapid, point-of-
care diagnostics, improved and innovative therapies, and vaccines to 
prevent infections. Utilizing additional resources provided by the 
Congress in fiscal year 2016, NIAID will continue to enhance 
partnerships with industry, academia, and other Federal Government 
agencies to support the goals of the National Strategy for CARB.
                            animal research
    Question. Great strides in medical research and treatment have come 
from the study of animal models. Whether a scientist is studying kidney 
failure or drug addiction, there is clear value in translating the 
lessons learned to the human population. Some in the industry have 
suggested that NIH may be backing away from its longstanding commitment 
to study certain species of animals due to pressure from activists. 
What is your intention related to animal research? How will you ensure 
that the humane and scientifically-justified use of animal models is 
permitted for those using NIH funds to support their research?
    Answer. NIH is committed to funding the most meritorious research 
projects, including those involving animal model(s). Research involving 
vertebrate animals is key to helping us understand and improve human 
health in a multitude of ways, including the development of treatments 
and interventions. For ethical reasons, these studies cannot be carried 
out in humans and require the use of animal studies to understand 
fundamental biological systems. Ultimately, these findings assist 
researchers in identifying potential treatments and interventions by 
helping to elucidate the mechanisms underlying health and disease.
    Figure 1 shows the success rates for new, competing R01 grant 
applications over the past 5 fiscal years, broken out by whether the 
application proposes only vertebrate animal research, only human 
subjects research, both vertebrate animal and human subjects research, 
or neither. The R01 grant is NIH's most commonly used funding mechanism 
and is used to support a majority of NIH's basic research portfolio. 
Success rates for studies involving only vertebrate animals and those 
involving both vertebrate animals and human subjects have increased in 
fiscal years 2014 and 2015, showing NIH's continued commitment to 
funding meritorious research using vertebrate animal models.



    Figure 1. Success rates for competing R01 applications, by type of 
research proposed, over the past 5 fiscal years.

    NIH takes animal welfare seriously, and has numerous policies and 
protocols in place to assure the ethical treatment and use of these 
invaluable resources. The agency remains confident that the oversight 
framework for the use of vertebrate animals in research is robust and 
has provided sufficient protections to date. NIH will continue to 
support the meritorious research proposals using vertebrate animals, so 
long as the research satisfies ethical principles of scientific rigor, 
appropriateness of the model, and consideration of animal welfare. 
Moreover, NIH has the necessary mechanisms to implement these relevant 
policies to ensure the continued responsible use of vertebrate animals 
in biomedical and behavioral research.
                              idea program
    Question. I know you are aware of how the IDeA program has helped 
build biomedical research capacity across the Nation. The fiscal year 
2016 omnibus provided additional funds, reflecting Congress's continued 
support for this program. What are your plans for the IDeA programs 
going forward? What are some particular success stories that have come 
from IDeA investments?
    What are your plans for the IDeA programs going forward?
    Answer. NIGMS foresees the IDeA Program as a long-term 
interventional capacity-building program targeting States and 
jurisdictions that have consistently trailed in obtaining significant 
NIH support. The intent is to transform institutions with 
infrastructure, human resource, and economic challenges to become more 
competitive biomedical research enterprises through various distinct 
but complementary initiatives.
    Currently, institutions in 23 States and Puerto Rico are eligible 
for funding from the IDeA Program.\14\ For fiscal year 2017 and in the 
foreseeable future, the IDeA program will continue to support 
investigators in eligible States through the following initiatives:
---------------------------------------------------------------------------
    \14\ Alaska, Arkansas, Delaware, Hawaii, Idaho, Kansas, Kentucky, 
Louisiana, Maine, Mississippi, Montana, Nebraska, Nevada, New 
Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, South 
Carolina, South Dakota, Vermont, West Virginia, Wyoming.
---------------------------------------------------------------------------
  --IDeA Networks of Biomedical Research Excellence (INBRE).--The INBRE 
        initiative enhances, extends, and strengthens the research 
        capabilities of biomedical research faculty in IDeA States 
        through a statewide program that links a research-intensive 
        institution with primarily undergraduate institutions. INBRE 
        supports institutional research and infrastructure development; 
        research by faculty, postdoctoral scientists and students at 
        participating institutions; and outreach to build science and 
        technology knowledge in the States' workforces. Only one award 
        is made per eligible State. Currently (fiscal year 2016), NIGMS 
        supports 24 INBRE awards. For fiscal year 2017, NIGMS 
        anticipates continuing support for these 24 INBRE awards.
  --Centers of Biomedical Research Excellence (COBRE--Phases I, II, and 
        III).--The goal of the COBRE initiative is to strengthen 
        institutional biomedical research capabilities in IDeA States 
        through three 5-year phases of infrastructure and faculty 
        development of thematic and multidisciplinary research centers. 
        In fiscal year 2015, NIGMS supported 107 COBRE awards. For the 
        current year (fiscal year 2016), 12 new Phase I COBRE grants 
        will be awarded. In fiscal year 2017, NIGMS will support non-
        competing awards and continue to hold open competitions for new 
        and continuing COBRE awards.
  --IDeA Program Infrastructure for Clinical and Translational Research 
        (IDeA-CTR).--The IDeA-CTR initiative develops network 
        infrastructure and capacity in eligible States to conduct 
        clinical and translational research focused on health concerns 
        that affect medically underserved populations and/or that are 
        prevalent in IDeA States. IDeA-CTR awards support mentoring and 
        career development activities in clinical and translational 
        research. In fiscal year 2015, NIGMS supported 3 IDeA-CTR 
        awards. In the current year (fiscal year 2016), 4 new IDeA-CTR 
        awards will be made. In fiscal year 2017, NIGMS will support 
        non-competing awards and continue to hold open competitions for 
        new and continuing IDeA-CTR awards.
  --Research Co-Funding.--IDeA co-funding is provided to eligible 
        applications that have already been judged meritorious by NIH 
        peer-review committees and national advisory councils but are 
        outside the range of applications under consideration for 
        funding by the other NIH Institutes and Centers (ICs). In 
        fiscal year 2015, IDeA co-funded 25 R01/R15 awards to 18 NIH 
        ICs. For the current year (fiscal year 2016), $9 Million is 
        allocated for the co-funding initiative. In fiscal year 2017, 
        NIGMS anticipates to continue soliciting applications from 
        other ICs for co-funding.
  --Administrative Supplements.--Based on continuing evaluation of the 
        IDeA program, NIGMS will occasionally solicit applications for 
        administrative supplements from current grantees in order to 
        address emerging areas for development or enhancement. For the 
        current year (fiscal year 2016), the Institute published an 
        administrative supplement solicitation for the optimization 
        and/or consolidation of core facilities supported by the IDeA 
        program. The projected budget for this initiative in fiscal 
        year 2016 is $8 Million.
    Additionally, for fiscal year 2017, the IDeA program will provide 
continuing support for the non-competing INBRE, COBRE, and IDeA-CTR 
awards; these awards constitute the IDeA program budget base. As 
indicated above, the rest of the IDeA program budget will support new 
competing COBRE and IDeA-CTR awards, and co-funding of meritorious 
applications from other ICs.
    Question. What are some particular success stories that have come 
from IDeA investments?
    Answer. Investigators in a COBRE at the University of Mississippi 
that is focused on finding natural products that affect neurological 
processes (Principal Investigator: Steve Cutler) are developing melt-
cast films for the efficient and prolonged topical delivery of 
therapeutic small molecules to the posterior segment of the eyes. 
Diseases affecting the posterior segment of the eye such as diabetic 
retinopathy, age related macular degeneration, diabetic macular edema 
and proliferative vitreo-retinopathy are some of the major causes of 
blindness in the United States. Treating posterior segment eye diseases 
has always been a great challenge because of the unique physiological 
and anatomical barriers of the eye. In a recent publication from this 
group, the COBRE investigators demonstrated that melt-cast films based 
on polyethylene oxide N10 can serve as a viable platform for sustained 
topical delivery of therapeutic agents into tissues in the back of the 
eye.
    Jennifer Sasser, a COBRE-supported junior investigator at the 
University of Mississippi Medical Center, characterized a novel model 
of the pregnancy-related disease superimposed preeclampsia. This new 
model of the disease in rats provides a powerful tool to gain a greater 
understanding of the pathogenesis of preeclampsia. Preeclampsia is a 
leading cause of maternal morbidity and mortality worldwide with 
currently no effective treatments other than delivery of the placenta. 
The new rat model of preeclampsia allows for the analysis of changes 
throughout pregnancy in the placenta, vasculature, and kidney, as well 
as the discovery of new biomarkers that are present early during 
pregnancy and would allow early detection of the condition. Using this 
new rat model, Sasser and colleagues found that the phosphodiesterase 
inhibitor drug, sildenafil, improves the maternal syndrome of 
preeclampsia as well as blood flow to the fetus and placenta, providing 
preclinical evidence to support the hypothesis that inhibiting the 
enzyme phosphodiesterase type 5 may be a therapeutic strategy for the 
treatment of preeclampsia.
    The IDeA Program appropriation has been successfully leveraged by 
IDeA investigators to provide additional NIH funding to the eligible 
jurisdictions. For the 8-year period spanning fiscal years 2007-2014, 
the IDeA Program appropriation totaled $1.9 billion. Additional NIH 
funding obtained during this period totaled $12 billion, close to a 7-
fold return in investment.
    While the number of COBRE-supported investigators increased 
modestly during the 8-year period spanning fiscal years 2007-2014, the 
productivity of the investigators increased significantly. Whereas the 
number of COBRE-supported investigators increased only 9 percent when 
comparing fiscal years 2007-2010 (4-year average = 950) to fiscal years 
2011-2014 (4-year average = 1,034), the number of COBRE-enabled 
publications increased 43 percent in the corresponding period [fiscal 
year 2007-2010 (4-year total = 3,951) vs fiscal year 2011-2014 data (4-
year total = 5,651)].
    Blake Wiedenheft, a COBRE-supported Assistant Professor at Montana 
State, has moved beyond IDeA support and is now funded by an NIGMS R01. 
He was recently invited to give the first Annual NIGMS Director's Early 
Career Investigator Lecture. Wiedenheft was honored for his 
contributions to understanding the three-dimensional structures of key 
components of the CRISPR-Cas9 gene editing system. Even though he is 
still early in his career, Wiedenheft has already established himself 
as one of the international leaders in this field.
    In 2014, when Professor Susan Harkema's research at the University 
of Louisville in Kentucky was published in the journal Brain, it became 
an overnight sensation and was featured prominently in all the major 
print and broadcast media outlets. Harkema and her team demonstrated 
that modulating the spinal circuitry with epidural stimulation enabled 
completely paralyzed individuals to process conceptual, auditory and 
visual input to regain relatively fine voluntary control of paralyzed 
muscles. Harkema conducted the research as one of the project leaders 
in the Kentucky Spinal Cord Injury Research Center, a COBRE funded by 
the IDeA program.
    A COBRE focused on regeneration medicine based at the Mount Desert 
Island Biological Laboratory (MDIBL) in Maine has spun off the first 
company in the Laboratory's 115-year history, led by the Principal 
Investigator Kevin Strange and junior investigator Voot Yin. The new 
company, Novo Biosciences Inc., will look at the therapeutic potential 
of drugs that speed tissue healing and stimulate the regeneration of 
lost and damaged body parts. Strange and Yin serve as the CEO and Chief 
Scientific Officer, respectively, of the new company. Yin, an Assistant 
Professor at MDIBL, discovered the tissue regenerative effects of an 
experimental drug in a zebrafish model of regeneration using COBRE 
funds.
    COBRE investigators at the University of Arkansas for Medical 
Sciences set up telemedicine (TM) capabilities statewide in an effort 
to improve clinical outcomes for very low birth weight (VLBW) neonates. 
A prospective study (July 2009 to March 2010) that looked at the 
availability of TM consultation capabilities and neonatal interventions 
showed decreased deliveries of VLBW neonates in hospitals without NICUs 
and was associated with decreased statewide infant mortality. 
Telemedicine can be an effective way to translate evidence-based 
medicine into clinical care.
    A group of researchers at the University of Arkansas for Medical 
Sciences (UAMS) have discovered a new molecular ``earmark'' on DNA that 
may determine the sex of all mammals. COBRE-supported UAMS biochemist 
Alan Tackett, professor of Biochemistry and Molecular Biology in the 
College of Medicine, led a team of researchers that uncovered the 
earmark, N6-methyladenine, found to regulate access to DNA on the X-
chromosome that ultimately determines the sex of mammals. In addition, 
the research has the potential to uncover new targets for therapeutic 
development for cancer and other diseases. Their findings were 
published in the April 2016 issue of the journal Nature.
    Alayna Caffrey, a doctoral student in Montana State University's 
Department of Microbiology and Immunology, published important new 
findings about how healthy immune systems fight off deadly fungal 
infections. She was also one of only 10 people selected to present her 
work at an international scientific conference in Galveston, Texas. 
Caffrey studies the early immune response against Aspergillus 
fumigatus, a common mold that can be found in soil or compost piles. 
The mold causes severe lung infections in people with weakened immune 
systems, such as individuals with leukemia, chemotherapy or organ 
transplants. To help lower the percentage of deaths and understand what 
goes wrong in weakened immune systems, Caffrey looked at healthy immune 
systems to see how they respond to Aspergillus fumigatus. She 
discovered that a molecule called IL-la is critical for recruiting 
white blood cells to an infection site. Caffrey conducted the studies 
in the lab of Josh Obar, a COBRE-supported investigator. The work 
published in PLoS Pathogens was a collaboration between Obar's group 
and another COBRE at the Geisel School of Medicine at Dartmouth.
               atherosclerosis risk in communities study
    Question. The University of Mississippi Medical Center serves as a 
field center and conducts research in the NIH's Atherosclerosis Risk in 
Communities (ARIC) Study, which examines cardiovascular disease in over 
15,000 volunteer participants across the country. This original cohort 
of people who participate in this study enrolled in 1987, so they are 
well into old age today. What are the NIH's plans for recruiting the 
adult children of the current ARIC cohort, in the model of the 
Framingham Heart Study, in order to continue this important research?
    Answer. The Atherosclerosis Risk in Communities (ARIC) Study has 
resulted in outstanding contributions to the understanding of 
atherosclerosis and cardiovascular disease (CVD) as evidenced by the 
more than 1,700 publications from the study to date. With almost 30 
years of follow-up, the ARIC Study is among the longest-running cohort 
studies with a large number of African American participants. The ARIC 
study data on risk factors and incidence rates shows that African 
Americans are at very high CVD risk.
    This long-running multi-site cohort study has produced a number of 
significant research findings including the following:
  --The ARIC Study provided some of the first documentation that 
        diabetes is associated with accelerated cognitive decline.
  --Results from the ARIC Study include some of the first evidence for 
        lifestyle factors contributing to risk of venous 
        thromboembolism, offering possible keys to prevention.
  --Despite the higher prevalence of hypertension and diabetes in 
        African Americans, the magnitude of the association of these 
        two conditions with CVD is similar to the associations in 
        whites.
  --The ARIC Study helped establish that risk of atrial fibrillation is 
        lower in African Americans than whites and that there is a link 
        between obesity and atrial fibrillation.
    In 2013, the NHLBI Director charged a working group of our National 
Heart, Lung, and Blood Advisory Council to consider the future course 
for CVD epidemiology studies. Published in 2015 (Roger VL et al. Amer J 
Epidemiol 2015), the group's recommendations included ``fostering a 
more open, competitive approach to evaluating large-scale longitudinal 
epidemiology and population studies.'' NHLBI is developing a process to 
fund new and renewed epidemiologic studies that incorporates the 
recommendations from this working group. One goal is to solicit from 
investigators, innovative research ideas that leverage existing 
scientific resources, such as a cohort study of the adult children of 
the current ARIC study. Using the Framingham Heart Study, which 
includes three generations of participants, as an example, an offspring 
cohort of the ARIC study is possible.
                          alzheimer's research
    Question. Last year, this Committee provided a $350 million 
increase to funding for Alzheimer's disease research. This additional 
funding will help researchers, like those at the Memory Impairment and 
Neurodegenerative Dementia (MIND) Center at the University of 
Mississippi Medical Center, find a way to alleviate the dreadful 
symptoms and realities of this heinous disease. Please give us examples 
of any recent breakthroughs that are a result of investment in 
Alzheimer's research at the NIH.
    Answer. Research on Alzheimer's disease in the United States has 
benefited from the provision of additional funds in the past several 
years. Many of the studies that the National Institute on Aging (NIA) 
and other NIH Institutes supported with these funds are ongoing, and we 
look forward to reporting on the results as they become available. Most 
notably, the $350 million we received in fiscal year 2015 to support 
Alzheimer's research will fund, among other initiatives, research under 
10 Program Announcements soliciting funding applications across the 
spectrum of Alzheimer's disease research. The initial response to these 
Program Announcements was extremely robust, and initial awards are 
anticipated for late fiscal year 2016.
    Promising new therapeutics currently in clinical testing include:
  --LM11A-31, a compound able to enter the brain and prevent the loss 
        of nerve cells and the connections between them. NIA supported 
        preclinical testing of this compound, and an industry-supported 
        Phase I safety trial in young and in elderly normal subjects 
        showed no significant adverse effects for a wide range of 
        doses. Further human testing is planned.
  --BPN14770, which restores function of damaged synapses in the brain. 
        NIA, along with the NIH Blueprint Neurotherapeutics Network, 
        also supported the early development of the compound--which, if 
        effective, may benefit patients not only with Alzheimer's but 
        with other brain disorders, such as schizophrenia, as well. 
        This compound recently entered Phase I clinical trials.
  --Allopregnanolone, a neurosteroid that promotes growth of new 
        neurons and may protect against Alzheimer's pathology. NIA-
        supported researchers recently concluded a Phase I clinical 
        trial and are currently analyzing the results.
    Ongoing initiatives include:
  --NIH Accelerating Medicines Partnership (AMP), a joint public-
        private partnership to identify and validate promising 
        biomarkers of disease. In March, AMP launched its Alzheimer's 
        Big Data Portal and concomitantly released the first wave of 
        data through this new resource.
  --Molecular Mechanisms of the Vascular Etiology of Alzheimer's 
        Disease Consortium, a team-science venture to build a nuanced 
        model of Alzheimer's disease that more accurately reflects its 
        many causes and pathways. Scientists from diverse fields using 
        the latest methodologies will work collaboratively towards 
        shared goals: to dissect the complex molecular mechanisms by 
        which vascular risk factors influence Alzheimer's disease and 
        identify new targets for treatment and prevention.
  --MIND Diet Intervention to Prevent Alzheimer Disease: NIA has 
        recently funded this Phase III randomized controlled trial 
        designed to test the effects of a 3-year intervention of a 
        hybrid of the Mediterranean and DASH diets, called MIND, on 
        cognitive decline among 600 individuals 65+ years without 
        cognitive impairment who are overweight and have suboptimal 
        diets that may place them at risk for developing dementia.
  --Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, 
        led by researchers at the Memory Impairment and 
        Neurodegenerative Dementia (MIND) Center at the University of 
        Mississippi Medical Center. Researchers are studying, in a 
        biracial population, age-related cognitive decline and the 
        transition from mild cognitive impairment to dementia, with an 
        emphasis on potentially modifiable vascular risk factors. 
        Funding for this important study was renewed in 2015.
                                 ______
                                 
           Questions Submitted by Senator Shelly Moore Capito
                     medication-assisted treatment
    Question. Ensuring access to treatment for opioid addiction is 
essential to reversing the number of overdose deaths and the overall 
opioid epidemic. Medication-Assisted Treatment (MAT) plays an important 
role in this treatment. Current treatments such as methadone and 
buprenorphine--while effective in many cases--often require continued 
use for long periods of time, sometimes years, and daily maintenance. 
Is NIDA researching new methods of MATs which would address these 
issues?
    Answer. MAT, which includes the use of methadone, buprenorphine, or 
naltrexone in combination with behavioral therapy and appropriate wrap-
around services, is highly effective for the treatment of opioid use 
disorders (OUDs). Like other chronic illnesses (diabetes, 
cardiovascular disease), effective treatment for OUD currently requires 
ongoing treatment. Abundant scientific data show that long-term use of 
maintenance medications successfully reduce illicit drug use, reduce 
the risk of relapse and overdose, reduce associated criminal behavior, 
and help patients return to a healthy, functional life.\15\
---------------------------------------------------------------------------
    \15\ The American Society of Addiction Medicine (2013). Advancing 
Access to Addiction Medications.
---------------------------------------------------------------------------
    MAT is the current standard of care for OUD; however, there is a 
longstanding misconception that methadone and buprenorphine, which 
control opioid craving and withdrawal, merely ``substitute one 
addiction for another''. This belief has reinforced scientifically 
unsound ``abstinence-only'' philosophies in many treatment centers and 
limited the use of these medications. In reality, when properly 
prescribed, these medications do not get the patient ``high'', they 
restore balance to brain circuits that are impaired by addiction and 
allow the patient to return to more normal levels of functioning. 
However, these medications require regular dosing and frequent--
sometimes daily--healthcare appointments that can be burdensome for 
many patients. NIDA research is exploring ways to improve the treatment 
of OUDs including:
    Development of non-opioid based medications and treatments:
  --Lofexidine is an alpha2A-adrenergic receptor agonist that is 
        currently being evaluated as an adjunct treatment for cravings 
        and withdrawal to reduce the doses of buprenorphine or 
        methadone needed to treat OUD. NIDA, through a public-private 
        partnership with US WorldMeds LLC, supported a Phase III 
        Clinical Trial examining the safety and efficacy of Lofexidine 
        in buprenorphine-maintained patients at 13 sites. If approved, 
        Lofexidine will be the first non-narcotic medication approved 
        by the FDA to treat opioid withdrawal.
  --NIDA is supporting research examining multiple new targets to treat 
        OUD, including Doxazosin (alpha1 adrenergic receptor blocker); 
        Zonisamide (sulfonamide anticonvulsant); Lorcaserin (5HT2C 
        serotonin agonist); and NT-814 (neurokinin receptor 
        antagonist).
  --Anti-opioid vaccines--NIDA is currently supporting the development 
        of several vaccines that bind to opioids within the body and 
        prevent them from entering the brain. Vaccines currently in 
        development can bind to heroin or prescription opioids or both, 
        while another targets both opioids and HIV to simultaneously 
        protect against HIV infection while reducing the rewarding 
        effects of opioids.
    Improving current medications and treatment regimens:
  --Probuphine Buprenorphine Implant.--Probuphine provides a new 
        treatment option for people in recovery who may value the 
        unique benefits of a six-month implant compared to other forms 
        of buprenorphine, such as the possibility of improved patient 
        convenience from not needing to take medication on a daily 
        basis. A New Drug Application (NDA) that includes results from 
        a Phase III double-blind clinical study was resubmitted in 
        September of 2015. FDA action is expected this year.
  --Re-Engineering Methadone Treatment.--Ongoing research is testing 
        strategies to redesign methadone treatment programs to offer 
        more patient-centered care that improves the counselor-client 
        relationship, treatment retention, patient outcome, and cost-
        efficiency.
  --Comparative Effectiveness of MATs.--Methadone, buprenorphine, and 
        naltrexone are all effective for treating OUD. NIDA is funding 
        comparative effectiveness studies to determine which 
        medications work best for specific populations including 
        opioid-dependent youth and HIV-positive patients.
  --Biomarkers for Pain.--NIDA supports imaging studies of pain-altered 
        brain function as well as molecular markers in order to 
        identify biomarkers for pain conditions. .
  --Partnerships to Improve Service Delivery.--In response to the high 
        rates of opioid overdose in Appalachia, NIDA has partnered with 
        the Appalachian Regional Commission to fund research to address 
        injection opioid use and its consequences in the Appalachian 
        Region to determine how best to leverage available resources 
        and programs to address the epidemic, and to improve service 
        delivery.
  --Implementation Science for Improved Medication Assisted Treatment 
        (MAT) Delivery.--Several NIDA-supported investigators are 
        developing and testing strategies to facilitate the effective 
        and sustainable implementation of MAT in settings with high 
        rates of opioid use disorders including criminal justice 
        settings, emergency departments, and HIV treatment settings.
  --Mobile Health and Telehealth for Improved Delivery of MAT.--NIDA 
        also funds the development and testing of technology-based 
        tools to facilitate communication between patients and 
        providers; improve patient adherence; help providers deliver 
        more patient-centered care for OUD; and improve client 
        motivation and build their skills to achieve better outcomes.
                                 ______
                                 
             Questions Submitted by Senator Jeanne Shaheen
                institutional development award program
    Question. Dr. Collins, I was very pleased Congress provided a 
significant increase in funding for NIH in last year's budget. So many 
people who are affected by disease look to the NIH for hope that one 
day a cure can be found that will help them live longer and healthier 
lives. Thank you for your leadership.
    I was also very pleased that the NIH Institutional Development 
Award program received a significant increase in the fiscal year 2016 
omnibus. As you know, New Hampshire is a very active participant in the 
program and it has helped us build new research infrastructure and 
recruit the new generations of research scientists our Nation needs for 
the future. I think New Hampshire has important contributions that we 
can make to support NIH's biomedical research mission.
    The president's request has an over budget increase for fiscal year 
2017. Do you think the budget for the Institutional Development Award 
program should grow along with the budget for NIH?
    Answer. Funding for the IDeA program was held flat relative to 
fiscal year 2016 in the President's fiscal year 2017 Budget Request, 
consistent with the overall proposed fiscal year 2017 NIGMS budget and 
the proposed budget for other NIH Institutes and Centers excluding 
special targeted Presidential initiatives.
                                 ______
                                 
              Questions Submitted by Senator Brian Schatz
                                opioids
    Question. When discussing the urgent need to address the public 
health crises of chronic pain and opioid abuse, you stated that ``we 
need new alternatives for pain management and the NIH and our partners 
will develop them.'' Despite the substantial human and economic burden 
of chronic pain on our Nation, according to the NIH Estimates of 
Funding for Various Research, Condition, and Disease Categories (RCDC), 
the NIH only spent $463 million on pain research in fiscal year 2015, 
with a near-flat estimate of $481 million for fiscal year 2016 and 
fiscal year 2017 (equal to an investment of less than five cents per 
person with chronic pain). Please outline the NIH's specific plan for 
fiscal year 2017 to increase the NIH's investment in pain research and 
to develop and implement a targeted basic, translational, and clinical 
research effort that will: elucidate the underlying biological 
mechanisms of chronic pain; develop and discover safe, effective 
pharmacologic and non-pharmacologic therapies that can replace the use 
of addictive medications in the treatment of chronic pain; and populate 
an evidence base that can inform clinical strategies and care. With 
which Federal agencies will the NIH partner? Which person, 
institute(s), center(s), or office(s) within the NIH will be 
responsible for overseeing and implementing this effort across the NIH 
and in conjunction with other agencies? Which NIH initiatives hold the 
most promise for achieving these goals in a time- and cost-effective 
manner (e.g., Advanced Medicines Partnership, public-private 
partnerships through NCATS, Precision Medicine Initiative, BRAIN 
Initiative)? What is the associated timeline and budget for this 
effort?
    Answer. The societal and individual benefits derived from improved 
pain management are significant, and a continued investment in NIH is 
needed to advance research to discover new and effective therapies. NIH 
is committed to advancing pain research with the ultimate goal of 
reducing the burden of pain and improving safe and effective pain care. 
Several principles govern how NIH sets its research priorities: 
scientific merit, scientific opportunities, public health needs, and 
portfolio balance. NIH funds a broad range of pain research spanning 
basic, translational and clinical studies. Through efforts of the NIH 
Pain Consortium, funding for pain research has nearly doubled since 
2003. In light of the heightened awareness of the opioid and chronic 
pain crises and the release of the HHS National Pain Strategy (NPS), 
NIH has responded to the need to enhance the pain research agenda and 
is acting through several strategies.
    NIH, along with Agency for Healthcare Research and Quality (AHRQ), 
Centers for Disease Control and Prevention (CDC), Department of Defense 
(DOD), Food and Drug Administration (FDA) and Veterans Administration 
(VA) currently is engaged in developing a long-term Federal Pain 
Research Strategy (FPRS). The effort is coordinated by NIH and the 
Interagency Pain Research Coordinating Committee (IPRCC). NIH's Office 
of Pain Policy under the direction of Dr. Linda Porter, National 
Institute of Neurological Disorders and Stroke (NINDS), is implementing 
the effort. The objectives of the strategy are to review the current 
state of federally supported pain research, identify gaps and research 
needs and prioritize recommendations to advance the Federal research 
agenda. A panel of experts will provide recommendations on basic, 
translational, and clinical research as it relates to the continuum of 
pain from prevention through chronic pain management. The full spectrum 
of research will be addressed, from biological mechanisms through 
development of novel safe and effective therapies. The timeline for 
completion of the strategy is January, 2017.
    Pain research is supported by nearly all Institutes across NIH. The 
NIH Pain Consortium is a trans-NIH entity that includes members from 25 
Institutes and Centers (ICs) and is chaired by Dr. Koroshetz, Director 
NINDS. It was established to coordinate pain research efforts across 
NIH. It supports many shared funding opportunities that span the 
interests of multiple ICs and in some cases those of other Federal 
agencies. See: http://painconsortium.nih.gov/Funding Opps/highlighted-
initiatives.html.
    The BRAIN initiative provides opportunities to elucidate the 
neuronal pain circuitry and dysregulation of neuronal processing 
associated with chronic pain and as such is highly relevant to the pain 
research agenda. In addition the Precision Medicine Initiative is 
creating a large dataset from a cohort of more than a million Americans 
that will include information about pain symptoms, analgesic use, 
patient characteristics, clinical outcomes, and self-reported 
outcomes--providing a resource with tremendous promise for advancing 
pain research.
    The reliance on opioids for chronic pain management and its 
associated harms has heightened the need to develop and promote novel 
approaches to integrated pain care that are safe, effective, and not 
reliant on opioids. NIH currently funds research that includes 
development of non-opioid and non-addictive opioid analgesics, trials 
for effectiveness of integrated pain care, development of novel non-
pharmacological treatment approaches, and exploration of new drug 
targets. NIH hosted the Pathways to Prevention Workshop on long-term 
use of opioids for chronic pain. Follow-up meetings with Federal 
partners, focused on research priorities from the workshop and ways 
that Federal agencies can coordinate efforts to address the priorities, 
including the development of non-opioid pain therapies and 
multidisciplinary approaches to care.
    One challenge faced by NIH is the small size of the pain research 
community, which limits the number of applications and in turn, the 
level of NIH funding for pain research. NIH continues its concerted 
effort to expand the field by encouraging junior and non-pain 
investigators to enter into pain research through funding incentives 
that promote early career stage pain researchers, and specifically call 
for multidisciplinary pain and non-pain investigators to collaborate 
(e.g., http://painconsortium.nih.gov/Funding_Opps/highlighted-
initiatives.html). NIH also regularly provides training workshops at 
scientific meetings of pain specialists. Expansion of the research 
community is a crucial step toward increasing funding levels for pain 
research to ensure that these dollars are directed to high-quality, 
innovative research.
    NIH hopes that the efforts described here will contribute to a 
Department of Health and Human Service (HHS)-wide effort to expand 
research needed to address the ongoing opioid crisis and the broad 
priorities identified in NPS and in the ongoing FPRS. It is NIH's hope 
that once fiscal year 2017 is completed, the full set of pain-related 
research applications awarded will lead to a higher amount of funding 
than the current fiscal year 2017 estimate indicates.
    NIH appreciates the significance of the public health and economic 
burden of pain and will continue to develop partnerships across our 
institutes and other Federal agencies to enhance and improve our pain 
research agenda.
                               Telehealth
    Question. We've spoken before about telehealth and remote patient 
monitoring, and how these technologies can improve outcomes and save 
money. I know that the NIH has supported a lot of work on mobile 
health, or mHealth. Can you please give me an update on the research 
currently being funded at NIH on telehealth?
    Answer. Telehealth approaches leverage communications technologies 
to provide and support healthcare at a distance. NIH is committed to 
the development of telehealth approaches that enable people to take 
advantage of medical advances, regardless of their circumstances. Many 
NIH-sponsored research projects are funded as parts of initiatives 
supporting small business innovations. These small businesses are 
translating scientific and technological advancements into tools for 
the practice of medicine in a diverse range of settings. Other projects 
are the result of investigator-initiated exploratory applications that 
push the boundaries of how we approach medical treatment and care.
    NIH has a history of targeted efforts to stimulate growth in the 
telehealth space. As early as 1994, the National Library of Medicine's 
High Performance Computing and Communications awards sought out 
applicants developing telemedicine and telehealth approaches.\16\ The 
National Institute of Biomedical Imaging and Bioengineering (NIBIB) has 
also championed the advancement of telemedicine with targeted programs 
and general support.\17\ These founder programs established NIH-wide 
support of telehealth development. Their impact is evidenced in the 
major themes of NIH-funded telehealth research:
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    \16\ Advanced Technology Focus of 12 HPCC Health Care Awards. 
(1997, April 3). Retrieved April 21, 2016, from https://
www.nlm.nih.gov/archive/20041229/research/telemedhpcc.html.
    \17\ Telehealth. (2013, January 22). Retrieved April 21, 2016, from 
https://www.nibib.nih.gov/science-education/science-topics/
telehealth#1431.
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  --Overcoming Barriers.--Today, there are many barriers for some 
        patients, including physical and logistical constraints, to 
        receiving adequate care and treatment in the traditional 
        medical setting. Telehealth research funded by the NIH aims to 
        bring the clinic to the patient, and the specialist provider to 
        the generalist, with tools that allow for healthcare-related 
        exchanges remotely. For example, investigators on a recently 
        funded project at the University of Texas, Austin, are piloting 
        teleconsultation methods that allow low-income, house-bound 
        seniors to receive mental health counseling.\18\ Other NIH-
        funded researchers are investigating the use of extant social 
        infrastructure, such as community churches, as hubs for the 
        receipt and distribution of medical care and information 
        related to obesity and type 2 diabetes.\19\ In addition, 
        researchers at the University of Washington are harnessing the 
        reach of telehealth approaches to help manage coordinated care 
        efforts for women with perinatal depression.\20\
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    \18\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8927954.
    \19\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8994598.
    \20\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9008381.
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  --Remote Access to Care.--While the last decade has brought major 
        technological and intellectual advances to the field of 
        medicine, these advances are not always readily available at 
        the myriad points of care upon which people are dependent. 
        Another focus of NIH-funded telehealth research is building 
        diagnostic tools that free patients and providers from the 
        constraints of the hospital or clinic. Along these lines, a 
        group at Massachusetts General Hospital is pioneering 
        technology to enable smartphones to be used as confocal 
        microscopes to help diagnose AIDS-related Kaposi sarcoma, while 
        scientists at Emory University are leveraging mobile 
        technologies to create automated web-based methods for early, 
        remote diagnosis of Alzheimer's disease.\21,22\ NIH funding is 
        also enabling the development of remote diagnostics for 
        conditions like traumatic brain injury, HIV, Ebola and other 
        infectious diseases, and breast cancer.\23,24,25,26,27,28\
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    \21\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9018555.
    \22\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=8704932.
    \23\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8969564.
    \24\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8905469.
    \25\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9141791.
    \26\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9115796&icde=
30006803&ddparam=&ddvalue=& ddsub=&cr=1&csb=default&cs=ASC.
    \27\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8891696.
    \28\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=9133217.
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  --Remote Patient Monitoring.--Diagnosis is a first step, but chronic 
        conditions regularly need frequent monitoring by healthcare 
        providers. Moreover, it is often critical that emergent, life 
        threatening events are identified as soon as possible to enable 
        effective interventions. NIH is funding research that enables 
        this remote patient monitoring, like efforts by biotechnology 
        companies to develop a disposable assay to monitor heart 
        failure at home in at-risk patients and imbedded biosensors to 
        monitor patients' blood levels of chemotherapy agents in real 
        time.\29,30\
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    \29\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8905933.
    \30\ Https://projectreporter.nih.gov/
project_info_description.cfm?icde=0&aid=8839582.
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    NIH recognizes the promise of telehealth approaches that allow for 
delivery of quality healthcare in a range of settings. Not only has NIH 
funded discrete research projects that advance the field of telehealth, 
the agency has woven telehealth applications development and evaluation 
into the fabric of large, trans-NIH and intergovernmental initiatives 
like the Precision Medicine
    Initiative. As one of its founding principles, NIH is committed to 
improving the health and wellbeing of all people, regardless of their 
circumstances. As such, NIH will continue to fund cutting edge 
research, such as telehealth development, that helps to realize these 
principles.
           research centers in minority institutions program
    Question. The legislation that established the Research Centers in 
Minority Institutions (RCMI) program in 1985 was intended to 
``strengthen the research environment'' of ``predominantly minority 
institutions'' that ``offer degrees in the sciences related to health 
but which heretofore have not received significant amounts of research 
support.'' NIH moved to accomplish this goal by, as stated in the most 
recent Funding Opportunity Announcement (FOA), providing funds to ``(1) 
develop and enhance the institutional research infrastructure necessary 
for the conduct of biomedical and/or behavioral research; (2) enable 
minority institutions to become more successful in obtaining 
competitive extramural support for the conduct of biomedical and/or 
behavioral research; and (3) enhance the biomedical research 
environment at these institutions.'' The RCMI program has benefited 
numerous minority institutions, including through the growth of NIH 
funding, increased publications and presentations, the recruitment and 
retention of excellent faculty, and much more.
    I support the intent of the RCMI program as originally enacted. 
However, we have been hearing that NIH may be considering changes to 
this program. Can you please address the following:
  --Will non-minority institutions become eligible for RCMI funding?
  --Will institutions that have received ``significant amounts of 
        Federal funding'' now be allowed to compete?
  --Will awardee institutions no longer be allowed to fund pilot 
        projects within the institution to increase the competitiveness 
        of their faculty?
  --Will it be necessary to distribute RCMI funding across a variety of 
        disciplines in the awardee institution, i.e., basic biomedical 
        science, socio-behavioral science, and clinical population 
        studies, rather than focusing on their institutional strengths 
        in order to increase competitiveness?
    Answer. Eligibility of the RCMI program has historically been tied 
to doctoral degree granting institutions of higher education designated 
as a ``minority institution'' by the Department of Education. The 
National Institute on Minority Health and Health Disparities (NIMHD) is 
committed to keep the intent of the RCMI program and will continue to 
engage institutions that are less research intensive based on overall 
NIH funding and have a history of supporting students and trainees 
underrepresented in biomedical research and to serving diverse 
populations.
    Consistent with the intent of the RCMI program, the priority 
continues to be strengthening the research environment at the 
institution. There are multiple ways to accomplish that goal, from 
providing specialized expertise such as biostatistics, health 
informatics or specific research skills in laboratory science, to 
conducting specific research projects in minority health or health 
disparities. Moreover, NIH recognizes the value of small scale pilot 
projects to enhance the expertise and career of junior faculty and 
agrees that it is a valuable component of the RCMI program.
    Individual RCMI institutions have and will continue to be able to 
focus on different scientific areas including basic biomedical, 
behavioral, and/or clinical research that best align with the strengths 
of their institution.
    Since the transfer of the RCMI program to NIMHD in 2012 with the 
dissolution of the National Center for Research Resources (NCRR), NIMHD 
has made it a priority to integrate the RCMI program into the existing 
NIMHD portfolio. NIMHD has focused on specific programmatic goals and 
objectives in order to minimize overlap and maximize the scientific 
benefit of the Federal resources and plans to provide updated guidance 
to the extramural research community in the summer of 2016.
                                 ______
                                 
              Questions Submitted by Senator Tammy Baldwin
             ethical issues surrounding non-human primates
    Question. Dr. Collins, I understand that NIH has plans to develop a 
summer workshop on ethical issues surrounding research with non-human 
primates. Can you please share additional background on this workshop?
    Which Institutes or Centers are organizing the workshop, and who 
will be responsible for choosing the participants?
    Is NIH employing a broad range of experts on research with these 
animals in order to ensure an open dialog that reflects the significant 
scientific investments NIH has in this type of research?
    Answer. Research with animals, including non-human primates, 
continues to revolutionize our understanding of human health and 
disease, and has enabled the development of treatments and cures for a 
wide array of devastating diseases and conditions. Non-human primates 
are a particularly valuable resource for answering the most complex 
questions facing human health, as these animals share similar anatomy, 
physiology, and behavior with humans. For instance, scientific and 
treatment advances for Parkinson's disease have been a direct result of 
research with non-human primates, both in the development of a disease 
model and the innovative clinical application of research technologies 
such as deep brain stimulation. Also, in response to the 2014-2015 
outbreak of Ebola in West Africa, research using non-human primates was 
critical in the development of potential new experimental vaccines now 
being evaluated in clinical trials.
    That being said, the decision to use non-human primates in a 
particular study is not taken lightly. Research must satisfy ethical 
principles of scientific rigor, appropriateness of the model, and 
consideration of animal welfare. Upholding these precepts remains a 
steadfast commitment of biomedical research and has been established in 
policy since the passage of the Animal Welfare Act in the mid-
1960s.\31\ All NIH-funded research with animals is reviewed to ensure 
that the science is highly meritorious and the welfare of the animals 
is appropriately protected. NIH has established numerous policies, 
procedures, and protocols to ensure all appropriate principles are 
followed, including taking animal welfare concerns very seriously. The 
Office of Laboratory Animal Welfare ensures this oversight framework is 
followed. Its mission is to address humane care and use of animals in 
HHS-supported research, testing, and training by guiding researchers 
and interpreting the Public Health Service Policy on Humane Care and 
Use of Laboratory Animals.\32\
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    \31\ Https://awic.nal.usda.gov/government-and-professional-
resources/Federal-laws/animal-welfare-act.
    \32\ Https://grants.nih.gov/grants/olaw/references/phspol.htm.
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    NIH remains confident that the oversight framework for the use of 
non-human primates in research is robust and has provided sufficient 
protections to date. However, the Agency acknowledges that a periodic 
review of its policies and processes ensures that this framework 
evolves in a manner consistent with emerging scientific opportunities 
and public health needs.
    Toward this end, NIH plans to convene experts in science, policy, 
ethics, and animal welfare to discuss the oversight framework governing 
the use of non-human primates in NIH-funded biomedical and behavioral 
research endeavors. At this workshop, NIH will explore the current 
state of science of NIH-supported research involving non-human primates 
as research models and discuss how existing regulations and policies 
address their continued responsible use in research.
    The NIH Office of Science Policy, which is part of the NIH Office 
of the Director, is organizing this workshop, which will occur later 
this fiscal year. During the planning process, the NIH Office of 
Science Policy will consult with NIH Institutes and Centers that fund 
research using non-human primates, the Office of Laboratory Animal 
Welfare, and the Department of Bioethics to identify a diverse and 
knowledgeable group of speakers and panelists for the workshop. The 
workshop participants, both internal and external to NIH, will 
represent the Agency's significant scientific investment in research 
utilizing non-human primates and provide a thorough and productive 
dialogue to support the continuation of ethical and responsible 
research using nonhuman primates.

                          SUBCOMMITTEE RECESS

    Senator Blunt. And the subcommittee stands in recess.
    [Whereupon, at 12:00 p.m., Thursday, April 7, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]

              MATERIAL SUBMITTED SUBSEQUENT TO THE HEARING

    [Clerk's Note.--The following outside witness testimonies 
were received subsequent to the hearing for inclusion in the 
record.]
Prepared Statement of Dr. James F. Battey, Jr., M.D., Ph.D., Director, 
    National Institute on Deafness and Other Communication Disorders
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2017 budget request for the 
National Institute on Deafness and Other Communication Disorders 
(NIDCD) of the National Institutes of Health (NIH).
    NIDCD conducts and supports research and research training in the 
normal and disordered processes of hearing, balance, taste, smell, 
voice, speech, and language. NIDCD focuses on disorders that affect the 
quality of life of millions of Americans in their homes, workplaces, 
and communities. The physical, emotional, and economic impact for 
individuals living with these disorders is tremendous. NIDCD continues 
to make investments to improve our understanding of the underlying 
causes of communication disorders, as well as their treatment and 
prevention. It is a time of extraordinary promise, and I am excited to 
be able to share with you some of NIDCD's ongoing research and planned 
activities on communication disorders.
inner ear blueprint may lead to treatment for hearing loss and balance 
                               disorders
    Approximately 50 percent of Americans ages 75 and older have a 
disabling hearing loss. In addition, more than 1 in 20 children in the 
United States between the ages of 3 and 17 have a dizziness or balance 
problem. To determine the causes of hearing loss and balance disorders, 
it is important to understand how the cells in the inner ear form. To 
do this, scientists are identifying gene expression maps of the inner 
ear cells. Understanding inner ear cell development could lead to ways 
to regenerate lost or damaged cells and restore hearing and balance.
    Specialized sensory epithelial cells in the inner ear are 
responsible for hearing and balance. These cells, which include hair 
cells and supporting cells, are located in the cochlea, the snail-
shaped structure in the inner ear, and work together to detect sound. 
Similar types of hair cells and supporting cells are also found in the 
utricle, a fluid-filled pouch located near the cochlea, which plays a 
critical role in helping us maintain our balance. These cells detect 
how we move our heads, how our heads are positioned and whether we are 
moving or stationary; this information tells our brain, for example, 
whether we are standing or lying down. The utricle is one of several 
structures and organs in the body that provide our sense of balance.
    Hair cells and supporting cells can be damaged by medications, 
infections or disease, injury, exposure to loud noises, or aging, 
leading to hearing loss and balance problems. In humans, these cells 
cannot naturally repair themselves, so effective treatments are 
limited. In addition, there are only a few thousand of these sensory 
cells and they are located in a bony channel embedded in the skull, 
making them difficult to study.
    Using a sensitive new technology called single-cell RNA-seq, NIDCD 
intramural scientists have created the first high-resolution gene 
expression map of a single cell within the newborn mouse inner ear. By 
analyzing the cell's gene activity profiles, the scientists were able 
to identify genes that are active at different stages of development. 
The findings provide new insights into how epithelial cells in the 
inner ear develop and differentiate into the specialized cells that 
serve critical functions for hearing and maintaining balance. 
Understanding how these important cells form may provide a foundation 
for the potential development of cell-based therapies for treating 
hearing loss and balance disorders.
   mini inner-ear drug delivery device could help common hearing and 
                            balance problems
    Approximately 37.5 million American adults report some degree of 
hearing loss and almost eight million adults report a chronic problem 
with balance. Common examples include middle-ear infections (otitis 
media), Meniere's disease, noise-induced hearing loss, tinnitus, age-
related hearing loss, dizziness, and vertigo. Hearing and balance 
disorders also decrease quality of life, and they cross all ethnic and 
socioeconomic lines.
    Developing drug treatments is a long and costly process. One of the 
first hurdles is developing drugs that are safe and effective. For drug 
therapies to treat hearing loss and balance disorders, a second hurdle 
is getting the drugs where they need to go, which is deep inside the 
skull to the inner ear. Developing a safe and efficient route to the 
inner ear represents a significant technical challenge. Another 
challenge is to determine the appropriate concentration or dosage of a 
drug to be delivered into the ear.
    NIDCD-supported scientists are tackling these hurdles. Using 
microfluidic and microelectromechanical systems technologies, 
researchers developed a wearable miniaturized pump system that safely 
and effectively delivers drugs in various dosages over time to the 
inner ear in animal studies. The device can also take samples of the 
inner ear fluid, which will aid scientists in drug development and 
treatment.
    The investigators hope to use this device in preclinical animal 
studies. They plan to make the micro-pump and its electronic components 
so small that someday the entire system can be implanted in an 
individual's mastoid cavity, an opening in the bone behind the ear. The 
device would enable programmable, automated, and long-term delivery of 
therapeutic compounds to the inner ear. Because it can target inner ear 
fluid precisely, the device will serve as a useful tool for 
investigating the molecular mechanisms associated with inner ear 
diseases and testing new drug treatments for hearing and balance 
problems.
    Problems with Ability to Taste or Smell are Common in Middle-Aged 
and Older Adults People who have a poor ability to taste or smell can 
miss important cues to help them avoid dangers such as gas leaks, fire, 
and spoiled food. Scientists in the NIDCD Epidemiology and Statistics 
Program collaborated with the Centers for Disease Control and 
Prevention to conduct the first nationally representative survey about 
perceived taste and smell problems in more than 3,600 adults aged 40 
and older. About 19 percent of U.S. adults ages 40 and older report 
having had a problem with their ability to taste, and approximately 23 
percent report having had a problem with their ability to smell. The 
likelihood that a person will report a diminished sense of taste and/or 
smell increases with age. In adults ages 80 or older, nearly 31 percent 
report having had a problem with their sense of smell, and more than 27 
percent have had a problem with their sense of taste. This survey was 
part of the Healthy People 2020 national objectives for improving the 
health of all Americans. The data help us gauge the scope of the 
problem. Future data releases will also include results of taste and 
smell tests and will give us our first look at prevalence of taste and 
smell problems in the United States.
              scientists grow vocal fold tissue in the lab
    Vocal fold tissue is a complex biological structure that is 
responsible for normal voice production. About 7.5 million people in 
the United States have trouble using their voices. Voice problems can 
cause significant personal and occupational difficulties, loss of 
income, and reduced quality of life. People who have sustained injuries 
to the larynx or have undergone head and neck surgery can exhibit voice 
disorders. These disorders can range in severity from mild to total 
voice loss if the surgery was extensive for removal of a malignancy. 
NIDCD-supported voice scientists in collaboration with other NIH-
supported researchers have bioengineered vocal fold tissue in the lab 
using human cells. Moreover, the tissue had physical qualities that 
allowed it to ``behave'' like normal vocal fold tissue. To see if it 
could transmit sound, the researchers transplanted the tissue into an 
animal model. The bioengineered tissue performed well and was not 
rejected by the recipient, which is usually a major obstacle in these 
types of surgeries. This proof-of-principle study provides hope that 
one day individuals who have lost the use of their voice because of 
loss of their laryngeal tissue will have better treatment options.
                                 ______
                                 
   Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S., 
     Director, National Institute of Environmental Health Sciences
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Environmental Health Sciences (NIEHS) of the National 
Institutes of Health (NIH).
                      understanding our exposures
    An oil rig explodes in the Gulf of Mexico impacting an entire 
region's way of life. A manufacturing plant spills thousands of gallons 
of toxic chemicals into a river in West Virginia creating unknown risks 
to nearby residents. A combination of aging pipes and corrosive water 
leaches lead into drinking water in Flint, Michigan, posing 
irreversible harm to the city's children. These recent events bring 
into stark relief the critical need for strong exposure science--the 
first step in responding to an environmental health emergency is to 
understand the nature of the threat. But as prominent, tragic, and 
increasingly common as such occurrences are, they represent only a 
small part of the thousands of potentially harmful chemicals, metals, 
and other environmental pollutants our Nation's people are faced with 
on a daily basis.
    Protecting people's health from the consequences of such encounters 
requires knowledge, not only of the nature of the hazard itself, but 
just as importantly, of the means, amount, and effects of exposure to 
it. And further complicating our ability to determine our risk is the 
combination of human response variability and disparate exposures to 
environmental health threats. But such knowledge must be obtained if we 
are not only to respond to exposures after they occur, but be 
successful in the larger goal of avoiding harmful exposures, and 
thereby preventing illness and disease from ever occurring. The 
recognition of this fundamental scientific need is the basis of the 
work of NIEHS and the reason why our Institute has prioritized exposure 
science in its Strategic Plan. Although the issue of exposures is 
integrated throughout the plan, specific goals call for NIEHS to 
``Transform exposure science by enabling consideration of the totality 
of human exposures and links to biological pathways, and create a 
blueprint for incorporating exposure science into human health 
studies,'' and to ``Understand how combined environmental exposures 
affect disease pathogenesis.'' I will describe just some of the ways in 
which NIEHS has made significant progress toward these goals and toward 
ensuring the health of the American people.
                    connecting exposures to outcomes
    Five years after the Deepwater Horizon (DWH) oil rig explosion, 
which caused the largest oil spill in U.S. history, NIEHS-supported 
researchers continue work in three related areas--a health effects 
study of oil spill cleanup workers called the GuLF Study, research 
partnerships between Gulf-area universities and community 
organizations, and an NIH disaster research response effort. The 
research team developed a job-exposure matrix that enabled scientists 
to characterize exposures of workers participating in the GuLF Study 
and assess possible links between reported health symptoms and the 
chemicals each worker was exposed to, and preliminary results are being 
analyzed. University-community partnerships are focusing on health 
concerns identified by communities after the oil spill, including 
pregnancy and birth outcomes, general physical and mental health of 
coastal residents, and seafood safety. A study of 2,126 adult women 
residing in Southern Louisiana enrolled in the Women and Their 
Children's Health (WaTCH) study showed that both physical/environmental 
and economic exposure to the oil spill was associated with an increase 
in self-reported physical health outcomes. On a positive note, a risk 
assessment of exposure to polycyclic aromatic hydrocarbons of 
Vietnamese-Americans, a large shrimp-consuming population in the area, 
showed no acute health risks or excess cancers, reducing concerns about 
shrimp consumption following the DWH spill.
    Following the spill of 10,000 gallons of the chemical 4-
Methylcyclohexanemethanol (MCHM) into the Elk River upstream of the 
municipal water intake of Charleston, West Virginia, NIEHS researchers 
were able to help allay the fears of the community and State officials 
through a timely assessment that combined exposure data with a suite of 
health effect prediction studies, including computer modeling and 
laboratory toxicity studies. Findings of these investigators provided 
additional support for the adequacy of the drinking water advisory set 
by the Centers for Disease Control and Prevention at the time of the 
spill as being protective of health.
    In response to the latest public health disaster, the exposure of 
the population of Flint, Michigan, to lead in contaminated drinking 
water, NIEHS staff and grantees are leading efforts to understand 
residents'--especially children's--lead exposures to inform the public 
health response, both immediately and over the long-term. A long and 
continuing history of support of research on lead enables such efforts. 
Recent research by NIEHS grantees in Michigan demonstrated, for the 
first time, that lead exposure of pregnant mothers can affect DNA 
methylation patterns in their grandchildren, suggesting that a much 
longer-term perspective may be needed when considering measures to 
protect environmental health in the future. Also, NIEHS-funded research 
of lead-poisoned children in China recently established that 
measurement of lead in bone (through X-ray fluorescence) is a useful 
biomarker of lead exposure in children. Such research illustrates the 
kind of knowledge that might be applied to situations like the one in 
Flint. It is this kind of useful knowledge that NIEHS hopes to enable 
researchers to obtain through its recently established Children's 
Health and Exposure Assessment Resource (CHEAR), which will provide a 
laboratory network, data repository, and an analysis center to leverage 
the public investments of NIH-funded scientists to better understand 
environmental exposures and human health.
    Public health disasters such as chemical releases, hurricanes, 
infectious disease outbreaks, and others comprise unique exposure 
scenarios that can offer insights into environmental exposures 
encountered, not only by the affected communities and responders, but 
also by a broader range of the population. NIEHS, in collaboration with 
the National Library of Medicine, has developed the Disaster Research 
Response (DR2) program to further our national ability to gather time-
critical exposure and health information to reduce adverse health 
effects and improve response, recovery, and preparedness for future 
events. At the same time, this program will facilitate discovery 
research and generate novel hypotheses that will add to the body of 
knowledge underlying exposure related conditions such as cancer, 
neurological, and immune diseases and disorders.
    Disasters are compelling for both public and research attention, 
and deservedly so. But NIEHS efforts to elucidate the broad range of 
environmental exposures are far more proactive than responsive, and 
consistently generate findings that increase our ability to protect and 
improve people's health. For example, an ongoing project is using a 
matrix biomarker of tooth development to reconstruct the exposome--the 
compilation of multiple chemical exposures--over different life stages. 
A better understanding of how and when specific exposures occur will 
improve our ability to target interventions, particularly during 
critical windows of development. NIEHS-funded investigators also are 
working at the cutting edge of research on the microbiome, 
investigating interactions between the gut microbiome and exposure to 
arsenic, a known human carcinogen, and uncovering the relationship 
between obesity and exposure to ozone.
                    translating science into action
    NIEHS efforts are directly supportive of major health initiatives 
in the United States including Big Data to Knowledge (BD2K), the 
National Cancer Moonshot, and the Precision Medicine Initiative.
    NIH's BD2K initiative is focused on developing new strategies to 
analyze and leverage the explosion of increasingly complex biomedical 
data sets. NIEHS is leading the program's Training and Workforce 
Development efforts. These awards support current and future 
generations of researchers to specialize in data science fields and in 
the use or generation of Big Data. A current awardee is working to 
establish new integrative and data-driven methods for building systems 
neuroscience models of executive functioning during childhood, 
reporting recent advances in improving the specificity of magnetic 
resonance imaging (MRI) scans.
    The recently announced National Cancer Moonshot aims to bring about 
a decade's worth of advances in 5 years, in part by improving our 
ability to prevent cancer and detect it at an early stage. Cancer, like 
most other non-communicable diseases, is a result of a person's 
genetics, age, and environment (including lifestyle), and the World 
Health Organization estimates that nearly 20 percent of cancers may 
result from toxic chemical exposures. NIEHS-supported researchers 
continue to make groundbreaking advances in our understanding of the 
complex interactions between these three factors, leading to knowledge 
to inform cancer detection and prevention strategies, as well as 
treatments and therapies. For example, polycyclic aromatic hydrocarbons 
(PAHs) are probable carcinogens found in coal tar, diesel exhaust, and 
wildfire, cookstove, and cigarette smoke. People are primarily exposed 
to PAHs in mixtures, though current risk assessments focus on 
individual components. An NIEHS grantee and colleagues have developed a 
faster, more accurate method to assess cancer risk from mixtures of 
PAHs by evaluating bioactivity after short-term exposure.
    An example of NIEHS contributions to potential cancer therapy lies 
in treatment of ovarian cancer. The recurrence rate of ovarian cancer 
exceeds 75 percent, and the success of subsequent chemotherapy is 
limited because of the progressive development of drug resistance. New 
NIEHS findings suggest that a novel mechanism, combined activation of 
an early growth factor (EGR1) and microRNA (MIR152), may provide a 
useful therapeutic strategy to overcome resistance to the chemotherapy 
drug cisplatin, and improve outcomes in ovarian cancer.
    NIEHS research spans the spectrum of scientific inquiry from basic 
mechanisms to exposure science to clinical research aimed toward 
intervention and treatment. Precision medicine is an emerging approach 
for disease treatment and prevention that takes into account individual 
variability in genes, environment, and lifestyle for each person. 
Advances by NIEHS scientists are poised to make great contributions to 
the promise of precision medicine. These contributions range from 
identifying factors including autoantibodies, clinical factors, and 
environmental exposures at illness onset associated with the disease 
course of juvenile myositis, a group of rare and life-threatening 
autoimmune diseases in children, to developing a method for isolating 
certain rare cells of metastatic breast cancers in blood and profiling 
their gene expression to provide real-time warnings of emerging 
chemotherapy resistance.
                               conclusion
    To conclude, NIEHS continues to be at the forefront of 
environmental health: identifying emerging health threats, developing 
and implementing new technologies to characterize and analyze our 
exposure to the world around us, and leading the generation of 
knowledge of how our environment interacts with our genetics to cause 
illness and disease. And consistent with our mission, we will continue 
to lead these efforts in support of the Nation's initiatives to improve 
and ensure the health of the American people.
                                 ______
                                 
  Prepared Statement of Josephine P. Briggs, M.D., Director, National 
            Center for Complementary and Integrative Health
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National Center 
for Complementary and Integrative Health (NCCIH) of the National 
Institutes of Health (NIH).
    The NCCIH is the lead Federal agency for scientific research on the 
usefulness and safety of complementary and integrative health 
practices. Complementary health approaches include mind and body 
interventions, such as massage, acupuncture, yoga, and meditation, and 
natural products, such as dietary supplements and probiotics. To 
address the need for objective evidence as to the safety and efficacy 
of many of these approaches, NCCIH supports rigorous scientific 
investigation to better understand how these interventions work, for 
whom, and the optimal method of practice and delivery.
    The 2012 National Health Interview Survey (NHIS), conducted by the 
Centers for Disease Control and Prevention (CDC) with support from 
NCCIH, showed that one-third of U.S. adults use complementary and 
integrative health approaches. Many of these individuals seek these 
approaches to improve their health and well-being or to manage symptoms 
of chronic diseases or the side effects of conventional medicine. 
Natural products (dietary supplements other than vitamins and minerals) 
are the most commonly used complementary health approach, followed by 
deep breathing exercises and yoga.
             reducing pain and improving symptom management
    Pain is a major public health problem and is the most common reason 
Americans turn to complementary and integrative health practices. Data 
from the 2012 NHIS found that an estimated 25.3 million adults in the 
United States (11.2 percent) experience daily pain. In addition, nearly 
40 million adults (17.6 percent) experience severe levels of pain and 
are likely to have worse health status than the general public.\1\
---------------------------------------------------------------------------
    \1\ Nahin RL. Estimates of pain prevalence and severity in adults: 
United States, 2012. Journal of Pain. 2015;16(8):769-780.
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    CDC has classified fatal overdoses involving opioid analgesics, 
medications used to treat pain, as an epidemic. To help address this 
crisis, we need improved strategies for pain management so that 
healthcare providers are less reliant on prescribing opioids. NCCIH 
supports research to better understand pain and to identify effective 
nonpharmacologic approaches to reduce the duration and intensity of 
pain. For example, our intramural research program studies the role of 
the brain in perceiving, modifying, and managing pain. Specifically, 
scientists are investigating the role of the brain in pain processing 
and how emotion, environment, and genetics affect its perception.
    Recent results from NCCIH's extramural research program are 
advancing our understanding of the mechanisms of action of mind and 
body interventions and helping determine their effectiveness for 
treating pain. For example, previous research showed that mindfulness 
meditation helps relieve pain, but the mechanism through which 
meditation exerts this effect is not well understood. New study 
results, funded in part by NCCIH, demonstrate that mindfulness 
meditation may work on a different pain pathway in the brain than 
opioid pain relievers. Since opioid and non-opioid mechanisms of pain 
relief interact synergistically, the results suggest that combining 
mindfulness-based and other pain-relieving approaches that rely on 
opioid signaling may be particularly effective.
    Furthermore, study results published in the Journal of the American 
Medical Association expand the evidence base for the effectiveness of 
mind and body interventions. In the first randomized clinical trial to 
rigorously evaluate mindfulness-based stress reduction (MBSR) for young 
and middle-aged adults with chronic low back pain, researchers compared 
MBSR with usual care (UC) and cognitive-behavioral therapy (CBT). They 
found that individuals with chronic low back pain who received training 
in MBSR and CBT, compared with UC, demonstrated greater improvements in 
functioning and reductions in chronic low back pain at 6 months and 1 
year following treatment. The persistence of these beneficial effects 
suggests that MBSR and CBT may provide patients with skills for long-
term management of pain.
    NCCIH is also working with other NIH Institutes and Centers, the 
Department of Veterans Affairs (VA), and the Department of Defense 
(DOD) to test improved pain management strategies. Military personnel, 
veterans, and their families often struggle with pain management and 
its associated comorbidities including opioid misuse, abuse, and 
disorder. NCCIH plans to support a clinical trial coordinating center 
to launch a multi-year program to develop and test the efficacy and 
effectiveness of nonpharmacologic approaches to pain management and 
comorbidities for our military and veteran populations. Additionally, 
NCCIH is collaborating on the NIH Brain Research through Advancing 
Innovative Neurotechnologies (BRAIN) Initiative to accelerate the 
development and application of technologies to study the brain. NCCIH 
also is leveraging its resources through the NIH Common Fund's 
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program 
to better understand the mechanisms of action and the development of 
``electroceuticals'' for therapies in which nerves are stimulated to 
control organ function.
                 advancing research on natural products
    Nearly one in five U.S. adults use botanical supplements and other 
non-vitamin, non-mineral dietary supplements, such as fish oil/omega-3 
fatty acids and probiotics, according to the 2012 NHIS. The use of 
dietary supplements at times poses risks. For example, adverse events 
related to dietary supplements are estimated to contribute to 23,000 
emergency department visits in the United States each year.\2\ To 
better inform consumers and their healthcare providers, NCCIH supports 
research on the biological mechanisms of the benefits and potential 
harmful effects of natural products, such as their interaction with 
medications and liver toxicity. In fiscal year 2015, NCCIH established 
a Center of Excellence for Natural Product-Drug Interaction Research. 
The Center is systematically examining methods for studying natural 
product-drug interactions; developing standardized protocols to clarify 
which interactions have clinical impact; and disseminating its findings 
and resources broadly. In essence, the Center is developing a roadmap 
for the study of natural product-drug interactions with the ultimate 
goal of improving the body of knowledge available to healthcare 
providers, patients, and researchers.
---------------------------------------------------------------------------
    \2\ Geller, AI, et al. Emergency department visits for adverse 
events related to dietary supplements. N Engl J Med, 2015;373:1131-40.
---------------------------------------------------------------------------
    To further enhance NCCIH's natural products portfolio, NCCIH 
partnered with NIH's Office of Dietary Supplements (ODS) to fund five 
research centers in fiscal year 2015. These research centers focus on 
the safety of natural products, how they work within the body, and the 
development of innovative research technologies. Specifically, the 
three Botanical Dietary Supplements Research Centers will advance the 
understanding of the mechanisms through which complex botanical dietary 
supplements may affect human health and resilience. The two new Centers 
for Advancing Natural Products Innovation and Technology aim to propel 
chemical and biological investigation of natural products. Each is 
tackling unique research challenges. One center is working to improve 
the speed, breadth, and precision of the characterization of natural 
products by developing innovative cell-based screening approaches to 
uncover bioactive molecules of interest and their corresponding 
biological targets. The other center is coordinating and disseminating 
research technologies aimed at mining bioanalytical knowledge of 
natural products.
    Spurring innovation and developing new methodologies may lead to 
alternative sources of medically relevant compounds. For example, 
researchers, supported in part by NCCIH, created an innovative method 
to produce opioid drugs from sugar using genetically modified yeast. 
Using genes from a variety of plants, mammals, and microorganisms, they 
created yeast cells that can perform the entire process of 
manufacturing the opioids thebaine and hydrocodone using sugar as the 
starting material--a process that involves more than 20 separate steps. 
This innovation opens the door to additional novel approaches to 
generating needed medically relevant compounds in diverse settings. The 
new technique illustrates the potential value of genetically engineered 
yeast as a platform for producing many complex chemicals and materials 
and may help lead to better drug development in the future. Given this 
advance is moving ahead of regulations and policy, open discussions and 
decisions for the use and application of this technology will be 
needed.
assessing cardiovascular benefit of chelation therapy in patients with 
                                diabetes
    NCCIH is leading a trans-NIH effort (with NHLBI, NIDDK, NIEHS) and 
funding a planning phase to replicate the previous NIH-funded Trial to 
Assess Chelation Therapy (TACT) in older heart attack patients with 
diabetes. ``TACT 2'' will assess if an intravenous solution, which 
includes ethylendiaminetetraacetic acid (EDTA)--a chemical used to 
treat environmental exposure to heavy metal toxicity such as lead or 
cadmium, will reduce cardiovascular events in diabetics. Its use for 
treating heart disease was found beneficial in TACT, particularly for 
diabetic patients over 50 years of age who had a previous heart attack, 
but needs replication before becoming universally accepted. Additional 
research to identify the mechanisms by which chelation may affect heavy 
metal body burden and cardiovascular disease risk is also being 
planned.
               inspiring public trust through stewardship
    NCCIH works diligently to be an efficient steward of the resources 
entrusted to us. Currently, we are undertaking strategic planning 
activities focused on prioritizing our future research investments in 
complementary and integrative health. Additionally, we are ensuring 
that research workforce needs, especially those of clinician-
scientists, are addressed. NCCIH's new strategic plan is expected to be 
released this summer.
    Due to the self-care nature of these complementary health 
approaches, the translation and dissemination of unbiased, evidence-
based information is of great importance to NCCIH. Therefore, helping 
consumers, healthcare providers, researchers, and policymakers be 
better informed about the safety and effectiveness of complementary 
interventions continues to be our primary communication goal. NCCIH 
makes research findings available to the public through multiple 
platforms, including video, social media, and mobile applications.
                               conclusion
    NCCIH continues to support research and leverage its strategic 
partnerships to build the scientific evidence needed by consumers, 
healthcare providers, and policymakers regarding the safety and 
efficacy of complementary health approaches. By catalyzing innovation, 
NCCIH is advancing research on natural products and mind and body 
interventions.
                                 ______
                                 
Prepared Statement of Bruce Cuthbert, Ph.D., Acting Director, National 
                       Institute of Mental Health
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2017 budget request for the 
National Institute of Mental Health (NIMH) of the National Institutes 
of Health (NIH).
    I am particularly excited to discuss the ways in which NIMH is 
working to accelerate scientific progress by supporting research that 
will improve our understanding of mental illnesses, fueling the 
transformation of care for the greatest public health impact.
                 public health burden of mental illness
    NIMH is vigorously pursuing its mission to transform the 
understanding and treatment of mental illnesses through basic and 
clinical research, paving the way for prevention, recovery, and cure. 
Mental illnesses account for 21.3 percent of all years lived with 
disability in the United States, and an estimated 9.8 million American 
adults suffer from serious mental illness (SMI) each year, according to 
the Substance Abuse and Mental Health Services Administration (SAMHSA). 
People with SMI (in which the ability to function in daily life is 
significantly impaired) die 8 to 10 years earlier than the general 
population. The Centers for Disease Control and Prevention report that 
over 42,773 Americans died from suicide in 2014, more than twice the 
mortality from homicide or AIDS. Mental illnesses rank as the third 
most costly medical conditions in the United States, in terms of 
overall healthcare expenditures, behind heart conditions and traumatic 
injury.
          improving precision in research on mental illnesses
    Precision medicine means getting the right treatment at the right 
time to the right person. While significant advances in precision 
medicine have been made for select cancers, this is still not feasible 
for most other disorders, including mental illnesses. NIMH's approach 
to precision medicine revolves around the Research Domain Criteria 
(RDoC) initiative, which is intended to break mental illnesses down 
into fundamental mental processes (e.g., attention) compared across 
biological (e.g., genes, brain circuits) and behavioral (e.g., 
wakefulness) measurements.
    Results from a recent NIMH-funded study lend support to the RDoC 
approach. The Bipolar Schizophrenia Network on Intermediate Phenotypes 
(BSNIP) study used ``biomarkers''--or measureable indicators of 
disease--to sort patients with psychotic symptoms into ``biotype'' 
categories. The BNSIP study demonstrated that biotypes outperformed 
traditional diagnostic categories of psychotic disorders, such that 
sorting individuals with psychotic symptoms into subgroups based on 
brain biology can lead to greater precision in diagnosis, and 
potentially treatment. In fiscal year 2017, NIMH will continue to 
solicit research using RDoC approaches.
    The success of RDoC relies heavily on a culture of open science and 
rapid data sharing, which NIMH has formalized by creating a set of data 
sharing repositories called the NIMH Data Archive (including databases 
for RDoC, autism research, and clinical trials). Through these types of 
initiatives, NIMH is maximizing the use and impact of a valuable asset: 
our shared data.
         revolutionizing our understanding of mental illnesses
    Together with other NIH Institutes and Centers, NIMH co-supports 
two large-scale neuroscience initiatives: The Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the Human 
Connectome Project (HCP). The BRAIN Initiative will accelerate the 
development and application of innovative technologies to identify how 
individual cells and complex neural circuits interact, filling major 
gaps in our knowledge about how the human brain functions. HCP is a 
collaborative neuroimaging effort to map the neural pathways underlying 
human brain function; the primary purpose is to acquire data on the 
structural and functional connectivity of the human brain and to 
facilitate rapid access to large HCP datasets for secondary data 
analyses by other researchers. HCP and the BRAIN Initiative will set 
the stage for future studies of abnormal brain circuits, thereby 
advancing our understanding of the origins of mental illnesses.
                 early intervention changes trajectory
    NIMH recognizes the vital importance of early diagnosis and rapid 
delivery of appropriate and comprehensive treatment for mental 
illnesses. Approximately 100,000 adolescents and young adults 
experience a first episode of psychosis (FEP) each year in the United 
States, and the majority of people with SMI experience significant 
delays when seeking care.
    To help reduce the duration of untreated psychosis, NIMH is 
collaborating with SAMHSA to translate findings from the NIMH Recovery 
After an Initial Schizophrenia Episode (RAISE) project into guidance 
for States regarding evidence-based approaches to early psychosis 
treatment. Utilizing coordinated specialty care (CSC), people 
experiencing FEP were connected with specialty care providers at the 
earliest stages of illness. RAISE investigators have shown that CSC is 
effective and can be implemented in community treatment settings 
nationwide. In fact, the Centers for Medicare & Medicaid Services 
recently extended Medicaid coverage of evidence-based interventions 
such as CSC for individuals experiencing FEP. This fast-paced expansion 
in reimbursement practices is rare, but is a promising example of how 
NIMH-funded research can be quickly translated into practice.
    NIMH will build on the RAISE project with plans to launch the Early 
Psychosis Intervention Network (EPINET). EPINET uses a learning 
healthcare model to optimize care for youth at high risk to reduce the 
incidence of psychosis. With patients' consent, EPINET clinics will 
create a database of clinical information to help clinicians and 
researchers learn more about the effectiveness of early psychosis 
treatment.
    In addition to early intervention for FEP, NIMH launched several 
major initiatives to intervene early to implement a prioritized 
research agenda for suicide prevention. The Emergency Department Screen 
for Teens at Risk for Suicide (ED-STARS) study is poised to improve 
screening for youth at risk of suicidality following an emergency 
department admission; the Suicide Prevention for at Risk Individuals in 
Transition (SPIRIT) study, a collaboration with the U.S. Department of 
Justice, will evaluate the effectiveness of an evidence-based 
intervention among persons recently released from jail or prison; and 
the Reducing the Incidence of Suicide in Indigenous Groups--Strengths 
United through Networks (RISING SUN) initiative aims to create common 
outcome measures for suicide prevention efforts among indigenous 
peoples. These efforts represent NIMH's continued commitment to 
determining the best methods to prevent suicide, particularly among 
high risk populations.
    In 2016 and beyond, NIMH will continue to strive toward achieving 
the ambitious goals of the NIMH Strategic Plan for Research by 
harnessing the potential of the BRAIN initiative, the RDoC and RAISE 
projects, and efforts to prevent suicide. These and many other research 
endeavors represent NIMH's ongoing commitment to achieving its vision 
of a world in which mental illnesses are prevented and cured.
                                 ______
                                 
   Prepared Statement of Anthony S. Fauci, M.D., Director, National 
                  Institute of Allergy and Infectious
                                diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Allergy and Infectious Diseases (NIAID) of the National 
Institutes of Health (NIH).
    NIAID has a dual mandate to not only pursue a robust research 
portfolio in the areas of microbiology, infectious diseases, 
immunology, and immune-mediated disorders, but also to quickly launch a 
research response to newly emerging and reemerging infectious diseases. 
This dual mandate has been particularly evident over the past 2 years 
as NIAID has accelerated research to address the unprecedented Ebola 
and Zika virus outbreaks.
                      infectious diseases research
    NIAID continues to advance research to address emerging and re-
emerging infectious diseases around the world. In recent years we have 
faced major threats from diseases that have caused substantial 
morbidity and mortality, with Ebola virus disease and Zika virus 
disease being perhaps the most notable; however, other diseases such as 
dengue and chikungunya also have raised significant concerns. NIAID 
research supports progress against these and other emerging and 
established infectious disease threats worldwide. Examples of notable 
NIAID-supported infectious diseases research are highlighted below.
    Zika and other mosquito-borne viruses. The appearance and rapid 
spread of Zika virus in the Americas has coincided with new and 
concerning presentations of disease. These include reported increases 
in the birth defect microcephaly and the immune-mediated neurological 
disease Guillain-Barre syndrome. NIAID has rapidly mobilized research 
to address the public health threat of Zika by building upon our prior 
successes with other flaviviruses, notably West Nile and dengue 
viruses. Ongoing NIAID efforts include studies of the natural history, 
viral genetics, and pathogenesis of Zika virus, including how infection 
may cause the development of microcephaly and other congenital 
abnormalities in the fetus. In addition, NIAID is expanding efforts to 
develop countermeasures for Zika virus that could help control current 
and future outbreaks. NIAID has developed an animal model to test 
whether therapeutic compounds with activity against other flaviviruses 
also are effective against Zika virus. NIAID-supported researchers are 
developing diagnostics that can distinguish Zika virus from other 
flaviviruses, as well as investigating unique biosignatures that could 
form the basis of rapid, specific, and sensitive Zika diagnostic tests. 
The development of safe and effective vaccines against not only Zika 
but also several other mosquito-borne viruses is a top priority of 
NIAID. The NIAID Vaccine Research Center (VRC) is developing a DNA-
based vaccine for Zika virus that is similar to a West Nile virus 
vaccine previously developed by NIAID. Phase I clinical testing of the 
West Nile vaccine candidate showed it was safe and generated a robust 
immune response, indicating it could be a promising platform for a Zika 
vaccine. NIAID scientists also are designing a live-attenuated Zika 
vaccine. This effort employs an approach similar to that used for an 
NIAID-developed dengue virus vaccine candidate currently in Phase III 
clinical trials in Brazil. In addition, NIAID is investigating a Zika 
virus vaccine candidate that uses the same platform as an Ebola vaccine 
tested in West Africa and is partnering with BARDA to support a whole-
particle inactivated vaccine candidate. We anticipate that one or more 
of these Zika virus vaccine candidates will begin clinical testing in 
September 2016. NIAID also has supported the development of additional 
vaccine candidates for mosquito-borne viruses, notably an NIAID VRC-
developed chikungunya vaccine candidate currently undergoing Phase II 
clinical trials in the Caribbean.
    Ebola. Longstanding NIAID investments in biodefense research and 
collaboration with industry partners enabled the rapid and successful 
execution of clinical trials of candidate Ebola countermeasures in 
response to the 2014-2016 Ebola outbreak in West Africa. Recently 
completed NIAID studies demonstrated that the experimental Ebola 
vaccines cAd3-EBOZ and rVSV-ZEBOV are safe and immunogenic. A clinical 
trial evaluating ZMapp, a cocktail of three Ebola virus antibodies, 
found that treatment with ZMapp likely benefits Ebola virus disease 
(EBVD) patients. ZMapp remains the leading Ebola therapeutic candidate 
and has been made available to the recent Ebola cases in Guinea. 
Finally, ongoing studies in Liberia are enhancing our understanding of 
the long-term health consequences in survivors of EBVD. NIAID 
researchers and colleagues recently described initial findings 
concerning the extent of eye, musculoskeletal, and neurological 
problems experienced by EBVD survivors, as well as a possible 
persistent risk of sexual transmission of the virus. These NIAID 
studies have validated the use of randomized, controlled clinical 
trials during an infectious disease outbreak. Our efforts continue to 
evaluate improved vaccine strategies to prevent Ebola virus infection 
and determine the long-term clinical and public health consequences of 
EBVD.
    HIV/AIDS. Significant progress has been made in combating HIV/AIDS 
through the implementation of treatment and prevention approaches 
supported by NIAID research. Despite this progress, continued 
investment in the development of a safe and effective HIV vaccine and 
cure is needed to achieve a durable end to the HIV/AIDS pandemic. 
Research supported by NIAID continues to provide the evidence that 
informs the development of improved HIV treatment and prevention tools. 
A recent groundbreaking NIAID study conclusively demonstrated the value 
of early use of antiretroviral drugs, showing that starting treatment 
as soon as possible after HIV diagnosis reduces the risk of developing 
AIDS or other serious illnesses. Growing evidence from clinical trials 
and real-world implementation supports an approach known as pre-
exposure prophylaxis, or use of antiretroviral drugs by high-risk HIV-
negative individuals to prevent HIV infection. NIAID also is pursuing 
research in the development of next-generation interventions, such as 
broadly neutralizing antibodies; long-lasting injectable therapeutics; 
multipurpose prevention technologies (including microbicides); and a 
safe, effective HIV vaccine.
    Antimicrobial resistance. NIAID plays an important role in the 
President's National Strategy for Combating Antibiotic-Resistant 
Bacteria (CARB) in collaboration with partners across the Federal 
Government. This year, NIAID will maintain and grow a robust 
antimicrobial resistance research portfolio to understand the 
mechanisms of resistance and to develop improved countermeasures. Key 
NIAID efforts include sequencing bacterial strains for the National 
Database of Resistant Pathogens; developing non-traditional 
therapeutics; optimizing current treatment strategies to reduce the 
emergence of drug resistance; and developing diagnostic platforms 
capable of detecting multiple resistant pathogens.
    Influenza. NIAID influenza research aims to address the constant 
threat of seasonal influenza and the potential for pandemic influenza. 
In particular, NIAID is pursuing several promising universal influenza 
vaccine candidates that could protect against multiple influenza 
strains over multiple influenza seasons. In animal models, NIAID 
investigators have shown that two different universal influenza vaccine 
candidates can protect against numerous influenza strains. Both of 
these vaccine candidates, a nanoparticle vaccine and a virus-like 
particle vaccine, will be investigated for further development and 
clinical testing.
    Malaria. NIAID research support contributed to the early stages of 
the development of the RTS,S vaccine, the first vaccine shown to 
protect against malaria in young children. In a recent study, NIAID-
supported scientists used advanced genomic sequencing technology to 
help explain why the RTS,S vaccine is only partially effective. The 
researchers found that children infected with malaria parasites 
harboring genetic variants that did not match the protein targeted by 
the vaccine were less likely to be protected. These results will inform 
pilot implementation of the RTS,S vaccine endorsed by the World Health 
Organization as well as future malaria vaccine development strategies.
    Tuberculosis (TB). NIAID is playing a critical role in accelerating 
basic and applied research to combat multidrug-resistant TB (MDR-TB) as 
part of the President's National Action Plan for Combating MDR-TB. With 
MDR-TB cases increasing worldwide, there is a need for new diagnostics 
to rapidly identify resistance, as well as biomarkers to determine 
whether a particular TB drug regimen is effective. NIAID scientists 
have identified two medical imaging technologies that may help predict 
TB drug treatment outcomes. Positron emission tomography and computed 
tomography images allow researchers to monitor the burden of bacteria 
remaining in the lungs after therapy. These technologies potentially 
could be used in combination to quickly assess effectiveness of drug 
treatments and shorten the duration of clinical trials. NIAID also 
supports efforts to develop improved TB vaccines. NIAID research has 
contributed to more than half of the current clinical pipeline of TB 
vaccine candidates, and NIAID is working with product developers to 
transition promising candidates to advanced clinical trials.
    Respiratory syncytial virus (RSV). RSV is a serious childhood 
respiratory infection. Each year in the United States, RSV causes an 
average of approximately 55,000 hospitalizations among children younger 
than 5 years. NIAID-funded researchers have developed a promising 
pediatric RSV vaccine candidate. Early tests in children and--adults 
show the vaccine is safe and elicits a stronger immune response than 
previously developed RSV vaccines. NIAID has launched an RSV human 
challenge model at the NIH Clinical Center to test the efficacy of this 
vaccine candidate in adults infected with RSV.
          research on immunology and immune-mediated disorders
    NIAID remains committed to advancing our understanding of the 
immune system and immune-mediated diseases. NIAID scientists and 
colleagues have created an extensive database of genetic information to 
facilitate research on immune disorders. These researchers used samples 
from twins to differentiate approximately 80,000 immune traits that are 
likely to be genetically regulated. NIAID has made this open-access 
resource available to researchers worldwide who are investigating 
diverse immune conditions.
    NIAID research also has led to significant progress on treatments 
for immune-mediated diseases. NIAID-supported researchers continue to 
investigate findings from the groundbreaking Learning Early About 
Peanut Allergy (LEAP) food allergy study, which demonstrated that 
consumption of peanut-containing foods beginning in infancy decreased 
the development of peanut allergy in young children. The recent LEAP-ON 
trial demonstrated that tolerance to peanut persisted even after 
stopping peanut consumption for 1 year. This result suggests that early 
peanut consumption may be a viable long-term strategy for preventing 
peanut allergy. NIAID also is supporting research to improve current 
treatments for asthma. The Preventive Omalizumab or Step-up Therapy for 
Severe Fall Exacerbation (PROSE) clinical trial demonstrated that 
treatment with the antibody omalizumab reduced the number of seasonal 
asthma attacks experienced by inner-city children with a history of 
asthma attacks. Finally, NIAID continues to investigate treatment 
options for type 1 diabetes. An NIAID-supported clinical trial of the 
immune-suppressing drug alefacept in patients newly diagnosed with type 
1 diabetes found that the drug helped preserve the function of insulin-
producing cells in the pancreas. This effect persisted for more than a 
year after treatment ended.
                               conclusion
    NIAID continues to confront important historic public health 
challenges by supporting an established research portfolio in 
infectious and immune-mediated diseases while also responding rapidly 
to emerging infectious disease threats. NIAID has assisted 
international efforts to combat newly emerging and re-emerging 
pathogens, such as the Zika, Ebola, and dengue viruses. Research 
supported by NIAID also has advanced progress on persistent infectious 
and immune-mediated diseases worldwide. NIAID will continue to pursue 
effective medical countermeasures for these diseases in an effort to 
improve health globally in collaboration with U.S. and international 
government partners, academia, and industry.
                                 ______
                                 
Prepared Statement of Gary H. Gibbons, M.D., Director, National Heart, 
                       Lung, and Blood Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National Heart, 
Lung, and Blood Institute (NHLBI) of the National Institutes of Health 
(NIH). NHLBI supports a large and diverse research portfolio including 
heart, lung, blood, and sleep (HLBS) disorders.
    NHLBI has a proud history of translating Federal research funding 
into public health successes. There was a time in our Nation's history 
when a heart attack was known as a ``widow-maker'' and a childhood 
diagnosis of either sickle cell disease or cystic fibrosis was 
considered an early childhood death sentence. Thanks to medical 
breakthroughs enabled by NHLBI research investments, there has been a 
dramatic reduction in deaths from cardiovascular disease by 70 percent 
and children born with sickle cell disease and cystic fibrosis have 
extended lifespans well into middle age. NHLBI has recently extended 
this legacy of funding major medical advances by conducting the 
Systolic Blood Pressure Intervention Trial (SPRINT) in patients with 
high blood pressure. This landmark study demonstrated that a more 
intensive treatment of high blood pressure prevents heart attacks, 
strokes, and heart failure while reducing death rates by 25 percent. 
SPRINT is the latest example of NHLBI's approach to turning discovery 
into better patient care outcomes. NHLBI's success serves as a 
compelling demonstration that a steadfast commitment to America's 
biomedical research enterprise yields a tremendous return on investment 
that enhances both the health and wealth of our Nation.
          building on success to address new health challenges
    Our past successes present new and compelling public health 
challenges that require strategic and timely investment in and by 
NHLBI. NHLBI's track record of success in keeping the Nation's blood 
supply safe in the face of the HIV/AIDS epidemic is proving to be a 
critically important foundation for building new initiatives that 
address the imminent threat to blood safety posed by the Zika virus. 
For example, NHLBI-supported investigators are developing ways to 
detect new and emerging microbes in donated blood and novel strategies 
to ``sterilize'' the blood prior to transfusion.
    While we as a Nation must tackle emerging infectious disease 
outbreaks, we must remain vigilant in the fight against the greatest 
long-term public threat to our Nation's health and wealth--the growing 
epidemic and cumulative burden of chronic, age-related conditions such 
as cardiovascular disease, lung diseases, and vascular dementia. As we 
have reduced death from heart attacks, we must pivot to the emerging 
threat of heart failure--a chronic, debilitating, and costly 
complication of heart attacks--that millions of heart attack survivors 
must now face. While it is true that Americans have benefitted from 
high blood pressure treatments to prevent heart attacks and strokes, we 
must still address disorders such as vascular dementia--the second most 
common form of dementia and a major public health challenge for our 
aging population--that can develop as a result of cardiovascular 
diseases such as high blood pressure and stroke. To overcome the 
emerging health challenges of chronic HLBS disorders, which are major 
drivers of Medicare and Medicaid costs, it is critical to fund 
biomedical research to elucidate the underlying root causes and 
molecular mediators of these chronic conditions long before the 
disorder progresses to the end-stage of symptomatic debility and death. 
This is a moment of urgency in which investments in biomedical research 
could provide enormous return on investment by reducing medical care 
expenditures.
    NHLBI funded discoveries are challenging the conventional viewpoint 
that chronic HLBS disorders are an intrinsic and inevitable consequence 
of the aging process. NHLBI is well poised to seize the scientific 
opportunities of today to advance research that can preempt or prevent 
chronic disease and overcome the economic and health challenges these 
disorders pose to millions of Americans. Our goal is to catalyze the 
next generation of discoveries and interventions designed to halt 
disease progression and promote the remission of chronic HLBS 
disorders. Not only do our existing and future research initiatives lay 
the foundation for mapping and therapeutically modulating biological 
pathways leading to chronic HLBS disorders, but they will help us 
understand how normal and diseased HLBS systems affect the health of or 
contribute to disease in other body systems.
  pioneering precision medicine to preempt, prevent, and predict hlbs 
                               disorders
    Continued investment in NHLBI research will allow us to leverage 
new scientific discovery to realize personalized care for HLBS 
disorders. Scientifically aligned with NIH's Precision Medicine 
Initiative, the NHLBI Trans-Omics for Precision Medicine (TOPMed) 
program is pioneering a new integrated approach to understanding HLBS 
diseases by combining genetic, environmental, imaging, clinical, and 
other data from existing NHLBI-supported population-based studies and 
disease-based cohorts to create an accessible, communal data resource 
for scientific inquiry. The cohorts and studies in TOPMed represent a 
broad cross-section of the U.S. population in terms of racial, ethnic, 
and cultural backgrounds, as well as medical histories including common 
HLBS disorders such as atrial fibrillation, asthma, COPD, high blood 
pressure, obesity, and sleep apnea and rare disorders such as sickle 
cell disease and pulmonary fibrosis. TOPMed will integrate these 
genetic data with other data sets to allow researchers to study and 
define health and disease across the lifespan, uncover novel disease 
risk factors, and identify subtypes of disease that may be amenable to 
personalized treatment. These new discoveries will help reduce the 
Nation's disease burden by increasing our capacity to preempt, prevent, 
and predict HLBS disorders.
    For many HLBS disorders we do not know the molecular cause of 
disease, and we lack effective early markers for clinicians to detect 
disease in the earliest stages. The complex nature of HLBS disorders 
often involves changing dynamics within individual organs and between 
multiple body systems and changes across the lifespan due to normal 
genetic variation and common environmental exposures. The TOPMed 
program provides the opportunity to develop a large normative dataset 
to begin defining the transitions from normal to pre-, early-, and 
late-disease States.
    Chronic Obstructive Pulmonary Disease (COPD) and pulmonary fibrosis 
are two diseases for which greater ability to recognize pre-disease 
States and early biomarkers can inform interventions to stop or even 
reverse early molecular changes, before the body has irreversibly begun 
down a path of developing lung disease. Current research through the 
TOPMed program and COPD cohorts has shed new light on how people with 
COPD respond differently to environmental factors such as tobacco smoke 
and has identified developmental and inflammatory pathways at the root 
of the different disease experiences. These studies identified lung 
function genes that are differentially expressed between control and 
COPD patients, which may make possible new COPD drug targets to reverse 
genetic signatures in some patients and prevent disease progression.
    Expanding research in disease diagnosis, prediction, and refinement 
of disease subtypes will inform medical practice and help clinicians 
deliver personalized interventions, sometimes based on a patient's 
genetic makeup, that have been proven effective for a patient's disease 
subtype. For example, NHLBI funded Center for Advanced Diagnostics and 
Experimental Therapeutics in Lung Diseases (CADET) found a genetic risk 
factor of pulmonary fibrosis that occurs in about 40 percent of 
patients with idiopathic pulmonary fibrosis. This discovery is driving 
new diagnostic test development to predict who may develop this form of 
idiopathic pulmonary fibrosis and drug development to counteract the 
effects of this genetic variation.
                         charting a new vision
    NHLBI believes a robust, diverse, and engaged community is 
essential to overcoming our future public health challenges. NHLBI also 
strive to capitalize on the synergies created and leveraged by patient-
centric care models and patient-driven movements. Over the past year, 
NHLBI has spearheaded several broad collaborative partnerships to 
connect scientists, policymakers, patients, and healthcare providers, 
in person and digitally, to meet people where they are to advance 
national public health missions and chart our course for the coming 
years.
    In June 2015, our Sickle Cell Disease Forum engaged over 400 
diverse community partners to understand their greatest needs in the 
area of sickle cell disease research. This Forum reviewed the current 
knowledge base, some of which NHLBI and our funded Centers of 
Excellence in Hemoglobinopathies have helped discover. While our eye is 
keenly focused on finding a future cure, possibly through adaptation of 
emerging gene editing techniques, the Forum also helped focus our 
attention on more immediate ways that NHLBI can significantly reduce 
the daily burdens and improve clinical health outcomes for patients 
with sickle cell disease. For example, NHLBI is committed to gaining 
higher clinical adoption rates of NHLBI's landmark study findings that 
hydroxyurea can reduce the risk of strokes in children with sickle cell 
disease. The 2014 Transcranial Doppler (TCD) With Transfusions Changing 
to Hydroxyurea (TWiTCH) Study confirmed with promising evidence that 
hydroxyurea works as well as blood transfusions to lower TCD 
velocities, a critical marker of stroke risk in very young children 
with sickle cell disease. Helping clinicians move beyond traditional 
transfusion-only treatment and increasing the use of hydroxyurea will 
allow us to realize a stroke-free generation of children. NHLBI's 
Sickle Cell Disease Implementation Consortium is facilitating research 
to assess how coordinated interventions that interweave the patient's 
home, work, and medical provider environments can improve the health 
and well-being of patients with sickle cell disease in the United 
States. Lastly, the Forum reinforced NHLBI's view that we are not an 
island and our global partnerships to research sickle cell disease in 
Sub-Saharan Africa and Brazil are instrumental to refining research and 
treatment development for Americans of African and Hispanic descent, 
who make up a large proportion of sickle cell disease cases in the 
United States.
    Our Strategic Visioning Initiative was one of our most notable 
engagement successes this year. NHLBI undertook a crowdsourcing effort 
to engage patients, investigators, professional societies, and the 
broader NHLBI community in an inclusive and iterative process to shape 
scientific priorities and guide our funding strategies over the next 
decade. During this process, more than 1,000 ideas were submitted and 
42,000 votes were cast by 4,000 members of the community from all 50 
States and 42 countries around the world. In alignment with NIH's 
strategic plan, the resulting NHLBI Strategic Research Priorities will 
be published in late spring 2016 and explore four major goal areas: 
normal biology and health, pathobiology and disease, clinical and 
translation research, and biomedical workforce and training. The 
strength of our Strategic Visioning process rests in the collective 
input of the entire HLBS community which helps to ensure that the 
research NHLBI supports continues to address the most important and 
timely scientific and public health questions related to HLBS disorders 
and that NHLBI strategically invests in research areas that critically 
require our facilitation.
                               conclusion
    NHLBI's portfolio, enhanced by our soon-to-be-released Strategic 
Research Priorities, addresses the enormous economic and health burdens 
of heart, lung, blood, and sleep disorders. Strategic NHLBI investments 
in critical challenges and unanswered research questions over the next 
decade will leverage past research and public health gains to help 
unlock the potential of precision medicine; strengthen existing and 
foster new public-private partnerships for quicker translation of 
research findings into new drugs, devices, diagnostics, and cures; and 
advance implementation science so existing and cutting-edge science can 
be adopted to improve health and reduce health inequities in the 
Nation.
                                 ______
                                 
     Prepared Statement of Roger I. Glass, M.D., Director, Fogarty 
                          International Center
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the Fogarty 
International Center (FIC) of the National Institutes of Health (NIH).
            strengthen and sustain the biomedical workforce
    The cutting-edge scientific advances that improve public health are 
built on foundations of research capacity and rigorous training for 
future scientific leaders. Through its research and research training 
programs, FIC is supporting the best science where problems are most 
acute, facilitating research collaborations between the United States 
and international investigators and institutions, and training the next 
generation of scientists to address global health challenges. FIC's 
niche of investing in future global health research leaders extends the 
reach of research institutions and equips scientists in the United 
States and low- and middle-income countries (LMICs) to solve health 
problems that affect us all.
    Addressing today's complex global health challenges requires a 
critical mass of first-class scientists who are well versed in regional 
health problems. To this end, FIC continues to support the training of 
early-career U.S. scientists at research centers in LMICs. Through 
programs like the International Research Scientist Development Award, 
FIC and its NIH partners provide experiences that encourage early-
career U.S. investigators to take risks and approach problems 
creatively and collaboratively under constraints that may not exist in 
high-income settings. For example, Dr. Maria Hyoun Kim of Baylor 
College of Medicine is working with mentors in Malawi and the United 
States to improve prevention of mother-to-child transmission of HIV in 
LMICs. Specifically, her research evaluates Malawi's novel national 
Option B+ (B+) program, which offers lifelong antiretroviral treatment 
to HIV-infected pregnant and breastfeeding women, and will shed light 
on how effective B+ may be for preventing babies from becoming 
infected.
    In addition, FIC has supported the training of thousands of 
scientists in LMICs who, with their intimate knowledge of the local 
context, are uniquely poised to make discoveries in global health 
research. Many of these investigators have become leaders in academic 
institutions and ministries of health in their home countries, and are 
involved in national efforts to improve the healthcare of the local 
population. For example, FIC's International Collaborative Trauma and 
Injury Research Training Program has expanded trauma and injury 
research partnerships between U.S. and LMIC scientists, and is 
generating data for evidence-based decisionmaking in injury-related 
clinical treatment and prevention programs. With support from this 
program, the University of California, Los Angeles, School of Medicine 
and the University of Cape Town in South Africa are working together to 
address the effects of sexual and physical violence during pregnancy on 
the growth and development of infants. Their study found that maternal 
exposure to physical violence in the year preceding delivery was 
significantly associated with lower birth weight in the infants. 
Further research is planned to assess relevant underlying mechanisms 
and methods in the communities so that effective intervention plans and 
health policies can be developed for South Africa and other sub-Saharan 
African countries.
    Past FIC investments have multiplied the number of foreign 
investigators working abroad who serve as change agents within their 
institutions, which are then positioned to participate in international 
scientific networks. For example, in partnership with the Office of the 
Global AIDS Coordinator at the Department of State, FIC administered 
the Medical Education Partnership Initiative (MEPI). MEPI provides 
medical education and research training for medical students, faculty, 
and other health professionals in sub-Saharan Africa. FIC is continuing 
to foster the next generation of researchers by providing training and 
mentored research opportunities specifically to junior faculty in MEPI-
supported institutions. The MEPI Junior Faculty Program builds on 
MEPI's momentum and existing platform to continue expanding research 
capacity of junior faculty from MEPI institutions. This second-
generation program is increasing retention of faculty who will focus on 
evidence-based clinical teaching as well as strengthen international 
research collaboration.
                                research
    Research supported by FIC's programs is generating critical 
scientific evidence that can lead to new diagnostics, prevention and 
treatment strategies. FIC's Global Brain Disorders Research (Brain) 
program has energized a global health research agenda around brain and 
nervous system diseases and disorders. In collaboration with several 
NIH Institutes and Centers (ICs), Brain has catalyzed innovations 
relevant across the lifespan, from fetal and neonatal neuro-development 
to neurodegenerative diseases of later life, such as Alzheimer's 
disease. For example, scientists at Albert Einstein College of Medicine 
are collaborating with colleagues in India to investigate cognitive 
decline in older adults. Recent findings report prevalence of motoric 
cognitive risk syndrome (MCR)--a newly described predementia syndrome--
and identify MCR in older adults as a strong, early risk factor for 
cognitive decline that can be used to identify seniors at high risk for 
dementia.
    Over the next 5 years, FIC's Global Environmental and Occupational 
Health Hub Program will support the establishment of seven regional 
research and training hubs. Each hub is based in an LMIC and consists 
of a multidisciplinary group of researchers and partner organizations 
who will collaborate on common research and training topics that 
address environmental and/or occupational health issues. For example, 
one hub in Thailand is investigating pesticides commonly used in 
agriculture across Southeast Asia, to see if they act as endocrine 
disrupters, increasing the risk of metabolic syndrome and associated 
diseases such as diabetes, stroke and heart disease. Another hub, in 
Peru, aims to build scientific capacity and support research on air 
pollution and climate change, with links to the neighboring countries 
of Ecuador, Bolivia and Chile.
    FIC is stimulating innovation in the development and implementation 
of technologies and other locally relevant solutions to address global 
health problems. In an effort to understand the impact of mobile 
technologies on health, FIC's Mobile Health: Technology and Outcomes in 
LMICs (mHealth) program supports research on the use of mobile devices 
to generate better health outcomes. One such example is a team of U.S. 
and South African scientists that are developing a mobile screening 
tool to be used by staff with minimal training to detect neurocognitive 
impairment resulting from HIV infection. Pioneering tools like this can 
improve care, reduce costs, and have potential relevance for the United 
States and worldwide.
    FIC's mathematical modelers have been at the forefront of 
addressing the recent Zika and Ebola outbreaks. Researchers at FIC are 
utilizing a novel methodology to analyze Internet news reports on Ebola 
from Africa to describe pathways of transmission. This methodology 
provided evidence that news reports can be a useful source of 
epidemiologic data. Researchers supported in part by FIC also are 
predicting the international spread of Zika virus in Brazil due to the 
August 2016 summer Olympic Games; these research findings were recently 
published in the Lancet in January 2016.
                                 other
    FIC leverages partnerships to maximize the impact of NIH 
investments globally. The Global Network for the Study of Malnutrition 
and Enteric Disease (MAL-ED) is an international collaboration of 
investigators led by FIC and the NIH Foundation. Established in late 
2008, the multi-year, multi-site project is supported by the Bill & 
Melinda Gates Foundation. The goal of MAL-ED is to investigate the 
interactions among exposure, infection, and disease associated with 
enteric pathogens; diet and nutritional status; and, socio economic 
status in relation to resulting impacts on gut physiology; immune 
function and vaccine response; physical growth; and, cognitive 
development. A prospective field, clinical, and laboratory based 
observational study of cohorts of neonates followed to 24 months has 
been established at geographically diverse sites in Asia, Latin 
America, and sub-Saharan Africa. The findings of such analyses will be 
applied toward improving long-term public health in resource-poor 
settings.
    Over the last few years, the emerging economies of Brazil, Russia, 
India, China and South Africa (BRICS) have built highly capable 
biomedical enterprises. NIH and BRICS countries are establishing 
innovative partnerships, funding individual teams of experts who work 
together sharing expertise to speed discovery. NIH is partnering with 
the Brazilian State of Sao Paulo's Science Foundation (FAPESP) to 
parallel-fund U.S.-Sao Paulo R01 applications that are meritorious in 
standard NIH peer-review. FIC developed and is implementing the 
program, which calls for FAPESP to fund the Brazilian institution while 
NIH funds the U.S. institution. To date, 22 NIH ICs have signed on, 
covering most research areas across NIH. Another example is the United 
States-China Program for Biomedical Research Cooperation, a 2010 
bilateral agreement that FIC helped draft and facilitate, that 
strengthens and develops cooperation in basic biomedical research. In 
this program, NIH provides funding to support U.S. scientists involved 
in the research collaborations, while the National Natural Science 
Foundation of China (NSFC) provides funding to support the Chinese 
scientists. So far, there have been a total of 109 awardees, addressing 
scientific questions in the areas of cancer, infectious diseases, 
neurological diseases, and mental health.
                               conclusion
    FIC will continue to invest in the most promising minds in global 
health research, strengthen the capacity of research institutions to be 
sustainable platforms for cutting-edge science, and catalyze meaningful 
international scientific collaborations in fiscal year 2017 and the 
years to come.
                                 ______
                                 
  Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN, Director, 
                 National Institute of Nursing Research
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 Budget request for the National 
Institute of Nursing Research (NINR) of the National Institutes of 
Health (NIH).
                              introduction
    The mission of NINR is to promote and improve the health of 
individuals, families, and communities. We achieve this mission by 
supporting research to: promote health and prevent disease; advance 
symptom science to develop personalized health strategies; enhance 
self-management of chronic conditions; improve end-of-life and 
palliative care; develop new technologies to improve health; and train 
nurse scientists. This year, we are pleased to commemorate NINR's 30th 
anniversary, which provides an opportunity to reflect on many of the 
accomplishments being made every day by nurse scientists across the 
Nation. In October 2015, NINR hosted the first in a series of 
scientific events to highlight significant contributions of nursing 
science for improving health. As we envision the next 30 years, we are 
confident that NINR's support of nursing research will continue to 
improve the lives of diverse individuals, families, and communities 
across the life span. I am grateful for this opportunity to share with 
you some examples of the innovative research that NINR supports.
            improving the health of children and adolescents
    Chronic conditions such as asthma, obesity, and diabetes have the 
potential to negatively affect the quality of life of children and 
adolescents. NINR-supported scientists are addressing this issue by 
developing innovative interventions to increase positive health 
outcomes in children. NINR-supported researchers demonstrated the 
effectiveness of a school-based healthy lifestyles program for 
overweight/obese and depressed teens. Results showed that a year after 
completing the program, there was a significant decrease in the 
proportion of overweight and obese students, and students who had begun 
the program with severely elevated depressive symptoms had 
significantly lower depression.
    NINR maintains its commitment to support research to improve health 
for children from vulnerable groups who are often disproportionately 
affected by chronic conditions. One recent NINR-supported study showed 
improvements in asthma episode management and prevention behaviors in 
medically underserved, inner-city school-age students who received a 
school and community based asthma health education and counseling 
program. In other ongoing efforts, NINR-supported investigators are 
testing a community-based participatory intervention aimed at American 
Indian/Alaska Native teens and their mothers to raise awareness of the 
risks of gestational diabetes mellitus, promote a healthy lifestyle, 
and prevent subsequent development of type 2 diabetes.
                 maintaining health in older adulthood
    In light of our rapidly aging population, it is more important than 
ever to support efforts to prevent chronic illness early in life and to 
promote active lifestyles, health, and independence as people age. One 
promising area of research focuses on developing new technologies to 
improve and maintain physical mobility for older adults. For example, 
NINR-supported researchers designed an innovative unpowered ankle 
exoskeleton that harnesses the power of a person's own muscles to make 
walking more efficient. Although scientists are still developing and 
testing the exoskeleton, it has the potential to make walking easier 
for people recovering from an injury or dealing with normal aging 
issues. Another recent NINR-led initiative focuses on development of 
technological and biobehavioral interventions to help persons with 
dementia or cognitive impairment maintain independence and quality of 
life, as well as to reduce stress and burden on caregivers. NINR-
supported researchers are also uncovering complex relationships among 
biological, physical, and behavioral factors that may play a role in 
depressive symptoms in older adults. A recent study revealed that 
mutations in a gene known to be related to depression, as well as pain, 
fear of falling, and low physical activity, were all associated with 
depressive symptoms in older adults. NINR is also leading an initiative 
to support prevention research in mid-life adults, which will inform 
efforts to optimize health and wellness as people age.
               enhancing end-of-life and palliative care
    As the lead NIH Institute for end-of-life research, NINR supports 
research to identify the most effective strategies to ease the symptoms 
of advanced illness and to assist families in making difficult end-of-
life decisions. In an effort to build the science of end-of-life and 
palliative care, we continue to support a palliative care research 
cooperative (PCRC), which brings together multidisciplinary researchers 
from universities, health systems, hospices, and hospitals across the 
United States. Recent findings from research supported by the PCRC 
revealed that discontinuing statin medication use in patients with 
advanced illness is safe and may increase quality of life, decrease the 
use of non-statin medications, and reduce costs. In 2015, NINR launched 
the second phase of NINR's Palliative Care: Conversations Matter 
initiative, which focuses on children, parents, and families, and 
includes a new brochure, in English and Spanish, to help raise 
awareness of the benefits of palliative care. NINR also is leading a 
new initiative to support research to better understand the unique 
perspectives, needs, wishes, and decisionmaking processes of youth 
living with serious illnesses and their families, and to enhance their 
quality of life.
              looking toward the future: nurse scientists
    One of NINR's fundamental goals is to develop the next generation 
of nurse scientists to address the Nation's most pressing health 
issues. NINR offers a variety of training opportunities to nurse 
scientists and trainees at all career levels, and recognizes the 
importance of supporting new investigators whose success is so critical 
to the future of innovative research and high-quality healthcare. In 
order to build a scientific workforce that is innovative, diverse, and 
ready for the future, NINR's training programs provide nurse scientists 
with the skills and tools to support continued advancements in science 
and improvements in health. For example, in 2015, NINR sponsored our 
second Big Data Research Boot Camp at NIH, a week-long intensive 
training that provides a foundation in big data science methodologies 
and strategies for incorporating new methods to strengthen research 
proposals. NINR's Summer Genetics Institute is an intensive program for 
graduate students, faculty, and clinicians designed to provide a 
foundation in molecular genetics to improve research and clinical 
practice.
                               conclusion
    Thank you for this opportunity to share some of NINR's 
accomplishments and the important work being done every day by nurse 
scientists across the country. NINR will continue to support innovative 
research to improve health now and in the future.
                                 ______
                                 
Prepared Statement of Eric Green, M.D., Ph.D., Director, National Human 
                       Genome Research Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National Human 
Genome Research Institute (NHGRI) of the National Institutes of Health 
(NIH).
    This past October, the scientific community celebrated a quarter 
century since the launch of the Human Genome Project. Now, roughly 13 
years since the successful completion of that landmark effort, NHGRI 
looks forward to the next quarter century of genomics and its 
applications to advance human health. To this end, NHGRI is fostering a 
continuum of research from basic studies of the structure and function 
of genomes to work that advances medical science and seeks to improve 
the effectiveness of healthcare. Research funded by NHGRI, especially 
in the area of genomic medicine, has laid the foundation for major 
transformational efforts, such as the Precision Medicine Initiative and 
the National Cancer Moonshot.
    As an example, NHGRI's partnership with the National Cancer 
Institute in leading The Cancer Genome Atlas for nearly 12 years has 
led to powerful new insights that will fuel the National Cancer 
Moonshot. Through the use of new genome-analysis technologies, data 
have been generated for over 10,000 tumor specimens, allowing the 
assembly of a rich data resource that is now freely available to any 
qualified researcher. This body of work is providing new insights about 
classifying and treating cancer, fundamental information for the 
National Cancer Moonshot.
    Another major research program supported by NHGRI, the 1000 Genomes 
Project, has now established a powerful data resource with information 
about how humans differ with respect to their genomic blueprint. With 
its final summary papers published in Nature this past October, this 
international effort analyzed the genomes of over 2,500 people from 26 
populations around the globe, identifying and cataloguing more than 88 
million places in the genome that humans differ. Together, the 
generated information accounts for more than 99 percent of the common 
genomic variants (or `spelling differences') that exist in the human 
population. By producing a global catalog of human genomic variation, 
researchers can now focus on which of the identified variants play a 
role in health and disease.
    Despite the remarkable progress in genomics over the past quarter 
century, more powerful and accessible approaches for studying genome 
structure and function are needed. To help address this need, the 
Centers of Excellence in Genomics (CEGS) program supports multi-
investigator, interdisciplinary teams that develop new approaches and 
technologies for using genomics in biomedical research. fiscal year 
2017 funds for NHGRI will support CEGS efforts that combine genome-
editing technologies and tissue-engineering methods to develop improved 
models of complex tissues such as the brain. The CEGS program 
exemplifies how basic research can be applied to specific problems, 
yielding solutions that can advance diverse fields of inquiry.
    The promise of genomics as a clinical tool for improving patient 
care is now coming into focus. A program that vividly highlights this 
capability is the Undiagnosed Diseases Network (UDN). An extension of 
the Undiagnosed Diseases Program launched within the NIH Intramural 
Research Program in 2008 and funded by the NIH Common Fund, the UDN 
embodies the promise of genomic and precision medicine. Under NHGRI's 
leadership, both programs are helping patients (and their families) 
that have faced diagnostic odysseys and are discovering the genomic 
bases of extremely rare disorders. The value of UDN is multifaceted, 
with some aspects related to the care and support it provides to its 
patients and other aspects related to robust approaches being developed 
for the study of rare medical conditions. fiscal year 2017 funds for 
the program will support an expansion in patient enrollment across the 
national network.
    NHGRI is further maximizing the potential for public benefit from 
the Federal investment in genomics with programs such as UDN by 
promoting synergy across research communities. Leveraging leading 
experts across national consortia directly stimulates dialog and an 
exchange of ideas that can prove mutually beneficial to all groups 
involved. An illustration of this can be seen with the collaboration 
between UDN and NHGRI's Centers for Mendelian Genomics program, a 
large-scale effort that is elucidating the genomic causes of rare human 
diseases. Through their synergistic interactions, these consortia are 
producing new insights about basic biological pathways that are 
relevant to both rare diseases as well as more common ones. Utilizing 
the discoveries emanating from rare disease studies should propel 
forward basic understanding of common diseases, particularly in the 
characterization of disease mechanisms and the establishment of new 
treatment options.
    NHGRI also recognizes the importance of examining and addressing 
the ethical, legal, and social issues associated with moving genomics 
initiatives forward and with implementing genomic medicine. In fiscal 
year 2017, NHGRI will thus continue to fund research that examines the 
increasing accessibility of genomic information and technologies within 
society. Such studies will investigate questions related to biobanking, 
clinical genome sequencing, and broad data sharing--all issues of great 
relevance to the Precision Medicine Initiative. A particular focus will 
be placed on how such issues affect studies involving vulnerable or 
underrepresented populations. Genomic privacy and genetic 
discrimination, as well as the complexities associated with the return 
of results from genomics research studies, will also be explored.
    Educating providers, patients, and the public about genomics is 
also imperative for the successful incorporation of genomics into 
healthcare. NHGRI dedicates significant time and attention to outreach 
efforts and the education of various stakeholders. The highly 
successful Genome: Unlocking Life's Code exhibition, developed in 
conjunction with the Smithsonian Institution, has now been seen by more 
than four million people as it travels to cities big and small across 
the United States.
    NHGRI's well-rounded portfolio of basic, translational, and 
clinical research programs has the long-term aim of using genomics to 
advance the health of all Americans. fiscal year 2017 funds will help 
to ensure that NHGRI continues to lead the genomics community, support 
the broader biomedical research community, and help realize a future of 
remarkable genomics-enabled healthcare innovations.
                                 ______
                                 
  Prepared Statement of Betsy L. Humphreys, Acting Director, National 
                          Library of Medicine
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Library of Medicine (NLM) of the National Institutes of Health (NIH).
                                overview
    NLM, the world's largest medical library, is the most visible face 
of NIH across the United States and around the globe. Through its 
information systems, a cutting-edge informatics research portfolio, 
extensive training programs, and many partnerships, NLM plays an 
essential role in catalyzing and supporting the translation of basic 
science into new treatments, new products, improved practice, useful 
decision support for health professionals and patients, and effective 
disaster and emergency preparedness and response. NLM coordinates a 
6,400 member National Network of Libraries of Medicine (NN/LM) that 
provides a field force for improving access to high-quality health 
information in communities nationwide, with an emphasis on populations 
with health disparities.
    Millions of scientists, health professionals, and members of the 
public use NLM's electronic information sources billions of times each 
year. The range of information that NLM organizes and disseminates is 
enormous, including genetic, genomic, and biochemical data; images; 
clinical trials; published and unpublished research results; historical 
archives; decision support resources; scientific and health data 
standards; informatics tools for system developers; and health 
information for the public. Every day, researchers submit 5 terabytes 
of data to NLM databases and users download more than 50 terabytes. 
Anyone can search or download information directly from an NLM website, 
find it via an Internet search engine, or use an ``app'' that provides 
value-added access to NLM data. Thousands of commercial and non-profit 
system developers regularly use the applications programming interfaces 
(APIs) that NLM provides to fuel private sector innovation and to embed 
access to NLM information services within electronic health records 
(EHRs).
    NLM actively conducts and supports basic research in computational 
biology and informatics and also funds development of computational 
tools and methods for analysis of scientific data, electronic health 
records, images, and publications. In fiscal year 2015, NLM intramural 
scientists were key members of an international CRISPR-Cas research 
team that identified three new naturally occurring systems that show 
potential for genome editing.
               biomedical and health information services
    In fiscal year 2015, NLM greatly expanded the quantity and range of 
high-quality information readily available to scientists, health 
professionals, and the general public. For example, more than 806,000 
new journal articles were indexed for PubMed/MEDLINE, NLM's most 
heavily used database, which contains more than 25 million references 
to articles in the biomedical and life sciences journals, with links to 
related scientific data and full-text articles on publishers' websites 
and in NLM's PubMed Central (PMC) repository. PMC now includes more 
than 3.6 million full-text research articles, including those submitted 
in accordance with the NIH Public Access Policy and similar policies of 
the Department of Health and Human Services (HHS) and several other 
Federal agencies.
    NLM's National Center for Biotechnology Information (NCBI) is a 
leader in and a hub for the international exchange of big data utilized 
in molecular biology, genomics, and clinical and translational 
research. Some of the largest datasets are available in the cloud to 
facilitate access and analysis by researchers who have insufficient 
bandwidth or computing power. In fiscal year 2015, the database of 
Genotypes and Phenotypes (dbGaP), which connects individual-level 
genomic data with individual-level clinical information, grew by more 
than 20 percent and now contains 600 studies involving more than one 
million people. The RefSeq database of curated reference sequences grew 
to nearly 15 million genomic records, an 88 percent increase, and more 
than 51 million protein records from over 54,000 organisms. Many NLM 
databases, including dbGaP, RefSeq, the Genetic Testing Registry, and 
ClinVar, are fundamental to the identification of important 
associations between genes and disease, and to the translation of new 
knowledge into better diagnoses and treatments.
    NCBI continues to collaborate with the Food and Drug Administration 
(FDA), Centers for Disease Control and Prevention, the Department of 
Agriculture, and other groups to maintain a database of whole genome 
sequencing (WGS) data for antibiotic-resistant bacteria along with 
tools to facilitate analyses of such data. The database provides an 
important resource for surveillance and research into the mechanisms 
underlying the emergence of antibacterial resistance. This program 
builds upon a successful collaborative project among these same 
agencies to use WGS to more quickly and accurately identify and 
investigate outbreaks of disease caused by foodborne bacteria.
    ClinicalTrials.gov, the world's largest clinical trials registry, 
now includes more than 200,000 registered studies in 190 countries and 
summary results for more than 18,700 trials, including many not 
available elsewhere. When finalized, regulations to implement the Food 
and Drug Administration Amendments Act of 2007 and a proposed NIH 
clinical trial reporting policy are expected to further increase the 
amount of information submitted each year to this valuable resource.
    NLM's MedlinePlus provides access to high quality consumer health 
information produced by NIH and HHS agencies, other Federal agencies, 
and authoritative private organizations. It also serves as a gateway to 
specialized NLM information sources for consumers, such as the Genetic 
Home Reference and the Household Products Database. Available in 
English and Spanish, with selected information in 40 other languages, 
MedlinePlus averages more than 1.6 million visits per day.
    In fiscal year 2015, NLM collaborated with the HHS Assistant 
Secretary for Preparedness and Response and the National Institute of 
Environmental Health Sciences to develop new information resources for 
pre- and post-disaster health issues and disaster research response.
          electronic health records and clinical data analysis
    For more than 40 years, NLM has supported seminal research in 
biomedical informatics, including EHRs, imaging, clinical decision 
support, and health information exchange. It has also been the 
principal funder of university-based programs that have trained many of 
today's leaders in informatics research and health information 
technology. As adoption and deployment of EHRs increases, so do 
opportunities to mine increasingly large stores of patient data for 
research and public health. NLM conducts and supports research to 
enable effective use of EHR data in knowledge discovery, public health 
surveillance, and healthcare quality improvement. In fiscal year 2015, 
NLM intramural scientists took advantage of the Centers for Medicare 
and Medicaid Services' (CMS) efforts to streamline research access to 
Medicare data to conduct studies about epidemiology of drug-drug 
interactions and the potential association between Simvastatin use (a 
drug used to lower cholesterol and triglycerides) and dementia/
Alzheimer's disease.
    In close collaboration with the HHS Office of the National 
Coordinator for Health Information Technology and with assistance from 
CMS, Veterans Health Administration, and FDA, NLM develops, funds, and 
disseminates the clinical terminologies designated as U.S. standards 
for meaningful use of EHRs and health information exchange. NLM 
produces a range of tools that help EHR developers and users to 
implement these standards and makes them available in multiple formats, 
including via APIs. NLM's technical and financial support enables 
clinical terminology standards to be updated regularly to reflect new 
drugs, tests, devices, and changes in medical knowledge and health 
practice--and also allows them to be used free-of-charge in U.S. 
healthcare, public health, biomedical research, and product 
development.
    The inclusion of standard terminology in EHRs enables more 
effective clinical decision support by making it easier to use 
information in a patient's record to retrieve knowledge relevant to 
that record. In fiscal year 2015, NLM's MedlinePlus Connect service 
increased its utility to EHR vendors seeking to connect their products 
directly to NLM's high quality information relevant to a patient's 
conditions, medications, and test results by expanding its links to 
standard terminologies and billing codes. Standardized EHRs are also an 
increasingly important source of data for cost-effective observational, 
clinical, and translational research and will enhance the value of the 
Precision Medicine Initiative cohort. NLM continued its work to 
facilitate the inclusion of standard clinical terminology in common 
data elements and patient assessment instruments used in NIH and HHS-
funded comparative effectiveness and clinical research. NLM's Unified 
Medical Language System (UMLS) resources provide essential 
infrastructure for advanced clinical decision support by connecting 
standard clinical terminologies to billing codes and more than 120 
other important biomedical vocabularies, such as those used in 
information retrieval and gene annotation. By linking the many 
different terms used to represent the same concepts and by providing 
associated natural language processing programs, NLM's UMLS resources 
help computer programs interpret biomedical text correctly. These 
resources are heavily used in NIH-funded research; in commercial 
product development; and in many electronic information services, 
including those produced by NLM.
                          reaching the public
    NLM has a range of programs to enhance awareness and use of NLM's 
information services among biomedical researchers, health 
professionals, librarians, patients, and the public. NLM works closely 
with more than 6,300 members of the NN/LM--academic health sciences 
libraries, hospital libraries, public libraries, and community-based 
organizations--and through formal partnerships with historically black 
colleges and universities, tribal colleges, and other minority serving 
institutions. In fiscal year 2015, dozens of community-based projects 
were funded across the country to enhance awareness and access to 
health information, including in disaster and emergency situations, and 
to address health literacy issues. Use of mobile sites, ``apps,'' APIs, 
and responsive design techniques help NLM tailor the delivery of 
content to the range of devices employed by its users.
    NLM is redesigning many of its web interfaces so that the 
information display adjusts automatically to the size of the device, 
including smart phones. In fiscal year 2015, the Library released new 
``responsive design'' versions of MedlinePlus and MedlinePlus en 
espanol. NLM continues to be a leading player in social media amongst 
HHS agencies with active Facebook, Twitter, Flickr, Pinterest, and 
YouTube accounts; several online newsletters; and its NN/LM, which 
covers the U.S. and hosts eight Facebook pages, nine Twitter feeds, and 
12 blogs. NLM is consistently ranked among the most liked, most 
followed, and most mentioned organizations amongst small government 
agencies with social media accounts.
    In conclusion, NLM is a trustworthy source of health information 
for the public and vital to the practice of 21st Century medicine and 
the progress of science. NLM's information services and research 
programs serve the Nation and the world by supporting scientific 
discovery, clinical research, education, healthcare delivery, public 
health response, and the empowerment of people to improve personal 
health. NLM is committed to the development and use of innovative 
computing and communications systems to enhance access to the results 
of biomedical research.
                                 ______
                                 
Prepared Statement of Stephen I. Katz, M.D., Ph.D., Director, National 
      Institute of Arthritis and Musculoskeletal and Skin Diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of 
the National Institutes of Health (NIH).
    As the primary Federal agency supporting medical research on 
diseases of the bones, joints, muscles, and skin, NIAMS touches the 
lives of nearly every American. Arthritis limits the activities of more 
than 22.7 million adults in the United States each year (National 
Health Interview Survey, 2010-2012); medical care and lost wages 
attributable to musculoskeletal conditions cost Americans $874 billion 
annually (Agency for Healthcare Research and Quality Medical 
Expenditures Panel Survey, 1996-2011); and skin conditions such as 
eczema and psoriasis affect more than 12 percent of people worldwide 
(Global Burden of Disease Study, 2010). NIAMS is working to enhance 
health, lengthen life, and reduce illness and disability by supporting 
basic, translational, and clinical research that will make a difference 
for patients; fostering innovation to meet current research needs and 
to support the next generation of biomedical researchers; and enhancing 
stewardship, while reducing administrative burdens on researchers.
          basic research leads to new understanding of disease
    NIAMS investments in basic research are uncovering the underlying 
mechanisms of biological systems and providing new understanding of the 
basis of disease. For example, NIAMS intramural researchers, as part of 
an international consortium, analyzed DNA from nearly 1,000 children 
with systemic juvenile idiopathic arthritis, a severe form of childhood 
arthritis. The researchers showed that changes in a section of the 
genome related to immune cell function are strongly associated with an 
increased risk of developing the condition; when combined with other 
knowledge about the gene region involved, the finding suggests that 
defects in both how the body immediately reacts to infection, and how 
it adapts over time, contribute to the disease.
    Long-term investments in data resources to facilitate basic science 
discoveries continue to produce results. One such resource, the 
Osteoarthritis Initiative, was established a decade ago as a repository 
for medical images, clinical data, and biospecimens from people who 
were at high risk of developing knee osteoarthritis. Recently, 
researchers mining the publicly available database found joint changes 
that may predict who will go on to develop osteoarthritis. This 
discovery is calling into question long-held beliefs about how 
osteoarthritis arises and may open new avenues for halting joint 
disease at its earliest stages.
    Basic research on fundamental biological processes in healthy 
tissues could of regeneration, and currently, we know little about the 
signaling pathways that are involved. NIAMS-supported researchers are 
beginning to uncover the basic molecular events that underlie recovery 
of certain tissues, such as hair follicle regeneration after skin 
wounding. Recently, two key regulators of this process were identified 
in mouse models. Interestingly, both of the molecules are also involved 
in immune system functions, such as protection against viral 
infections. By understanding regeneration in this model, scientists may 
one day be able to develop methods to stimulate repair of other human 
tissues. In fiscal year 2017, NIAMS plans to provide funding for small 
businesses to develop novel complex 3-dimensional (3-D) in vitro human 
musculoskeletal and skin tissue models. These models will facilitate 
the study of human tissue physiology and pathophysiology, and 
potentially lead to better interventions that prevent or cure diseases.
           biomarkers--a tool for discovery and clincal care
    Biomarkers are measurable biological or chemical indicators of 
health or disease that are accurate and reproducible. NIAMS research to 
identify, validate, and utilize biomarkers across the spectrum from 
basic to clinical research is bearing fruit. In a recent study, NIAMS 
intramural researchers examined the blood of patients with ANCA-
associated vasculitis (AAV), a systemic autoimmune disease that causes 
inflammation in the blood vessels. The researchers found that the 
amount of a distinct type of white blood cell in patients with 
vasculitis correlated with how they would respond to treatment. Once 
validated, this discovery could inform clinicians if a particular 
patient is likely to respond to an intervention, helping them to tailor 
treatment to the individual.
    In addition, biomarkers are important tools in monitoring disease 
status. Duchenne muscular dystrophy (DMD) is a genetic disorder 
characterized by progressive muscle weakness, and biomarkers that 
distinguish among stages of the disease could enable researchers to 
rapidly assess how well a novel intervention is working. NIAMS-
supported investigators have identified several different types of 
biomarkers for DMD using new techniques to monitor changes in muscle 
quality. Recently, other researchers found dozens of proteins in blood 
that were significantly different between DMD patients and individuals 
without the disease. Several of these proteins also changed during 
progression from early disease to its later stages. In the future, this 
information may help researchers develop new interventions, identify 
appropriate candidates for clinical trials, and more rapidly interpret 
trial results.
    Other biomarkers are being evaluated as surrogate outcomes when 
examining new interventions for diseases. For example, NIAMS-supported 
researchers tested a new drug to prevent scarring in patients with 
systemic sclerosis, a severe form of the chronic connective tissue 
disease scleroderma. The researchers showed that the drug significantly 
reduced the amount of two proteins in the skin of patients, and these 
reductions correlated with improvement in skin condition assessed via 
traditional clinical measures. The study results demonstrate the value 
of a biomarker-based approach to measuring treatment response and 
confirming clinical data.
              helping clinicians better care for patients
    While basic research into the underlying mechanisms of disease will 
always be an important focus, NIAMS research also helps ensure that 
physicians have up-to-date information to facilitate treatment 
decisions based on the current state of the science. For example, 
children with an abnormal curvature of the spine, called adolescent 
idiopathic scoliosis (AIS), often are instructed to wear braces to 
prevent worsening of the curve, but the effectiveness of this treatment 
had not been rigorously tested. In 2007, NIAMS-supported investigators 
launched the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) 
to compare the risk of curve progression in tweens and teens with AIS 
who wore a brace versus those who did not. In January 2013, the trial 
was stopped early after finding that bracing significantly reduced the 
risk of curve progression and the need for surgery, and that more hours 
of brace wear were associated with higher success rates. These results 
were the primary reason several healthcare provider organizations 
recently updated their recommendations regarding scoliosis screening 
for adolescents. In addition, the United States Preventive Services 
Task Force is currently revisiting its screening recommendations for 
AIS.
    NIAMS researchers are also leveraging existing data to aid 
physicians in everyday practice. Recently, NIAMS intramural scientists 
conducted a comprehensive review of clinical studies into the various 
treatments available for two major causes of back pain, ankylosing 
spondylitis and non-radiographic axial spondyloarthritis. Based on the 
systematic review, a series of treatment recommendations were 
developed, and they have been endorsed by the American College of 
Rheumatology. The recommendations provide clinicians with the current 
best-evidence for the treatment of these common conditions, and may 
facilitate the effective use of healthcare resources, reduce 
inappropriate care, and minimize variation in care.
    Looking to the future, NIAMS will capitalize on prior investments 
and recent advances in the science of patient-reported outcomes (PROs) 
to improve the health and well-being of pediatric patients. The Patient 
Reported Outcomes Measurement Information System, or PROMIS, was an 
NIH Common Fund project, co-led by NIAMS, to develop a system of highly 
reliable, precise measures of patient-reported health status for 
physical, mental, and social well-being. The PROMIS tools can give 
physicians a clearer understanding of how the patient is feeling and 
functioning, and can be used across a wide variety of chronic diseases 
and conditions in both research settings and in routine care. In fiscal 
year 2015, NIH funded the Validation of Pediatric Patient-Reported 
Outcomes in Chronic Diseases (PEPR) Consortium that will expand 
existing and new PRO tools for pediatric patients, ultimately improving 
the treatment of chronic diseases in children. PEPR is part of a trans-
NIH effort to lay the foundation for a new multi-year initiative called 
the Environmental Influences on Child Health Outcomes (ECHO) program 
set to begin in fiscal year 2017.
             fostering innovation and enhancing stewardship
    NIAMS is actively working to enhance and strengthen our scientific 
stewardship and encourage innovation. As part of these efforts, NIAMS 
is supporting several programs targeting the next generation of 
researchers. In fiscal year 2015, NIAMS launched a new program called 
the Supplements To Advance Research from Projects to Programs, or STAR, 
awards. STAR promotes innovation and exploration of high-risk ideas by 
providing flexible funding to early established investigators to expand 
upon their currently funded project and facilitate transition from a 
single project to a research program. NIAMS made three STAR awards in 
fiscal year 2015, and anticipates another group of awards in fiscal 
year 2016.
    In addition to STAR, NIAMS has implemented several programs to 
support clinician researchers, a vital population that faces unique 
challenges in pursuing research careers. Since fiscal year 2012, NIAMS 
has hosted an annual career development forum for extramural 
researchers who have received either a mentored clinical scientist 
development (K08) or patient-oriented research (K23) grant. The forum 
provides awardees with opportunities to network with each other, as 
well as NIAMS leadership and program, review, and grants management 
officials; and enhances the Institute's support of early-stage 
physician-scientists by encouraging and enabling awardees to continue 
performing basic, translational, or patient-oriented research in their 
chosen fields. In addition to the forum in fiscal year 2016, NIAMS will 
implement a new trans-NIH policy of increased salary support for these 
same K awardees, a year earlier than required by NIH. Finally, NIAMS is 
planning a new small grant program to assist early-stage clinician 
scientists as they pursue research independence through the so-called 
K-to-R transition, a particularly vulnerable period for investigators. 
Together, these and other training and fellowship programs will help 
ensure a robust pipeline of new investigators in the rheumatic, 
musculoskeletal, and skin disease mission areas.
    NIAMS is also encouraging innovation and stewardship by 
collaborating with the research community and other stakeholders to 
elaborate on exciting new research opportunities. For example, NIAMS, 
on behalf of NIH, led the development of a new Action Plan for Lupus 
Research, and also participated in the development of the Action Plan 
for the Muscular Dystrophies. Both plans represent a synthesis of NIH 
internal input, as well as significant external input from the 
scientific, clinician, and patient advocacy communities. They will help 
to inform priority-setting processes among all interested 
organizations--Federal, private, and non-profit--and may inspire 
individual investigators as they develop innovative, independent 
research proposals. In addition, NIAMS is leading the Accelerating 
Medicines Partnership in Rheumatoid Arthritis and Lupus (AMP RA/Lupus). 
This unique public-private partnership with NIH, pharmaceutical 
companies, and non-profit organizations aims to transform the model for 
identifying and validating promising targets for the development of new 
drugs and diagnostics. The AMP RA/Lupus program was funded in late 
fiscal year 2014, and researchers and other partners have developed a 
research plan with distinct milestones. Substantial progress has 
already been made incorporating cutting edge technologies and 
establishing standard operating procedures that the broader scientific 
community will be able to leverage in the future.
                                 ______
                                 
    Prepared Statement of George F. Koob, Ph.D., Director, National 
               Institute on Alcohol Abuse and Alcoholism
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2017 budget request for the 
National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the 
National Institutes of Health (NIH).
    Alcohol misuse has profound, adverse effects on individuals, 
families, and communities. Seventeen million people in the United 
States have alcohol use disorder (AUD), and the Centers for Disease 
Control and Prevention estimates that excessive alcohol consumption 
cost the United States $249 billion in 2010. NIAAA is grateful for the 
increase to the NIAAA budget provided in fiscal year 2016. This 
additional investment will allow NIAAA to increase support for research 
training and career development programs, fund additional cutting-edge 
alcohol research projects, and facilitate the translation of alcohol 
research into practice.
    AUD is a chronically relapsing brain disease. As individuals 
progress from initial alcohol use to risky drinking to AUD, changes 
occur in the structure and function of their brains. These changes 
perpetuate drinking and persist long after a person stops. A major 
focus of NIAAA's work is to develop a more thorough understanding of 
how these changes contribute to the development and maintenance of AUD. 
With the additional funding provided to the agency in fiscal year 2016, 
NIAAA is able to pursue several important new areas of inquiry in the 
neurobiology of alcohol misuse and AUD, including studies of the 
effects of adolescent drinking on brain development, exploration of 
neuroimunne function in the development of AUD, and identification of 
new AUD treatment targets.
    Alcohol consumption during pregnancy can have devastating effects 
on the developing embryo and fetus. Fetal alcohol spectrum disorders 
(FASD), an umbrella term for a range of developmental, cognitive, and 
behavioral problems caused by prenatal alcohol exposure, are the 
leading preventable causes of birth defects and developmental 
abnormalities in the United States. NIAAA supports research on the 
mechanisms through which alcohol disrupts prenatal development, to 
develop new biomarkers to improve detection of drinking during 
pregnancy, to improve FASD diagnosis and establish more precise 
prevalence estimates in the United States, and to develop effective 
interventions to mitigate the adverse effects of prenatal alcohol 
exposure.
    Adolescents are particularly vulnerable to the adverse effects of 
alcohol. Drinking during adolescence can impair the development of the 
frontal cortex, the region of the brain responsible for executive 
function and decisionmaking; compromise short- and long-term cognitive 
functioning; and increase risk for alcohol problems later in life. 
NIAAA supports a broad portfolio of research to identify the factors 
that contribute to adolescent alcohol misuse and the effects of alcohol 
on the developing adolescent brain. The NIAAA-funded National 
Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), for 
example, is a nationally-representative, longitudinal study evaluating 
brain structure and function in more than 800 youth before and after 
they start to drink. Building on NCANDA, NIAAA, along with other NIH 
Institutes and Offices, launched the Adolescent Brain Cognitive 
Development (ABCD) Study in September 2015. The study will recruit 
approximately 10,000 children ages 9-10, most of whom will not have 
initiated substance use, and followed into early adulthood. 
Participants' exposure to alcohol and other drugs (alone and in 
combination), academic achievement, cognitive skills, mental health, 
and brain structure and function will be tracked over a 10-year period. 
The findings will enable researchers to better understand the myriad 
factors that contribute to brain and cognitive development and how 
alcohol and other drugs affect these processes, and they will inform 
prevention and treatment interventions and public health strategies.
    Like adolescents, young adults are also highly vulnerable to the 
adverse effects of alcohol misuse, and binge drinking is a particular 
concern within this population. In September 2015, NIAAA released its 
College Alcohol Intervention Matrix, CollegeAIM, an evidence-based 
decision tool to help college and university administrators select 
interventions for addressing alcohol misuse on their campuses. 
CollegeAIM rates nearly 60 individual- and environmental-level 
intervention strategies based on factors such as effectiveness in 
achieving targeted outcomes; estimated cost of adoption, implementation 
and maintenance; and barriers to implementation. NIAAA will be working 
with its College President's Working Group to hold a series of regional 
workshops to introduce CollegeAIM to institutional officials and show 
them how it can be used on their campuses. NIAAA also is supporting 
research to evaluate the use of alcohol screening and brief 
intervention for preventing and reducing alcohol misuse among young 
adults in clinical and non-clinical settings.
    Alcohol use by older adults is emerging as an important area of 
emphasis for NIAAA. Older adults may be more sensitive to alcohol's 
effects, more likely to suffer from health problems exacerbated by 
heavy drinking, and more likely to experience adverse alcohol-
medication interactions. Additional research is needed to more fully 
understand how alcohol differentially affects this population.
    Reflecting its increased emphasis on developing new medications to 
treat AUD, NIAAA established a Division of Medications Development 
(DMD) to coordinate efforts to identify, screen, and evaluate promising 
compounds. Through the NIAAA Clinical Investigations Group (NCIG), DMD 
is conducting ``fast success/fast fail'' phase II clinical trials of 
novel and repurposed compounds in collaboration with the pharmaceutical 
industry. NCIG is currently evaluating gabapentin encarbil, an FDA-
approved medication for restless leg syndrome and nerve pain that has 
shown promise for reducing heavy drinking and promoting abstinence in 
individuals with AUD. NIAAA is also working to bridge the gap between 
basic and clinical research through the Small Business Innovation 
Research and Small Business Technology Transfer programs. Under these 
programs, NIAAA is funding studies intended to result in the submission 
of an Investigational New Drug application to FDA for the development 
of medications to treat AUD or related conditions.
    NIAAA continues to support the development of medications for 
alcoholic liver disease, especially alcoholic hepatitis, a serious and 
often fatal consequence of alcohol misuse for which there is a dire 
need for new treatments. Potential therapies for alcoholic hepatitis 
currently being tested include: probiotics; an interleukin inhibitor, 
which targets a signaling molecule produced by immune cells; and 
immunoglobulin, which binds lipopolysaccharides in the gastrointestinal 
tract. Through NIAAA's intramural research program, scientists are 
studying the link between endocannabinoids and hepatocellular 
carcinoma, a serious form of liver cancer with a high mortality rate 
and no adequate treatment. Their research supports a role for 
endocannabinoids in tumor promotion and raises the possibility that 
compounds that block endocannabinoid action could be used to treat this 
form of cancer. NIAAA intramural investigators have also developed and 
filed for a patent on compounds that inhibit both peripheral 
cannabinoid receptors and inducible nitric oxide synthase. These 
inhibitors show promise for treating liver and lung fibrosis in 
preclinical studies, and NIH's Office of Technology Transfer is 
currently pursuing licensing of these compounds to the private sector 
for further development and eventual commercialization.
    For individuals undergoing treatment for health conditions 
associated with excessive alcohol consumption, monitoring their alcohol 
use is important. NIAAA issued the ``Wearable Alcohol Biosensor 
Challenge'' to stimulate the development of an unobtrusive, real-time, 
continuous alcohol monitoring system. The biosensor is expected to 
facilitate alcohol research, enable clinicians to accurately assess 
their patients' alcohol intake, and help individuals monitor their own 
drinking. NIAAA is currently testing eight biosensor prototypes 
submitted in response to the Challenge.
    NIAAA participates with other NIH Institutes, the Department of 
Defense, the Department of Veterans Affairs, and the Department of 
Education to accelerate the discovery of underlying mechanisms of post-
traumatic stress disorder (PTSD). Approximately one-third of 
individuals who have had PTSD have had AUD at some point in their 
lives, and an estimated 30-60 percent of patients seeking treatment for 
AUD meet criteria for PTSD. Both conditions are linked to dysregulation 
of brain stress systems, and research suggests that alcohol use may 
increase PTSD risk by altering the brain's ability to recover from 
traumatic experiences. Scientists in NIAAA's intramural research 
program are conducting studies to understand how alcohol and stress 
affect the structure and function of brain circuits critical for the 
regulation of emotion, cognition, and behavioral control over alcohol 
and other drug seeking. NIAAA also supports research to develop 
interventions for preventing and treating co-occurring AUD and PTSD 
including studies aimed at identifying and overcoming barriers to the 
diagnosis and treatment of these conditions.
    For more than 45 years, NIAAA has supported a diverse portfolio of 
research and related initiatives aimed at understanding the effects of 
alcohol on health and wellbeing. Efforts such as the Brain Research 
through Advancing Innovative Neurotechnologies (BRAIN) initiative are 
expected to spur an explosion of new knowledge about brain structure 
and function and yield unprecedented insight into brain diseases 
including AUD. To capitalize on these and other opportunities in 
alcohol research, it is essential to cultivate a talented and diverse 
research workforce. Therefore, NIAAA will continue to support robust, 
research training and career development experiences for emerging and 
established scientists. NIAAA also will pursue efforts to enhance the 
incorporation of addiction medicine into clinical training, thereby 
facilitating the translation of alcohol research into practice.
                                 ______
                                 
    Prepared Statement of Jon L. Lorsch, Ph.D., Director, National 
                 Institute of General Medical Sciences
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of General Medical Sciences (NIGMS) of the National 
Institutes of Health (NIH).
                  investing strategically in discovery
    NIGMS-funded scientists investigate how living systems work at a 
range of levels, from molecules and cells to tissues, whole organisms, 
and populations. NIGMS believes that, as in finance, a diverse research 
investment is wise because it maximizes the opportunity for 
breakthroughs. NIGMS supports a diverse population of scientists and a 
broad portfolio of science at institutions dispersed across the United 
States.
    NIGMS has a longstanding commitment to nurturing creative thought 
that produces new knowledge. In turn, this knowledge grows into 
tangible health solutions. Again this year, two long-time NIGMS 
grantees won Nobel prizes in Chemistry for their groundbreaking work 
about basic biological processes: in this case, how cells repair 
damaged DNA. The work, which has led cancer researchers to develop 
useful drugs, explains how cells respond to DNA injuries from 
ultraviolet radiation or chemicals like the carcinogens found in 
cigarette smoke, as well as how cells fix copy errors in the genetic 
code that accumulate naturally during cell division. Another NIGMS 
grantee shared the 2015 Albert Lasker Basic Medical Research Award 
(``the American Nobel'') for his work on the DNA-damage response--a set 
of actions that cells undergo to protect their genomes against a nearly 
constant barrage of minor DNA damage. It is clear that seminal 
discoveries reflecting decades of careful study of fundamental living 
systems can have very practical outcomes in treating deadly conditions 
like cancer.
    NIGMS values the time-tested practice of supporting investigator-
initiated research grants that unleash the creativity and energy of 
investigators across the country to solve important biomedical problems 
essential to progress in medicine. Leaving discovery to scientists, 
NIGMS nonetheless charts its course guided by its strategic plan that 
commits to public service, careful stewardship of taxpayer funds, and a 
focus on efficiency and effectiveness.
  nigms strategic priority: support investigator-initiated biomedical 
                                research
    NIH-funded scientists have faced increased competition to obtain 
grant funding over the past several years. As one step in enhancing the 
efficiency of this process, NIGMS developed and is currently piloting a 
new way to fund scientists. The Maximizing Investigators' Research 
Award (MIRA) program provides support for the NIGMS-relevant research 
in an investigator's laboratory (via a single, 5-year grant), with the 
goal of giving investigators greater stability and flexibility and 
enhancing scientific productivity and the chances for important 
breakthroughs. The program also aims to help distribute funding more 
widely among the Nation's highly talented and promising investigators. 
NIGMS extended its first MIRA funding opportunity to established 
(experienced) investigators whose grant support would expire this year 
or next: approximately 25 percent of the eligible pool applied, using a 
streamlined application that outlined a broad vision for their work and 
its projected significance. Peer reviewers, the Institute's Advisory 
Council and NIGMS staff considered a number of criteria when judging 
MIRA proposals in addition to the applicants' research vision, 
including their record of scientific productivity and contributions to 
training the next generation of researchers. The program, which the 
Institute is also testing with a cohort of junior investigators, has 
been well-received by the community: ``[MIRA] appears to be more 
``organic'' and ``flexible'' than the traditional R01 model, and 
intuitively seems more compatible with the manner in which ideas, 
hypotheses, and unexpected discoveries emerge from focused and 
sustained lines of research,'' said one MIRA applicant. The Institute 
is capturing data to evaluate how well program goals are met.
    Some areas of biomedical investigation require groups of 
investigators to work together to ensure synergistic, interdisciplinary 
expertise and a diversity of thought applied to complex problems. In 
addition to our programs that support single investigators, NIGMS also 
funds larger, team-based scientific research. These programs involve 
multiple investigators and can include facilities or cores, and 
training and outreach activities. Important areas of team-based 
research supported by NIGMS are the specialized Centers for HIV/AIDS-
related structural biology. These Centers tackle difficult problems 
such as HIV interactions and viral evolution and mechanism of HIV-virus 
fusion dynamics with host cells. Their work has laid the foundation for 
the development of new AIDS drugs and possible vaccines. Other areas of 
team-based research funded by NIGMS that have had an important 
scientific impact include the National Centers for Systems Biology. By 
investing in these centers for over a decade, the program has funded 
228 group leaders and directly supported 268 graduate students and 278 
postdoctoral fellows; with an impact of approximately 2,000 peer 
reviewed research papers. As a testament to this program, today many 
universities have departments and training programs in systems biology, 
home to researchers whose work is now supported by investigator-
initiated R01 grants. Through its strategic plan, the Institute will 
explore new models for supporting team science that may be more 
efficient ways to promote important collaborations than are current 
funding strategies.
    nigms strategic priority: build and maintain a diverse research 
                               workforce
    Science has changed dramatically over the past three decades, and 
the amount of information available about biological systems has grown 
exponentially. New methods allow researchers to illuminate and 
investigate the inner workings of cells with unprecedented resolution 
(see, for example, the discussion below of cryo-EM technology), and to 
generate expansive datasets that monitor and measure hundreds to 
thousands of molecular entities in a system, in both time and space. 
Biomedical research is becoming increasingly interdisciplinary and 
collaborative, whilst the questions become ever more complex. NIGMS is 
working to catalyze modernization of the education and training of the 
next generation of biomedical researchers to meet the rapidly evolving 
challenges and opportunities of science and medicine. The Institute 
recognizes that teaching and learning are not one-size-fits-all 
endeavors, and that institutional context matters. To promote the 
necessary shifts, NIGMS is helping colleges and universities test new, 
innovative educational models that develop the skills required for 
students to become outstanding scientists who conduct rigorous and 
reproducible biomedical research. New training paradigms will also 
emphasize the essential role of mentoring in career development. The 
Institute hopes to promote a culture in the academic community that 
continually optimizes training strategies to meet the changing needs of 
the scientific enterprise. Toward achieving these goals, in April 2016, 
NIGMS is hosting a symposium on the NIH campus to convene stakeholders 
from the biomedical graduate education community to continue momentum 
for positive change and showcase innovative approaches in Ph.D. 
training.
    One key element of research excellence is scientific workforce 
diversity, because capitalizing on the full spectrum of skills, 
talents, and experiences is essential for solving complex human health 
challenges. Over the past several decades, the biomedical workforce has 
benefited from various NIH programs aimed at enhancing diversity. 
NIGMS, in particular, has demonstrated a strong commitment to training 
underrepresented individuals through programs supporting all stages of 
the career development pathway. The Institute has identified a pressing 
need to focus on career inflection points, notably the transition from 
trainee to career independence. The Institutional Research and Academic 
Career Development Award (IRACDA) program addresses this need by 
combining a traditional mentored postdoctoral research experience with 
an opportunity to develop academic skills, including teaching, through 
workshops and mentored teaching assignments at a partner (typically 
underserved) undergraduate institution. NIGMS recently began an 
analysis of how well this program is achieving its goals, and the 
initial results are very good. IRACDA has sponsored about 400 scholars 
who have completed training since the program's 1999 inception. A 
substantial number of these alumni (70 percent) hold academic positions 
at a variety of educational institutions: 35 percent of academic alumni 
are located at research-intensive institutions; 14 percent work at 
partner institutions; and the remainder are employed at other 
institution types. A particularly promising finding is that IRACDA 
scholars are considerably more diverse than either a comparable pool of 
NIH-funded postdoctoral fellows or the overall NIH-funded research 
workforce.
   nigms strategic priority: create and share cutting-edge tools and 
                               resources
    In addition to the creativity of the human mind, cutting-edge 
technology is a catalyst for innovation. However, technology resources 
are often not accessible to investigators because of limited supply, 
location, or cost. NIGMS is using a range of approaches to improve the 
Nation's research infrastructure, providing investigators better access 
to critical, shared research resources and technologies. For the past 
few decades, X-ray crystallography has been the method of choice to 
allow researchers to take three-dimensional ``pictures'' of proteins 
and other molecules important for health and disease. But recently, 
advances in another technique, cryo-electron microscopy, or cryo-EM, 
have moved it to the forefront of research into the structures of 
biological molecules. Unfortunately, despite cryo-EM's advantages over 
X-ray crystallography and its great promise for helping scientists 
understanding cell function and dysfunction, state-of-the-art cryo-EM 
equipment is out of the reach of most of the country's researchers 
because of its very high cost. To begin to address this problem, NIGMS 
has started a program to support the purchase and maintenance of cryo-
EM technology by regional consortia, giving multiple research groups 
and institutions access to the equipment. NIGMS hopes to expand this 
consortia model into larger, regional facilities that will produce 
significant economies of scale and expand greatly the number of 
scientists who can use important, cutting-edge technologies.
    Through its Institutional Development Award (IDeA) program, NIGMS 
provides targeted support to increase research capacity in States that 
historically have had little NIH funding. The IDeA program investment 
is catalytic and has been successfully leveraged into additional 
investigator-initiated grants to researchers in IDeA States. For the 8-
year period spanning fiscal year 2007 to fiscal year 2014, this 
additional funding support was $12 billion, almost a seven-fold return 
on investment, according to a recent NIGMS program analysis. The IDeA 
Centers of Biomedical Research Excellence (COBRE) program supports 
thematic, multidisciplinary centers that expand and develop biomedical 
faculty research capability and enhance research infrastructure, in 
part through development of core facilities needed to carry out modern 
multidisciplinary collaborative research. While the number of COBRE-
supported scientists increased only 9 percent between fiscal year 2007 
and fiscal year 2014, the productivity of those investigators in terms 
of scientific publications increased much more--an impressive 43 
percent--suggesting that resources are integral to priming the 
biomedical capabilities of recipient institutions. NIGMS is also 
supporting the development of clinical research capacity in IDeA States 
through IDeA Infrastructure for Clinical and Translational Research 
awards and through joint management, along with the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development, of 
the new IDeA States Pediatric Clinical Trials Networks.
    While the number of scientific publications per scientist is one 
metric of success, others include patents and generating interest in 
commercialization. The Lexington, Kentucky COBRE, for example, has 
launched two start-up companies to further develop potential cancer 
treatments identified through NIGMS-funded research. One is pursuing 
drug development of a substance that targets molecules that are 
overactive in certain colorectal and liver cancers.
    In this statement, I have shared just a few examples of the 
remarkable types of returns received from NIGMS' investment in 
fundamental biomedical research. NIGMS looks forward to the many more 
advances that will emerge from laboratories across the Nation.
                                 ______
                                 
Prepared Statement of Eliseo J. Perez-Stable, M.D., Director, National 
          Institute on Minority Health and Health Disparities
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute on Minority Health and Health Disparities (NIMHD) of the 
National Institutes of Health (NIH).
                 advancing health disparities research
    Medical and technological advances have afforded individuals with 
the potential for longer and healthier lives. However disparities 
between racial and ethnic minorities, rural, and disadvantaged 
socioeconomic populations continue to persist. NIMHD leads scientific 
research that advances understanding of minority health and health 
disparities. Understanding the complexity of health disparities 
requires examining how health determinants, biological, social, 
individual behavior, health system, and environmental factors interact 
with race/ethnicity and socioeconomic status (SES) to influence health 
outcomes. For example, studies have shown racial and socioeconomic 
disparities in pain management, with African American and low SES 
patients less likely to receive first-line care. NIMHD currently 
supports a project that examines the use of computer-simulated patients 
and environments to assess, understand and alleviate pain treatment 
disparities that are associated with clinician bias. Findings from the 
study indicate that the utilization of virtual patients allows for 
greater exposure to racially and socioeconomically diverse patients 
than what can be found in traditional training settings. As a result, a 
significant decrease was found in decisionmaking bias for how best to 
care for the virtual patient.
    As the primary Federal agency for guiding and coordinating research 
to improve minority health and reduce health disparities, NIMHD has 
taking significant steps in setting a transformational agenda for the 
field. Recognizing the many factors that drive health disparities and 
overall health outcomes in minority health, NIMHD is completing a 
scientific visioning process that will establish a standard social-
ecological-biological framework to advance the science of minority 
health and health disparities.
                         collaborative research
    A cornerstone of NIMHD's mission is to foster innovative 
collaborations and partnerships. In order to effectively address health 
disparities, a multidisciplinary approach involving community, 
academia, clinicians, service providers, and Federal partners is 
necessary. NIMHD has a long standing history of fostering partnerships 
both within and outside of NIH. For example, NIMHD supported Georgetown 
University, Howard University, and MedStar in their goal to eliminate 
breast cancer and stroke disparities by transferring knowledge from 
research to practice within a community setting. Advances of this 
collaborative effort have led to a community scholars curriculum 
designed to provide education in research engagement and capacity for 
community partner organizations to develop and maintain their own 
research and data systems infrastructure. This partnership also has 
strengthened the research workforce by developing a fellows program 
that trains, funds, and mentors students and early stage investigators 
who are pursuing careers in minority health and health disparities 
research. More recently, NIMHD in collaboration with the U.S. 
Environmental Protection Agency, National Institute of Environmental 
Health Sciences, and the Eunice Kennedy Shriver National Institute of 
Child Health and Human Development, supported the establishment of an 
indigenous environmental health research center aimed at providing the 
Hopi and Navajo communities with the ability to conduct their own 
environmental exposure research. A unique approach to the study is the 
emphasis on identifying culturally appropriate research methods to be 
carried out by a multidisciplinary team involving American Indian 
researchers.
    An ultimate example of collaboration is the launch of the Precision 
Medicine Initiative (PMI). PMI has afforded NIH with the opportunity to 
form a strong network among several of its Institutes and Centers. 
NIMHD plays a leadership role in the efforts to ensure that the 
establishment of the Precision Medicine Cohort includes standard 
measures of social determinants of health at baseline and exhibits the 
diversity necessary for the outcomes of the study to pertain to all 
Americans. Community engagement is vital to the inclusion of all health 
disparities populations and therefore, NIMHD has engaged researchers to 
conduct studies aimed at identifying biomarkers for disease progression 
(e.g., prostate cancer in African Americans) and drug response in 
diverse populations (e.g., asthma treatment in Latinos of different 
national origin) and to examine facilitators and barriers to 
implementing precision medicine findings in disadvantaged populations. 
In addition, NIMHD has been at the forefront of ensuring that community 
organizations are well-informed about the promises of precision 
medicine. Participation in three White House briefings, meetings and 
workshops with community organizations, and presentations at national 
scientific meetings are examples of NIMHD's commitment to engaging all 
communities in the Precision Medicine efforts.
                  enhancing diversity of the workforce
    NIMHD recognizes a unique and compelling need to promote diversity 
in the biomedical, behavioral, clinical, and social sciences research 
workforce. NIMHD expects that efforts to diversify the workforce will 
lead to the recruitment of the most talented researchers from all 
groups into research areas relevant to the mission of NIMHD; improve 
the quality of the educational and training environment; balance and 
broaden the perspective in setting research priorities; improve the 
ability to recruit participants from diverse backgrounds into clinical 
research protocols; and improve the Nation's capacity to address and 
reduce health disparities.
    As the U.S. population becomes increasingly diverse, reflection of 
that diversity among the biomedical research workforce is vital to the 
NIMHD research mission. To develop, maintain, and renew our scientific 
talent pool, it is imperative that we create a climate of opportunity 
to attract and retain the most talented individuals who can capitalize 
on innovation and advance scientific discovery. Research has 
demonstrated that a diversity of perspectives leads to better solutions 
to complex challenges, including healthcare research and education. 
NIMHD's commitment to enhancing the biomedical research workforce is 
evident in our continued support of the Loan Repayment Program, an 
annual Health Disparities course targeting early career investigators, 
Clinical Research Education and Career Development Awards, Research 
Centers in Minority Institutions, and our partnership in the NIH 
Medical Research Scholars Program. NIMHD's role in all of these 
programs has produced marked increase in the number of diverse 
scientists entering and persisting within the research arena.
                               conclusion
    Despite medical and scientific advances there continues to be a 
disproportionate burden of illness and disease among racial and ethnic 
minorities and other health disparities populations. Ameliorating these 
disparities in health outcomes is central to NIMHD's mission. NIMHD 
envisions an America in which all populations will have an equal 
opportunity to live long, healthy, and productive lives. Therefore, 
NIMHD remains committed to scientific leadership in coordinating and 
supporting highly meritorious research on minority health and health 
disparities with the goal of improving public health and promoting 
healthier lives.
                                 ______
                                 
   Prepared Statement of Roderic I. Pettigrew, Ph.D, M.D., Director, 
      National Institute of Biomedical Imaging and Bioengineering
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the 
National Institutes of Health (NIH).
    The mission of NIBIB is to improve human health by leading the 
development of biomedical technologies and accelerating their 
application. NIBIB supports research that integrates engineering with 
the physical and life sciences to develop emerging technologies that 
can be applied to a broad range of biomedical and healthcare problems. 
The scope of NIBIB-supported research is vast, from innovations to 
address paralysis to novel ways to deliver vaccines.
    NIBIB is a leader in bringing together many disciplines to solve 
great biomedical challenges, with a mission that spans all diseases. To 
achieve that mission, NIBIB supports researchers from every field of 
medicine and gathers teams of scientists and engineers from diverse 
backgrounds. These researchers work to develop innovative approaches to 
advance scientific discovery and address real-world health issues 
through new knowledge and new technologies. I am pleased to share a few 
highlights from the breadth of NIBIB-funded research efforts that are 
working toward our shared goal of improving public health.
    delivering a vaccine without a needle or need for refrigeration
    NIBIB's Quantum Grants Program is designed to have a profound, or 
quantum, impact on a particular healthcare problem. In keeping with 
NIBIB's mission, projects in this program take an approach that is 
highly collaborative and interdisciplinary with a focused goal that is 
achieved through technological innovation. In one Quantum Grant 
example, researchers have developed a microneedle patch to deliver 
vaccines without the traditional ``shot in the arm.'' This technology 
could lead to self-administered vaccines with an easy-to-use, more 
widely available device that is about the size of a quarter.
    The first targeted application is flu vaccination. Influenza is a 
major cause of illness and death worldwide. While vaccines are 
effective in preventing infection, access in rural and medically 
underserved areas is a challenge. A new microneedle patch addresses 
these challenges in that it can be self-administered, does not require 
refrigeration, and could be delivered in the mail. The single-use patch 
is also painless and research has indicated that all of these benefits 
could lead to higher rates of immunization and reduce flu-related 
deaths and hospitalizations.
    A clinical trial is underway to assess the use of microneedle 
patches in vaccinating against influenza. The patches contain very thin 
and short microneedles, which are barely visible to the eye. As the 
patch is applied to the skin, these microneedles painlessly penetrate 
the upper layers of the skin and deliver the vaccine. The study 
includes 100 healthy adults and seeks to assess the safety of the 
microneedle patch, how the body's immune system responds to the vaccine 
delivered through the patch, and participants' opinions about using the 
patch. Initial results indicate that influenza vaccination using the 
microneedle patch generates immune responses at least as good as 
conventional injection, that the microneedle patch has a very good 
safety profile, and that study participants strongly prefer vaccination 
by the microneedle patch over a traditional flu shot.
      using imaging technology to both diagnose and treat disease
    For decades, imaging technologies such as magnetic resonance 
imaging (MRI), ultrasound, and computed tomography (CT) have provided a 
window for a non-invasive look inside the body to locate and assess 
tumors or damaged tissue. Increasingly, research in imaging technology 
is not only discovering improved ways to see inside the body but also 
developing highly integrated systems to provide rapid feedback to guide 
treatment.
    In another Quantum Grant Program example, researchers are using an 
improved imaging technology that combines diagnosis and an intervention 
for acute ischemic stroke. Strokes are a major cause of death and 
neurological injury. Acute onset of stroke-like symptoms is a medical 
emergency and rapid diagnosis and treatment are critical to saving as 
many brain cells as possible. This novel method is estimated to save 
from one to two hours per patient, and therefore save considerable 
brain tissue.
    Currently, stroke diagnosis and monitoring is performed with 
imaging in dedicated CT or MRI imaging suites separate from where 
stroke is treated, requiring the patient to be moved and costing 
precious time while brain tissue is damaged through loss of blood 
supply. The treatment of stroke caused by blocked blood vessels 
involves specialized catheter-based angiography to restore blood supply 
to the affected brain area. The breakthrough of this Quantum Grant 
award is the integration of angiography with advanced imaging 
capabilities into a time-saving and cost-efficient platform that is 
housed on a single machine. This is possible through a revolutionary 
image acquisition and reconstruction technique that fundamentally 
challenges the traditional methods now in use. For the first time, this 
new technique produces rapid, high resolution CT images and enables 
immediate treatment of strokes caused by blood vessel occlusion 
(blockage).
    Advances to current imaging technologies such as this could lead to 
more rapid and personalized treatment of occlusion stroke, potentially 
resulting in better neurological outcomes for patients.
    finding rare cells among billions for early detection of cancer
    Cancer tumors shed tiny fragments that can enter the blood stream. 
Capturing these obscure traces of cancer allows them to be analyzed so 
that treatment can be designed specifically for each patient. 
Similarly, the technology can be used to monitor treatments for 
effectiveness. This individualized approach, which identifies and 
targets the specific genetic features in each person, is the hallmark 
of the President's Precision Medicine Initiative.
    In an initial phase of an ongoing NIBIB Quantum Grant Program, 
researchers developed the iChip, a microfluidic device that can capture 
one circulating tumor cell (CTC) among one billion red blood cells. 
This means that in a small vial of blood there could be from 1--100 
CTCs among 80 billion red-blood cells. In one study, human cancer cells 
were captured using this technology and analyzed, then tested in animal 
models to see which treatment was most effective. Researchers are also 
working to make the device so small that it can be used at the point-
of-care to deliver results rapidly. This real-time measurement of CTC 
numbers could one day allow doctors to promptly change or stop 
ineffective treatments, such as when cancer cells become resistant to a 
particular chemotherapy drug.
    The technology has also been developed to isolate clusters of CTCs. 
Clusters are even rarer than single CTCs, but are 50 times more potent 
in producing metastatic spread of cancer. Identifying and capturing CTC 
clusters could help identify and study more aggressive cancers.
    Building on this research, the investigators are now turning toward 
a new phase of development that can capture pieces of DNA shed from 
cancer tumors. Researchers are looking at this new use of the 
technology as a sensitive method for early identification of prostate 
and lung cancer. In both types of cancer, detection is challenging and 
cancers are often discovered when tumors are of a significant size, or 
the cancer has spread. This technology also has the potential for non-
invasive monitoring to determine if the selected treatment is working. 
The new approach integrates the CTC iCHIP technology with known methods 
to identify genetic markers for early detection.
             using neural stimulation to address paralysis
    Each year 12,500 new cases of severe spinal cord injury (SCI) occur 
(2015, National SCI Statistical Center). Currently, the approach for 
treating this type of injury is to provide rehabilitation therapy to 
limit further damage. In these patients, the pathways that send 
information about sensation from the legs to the brain and from the 
brain to the legs to control movement are disrupted. For years 
physicians thought that recovery of function in spinal cord injury was 
not possible.
    Now, after years of basic research and recent developments in a 
very small number of patients, investigators are working to understand 
how neurostimulation of the spinal cord might help patients regain 
function. Recent studies have shown that it might be possible to 
reawaken the neural pathways along the spinal cord after injury. A 
small number of patients have received electrical stimulation either 
implanted under the skin next to the spine (epidural) or placed on top 
of the skin along the spine (transcutaneous) and have regained the 
ability for some limb movement and the ability to stand unassisted for 
a brief period of time. Patients receiving stimulation also report that 
they have regained other functions important for improved quality of 
life, such as control of blood pressure, temperature, bladder, bowel, 
and sexual function. Further study is aimed at understanding how 
electrical stimulation can most effectively lead to restored function 
and how stimulation can be customized to work best for individual 
patients.
    NIBIB is also part of the President's BRAIN Initiative and part of 
this effort is to develop tools and technologies that lead to a better 
understanding of brain function. Many of the technologies developed for 
understanding the brain can be used to understand the spinal cord and 
the peripheral nervous system. Understanding these systems will help us 
know how to help people overcome these devastating injuries.
                               conclusion
    Advances in technology are catalyzing the development of solutions 
to previously intractable disorders and improved approaches to 
biomedical research. As these examples illustrate, this type of 
research requires many disciplines to work together and this 
integration of disciplines is what defines NIBIB's approach. NIBIB is 
committed to supporting such convergent teams of researchers to solve 
major biomedical challenges that will improve the health of all 
Americans.
                                 ______
                                 
 Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P. , Director, 
    National Institute of Diabetes and Digestive and Kidney Diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the 
National Institutes of Health (NIH). NIDDK supports research on many 
chronic, consequential, and costly diseases and conditions that affect 
millions of Americans. These include diabetes and other endocrine and 
metabolic diseases; digestive and liver diseases; kidney and urologic 
diseases; blood diseases; obesity; and nutrition disorders.
                           discovery research
    NIDDK-supported scientific research is expanding knowledge of human 
health and disease. Testing novel approaches and hypotheses has led to 
new discoveries that continue to build foundations for innovative 
strategies to improve health and quality of life. These advances 
include researchers revealing a critical role for immune cells in the 
development and activity of calorie-burning beige fat, a finding which 
could provide new therapeutic targets to treat obesity and metabolic 
diseases. Genetic research examining data from hundreds of thousands of 
people has more than doubled the number of genetic regions known to be 
associated with obesity and body fat distribution patterns. 
Additionally, studies have found that a virus in the intestinal tract 
could have beneficial effects similar to those granted by gut bacteria, 
and research in humans and in mice has shed new light on how genetic 
factors shape the composition of the gut microbial community and affect 
metabolism. New discoveries could also yield novel, non-antibiotic 
approaches to treat or prevent urinary tract infections (UTIs). One 
group of scientists discovered a new mechanism by which bacteria such 
as E. coli survive and promote UTIs, and another found that in mice, 
bacteria that do not cause symptomatic UTIs may be an effective therapy 
against ones that do. These and other discovery-based investigations 
continue to seek fundamental knowledge about living systems that can 
form the basis for new strategies to protect and improve health.
    In fiscal year 2017, NIDDK will continue to support pioneering 
discovery-based research, including efforts to build integrated human 
pancreatic islet and liver tissue chips that can be used to study 
metabolism and model human diseases such as diabetes. NIDDK also will 
support research to define interactions between the host and the gut 
microbiota that can regulate both healthy and disease-related 
physiological processes. These projects aim to discover specific human 
gut microbiota-derived factors that affect or are affected by the human 
host's own physiology and disease and then investigate how these 
factors affect the gut and other organs. Harnessing knowledge of normal 
kidney development, the NIDKK-funded (Re) Building A Kidney consortium 
continues to forge new approaches to treat kidney injury and disease by 
enhancing kidney repair and promoting the generation of new kidney 
cells. Additionally, the Human Heredity and Health in Africa (H3Africa) 
Initiative will continue to support a network of African investigators 
to study the interplay between environmental and genetic factors 
affecting
    the health of African populations. To accomplish this, the H3Africa 
Initiative aims to enhance infrastructure and support collaborations to 
enable African researchers to carry out large-scale studies on African 
populations.
                           clinical research
    Clinical studies are integral to research on the broad spectrum of 
diseases for which NIDDK has research responsibility. Through 
innovative design and rigorous testing of interventions, NIDDK-
supported researchers are improving lives with new approaches to 
prevent, treat, and reverse diseases and disorders. For example, 
researchers have developed a potential new method to use examination of 
the eye to diagnose diabetes-related nerve complications, a strategy 
that could replace the use of skin biopsies to diagnose these problems. 
A new research model of the human small intestine was developed by 
growing intestinal tissue from human stem cells, resulting in tissue 
that can perform digestive functions and be transplanted into mice. 
This advance expands scientists' ability to study the intestine under 
conditions similar to those in the human body. Researchers found that a 
process called ``desensitization'' can alter the immune system of a 
person with kidney failure so that their body can accept a kidney 
transplant from an incompatible live donor, rather than waiting for a 
more compatible cadaveric donor or remaining on dialysis. Another group 
found that people who choose to donate one of their kidneys to someone 
with kidney failure remain relatively healthy 3 years after their 
donation, suggesting that living donor kidney donation can improve the 
health of donor recipients without compromising the health of the 
donor, at least within the first 3 years after donation. Genetic 
studies also found six new genetic regions associated with risk of 
developing both inflammatory bowel disease and immunoglobulin A 
nephropathy, a major cause of kidney failure worldwide. These findings 
may lead to better understanding of the causes of both diseases and, 
eventually, to new treatments.
    NIDDK-supported clinical research will continue to pursue improved 
treatments for diseases and conditions relevant to the Institute's 
mission. The Glycemia Reduction Approaches in Diabetes: A Comparative 
Effectiveness Study (GRADE) is a major trial that recently began to 
compare commonly used diabetes medications, with the goal of 
determining which drug--in combination with metformin--is most safe and 
effective for patients. NIDDK will also continue its participation in 
the Accelerating Medicines Partnership (AMP) Type 2 Diabetes Project--a 
public-private partnership between NIH, the Food and Drug 
Administration, biopharmaceutical companies, and non-profit 
organizations--that seeks to identify and validate the most promising 
biological targets for diagnostic and drug development. AMP has 
developed and is expanding a Knowledge Portal that consolidates results 
from 28 large human genetic studies of type 2 diabetes and supports 
analyses that can shed light on possible drug targets. The Predicting 
Response to Standardized Pediatric Colitis Therapy (PROTECT) study--
conducted in collaboration with the Crohn's and Colitis Foundation of 
America's Pediatric Research Organization for Kids with Intestinal 
Inflammatory Diseases (PRO-KIIDS) Network--will continue its efforts to 
provide a better understanding of how children newly diagnosed with 
ulcerative colitis (UC) respond to corticosteroids, the standard 
initial therapies used to treat this disorder. The PROTECT study 
results could help predict how children with UC will respond to 
treatment and thus lead to more personalized therapies and improved 
outcomes. Also, NIDDK-sponsored Multi-Disciplinary Approach to the 
Study of Chronic Pelvic Pain (MAPP) Research Network continues to 
conduct innovative, collaborative studies of interstitial cystitis/
painful bladder syndrome (IC/PBS) and chronic prostatitis/chronic 
pelvic pain syndrome (CP/CPPS). The MAPP Research Network's work can 
pave the way to better understanding of what causes these conditions, 
improved diagnosis, ways to prevent onset, and more effective 
treatments. The Network is also studying the possible relationships 
between urologic pelvic pain and other chronic pain disorders, such as 
irritable bowel syndrome and fibromyalgia.
    New clinical research initiatives include the launch of the 
Consortium for the Study of Chronic Pancreatitis, Diabetes and 
Pancreatic Cancer. This consortium (co-funded by NCI) will study 
chronic pancreatitis (CP) and factors that link CP to other diseases. 
The consortium will conduct studies to improve understanding of CP's 
disease processes and how these processes are related to outcomes such 
as diabetes and development of pancreatic cancer. NIDDK will also 
support clinical research into how normal or altered sleep and 
circadian rhythms affect metabolism and disease outcomes such as 
diabetes. Additionally, through NIH's Common Fund, the ICD-Pieces trial 
will test whether a collaborative model of primary and subspecialty 
care enhanced by a novel health information technology platform could 
result in better care and quality of life for those with multiple 
conditions, such as chronic kidney disease, diabetes, and hypertension.
                  sustaining the biomedical workforce
    The future of biomedical research and the continued improvement of 
the Nation's health depend critically on maintaining a strong and vital 
work force. NIDDK strives to ensure that new investigators can realize 
their potential for contributing to biomedical research, and that 
today's generation of young scientists will view research as a viable 
career. To this end, NIDDK offers a comprehensive set of programs that 
support investigators from their initial training as medical and 
graduate students through their evolution into established scientists. 
In addition to providing institutional and individual grants to support 
graduate and post-graduate trainees and physician-scientists, NIDDK 
supports one of the largest career development programs at NIH. It 
complements this program with a biennial workshop that provides 
knowledge and skills necessary to transition to independent research 
careers, including career advice and information about the NIDDK's 
grant review process. NIDDK also offers career development awardees a 
small supplemental grant program to help establish an independent 
research program. Early stage independent investigators (ESIs) are 
generously supported with priority funding. Recognizing that the first 
renewal of an ESI's first grant is typically the final barrier to 
becoming an established investigator, NIDDK has targeted ESIs with a 
workshop that provides additional guidance, and it has instituted a 
pilot program that offers them priority funding when they renew.
    To build and sustain a diverse research pipeline, NIDDK has several 
programs aimed at facilitating research by and mentorship of 
underrepresented groups at various career stages. The Short-Term 
Research Experience for Underrepresented Persons (STEP-UP) program 
provides hands-on summer research experience for high school and 
undergraduate students interested in exploring research careers. 
NIDDK's Network of Minority Health Research Investigators fosters 
mentoring relationships between senior and early-career scientists, and 
NIDDK-supported awards enable mid-career health professionals to 
conduct research while acting as mentors to early-stage investigators 
from diverse backgrounds underrepresented in biomedical and behavioral 
research.
    In closing, NIDDK is committed to a vigorous, multi-pronged 
research portfolio including both discovery-based and clinical 
research. Five principles continue to guide NIDDK's future research 
investments: maintain a vigorous investigator-initiated research 
portfolio, support pivotal clinical studies and trials, preserve a 
stable pool of new investigators, foster research training and 
mentoring, and disseminate science-based knowledge through education 
and outreach programs.
                                 ______
                                 
Prepared Statement of Paul Sieving, M.D., Ph.D., Director, National Eye 
                               Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National Eye 
Institute (NEI) of the National Institutes of Health. Vision science is 
at the leading edge of neuro-regenerative medicine and discovery 
science in brain connectivity. I want to share our latest progress and 
goals in neuroscience, regenerative medicine, gene discovery, and gene 
therapy.
                     nei audacious goals initiative
    The NEI Audacious Goals Initiative (AGI) is a bold, strategic 
investment in neuro-regenerative medicine that will enable the 
restoration of vision through regeneration of the retina--the light-
sensitive tissue in the back of the eye. AGI focuses on photoreceptor 
neurons and retinal ganglion cells. Photoreceptors capture the light 
necessary for initiating vision, while retinal ganglion cells transmit 
these light-induced signals to the brain and can degenerate in glaucoma 
and other optic nerve diseases. Vision scientists have taken the first 
steps toward achieving the regeneration of these cells by converting 
stem cells into mature retinal cell types and are integrating these 
cells into existing retinal circuits. In order for these regenerated 
neurons to send signals to the brain, they need to grow long 
connections, called axons, and correctly wire themselves to the 
appropriate partners in the retina and the brain--a goal that will 
require new tools and a better understanding of the underlying 
biological processes.
    Last year, NEI awarded the first five AGI projects to develop 
functional and metabolic imaging technologies that are capable of 
visualizing a single live cell. For example, adaptive optics (AO) 
technology has been developed to successfully image a single 
photoreceptor in patients and track that particular cell in subsequent 
patient visits. This powerful tool allows clinicians to non-invasively 
monitor the degeneration of the cell and conversely to image its 
replacement by healthy stem cells. Prior to this technology, imaging 
was severely limited by distortions that bent light waves irregularly. 
In addition to AO, advanced magnetic resonance imaging technology is 
being developed to assess regeneration of damage to the optic nerve. 
These five imaging teams were brought together in a collaborative 
consortium to share data, technology, and early results in order to 
speed progress toward scientific goals. This consortium also 
facilitates input and guidance by NEI program staff as well as by an 
external scientific oversight committee. Importantly, the AGI is a 
participatory scientific endeavor that actively gathers input from the 
vision community and the broader neuroscience community in the form of 
expert workshops and town hall meetings.
    NEI is currently reviewing applications from a second AGI funding 
opportunity to screen cellular and molecular entities critical to the 
regeneration of neurons, guiding their axons to targets, and making new 
functional connections. NEI anticipates that once the unknown factors 
(genes, proteins, signaling molecules, etc.) involved in regenerating 
retinal ganglion cells and photoreceptors are discovered, the work will 
advance to specific projects to understand the biological mechanisms 
through which these factors influence regeneration.
    It is noteworthy that AGI has catalyzed the field of neuro-
regenerative medicine, with over 20 investigator-initiated projects 
awarded by NEI in fiscal year 2015. While AGI is independent of the 
President's BRAIN Initiative, many vision scientists are BRAIN 
grantees, and BRAIN research will accelerate AGI efforts to regrow and 
regulate retinal neurons and their connections in the eye and brain.
               translational research and clinical trials
    Proliferative diabetic retinopathy (PDR) is a serious complication 
of diabetes, in which vascular endothelial growth factor (VEGF) 
secreted by the retina triggers the proliferation of abnormal leaky 
blood vessels. Accompanying vitreous hemorrhage and retinal detachment 
can lead to permanent vision loss. Since the 1970s, doctors have 
treated PDR with a laser therapy, but this treatment can damage night 
and side vision, so researchers have sought improved therapies. 
Lucentis is one of several drugs that block VEGF and has been shown to 
be effective in other eye diseases. Diabetic Retinopathy Clinical 
Research Network (DRCR.net) has 400 retina specialists in over 41 
States, one third are university based, and the rest are from 
community-based practices. A DRCR.net trial found that Lucentis is 
highly effective in treating PDR, reversing some vision loss without 
affecting side vision. By comparison, laser treatment merely preserves 
existing central vision but does not reverse losses. The new research 
findings demonstrate the first major therapy advance for PDR in nearly 
40 years. The network also conducted a study of three anti-VEGF drugs 
for diabetic macular edema: Lucentis, Eylea and Avastin. After 2 years, 
patients with mild vision loss at baseline had similar improvements in 
visual acuity from all three drugs. However, patients with moderate to 
severe vision loss at the start of the trial had slightly better 
improvement with Eylea and Lucentis than the less costly drug, Avastin. 
From these results, patients and doctors can weigh baseline vision, 
expected clinical outcomes, and costs when choosing a personalized 
treatment strategy.
    For patients who live in rural or urban underserved communities, 
telemedicine can be used to remotely screen, monitor and diagnose 
disease. DRCR.net just launched a new protocol to explore whether 
telemedicine using a new ultra-wide field imaging technology can allow 
specialists to remotely identify DR in a patient and to determine what 
follow up care is indicated. NEI also has supported telemedicine 
technology development through its Small Business Innovation Research 
program, e.g., automated retinal scanning technology to detect DR and 
monitor images at remote clinical sites.
    Using patient-specific induced pluripotent stem cells (iPSCs), NEI 
researchers are developing the first personalized therapy for the 
``dry'' form of AMD. The retinal pigment epithelium (RPE) is a single 
layer of cells that carry out the critical function of nourishing and 
supporting the adjacent photoreceptor cells. In dry AMD, RPE cells 
start to die, leading to photoreceptor cell loss and visual impairment. 
The NEI intramural research team has developed a clinical-grade 
manufacturing process to derive iPSCs from AMD patients and convert 
them into RPE tissue. The RPE tissue is delivered using a biodegradable 
scaffold that helps integrate and maintain proper orientation of the 
tissue in the back of the eye. The entire RPE tissue manufacturing 
process takes only 142 days after a blood draw from an AMD patient. 
Patient-derived tissue has the distinct advantage over donor tissue as 
it is less likely to be rejected by the immune system. In preclinical 
work to prepare for a human trial, the NEI team demonstrated that 
transplanted tissue integrates in the retina and restores lost function 
in a pig model of retinal degeneration. Success in the pig model, along 
with production of clinical grade iPSC has paved the way toward filing 
an application for Investigational New Drug (IND) with FDA in 2017.
    iPSC technology is a potentially powerful research tool that 
enables scientists to transfer their knowledge of known disease 
pathways in particular cells and organs to shed light on the impact of 
these same disease mutations in entirely different cell types of other 
organs. For example, iPSCs derived from a heart disease patient have a 
mutation in the gene STAT3. This mutation impairs blood vessel growth, 
and immune and wound-healing responses. The STAT3 gene has also been 
suggested to play a role in RPE immune responses and in molecular 
signaling that may lead to AMD-like symptoms in patients. The NEI team 
is now testing RPE tissue derived from this patient's cells to 
understand the role of STAT3 in AMD.
    Cataracts are a clouding of the lens caused by misfolding and 
aggregation of lens crystallin proteins, and can result from many 
causes including side-effects of drugs like steroids, or surgery, or 
most commonly from aging. Cataracts occur in over half the population 
over age 70 and are a major cause of vision loss in older adults. 
Researchers identified a class of molecules that bind to crystallins, 
reverse their aggregation and restore lens transparency in mouse models 
of cataract. These agents could be delivered via eye drops, potentially 
eliminating the need for costly surgical cataract removal.
                       genetics and gene therapy
    In the largest-ever Genome Wide Association Study (GWAS) for AMD, 
NEI investigators were part of an international team that studied more 
than 12 million gene variants from more than 43,000 participants with 
and without AMD. The group identified 52 associated common and rare 
gene variants associated with AMD. The success of this study, 
particularly for rare variants, was predicated on the extremely large 
sample size of participants and bringing together an interdisciplinary 
team of clinicians, geneticists, and bioinformatics experts to analyze 
``big data.''
    Glaucoma is the second leading cause of blindness globally. It is a 
group of conditions that damage the optic nerve and have a genetic 
predisposition. A consortium called the NEI Glaucoma Human Genetics 
Collaboration Heritable Overall Operation Database (NEIGHBORHOOD) 
recently identified three new genes that contribute to the most common 
form of glaucoma, increasing the total number of such genes to 15. One 
new gene is an enzyme that protects cells from oxidative stress. 
Another gene had previously been implicated in a rare form of severe 
early onset glaucoma. Despite the high heritability of glaucoma, 
identifying glaucoma genes has been a challenge and the biological 
mechanisms are poorly understood. To address the mechanistic challenge, 
NEIGHBORHOOD researchers integrated eight independent GWAS, involving 
over 37,000 glaucoma patients and controls to better understand genes 
and phenotypes.
    A pioneering technology called optogenetics introduces light-
sensing proteins into cells that are not otherwise light sensitive. In 
retinitis pigmentosa (RP), the light-sensitive photoreceptor neurons 
have died, however many other neurons in the retina are preserved. NEI 
investigators have established proof-of-principle with optogenetics 
gene therapy in blind mice. By delivering light-sensing proteins 
directly to retinal bipolar cells, they effectively bypass the dead 
photoreceptor neurons upstream and can elicit a visual response. This 
exciting work is being translated into a clinical trial. There are many 
gene mutations that cause RP, yet optogenetics is not treating a single 
mutation; a single therapy that restores visual responses could have 
widespread application.
    A major scientific breakthrough in the past few years was the 
development of a gene editing tool called CRISPR/Cas9, in which 
specific DNA mutations can be changed in specific cells. As a research 
tool, this system allows researchers to introduce molecular changes in 
cell cultures or animal models to study the function of individual 
proteins. The tool also has fundamentally important implications for 
clinical therapy in adult tissues. NEI is funding research that is 
correcting genetic mutations in stem cells created from patients with 
genetic mutations for RP, Usher syndrome, and Best disease. In the 
future, these corrected stem cells could be used as a cell therapy. NEI 
also is funding research using CRISPR/Cas9 for a wide variety of other 
ocular disorders affected by specific gene mutations such as a form of 
glaucoma and Fuchs' corneal dystrophy.
                 retina organoid challenge competition
    NEI is preparing to launch a $1.5 million challenge competition to 
catalyze therapies for retinal diseases by developing retina organoids. 
Organoids are 3D, self-assembling, mini-organs grown in a dish from 
human stem cells. They can be used for disease modeling, drug 
development, and therapeutic transplantation. On April 4, 2016, NEI 
held a technical planning meeting of industry and academic experts to 
review progress in organoid engineering of the retina and other organs, 
and to help design challenge parameters. The Congress requested a 
retina disease challenge in NEI's fiscal year 2016 Appropriations 
Report. This competition dovetails with the AGI and will accelerate 
retinal therapies since the human tissue-based models will aid in 
developing and testing regenerative therapies for retinal neurons.
                           future directions
    The audacious goal to regrow new neurons in the retina and restore 
vision builds on a foundation of audacious science that is described 
here. In the near terms, we will advance the understanding of 
mechanisms that underlie eye disease. The mechanistic knowledge will 
propel the drive for clinical applications that help fulfill the 
promise of gene and cell therapies that benefit patients.
                                 ______
                                 
  Prepared Statement of Martha J. Somerman, D.D.S., Ph.D., Director, 
         National Institute of Dental and Craniofacial Research
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the National 
Institute of Dental and Craniofacial Research (NIDCR) of the National 
Institutes of Health (NIH).
    The mission of NIDCR is to improve dental, oral, and craniofacial 
health through research, research training, and the dissemination of 
health information. In keeping with this mission, NIDCR's research 
spans multiple disciplines, scientific approaches, and research 
directions. Today, I will highlight selected areas of NIDCR-supported 
research that hold particular promise to improve oral health. These 
include efforts to understand the role of the oral microbiome, develop 
innovative tools and technologies, address emerging public health 
challenges, and strategies to cultivate and sustain future oral health 
researchers.
                        foundational discoveries
    The community of bacteria and other microbes that live in our 
mouths (the oral microbiome) not only has the potential to cause 
disease, but also plays a critical role in maintaining our health. 
Although we have learned much about the oral microbiome, one of the 
most important unexplored questions is how health-promoting and 
disease-causing bacterial communities are acquired at birth and how the 
balance between the two is developed and maintained over time. To 
answer this question, NIDCR-supported researchers are studying the oral 
microbiomes of children from birth to adolescence to determine what 
happens to bacterial communities during different stages of childhood. 
Scientists are using genetic techniques as well as considering specific 
environmental factors such as the delivery method at birth, the use of 
antibiotics in the hospital, and whether the infant was fed breast milk 
or formula. More knowledge about how individuals acquire their own 
unique oral microbiome could result in new strategies to help keep our 
mouths and bodies healthy.
    We have made tremendous progress in developing new approaches to 
catalogue the oral microbiome. However, understanding the types of 
bacteria present isn't enough. We also need to understand how the 
microbiome community in the mouth is organized and how its complex 
structure helps to maintain health and contributes to disease. NIDCR-
funded scientists have developed a new imaging technique to visualize 
the multiple layers of bacteria that live on each surface of the oral 
cavity. They have observed that some microbial communities gather and 
form distinctive three-dimensional structures on teeth that look like 
spiny hedgehogs and cauliflowers. These structures create the 
foundation upon which other bacteria attach and grow and eventually 
become the plaque that causes dental caries (tooth decay) and 
periodontal disease (an inflammation of the tissues supporting the 
teeth). This new imaging technique will also be a valuable tool for 
researchers exploring potential drug therapies to change the structure 
of the microbial community and treat oral infections.
                   innovative tools and technologies
    Early detection and diagnosis of oral cancer is essential for 
successful treatment. Because most people are not diagnosed until after 
a tumor has spread to other tissues, the survival rate for people with 
oral cancer--especially for African American males--is among the lowest 
for the major cancers. The current procedure for detecting oral cancer 
starts with inspecting the oral cavity for suspicious lesions. If a 
suspicious lesion is identified, a sample of the tissue is typically 
removed (i.e., a biopsy) and sent to a lab to check for cancer cells. 
To increase the likelihood that oral cancer will be detected earlier 
and more accurately, NIDCR-supported researchers have developed a 
handheld microscope to screen for oral cancer in the dental office. 
Roughly the size of a pen, the microscope uses an innovative technology 
called `dual-axis confocal microscopy' to make it easier to 
discriminate between healthy and potentially cancerous tissue. Using 
this tool, clinicians will be able to make more informed decisions 
about whether or not to remove suspicious-looking lesions for 
analysis--thus reducing the need for unnecessary invasive procedures. 
This novel technology will help meet a critical need for more effective 
tools to screen individuals at risk for oral cancer and could also be 
used to detect the recurrence of cancer following treatment.
    Mobile health, or mHealth, is an exciting technology that 
encourages people to make healthy lifestyle changes. For example, many 
of us wear wrist bands to count the number of steps we take every day 
or we use mobile applications to keep records of what we eat and drink. 
NIDCR-supported researchers are taking a lead in developing mHealth 
tools to easily and accurately track oral health behaviors, such as 
tooth brushing. In collaboration with engineers at Oral-B, NIDCR-
supported researchers have developed an electronic toothbrush with a 
built-in sensor that collects precise data about tooth brushing 
frequency and duration. By collecting real-time data, this mHealth 
sensor is helping investigators bypass the need for research 
participants to remember and accurately report their tooth brushing 
habits. The objective data gained from this innovative device will 
increase our understanding about actual tooth brushing behavior and 
potentially lead to new approaches to increase motivation for improved 
oral health behavior.
                    emerging public health concerns
    After years of declining cigarette sales in the United States, 
spurred in part by awareness of the adverse health effects of tobacco 
use, a new form of nicotine delivery has emerged--the electronic 
cigarette, commonly called the e-cigarette. The use of e-cigarettes is 
increasing dramatically among young adults. In fact, according to the 
Centers for Disease Control and Prevention, e-cigarette use by middle 
and high school students in the United States tripled between 2013 and 
2014. However, very little is known about the chemicals in the aerosol 
mixtures released by e-cigarettes or the impact those chemicals might 
have on health. NIDCR recently developed an initiative that funded a 
number of grants to investigate the effects of e-cigarette chemicals on 
oral health. A broad range of studies are being supported that include 
human participants, as well as cell and animal model systems. This 
research will offer valuable insights into the safety of e-cigarettes 
and how they affect the oral microbiome, the immune system, and the 
ability of damaged tissues in the oral cavity to heal.
    Many people visit their dentist regularly, which puts dental 
practitioners in a prime position to address public health issues. 
Currently, one particularly pressing public health concern is 
prescription opioid abuse. Because dentists prescribe opioids to treat 
acute dental and oral pain following dental procedures, it is important 
to understand the opioid prescribing practices of dentists. NIDCR 
invests in a valuable resource for conducting these types of clinical 
studies in real world settings, called the National Dental Practice-
Based Research Network (NDPBRN). The Network consists of more than 
6,000 dental practitioners in the United States who see patients on a 
regular basis and are interested in conducting research in their 
practices. Dental practitioners will participate in a study to assess 
dentists' knowledge of opioids and the decisionmaking processes and 
behaviors related to opioid prescription. The findings from this NDPBRN 
study will increase our understanding about how and why opioids are 
prescribed by dentists in order to develop strategies to help halt 
opioid abuse in the United States.
            recognizing outstanding oral health researchers
    NIDCR is proud to support three scientists who have been recognized 
for their innovative research. Two of these scientists are recipients 
of the Presidential Early Career Award for Scientists and Engineers 
(PECASE), the highest honor bestowed by the Federal Government upon 
outstanding scientists and engineers beginning their independent 
careers. The success of NIDCR-funded scientists in receiving this award 
is a testament to our commitment to support research training and 
career development. The third scientist is a longtime NIDCR-supported 
investigator who recently received recognition as part of the NIH 
Common Fund's Gabriella Miller Kids First Research program. The program 
is named for a brave girl who raised funds to support research on 
childhood illnesses before she died of cancer at age ten. This 
investigator is identifying the genetic basis for orofacial clefting 
using DNA sequencing to identify common genes in a large cohort of 
families. These honors recognize exceptional NIDCR researchers who are 
striving to improve the lives of children like Gabriella Miller and the 
oral health of all Americans.
                                 ______
                                 
Prepared Statement of Catherine Y. Spong, M.D., Acting Director, Eunice 
     Kennedy Shriver National Institute of Child Health and Human 
                              Development
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development 
(NICHD) of the National Institutes of Health (NIH).
    Understanding human development, both normative and atypical, is at 
the core of NICHD's mission. Unlike many of the other NIH Institutes 
and Centers (ICs), NICHD takes a lifespan approach to its work, 
supporting research that ranges from efforts to increase our 
understanding of basic biological mechanisms to testing health 
interventions aimed at improving the lives and health of children, 
women, and families, including those with disabilities.
              minimizing duplication, maximizing expertise
    In this increasingly complex world, highly specific expertise may 
be required to ensure that any preventive measures or development and 
application of therapies will meet the needs of each affected 
population. Because of the breadth of its mission, NICHD can provide a 
lifecourse perspective and a depth of expertise to research efforts 
related to pregnancy, infants, and the typical or atypical development 
of children through young adulthood. This breadth also means that NICHD 
works across scientific disciplines and often seeks or is tapped to 
lead trans-NIH, collaborative efforts that bring together other ICs' 
and non-NIH scientists' knowledge and skills so that the overall 
efforts are additive, not duplicative.
    Human Placenta Project.--NICHD is leading an initiative known as 
the Human Placenta Project that will develop technologies to assess, in 
real time, the structure and function of the human placenta. The least 
understood human organ, the placenta has substantial implications for 
the lifelong health of both mother and child, since so many health 
issues can be traced back to the earliest stages of development. The 
Project's goals include understanding normal and abnormal placental 
development, developing biomarkers to predict adverse pregnancy 
outcomes, examining the effects of environmental factors, and 
developing interventions to prevent abnormal placental and fetal 
development. Each year, NICHD brings together a group of broad thinkers 
that includes subject matter experts in various technologies, placental 
biologists, and clinicians to generate creative approaches to 
developing and applying technologies in new, noninvasive ways to 
understand placental function. The impact of the Human Placenta Project 
extends beyond enhancing pregnancy to providing additional insights 
into health and disease. New knowledge will increase our understanding 
of tumor biology and transplant medicine as the placenta mimics tumor 
growth and invasion early in gestation and mediates and promotes the 
health of two genetically distinct entities.
    PregSourceTM.--About 6.5 million pregnancies occur each 
year in the United States, and yet we have relatively little scientific 
information about what constitutes a normal pregnancy. In the coming 
year, NICHD will launch ``PregSourceTM,'' a longitudinal, crowd-
sourced, citizen science approach that will gather information about 
pregnancy from the experts--pregnant women. Through web-based 
questionnaires or mobile apps, PregSourceTM will expand our knowledge 
about what women experience physically and emotionally during pregnancy 
and after giving birth, the effects of pregnancy on women's lives, the 
special challenges some pregnant women face (such as health issues 
related to disability or a chronic health condition), and what features 
are common to many pregnancies. Ultimately, this information will help 
to fill the large gap in knowledge about medications used by pregnant 
women and other issues commonly experienced during pregnancy. In 
return, PregSourceTM will provide participants with links to evidence-
based information about pregnancy from 20 trusted national partners, 
including several NIH ICs and professional societies. Approved 
researchers can view de-identified, amalgamated information that may 
suggest fruitful research avenues about pregnancy. This innovative 
approach to gathering information was based on the highly successful 
DS-Connect: The Down Syndrome Registry, which was launched by NICHD 
and its Down Syndrome Consortium partners in 2013. With more than 3,200 
registrants across the United States, DS-Connect has facilitated 
recruitment into clinical trials on several aspects of Down syndrome.
    Birth Defects.--With other NIH ICs and the Common Fund of the NIH 
Office of the Director, in fiscal year 2017 NICHD will continue to 
provide leadership for extended basic and translational research 
efforts related to birth defects. Structural or functional anomalies 
affect about 3 percent of births and are the leading cause of infant 
death in the United States. Through intramural and extramural programs, 
NICHD supports collaborative teams of basic and clinical scientists 
studying the developmental biology, epidemiology, and genetics of 
structural birth defects. New fiscal year 2017 initiatives in 
structural birth defects research will catalyze the development of new 
research teams and support data analysis that uses and complements the 
genomic sequencing data developed under the Gabriella Miller Kids First 
Pediatric Research program, funded by Congress since fiscal year 2014.
    Best Pharmaceuticals for Children.--Although progress has been made 
in recent years, approximately three-quarters of all medicines marketed 
still do not carry Food and Drug Administration (FDA) approved labeling 
for use in neonates, infants, children, and adolescents. Although it is 
widely recognized that children are not small adults, only five of the 
80 drugs most frequently used in newborns and infants are labeled for 
pediatric use. For many drugs, developmental, metabolic, and 
pharmacokinetics-pharmacodynamic data are needed for their safe and 
effective use in children, yet sometimes private pharmaceutical 
companies are reluctant to incur the expense of gathering these data. 
In the Best Pharmaceuticals for Children Act of 2002, which was 
reauthorized in 2007 and 2012, the Congress charged NIH with setting 
priorities and funding research on pediatric therapeutic needs, tapping 
NICHD to lead this effort. Through an active trans-NIH Working Group, 
NICHD has collaborated with other ICs to identify therapeutic gaps in 
pediatric diseases, disorders, or conditions for which more complete 
knowledge of drugs and biologics would benefit specific pediatric 
populations, and develop future clinical trials. Using this approach, 
and also consulting with pediatric experts from FDA, academia, and 
industry, NICHD regularly publishes a prioritized list of drugs or 
indications that require further investigations. Four additional drugs 
commonly prescribed for children now have pediatric labeling, with 
others pending approval at FDA. Most recently, NICHD staff met with FDA 
pediatric leadership in December 2015 to discuss how to further improve 
the process for getting drugs labeled for pediatric use.
    Rehabilitation Research.--Although NIH was already supporting 
multiple lines of research focused on medical rehabilitation for 
physical, sensory, and cognitive disability across the lifespan, the 
establishment of the National Center for Medical Rehabilitation 
Research (NCMRR) by the Congress in 1990 provided a new focus on the 
science of medical rehabilitation and how results could be used to meet 
the challenges facing individuals with physical disabilities. A 
component of NICHD, NCMRR leadership emphasizes the need for medical 
rehabilitation across the lifespan, working across the various NIH ICs 
that have relevant and complementary missions. NCMRR serves as the 
focal point for the coordination and development of policies, plans, 
initiatives, and objectives that further rehabilitation research, 
convening the NIH Medical Rehabilitation Coordination Committee (MRCC) 
on a monthly basis to coordinate ongoing research and training 
activities. In addition, MRCC works with other agencies within the 
Department of Health and Human Services, the Department of Veterans 
Affairs, the Department of Defense, and the National Science Foundation 
to develop collaborative projects that serve to enhance and encourage 
rehabilitation science. A major conference on rehabilitation research 
in May 2016 will bring together scientists from across the 
rehabilitation research spectrum, which will serve to inform and 
catalyze the research community through a new rehabilitation research 
plan, expected in early fiscal year 2017.
    Training Opportunities in Endocrinology.--NICHD's intramural 
researchers also engage in regular collaborations with scientists from 
other ICs. Together with the National Institute of Diabetes and 
Digestive and Kidney Diseases, and the National Institute of Dental and 
Craniofacial Research, NICHD collaborates on the Inter-Institute 
Endocrinology Training Program, an accredited program that provides a 
comprehensive training experience for physicians who seek a broad 
education in both research and clinical endocrinology. Led by world-
renowned experts in the field, trainees can learn how to manage a wide 
variety of common and rare endocrine disorders. For example, the 
program provides training in specialized diabetes clinics to teach how 
to provide intensive insulin therapy in pediatric patients with severe 
diabetes.
    IDeA States Pediatric Clinical Trials Network.--Following the 
closing of the National Children's Study in late 2014, passage of the 
National Pediatric Research Network Act, and after extensive input from 
the research and other stakeholder communities about pediatric research 
priorities, NIH decided to augment its pediatric research efforts 
through the creation of a new national pediatric network, the IDeA 
States Pediatric Clinical Trials Network (ISPCTN). The new ISPCTN will 
utilize the Institutional Development Awards (IDeA) Program, which was 
authorized and funded by the Congress to broaden the geographic 
distribution of NIH funding across the United States by enhancing the 
ability to compete for funding of institutions located in States in 
which the success rate for NIH grant applications historically has been 
low. The goal of ISPCTN is to develop a pediatric research 
infrastructure and build capacity at academic institutions in IDeA 
States for pediatric clinical trials; increase access to clinical 
trials for children (some of whom may have rare conditions) in rural 
and medically underserved areas who are unable to travel long 
distances; and allow researchers across the country who are conducting 
pediatric clinical trials to recruit a greater diversity of pediatric 
participants in a cost-effective manner. By creating teams of pediatric 
clinical trial specialists in IDeA States throughout the country, 
children who have never before had realistic access to cutting edge 
research will have the opportunity to participate. In addition, 
investigators conducting any IRB-approved, funded pediatric clinical 
trial (not only those in the IDeA States) may work with the Data 
Coordinating and Operations Center to recruit additional pediatric 
participants from IDeA State sites for their trials; thus, trials on 
rare conditions may be able to complete recruitment within a shorter 
period of time, even though there might be a limited number of 
individuals in any one geographic area. ISPCTN will be overseen by the 
Program Director for the new Environmental influences on Child Health 
Outcomes (ECHO) program in the NIH Office of the Director, and managed 
by NICHD.
    Zika Virus.--The rapid spread of the Zika virus across the Americas 
has emerged as a potentially critical public health issue. Although the 
virus was initially discovered in 1947, recent reports from Brazil 
suggested a possible connection with an increase in severe birth 
defects, including microcephaly, which sounded the alarm to the public 
health community. NICHD is coordinating with and contributing to the 
overall effort by providing expertise in developmental biology, 
pregnancy, and preventive measures such as contraception. Efforts 
include work to understand how the virus is transmitted and how best to 
prevent it; the effects of the virus on the body, especially during 
pregnancy and timing of the infection; the impact on the developing 
fetus; new assays to test therapeutic candidates, and improved 
diagnostics to rapidly identify the virus and distinguish it from 
related viruses. Joined by six other NIH ICs, NICHD issued a rapid 
funding opportunity announcement to stimulate research on Zika, 
particularly on the seminal issue of whether the virus causes fetal 
abnormalities and pregnancy complications (fetal loss, stillbirth, 
microcephaly, ventriculomegaly, brain anomalies, and ocular 
abnormalities). In addition, NICHD is coordinating with the National 
Institute of Allergy and Infectious Diseases and sites in several 
countries, including Brazil, to conduct a prospective longitudinal 
study on Zika-related adverse pregnancy and infant outcomes. Since 
evidence of a link between the Zika virus and microcephaly and other 
abnormalities is now sufficiently strong, NICHD will again be called 
upon to utilize its knowledge base on the long-term consequences of 
physical and intellectual disabilities to help children and families 
affected by the consequences of the disease.
                                 ______
                                 
   Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal 
                Deputy Director, Office of the Director
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2017 budget request for the Office 
of the Director (OD) of the National Institutes of Health (NIH).
    The OD promotes and fosters NIH research and research training 
efforts in the prevention and treatment of disease through the policy 
oversight of both the extramural grant and contract award functions and 
the Intramural Research program. The OD stimulates specific areas of 
research to complement the ongoing efforts of NIH Institutes and 
Centers (ICs) through the activities of several cross-cutting program 
offices. The OD develops policies in response to emerging scientific 
opportunities employing ethical and legal considerations; coordinates 
the communication of health information to the public and scientific 
communities; provides oversight and management of peer review policies; 
and coordinates information technology across NIH. The OD also provides 
the core administrative and management services, such as budget and 
financial management, personnel, property, and procurement services, 
ethics oversight, and the administration of equal employment policies 
and practices. The fiscal year 2017 budget request also will support 
activities managed by the OD's operational offices. The OD Operations 
is comprised of several OD Offices that provide advice to the NIH 
Director, policy direction and oversight to the NIH research community, 
and administer centralized support services essential to the NIH 
mission.
    The functions and initiatives of the OD's research offices, also 
known as Program, Projects, and Activities, are described in detail as 
follows:
 division of program coordination, planning, and strategic initiatives
    DPCPSI (Division of Program Coordination, Planning, and Strategic 
Initiatives) provides leadership for identifying, reporting, and 
funding trans-NIH research that represents important areas of emerging 
scientific opportunities, rising public health challenges, or knowledge 
gaps that merit further research and would benefit from collaboration 
between two or more ICs, or from strategic coordination and planning.
    DPCPSI includes major programmatic offices that coordinate and 
support research and activities related to HIV/AIDS, women's health, 
behavioral and social sciences, disease prevention, dietary 
supplements, research infrastructure, and science education. DPCPSI 
serves as a resource for ICs and OD for portfolio analysis by 
developing, using, and disseminating data-driven approaches and 
computational tools. DPCPSI serves as the focal point for coordinating 
research to advance the health and wellbeing of sexual and gender 
minorities and for American Indians and Alaska Natives, and 
coordinating tribal consultation activities for the NIH.
               office of research infrastructure programs
    ORIP (Office of Research Infrastructure Programs ) provides support 
for research into model systems of human diseases and a variety of 
research infrastructure needs. ORIP supports a number of repositories 
of animal models, biological materials, genetic information, and human 
biospecimens. ORIP also makes grant awards to fund the purchase of 
expensive state-of-the-art scientific instruments and to modernize 
animal research facilities. ORIP supports training and career 
development for veterinarians engaged in biomedical research, and the 
diversity of the future biomedical workforce by investing in pre-
kindergarten to grade 12 and museum-based science education programs.
    Science Education Partnership Awards
    The goal of the Science Education Partnership Awards (SEPA) program 
is to invest in educational activities that enhance the early training 
of a workforce to meet the Nation's biomedical, behavioral, and 
clinical research needs. The SEPA program encourages the development of 
innovative educational activities for pre-kindergarten to grade 12 (P-
12), teachers and students from underserved communities with a focus on 
Courses for Skills Development, Research Experiences, Mentoring 
Activities, Curriculum or Methods Development or Informal Science 
Education (ISE) exhibits, and Outreach activities. The SEPA program 
will be coordinated with the Department of Education to ensure that 
program activities are aligned with ongoing P-12 reform efforts 
included in the fiscal year 2017 President's Budget request.
                        office of aids research
    OAR (Office of Aids Research) plays a unique role at NIH by serving 
as a model of trans-NIH planning and management, vested with primary 
responsibility for overseeing all NIH AIDS-related research. OAR 
coordinates the scientific, budgetary, legislative, and policy elements 
of the NIH AIDS research program. OAR's response to the AIDS epidemic 
requires a unique and complex multi-institute, multi-disciplinary, 
global research program. This diverse research portfolio demands an 
unprecedented level of scientific coordination and management of 
research funds to identify the highest-priority areas of scientific 
opportunity, enhance collaboration, minimize duplication, and ensure 
that precious research dollars are invested effectively and 
efficiently.
    Office of Behavioral and Social Sciences Research
    OBSSR (Office of Behavioral and Social Sciences Research ) furthers 
the mission of NIH by emphasizing the critical role that behavioral and 
social factors play in health, healthcare, and well-being. OBSSR serves 
as a liaison between NIH and the extramural research communities, other 
Federal agencies, academic and scientific societies, national voluntary 
health agencies, the media, and the general public on matters 
pertaining to behavioral and social sciences research. OBSSR's vision 
is to bring together the biomedical, behavioral, and social science 
communities to work more collaboratively to solve the pressing health 
challenges facing our Nation. OBSSR also coordinates and helps support 
the NIH Basic Behavioral and Social Science Opportunity Network, a 
trans-NIH initiative to expand the Agency's funding of basic behavioral 
and social sciences research.
                  office of research on women's health
    Since its creation in 1990, ORWH (Office of Research on Women's 
Health) has worked to ensure the inclusion of women in NIH clinical 
research, advance and expand women's health research, and promote 
advancement of women in biomedical careers. ORWH is the focal point for 
NIH women's health research and works in partnership with ICs to 
incorporate a women's health and sex differences research perspective 
into the NIH scientific framework. ORWH activities are guided by the 
2010 NIH Strategic Plan for Women's Health Research. This strategic 
plan outlines six goals to maximize impact of NIH research effort. The 
NIH strategic plan for women's health and sex differences research 
serves as a framework for interdisciplinary scientific approaches.
                      office of disease prevention
    ODP (Office of Disease Prevention) is responsible for assessing, 
facilitating, and stimulating research in disease prevention and health 
promotion, and disseminating the results of this research to improve 
public health. Research on disease prevention is an important part of 
the NIH mission because the knowledge gained from this research leads 
to stronger clinical practice, health policy, and community health 
programs. In early fiscal year 2014, ODP released its first strategic 
plan. This plan outlines the priorities that ODP will focus on over the 
next 5 years and highlights ODP's role in advancing prevention research 
at NIH. The Office of Dietary Supplements (ODS) is within the ODP 
organizational structure. The mission of ODS is to strengthen knowledge 
and understanding of dietary supplements by evaluating scientific 
information, stimulating and supporting research, disseminating 
research results, and educating the public to foster an enhanced 
quality of life and health for the U.S. population.
          office of strategic coordination and the common fund
    OSC (Office of Strategic Coordination) manages the Common Fund 
(CF), working with trans-NIH teams for each of the more than 30 CF 
programs. These teams ensure that each program meets the criteria of CF 
programs to synergize with IC-funded research. CF was created by the 
2006 NIH Reform Act, which codified the approach of the NIH Roadmap for 
Medical Research to support cross-cutting, trans-NIH programs that 
require participation by at least two ICs or would otherwise benefit 
from strategic planning and coordination. CF programs tackle major 
challenges in biomedical research that affect many diseases or 
conditions or that broadly relate to human health. CF provides limited-
term funding for goal-driven, coordinated research networks to generate 
data, solve technological problems, and/or pilot resources and tools 
that will stimulate the broader research community.
           intramural loan repayment and scholarship programs
    The mission of ILRSP (Intramural Loan Repayment and Scholarship 
Programs) is to develop and manage programs that offer financial 
incentives and other benefits to attract highly-qualified physicians, 
nurses, and scientists into careers in biomedical, behavioral, and 
clinical research as employees of NIH. There are two education programs 
offered: the Intramural Loan Repayment Program (ILRP) and the NIH 
Undergraduate Scholarship Program (UGSP).
    ILRP repays outstanding eligible educational debt for NIH Full-Time 
Equivalent employee postgraduates, and in return, participants must 
enter into a contractual agreement to conduct qualified research in the 
three statutorily governed targeted ILRPs: (1) the AIDS Research ILRP; 
(2) the Clinical Research ILRP for Individuals from Disadvantaged 
Backgrounds; and (3) the General Research ILRP.
    UGSP offers competitive scholarships to exceptional undergraduate 
college students from financially disadvantaged backgrounds. Awardees 
must be committed to biomedical, social or behavioral science health-
related research career paths available at NIH. Award recipients also 
are obligated to work as employees of the NIH Intramural Research 
Program in exchange for each year or partial year of scholarship 
funding.
                                 ______
                                 
Prepared Statement of Daniel G. Wheeland, Director, Office of Research 
     Facilities and Development Operations, Office of the Director
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2017 budget request for the Buildings and 
Facilities (B&F) appropriation of the National Institutes of Health 
(NIH).
           criticality of facilities to the research mission
    NIH strives to strike a balance between the infrastructure needs of 
tomorrow's research to address a broad spectrum of emerging health 
threats and the need for responsible stewardship of our real property 
assets supporting the research enterprise. State-of-the art facilities 
for scientific research and research support facilities are critical to 
the continuing vitality of basic, translational, and clinical research. 
The B&F program supports the design, construction, repair, and 
improvements of the NIH's portfolio of laboratory, clinical, animal, 
administrative, and support facilities at its six campuses in four 
States. These facilities house NIH researchers conducting intramural, 
basic, translational, and clinical research programs, science 
administrators who oversee NIH grant and research contract programs, 
the NIH leadership, and various programs that support NIH's operations. 
The fiscal year 2017 B&F budget request focuses on the need for 
responsible use and stewardship of NIH's past and recent investments in 
the ``bricks and mortar'' of the research enterprise. In addition, this 
budget seeks to minimize the growing backlog of maintenance and repairs 
required to sustain the condition of existing facilities to prevent 
further deterioration and, over time, further decreases to the 
Condition Index of our existing facilities. To stay abreast of the 
changing needs of the NIH programs, it is imperative that we provide 
reliable, safe, and secure research support facilities that are 
appropriately equipped, operated, and maintained.
    The B&F budget request is the product of a comprehensive, corporate 
capital facilities planning process. It begins with extensive 
consultation across the research community by professional facilities 
staff, which results in identifying the most critical NIH facility 
needs. We analyze, prioritize, and submit these facility needs to the 
Facilities Working Group, an advisory committee to the NIH Steering 
Committee, and the HHS Capital Investment Review Board. Through this 
process, NIH prioritizes its facilities investments in order to assure 
safe, reliable, energy efficient and maintainable facilities to support 
current and emerging biomedical research.
    The fiscal year 2017 B&F budget request provides funds for specific 
repair and improvements projects that resulted from the aforementioned 
NIH facilities planning process.