    [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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                           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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        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.
    ---------------------------------------------------------------------------
        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.
    ---------------------------------------------------------------------------
    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.
    ---------------------------------------------------------------------------
        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.
    ---------------------------------------------------------------------------
        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\
    ---------------------------------------------------------------------------
        \7\ Https://www.childrensoncologygroup.org/.
        \8\ Https://www.childrensoncologygroup.org/index.php/phase-1-home.
    ---------------------------------------------------------------------------
      --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\
    ---------------------------------------------------------------------------
        \10\ Http://www.cancer.gov/cancertopics/types/childhoodcancers/
    ccss.
        \11\ Https://www.stjude.org/research/clinical-trials/sjlife-long-
    term-effects.html?vgnextoid=1c4303fb30c23110VgnVCM1000001e0215acRCRD.
    ---------------------------------------------------------------------------
      --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/.
    ---------------------------------------------------------------------------
      --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\
    ---------------------------------------------------------------------------
        \13\ Https://ccr.cancer.gov/pediatric-oncology-branch.
    ---------------------------------------------------------------------------
                                     ______

                  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:
    ---------------------------------------------------------------------------
        \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.
    ---------------------------------------------------------------------------
      --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\
    ---------------------------------------------------------------------------
        \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.
    ---------------------------------------------------------------------------
      --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\
    ---------------------------------------------------------------------------
        \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.
    ---------------------------------------------------------------------------
      --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\
    ---------------------------------------------------------------------------
        \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.
    ---------------------------------------------------------------------------
        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\
    ---------------------------------------------------------------------------
        \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.
    ---------------------------------------------------------------------------
        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.
    ---------------------------------------------------------------------------
        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.