    [Senate Hearing 116-]
    [From the U.S. Government Publishing Office]

      DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
              RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2020

                                  ----------

                            THURSDAY, APRIL 11, 2019

                                           U.S. Senate,
               Subcommittee of the Committee on Appropriations,
                                                        Washington, DC.
        The subcommittee met at 10 a.m. in room SD-124, Dirksen
    Senate Office Building, Hon. Roy Blunt (chairman) presiding.
        Present: Senators Blunt, Shelby, Alexander, Moran, Capito,
    Lankford, Murray, Durbin, Shaheen, and Baldwin.

                    DEPARTMENT OF HEALTH AND HUMAN SERVICES

                         National Institutes of Health

    STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR
    ACCOMPANIED BY:
            ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
                AND INFECTIOUS DISEASES
            RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
            GRIFFIN P. RODGERS, M.D., M.A.C.P., DIRECTOR, NATIONAL
                INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
            JON LORSCH, PH.D., DIRECTOR, NATIONAL INSTITUTE OF GENERAL
                MEDICAL SCIENCES
            DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
            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.
        This is always a good hearing for us. I think, in the 4
    years that Senator Murray and I have worked on this committee
    together, we clearly have made NIH one of our priorities, and
    we're glad it has been.
        We have increased funding by $9 billion, a 30 percent
    increase over 4 years, and hopefully we are not done with that
    process yet, but hearing what you are doing with that money
    always helps encourage us to not only make those dollars
    available, but even more.
        We have seen real progress in vaccine research from Ebola
    to Zika, we have seen the development of blood tests to detect
    different kinds of cancer earlier than had been before, the
    first-ever drug used specifically for postpartum depression has
    been developed during this period of time. Obviously, what is
    happening in immunotherapy, which at our first hearing was
    something that had to be explained to all of us and even a few
    of your colleagues, as it was developing in the amazing way it
    has already.
        I think we have seen ways that you have found to encourage
    young researchers and hopefully we will be able to hear a
    little more about that today, as well.
        In my home State of Missouri, research has demonstrated
    that interactive therapy can reduce rates of childhood
    depression, a discovery of an enzyme responsible for the spread
    of cancer, and we have seen research supported that aimed at
    improving the scaling-up of immunotherapy and how to make that
    more available in a more affordable way for more people.
        I am disappointed of course, that the 2020 budget request
    would cut the agency by 13 percent. I am confident that this
    committee will not do that, but we will talk to you today about
    the reasons that we should continue in the direction we are in,
    rather than head in another way.
        I am deeply concerned about an issue that I have seen
    develop, and I hope Dr. Collins, you have a chance to talk
    about that too. It is something that the research community
    needs to take more seriously, and that is that foreign
    governments are initiating systematic ways to influence our
    research, and frankly, to take advantage of our research by
    stealing it.
        There is a Chinese Government program to recruit NIH
    (National Institutes of Health) funded researchers to encourage
    them to steal intellectual property; cheat the peer review
    system; establish shadow laboratories in China; and help the
    Chinese Government obtain confidential information about NIH
    research grants. That cannot continue to happen, and I look
    forward to hearing your discussion of that issue.
        Obviously, there is an important balance here, of
    protecting our research from both foreign threats and other
    kinds of piracy and having the kind of collaborative
    environment you want to have to bring the best people into that
    research community you can. I know that is a challenge, and I
    have seen some challenges that you have faced even recently on
    that topic of who should be there and where they should be, but
    we benefited from them, they have benefited from us. This is a
    system that has worked, and we need to be sure we continue to
    protect it. Not everyone is well-intentioned.
        I know there is an ongoing FBI investigation, and that it
    is investigating specifically what the Chinese government is
    trying to do to undermine our research structure. This is a
    serious threat to all of the things that make that structure
    work.
        The NIH Advisory Committee has recommended several steps,
    including implementing a broad education campaign about the
    requirements to disclose foreign sources of funding, and
    developing enhanced cybersecurity protocols.
        And while I appreciate those recommendations, I think that
    NIH has to be sure that the research community is fully aware
    of the threats, and more importantly, how to combat those
    threats.
        NIH has sent only one letter to the community on the
    subject, but I am going to let you talk about that a little
    more either in your prepared remarks, or later in questions. It
    is a vulnerable environment. It is a critically important time
    to look to the future. A number of individuals that are part of
    the so-called Thousand Talents program may be few, but I think
    we should not just assume that that is the only program out
    there trying to do exactly the same thing, either.
        So, Dr. Collins, certainly, I am pleased with the
    relationship you have had with this committee, with your
    leadership, I admire the team that you and your colleagues have
    put together. I am excited about the opportunity of the moment
    and glad you are here with us again today.
        [The statement follows:]
                    Prepared Statement of Senator Roy Blunt
        Good morning. Thank you, Dr. Collins and the Institute Directors,
    for appearing before the Subcommittee today to discuss the National
    Institutes of Health's fiscal year 2020 budget request.
        As Chairman of this Subcommittee, re-prioritizing funding for the
    National Institutes of Health after a decade of stagnation has been my
    number one priority. Over the past 4 years, we have increased funding
    by $9 billion or 30 percent.
        This increase has funded significant progress on vaccines for Ebola
    and Zika, developed blood tests to detect different types of cancer,
    and led to the first-ever drug specifically for postpartum depression.
    In my home State of Missouri, NIH research has demonstrated that
    interactive therapy can reduce rates of childhood depression,
    discovered an enzyme responsible for the spread of cancer, and
    supported research aimed at improving cancer immunotherapy.
        I am disappointed the fiscal year 2020 budget request cut the
    agency by $4.9 billion or 13 percent. This is not a choice I will make
    when we write the fiscal year 2020 Labor/HHS appropriations bill.
        While my commitment to biomedical research remains strong, I am
    deeply concerned about an issue I think NIH and the entire research
    community needs to take more seriously. Foreign governments are
    initiating systematic programs to influence the American research
    enterprise.
        There is a Chinese government program to recruit NIH-funded
    researchers to steal intellectual property, cheat the peer-review
    system, establish shadow laboratories in China, and help the Chinese
    government obtain confidential information about NIH research grants.
        I understand and support the need to balance protecting against
    foreign threats with the collaboration and open access that has long
    been prioritized in the medical research community. And in almost every
    case, talented foreign researchers have benefited the U.S. research
    community and moved medical research forward. As I have said many
    times, I believe that any foreign student coming to the United States
    for advanced education should be able to stay in the U.S. after that
    training is complete.
        However, we must recognize that not everyone is well intentioned.
    We know from an ongoing FBI investigation that the Chinese government
    is trying to undermine the U.S. research infrastructure. This is a
    serious threat to NIH peer-review system, to universities and research
    institutions' intellectual property, and to corrupting a system that
    has long been held as the gold standard in research worldwide.
        The NIH Advisory Committee has recommended several steps, including
    implementing a broad education campaign about the requirement to
    disclose foreign sources of funding and developing enhanced
    cybersecurity protocols. While I appreciate the Advisory Committee's
    recommendations, I do not think NIH has made the research community
    fully aware of the exact threats they face, and more importantly, how
    to combat them. In fact, NIH has only sent one letter to the community
    on the subject. The research community needs to understand that this is
    a serious, immediate, and specific threat, and that some foreign
    governments will use any means necessary to obtain a competitive
    advantage over the U.S.
        In this vulnerable environment, I think it is prudent for NIH to be
    even more cautious about ensuring systems and protocols are in place to
    protect the research community. But I am unconvinced that is happening
    now.
        Moving forward, I want to see clear steps taken to ensure all NIH
    grantees are trained to understand their roles and responsibilities
    within current policy. NIH needs to evaluate their peer-review system
    and internal controls through a lens that takes into account national
    security threats. And, finally, those who inappropriately share
    information from the peer-review process or illegally share
    intellectual property need to be held accountable.
        While the number of individuals that are part of China's Thousand
    Talents program may be few, this program has uncovered a systematic
    flaw. We must take this threat seriously and NIH should take definitive
    steps today to maintain the integrity of the NIH system.
        Thank you.

        Senator Blunt. I would like to turn to Senator Murray for
    her opening comments.

                       STATEMENT OF SENATOR PATTY MURRAY

        Senator Murray. Well thank you very much, Mr. Chairman. Dr.
    Collins, good to see you and all of your team. Thank you to all
    of you for being here today and for the work you are doing.
        The National Institutes of Health is perhaps the best
    example of an issue, where members on both sides of the aisle
    have been able to come together. We have repeatedly worked in a
    bipartisan way to provide increased investment in research that
    improves the health and well-being of people, invests in our
    local communities, and supports our Country's continued
    leadership in science.
        NIH is the largest funder of basic research in the world
    and I am very proud that Chairman Blunt, thank you, and I, and
    others on this committee have been able to increase its budget
    by $9 billion over the last 4 years, despite opposition, by the
    way, from the Trump Administration.
        Now we are here today to talk about President Trump's
    latest budget, and it stays true to form and proposes severe
    cuts across the spectrum of healthcare activities. In his
    budget, President Trump proposes steps that would undermine
    healthcare protections for 130 million people in this country
    living with a pre-existing condition. It strips healthcare away
    from tens of millions of people and we should not forget he is
    arguing in court for a ruling that would do all of that and
    more.
        President Trump's budget proposes slashing the Centers for
    Disease Control and Prevention, including their work on birth
    defects and disabilities, their efforts to combat antibiotic
    resistant pathogens, and emerging infectious diseases and more.
    It slashes funding for the healthcare workforce training
    programs at a time when our Nation is facing a healthcare
    provider shortage, particularly in our rural areas, and it
    proposes eliminating funding for the Teen Pregnancy Prevention
    Program and cutting funding for rural health and maternal and
    child health.
        And at a time of remarkable possibility in medical
    research, a time where we can and should continue leading the
    world in medical discovery, the Trump administration wants to
    cut funding for NIH.
        President Trump's budget offers one small step forward for
    pediatric cancer research and a marathon sprint backward for
    everything else.
        While he proposes increasing pediatric cancer research by
    $50 million, he proposes cutting $100 million, twice that
    amount, from diabetes research. He proposes cutting $300
    million, six times that amount, from Alzheimer's research, and
    he proposes cutting over $1 billion, 20 times that amount, from
    efforts to discover treatments for every other kind of cancer.
    In fact, for every new penny President Trump proposes for
    pediatric research, he proposes cutting a dollar from NIH. He
    would cut funding from just about everything, which would mean
    delaying, or even missing opportunities to find treatments and
    cures that could save lives, like a universal flu vaccine, or a
    vaccine for HIV.
        President Trump's damaging budget is wildly out of step
    with the sentiments of Congress, thankfully, and the American
    people, and I feel confident working with our chairman that we
    will once again reject it.
        Now, I do want to say that with that support for NIH,
    however, comes the expectation that NIH will lead in all the
    fields in which it is involved, including setting the highest
    standards for the behavior of the research community it funds.
        Last summer, the National Academies of Science,
    Engineering, and Medicine released a report that found sexual
    harassment is common in all three fields.
        Dr. Collins, you and I have had numerous discussions about
    this. The report found that almost half of women in medical
    school or enrolled as a graduate student in a college of
    medicine, and more than half of women faculty in academia
    reported having experienced some form of sexual harassment.
        The Academies recommended Federal research agencies require
    institutes to report when people on grants have violated sexual
    harassment policies or have been put on administrative leave
    due to harassment allegations. A recommendation the National
    Science Foundation has since adopted.
        NIH needs to step up and demonstrate greater leadership in
    holding its partners and extramural grantees accountable, as
    well. It is not acceptable for NIH to defer to its grantee
    institutions or other agencies to address harassment, rather
    than actually requiring them to report when it happens in
    research settings, or by researchers funded by NIH grants,
    especially when NIH's funding gives the agency such sway with
    the research community.
        Harassment undermines scientists and researchers
    professional and educational obtainment and erodes the
    integrity of the research enterprise. It makes survivors feel
    inferior or that they do not belong, and it draws promising
    young scientists away from research at great cost to our Nation
    and our scientific advancement.
        I expect more from NIH on this issue, and Chairman Blunt
    and, Dr. Collins, I would like to work with you both on
    direction that requires NIH to take meaningful action to
    address harassment that occurs in both intramural and
    extramural settings, including implementing recommendations
    from the Academies report, some of which the National Science
    Foundation has already done.
        Thank you, Mr. Chairman.
        Senator Blunt. Thank you, Senator Murray. As Senator Murray
    pointed out, the committee has worked hard on this together, as
    Senator Durbin, Senator Alexander, great advocates, along with
    Senator Shaheen, and Senator Moran, but the two people at the
    top of the committee have also been incredibly important in
    encouraging us to move forward.
        I might point out that it is not just the current budget,
    the past administration actually proposed cutting NIH research
    at a time or two, and never proposed, as far as I know,
    increasing it, at least it did not get increased. So, we have
    sort of had a bipartisan determination to correct a bipartisan
    failure to move forward for a long time. We are going to
    continue to do that and one of the reasons we will be able to
    do that is the great leadership of the Chairman, who joined us
    today.
        And Chairman Shelby, do you have some comments?

                     STATEMENT OF SENATOR RICHARD C. SHELBY

        Senator Shelby. Thank you. Thank you, Chairman Blunt,
    Ranking Member Murray.
        First, I would like for my written statement to be made
    part of the record.
        Senator Blunt. Without objection.
        Senator Shelby. And I will be very brief. I am going to
    tell you, and I agree with those Senator Blunt and Senator
    Murray, this is an important hearing. What you do is more
    important than most of what we do in America. I am not
    interested in cutting your budget, I am interested in
    increasing it; so, are they. We are going to have a big
    struggle this year, dealing with the budget, but I think this
    is a great investment for America, for the world, for humanity,
    what you do.
        Sitting at the table here, all of you distinguished in your
    own right; we are fortunate to have you, to have your
    dedication and we are going to stay with you, and we are going
    to continue to do it.
        I believe it is not only a financial investment, which is
    good for the economy, it is the leading scientist at cutting
    edge of scientific research that you had. We all benefit from
    it immensely.
        Thank you, Mr. Chairman.
        [The statement follows:]
                Prepared Statement of Senator Richard C. Shelby
        Dr. Collins, I want to thank you and your colleagues for coming
    today to give us updates on the great work that you are doing at the
    National Institutes of Health (NIH).
        I have enjoyed our conversations in the past about the importance
    of research, and I applaud the job that you have done as Director of
    the NIH.
        Research institutions in Alabama have done some wonderful
    advancements with the funding they receive from the NIH.
        Not only do our institutions in Alabama reap the benefits by
    attracting the brightest minds to perform the research, but the Alabama
    economy as whole capitalizes on the above average wages of researchers
    and the buying power they add to local businesses.
        It is important to Alabama and the rest of the country that we
    continue to increase funding for medical research at the NIH. America
    needs to remain at the forefront of advanced medical research, and
    investigators want to know that Congress is committed to pursuing new
    treatments and cures.
        Thank you all for coming today, and I look forward to asking you
    some important questions.

        Senator Blunt. Well, thank you, Chairman.
        Again, Dr. Collins, welcome to you and the directors of
    several of the institutes that are with you today. We look
    forward to hearing what they have to say as well, but if you
    would like to start with your opening statement, this would be
    the time to do that.

              SUMMARY STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D.

        Dr. Collins. Well, thank you.
        Let me introduce the people at the table. On my left, your
    right, starting over at the end, someone well known to this
    particular panel of Senators. We estimate this might be about
    his 400th hearing, Dr. Tony Fauci, Director of the National
    Institute of Allergy and Infectious Diseases.
        Next to him our Director of the National Institute on
    Aging, Richard Hodes. Then next to me, Dr. Griffin Rodgers,
    Director of the National Institute of Diabetes, Digestive and
    Kidney Diseases. On my right, Jon Lorsch, Director of the
    National Institute of General Medical Sciences. Next Doug Lowy,
    who has stepped back into the role as now Acting Director of
    the National Cancer Institute, as Dr. Sharpless has moved over
    to FDA (Food and Drug Administration) just in the last few
    days. And then on the end of the table, Dr. Nora Volkow,
    Director of the National Institute on Drug Abuse. I am honored
    to have these colleagues with me today for what I hope is going
    to be a really important exchange of ideas and information.
        So, Chairman Blunt and full committee Chair Shelby, Ranking
    Member Murray, members of the subcommittee, I want to thank you
    most sincerely for your strong and consistent, and bipartisan
    support of NIH. In fiscal year 2019 we received a most welcome
    increase of $2 billion, enabling us to continue our mission of
    turning scientific discovery into healing and hope, and we will
    have a chance to tell you about some of those things in the
    course of this hearing.
        I take very seriously the comments that were raised by the
    Chairman about foreign influence, and by the ranking member
    about sexual harassment. These are issues of incredible
    intensity and importance and I hope we can discuss some of
    those in the course of the questions.
        But I wanted to introduce you today to just a few of the
    millions of people who over the years have made medical
    research progress possible by volunteering to take part in NIH
    funded research. Instead of focusing on the researchers, I am
    going to focus on our really important partners, the people who
    take part in these clinical studies, and tell you something
    about three examples of them.
        [The graphic follows:]

        Let's begin with Richard Hockfelder. Six years ago, this
    retired aerospace engineer had a blood test called hemoglobin
    A1c that showed that he was at high risk of developing
    diabetes, a pre-diabetes diagnosis. So, he took some
    preventative steps like cutting down on carbohydrates and
    exercising more to get his health back on track and that work
    really well.
        [The graphic follows:]

        Now he could have kept that success to himself but instead
    he decided to help others and he joined NIH's All of Us
    research program, which is building an unprecedented resource
    to explore what health approaches work best for each
    individual, and why. This is precision medicine on a scale we
    have never attempted before.
        [The graphic follows:]

        We are making great progress toward enrolling our goal of 1
    million or more people. And you can see from the graph where we
    are in less than a year, more than 200,000 people have, in
    fact, begun enrollment, and about 50 percent of those are from
    traditionally underrepresented racial and ethnic minority
    groups. Because we want very much to have an opportunity with
    this resource to understand health disparities, it is a very
    diverse population.
        [The graphic follows:]

        Now all the information that they contribute of various
    types, will go into a highly secure database that researchers
    can get access to, to make discoveries. Success is going to
    depend on involvement of people from all walks of life, so we
    encourage you to join too. All you have to do is go to
    joinallofus.org, and anybody in our country can join this
    effort. And we do hope by the next 3 years to take this already
    quarter of a million and bring it to a million people. This is
    unprecedented. It is already the largest study that we have
    mounted in a very long time and we are only a quarter of the
    way there.
        [The graphic follows:]

        Let me turn to another example of somebody who has
    volunteered to help us with research. This is Frank Stevens.
    Frank belongs to a community with unique biological
    characteristics that has been offering to volunteer for
    research for years, but too often has not really had that
    opportunity. I am talking about individuals with Down Syndrome.
    We need to do better for them.
        [The graphic follows:]

        Frank actually did testify before Congress in October 2017,
    that is where this picture is taken. Now Down Syndrome usually
    results from having an extra chromosome 21, each year about
    6,000 babies are born with this condition in the U.S., and the
    average life span has doubled in recent years, but these folks
    still face significant health challenges. They include an
    increased risk of heart defects, of leukemia, of immune
    problems, of autism, and Alzheimer's disease.
        [The graphic follows:]

        On the other hand, interestingly, Down Syndrome individuals
    have a lower risk of coronary artery disease and a lower risk
    of solid tumors, even when you age-match. We do not know why
    that is and it would be very important to figure that out.
        So, because of this studying Down Syndrome may hold the key
    not only to helping those who have the condition, but also to
    understanding common diseases in all people. And this is a good
    example how rare diseases can inform about things that go well
    beyond that particular condition. NIH is stepping our efforts
    to do just that.
        [The graphic follows:]

        This should come as good news to Frank and his Mom, you see
    here vacationing, and his mom Cornelia, actually herself, has
    already shown signs of Alzheimer's disease. Frank faces a
    greatly increased risk of that because of his Down Syndrome,
    but his Mom already has it, and he wants to try to help her as
    well. As Frank once put it, ``My extra chromosome provides a
    blueprint for medical research that could reveal answers to
    this heartbreaking disease.''
        [The graphic follows:]

        Well speaking of heartbreaking diseases, I told this
    subcommittee last year that we might be on the verge of a cure,
    I used the C word, cure, for sickle cell disease. A life-
    threatening genetic disorder that bends red blood cells into a
    sickled shape because of a mistake in the gene that codes for
    one of the hemoglobin proteins, and they are bending then into
    this sickled shape that blocks blood vessels, causing
    excruciating pain in a sickle cell crisis, and damage to
    organs, which sadly shortens the lives of people with this
    condition, substantially.
        So, we talked about last year, maybe we are on the brink of
    something, today I am thrilled to say, I think we have reached
    a remarkable milestone.
        [The graphic follows:]

        Let me introduce you to Janelle. Janelle Stevenson is one
    of the brave research participants who has helped make this
    happen and whose story was recently featured on CBS's 60
    Minutes. Throughout her young life, as you can see, she was
    often hospitalized, even at, Christmas; you see there with
    Santa Claus next to her bed and has experienced over the course
    of her 20 years, just about the worst pain that a human can
    imagine from these crises.
        [The graphic follows:]

        But she decided to take a bold step for herself and for
    others with this condition and signed up for a gene therapy
    trial at the NIH Clinical Center. This trial, her own bone
    marrow stem cells were removed; modified to compensate for that
    sickle mutation, and then infused back into her body where they
    began producing healthy red blood cells. The transformation has
    been pretty incredible.
        Here is Janelle, sitting alongside her father, Ray wearing
    her white jujitsu uniform. And here she is--remember this is
    somebody who was pretty much almost bedridden before this
    procedure [Video shown].
        So, our Nation needs a lot more stories like this, but that
    one certainly heartening to anybody who has wondered are we
    going to come to an answer for that first molecular disease,
    sickle cell. We have known about it for more than 100 years and
    now, a molecular cure for that molecular disease in a very
    rigorous research protocol, and the treatment was challenging
    to endure, but you can see this is working.
        The promise is now real for the nearly 100,000 Americans
    who suffer from this devastating disease.
        [The graphic follows:]

        So, we need a lot more stories like this through the
    generosity and courage of people like Richard, Frank, and
    Janelle, along with your strong and sustained support. NIH
    research is making it possible for these kinds of stories to
    emerge every day and the world can look forward to a healthier
    and happier future.
        So, thank you, Chairman. We 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. I am Francis S. Collins,
    M.D., Ph.D., and I have served as the Director of the National
    Institutes of Health (NIH) since 2009. It is an honor to appear before
    you today.
        Before I discuss NIH's Budget request for the upcoming fiscal year
    and some of the exciting scientific opportunities on the horizon, I
    want to express my gratitude to the leadership and members of this
    Subcommittee. In fiscal year 2019, NIH received an increase of $2
    billion.I can promise you that we are investing those resources in
    groundbreaking research as quickly as we can.
        Biomedical research at NIH seeks to push forward the frontier of
    knowledge, from basic science to translational research to clinical
    trials, and success relies on vision, risk-taking, and a tireless
    pursuit of the next scientific question. NIH will continue to invest in
    people, programs, infrastructure, and technology with these goals in
    mind, consistently striving for breakthroughs that culminate in
    improvements in human health and wellbeing. From harnessing new
    technologies to supporting the next generation of researchers, NIH will
    invest its resources to ensure that the U.S. remains at the forefront
    of innovation and discovery.
        The fiscal year 2020 President's Budget provides $34.4 billion for
    NIH, seeking to fund the highest priority scientific discoveries while
    also maintaining fiscal stewardship of Federal resources. This Budget
    will prioritize biomedica l research to confront our Nation's greatest
    medical challenges, including the opioid crisis, precision medicine,
    and pediatric cancer.
        As in previous years, the Budget proposes to streamline Federal
    research by consolidating activities of the Agency for Healthcare
    Research and Quality (AHRQ) into a new National Institute for Research
    on Safety and Quality (NIRSQ) within the NIH. The Budget provides NIRSQ
    $256 million to support its activities to improve the quality, safety,
    effectiveness, and efficiency of healthcare.
        America's continuing leadership in biomedical research requires
    infrastructure and facilities capable of housing safe, reproducible
    research in compliance with all laws and regulations and conducive to
    cutting edge research. NIH buildings include inpatient hospital beds,
    Biosafety containment facilities, biomedical research laboratories,
    animal holding facilities, and even a utility plant. NIH's backlog of
    maintenance and repair now exceeds $1.8 billion.
        NIH is aggressively using fiscal year 2019 funding to address some
    of this backlog and ensure our facilities are both safe for patients
    and conducive to cutting-edge research and research support. The fiscal
    year 2020 Budget invests in NIH's facilities by again proposing $200
    million to support multiple biomedical research infrastructure
    priorities at NIH-owned sites.
        One of my personal priorities since joining NIH has been to develop
    and support the next generation of biomedical researchers. In August
    2017, NIH launched the Next Generation Researchers Initiative to
    address the challenges faced by researchers trying to embark upon and
    sustain independent research careers. I am pleased to report that NIH
    met its ambitious goal of funding 1,100 early-stage investigators in
    fiscal year 2018. In fact, we funded 1,287, the largest number in
    history. The fiscal year 2020 Budget includes a dedicated fund of $100
    million in the Office of the Director to support the prioritization of
    meritorious applications to support early stage investigators that have
    never been funded by an award, or current NIH- supported researchers at
    risk of losing support. NIH remains committed to the development,
    support, and retention of our next generation of investigators.
        This is a remarkable time in biomedical research. Truly exciting,
    world class science is taking place through NIH support, and leading to
    breakthroughs in multiple areas. I would like to provide just a few
    examples of the depth and breadth of the amazing research the fiscal
    year 2020 Budget supports.
        The fiscal year 2020 Budget continues to invest in Precision
    Medicine. Less than 1 year ago, NIH formally launched national
    enrollment for the All of Us Research Program. This program is on pace
    to enroll one million or more U.S. volunteers in an ambitious effort to
    accelerate health research and medical breakthroughs. With this
    Committee's long-standing support, we are closer than ever to building
    the most diverse biomedical data resource of its kind. By analyzing
    individual differences in lifestyle, environment, and biology,
    researchers will uncover paths toward delivering precision medicine, an
    emerging approach for disease prevention and treatment.
        As of April 7, 2019, more than 212,000 people have begun the
    enrollment process, and more than 129,000 have completed all the steps
    in the protocol. The All of Us Research Program is committed to
    engaging individuals from all walks of life, including those who may
    not have been asked to participate in research previously, and more
    than 75 percent of participants are from communities that have been
    underrepresented in biomedical research. This diversity has the power
    to revolutionize standards for inclusivity in research and for
    generalizability of biomedical research findings across many
    communities, with the ultimate goal of spurring discoveries that bring
    the promise of precision medicine to all of us. The fiscal year 2020
    Budget provides $313 million to support the All of Us Research Program.
        Millions of Americans across the Nation have been devastated by
    opioid misuse, addiction and overdose. To help bring scientific
    solutions to this crisis, and to provide safe and effective options for
    the more than 25 million Americans who suffer from daily chronic pain,
    NIH launched the Helping to End Addiction Long-term (HEAL) Initiative.
    This Committee made a historic investment of $500 million in our work
    in fiscal year 2018 and built upon that investment in fiscal year 2019
    with an additional investment of $500 million. Through HEAL, NIH will
    build on basic science discoveries to accelerate the development of
    novel medications and devices to treat all aspects of the opioid
    addiction cycle, including chronic use, withdrawal symptoms, craving,
    relapse, and overdose. NIH has launched a series of new studies to test
    both new non-addictive medications and non-pharmacologica l strategies
    for pain management, with the goal of targeted treatments for the
    millions of Americans living with chronic pain. The fiscal year 2020
    Budget continues the special investment of $500 million that was
    started in fiscal year 2018, and supports a total of $1.3 billion for
    opioids and pain research across NIH, ensuring that we continue to
    respond aggressively to the crisis of pain and addiction in our
    communities.
        Cancer is the leading cause of death from disease among children
    and adolescents in the United States. Although substantial progress has
    been made in the treatment of several types of childhood cancer,
    progress against other types has been limited. Even when long-term
    survival is achieved, many survivors of childhood cancer may experience
    long-term adverse effects from the disease or its treatment. More
    research is needed to develop new, more-effective, and safer treatments
    for childhood cancer. The President recently launched an initiative to
    support pediatric cancer research. The fiscal year 2020 Budget provides
    $50 million for a data initiative that will support the development of
    new, more effective, and safer treatments for childhood cancers, and
    will facilitate aggregation of data to create a federated,
    comprehensive, and shared resource to support childhood cancer
    research.
        First identified in 1981, AIDS is one of humanity's deadliest and
    most persistent epidemics. Although significant progress has been made
    in the fight against new infections and AIDS deaths, the HIV/AIDS
    pandemic continues around the world. The development of a safe and
    effective HIV vaccine remains a key component to realizing an end to
    the HIV/AIDS pandemic. The NIH-wide HIV research program will continue
    to sustain the accomplishments already made and secure future advances
    to prevent the spread of HIV; improve health outcomes for persons with,
    at risk for, or affected by HIV; and ultimately to find a cure for HIV.
    The fiscal year 2020 Budget includes $6 million for NIH to support the
    President's Ending HIV Epidemic Initiative. The NIH-funded Centers for
    AIDS Research and AIDS Research Centers are leveraging critical
    relationships with local and State public health services, communities,
    and research institutions to develop and refine evidence-based,
    community-specific strategies that will help guide this initiative.
        The fiscal year 2020 Budget continues to invest in research
    progress toward the important but scientifically challenging effort to
    develop a universal influenza vaccine. NIH-supported research is
    helping advance understanding of how influenza strains emerge, evolve,
    infect, and cause disease. These research results are informing design
    of new and improved therapies, diagnostics, and vaccines. Influenza
    viruses pose an ever-present public health threat and place substantial
    health and economic burdens on the U.S. and the world. The fiscal year
    2020 Budget will accelerate research progress to achieve the end goal
    of a universal influenza vaccine, which is vital to protecting millions
    of people from infection and mitigating the public health threat posed
    by influenza viruses.
        NIH is at the vanguard of biomedical research, leading the world in
    support of groundbreaking science. Thank you again for inviting NIH to
    testify today. We look forward to answering your questions.

                               FOREIGN INFLUENCE

        Senator Blunt. Thank you, Dr. Collins.
        Why don't we talk a little bit about the efforts you have
    made on the concern about foreign involvement, about duplicate
    labs in other countries, and information being shared that
    should not be, and then what we are going to do about it.
        Dr. Collins. I would be glad to do that. We are deeply
    concerned about the evidence which has been growing and which
    we have become increasingly aware of over the course of more
    than a year, that there are instances, egregious instances,
    where our funding of grants in this country is being taken
    advantage of by individuals who are not following the
    appropriate rules. This is utterly unacceptable.
        We have had multiple opportunities to interact with the
    FBI, who have been investigating this vigorously. Some of this
    is classified information, some of it is not. And as a result
    of that have uncovered what has now led to more than 55
    investigations that are ongoing of institutions where we
    believe there may be investigators who are double dipping,
    receiving foreign government money without disclosing it, or in
    some instances, diverting intellectual property that was
    rightly the property of the institution where they are working,
    to China. Or, maybe most egregiously at all because it violates
    such an important principle for us, taking grants that they are
    asked to review as part of the peer review process and
    distributing those to another country even before those grants
    have gone through the full review process, giving therefore an
    opportunity for somebody else's ideas to be stolen.
        Knowing the seriousness of this, I did something
    unprecedented and wrote--first time since I have been NIH
    director, to every one of our grantee institutions, and that is
    more than 10,000, a very strongly worded letter saying this is
    an issue they all need to take with great seriousness, and if
    they are not aware of what their own faculty are doing in terms
    of these kinds of relationships, need to begin to find that
    out.
        I think there was initially some surprise and maybe even
    denial that that could be happening in these institutions. I
    think we are past that now and we are now seeing statements
    from some of those institutions, very strongly worded to their
    own faculty saying, we realize we have a problem too. There
    increasing instances where faculty members have been fired,
    have been asked to leave the institution, many of them then,
    returning back to their previous foreign base. And I should say
    while China has certainly been mentioned a lot, this is not
    only China.
        So, actions are being taken and you will see more evidence
    of that in the press, and particularly in the coming week or
    two, to show just what is now necessary in order to respond to
    this. We will not rest until we have looked at every possible
    example. We have to depend on the universities as our partners
    in this, but we are driving this process as vigorously as we
    can.
        Senator Blunt. Within those 55 instances, how many
    different institutions would that involve?
        Dr. Collins. That is 55 institutions.
        Senator Blunt. 55 different grantee institutions?
        Dr. Collins. Yes, and basically, we are triggered by noting
    in a grantee that there is a publication that comes out that
    seems to involve a lot of authors and a lot of other
    institutions that were not mentioned in their grant
    applications. Now, maybe that is an appropriate collaboration;
    I am not going to tell you that every one of these
    investigations is going to reveal something bad happened, but
    some of them will.
        Senator Blunt. Well, we clearly benefit from having people
    from other countries here; to have their skill level here.
    Frankly I think we benefit to have them, if they want to stay
    here, to let them stay here.
        Dr. Collins. Absolutely.
        Senator Blunt. It is difficult to look at this from the
    point of view of where somebody comes from, but no matter where
    they come from, if they are involved in this, we are going to
    have to obviously be at a higher level of on-guard, than we
    have been.
        Dr. Collins. Mr. Chairman, I am totally with you, as are my
    colleagues. I am glad you raised, though, the concern though
    that we not carry this to the point where anybody who is a
    foreign national begins to feel like they are under suspicion,
    even if they are honorable contributors to our workforce,
    because almost all of those folks are. We need to be careful
    that we do not step into something that almost seems a little
    like racial profiling.
        I think Chinese scientists working in the U.S. have already
    written some letters to Science Magazine to express their
    concern about not being swept into this same framework where
    everybody is under suspicion, because the vast majority of
    these folks have been incredibly important and honorable
    contributors to our workforce.
        Senator Blunt. Now, there is a research synergy that you
    achieve by bringing people together from totally different
    preparation, styles, and everything else into that research
    moment, I think.
        Dr. Collins. Yes. Diversity contributes to productivity in
    every way, and all kinds of diversity that is true, including
    gender diversity, including people from different socioeconomic
    backgrounds, and from different countries.
        Senator Blunt. Yes. I am sure we are going to have lots of
    questions. Let's try to stay with the 5-minute time, but we
    can, anybody that wants to stay beyond their first round, we
    will get to as many questions as we can possibly get in between
    now and the time we are done.
        Senator Murray.

                                  DATA COMMONS

        Senator Murray. Thank you very much, Mr. Chairman.
        You know, many research organizations are now exploring the
    best ways to create research data commons. Private sector
    communities of companies and extramural research institutions
    like, science bound networks, Penn State, and Google's
    datacoms.org have demonstrated success, while other Federal
    agencies are already further along than NIH in successfully
    establishing data commons, like the National Science Foundation
    big data innovation hubs. It is really important that we learn
    from them, as well as from some less successful attempts at
    driving data instruction, like CA Bigg, which saw very little
    traction in the community and was widely criticized.
        So, Dr. Lorsch, let me start with you. What is NIH doing to
    avoid reinventing the wheel, and how is NIH planning to
    leverage data commons work that is already being done
    extramurally?
        Dr. Lorsch. Thank you very much Senator. That is a very
    important question. If we can connect disparate types of data,
    so, say data from the Jackson Heart Study with data from Dr.
    Hodes' Alzheimer's disease databases, the power of that could
    be enormous in terms of generating new ideas, new connections
    between these diseases, or in that case, between cardiovascular
    health and dementias, for example. That might lead to new ideas
    about treatments that could be possible or earlier detection
    strategies.
        This is what we call interoperability, making data that is
    in different languages, essentially, able to talk to each other
    so the scientists can use that data for these kinds of
    discoveries.
        We are working very closely right now with our partners in
    academia, as well as experts in the tech industry, particularly
    through the STRIDES Initiative, which is an arrangement with
    Google and Amazon that we have right now, to develop ways to
    connect the high-value data sets that NIH has, the Jackson
    Heart study, for example and Alzheimer's data together, to
    create this interoperability.
        We are definitely looking at past examples, both successful
    and unsuccessful, to help guide us, and we are definitely
    taking a lot of input from experts, particularly in the tech
    industry through that STRIDES initiative.

                          DATA SCIENCE IN OTHER FIELDS

        Senator Murray. Okay. Dr. Collins, what is the agency doing
    to really encourage and support data science training in other
    scientific fields beyond those like genomics and neuroscience,
    which really have embraced this?
        Dr. Collins. I appreciate that you are raising this issue,
    and John Lorsch has been very much a leader in the space.
        You see here our website, which will show you our strategic
    plan for data science, which has been a way in which we have
    tried to put together a lot of ideas. I totally take your point
    about not reinventing wheels that have already been tried
    either successfully, or otherwise. So, I think we are pretty
    well invested in that.
        And certainly, a big part of this is training. We are
    seeking to bring more fellows to NIH to bring the skill sets
    that exist in Silicon Valley and get them excited about
    biomedical research, because that is where a lot of the talent
    is. We are recruiting a chief data strategist, probably
    somebody from the private sector, to help us with that kind of
    culture change and recruiting of talent that we know we need.
    We need our bench to be a lot deeper, we aim to get it there.
        Senator Murray. Okay, good. Thank you. I really appreciate
    it.

                             NCI AWARD PERCENTAGES

        Dr. Lowy let me turn to you. While Congress has been
    providing the NIH, including the National Cancer Institute,
    with more funding each of the past 4 years, the odds of
    securing a grant from NCI (National Cancer Institute) have
    actually been getting more difficult. Can you tell us what is
    driving that trend and what its significance is, and do you
    expect it to continue?
        Dr. Lowy. Thank you very much, Senator Murray. Thanks to
    the generosity of Congress, we have received an increase in our
    appropriation for the last several years, approximately 17
    percent through 2018, to the regular appropriation during that
    time. During that time we have increased the number of awards
    made for investigator initiated research by about 20 percent,
    the number of new people in the awards system and the NCI by 20
    percent, and so this is, I think, very much in line with what
    you and your colleagues have had in mind.
        On the other hand, we have had over that period a 50
    percent increase in the number of grant applications, and so it
    has not been possible to keep up with the number of awards that
    we would like to make, although we are very pleased we have
    been able to make more.
        It has led to the success rate for investigator-initiated
    research going from 15 percent down to a little bit below 12
    percent during that time period, and we certainly hope that we
    will be able to increase the success rate going forward. For
    example, this year we are planning to put in more money to the
    RPG (Research Project Grant) pool than even with the generosity
    of Congress is, has added to the NCI regular appropriation.
        Senator Murray. Okay thank you, very much. I appreciate
    that.
        Senator Blunt. Senator Shelby.

                           PUBLIC SECTOR PARTNERSHIPS

        Senator Shelby. Thank you.
        Dr. Collins, you previously said that the private sector
    research outspends public sector research three to one; three
    to one. To prevent overlap, investigators in the public and
    private sector, I believe, should coordinate research where
    they can so that efforts would not be duplicated so much. I
    know there is an accelerated medicines partnership, AMP, going
    on, you have talked about it before. Would you give us an
    update on this and how we are working together to get the good
    results?
        Dr. Collins. I am happy to talk about that. Yes, I think it
    is a great opportunity to bring the best and brightest of skill
    sets in terms of scientists and also the areas of expertise.
    NIH is in the basic science in translational arena, but we do
    not make pills and the industry does, and we have to figure out
    how to do that hand-off so that this ecosystem really
    flourishes.
        I get invited each year to a meeting of the heads of
    research and development of the largest pharmaceutical
    companies; we just met this past weekend. And we have
    developed, I think, a very functional working relationship
    there to identify opportunities for shared collaborative
    precompetitive efforts, and AMP that you just mentioned, the
    Accelerating Medicines Partnership, is one of those which I
    think has been particularly successful.
        This allowed us to come together around several diseases,
    and that includes Alzheimer's disease, and rheumatoid
    arthritis, and lupus, and diabetes, and basically to work
    together to identify whether there were areas that we could as
    a group do, that neither could do alone, yet make all the data
    available. We have to do that, we are NIH.
        In those projects which are now almost 5 years along, we
    have met every milestone, and everybody who is involved would
    say we have accelerated the progress in finding new treatments
    for those diseases.
        Everyone is a little different in terms of the particular
    science that is being supported. My colleagues here are a part
    of that so, Dr. Rogers oversees the NIH part of the diabetes
    effort, Dr. Hodes oversees the part of the Alzheimer's effort,
    Dr. Carter, who is not here, the rheumatoid arthritis and
    lupus, and we have just started a new one on Parkinson's. And
    we are talking about a new one on schizophrenia where we
    desperately need some new ideas, and industry after being a
    little reluctant before, is now looking as if they could
    embrace that, too. There is a separate project on cancer
    immunotherapy called PACT, which is a relationship we have with
    industry.
        I think we are finding ways, obviously recognizing we have
    different goals, to make that happen and that is a personal
    priority for me to be sure we do not miss those opportunities.

                                CYSTIC FIBROSIS

        Senator Shelby. What about cystic fibrosis? Where are you
    going there, and where do you hope to go? You have come a long
    way.
        Dr. Collins. Well, this is also something I have a personal
    passion about, having had the opportunity to co-discover the
    gene for cystic fibrosis exactly 30 years ago. And now to see,
    although it took 30 years and I wish it had been faster, the
    emergence of highly effective, triple therapy with a very well
    designed molecular-based drugs that looks as if something like
    90 percent of people with cystic fibrosis are now going to have
    a treatment that allows them to live out what could be almost
    normal lives. Which is an amazing thing to be able to say.
        It took a huge amount of work from NIH funded resources to
    try to figure out exactly what the mechanism is for this
    disease, and what kind of drug might work, and then a close
    partnership with a company called Aurora which then became
    Vertex, and now here we are. And it is incredibly gratifying to
    see that for all those kids and families that have been waiting
    for this all this time.
        Senator Shelby. Doctor, you have been very involved in the
    National Center for Advancing Translational Sciences, and so
    forth.
        Dr. Collins. Yes.

                            RURAL HEALTHCARE ACCESS

        Senator Shelby. Could you elaborate on how NIH is
    implementing this program to address healthcare access and
    delivery in rural areas across the country?
        Dr. Collins. So NCATS, the National Center for Advancing
    Translational Sciences, is one of our newest entities. I have
    been very excited to see this emerge, trying to identify ways
    that we can help research projects that sometimes get stuck in
    the valley of death actually move across for benefit to people
    out in the clinics and the hospitals.
        NCATS also runs the CTSAs, the Clinical and Translational
    Science Awards, which is this network of 57 centers across the
    country. But we are aware that those are generally located in
    more urban settings and there is an opportunity and a
    responsibility to reach out to rural communities.
        NCATS has out right now, a notice of interest out there to
    think about how to link up in that way. One possibility is to
    link up with the idea states clinical trial research networks,
    which are also often times more in an opportunity where there
    is a rural setting. And also, to see if there is a way to work
    in the pediatric clinical trial network which is also been put
    forward as part of the effort to deal with the opioid crisis.
        So, we have a lot of connections here that are being built.
    There was a meeting at the University of Florida to talk about
    this two days ago, I am waiting to hear what the results of
    that were.

                                 FUNDING LEVELS

        Senator Shelby. Doctor, lastly, could you explain how NIH
    determines funding levels for research within its larger
    funding number, because all of us advocate for certain diseases
    that touch us and touch our friends and family, and
    constituents in many ways.
        Dr. Collins. In the minus 21 seconds I have, let me see
    what I can do to outline.
        [Laughter.]
        Senator Shelby. Well, I think I am over.
        Dr. Collins. It is a critically important question. All of
    us around this table work with that issue virtually every week
    trying to be sure we have our priorities set. I might point you
    to the strategic plan that we put forward a couple of years
    ago, which tries to go through in a very clear fashion how
    those priorities get set.
        May I say, we appreciate the fact that the Congress
    generally does not give us a lot of recommendations about
    specific disease areas, because we think science is in the best
    place to make those decisions along with what the public health
    need is, and that is what we try to do every day.
        Senator Shelby. Mr. Chairman, could I just, not a question,
    make a request? Dr. Vickers invited you to be the keynote
    lecturer, I am sure all over the world, but in Birmingham and
    at the lecture, Academic Leadership Medicine, Academic
    Leadership Series. I hope if you can work that out you would
    go; you have been there before. They asked me to do this and I
    told them I would follow their request.
        Dr. Collins. I will be there.
        [Laughter.]
        Senator Shelby. Okay. Thank you.
        Senator Blunt. That is the right answer, I am sure.
        [Laughter.]
        Senator Blunt. Senator Durbin.
        Senator Durbin. Once again proving all politics is local.

                       RESEARCH INTEGRITY AND STEWARDSHIP

        Dr. Collins, it was about 5 years ago when I visited the
    NIH and you and I had a conversation which informed and
    inspired me about 5 percent real growth a year in funding on
    medical research. The education of a United States Senator is a
    daunting task, and I thank you for taking the time to explain
    to me how consistency is as important as amounts.
        It is a new challenge to you too, in this day and age, to
    justify the amount that is being added each year when I look at
    the record. And I want to give special shout-outs to our
    Chairman here, Senator Blunt, Senator Murray, who just in both
    authorizing and appropriating committees, has been a national
    leader on the subject, and Senator Alexander who is retiring. I
    am hoping that someone with his skill and determination will
    replace him to continue this battle, but since fiscal year 2014
    we have seen the 30.6 percent increase in NIH funding, a 40.6
    percent increase in Department of Defense medical research and
    a 33 percent increase in VA (Department of Veterans Affairs)
    medical research. The CDC (Centers for Disease Control and
    Prevention), 7.4; I wish it could have been more because it is
    a deserving agency.
        But when you answer the question of the Chairman about the
    integrity of the research undertaking and endeavor,
    particularly our concern about falsification of data or the
    stealing of information, I think it really goes to the heart of
    this. Those of us who deeply believe in what you are doing and
    believe it is one of the most important parts of our public
    lives, really need to count on you, as well, to join in in
    proclaiming that integrity is not being compromised and money
    is being well spent. Our critics are going to be watching to
    find evidence to the contrary.
        Would you like to comment on that?
        Dr. Collins. I could not agree more. Let me say, I
    appreciate your beginning your comments about this importance
    of predictable, steady trajectory for support that has been
    such a source of encouragement, particularly to young
    investigators who are seeking to know whether they had a path
    for their careers.
        And frankly, things were looking pretty tough for them, 6
    or 7 years ago as we had lost a fair amount of purchasing
    power. Now to have this, 4 years in a row of a steady upward
    trajectory, has changed the dynamic completely in the
    institutions that I go and visit, where the postdocs, and the
    graduate students, and the junior faculty are now really fired
    up about the opportunity.
        But you are right, this puts great responsibility on us to
    be stewards of every dollar of that and if we find misuse of
    that information, to move swiftly to make sure that that is
    quickly stopped. We are doing everything I think we can in that
    regard, with help from our institutions to root out that
    problem and I think we have made a lot of progress, but we are
    nowhere near done.

                         AMYOTROPHIC LATERAL SCLEROSIS

        Senator Durbin. I would like to get more specific and
    personal in this next question. Tuesday morning a young man
    from Chicago named Brian Walleck, and his wife Sondra came in
    to see me. A year and a half ago, 18 months ago, he was
    diagnosed with ALS, Lou Gehrig's disease, and they wanted to
    come and talk to me about their determination to try to spark
    more interest, more research, more focus on this disease.
        Sadly, the life expectancy of those diagnosed is not long
    and they fear that many of the people who are the most
    passionate advocates will not be here long enough to fight the
    good fight and see good results.
        What can you say to the couple and others that face this
    particular disease?
        Dr. Collins. This is a particularly critical and
    heartbreaking condition, as you well know. We have redoubled
    our efforts to try to take advantage of some of the newer
    discoveries to come up with clinical applications. There is a
    consortium now called CReATe, which is Clinical Research in ALS
    and Related Disorders for Therapeutic Development.
        We have been heartened by the success, which, I think I
    talked to this committee last year of a gene therapy for the
    infantile version of ALS called spinal muscular atrophy, which
    actually has worked quite well. And now the question is could
    that same approach be successful, at least for some individuals
    with ALS where we know what the genetic mutation is, and there
    are families where that is the case.
        That is a big area of focus at the present time, but not
    the only one. So, we at least now have a consortium to put all
    the ideas that we can come up with into this space. It is a
    very hard problem, but I think our chances are better now than
    ever to make some real forward motion and maybe even some
    breakthroughs.

                         MATERNAL AND INFANT MORTALITY

        Senator Durbin. Thank you. My last point is this, as we are
    dazzled by your work and the breakthroughs in cystic fibrosis
    and other things, we also face the grim reality that this great
    Nation, this United States of America, maternal and infant
    mortality rates are absolutely unacceptable, particularly among
    some segments of our population. We cannot forget the basics
    here, and I know you are not, and I hope that you will be able
    to tell us--I have run out of time now, but in some other
    context, the work that is being done in these two particular
    areas.
        Dr. Collins. I would be glad to for the record, give you
    quite a summary of all the things that are happening there,
    particularly supported by National Institute of Child Health
    and Human Development which also covers maternal health. We
    agree that is a very high priority.
        Senator Blunt. Thank you, Senator Durbin.
        Senator Moran.

                                PEDIATRIC CANCER

        Senator Moran. Thank you, Mr. Chairman. Dr. Collins, thank
    you and your colleagues for joining us today and for the work
    that you and your team across the country, do.
        Let me start with Dr. Lowy. Doctor, the President has
    proposed a Pediatric Cancer Research Initiative, safer
    treatments for children, and better data.
        What can you tell me about the challenges we face in
    fighting cancer among children, as compared to adults? Are
    there sufficient numbers of children who were willing to
    participate in clinical trials? What are the issues that are
    unique to childhood cancers?
        Dr. Lowy. Thank you Senator Moran. One of the most
    important things to understand is that children who have cancer
    are not just small people who have adult cancer, but childhood
    cancer is qualitatively different. Whereas adult cancer has
    many mutations, often there are just are a few mutations that
    arise in children with cancer.
        In addition, while there is a tremendous amount of interest
    in cancer treatment for adult cancer, there is less involvement
    in the private sector, so that NCI has a particular obligation
    to do research in this area, and we have substantially
    increased the amount of research that we do in this area over
    the last few years.
        The particular proposal from the President is really along
    the lines of something that Senator Murray was asking about,
    which is how to efficiently and constructively aggregate data.
    And the goal as we envision it is to take pediatric cancer as
    an example, where some of the information is still quite
    siloed, and by aggregating it and pulling it together with an
    interoperable system, to be able to address important questions
    in pediatric cancer.
        Fortunately, in the terms of participation in clinical
    trials, a high percentage of children with cancer participate
    in that and a lot of that is through the Children's Oncology
    Group sponsored by the National Cancer Institute, and because
    all childhood cancers are rare cancers this is actually an
    international effort that is part of the COG.

                              ALZHEIMER'S DISEASE

        Senator Moran. Thank you. Thank you very much.
        Dr. Hodes, we have recently seen a number of late stage
    clinical trials focused on addressing Alzheimer's, that have
    shut down, highlighting the difficulty in achieving meaningful
    progress in combating Alzheimer's. What is your view on the
    current state of Alzheimer's research? Where is the future
    potential? And, maybe that is the questions.
        Dr. Hodes. Well, beginning with the failures in recent
    clinical trials, of course all of us are deeply disappointed at
    them, and these are efforts that are generally been targeted at
    amyloid protein individuals who already have symptoms. There
    are cases where there is very strong evidence to think that
    this amyloid pathway still may be important, in particular, in
    some of the early onset familial cases, but also by targeting
    earlier in disease, and so we are pursuing those specific
    areas.
        But in addition, thanks very much to the increased funding
    that has come from Congress over past years, our understanding
    of the processes underlying Alzheimer's has improved
    enormously. Last year, for example, some 32 new genes were
    identified, more than had previously identified all around.
        This has led to the ability to identify from those genes,
    bioinformatics, sys-biology, new targets. The number of targets
    is illustrated, Francis, we actually have a visual to look at.
    This is meant to show at stages from drug discovery, drug
    development, the phase one/two trials, the phase three trials,
    starting at the left the early stage of discovery, each of
    those bars represents a different kind of target currently
    under study. You can see the number of targets whether its
    inflammation or protein trafficking or proteostasis, that we
    are discovering more and more about as potential avenues.
        So, the more targets we approach, the greater the
    probability and individuals with particular syndromes that we
    are going to have success. Out of some 35 clinical trials now
    ongoing, 13 are targeting amyloid, the rest have this multitude
    of targets.
        So, a new generation of investigators, new science is
    leading us to this multitude of opportunities to make sure we
    have the way paved for a multitude of approaches to Alzheimer's
    disease.

                          NEXT GENERATION RESEARCHERS

        Senator Moran. Dr. Collins, the new set of scientists, the
    next generation, I cannot think of the young lady's name on
    your screen years ago, but you highlighted her as somebody we
    are going to lose because of the instability in research
    funding. And while I suppose we are always looking for the
    concrete evidence that the funds have resulted in a cure or a
    treatment, perhaps in the interim, between now and when we find
    all those cures and treatments, you can reassure me that the
    investment led by this subcommittee has made a difference in
    keeping, retaining, and encouraging young people to pursue
    careers in science and research.
        Dr. Collins. I can, and I appreciate the question very
    much. Yes, that was a young woman as a graduate student at MIT
    who was about ready to give up.
        That was a while ago and look at this curve which shows you
    our ability, thanks to you, to be able to ratchet up the awards
    that we have given to early stage investigators, that is people
    who have not previously been a principal investigator on an NIH
    grant. In 2013, that was a little less than 600, last year we
    challenged all the institutes to try to really push this
    forward and get us to 1100, we got to 1,287, by far the largest
    in history. We have made this a priority and every one of those
    individuals represents somebody with a lot of energy, a lot of
    innovative ideas. This is the most important investment we
    could make.
        Senator Moran. Senator Shelby would have asked had he not
    run out of time, but on his behalf, I would ask if you would
    come to Kansas.
        [Laughter.]
        Senator Blunt. Thanks Senator Moran.
        Senator Shaheen.
        Dr. Collins. I am going to be on a lot of airplanes here, I
    can tell.
        [Laughter.]
        Senator Shaheen. Well thank you, Chairman and Senator
    Murray for holding this important hearing, and thank you Dr.
    Collins and to all of you, for the amazing work that you do.

                                OPIOID EPIDEMIC

        I want to begin with you Dr. Volkow, because as I know you
    are aware, we have a horrible epidemic in this country of
    substance misuse, and in New Hampshire we have been
    particularly hard-hit. I appreciate your coming up and meeting
    with some of the folks in New Hampshire who address this
    challenge.
        Can you talk about what you are doing at NIDA (National
    Institute on Drug Abuse) that might give us some hope that
    there are additional medications, there are additional
    therapies on the way that might be able to help us address this
    epidemic?
        Dr. Volkow. I think my microphone is not working, so can I
    borrow yours?
        Indeed, this has become an area of priority area, and not
    just for NIDA but for the whole NIH and multiple institutes are
    working on it. And we have different strategies of research
    that are relevant to actually address a crisis.
        With respect to medication development, for example, it has
    been a unique opportunity to bring in the expertise from the
    NCATS (National Center for Advancing Translational Sciences)
    Institute, the translational institutes, but also even from the
    expertise that comes from the NIAID Institute as it relates to
    that development of immunotherapies for addiction.
        There are some exciting projects that are likely to bring
    us more rapidly alternatives like extended release formulation
    that improve the compliance of patients with their medications.
    We are also very interested in developing new tools that can be
    more effective in reversing overdoses that we are seeing, and
    people are reporting a higher dose of naloxone is needed to
    reverse overdose, when individuals are overdosing with drugs
    like fentanyl.
        In the field of expanding access to treatment, we now know,
    and we do not need to do anymore research, that medications are
    extraordinarily effective in preventing relapse, and in
    preventing the overdosing, and in preventing infectious
    diseases, including hepatitis C, or in outcomes in Neonatal
    Abstinence Syndrome, but they are not being used.
        The part of the problem is stigma, but another part of it
    is that we do not have sufficient infrastructure. So, we are
    working with researchers to develop models of care that they
    can advance the healthcare system, on the one side, and adjust
    the setting on the other one. These two systems have been
    almost like different universes. So, we are using the funding
    that we are getting to bring them together and figure out how
    we can come with models of care that will treat the individual
    and sustain them in care.
        And then a third.
        Senator Shaheen. There has been an issue in New Hampshire,
    as you know.
        Dr. Volkow. Yes, I know, and it is also a unique
    opportunity. We look at it in terms of preventing overdoses
    targeting both of them, as well as taking advantage, you just
    made me think, because New Hampshire has been incredible in
    terms of coming up with community solutions.
        Senator Shaheen. Right.
        Dr. Volkow. So, my perspective is how do we learn from
    those community solutions so that we can apply them to other
    States. We have an initiative called the HEALing Communities
    study that aims to do that.
        And finally, an extremely important aspect that we have to
    keep in mind when we are addressing the crisis is research for
    prevention. And why is that so? Because if we do not prevent
    opioid use disorders, or we do not do interventions to prevent
    other addictions, we will be changing one for the other.
        So, we have a very broad portfolio that covers these three
    different buckets.
        Senator Shaheen. Thank you very much.

                               DIABETES RESEARCH

        Dr. Rodgers, as you know, diabetes is one of the most
    expensive diseases in this country, and I was very disappointed
    to see that the President's budget actually called for a $280
    million decrease in funding for NIDDK (National Institute of
    Diabetes and Digestive and Kidney Diseases).
        I wonder if you could--I do not think this committee will
    go along with that. I think we appreciate that investment in
    addressing diabetes research will help us in the long term to
    be more cost-effective, as well as to address the challenge
    that folks with diabetes face.
        Can you talk about some of the breakthroughs that you are
    looking at now in terms of the artificial pancreas, which is
    really the most hopeful innovation to help folks with Type I,
    in particular?
        Dr. Rodgers. Absolutely, thank you for the question. Yes,
    the FDA recently approved what have been truly breakthroughs
    for treatment of patients with type 1 diabetes, such as the
    first hybrid, artificial pancreas and the next generation of
    continuous glucose monitors that no longer require a finger
    stick for calibration, or that those are fully implantable.
        I am happy to report that supported and the Special
    Diabetes Program have contributed to testing of all of these
    FDA approved therapies, and we continue to support cutting-edge
    research in this area. We are supporting advances in artificial
    pancreas in four very large, international clinical trials now,
    conducted at academic medical centers. Research using our
    special business funds is developing the next generation of
    management technologies.
        The goal is to provide the patient and their healthcare
    provider with different options to decide what is the best
    artificial pancreas that could be used for that individual.
        Senator Shaheen. Well, thank you very much. I am out of
    time, but I hope that our healthcare system and our health
    insurance companies will be willing to cover these kinds of
    innovations so people can actually benefit from them.
        Dr. Rodgers. I agree.
        Senator Shaheen. Thank you.
        Senator Blunt. Thank you Senator Shaheen.
        Senator Capito.
        Senator Capito. Thank you. Thank you, Mr. Chairman and
    thank you Dr. Collins and everybody for being here.

                            FUNDING NEW RESEARCHERS

        The first question I was going to ask Dr. Collins, I think,
    has been asked a couple of times. We were really lucky to get
    Dr. Marie Bernard to come. Dr. Hodes was supposed to come but
    doing what he should be doing with his family, and one of the
    doctors in the room, researchers in the room expressed his
    concern about talented young scientists being frustrated with
    not being able to get into the queue.
        So, you gave us the statistics of past had been 600, and
    now 1287, is that?
        Dr. Collins. That is correct. That was for last year and we
    are going to aim to make a very good result this year. We are
    already starting to count these up and make sure that any
    investigator who scores in sort of, the top 25 percent as a
    first-time applicant, ought to have a very good chance, a very
    high chance of getting funded.
        Senator Capito. Would you say those are geographically
    pretty much spread across the country then?
        Dr. Collins. They are, as much as our grant portfolio is in
    general, and of course there are institutions that send more
    grants and others that send fewer, and the IDeA (Institutional
    Development Award) program helps us by balancing that.
        Senator Capito. Right. Right. Thank you.

                       COORDINATING ALZHEIMER'S RESEARCH

        Dr. Hodes, we did have a great visit and you were, as I
    said, well represented by Dr. Bernard.
        One of the things that we talked about during the visit to
    West Virginia University was the work that is being done with
    the other institutes at NIH in conjunction with NIA, the
    National Institute of Aging, on different aspects of
    Alzheimer's. For instance, it was mentioned like a possible
    connection of low blood pressure and decreased cognitive
    impairment.
        Can you talk about what kind of coordinating, you are doing
    at the Institute of Aging when you are looking and researching
    across the spectrum of NIH?
        Dr. Hodes. Thank you. It is a very important question and
    part of the success that we are going to have in addressing
    Alzheimer's disease, or other complex problems, of course,
    would be to recruit the best talent from a diverse area of
    science and expertise. So, along the lines of previous
    conversation, over the past 4 years about one quarter of all of
    the awards have gone to new and early stage investigators.
    About one third have gone to new-to-the-field investigators who
    never even applied for research in Alzheimer's before, and last
    year a particular program, for example, invited grantees of all
    institutes whose research was not Alzheimer's directed, but who
    proposed a supplement to bring their creativity, their
    technology, their genius to the field to do so, and last year
    awarded some 300 supplements.
        This we expect, and we are following up upon, will bring
    these people into the field. We directly fund the research on
    Alzheimer's and related dementias across all the institutes of
    NIH, so about $200 million last year actually supported awards
    to other institutes that are relevant to Alzheimer's and
    related dementias.
        Senator Capito. Yes, I think that obviously brings an
    economy of scale a bit, but knocks down, I am sure like
    everybody else has, silos. I am sure NIH has had silos, not as
    many maybe.
        Dr. Collins. Yes, past tense.
        Senator Capito. Past tense. Yes.
        Dr. Collins. We hope to knock them all down and we did
    pretty well, but we are still watching for them to try to come
    back.
        Senator Capito. Right. Great.

                      NEONATAL ABSTINENCE SYNDROME BABIES

        Dr. Volkow, as you know, my fellow Senator from New
    Hampshire, I know you have been to West Virginia. How many
    times now, two or? Three times and thank you for that visit;
    those visits that the NAS (neonatal abstinence syndrome)
    babies, Lily's Place and others, we do not know what the long-
    term effects of all of this is, I do not think. I think a lot
    of it may be in the science of the person's--as the child
    grows, their own health, but there are always external factors
    that are going to be impacting this, what kind of education,
    family life, etc. etc.
        What are you doing with the NAS babies in terms of
    pharmacological research and specialized treatment strategies?
        Dr. Volkow. Yes, and this is one of the priority areas for
    the HEAL initiative, to actually develop better treatment
    interventions that will improve the outcomes for the infants
    and that will lead us to understand better what are the
    consequences on the one hand, for a newborn that has during
    pregnancy their mother was taking opioids, but importantly, as
    they grow up in an environment where the mother may still be
    taking drugs and be subjected to a social deprivation.
        So, on one hand one strategy is can we develop better
    treatments for Neonatal Abstinence Syndrome, and we typically
    treat them with, for example, morphine. Now, it is said that if
    you treat them with that small dose buprenorphine you
    significantly decrease the number of days that they actually
    have to be given the medication.
        Just like we had also shown before that if you treat the
    mother with buprenorphine, as opposed to methadone, you
    decrease almost by half the number of days that you actually--
    the infant that is born out of that mother will have with her
    withdrawal symptoms.
        We are also funding research, and again, this is in
    partnerships with other institutes, including the National
    Institute of Child Health and Human Development about non drug
    interventions, and this has emerged out of root grass of
    communities that have had to deal with the problem. And, for
    example there is recognition now that physical contact of the
    infant with the mother, could actually decrease the amount of
    morphine that is necessary to control withdrawal. So, we are
    funding research to develop the evidence about what are the
    optimal interventions.
        And finally, as it relates to your question about what is
    going to happen with these children. There has been already
    some research that shows that in infants that are born out of
    mothers who were exposed to opiates, if you provide a
    supportive environment those children grow up to not have
    evidence of cognitive impairments.
        But we are actually in the planning phases of launching a
    very, very large study that will follow close to 8,000 infants
    as they go from infancy to adolescence to evaluate how exposure
    to drugs influences brain development trajectories.
        Senator Capito. Yes, I mean that sounds very powerful and
    the troubling part is, it has to be a long-term study to be
    able to see the effect and by that time, the effect has taken
    hold.
        Thank you so much for your good work. Thank you.
        Senator Blunt. Thank you Senator Capito.
        Senator Lankford.
        Senator Lankford. Thank you, Mr. Chairman. Thank you all.
        A quick story. I was sitting on an airplane about 3 months
    ago, sitting next to a gentleman flying back to Oklahoma. He
    leaned over, introduced himself as a fellow Oklahoman and we
    chit chatted for a while, and I said, what brings you to
    Washington? He said, ``I come often. I am in an NIH trial, and
    I have been for years'' and he smiled, and he said, ``And, I am
    still here.''
        And from watching his smile and chit-chatting with him on
    the two-hour flight back home, it reminded me again of how many
    people that are still around, just like he said, because of the
    work that you are doing.
        So, thanks for continuing that work and for helping folks
    that, literally for him, as you know, he had been through
    everything to be able to get to your desk, to be able to get to
    that spot. So, we appreciate it very much.

                                 BRAIN MAPPING

        Dr. Collins give me an update on the brain mapping. I want
    to walk through several things we talked about in the past. We
    have obviously made significant investments into that. I missed
    the very opening statement of this in a previous thing that I
    had to be able to get to as well this morning. Tell me where we
    are on brain mapping.
        Dr. Collins. I would love to talk about this. This project,
    which began 4 years ago has very ambitious goals to really
    understand, what are the cell types in the brain? There are 86
    billion of those cells, so that is a pretty big challenge. And
    how are they connected together and how do the circuits in the
    brain do the amazing things that they are capable of, and how
    can that go awry and result in disorders like Parkinson's
    disease or epilepsy, or a long list of others?
        We, after 4 years, I would say have met or exceeded every
    one of the milestones that was put in place when the original
    plan for the 10-year program was put forward.
        So, you are asking the question at an appropriate moment.
    Right now, we are having a meeting of all the brain
    investigators at the Marriott at Wardman Park, and this evening
    I will chair a panel that will look at the plan now that is
    being revised, we can call it brain 2.0, of what we might be
    able to accomplish given the platform that has already been
    built.
        It is exciting from what we have already learned in terms
    of new principles about how brain actually does what it does.
    It is exciting by the people that have come into it, and the
    latest couple of rounds of grant awards, more than half of them
    were engineers, who would not necessarily be coming to NIH with
    grant applications, but they are fired up about this too. And
    that interdisciplinary part of this is part of the reason that
    I think it is turning out to be so successful.
        Senator Lankford. Okay, thank you. Well, we will want to
    get a detailed update because we want to make sure it stays on
    track, obviously, but this is a massive project, as you
    detailed before.
        Dr. Collins. Yes.

                          NONADDICTIVE PAIN TREATMENT

        Senator Lankford. You have brought together folks from the
    outside and from private companies to be able to talk about
    alternatives to opioids and developing a nonaddictive pain
    treatment.
        How are the outside groups, private entities,
    pharmaceutical companies, cooperating with you? Is that group
    still together, still working?
        Dr. Collins. Actually, quite well. We have in fact, put in
    place a combination of scientific expertise from academia from
    NIH and from industry, and we are now trying to prioritize what
    may be, is many as 60 or 70 possible therapeutics that would be
    nonaddictive treatment for pain, but which have been slowly
    moving through the pipeline.
        We at NIH are setting up a clinical trial network for
    people with chronic pain syndromes so that these can be tried
    out in a rigorous way, and companies are willing to contribute
    those.
        Senator Lankford. They are staying engaged?
        Dr. Collins. They are staying engaged.
        Senator Lankford. Okay, that was the risk at the beginning,
    to say you are bringing together competitor groups to be able
    to say we have got to sit down and solve this right now,
    together, so.
        Dr. Collins. Yes, I met with the 20 pharmaceutical
    companies that have the largest budgets last weekend and they
    were all on board.

                              DUPLICATIVE RESEARCH

        Senator Lankford. Okay, thank you. Let me read a GAO report
    real quick and I want to be able to get a follow-up from you.
        Their statement was, they talked about VA, CDC, NSF
    (National Science Foundation), DoD, NIH and they said, ``Each
    lack a comprehensive information on health research funded by
    the other agencies, which limits their ability to identify
    potential areas of duplication in the health research they
    fund.''
        They made that comment just looking at the broad picture of
    all of the research that is happening in multiple different
    areas, the Appropriations Committee appropriates.
        How is it working to be able to cooperate with VA, DoD,
    especially large programs, NSF, to make sure, because as you
    would know, grant folks are requesting of everybody. So, they
    will have a slightly different name for similar research and go
    to as many institutions as they can to be able to see if they
    cannot find money to do the research on it.
        How are we doing being able to avoid the duplication and
    communication on agencies?
        Dr. Collins. Senator it is a great question and it is
    something we are quite invested in. We have a whole office of
    portfolio analysis that has now been working at coming up with
    tools to allow us to look, very complicated research portfolios
    what are the areas of overlap?
        We have done that kind of analysis comparing NIH to NSF,
    comparing NIH to the DoD programs, comparing NIH to ARC. It is
    very informative to be able to see that in a visual form, and
    we have in few instances identified places where there was
    duplication and acted upon it.
        We have not yet done this as much for VA, but that is next
    on the agenda. As long as we have access to the abstracts for
    the grants that are being funded, we can do this right away.
        Senator Lankford. You are breaking down silos at NIH. The
    challenge is going to be for us to break down silos in medical
    research across multiple agencies to make sure researchers can
    meet with each other, and we know we've got similar research
    and we are sharing that information, and we are not duplicating
    it.
        I will have a question for the record that I will follow up
    with you, I know you had an interchange with Representative
    Harris on fetal tissue research. HHS is in the process of doing
    a review of all fetal tissue right now and I know there is
    somewhat of a pause going on as they are waiting for that to be
    responded on, but I will do some follow up with some questions
    for the record with you on that as well.
        Dr. Collins. I will be glad to answer for the record.
        Senator Lankford. Thank you.
        Senator Blunt. Thank you, Senator Lankford. We will
    probably have a chance for a second round, if you want to stay.
        Senator Baldwin.
        Senator Baldwin. Thank you, Mr. Chairman.

                     NEXT GENERATION RESEARCHERS INITIATIVE

        Dr. Collins, you and I share a passion on a personal
    priority of investing in our Nation's next-generation of
    researchers. I think most everyone on the subcommittee knows
    from my retelling the story that I was raised by my
    grandparents, and my grandfather was an NIH-funded scientist, a
    biochemist. So, I grew up understanding the importance of the
    contributions of our researchers to biomedical leadership.
        In 2013, I had a particularly powerful meeting with a high
    school student. He was a bone cancer survivor from Fond du Lac,
    Wisconsin, and his name is Ian and Ian told me that cancer
    research helped save his life. He decided at that point that he
    wanted to grow up to be a scientist and to help others who had
    the disease. But he was concerned that it would not be possible
    for him to break in as a new researcher due to NIH funding
    cuts.
        Ian inspired me to author the Next Generation Researchers
    Act with my colleague, Susan Collins, to improve NIH
    opportunities for our new and early-stage researchers.
        I am proud to report to you that Ian has graduated from
    college and is now working in a lab with a scientist at
    Huntsman Cancer Institute in Salt Lake City, Utah studying
    pediatric cancers like osteosarcoma.
        I applaud NIH's progress in implementing my Next-Generation
    Research's Initiative to help support future scientific leaders
    like Ian. In fact, as you noted, NIH funded 1287 early-stage
    investigators in 2018, as part of this work, the largest number
    in history.
        I would love it if you could elaborate on NIH's work to
    implement this initiative since it was signed into law back in
    2016, and your plans for implementing it moving forward, and
    any comments you might have about the National Academies
    Consensus Study Report on the Next Generation of Biomedical and
    Behavioral Sciences researchers.
        Dr. Collins. Well Senator, I really appreciate the way you
    have drawn attention to this critical issue, and we have named
    our initiative the Next Generation Researchers Initiative after
    what you authored, because we were totally in sync with this as
    one of our highest priorities.
        When Ian asked you the question how we were funding,
    according to the graph here if it was 2013, less than 600
    early-stage investigators, and that was a time where it was
    challenging for somebody trying to get their career started to
    have confidence that there was going to be a path forward.
        And notice what has happened since then, thanks to the
    strong support of this committee, and to our prioritizing
    early-stage investigators as the most important applicants that
    we see, and yes, we are now in 2018, up to 1287. We aim to try
    to keep a level in that space going forward. I think that is a
    pretty healthy number. This is not one of those where we want
    to go up and then go back down again, because there is plenty
    of remarkable talent out there.
        So, in addition to, of course, trying to be sure that we
    are doing this in a fashion that attracts really talented
    people, we also are focused on diversity. We want to have more
    women in this category, because we still have not achieved the
    point where our grantee pool is what it could be, given that
    PhD's now are being granted 50-50 to men and women, yet we
    still as first-time applicants to NIH, it is about 30 percent
    that are women.
        We are coming up with ways to try to make this pathway seem
    more appealing, and for us to be more welcoming, and of course
    that means dealing with the sexual harassment issues that
    Senator Murray rightly brought up earlier.
        We did support that report from the National Academy and we
    have strong agreement with many of its recommendations in terms
    of what we need to be doing to sustain this, but as I briefly
    said earlier, I am perceiving, and Ian is a great example, of a
    good deal of the change in the enthusiasm and excitement out
    there in institutions of young graduate students, postdocs,
    junior faculty really see, okay this is a good time to be in
    science, not a time where we have to worry about our future
    quite as much as we did 5 or 6 years ago. So, thank you for the
    way you have supported this.
        Senator Baldwin. Well, thank you.
        I have been concerned that President Trump's budget would
    cut NIH funding by over $4 billion, as years of budget cuts are
    one of the primary factors in discouraging historically, young
    scientists from getting into the field or forcing them to leave
    the field to pursue careers in other countries or in other
    realms. Yet, no investment in my mind promises greater returns
    for America than our investment in biomedical research.
        Will the Next Generation Researchers Initiative deliver on
    its promise and be able to continue to hit such ambitious
    milestones as you are describing, under the administration's
    proposal to reduce overall funding for the NIH?
        Dr. Collins. Well of course, everything we do depends on
    the overall support that we have available. This Congress, and
    this particular subcommittee has been very attentive to that
    and the opportunities that we have had over these 4 years of
    seeing our budgets go up by a total of 30 percent, have made a
    lot of these things possible.
        We always though, have to adjust based upon the resources
    that we have. I will tell you of the institutes at this table
    and the others who are not here, this funding of early-stage
    investigators is one of our highest priorities. We will seek to
    make that happen to the level that we can with the resources
    we've got.
        Senator Baldwin. Thank you and Chairman Blunt and Ranking
    Member Murray, I oppose the President's budget request to slash
    funding for NIH, and I look forward to working with both of you
    to increase funding both for NIH and for a special focus on the
    Next Generation Researchers Initiative in the fiscal year 2020
    budget.
        Senator Blunt. Well thank you, Senator Baldwin.
        Senator Alexander.
        Senator Alexander. Thank you, Mr. Chairman. Dr. Collins and
    your team welcome.
        First I want to once again salute Chairman Blunt and
    Senator Murray, and others who have worked over the last 4
    years for such steady progress in funding for the National
    Institutes of Health. One reason we have done that is because
    we had such great confidence in your leadership and that of
    your team that you would spend the money well. So, it is a
    testimony to you and very important.

                         OTHER TRANSACTIONAL AUTHORITY

        In the opioid's legislation, we did something that you had
    asked us to do when we talked about 21st century cures. That
    was to give you other transactional authority so you could deal
    with such things as a nonaddictive pain medicine.
        The committee that Senator Murray and I are ranking on, we
    recently had a hearing on pain and that exacerbated-- that
    reminded us that when we limit the supply of the most effective
    pain medicine, opioids, to millions of Americans, that causes a
    lot of worry among people who live with pain every day, and
    there are millions of them.
        So, my question is, what have you been able to do with the
    other transactional authority that we gave you to help find new
    nonaddictive painkillers?
        Dr. Collins. It was very helpful, in fact essential, to
    have that kind of authority to move quickly in this space of
    putting together an unprecedented public/private partnership to
    try to speed up the development of those nonaddictive pain
    medicines.
        As I mentioned a couple minutes ago, we are working now
    with pharmaceutical companies who were willing to put forward
    compounds, we are calling them assets, but basically, they are
    untested drug compounds that are ready for clinical trials but
    have been slow moving through that pipeline.
        We then need to do a very quick review of how to prioritize
    these, we cannot test 60 of them, but we might be able to
    ultimately run trials on a dozen or so. Which means we need to
    have a process of review that is very streamlined, and it needs
    to be supported in a way that would be very hard to do with a
    traditional grant mechanism.
        The other transaction authority is exactly the tool that we
    have needed in that space; it has been essential, and so we are
    grateful for it.
        Senator Alexander. Good. Well, there is--I have an even
    higher sense of urgency about the nonaddictive pain medicine
    and treatment and accelerating our effort for that.
        Let me go back to April 2016, you testified before this
    subcommittee and made 10 bold predictions of what might be able
    to happen in the world of medical miracles over the next
    several years. A lot of them are happening, and you have
    mentioned them today. Are you ready to update your 10 bold
    predictions for the next 10 years?
        [Laughter.]
        Dr. Collins. I probably could do that. It would be kind of
    fun because there were some things that I do not think I put
    down in 2016 that I could now be pretty enthusiastic about. So,
    for instance, in 2016, I do not think I would have been bold
    enough to say that we would be curing sickle cell disease, and
    yet we are now seeing in at least three clinical trials that
    NIH is supporting, examples of individuals who are cured.
        Senator Alexander. Is that because of CRISPR?
        Dr. Collins. That is, CRISPR is in there, and other kinds
    of gene therapy making this possible. Some of the things we put
    down at that point, I thought were a bit overly optimistic, and
    yet maybe I underestimated how quickly things would go. We
    earlier talked about the artificial pancreas and, you know, I
    put that one down and a year later FDA approved the first one.

                             REGENERATIVE MEDICINE

        Senator Alexander. That is pretty common, right.
        Well, what about regenerative medicine? The juvenile
    diabetes folks say that the next step is regenerative medicine
    might help actually change the cells so you would not have to
    use the device. Is that possible?
        Dr. Collins. I think that is the ultimate goal. Maybe Dr.
    Rodgers would like to make a quick comment, to go from what is
    currently a technology that is like a servo mechanism with some
    nonhuman materials, into a human version of an artificial
    pancreas derived from stem cells.
        Senator Alexander. But the impact of that would be
    astonishing, wouldn't it?
        Dr. Collins. Profound, and it would be your own cells so
    this would not be a transplant, it is basically----
        Senator Alexander. So, you would not have to prick for your
    blood every day?
        How would that work Dr. Rodgers?
        Dr. Rodgers. Well, that is a great question. Cell
    replacement therapy is certainly an area that we are also, in
    addition to the artificial pancreas technology looking for a
    curative therapy. The goal here would be to stimulate the
    person's own beta cells, those cells that are lost due to
    autoimmune disease, and get them to replicate to expand them.
    Or alternatively, use of the remaining cells, such as the alpha
    cells that make glucagon, and trick them into actually becoming
    beta cells so that insulin can then be produced as well.
        One thing that we are doing in that space, using these
    islets, the cells that make insulin, is actually putting them
    on a chip. I have actually brought a copy of one to illustrate
    for the committee. These islet cells are put on this chip
    together with cells that replicate the pancreas environment
    blood vessels, as well as components of the immune system. In
    that, you can mimic the disease on a chip.
        The potential of this is that we may be able to test
    therapies in advance and save some of the expense and time
    associated with testing novel technologies in humans and get
    those that are likely to fail out of the way. So, we really
    have a lot of enthusiasm about this type of work.
        Senator Alexander. Thank you. My time is up.
        But I look forward to you updating your bold predictions,
    Dr. Collins.
        Dr. Collins. You are on.
        Senator Blunt. Alright. We will look forward to the list of
    bold predictions.
        Dr. Fauci, I am going to take 5 minutes here, and I have
    three questions and maybe we can deal with all of them in 5
    minutes. One, is measles. What do you think is happening and
    how concerned we should be about it?
        Two, the antibiotic resistance, the fungus that we are
    having problems, big problems in a couple places in the country
    now. Then, three would be the President's HIV 10-year
    prediction to not have transmission, or not have this as a
    problem anymore.
        So, start with measles.

                                    MEASLES

        Dr. Fauci. Thank you, Mr. Chairman. Measles is really a
    formidable problem that is growing. It is a completely
    avoidable problem, which is the reason why we in the scientific
    and public health field are so frustrated by it.
        If you look at the year 2000, we here in the United States
    had essentially eliminated measles. By elimination, it means
    that there are no transmissible cases in the country over a 12-
    month period. Yet over the last several years there has been
    increasing numbers of cases of measles, and I will explain in a
    moment why that is occurring.
        The problem right now, this past 3 months of 2019, we have
    had 465 cases of measles in the United States, which is more
    than we saw all of last year. And the cause of that is very
    clear, it is individuals in the community who are not
    vaccinating their children, leaving a vulnerable group such
    that when someone comes in from the outside, from another
    country where measles might be rampant and into the community,
    that if you have that veil of protection that you need when you
    need a certain critical percentage of the population is
    vaccinated, and for measles that means between 93 and 95
    percent.
        But look at what is going on now, in the State of
    Washington, in the Rockland County, New York and very, very
    importantly, in the middle of New York City in the Williamsburg
    section, where the Hasidic Jewish community goes down to around
    70 percent protection, which means that veil of community
    immunity is gone.
        That is the reason why we are having this outbreak. It is
    very frustrating, because measles is one of the most
    transmissible viruses known to man and we have a vaccine
    against measles, which is one of the most effective vaccines
    known to man, and yet those two are not coming together with
    this hesitancy to get vaccinated.
        So, our goal and our purpose now, is to try and educate
    people to understand the importance of not only protecting
    their own children but protecting the community. That is
    measles.

                              CANDIDA AURIS FUNGUS

        The fungus that you alluded to; it is called Candida auris.
    Fungi in general that we see are mostly, I would not say
    benign, but relatively easily treatable. The problem with this
    fungus that is now come out about 500 or so cases, is that we
    are seeing in hospitals particularly, a fungus that is rather
    resistant, if not completely resistant to the antifungal
    agents.
        This is particularly important for individuals who are
    immuno-suppressed, people on cancer chemotherapy, or people who
    have underlying immunosuppression. You have read about it in
    the front page of the New York Times, but this is becoming a
    problem that we have to address, and it falls under the big
    umbrella of the anti-microbial resistance.

                                      HIV

        Third, the President's announcement at the February 7th
    State of the Union Address about ending the HIV epidemic as we
    know it in the United States, and this is based on something
    that has happened for many years largely supported by this
    committee, is the development of the tools to do just that.
        We have drugs right now as you well know, I have spoken to
    you about this, that if you treated an individual who is HIV
    infected and bring down the level of virus to below detectable
    level, not only do you save that person's life but you make it
    essentially impossible for that person to transmit the virus to
    someone else.
        And then there is preexposure prophylaxis or PREP, which
    means that if you are at high risk of getting infected and you
    take one pill a day, you can decrease by 97 percent the
    likelihood that you actually will acquire infection.
        You put those two things together and you look at the map
    of the United States, why it is so unique. We have 3,007
    counties in the United States, in 48 of those counties, plus
    the Washington District of Columbia, plus San Juan, more than
    50 percent of all the infections in the United States come from
    that very restricted group.
        So, the plan is to take this demographically and
    geographically concentrated area, and as I say, put a full
    court press on getting into the community and implementing each
    of those.
        So, I will stop there, and I give you back 10 seconds.
        [Laughter.]
        Senator Blunt. Well, that is back to the observation
    earlier that you have testified before, you have three
    questions, exactly have timed them out and land on time.
        Senator Murray.

                               SEXUAL HARASSMENT

        Senator Murray. Thank you very much and Dr. Collins I know
    you are aware of a recent study in the Journal of American
    Medical Association, which found the gender differences, you
    talked a minute ago about that, in the amount of NIH funds
    awarded to first time female, and male principal investigators
    that favored men receiving larger grants than women. And data
    shows that in academic medicine, which for years has trained
    just as many women as men, the percentage of women in the
    workforce decreases at every career stage, such that women make
    up only 25 percent of the professorate.
        And your conversation with Senator Baldwin indicates you
    are aware of a study that also found that women held fewer
    grants, submitted fewer applications, and were less successful
    at renewing grants than their male counterparts.
        So, in light of the National Academy's report last summer,
    which showed that sexual harassment is rampant in academic
    science and undermines women's professional attainment, in some
    cases, leaving women to leave the scientific workforce
    entirely, the cumulative effect results in significant damage
    to research integrity and a considerable loss of talent in our
    country.
        So aside from its economic and potential scientific impact
    that loss of talent actually represents a significant cost to
    our taxpayers. It has been estimated that each newly minted
    Ph.D. costs $500,000, and of course it is a personal loss to
    women who feel pushed out of the field they love.
        So, given all that, can you comment on actions that NIH is
    taking to address this attrition of women from the biomedical
    workforce?
        Dr. Collins. I would be happy to. This is a very critical
    issue and there are multiple factors, but certainly the
    realization of how prominent and pervasive sexual harassment
    has been leads us to push even harder to address this issue. It
    is unacceptable, it is morally indefensible, and it drives
    talented women away from the workforce who could make wonderful
    contributions.
        If you look at this graph, it sort of shows you what has
    happened as far as the percent of various types of grants that
    are going to women. You can see in the career awards, which are
    generally people early in their independent phase we are doing
    better over time, we are actually doing better with research
    project grants, but the curve is way too slow in terms of its
    upward movement. That ought to be 50 percent, and it is not
    that there is a discrimination against women who apply for
    grants, if you look at the likelihood of getting funded, men
    versus women, it is almost exactly the same. The problem is we
    are not getting the applications.
        Senator Murray. They do not apply.
        Dr. Collins. And that is clearly an indication that there
    is something about our environment that is not welcoming, it
    does not feel like to many women, a place they really want to
    be. There are lots of factors in there in addition to the
    sexual harassment issue, there are family issues, and there are
    the issues about who has responsibilities for other parts of
    the community that people are coming out of. There is this sort
    of concern that if you look around, where are the mentors.
        I believe we really need, not just to try to address the
    things that are the most egregious as far as the sexual
    harassment, but also the gender harassment. The way in which
    our culture encourages women, often times to think they do not
    belong there by subtle comments that are made, usually by men.
    We have to change that, the best way to change that is to get
    more women into leadership positions.
        Senator Murray. I am looking at your panel, it's great,
    but----
        [Laughter.]
        Dr. Collins. Well, yes, look at our panel, just take a
    snapshot here, this is a good example of what we need to
    change.
        We are actually looking at our intramural program right now
    to try to see, are we doing enough there to provide
    opportunities for talented women to rise through the ranks or
    are we too ossified by people who get into a position and stay
    there too long.
        We are taking this with great seriousness. I grant you, we
    should have done so sooner, and I am apologetic to those who
    think we have not done enough. We are determined to do better.
        Senator Murray. Okay, I appreciate that. Thank you very
    much and of course, we all have to participate, and appreciate
    your taking this seriously, look forward to working with you on
    it. I think we are losing talent from an early age and it gets
    worse as we go on. We have to make sure we have all of our
    talent at the table. So, thank you.
        Dr. Collins. I agree with you.

                           METHAMPHETAMINE DEPENDENCE

        Senator Murray. Dr. Volkow, my last question. There is a
    lot of hope in my home State that opioid-related overdoses may
    have peaked, but we have been seeing an alarming increase in
    methamphetamine overdoses now, and as you know there is no FDA
    approved treatments for methamphetamine dependence.
        Can you tell me what NIDA's efforts to development
    treatment for methamphetamine addiction is right now?
        Dr. Volkow. Well, you are asking me a question that
    actually literally makes me extraordinarily anxious and keeps
    me awake at night, because we are seeing the numbers of
    mortality increasing for methamphetamine and cocaine too, and
    even though we funded research to come up with treatments none
    of them have reached the outcomes that are actually necessary
    to get them approved and show them effective.
        However, what is very exciting in the whole area and
    possibility, relates to immunotherapies, and in fact, where we
    have done the greatest advance is developing monoclonal
    antibodies for capturing the drug so that the drug gets
    sequestered in the blood and never gets into the brain
    obviating any pharmacological effects, happens to be for its
    application on methamphetamine.
        So, we have brought those antibodies already into humans,
    and what we are trying to work right now is the extent to,
    which by partnering with some of the scientists who are part of
    the NIAID Institute and the Cancer Institute, on developing
    longer lived, the monoclonal antibodies extent to which we
    could apply them. Because they work, they capture it, the
    problem is they are not long-lasting, so you have to repeatedly
    immunize.
        So, this is one of our priorities as it relates to
    medications.
        In parallel of course, we are funding research in terms of
    behavioral interventions to try to actually improve the
    outcomes on individuals that are suffering from methamphetamine
    addiction.
        Senator Murray. Okay. Thank you very much, I really
    appreciate it. And thank you to all of you for being here
    today. I appreciate the great work you do.
        Senator Blunt. I have just a couple of more things as we
    finish up here.

                               YOUNG RESEARCHERS

        Dr. Lorsch, we talked about young researchers. I think you
    have also been experimenting with longer research times for
    grants. Would you talk about that and talk about whether there
    is any impact that your appropriation stream has on being able
    to do that?
        Dr. Lorsch. Thank you very much, Senator. We have developed
    a new program called Maximizing Investigators Research Awards,
    or MIRA, which has several goals, but one as you said, is to
    give a longer and more stable funding stream to investigators.
    We hope that by doing that, and by also giving them more
    freedom to basically follow their noses as their research
    evolves, we will allow them to do more ambitious research and
    to get faster to discoveries through this process.
        There are two parts of it; one is the established
    investigator part, and the other is the early-stage
    investigator part.
        The early-stage investigator part is actually particularly
    exciting right now because since the program started in 2016,
    we have seen a doubling of the number of early-stage
    investigators that we fund at the Institute, primarily through
    the MIRA program. We have seen a 60 percent increase in the
    number of applications from early-stage investigators. So, they
    are clearly speaking with their feet that this is the way they
    want to see science supported.
        And what is particularly exciting is we are actually
    funding them at a younger age, so all 3 years of the program,
    the median age of funding for early-stage investigators in MIRA
    is 37, whereas it is 38 for early-stage investigators funded
    through RO1s and we are hoping that trend is going to continue.
        What I will say for the record, is that one of my strategic
    goals for the Institute is to try to push that age of funding
    for MIRA down to 35. I think 37 is still too late to be getting
    your first grant award.
        Senator Blunt. Well, thank you for that.

                         NON-ADDICTIVE PAIN MEDICATION

        Dr. Volkow, you know we have had a 30 percent increase in
    NIH and we are all pleased about, and during that same period
    of time we have had a 1300 percent increase in money going to
    the opioid fight.
        I do not know that we have talked yet today about
    alternative research to have pain medicine that is not
    addictive. Do you have any more you want to add to that?
        Dr. Volkow. There are two components to it, one of them is
    in terms of the basic science that Francis was speaking of that
    allowed us to identify completely novel treatment targets,
    molecules or immunotherapies for management of pain.
        And then those interventions that do not rely on biologics
    or medicine, and that includes behavioral interventions to
    evaluate the extent that they can improve the outcomes, as well
    as an area that is very exciting in the whole area of brain
    diseases, is the use of neuromodulation technologies like
    magnetic resonance, transcranial magnetic resonance
    stimulation, or direct electrical stimulation, to modify
    certain areas of the brain, in means to improve outcomes.
        The research, for example, there are several papers that
    have shown positive effects for various chronic pain conditions
    that offers an opportunity. There is also, as part of the HEAL
    initiative, a project that is going to be evaluating
    comprehensive models of care, just as the CDC recommends for
    the management of chronic pain, that will determine the extent
    for which they are effective and optimize our understanding
    about what are the active ingredients and how to sustain them.
    And too, at the end recognize that chronic pain is an
    extraordinary, difficult condition to treat, and that it is
    terrigenous and that we may require to do what is done in
    cancer, personalize intervention.
        So, doing that research that will enable us to get there
    will be very important in helping patients suffering from
    severe chronic pain conditions.
        Dr. Collins. I just want to weigh in for a minute here and
    say how incredibly helpful it was for the Congress to identify
    this as an area, both of great need and of great opportunity,
    and the $500 million that you put into the budget beginning in
    fiscal year 2018 has made it possible for us to solicit truly
    bold ideas across all of NIH.
        We now have 20 of our institutes engaged in this, more than
    40 different funding opportunity announcements, some of which
    have already received grants, have been reviewed and are
    starting to be funded; some of which are still out there for
    solicitations. By the end of this fiscal year we will have put
    the largest infusion of research into finding nonaddictive
    alternatives for pain that has ever happened at NIH, in
    addition to funding a very large amount of efforts to try to
    help how to manage opioid use addiction, which is obviously our
    National crisis.
        We could not have done this at this scale without your
    help, and it has made all the difference.

                                     SEPSIS

        Senator Blunt. Good. I do not remember the first time I
    noticed that somebody's cause of death was sepsis. It does not
    seem to me it was that long ago, but it does seem to me that I
    see that often now.
        What are we trying to do there, and is that an NIH issue
    that you are dealing with?
        Dr. Collins. It is. Maybe I will ask Dr. Lorsch to say a
    little bit about the basic science part, and Dr. Fauci about
    the clinical efforts, because those are hand in hand.
        Dr. Lorsch. Thank you very much. Sepsis research is
    supported jointly by three main institutes, one is NIGMS, one
    is Dr. Fauci's Institute, NIAID, each of which fund about a
    third of sepsis research, and Heart, Lung, and Blood funds
    about a quarter of it and the remainder is Child Health and Dr.
    Rodger's institute.
        I became concerned a couple of years ago that the pace of
    research in the basic part of sepsis understand the mechanisms
    underlying the condition was not fast enough. So I put together
    a working group of our advisory council, which right now is
    examining our portfolio and the field and how it fits in with
    the rest of what NIH is funding, and they will be making
    recommendations to us at the May council meeting that we will
    have next month.
        Particularly they are going to be looking at the balance of
    research in animal models versus in humans. We are concerned
    that perhaps there is too much emphasis on looking at sepsis-
    like conditions in mice and not enough in actual human
    condition. And we are also looking at ways we can leverage
    clinical trials networks that are funded by other institutes
    that are already enrolling critically ill patients who may
    develop sepsis.
        And perhaps, Dr. Fauci wants to say a little bit about
    that.
        Dr. Fauci. Thank you, Mr. Chairman. The effort against
    sepsis as Dr. Lorsch has mentioned, is really multifaceted,
    because you have a micro-organism, a pathogen that triggers a
    process that is a physiologic and pathological process that
    leads to what we now know as sepsis. It is not just the microbe
    and it is not just the response; it is a combination of the
    two.
        NIAD's role is to study specifically the microbe itself,
    the virilism of the microbe, the processes that trigger these
    physiological and patho-physiological events, as well as
    treatment.
        And as Dr. Lorsch mentioned, we have a clinical trials
    network that we look at these patients, it is very difficult to
    actually study them, because when they come in it is such an
    acute situation that you have to move very quickly when you are
    doing a clinical trial. But we are working with other
    institutes, including the National Heart, Lung and Blood
    Institute, to do this kind of synergy of multiple approaches to
    what is a very complex and heterogeneous problem.
        Senator Blunt. Well, Senator Murray, we are about to finish
    here, is there anything that we should have asked that we did
    not ask Dr. Collins?
        Dr. Collins. You did a pretty fine job of covering a lot of
    the landscape with the folks who are here. And again, I have to
    say how much it has impressed me over the years about how much
    the members of this subcommittee have become so deeply
    knowledgeable about what we do.
        These conversations always end up being full of really rich
    details and digging into areas that we love to talk about. So,
    many thanks to you for all of the ways in which you have spent
    your time on these issues, and of course, we would love to
    invite you back out to NIH any time because we always have new
    things to show you.

                         ADDITIONAL COMMITTEE QUESTIONS

        Senator Blunt. All right. 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 to Francis S. Collins, M.D. Ph.D.
                    Questions Submitted by Senator Roy Blunt
                        china's thousand talents program
        Question. I'm very concerned that the NIH research community is not
    being adequately informed of the threats they are facing from foreign
    government programs specifically designed to undermine U.S. research.
    What specific steps are being taken to: (1) better inform the research
    community of the specific threat; (2) ensure there is disclosure of
    foreign collaborations and affiliations; and (3) implement controls to
    protect the integrity of the peer review system?
        Answer. NIH shares your concern about foreign government programs
    that are designed to undermine U.S. research. NIH is committed to
    working with other agencies and offices, including law enforcement, as
    well as with the extramural community, to identify and confront the
    risks these programs pose and to combat them. As described further
    below, NIH is employing a multi-pronged approach addressing individual
    situations and developing proactive programs to address these threats.
    Informing the Research Community
        NIH's efforts to inform and engage the research community are
    proceeding across multiple platforms. For example, multiple
    communications to the research community over the last several years
    have focused on the imperative that applicants and recipients inform
    NIH of foreign support, and the obligations and certifications of
    reviewers to protect the confidentiality of grant applications, study
    section deliberations, preliminary scoring and reviews. For example, an
    NIH Guide Notice \1\ issued in March 2018 reminded applicants and
    recipients of the requirement to disclose to their institution
    significant financial interests, which can include support coming from
    foreign governments or other foreign entities; the institution
    determines financial conflicts of interest that must be reported to NIH
    and managed on an ongoing basis by the institution. On August 23, 2018,
    the NIH Director took the unusual action of issuing a comprehensive
    statement on protecting the integrity of U.S. Biomedical Research. The
    Director also took the unprecedented step of issuing a letter to
    officials at approximately 10,000 recipient institutions. This letter
    informed the research community that the agency is aware that some
    foreign entities have mounted systematic programs to influence NIH
    researchers and peer reviewers, as well as to take advantage of the
    long tradition of trust, fairness, and excellence of NIH supported
    research activities. Furthermore, NIH convened a working group of the
    Advisory Committee to the NIH Director on Foreign Influences on
    Research Integrity. This panel was comprised of leaders in higher
    education, members of the extramural community, and experts in
    security, and was charged with assisting the Advisory Committee in
    making recommendations to the agency, which are currently being
    implemented.
    ---------------------------------------------------------------------------
        \1\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-
    160.html.
    ---------------------------------------------------------------------------
        In order to address specific cases brought to the attention of the
    agency, NIH has contacted nearly sixty institutions regarding concerns
    about scientists who may have failed to disclose foreign affiliations
    or significant financial interests stemming from foreign-based entities
    or governments. This approach has proven highly effective in both
    communicating concerns to the extramural research community,
    engendering partnerships to develop best practices, and gaining
    compliance with Federal and NIH grants requirements and policies. NIH's
    efforts have been widely reported within the science and popular press,
    e.g., by the Houston Chronicle,\2\ Science Magazine,\3\ and The Cancer
    Letter,\4\ which is expanding our impact. We are actively engaging the
    research community and in turn, they are actively partnering with us.
    For example, Penn State University,\5\ M.D. Anderson,\6\ and the
    University of California San Diego \7\ have posted new guidelines for
    faculty. Professional societies such as the American Society for
    Biochemistry and Molecular Biology \8\ are acting to share our concerns
    across the research community. We appreciate all the members of the
    research community who proactively work with us to address these
    matters.
    ---------------------------------------------------------------------------
        \2\ https://www.houstonchronicle.com/news/houston-texas/houston/
    article/MD-Anderson-fires-3-scientists-over-concerns-13780570.php.
        \3\ https://www.sciencemag.org/news/2019/04/universities-will-soon-
    announce-action-against-
    scientists-who-broke-nih-rules-agency.
        \4\ https://cancerletter.com/articles/20190426_3/.
        \5\ https://www.research.psu.edu/international_affiliations.
        \6\ https://www.mdanderson.org/newsroom/md-anderson-addresses-
    national-threat-of-foreign-
    influence-.h00-159302256.html.
        \7\ https://medschool.ucsd.edu/vchs/research-services/hssppo/
    review/Pages/Foreign-Involvement-.aspx.
        \8\ http://policy.asbmb.org/2019/01/02/updates-from-the-nih-
    advisory-committee-to-the-directors-december-meeting/.
    ---------------------------------------------------------------------------
        Furthermore, NIH regularly communicates with grantees to provide
    training and compliance support for issues involving conflict of
    interest requirements at NIH-led conferences such as the NIH Regional
    Seminars. This information is also communicated by NIH through
    professional organizations such as the Federal Demonstration
    Partnership, Society for Research Administrators, American Association
    of Universities, Council on Governmental Relations, Association of
    Public & Land Grant Universities, and the National Council of
    University Research Administrators. There have been a number of special
    meetings involving these groups and others to address the recent
    concerns on foreign influence. In addition, NIH recently developed an
    online training module on Financial Conflict of Interest as a resource
    for both NIH staff and the extramural community. NIH's outreach and
    engagement have facilitated extensive faculty outreach at research
    organizations as well as led to developing and sharing best practices.
        Moving forward, as Dr. Collins said during the Senate Appropriation
    hearing, ``We will not rest until we've looked at every possible
    example. We have to depend on the universities as our partners in this,
    but we are driving this process as vigorously as we can.'' Additional
    institutions will be contacted when new discoveries are made. NIH will
    continue to remind the extramural research community of the need to be
    transparent regarding other support, financial conflicts of interest
    and foreign components, to better address research threats.
        Finally, NIH is actively partnering with other Federal departments
    and agencies to address concerns related to undue foreign influence on
    the biomedical research enterprise. These Federal partners include the
    Central Intelligence Agency, Federal Bureau of Investigation, HHS
    Office of Inspector General, Department of Defense, Department of
    State, and the National Science Foundation.
    Ensuring Disclosure of Foreign Collaborations and Affiliations
        NIH requires institutions, as the applicants for and recipients of
    NIH funding, to ensure that individual investigators make all
    appropriate disclosures to their institution regarding other support,
    affiliations, and financial interests, whether or not they are
    employees of the institution. Institutions, in turn, must ensure that
    all applications and reports submitted to NIH are complete and
    accurate.
        Prior to making an award, NIH requests and reviews updated ``other
    support'' information for the program director/principal investigator
    and other key personnel identified in the grant application to ensure
    that updated information on all financial resources, whether Federal or
    non-Federal, foreign, commercial or institutional, available in direct
    support of an individual's research endeavors, are known and considered
    prior to award. This includes foreign financial support. NIH uses this
    information to ensure that sufficient levels of effort are committed to
    the project, there is no scientific, budgetary, or commitment overlap,
    and only the funds necessary to the approved project are included in
    the grant award.
        In addition, NIH applicants and recipients must request and receive
    approval for the inclusion of any foreign components of an NIH award. A
    foreign component is the performance of any significant scientific
    element or segment of the project outside of the United States, either
    by the recipient or by a researcher employed by a foreign organization,
    whether or not grant funds are expended.
        Among other obligations, the applicant organization must certify,
    and in some cases submit assurances, that they comply with the public
    policy requirements provided in the NIH Grants Policy Statement. These
    requirements are intended to ensure that recipient organizations handle
    their Federal awards responsibly. While NIH maintains oversight of our
    awards, we entrust our recipient organizations with the responsibility
    and accountability for successfully administering their grant award,
    including prudent fiscal management and other requirements spelled out
    in the NIH Grants Policy Statement.
        NIH will take action and has taken action where appropriate under
    its authority to address such concerns as part of its proper oversight,
    compliance, and stewardship roles. As an example, when NIH identifies
    noncompliance with the terms and conditions of award, it may take
    actions consistent with the regulatory requirements found in 45 CFR
    75.207 and 75.371 for grants and FAR 52.227-11 for contracts. Depending
    on the severity and duration of the noncompliance, NIH may decide to
    take one or more actions, which are also described in the NIH Grants
    Policy Statement, Section 8.5, Specific Award Conditions and Remedies
    for Noncompliance, including imposing specific award conditions,
    disallowing costs, withholding future awards for the project or
    program, suspending the award activities, making a referral for
    suspension or debarment, or terminating the award.
    Protecting the Integrity of the Peer Review System
        All participants in the NIH peer review system are responsible for
    promoting integrity. Maintaining integrity--including obligations of
    reviewers to keep application information confidential and secure,
    consistent with their certifications--in the peer review process is
    essential for ensuring robust exchange of scientific opinions and
    providing reliable input to NIH about which research projects it should
    support and maintaining public trust in science.
        In recent years, NIH has taken numerous steps to protect the
    integrity of the peer review process. In addition to issuing several
    Guide Notices and blogs on the confidentiality and integrity of peer
    review, NIH has referred many cases to the HHS Office of Inspector
    General for consideration of further action, including referrals for
    debarment or suspension, as well as removed the affected individuals
    from peer review service. Also, in the end of 2018, reviewer conflict
    of interest certifications were converted to completely electronic
    format, enabling more thorough assessment of compliance across the
    agency and in cases of individual breaches.
        The NIH Office of Extramural Research (OER) has expanded its
    internal training for NIH Scientific Review Officers (SROs) to raise
    their awareness of integrity concerns. OER held three interactive
    training sessions on peer review integrity in the last year, each event
    drawing hundreds of SROs. These events covered case studies largely
    based on actual events and stimulated lively discussion of the best
    course of action in each scenario. The NIH is also working to implement
    recommendations from the NIH Advisory Committee to the Director on
    Foreign Influences on Research Integrity that focus on peer review
    integrity. Further, NIH continues to explore new technologies and ideas
    to protect the integrity of the peer review process. For example, a new
    dashboard is being developed to assist the Office of the Director in
    identifying data needed to review possible peer review integrity
    violations. Finally, policies for permissions to access certain
    information are being re-assessed. Taken together, these efforts to
    communicate internally and externally, as well as modernize controls,
    are raising the profile on peer review integrity concerns and reducing
    risks.
                        research on social media impacts
        Question. Dr. Collins, as a father of a 14 year old, I understand
    the role that cell phones, social media, and video games play in an
    adolescent's life. There is a lot of competing research available that
    shows the potential mental and emotional effects that media may play.
    Conversely, media also may be a resource to find social and emotional
    support for teens. Can you discuss what role NIH is playing in this
    research? Specifically, can you provide a few examples of what type of
    studies you are doing?
        Answer. NIH is vigorously pursuing this area of research. Several
    NIH Institutes and Centers, including the Eunice Kennedy Shriver
    National Institute of Child Health and Human Development (NICHD), are
    researching the effects of increasing use of media by children and
    adolescents. New evidence shows that screen time use is growing with
    unknown long-term effects on health and development. Early data from
    the NIH-funded Adolescent Brain Cognitive Development (ABCD) study
    shows that only 37 percent of children in the study met the less than
    two hours per day of recreational screen time recommended by American
    Academy of Pediatrics (AAP) guidelines. According to the AAP, 95
    percent of teens have access to a smartphone, and 45 percent say they
    are online ``almost constantly.'' In April 2019, the World Health
    Organization issued new guidelines stating that to grow up healthy,
    ``children under five must spend less time sitting watching screens,''
    emphasizing that screen time should be replaced with interactive non-
    screen-based activities.
        NIH is committed to learning more about this issue. Just last year,
    NICHD hosted a workshop on media exposure and early child development,
    bringing together experts in this new field to share their individual
    perspectives regarding research gaps. Recommendations from some of the
    workshop panelists included developing meaningful measures of the
    impact of exposures to media, conducting neuroimaging research to look
    at the effects on developing brains, and parent education approaches. A
    recent NICHD-funded study found that exposure to media violence is a
    strong predictor of aggression and that parental monitoring is a
    significant factor against aggressive behavior. At the same time,
    social media can have positive effects; through its Adolescent Trials
    Network, NICHD is exploring the use of an interactive smartphone app as
    an intervention to help prevent the spread of HIV. Another study funded
    in 2018 is exploring whether books presented on a screen or with
    interactive enhancements confer the same benefits to a child's reading
    skills and socio-emotional development as print books. Screens also
    have been associated with delayed or insufficient sleep, which can lead
    to a number of chronic medical conditions in children and adolescents;
    another NICHD-funded study is exploring whether the light emitted by
    screens and other mechanisms affect children's circadian clocks.
        The ABCD \9\ is a longitudinal study of close to 12,000 children
    beginning at age 9-10 and continuing through adolescence and into early
    adulthood to understand how the experiences of adolescence shape brain,
    cognitive, social, and emotional development. When the children are 9
    and 10, they are asked questions about how much time they spend on
    different activities related to digital media (e.g., watching TV,
    playing video games, on social media, texting, video chatting). As they
    get older, they will be asked more in-depth questions about technology
    use. These data can then be correlated with other assessments within
    the study such as structural and functional MRI and measures related to
    mental health, cognition, and sleep, as well as be tracked over time as
    they mature. This comprehensive data set, led by the National Institute
    on Drug Abuse and supported by NICHD, the National Institute on Alcohol
    Abuse and Alcoholism, and the National Cancer Institute (NCI), will be
    disaggregated by sex, racial/ethnic group, and socioeconomic status, to
    allow researchers to address numerous questions related to adolescent
    brain development, thus informing future prevention and treatment
    efforts and public health strategies.
    ---------------------------------------------------------------------------
        \9\ https://abcdstudy.org/.
    ---------------------------------------------------------------------------
                                     ______

              Questions Submitted by Senator Shelley Moore Capito
                               pulmonary fibrosis
        Question. I have a question for you about pulmonary fibrosis, a
    devastating disease that affects many people in my State. A major area
    of interest in pulmonary fibrosis-related research is patient-centered
    clinical research--research that directly addresses issues of most
    importance to those suffering from the disease. This would include
    studies looking at reducing hospitalizations, improving symptoms, and
    prolonging life. For example, researchers are currently examining the
    chronic cough that pulmonary fibrosis patients cite as one of the
    symptoms that most affects their quality of life.
         In the context of pulmonary fibrosis, what are the NIH and the
    NHLBI doing to support clinical researchers focused on patient-centered
    outcomes, and how they are promoting the use of novel data sources such
    as real-world registries, wearables and other technology?
        Answer. The NHLBI continues to support a wide array of clinical
    trials and fundamental research studies as part of a multi-pronged
    approach to identify and enhance treatments for patients who suffer
    from pulmonary fibrosis (PF).
        In the fundamental discovery science area, NHLBI-funded researchers
    are studying the mechanisms of lung fibrosis. One research team
    recently found that fibrotic cell invasion in PF could be driven by a
    problem with immune checkpoints, which are cell surface proteins that
    keep immune responses in check. These same proteins are hijacked by
    cancer cells to evade the immune system, and are the target for a new
    class of cancer drugs, suggesting that similar drugs could be used to
    treat PF.\10\ Another group's research suggests that toxic byproducts
    of oxygen consumption (reactive oxygen species) may contribute to lung
    injury in idiopathic PF (IPF), which has led to a clinical trial of a
    potential new drug.\11\
    ---------------------------------------------------------------------------
        \10\ https://www.ncbi.nlm.nih.gov/pubmed/30763282.
        \11\ https://clinicaltrials.gov/ct2/show/NCT03865927.
    ---------------------------------------------------------------------------
        NHLBI supports trials evaluating a number of other potential
    therapies that target different aspects of pathology in IPF. Two multi-
    site clinical studies are investigating a combination of therapies that
    target autoantibodies--which stimulate the immune system to attack the
    body's own tissues; in PF, certain autoantibodies are known to cause
    acute breathing exacerbations.\12\ NHLBI's Pulmonary Trials Cooperative
    supports an ongoing study of antimicrobial therapy to reduce the risk
    of hospitalization and death from PF.\13\ Additionally, NHLBI's Centers
    for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases
    (CADET) program conducts preclinical research to help translate new
    understanding of disease mechanisms into better treatment for lung
    diseases, and is a developing potential new therapeutics for PF.
    ---------------------------------------------------------------------------
        \12\ https://clinicaltrials.gov/ct2/show/NCT03286556
    and https://clinicaltrials.gov/ct2/show/NCT01969409.
        \13\ https://clinicaltrials.gov/ct2/show/NCT02759120.
    ---------------------------------------------------------------------------
        The NHLBI also strongly encourages investigators to utilize patient
    registries, such as the Pulmonary Fibrosis Foundation's registry,
    whenever appropriate to identify, recruit, and retain patients for
    clinical research, including intervention trials and studies to better
    understand the disease process. Several current funding opportunities
    allow PF researchers to leverage existing registries and resources.
        The NHLBI also encourages PF researchers to contribute and use
    whole genome sequencing data that is available through our Trans-omics
    for Precision Medicine (TOPMed) program. TOPMed is one of three massive
    datasets that researchers will be able to access and query during a
    pilot phase of the NIH Data Commons, a cloud-computing environment that
    is part of the NIH Science and Technology Research Infrastructure for
    Discovery, Experimentation, and Sustainability (STRIDES) initiative.
    The NHLBI is also developing another resource called Data Storage,
    Toolspace, Access and analytics for biG-data Empowerment (DataSTAGE)
    that will integrate TOPMed and other datasets with analytical tools to
    provide computing power that will help researchers explore precision
    medicine for PF and other disorders.
        The NHLBI and other Institutes continue to support the development
    of technologies to ameliorate symptoms such as cough in patients with
    chronic lung diseases, including PF, in part through our small business
    research programs. For example, researchers supported by the National
    Institute on Aging (NIA) are developing a wearable monitoring device to
    better assess patients with chronic respiratory disease.\14\
    ---------------------------------------------------------------------------
        \14\ https://projectreporter.nih.gov/
    project_info_details.cfm?aid=9465334.
    ---------------------------------------------------------------------------
        The NHLBI also recognizes that aging has a significant impact on
    disease progression in patients with fibrotic lung diseases, and that
    there is a need for improved methods and tools to account for the
    interplay between aging and fibrosis. To this end, the NHLBI developed
    an initiative aimed at Deciphering the Molecular Landscape of Lung
    Aging in Humans,\15\ which is supporting four projects, including a
    Normal Aging Lung Atlas that will catalog dynamic gene expression
    changes in aging lung tissue at the single-cell level.\16\
    ---------------------------------------------------------------------------
        \15\ https://grants.nih.gov/grants/guide/rfa-files/rfa-hl-19-
    012.html.
        \16\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9657483.
    ---------------------------------------------------------------------------
                               vascular dementia
        Question. Vascular dementia is the second most common form of
    dementia, after Alzheimer's disease, affecting almost a third of people
    over age 70. The NIH just completed the first randomized clinical trial
    demonstrating that lowering of systolic blood pressure significantly
    reduces the occurrence of mild cognitive impairment, which is an
    established risk factor and often a precursor for dementia.
        As the incidence of dementia continues to rise, what is NHLBI doing
    to understand the connection between heart health and brain health--
    e.g. vascular dementia? What can people do to prevent it?
        Answer. Cardiovascular disease (CVD) is increasingly recognized as
    an important contributor to cognitive impairment and dementia.
    Fortunately, the science also suggests that maintaining a healthy heart
    can help maintain a healthy brain. A recent Alzheimer's Disease-Related
    Dementias (ADRD) Summit at NIH included a discussion of vascular
    dementia and how to continue to move the field forward.\17\
    ---------------------------------------------------------------------------
        \17\ https://meetings.ninds.nih.gov/?ID=21149.
    ---------------------------------------------------------------------------
        NIH is already leveraging several of its long-established cohort
    studies to better understand the connections between heart disease and
    dementia. NHLBI's Framingham Heart Study began 70 years ago, and has
    since expanded to include three generations of participants. The study
    has found that many of the risk factors for dementia are the same as
    those for heart disease, such as high blood pressure, cigarette
    smoking, lack of physical activity, obesity, and diabetes. A recent
    NIH-supported analysis of Framingham data found that high blood
    pressure during mid-life increases the risk of dementia later,
    suggesting that there are potential cognitive benefits from managing
    blood pressure in mid-life.\18\
    ---------------------------------------------------------------------------
        \18\ https://www.ncbi.nlm.nih.gov/pubmed/29117954.
    ---------------------------------------------------------------------------
        Several NIH cohort studies focused on minority populations have
    added new objectives to better understand the connection between
    vascular risk factors and brain health. NHLBI's Jackson Heart Study of
    CVD in African Americans was renewed in August 2018, and new clinical
    exams beginning in 2020 will include tests of cognitive function as
    well as brain imaging. Additionally, the National Institute of
    Neurological Disorders and Stroke (NINDS) is supporting projects that
    leverage data from cohort studies such as the Reasons for Geographic
    and Racial Differences in Stroke (REGARDS) study and the Northern
    Manhattan Study (NOMAS). To better understand and prevent risk of
    vascular brain disease in women, participants from the NHLBI-supported
    Women's Health Initiative are part of the Women's Health Initiative
    Strong & Healthy (WHISH), trial which is testing whether increasing
    physical activity will reduce the risk of CVD and cognitive decline in
    older women.\19\
    ---------------------------------------------------------------------------
        \19\ https://whish.stanford.edu/about/.
    ---------------------------------------------------------------------------
        In the basic research arena, the Molecular Mechanisms of the
    Vascular Etiology of Alzheimer's Disease (M\2\OVE-AD) Consortium,
    developed by the NIA in collaboration with NINDS, brings together six
    multi-disciplinary research teams to use a variety of computational and
    animal model approaches to better understand the complex molecular
    mechanisms by which vascular and metabolic risk factors influence the
    development of Alzheimer's and related dementias, with the ultimate
    goal to identify therapeutic targets and biomarkers.\20\
    ---------------------------------------------------------------------------
        \20\ https://www.nih.gov/news-events/news-releases/decoding-
    molecular-ties-between-vascular-disease-alzheimers.
    ---------------------------------------------------------------------------
        It is now known that brain changes typically begin years--if not
    decades--before people show symptoms, which suggests that a window of
    opportunity exists to prevent, slow, or delay the onset of cognitive
    decline. A recent analysis of the Framingham Heart Study examined
    whether adherence to the American Heart Association's (AHA)
    Cardiovascular Health Guidelines was associated with improved brain
    health. The analysis found a lower risk of incident stroke, dementia,
    cognitive decline, and brain atrophy among participants who adhered to
    the AHA recommendations, which includes maintaining a healthy body mass
    index, healthy diet, nonsmoking status, normal total cholesterol,
    normal blood pressure, and physical activity.\21\
    ---------------------------------------------------------------------------
        \21\ https://www.ahajournals.org/doi/full/10.1161/
    strokeaha.115.012608.
    ---------------------------------------------------------------------------
        A 2017 National Academies of Sciences report supported by NIH
    concluded that there is encouraging but inconclusive evidence for
    several potential approaches to guard against cognitive decline and
    dementia, including blood pressure management for people with
    hypertension, increased physical activity, and cognitive training.\22\
    Recent NIH-funded studies add to the weight of evidence that aggressive
    treatment of hypertension may protect against cognitive decline. The
    NIH-funded Systolic Blood Pressure Intervention Trial (SPRINT) trial
    investigated whether aggressive systolic blood pressure reduction--down
    to less than 120 mm Hg, rather the prior target of 140 mm Hg--could
    reduce the risk of heart attack, stroke, and death in people over age
    50 who have hypertension. A sub-study, the SPRINT Memory and Cognition
    IN Decreased Hypertension (MIND) trial, evaluated whether this
    aggressive treatment would also lower the risk of dementia. These
    studies were stopped early because the treatment clearly protected
    against CVD. After about 5 years of follow-up in SPRINT MIND, there was
    no significant change in dementia risk, perhaps because of the study's
    shortened duration. However, there was almost 20 percent lower risk of
    mild cognitive impairment, a well-established precursor of
    dementia.\23\
    ---------------------------------------------------------------------------
        \22\ http://www.nationalacademies.org/hmd/Reports/2017/preventing-
    cognitive-decline-and-
    dementia-a-way-forward.aspx.
        \23\ https://jamanetwork.com/journals/jama/fullarticle/2723256.
    ---------------------------------------------------------------------------
                                     ______

                Questions Submitted by Senator Cindy Hyde-Smith
                                opioid addiction
        Question. Dr. Collins, how is NIH investing in research to identify
    genetic components that may make particular individuals more
    susceptible to opioid addiction? What is the current status of the
    science in this area? Are additional funds needed to expand this
    research?
        Answer. Many individuals affected by OUD have a family history of
    addiction to opioids or other substances, however, research to date
    indicates that OUD does not have a clear pattern of inheritance. The
    increased risk among members of an affected family is likely due in
    part to shared genetic factors, but it is also likely related to
    environment and other non-genetic influences that are shared by family
    members.
        Separating the complexities of genetic and non-genetic factors that
    affect OUD risk is a crucial pillar of efforts to stem the tide of the
    opioid crisis and advances NIH's broader goals of understanding the
    mechanisms underlying addiction to inform effective prevention and
    treatment strategies. Accordingly, NIH has fostered a robust and
    multidisciplinary research portfolio to examine the genetic
    underpinnings of OUD. There are currently 67 active NIH-funded projects
    focused on opioid addiction and genetics, as identified in NIH's public
    database, RePORTER. Some of these projects are highlighted below.
        One of the common tools in NIH's arsenal to investigate the role of
    genetics in disease is a genome-wide association study, or GWAS. A GWAS
    involves examining genetic variations (genotypes) across the complete
    sequences of DNA, or genomes, of many different people to find genetic
    variants associated with a disease or trait (phenotypes). There have
    been six GWAS projects studying OUD phenotypes that identify several
    single nucleotide polymorphisms (SNPs), or variations in a single DNA
    nucleotide, as potentially significant. These variations are being
    examined to validate their association with OUD. The National Institute
    on Drug Abuse's Genetics Consortium, founded in 1999 to coordinate
    efforts of investigators studying substance use disorders and addictive
    behaviors, is currently conducting its own GWAS, which includes samples
    from more than 10,000 people. Recent work in psychiatry genetics
    suggest that sample sizes larger than 10,000 are needed to identify
    genome wide significant results.
        In addition, NIDA is seeking to leverage resources of commercial
    companies to identify genetic variants for prescription opioid misuse
    and has issued a Request for Information via FedBizOpps to identify
    companies that can execute such an initiative (Solicitation
    75N95019R00053: Addressing the Opioid Crisis: Genetic Variants for
    Prescription Opioid Abuse).
        Current Status of the Science: While research in this field is
    still underway, there is already a body of evidence that suggests a few
    key themes in the complex interplay between genetics and addiction:
      --The dose of methadone needed to successfully treat OUD is affected
            by genetic variations in the mu opioid receptor gene and in the
            gene for the enzyme that metabolizes methadone.\24,25,26\
    ---------------------------------------------------------------------------
        \24\ Smith AH, Jensen KP, Li J, et al. Genome-wide association
    study of therapeutic opioid dosing identifies a novel locus upstream of
    OPRM1. Mol Psychiatry 2017;22:346-52.
        \25\ Crist RC, Doyle GA, Nelson EC, et al. A polymorphism in the
    OPRM1 3'-untranslated region is associated with methadone efficacy in
    treating opioid dependence. The pharmacogenomics journal 2018;18:173-9.
        \26\ Dennis BB, Bawor M, Thabane L, Sohani Z, Samaan Z. Impact of
    ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose
    and treatment response in patients with opioid addiction: a systematic
    review and meta-analysis. PloS one 2014;9:e86114-e.
    ---------------------------------------------------------------------------
      --Genetic variations in the mu opioid receptor gene are also
            associated with risk for heroin addiction and with severity of
            heroin addiction.\27,28,29,30\
    ---------------------------------------------------------------------------
        \27\ Schwantes-An TH, Zhang J, Chen LS, et al. Association of the
    OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to
    Substance Dependence in a Collaborative de novo Meta-Analysis of
    European-Ancestry Cohorts. Behavior genetics 2016;46:151-69.
        \28\ Hancock DB, Levy JL, Gaddis NC, et al. Cis-Expression
    Quantitative Trait Loci Mapping Reveals Replicable Associations with
    Heroin Addiction in OPRM1. Biological Psychiatry 2015.
        \29\ Zhang Y, Picetti R, Butelman ER, Ho A, Blendy JA, Kreek MJ.
    Mouse model of the OPRM1 (A118G) polymorphism: differential heroin
    self-administration behavior compared with wild-type mice.
    Neuropsychopharmacology : official publication of the American College
    of Neuropsychopharmacology 2015;40:1091-100.
        \30\ Xu J, Lu Z, Xu M, et al. A heroin addiction severity-
    associated intronic single nucleotide polymorphism modulates
    alternative pre-mRNA splicing of the ? opioid receptor gene OPRM1 via
    hnRNPH interactions. J Neurosci 2014;34:11048-66.
    ---------------------------------------------------------------------------
      --Copy Number Variations (CNVs) (or variability in the number of
            times a sequence of DNA is repeated) are associated with opioid
            dependence. In one sequence, a chromosomal deletion is
            associated with being protective against opioid dependence, and
            duplication of the same part of the chromosome increased risk
            for opioid dependence.\31\
    ---------------------------------------------------------------------------
        \31\ Li D, Zhao H, Kranzler HR, et al. Genome-wide association
    study of copy number variations (CNVs) with opioid dependence.
    Neuropsychopharmacology 2015;40:1016-26.
    ---------------------------------------------------------------------------
      --Variations in genes that code for proteins associated with the
            signaling of glutamate, a widespread neurotransmitter in the
            brain, have also been associated with development of opioid
            addiction and regulation of opioid withdrawal.\32,33,34\
    ---------------------------------------------------------------------------
        \32\ Nelson EC, Agrawal A, Heath AC, et al. Evidence of CNIH3
    involvement in opioid dependence. Mol Psychiatry 2016;21:608-14.
        \33\ Reti IM, Crombag HS, Takamiya K, et al. Narp regulates long-
    term aversive effects of morphine withdrawal. Behavioral neuroscience
    2008;122:760-8.
        \34\ Crombag HS, Dickson M, Dinenna M, et al. Narp deletion blocks
    extinction of morphine place preference conditioning.
    Neuropsychopharmacology 2009;34:857-66.
    ---------------------------------------------------------------------------
      --A gene coding for a protein that is important for the way neurons
            form connections with one another regulates opioid tolerance
            and opioid-induced hyperalgesia.\35\
    ---------------------------------------------------------------------------
        \35\ Donaldson R, Sun Y, Liang D-Y, et al. The multiple PDZ domain
    protein Mpdz/MUPP1 regulates opioid tolerance and opioid-induced
    hyperalgesia. BMC Genomics 2016;17:313.
    ---------------------------------------------------------------------------
        Question. Are additional funds needed to expand this research?
        Answer. Investing in research is fundamental, and NIH will continue
    to explore opportunities to expand the scope and impact of genetic
    research on OUD. For example, an expert panel convened by the NIDA
    Genetics Consortium recently highlighted the value in conducting a GWAS
    on opioid naive surgical patients to identify genetic variants
    associated with persistent opioid use and other opioid-related
    outcomes. This would be an opportunity to potentially identify genetic
    variants among surgical patients who become opioid dependent.
                                     ______

                 Questions Submitted by Senator James Lankford
                            fetal tissue/stem cells
        Question. During an appropriation hearing in the House of
    Representatives, Rep. Andy Harris asked you about the ongoing fetal
    tissue research at NIH, but there were some outstanding questions from
    his line of questioning. I share Rep. Harris' concern over the use of
    fetal tissue research at NIH and would like more information as it
    relates to ongoing studies that use fetal tissue research.
        From my understanding, you recently extended a fetal tissue
    contract with the University of California San Francisco (UCSF).
        From where is the tissue obtained that UCSF is providing to NIH?
        Answer. UCSF obtained fetal tissue as it became available from
    elective and legal abortions performed at the UCSF clinic in San
    Francisco and that would otherwise be discarded. Per the June 5, 2019,
    statement from the Department of Health and Human Services, the
    contract expired on June 5, 2019, and there will be no further
    extensions.\36\
    ---------------------------------------------------------------------------
        \36\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
    department-of-health-and-human-services.html.
    ---------------------------------------------------------------------------
        Question. How old are the fetuses that were obtained from UCSF that
    are used in the study?
        Answer. The contract required the delivery of humanized mouse
    models. The contractor proposed the collection of human fetal tissue in
    order to create the humanized mouse models. NIH did not specify
    gestational age of the tissue being collected. As noted above, this
    contract expired on June 5, 2019, and there will be no further
    extensions.
        Question. Why was the decision made to extend this contract before
    HHS finished its audit of fetal tissue research?
        Answer. The contract with UCSF had an option year that needed to be
    exercised prior to the completion of the HHS audit. The contract was
    extended to ensure continuity of service until the audit is completed
    and a final decision was made about the contract. As noted above, this
    contract expired on June 5, 2019, and there will be no further
    extensions.
        Question. How many studies is NIH conducting with fetal tissue?
        Answer. The Estimates of Funding for Various Research, Condition,
    and Disease Categories (RCDC) provides official NIH figures on research
    spending by category. For fiscal year 2018, RCDC lists 200 grants and
    projects that involve research with human fetal tissue.\37\ Please also
    see the June 5, 2019, statement from the Department of Health and Human
    Services about NIH-supported research using human fetal tissue.
    ---------------------------------------------------------------------------
        \37\ https://report.nih.gov/categorical_spending.aspx.
    ---------------------------------------------------------------------------
        Question. The research conducted by the NIH affords invaluable
    knowledge and understanding of the infectious diseases we face today.
    Indisputably, NIH funding is vital to improving healthcare and
    protecting American lives. That being said, we must ensure that we hold
    taxpayers' dollars with highest regard and direct our limited resources
    to projects that not only better our country but reflect the will of
    the people.
        As revealed by the Select Panel on Infant Lives investigation,
    Planned Parenthood officials have admittedly changed abortion
    procedures to procure intact fetal body parts for sale. The fact that
    an industry has been created around the sale of aborted baby parts is
    deeply disturbing, and I firmly believe we must do all that we can to
    ensure taxpayers' dollars are used responsibly and ethically when it
    comes to federally funded research involving fetal tissue.
        What steps has NIH taken to partner with hospitals to procure fetal
    tissue that has been donated after a spontaneous abortion or
    miscarriage as opposed to tissue that is acquired after an elective
    abortion?
        Answer. NIH funded a major effort through five tissue bank programs
    to collect and examine tissue donated from women who had spontaneous
    abortions or ectopic pregnancies. The results were published in the
    Journal of the American Medical Association in 1995.\38\ From over
    22,000 obstetric admissions, tissue from 1,250 spontaneous abortions
    and 247 ectopic pregnancies was obtained. Most of the specimens
    recovered consisted of maternal or extraembryonic tissue. Of the
    embryonic collections, less than 1 percent would have been useful for
    clinical use. 71 percent of embryonic samples were degenerated; 79
    percent had bacterial contamination (despite use of aseptic collection
    techniques); and 40 percent had chromosomal abnormalities.
    ---------------------------------------------------------------------------
        \38\ https://jamanetwork.com/journals/jama/fullarticle/385456.
    ---------------------------------------------------------------------------
        Question. Has NIH considered limiting its procurement of fetal
    tissue obtained this way? If not, please explain why.
        Answer. NIH-funded research summarized above has established that
    fetal tissues from miscarriages (spontaneous abortions) and ectopic
    pregnancies are not feasible sources for research. Please also see the
    June 5, 2019, statement from the Department of Health and Human
    Services about NIH-supported research using human fetal tissue.\39\
    ---------------------------------------------------------------------------
        \39\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
    department-of-health-and-human-services.html.
    ---------------------------------------------------------------------------
        Question. Since President Obama's Executive Order 13505 ``Removing
    Barriers to Responsible Scientific Research Involving Human Stem
    Cells'' in March 2009, NIH has had wide access to human embryonic stem
    cells. As you know, this EO revoked a previous EO from President Bush
    that outlined ethical principles for stem cell research.
        As you know, some may claim that because stem cells themselves are
    not human embryos, there is no need to limit the amount available. But
    because the cells come from human embryos, NIH has an ethical
    obligation to value and honor the human life that contributed to such
    cells.
        While I have received some information on the types of research in
    which NIH uses ``human embryonic stem cells (hESCs)'', I am unaware of
    any validated, successful patient treatment from embryonic stem cells.
        Additionally, as you know alternatives to embryonic stem cell
    research exist. In 2012, the Nobel Prize in Physiology or Medicine was
    awarded to two researchers for their discovery of induced pluripotent
    stem (iPS) cells, which mimic the qualities of embryonic stem cells but
    do not use embryos in any way. Similarly, NIH has had great success in
    treating and curing more than 70 diseases using adult stems cells and
    iPS cells. Despite this, it is my understanding that NIH continues to
    expand its embryonic stem cell research to cell lines not already
    included on the NIH Human Embryonic Stem Cell Registry.
        How many new cell lines has NIH added to its Registry since EO
    13505 was enacted?
        Answer. Executive Order 13505 directed NIH to issue new guidance on
    research with human stem cells, including human embryonic stem cells
    (hESCs).\40\ NIH subsequently issued the NIH Guidelines for Human Stem
    Cell Research (Guidelines) on July 7, 2009.\41\ The Guidelines
    established strict new criteria for the NIH Director to determine the
    eligibility of the use of specific hESC lines in NIH-funded research.
    The NIH Director has approved 398 hESC lines for use in NIH-supported
    research under this policy, including 10 of the 21 cell lines that were
    also eligible for use under the policy of the prior administration. The
    NIH Director has also determined that 70 hESC lines are not eligible
    for use in NIH-supported research, primarily due to inadequacies in the
    embryo donation consent process.
    ---------------------------------------------------------------------------
        \40\ https://www.govinfo.gov/content/pkg/FR-2009-03-11/pdf/E9-
    5441.pdf.
        \41\ https://stemcells.nih.gov/policy/2009-guidelines.htm.
    ---------------------------------------------------------------------------
        Question. Why has NIH chosen to add more cell lines to its registry
    instead of using cells already on the registry?
        Answer. Part of the stated purpose of the Executive Order was `` .
    . . to expand NIH support for the exploration of human stem cell
    research.'' So, NIH developed a new policy, which included stricter new
    requirements regarding the embryo donation process. Under current
    policy, hESCs can only be used by NIH funded researchers if the embryos
    were created using IVF for reproductive purposes, no longer needed by
    the parents, and the embryos were donated by those parents with
    voluntary, written, informed consent. NIH also included new
    requirements that certain information be given to the potential donors
    during the consent process, such as what will happen to the embryos,
    and how long they have to change their minds.
        Some of the newer hESC lines have characteristics that are more
    suitable for clinical use, including reduced exposure to animal
    products and viruses. Some are also more flexible in their ability to
    form different tissue types. There are more than 100 hESC lines
    approved under the current policy that have mutations associated with
    particular diseases, providing useful cell models for studying those
    diseases.
        Question. Why has NIH not used IPS cells for research instead of
    using hESCs?
        Answer. NIH funds a range of stem cell research, using induced
    pluripotent stem cells (iPSCs) as well as hESCs. In fiscal year 2018,
    NIH awarded $468 million for human iPSC research and $278 million for
    hESC research. NIH is currently funding a significant amount of pre-
    clinical research using iPSCs. For example, an investigator in the
    National Eye Institute's intramural program is developing an iPSC-
    derived cell therapy for age-related macular degeneration.\42\ There
    are also other investigational cell therapies developed from human
    induced pluripotent stem cells (hiPSCs) in clinical trials now (not
    funded by NIH) for age-related macular degeneration, graft versus host
    disease, and Parkinson's disease.
    ---------------------------------------------------------------------------
        \42\ https://irp.nih.gov/pi/kapil-bharti.
    ---------------------------------------------------------------------------
                                     ______

                  Questions Submitted by Senator Patty Murray
                             chief data strategist
        Question. For the past 3 years, this committee has urged NIH to
    focus on developments in data science as it relates to biomedical
    research. What is possible to achieve by harnessing the vast amount of
    data produced in science is still unknown. But what we do know, is with
    proper leadership, vision, and tools, big data has the potential to
    help scientists unlock infinite breakthroughs and discoveries in
    biomedical research. At the direction of this committee, in May 2018
    NIH released a strategic plan for data science, which includes
    recommendations to advance data infrastructure and data stewardship in
    support of the data ecosystem at NIH and improve NIH's expertise in
    this space.
        After a year of efforts to recruit for the new CDS position, NIH
    still has not filled this role.
        What is the status of the job search for the Chief Data Strategist?
    Please include details on the recruitment, number of applicants and
    interviews, significant next steps, and timeline for completion. Are
    there specific obstacles to filling this role that NIH needs to
    address?
        Answer. The recruitment for the NIH Chief Data Strategist is
    currently open for receiving applications, until filled. The
    recruitment for this position opened on May 9, 2018. To date, NIH has
    received 59 application packages which met the basic qualifications for
    the position, held rating meetings, and conducted interviews. An
    external search firm was secured to work in concert with the search
    committee to seek and encourage highly qualified candidates to apply.
    Over 20 ads were placed online with periodicals, data science
    organizations, and diversity associations. Currently, a video is being
    produced to highlight the data science activities at NIH, which will be
    released to encourage candidates to apply to this position. The
    recruitment timeline is currently open ended.
        Data science is a burgeoning field of study, involving both private
    sector and academic leaders. The NIH is hoping to fill this position
    with an individual who has the knowledge and unique skill set needed to
    accelerate NIH progress in data science and to expand collaborations
    worldwide. As you note, it has been exceedingly challenging to attract
    someone that would bring the unique combination of knowledge and skills
    to the position. Federal salary limits are one limiting factor and the
    constraints related to financial holdings that result from Federal
    employment are another. The NIH is committed to filling this position
    as soon as possible and is determined to fill the position with the
    ideal candidate.
        Question. Since the recruitment process is taking a considerable
    amount of time, what is NIH doing during this interim period, prior to
    hiring a CDS, to move the work forward?
        Answer. Executive leadership of data science efforts at the NIH
    continues to be provided by the Interim Associate Director for Data
    Science, a position temporarily being filled by the Principal Deputy
    Director, NIH. The Scientific Data Council, co-chaired by the Director,
    National Institute of General Medical Sciences, and the Director,
    National Institute of Biomedical Imaging and Bioengineering, is also
    providing advice and oversight to ensure forward movement on trans-NIH
    data science activities. Other executive staff, including the Directors
    of the Center for Information Technology and the National Library of
    Medicine have been playing key roles in moving forward critical data
    science efforts. The Director of the NIGMS Division of Biomedical
    Technology, Bioinformatics, and Computational Biosciences is providing
    essential leadership for, and helping to fully operationalize, the
    Office of Data Science Strategy (ODSS). Other Office of the Director
    staff are also playing key roles for activities that are being led and
    funded by ODSS. While we have not yet been able to fill the Chief Data
    Strategist position, we have made significant progress in implementing
    components of the NIH Strategic Plan for Data Science.
        Question. Given the challenges of bringing someone with the
    appropriate skills, vision and background into the CDS position, what
    alternatives is NIH exploring?
        Answer. As noted above, NIH contracted with an external search firm
    to work closely with the search committee to seek and encourage highly
    qualified candidates to apply. Over 20 ads were placed online with
    periodicals, data science organizations, and diversity associations. A
    video is being produced to highlight the data science activities at NIH
    which will be released to encourage candidates to apply to this
    position. In the meantime, NIH leadership is considering whether other
    NIH employees could fill this vacancy on a temporary basis.
        Question. Has NIH consulted with organizations that face similar
    challenges, such as DoD, NASA, and universities attempting to solve
    some of the same cutting edge data challenges?
        Answer. Yes. Through both formal interagency processes and informal
    leadership and staff level conversations, NIH consults and shares
    information with other Federal research agencies facing similar
    challenges. As part of the search for the CDS, we have also engaged in
    extensive outreach, including to other Federal agencies, e.g.,
    Department of Energy and the National Science Foundation.
        We are continuing efforts to find the best candidate for this
    critical position at NIH. Some important new approaches we will be
    taking are listed below:
      --NIH is about to launch a social media and marketing campaign for
            the CDS position--possibly as early as the week of May 28. You
            may see Twitter and Facebook posts from NIH, Dr. Collins, the
            CDS Search Committee co-chairs, and various other NIH-related
            handles. NIH is also asking other Federal government agencies
            to help amplify our posts. An executive search firm will be
            helping NIH cross-promote on LinkedIn.
      --NIH has produced a final cut of a 5-minute video about the
            position. View on YouTube here: https://youtu.be/92arhggy4xI.
      --Dr. Collins will use his blog to highlight the important of this
            position to NIH's future with an embedded version of the video.
      --An easier-to-use URL for the position is now available:
            www.nih.gov/CDS http://www.nih.gov/CDS.
      --NIH will make additional efforts to identify and capitalize on NIH
            leadership that have personal connections with Silicon Valley
            and other tech company executives/VIPs who may have good
            candidates to recommend.
      --A slide will be provided for use by NIH leadership in any
            presentations they are making to the tech community.
      --A 30 second teaser video, based on the YouTube video linked above,
            will be released as part of a social media marketing campaign
            to attract candidates.
        Question. Last year, the Committee assumed that implementation of
    certain components of the strategic plan--including developing
    performance measures and specific milestones for the plan's
    objectives--was delayed due to the open job search. What, if any, steps
    in the strategic plan have been implemented to date?
        Answer. The NIH has moved forward in implementing multiple
    components of the NIH Strategic Plan for Data Science. Currently, a
    team of NIH employees detailed to the ODSS is coordinating the efforts
    of nearly thirty implementation working groups with members
    representing nearly all NIH Institutes and Centers. ODSS has also
    established a Technical Implementation Working Group composed of high-
    level data science experts across NIH to advise the Office on technical
    matters related to implementation tactics. A non-exhaustive summary of
    current activities aligned with each goal of the strategic plan is
    provided below:
        Goal 1: Support a highly efficient and effective biomedical
    research data infrastructure.
      --ODSS executed a contract with BioTeam, Inc. to develop a basic
            needs requirement document that would directly inform the
            infrastructure development of a NIH-wide data ecosystem that
            meets FAIR principles. The contractor is currently in the
            process of collecting data ecosystem use cases and conducting a
            gap analysis across high-profile NIH data systems. A final
            report is anticipated in September 2019.
      --ODSS is providing technical assistance to the NIH Office of Science
            Policy (OSP) in the review of current policies regarding Data
            Access Committees to streamline and increase the efficiency of
            review.
      --The National Center for Biotechnology Information and CIT have
            developed an initial strategy for a trans-NIH approach to user
            authentication and authorization for access to data sets. This
            technical solution will be developed into a testable prototype
            in the next few months.
      --The STRIDES Initiative, a NIH partnership with industry-leading
            cloud service providers (currently, Google and Amazon) to
            provide discounted cloud storage and compute access to
            biomedical researchers, continues to migrate high-value data
            sets to cloud platforms. ODSS is providing oversight of this
            CIT-managed initiative and has engaged nearly 40 data programs
            in both the intra- and extra-mural communities. NIH is
            developing the policies and procedures for making this
            innovative partnership available to all NIH-funded biomedical
            researchers in order to accelerate scientific discoveries
            leading to new health technologies.
        Goal 2: Promote modernization of the data-resources ecosystem.
      --A strategic plan implementation team co-led by NLM and NIGMS
            developed new funding opportunity announcements (FOAs) that
            will address the objective of separating support for databases
            and knowledgebases and sets forth appropriate resource criteria
            and review criteria that must be met in order to receive NIH
            support. These FOAs are currently under review with an
            anticipated release date this summer.
      --This April, NIH held a workshop to share criteria for
            trustworthiness of data repositories and to educate biomedical
            data managers on the CoreTrustSeal certification requirements.
            Information from the workshop will be used to promote
            sustainable and trustworthy data infrastructures in the
            biomedical arena. In a related effort, NLM conducted a
            comprehensive analysis of criteria for open-access data sharing
            repositories that receive NIHsupport and will soon publish a
            public request for information to solicit additional input on
            draft criteria.
      --The NIH Scientific Data Council is reviewing how NIH could
            potentially integrate existing clinical data elements with the
            industry-adopted fast healthcare interoperability resources
            (FHIR) specification to enable the exchange of healthcare,
            clinical and basic research data across different systems.
        Goal 3: Support the development and dissemination of advanced data
    management, analytics, and visualization tools.
      --ODSS is engaged in planning a workshop to bring systems integration
            specialists from the private sector so that NIH data scientists
            can learn the latest approaches to the optimization of data
            analysis tools and algorithms.
      --NSF and NIH/ODSS will hold a workshop in June to discuss
            opportunities for joint funding of data science research
            programs, with a particular emphasis on AI/ML approaches to
            solving complex data analysis problems in biology and medicine.
      --ODSS executed a contract with FigShare, providing NIH-funded
            researchers with access to online open access repository where
            researchers can preserve and share their research outputs,
            including figures, datasets, images, and videos.
        Goal 4: Enhance workforce development for biomedical data science.
      --Please refer to NIH's description of efforts in data science
            workforce development addressed in the response to a specific
            question for the record on this topic.
        Goal 5: Enact appropriate policies to promote stewardship and
    sustainability.
      --The NIH OSP recently completed its analysis of public comments on
            proposed provisions for a draft data management and sharing
            policy. OSP is in the process of incorporating the public
            feedback and will release a draft policy statement for further
            public consultation.
        Question. The Committee included $30 million to support the Chief
    Data Strategist's work in fiscal year 2019. What is the status of NIH's
    plan for this funding?
        Answer. The NIH has engaged in a multi-step planning process to
    identify the most pressing trans-NIH needs for the data science funding
    provided by Congress. The $30 million is being used to advance the
    trans-NIH data ecosystem--that is, we are working to make currently
    siloed data storage and workspaces connect (interoperable) by
    establishing standards, building infrastructure and tools to allow
    different data repositories to talk to each other, and defining common
    data elements and standards.
                    dpcpsi/office of strategic coordination
        Question. The Data Commons Pilot Phase was initiated under the New
    Models of Data Stewardship program, implemented in support of the
    Strategic Plan for Data Science. This project was supposed to run
    through fiscal year 2020 and was tasked with developing a four-year
    roadmap for the data commons. What is the status of this roadmap, how
    is NIH implementing the associated recommendations, and what are the
    next steps for this initiative?
        Answer. The NIH Data Commons Pilot, part of the Common Fund's New
    Models of Data Stewardship program, aimed to accelerate new biomedical
    discoveries by developing and testing a cloud-based platform where
    investigators could store, share, access, and interact with digital
    objects (data, software, etc.) generated from biomedical and behavioral
    research. By connecting the digital objects and making them accessible,
    the Data Commons was intended to foster novel scientific research that
    wasn't possible before, including hypothesis generation, discovery, and
    validation. The program supported the NIH Strategic Plan for Data
    Science \43\ goal to develop new, cutting-edge methods for storing,
    sharing, and analyzing NIH supported datasets in the cloud.
    ---------------------------------------------------------------------------
        \43\ https://datascience.nih.gov/strategicplan.
    ---------------------------------------------------------------------------
        From 2017-2018, researchers funded as part of the NIH Data Commons
    Pilot Phase Consortium (DCPPC) tested the best ways to build and
    implement the cloud-based platform described above. They iteratively
    experimented with a series of key capabilities needed for the Commons
    to operate and meet standards for being FAIR--findable, accessible,
    interoperable, and reusable. Three different and high-value test case
    data sets helped in setting policies, processes, and architecture for
    the Data Commons Pilot Phase.
        Development of a roadmap for modernizing the biomedical data
    science ecosystem requires trans-NIH coordination, most appropriately
    managed by the NIH Office of Data Science Strategy (ODSS). Therefore,
    ODSS is developing a broad, trans-NIH data ecosystem strategy informed
    by the tools and best practices developed by the DCPPC. The Common Fund
    will continue to test, evaluate, and refine a subset of deliverables
    from the Data Commons Pilot Phase, working with Common Fund programs to
    establish a cloud-based data ecosystem for Common Fund datasets.
                     dpcpsi/office of data science strategy
        Question. Research organizations are exploring the best ways to
    create research data commons. Private sector communities of companies
    and extramural research institutions, like Sage Bionetworks, Penn
    State, and Google's datacommons.org have demonstrated success. Even
    other Federal agencies have successfully established data commons, such
    as the National Science Foundation big data innovation hubs, and are
    further along than NIH. Furthermore, we must ensure NIH is also
    learning from less successful attempts at driving data infrastructure,
    such as caBIG, which saw little traction in the community and was
    widely criticized. As good stewards of taxpayer investments, what is
    NIH doing to avoid ``reinventing the wheel'' and how is NIH planning to
    leverage data commons work already being done extramurally?
        Answer. NIH appreciates the opportunity to highlight how we are
    building upon the advances in academia and industry to create a highly
    integrated biomedical research data ecosystem. A principle stumbling
    block across data science is the compartmentalization of data--from
    biomedical research data, disease specific data, health records and
    data resulting from clinical trials. These data silos impede discovery
    of commonalities across diseases and inhibit a cross-disciplinary
    understanding that will rapidly accelerate innovation in the biomedical
    research enterprise. Our goal at NIH is to leverage data and
    information from different studies and across diseases to empower
    investigators to ask new questions and make new discoveries to improve
    human health.
        To do so, NIH is investing in many data commons efforts, including
    NHGRI ANVIL, NCI Cancer Research Data Commons, All-of-Us Research
    Program, NIMH Data Archive, NHLBI Data STAGE and others.\44\ We have
    recently completed a NIH Data Commons Pilot study and we have
    undertaken a comprehensive analysis of this, and the other commons
    efforts listed above, to learn from our past and current efforts and to
    determine successful approaches with existing capabilities.
    ---------------------------------------------------------------------------
        \44\ NHGRI AnVIL is designed to be an interoperable resource for
    the genomics community to co-locate data, storage and computing with
    commonly used services for analyzing and sharing data.
        NCI Cancer Research Data Commons is a virtual, expandable
    infrastructure to provide secure access to cancer-specific data to
    allow researchers to analyze, share and store their work, in a cloud
    environment.
        NIMH Data Archive is a collaborative resource that contains human
    subjects research data for Autism research
        NHLBI Data STAGE is a digital environment that allows for access to
    NHLBI datasets and innovative data analysis capabilities, in a cloud
    environment.
        All-of-Us Research Program provides a cloud-environment to gather
    and serve data from one million or more people living in the United
    States.
    ---------------------------------------------------------------------------
        NIH is also working with leading industry partners, including
    Google and Amazon, and academic collaborators, to leverage those
    experience, expertise and technologies as we work to connect high-value
    NIH data systems. An early example of this is the cross-NIH effort to
    create an industry-standard system that will allow any NIH researcher a
    single-entry point to NIH data resources, with the appropriate
    security-enabled data access.
        In addition, the National Center for Advancing Translational
    Sciences' (NCATS) Biomedical Data Translator program is building an
    informatics platform that aims to bridge the current symptom?based
    diagnosis of disease with research?based molecular and cellular
    characterizations through interrogation of relationships across the
    full spectrum of data types (e.g., disease names, clinical signs and
    symptoms, to organ and cell pathology, genomics, and drug effects). The
    Translator is not a database but rather is focused on identifying data
    integration and inclusion barriers and exploring inferential or
    predictive models that would provide new insights into biology, health,
    and disease. The Translator will find and connect existing data,
    provide previously unknown insights into diseases and possible
    treatments, and make inferences and predictions even when data are
    missing to translate basic data science to clinical and public health
    practices.
        Together these, and other efforts articulated in the NIH's
    Strategic Plan for Data Science, aim to maximize the value of the data
    generated through NIH-funded efforts to enable biomedical discovery and
    innovation. Doing so is critical for keeping the United States at the
    forefront of biomedical research and ensuring continued advances toward
    improving the Nation's health.
        Question. Beyond the efforts in NIGMS, what is the NIH doing to
    encourage, support and incorporate computational science training in
    other scientific fields beyond those like genomics and neuroscience
    which have already embraced it?
        Answer. NIH is committed to training the next generation of
    researchers across biomedical related disciplines, including computer
    science. Twelve of the agency's Institutes, Centers, and Offices (ICOs)
    support a funding opportunity, the Mentored Quantitative Research
    Career Development Award (K25), to attract investigators whose
    quantitative science and engineering research has thus far not been
    focused on questions of health and disease. This funding opportunity
    supports professionals with quantitative (e.g., mathematics,
    statistics, economics, computer science, imaging science, informatics,
    physics, chemistry) and engineering backgrounds to integrate their
    expertise with NIH-relevant research. Another cross-NIH effort,
    Predoctoral Training in Advanced Data Analytics for Behavioral and
    Social Sciences Research--Institutional Research Training Program
    (T32), is funding training opportunities for predoctoral students in
    data analytics for behavioral and social science research and is
    supported by a number of ICOs. Other trans-NIH funding opportunities
    are being planned to broaden the expertise of the extramural biomedical
    community and will be released in the coming months. Additionally, the
    National Library of Medicine recruits data scientists to work in their
    institute through several coordinated postdoctoral training programs,
    and has a joint program with the National Institute of Dental and
    Craniofacial Research to recruit computer scientists to postdoctoral
    studies in the dental field. Other ICOs across NIH recruit
    computational experts to work in their intramural research programs
    based on the lab's specific needs.
        Training programs for NIH staff and extramural researchers who are
    putting data into Science and Technology Research Infrastructure for
    Discovery, Experimentation, and Sustainability Initiative are currently
    being offered. These trainings target general use of the cloud
    platforms as well as generic [mock/dummy] tool and dataset use in cloud
    environments.
        NIH has also initiated several fellowships to expand the expertise
    of the NIH internal workforce, by bringing computationally-savvy
    individuals to work in NIH offices. For example, through Coding it
    Forward's Civic Digital Fellowship and the NIH Office of Intramural
    Training and Education Graduate Data Science Summer Program, ODSS will
    bring 23 data scientists to NIH campus this summer to be placed in
    offices and laboratories throughout the agency. Other programs led by
    NIH to bring computational experts into the Federal workforce include
    the Emerging Leaders in Data Science Fellowship, led by NIAID, and the
    Big Data Scientist Training Enhancement Program, co-led by NCI and the
    Department of Veterans Affairs.
                                  rare cancers
        Question. At least 95 percent of 400 known forms of cancer meet the
    American Cancer Society criteria of affecting fewer than 6 Americans
    per 100,000 per year, yet in 2018 nearly 80 percent of cancer patients
    with no approved targeted therapeutic for their cancer have a rare
    cancer. Many of these cancer patients are faced with decades-old
    treatment protocols that include harsh chemotherapies which are
    frequently ineffective for their cancers. What are NIH, NCI and NCATS
    doing to develop more therapeutics for these neglected rare cancers?
        Almost 1 in 3 new cancer diagnoses is for a rare cancer. However,
    rare cancers suffer from critical gaps in funding, available data, and
    basic and translational science. In 2017, over 148 forms of rare cancer
    received no direct funding from NIH, and that gap in spending is
    associated with a lack of FDA-approved targeted therapies available for
    those cancers. Simultaneously, just 34 out of 380 forms of rare cancer
    received almost 40 percent of NIH funding that was directed to rare
    cancers. What is being doing to encourage greater support for research
    into rare cancers?
        I understand 95 percent of all cancers are rare forms, and
    increased use of molecular subtyping can lead to more accurate
    diagnoses of those precise forms. But that is only if this subtyping is
    done. I understand molecular diagnostics are seldom used for the
    majority of patients and data on cancer subtypes is rarely shared among
    researchers and physicians. What can be done to improve molecular
    analysis for patients, and to permit patients to anonymously and
    publicly share their data with researchers and drug developers?
        A key to understanding and developing targeted cancer treatments is
    the ability to research tumor cell lines, yet cells lines for rare
    cancers are frequently difficult to obtain, especially for smaller
    companies, due to high costs or licensing restrictions. When they are
    available, they sometimes do not share the genetic profiles of the
    cancers they are meant to represent. Why is that? How can we change
    that to accelerate research to save lives in the near-term?
        Treatment for pediatric cancers carries a tremendous burden for
    survivors throughout their childhood and adult lives, frequently due to
    the use of caustic chemotherapy agents. There is only one currently
    available targeted therapy that is specifically approved for a
    childhood cancer, neuroblastoma. What is being done to ensure that
    childhood cancers receive appropriate levels of funding for
    translational research that turns basic science into new therapies?
        Over 550,000 Americans were newly diagnosed with a rare cancer in
    2018, but SBIRs, which are a major source of translational funds to
    bridge the drug development 'valley of death', primarily fund common
    cancers. In fact, in the 5-year span between 2013 and 2017, 262 forms
    of cancer, all rare, did not receive any directed funding--that's over
    65 percent of all types of rare cancer. What is being done to ensure
    that SBIR funding is addressing the critical translational gap for
    these neglected rare cancer patients?
        Over half a million Americans were newly diagnosed with a rare
    cancer in 2018. For over 100 of those cancers, there are no available
    datasets in the most significant microarray repository in the world,
    GEO. Unfortunately for those patients whose cancers are not
    represented, they have an almost 7-fold decreased likelihood of having
    a targeted therapy. What is being doing to ensure that all forms of
    cancer have significant dataset presence in publicly available data
    repositories?
        Answer. Rare cancers all qualify as rare diseases, which are
    diseases or conditions affecting fewer than 200,000 people in the U.S.
    The National Center for Advancing Translational Sciences (NCATS) has
    several programs and initiatives focusing on rare diseases, including
    rare cancers. Specifically, the Office of Rare Diseases Research (ORDR)
    is dedicated exclusively to accelerating treatments and research to
    benefit rare disease patients.
        Advancing research on rare cancers is an important focus across the
    NCI portfolio as well. As our understanding of cancer expands, we now
    know it is not one disease, but hundreds, if not thousands, of cancer
    types and subtypes--a collection of rare diseases. A quarter of all
    cancer deaths each year are due to rare cancers. Although new
    treatments are always being developed, finding new effective treatments
    for rare cancers is challenging for many reasons. Additionally, this
    translational and clinical research is only possible due to NCI's
    sustained investment in basic science that advances understanding and
    progress for all cancer types, including rare cancers.
        Question. What are NIH, NCI and NCATS doing to develop therapeutics
    for these neglected rare cancers?
        Answer. Several NCI-supported research efforts aim to advance and
    accelerate the development of targeted cancer therapies for rare cancer
    types and subtypes diagnosed in children and adults. The following
    narrative describes some of the major NCI initiatives that may benefit
    rare cancer patients, but it is not an exhaustive list of the
    Institute's investments in rare cancer research.
        The cancer research community continues to recognize that cancer is
    made up of a collection of hundreds, if not thousands, of subtypes
    defined by these characteristics. NCI-supported research like The
    Cancer Genome Atlas \45\ and the Pediatric TARGET (Therapeutically
    Applicable Research to Generate Effective Treatments) Initiative,\46\
    as well as the Pediatric Cancer Genome Project led by Washington
    University and St. Jude Children's Research Hospital,\47\ have been
    critical to advancing this field. As a result of these efforts and
    other relevant research, ``cancer'' is increasingly recognized as a
    collection of rare cancer subtypes, each of which will likely require a
    somewhat different treatment. NCI's ongoing efforts include research to
    support the development and evaluation of precision approaches to
    cancer therapy--including targeted chemotherapy and immunotherapy, and
    combination therapy approaches based on the molecular profile of the
    cancer.
    ---------------------------------------------------------------------------
        \45\ https://cancergenome.nih.gov/.
        \46\ https://ocg.cancer.gov/programs/target.
        \47\ https://www.stjude.org/research/pediatric-cancer-genome-
    project.html.
    ---------------------------------------------------------------------------
        As part of the Cancer Moonshot, NCI launched the Rare Tumor Patient
    Engagement Network in fiscal year 2018, leveraging the unique resources
    of the NCI intramural research program and the NIH Clinical Center to
    bring together national and international investigators, patients,
    advocacy groups, and industry to comprehensively study rare tumors and
    provide exceptional patient care. Under the umbrella of this effort,
    NCI has also launched the Moonshot Pediatric, Adolescent, and Young
    Adult Rare Tumors (MyPART) Network, a collaboration of scientists,
    patients, family members, advocates and healthcare providers to find
    treatments for rare cancers.\48\ The MyPART Network will collect
    samples like blood, saliva, and biopsy tissue from people with rare
    tumors to study how rare tumors grow, share data from rare cancer
    samples with other scientists, build new ways of testing new
    treatments, and design new clinical trials for rare cancers.\49\
    Another component of this rare tumors initiative, the NCI Comprehensive
    Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) within the
    intramural program aims to advance the understanding of rare adult
    central nervous system (CNS) cancers by establishing and fostering
    patient-advocacy-provider partnerships and networks to improve
    approaches to care and treatment. Although all primary adult CNS tumors
    can be considered rare, NCI-CONNECT is starting with 12 types, each
    with less than 2,000 patients diagnosed a year. NCI-CONNECT intends to
    address these challenges and unmet needs by connecting patients,
    providers, researchers and community organizations to work in
    partnership.\50\
    ---------------------------------------------------------------------------
        \48\ https://ccr.cancer.gov/research/cancer-moonshot.
        \49\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor/about/
    what-is-mypart.
        \50\ https://ccr.cancer.gov/neuro-oncology-branch/connect.
    ---------------------------------------------------------------------------
        The NCI-MATCH Trial \51\ is an important research program for rare
    cancers for which there is not a standard of care or cancers that no
    longer respond to standard treatment. This nationwide trial, which has
    enrolled patients in all 50 States, analyzes patients' tumors to
    determine whether they contain gene abnormalities for which a targeted
    drug exists and then assigns patients to treatment based on the
    abnormality. Using this approach, the NCI-MATCH trial holds promise for
    improved treatment options for both common and rare cancers. The trial
    originally had ``set aside'' 25 percent of screening accrual to be for
    rare cancers, to ensure that more common cancers were not over-
    represented. Ultimately 62.5 percent of the over 6,000 patients
    screened for MATCH represented rare cancers. However, even with 6,000
    patients screened, some trial arms did not complete accrual due to the
    low frequency of a particular variant in the population. Thus, patients
    continue to be enrolled in these trial arms through the Rare Variants
    Initiative. Launched in May 2017, the Rare Variants Initiative casts a
    wider net for patients through collaborations with additional
    commercial and academic partners that will help find patients with
    uncommon genetic variants and let their doctors know they may be
    eligible for the MATCH trial.
    ---------------------------------------------------------------------------
        \51\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
    nci-supported/nci-match.
    ---------------------------------------------------------------------------
        The mission of the NCI Experimental Therapeutics (NExT) Program
    \52\ is to advance clinical practice and bring improved therapies to
    patients with cancer by supporting the most promising new drug
    discovery and development projects. For those institutions
    collaborating with NCI, NCI may leverage its scientific expertise and
    various contract and grant resources toward the implementation and
    development of submitted projects. The NCI will partner with successful
    applicants to facilitate the milestone-driven progression of new
    anticancer drugs (small molecules, biologics) and imaging agents
    towards clinical evaluation and registration.
    ---------------------------------------------------------------------------
        \52\ https://next.cancer.gov/entryToPipeline/default.htm.
    ---------------------------------------------------------------------------
        Additionally, NCATS supports the Tissue Chip for Drug Screening
    Program, which is an innovative program that enables the development of
    microphysiologic systems to develop human tissues on bioengineered
    chips. This program seeks to better understand human disease, model
    human organs and organ systems, and potentially serve as toxicology and
    drug screening systems. Many rare disease indications have been
    included in the tissue chip program, including tuberous sclerosis,
    which is a rare disease that leads to benign tumor growth in the brain.
    This program is planning to support development of chips that can be
    used to inform potential clinical trials on rare diseases and, in
    conjunction with NCI, rare cancers will be included as part of the
    research focus.
        NCATS also supports the Therapeutics for Rare and Neglected
    Diseases (TRND) and the Bridging Interventional Development Gaps
    (BrIDGs) programs. TRND supports pre-clinical development of
    therapeutic candidates intended to treat rare or neglected disorders
    with the goal of enabling an Investigational New Drug application
    (IND). TRND works in collaboration with external partners, such as
    academia and industry on these projects, and TRND provides scientific
    expertise and resources to further therapeutic development. Researchers
    working on rare cancers are eligible for assistance from this program.
    Similarly, BrIDGs assists researchers in advancing promising
    therapeutic agents thought late-stage pre-clinical development toward
    an IND and clinical testing. Currently, these programs are working on
    several rare cancer-related projects, including work on pancreatic
    cancer and core binding factor (CBF) leukemia.
        Notable NCATS programs led through the ORDR relevant to rare
    cancers include:
      --The Rare Diseases Clinical Research Network (RDCRN) \53\ provides
            cooperative awards to multi-center multi-disciplinary consortia
            who study three or more related rare diseases at a time. This
            program has supported research into >250 rare diseases since
            its inception, including some rare cancer-related diseases and
            conditions. Applications for new consortia members are
            currently being considered and awards will be announced around
            June-July 2019. Some of the applications being considered
            include rare cancers and cancer-related conditions that may be
            funded in collaboration with NCI.
    ---------------------------------------------------------------------------
        \53\ https://ncats.nih.gov/rdcrn.
    ---------------------------------------------------------------------------
      --The Bench-to-bedside (B2B) grant program \54\ is run by the NIH
            Clinical Center (CC), and NCATS ORDR supports four B2B awards
            each year for rare disease indications. These grants are for
            intramural/extramural partnerships leveraging the CC and other
            resources to facilitate translating bench research toward
            clinical trials. Several rare cancer-related B2B grants have
            been supported through this program over the past 15 years.
            Some examples of rare cancer and cancer-related B2B awards
            include, but are not limited to: T-cell adoptive therapy for
            viral infection after stem cell transplantation and CAR-
            modified CD8+ memory stem cells targeting B-cell malignancies,
            among others.
    ---------------------------------------------------------------------------
        \54\ https://clinicalcenter.nih.gov/ccc/btb/.
    ---------------------------------------------------------------------------
      --The Toolkit for Patient-focused Therapies Development (``Toolkit'')
            \55\ and the Rare Diseases Registry program (RaDaR) \56\ assist
            patients and patient groups, who play a large role in
            therapeutics development and research for rare diseases,
            including rare cancers. Toolkit and RaDaR provide advice,
            tools, templates and best practices for initiating and
            furthering rare disease research programs and registries,
            respectively. Toolkit and RaDaR are web-based freely accessible
            resources that anyone can access and use.
    ---------------------------------------------------------------------------
        \55\ https://rarediseases.info.nih.gov/toolkit.
        \56\ https://registries.ncats.nih.gov/.
    ---------------------------------------------------------------------------
      --The Scientific Conferences (R13 and U13) Grant program \57\
            provides small grants to help co-fund scientific conferences
            and meetings. Priority areas for NCATS include translational
            sciences and rare diseases, including rare cancers. In the past
            several years, grants have included conferences on rare cancers
            and cancer-related indications, including, but not limited to,
            cholangiocarcinoma, cancer vaccines, RASopathies, and cancer
            immunotherapy, among others.
    ---------------------------------------------------------------------------
        \57\ https://grants.nih.gov/grants/funding/r13/index.htm.
    ---------------------------------------------------------------------------
        Question. What is being doing to encourage greater support for
    research into rare cancers?
        Answer. The NIH and the NCI rely heavily on scientific peer review,
    in which highly trained outside scientists initially review
    investigator-initiated research proposals and score them based on
    factors such as scientific merit, potential impact, likelihood of
    success, and disease burden. Thereafter, the National Cancer Advisory
    Board conducts a review of the research proposals. NCI does not
    establish predetermined targets for a specific disease area or research
    category, and does not set preestablished funding levels for cancer
    types or specific areas of cancer research. It is important to note
    that NCI and NIH do not consider disease burden to be limited to how
    many people are diagnosed with a disease or condition, but rather uses
    a broader lens to capture the impact of a health condition as measured
    by mortality, morbidity, financial cost, and other indicators.
    Accordingly, NIH's Institutes and Centers support special initiatives
    based on public health need, including burden of disease. Comprehensive
    portfolio analysis and programmatic evaluation are also critical to
    these programmatic decisions and development of special initiatives.
    Examples span common and rare cancers, such as NCI's RAS Initiative,
    which focuses on molecular alterations in the RAS family of genes and
    pathways, responsible for driving the development and progression of
    several common and rare cancers. Other examples include the Cancer
    Moonshot, which is supporting research relevant across cancer types and
    scientific areas, and NCI's proposed Childhood Cancer Data Initiative.
        In addition, the Institute strives to balance strategic efforts to
    address public health needs with its basic scientific research
    portfolio. Basic research, which represents approximately half of the
    NCI research portfolio, is vital to achieve progress in the cancer
    types for which little or no progress has been made. Decades of basic
    research investments from NCI and NIH have demonstrated the value of
    basic research as a foundation for clinical advances, even though the
    basic research may lack a direct initial connection to a specific
    disease, the serendipitous discoveries of basic research illuminate
    pathways for future clinical breakthroughs.
        Question. Molecular diagnostics are seldom used for the majority of
    patients and data on cancer subtypes is rarely shared among researchers
    and physicians. What can be done to improve molecular analysis for
    patients, and to permit patients to anonymously and publicly share
    their data with researchers and drug developers?
        Answer. Detailed molecular characterization of tumors has
    demonstrated the heterogeneity of cancer and can identify genetic
    alterations that may allow for the selection of targeted therapies for
    patients based on the unique profile of a patient's tumor. This is the
    basis for the NCI-MATCH trial mentioned above. However, it is important
    to point out that targeted therapies currently only exist for a small
    number of known genetic alterations.
        Although comprehensive genomic profiling is technically feasible,
    its current application in clinical practice is fragmented and there
    are barriers to wide-spread profiling. These barriers include cost,
    lack of standardized genomic profiling panels and tumor collection,
    insufficient evidence of broad-based clinical utility, and lack of
    infrastructure to harmonize and share data across the clinical and
    research community.
        The NCI is addressing several of these barriers. Precision medicine
    clinical trials like NCI-MATCH and others seek to provide the evidence
    of clinical utility of treating a patient based on a unique
    characteristic of the patient's tumor regardless of the type of tumor.
    In addition, other NCI research supported through the Cancer Moonshot's
    direct patient engagement efforts,\58\ including the Rare Tumor Patient
    Engagement Networks mentioned above, will support molecular
    characterization of patients' tumors, directly engage patients to
    participate in clinical trials, and share tumor profiling data with the
    research community and the individual patient participants through a
    secure linked network of databases.
    ---------------------------------------------------------------------------
        \58\ https://www.cancer.gov/research/key-initiatives/moonshot-
    cancer-initiative/implementation/patient-engagement.
    ---------------------------------------------------------------------------
        The NCI has established the Cancer Research Data Commons as a part
    of a larger National Cancer Data Ecosystem to support precision
    medicine. The Data Commons will provide an information platform to
    support the integration of genetic information about patients and their
    tumors with data on how the tumors respond to therapy. The Data Commons
    will also incorporate additional data such as imaging and clinical data
    from patients to identify approaches to cancer care that will improve
    patient outcomes. Other NCI efforts include the development of a cancer
    data aggregator to link various data types across the Data Commons and
    ultimately allow for analysis of multimodal data sets; and an encrypted
    unique patient identifier to link patient level data while protecting
    personally identifiable information. The former is critically important
    to address patient privacy issues that exist with publicly sharing
    their data.
        Cost is an important issue outside of the scope of the NCI mission.
    However, NCI notes that in March 2018 CMS took an important step in
    addressing this barrier by finalizing a National Coverage Determination
    that covers diagnostic laboratory tests using Next Generation
    Sequencing for patients with advanced cancer.\59\
    ---------------------------------------------------------------------------
        \59\ https://www.cms.gov/newsroom/press-releases/cms-finalizes-
    coverage-next-generation-
    sequencing-tests-ensuring-enhanced-access-cancer-patients.
    ---------------------------------------------------------------------------
        Question. A key to understanding and developing targeted cancer
    treatments is the ability to research tumor cell lines, yet cells lines
    for rare cancers are frequently difficult to obtain, especially for
    smaller companies, due to high costs or licensing restrictions. When
    they are available, they sometimes do not share the genetic profiles of
    the cancers they are meant to represent. Why is that? How can we change
    that to accelerate research to save lives in the near-term?
        Answer. As a public sponsor of biomedical research, NIH, including
    the NCI, is committed to supporting national and international efforts
    that encourage the sharing and dissemination of important research
    resources. NIH also recognizes the need to support reasonable incentive
    structures that facilitate commercial development or translation of
    basic research findings. Restricted availability of unique research
    resources, upon which further studies depend, can impede the advance of
    research. Conversely, sharing biomaterials, reagents and data in a
    timely manner has been an essential element to stimulate rapid research
    progress on many model organisms for biomedical research. The NIH is
    interested in continuing to ensure that the research resources
    developed with NIH funding are made readily available in a timely
    fashion to the research community for further research, development,
    and application, which will further the research enterprise and
    accelerate the development of products and knowledge of benefit to the
    public.
        With regard to rare cancers specifically, low incidence rates of
    rare cancers mean both patients and researchers face unique challenges.
    To address these concerns, NCI supports development of several research
    resources and makes them available to the extramural research community
    for use in investigator-initiated research projects and NCI-supported
    programs. Such resources include the Human Cancer Models Initiative
    (HCMI) \60\ and the NCI Patient-Derived Models Repository (PDMR).\61\
    Many of NCI's resources are catalogued on the Resources for
    Researchers\62\ website which provides information on how to obtain the
    resources.
    ---------------------------------------------------------------------------
        \60\ https://ocg.cancer.gov/programs/HCMI.
        \61\ https://pdmr.cancer.gov/, https://www.cancer.gov/news-events/
    cancer-currents-blog/2018/nci-pdmr-cancer-research-models.
        \62\ https://www.cancer.gov/research/resources.
    ---------------------------------------------------------------------------
        The HCMI is a collaborative international consortium that is
    generating 1,000 novel, next-generation, cancer models from patient
    tumors that are clinically and molecularly characterized. HCMI-
    developed models and related genomic and clinical data are available as
    a community resource without excessive intellectual property (IP)
    constraints. The NCI is contributing to the initiative by supporting
    four Cancer Model Development Centers (CMDCs) at the Broad Institute,
    Cold Spring Harbor Laboratory, Weill Cornell Medicine, and Stanford
    University. These cancer models will serve as valuable resource for
    translational cancer research and will contribute to developing
    innovative therapeutic strategies, identifying novel diagnostic
    markers, and individualizing patient treatment plans. In addition, the
    initiative will make resources such as protocols used for model
    development, SOPs, and other model-associated support available to aid
    the research community to generate additional models. There are
    currently 19 models available through the HCMI searchable catalog.\63\
    ---------------------------------------------------------------------------
        \63\ https://hcmi-searchable-catalog.nci.nih.gov.
    ---------------------------------------------------------------------------
        The PDMR is mainatained by the Frederick National Laboratory for
    Cancer Research and is a national repository of patient-derived
    xenografts developed from patients with solid tumors. These models are
    clinically-annotated with molecular information available in an easily
    accessible database for the extramural community. Since the launch of
    the PDMR in early 2017, 166 public models have been developed from 163
    unique patients, and new models continue to be added for cancer types
    already existing in the repository. Several new cancer types are now
    available in the PDMR collection, including some rare cancers. These
    new cancer models are of high value to the research community and
    include: several gynecologic cancers (ovarian, vaginal, carcinosarcoma,
    and cervical), small cell lung cancer (a subtype of lung cancer that is
    a rare disease), Hurthle cell neoplasm (a rare and often aggressive
    form of thyroid cancer), Osteosarcomas, chondrosarcoma, squamous cell
    skin carcinoma, Merkel cell carcinoma (a rare and aggressive form of
    skin cancer), mesothelioma (a rare type of lung cancer). The primary
    goal of this repository is to make a publicly available archive and
    repository of tumor samples and models that are fully characterized
    from a molecular and clinical perspective, and that are easily
    accessible to the extramural community at a very modest cost.
        NCI also supports pediatric cancer cell lines and models to address
    key challenges in the development of new therapies for children with
    cancer (all childhood cancers are considered rare diseases). NCI's
    Preclinical Testing Consortium (PPTC) \64\ develops reliable
    preclinical testing data for pediatric drug candidates that can be used
    to inform new agent prioritization decisions. The PPTC consists of a
    Coordinating Center and five Research Programs that perform in vivo
    testing of pediatric anticancer drug candidates for a particular cancer
    (sarcoma and renal, neuroblastoma, osteosarcoma, leukemia, and brain
    tumors). The PPTC collaborates with pharmaceutical companies and
    academic drug developers to systematically test candidate agents
    against well-credentialed panels of genomically characterized childhood
    cancer models to identify those investigational agents most likely to
    have clinical activity against childhood cancers. For example, in 2011,
    the PPTC developed a model for a subtype of pediatric low-grade
    astrocytoma (PLGA, a type of brain tumor) with a mutation in a gene
    called BRAF and identified a targeted therapy, selumetinib, for
    additional research. Building upon these findings, the PBTC conducted a
    Phase 1 trial of selumetinib.\65\ In this trial, children with BRAF-
    mutated PLGAs responded to treatment by showing tumor shrinkage. Based
    on these promising findings, the trial is now in a Phase 2 expansion
    with results from several cohorts reported in 2017 showing that
    selumetinib is active for patients with two subtypes of BRAF-mutated
    PLGAs.\66\
    ---------------------------------------------------------------------------
        \64\ http://www.ncipptc.org/.
        \65\ https://clinicaltrials.gov/ct2/show/NCT01089101.
        \66\ http://ascopubs.org/doi/abs/10.1200/
    JCO.2017.35.15_suppl.10504.
    ---------------------------------------------------------------------------
        Question. What is being done to ensure that childhood cancers
    receive appropriate levels of funding for translational research that
    turns basic science into new therapies?
        Answer. Pediatric cancer research remains a top priority for the
    NCI. Each year the Institute identifies the best research opportunities
    to build upon the foundation of basic science, further develop the
    scientific understanding of genetic drivers of childhood cancers,
    identify effective therapies, and enhance the quality of life for
    pediatric cancer survivors.
        When considering the Institute's investments in any category of
    disease research, NCI does not make decisions about funding based on
    predetermined targets for a specific disease area or research category.
    Rather, NCI relies on technical and scientific peer review, in which
    highly trained outside investigators perform an initial review of
    research proposals and evaluate them on factors such as scientific
    merit, likelihood of success, and potential impact. Thereafter, the
    National Cancer Advisory Board, which includes members with pediatric
    oncology expertise, also conducts a review of the research proposal.
    NCI leadership further evaluates proposals to consider factors such as
    scientific novelty and overall representation of the research topic
    within the NCI portfolio.
        Recognizing that childhood cancers are distinct from adult cancers,
    NCI supports numerous targeted programs aimed at advancing research in
    pediatric oncology. These efforts include:
      --The Children's Oncology Group (COG),\67\ part of NCI's National
            Clinical Trials Network (NCTN), develops and coordinates
            pediatric clinical trials across more than 200-member
            institutions. In addition to conducting late-phase clinical
            trials, the COG receives NCI support for the Phase 1 and Pilot
            Consortium,\68\ which conducts early-phase trials and pilot
            studies to rapidly introduce new anticancer agents into
            pediatric care.
    ---------------------------------------------------------------------------
        \67\ https://www.childrensoncologygroup.org/.
        \68\ https://www.childrensoncologygroup.org/index.php/phase-1-home.
    ---------------------------------------------------------------------------
      --The Pediatric Oncology Branch (POB) \69\ in NCI's Center for Cancer
            Research, part of NCI's intramural research program, conducts
            high-risk, high-impact basic, translational, and clinical
            research.
    ---------------------------------------------------------------------------
        \69\ https://ccr.cancer.gov/Pediatric-Oncology-Branch.
    ---------------------------------------------------------------------------
      --The NCI-COG Pediatric MATCH Trial,\70\ launched in July 2017, tests
            molecularly targeted therapies in children and adolescents with
            advanced cancers who have few other treatment options. This
            nationwide trial is open to children and adolescents from 1 to
            21 years of age and currently has eight treatment arms.
    ---------------------------------------------------------------------------
        \70\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
    nci-supported/pediatric-match.
    ---------------------------------------------------------------------------
      --Other efforts include the Pediatric Preclinical Testing Consortium
            (PPTC),\71\ the Therapeutically Applicable Research to Generate
            Effective Treatments (TARGET) \72\ program, the NCI
            Experimental Therapeutics (NExT) Program,\73\ the Childhood
            Cancer Survivor Study (CCSS),\74\ the Pediatric Provocative
            Questions (PQ) Program,\75\ the Pediatric Brain Tumor
            Consortium (PBTC),\76\ the Pediatric Cancer Immunotherapy
            Trials Network (CITN),\77\ and the New Approaches to
            Neuroblastoma Therapy (NANT) \78\ Consortium.
    ---------------------------------------------------------------------------
        \71\ http://www.ncipptc.org/.
        \72\ https://ocg.cancer.gov/programs/target.
        \73\ https://next.cancer.gov/.
        \74\ https://www.cancer.gov/types/childhood-cancers/ccss.
        \75\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-217.html.
        \76\ https://www.pbtc.org/.
        \77\ https://ctep.cancer.gov/MajorInitiatives/
    cancer_immunotherapy_trials_network.htm.
        \78\ http://www.nant.org/.
    ---------------------------------------------------------------------------
      --The Childhood Cancer Data Initiative proposed in the President's
            Budget will seek to leverage existing Federal authorities to
            effectively and efficiently coalesce different types of data
            currently collected for pediatric cancer cases across the wide
            variety of entities that produce and maintain it. As childhood
            cancers represent less than 1 percent of all new cases of
            cancer diagnosed in the United States each year, NCI recognizes
            the need to study the basic biology of pediatric cancers to
            develop relevant preclinical models and support clinical trials
            that are accessible to every child with cancer. Furthermore, it
            is critical that the data garnered from these studies is
            aggregated and appropriately shared. In addition, the
            integration of longitudinal data from pediatric cancer patients
            into adulthood, and the ability to compare adult and pediatric
            data broadly will have a profound impact upon our understanding
            of the etiology of cancer and our ability to advance research
            that can lead to new and better treatments.
        For decades, the foundations of both childhood and adult cancer
    treatment were surgery, chemotherapy, and radiation therapy. Recently,
    immunotherapy, in which a patient's own immune system is harnessed to
    fight cancer, has emerged as a new pillar of cancer treatment. While
    some immunotherapy approaches have been effective in treating certain
    pediatric cancers, many immunotherapy treatments being developed for
    adult cancers will likely not be applicable to childhood cancers.
    Therefore, this area remains a critical research focus.
        Recent clinical advances in immunotherapy include the 2017 FDA-
    approval of Keytruda (pembrolizumab), a checkpoint inhibitor, for
    pediatric and adult patients with classical Hodgkin lymphoma that
    cannot be cured with existing treatments, as well as pediatric patients
    with solid tumors that have specific genetic features known as mismatch
    repair deficiency and high microsatellite instability. This approval is
    significant because targeting genetic characteristics, rather than
    where the cancer originates in the body, creates new options for
    patients who might otherwise not be considered candidates for a drug.
    NCI is now sponsoring early-phase clinical trials of pembrolizumab in
    children with aggressive brain tumors.
        In 2017 the FDA also approved KymriahTM
    (tisagenlecleucel), a chimeric antigen receptor (CAR) T-cell therapy,
    for children with acute lymphoblastic leukemia (ALL). This NCI-
    supported discovery was first published in the New England Journal of
    Medicine in 2014. NCI is currently sponsoring nine clinical trials of
    CAR T-cell therapy in pediatric patients with other types of
    cancer.\79\
    ---------------------------------------------------------------------------
        \79\ https://clinicaltrials.gov/ct2/results?cond=&term=CAR+T-
    cell&type=&rslt= &recrs=b&recrs=
    a&recrs=f&recrs=d&age_v=&age=0&gndr=&intr=&titles=&outc=&spons=National+
    Cancer+
    Institute&lead=&id=&cntry=&state=&city=&dist=&locn=&strd_s=&strd_e=&prcd
    _s=
    &prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=.
    ---------------------------------------------------------------------------
        In April 2019, selumetinib was awarded Breakthrough Designation by
    the FDA,\80\ following Orphan Drug Designation in February 2018,\81\
    for treatment of neurofibromatosis type 1 (NF1), a rare pediatric
    disease that can cause malignant tumors. Although Breakthrough
    Designation does not guarantee final approval of the drug for this
    purpose, it is promising news for the future of this rare pediatric
    disease. NCI's POB led the Phase I and II trials of selumetinib,
    through an intramural and extramural collaboration. Early results from
    the phase II trial are promising--72 percent of the 50 pediatric
    patients between the ages of 2 and 18 enrolled in the trial are
    responding to the treatment. Not only are some patients seeing their
    tumors shrink more than 50 percent, but many patients report less pain
    intensity and pain interference, as well as increased strength and
    range of motion.\82\ If this trajectory continues, selumetinib will be
    the first drug ever approved for this disease.
    ---------------------------------------------------------------------------
        \80\ https://ccr.cancer.gov/news/article/mek-inhibitor-selumetinib-
    granted-breakthrough-
    designation-by-fda-to-treat-neurofibromatosis-type-one-in-pediatric-
    patient.
        \81\ https://ccr.cancer.gov/news/article/fda-grants-orphan-drug-
    status-to-selumetinib-for-neurofibromatosis-type-1-nf1-treatment.
        \82\ https://meetinglibrary.asco.org/record/159508/abstract.
    ---------------------------------------------------------------------------
        Innovative clinical trials would not be possible without the basic
    research conducted to understand the biological mechanisms of disease
    and to identify molecular targets for therapies. The NTRK family of
    genes is one such example. Describing the role of this family of genes
    was first made possible as a result of a basic science discovery in the
    1980's at NCI's Frederick National Laboratory for Cancer Research by
    Dr. Mariano Barbacid. Dr. Barbacid was not studying pediatric cancers,
    or any particular cancer type--he was on the hunt for unique genetic
    drivers of cancer, called oncogenes. At the time, he could not have
    anticipated that his discovery would eventually lead to an effective
    therapy for rare cancers diagnosed in children and adults.
        This discovery led to the development of an NTRK inhibitor, LOXO-
    101 or larotrectinib, which works against unique fusion oncoproteins
    that drive certain pediatric and adult cancers. In May 2018, FDA issued
    larotrectinib an orphan drug status and Priority Review, and in
    November 2018, FDA granted accelerated approval to larotrectinib. This
    is the second FDA approval for a precision cancer therapy that is based
    on a particular genetic alteration, rather than the site in the body in
    which a cancer occurs. Larotrectinib was evaluated in both the NCI
    adult and pediatric MATCH phase II clinical trials.
        Investigators are hopeful that the story of crizotinib (Xalkori)
    will be similar. Crizotinib was first developed to target a protein
    produced by the oncogene MET but was later found to inhibit cancer-
    causing forms of the ALK gene, found in anaplastic large cell lymphomas
    (ALCL), certain neuroblastomas, and some non-small cell lung cancers
    (NSCLC). ALCL and neuroblastoma both occur in pediatric patients; the
    connection between ALCL and ALK was established in 1994, while the
    identification of ALK as a driver of neuroblastoma occurred in 2008.
    Crizotinib was first approved for NSCLC in March 2016, and it is part
    of the NCI adult and pediatric MATCH trials. In 2018, the FDA granted
    breakthrough approval of the drug for ALCL, and COG launched a phase
    III trial with crizotinib in combination with chemotherapy for high-
    risk neuroblastoma patients.
        NCI will continue to support basic, translational, and clinical
    research to help develop new and less toxic therapies for children with
    cancer. NCI is also committed to supporting cancer survivorship
    research to better understand and develop interventions to address the
    late effects of cancer and its treatment in childhood, and adolescent
    and young adult (AYA) cancer survivors. NCI is currently implementing
    new research efforts in this area and is also supporting efforts to
    enhance biospecimen collection and biobanking efforts with an emphasis
    on pediatric cancer types and subtypes for which treatments have been
    least effective. Both activities are aligned with provisions of the
    Childhood Cancer STAR Act directed toward NCI.
        Question. What is being done to ensure that SBIR funding is
    addressing the critical translational gap for these neglected rare
    cancer patients?
        Answer. Consistent with the statutory mandate established by
    Congress, the NCI SBIR/STTR program is one of the largest sources of
    early stage technology financing in the United States. The program
    supports a diverse portfolio of research, from projects focused
    specifically on evaluating new treatments for rare cancers, to the
    development of cross-cutting technologies that enable research across
    cancer types. The NCI SBIR/STTR program does not direct funding based
    upon cancer type or research area. Funding is awarded through a
    rigorous and competitive peer review process, to identify the most
    promising research applications. NCI, including the SBIR/STTR program,
    recognize that there is a clear need to develop more effective
    treatments for many rare cancers and rare cancer subtypes that are
    refractory to currently available treatment options.
        Examples of current SBIR projects focusing on translational and
    clinical research for rare cancers include:
      --In 2018, NCI awarded a SBIR Phase IIB Bridge Award to Oncoceutics,
            Inc., which seeks to develop a new cancer drug, ONC201, for
            patients who have been diagnosed with recurrent glioblastoma
            and high-grade glioma with limited treatment options and very
            poor prognoses, including a pediatric high-grade glioma called
            Diffuse Intrinsic Pontine Glioma (DIPG).\83\ Approximately 200-
            300 children are diagnosed with DIPG each year in the U.S., and
            the median survival time from diagnosis is less than 1 year.
    ---------------------------------------------------------------------------
        \83\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9524880&icde=
    44259659&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&pball=.
    ---------------------------------------------------------------------------
      --In 2018, NCI supported PEEL Therapeutics with an STTR award focused
            on pre-clinical evaluation of a novel potential therapy for
            osteosarcoma, a deadly pediatric bone tumor. The project is led
            by Dr. Josh Schiffman, who is also a researcher at the Huntsman
            Cancer Institute at the University of Utah.\84\
    ---------------------------------------------------------------------------
        \84\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9559358&icde=44276787.
    ---------------------------------------------------------------------------
      --In fiscal year 2018, NCI also funded a Phase I clinical trial of a
            novel first-in-class drug combination of two agents (IV
            fenretinide + IV safingol) through an SBIR Fast-Track Phase I/
            II award to CerRx, Inc. This trial, conducted at the South
            Plains Oncology Consortium based at the Texas Tech University
            Health Sciences Center, is testing for the treatment of
            multiple relapsed rare cancer types including Non-Hodgkin's
            Lymphoma, Peripheral T-Cell Lymphoma, and Esophageal
            Adenocarcinoma. If successful, this novel biochemistry may
            constitute a broad-based widely active treatment option for
            both adult and pediatric malignancies.\85\
    ---------------------------------------------------------------------------
        \85\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9485913&icde=44283562.
    ---------------------------------------------------------------------------
        While these are all important examples of research underway to
    support development of new therapies for rare cancers, the SBIR
    Program's investment in cross-cutting technologies and tools is equally
    important to progress in this field. A notable example of this is NCI's
    support of Illumina, Inc. With support from NCI's SBIR program and its
    Innovative Molecular Analysis Technologies (IMAT) program,\86\ Illumina
    developed the base technology for the Infinium assay for genotyping,
    which is being used in the NIH All of Us Research Program, in other
    basic and clinical research, as well as by commercial companies like
    23andMe and Ancestry.com.\87\ In collaboration with NCI's SBIR/STTR
    program, the IMAT program is another opportunity for small businesses
    to pursue NCI support. IMAT aims to support the development and
    dissemination of novel and potentially transformative next-generation
    technologies, and uses a variety of investigator-initiated research
    project grant mechanisms to support cross-cutting, research-enabling
    disciplines.
    ---------------------------------------------------------------------------
        \86\ https://imat.cancer.gov/, https://imat.cancer.gov/about-imat/
    outputs-and-achievements/individual-technologies-and-platforms/
    sentrix%C2%AE-beadchip-and.
        \87\ https://www.cancer.gov/news-events/cancer-currents-blog/2019/
    nci-sbir-working-with-small-business.
    ---------------------------------------------------------------------------
        These SBIR and IMAT examples, along with other NCI research efforts
    described in this response, represent important steps NCI is taking to
    support basic, translation, and clinical research to make progress for
    patients with rare cancers. NCI encourages small businesses interested
    in pursuing NCI funding to consider opportunities to apply for SBIR/
    STTR \88\ and IMAT support,\89\ as well as support through the NExT
    program,\90\ also highlighted in this response.
    ---------------------------------------------------------------------------
        \88\ https://sbir.cancer.gov/funding.
        \89\ https://imat.cancer.gov/funding-opportunities.
        \90\ https://next.cancer.gov/entryToPipeline/default.htm.
    ---------------------------------------------------------------------------
        Question. What is being doing to ensure that all forms of cancer
    have significant dataset presence in publicly available data
    repositories?
        Answer. There are several data resources available from NCI that
    serve as data repositories for all forms of cancers, including rare
    cancers. Examples include the Genomic Data Commons (GDC) and the NCTN
    Navigator. The GDC \91\ is a data portal that serves as a centralized
    location to integrate and store the diverse datasets from NCI programs.
    The GDC includes cancer genomic data from over 32,000 cancer cases. All
    GDC data is available to qualified researchers free of charge and
    includes data from The Cancer Genomic Atlas (TCGA),\92\ where about
    one-third of cancer types within the TCGA resource are rare cancers;
    Therapeutically Applicable Research to Generate Effective Treatments
    (TARGET), where all of the cancers included in this pediatric genomics
    resource are considered rare; The Clinical Trials Sequencing Program
    (CTSP); and the Exceptional Responders Initiative. The GDC will also
    include data from future NCI Center for Cancer Genomics-sponsored
    cancer research programs.
    ---------------------------------------------------------------------------
        \91\ https://gdc.cancer.gov/.
        \92\ Rare cancer types within TCGA are: mesothelioma, adrenal gland
    tumors, testicular germ cell cancer, uveal melanoma, adrenocortical
    carcinoma, cholangiocarinoma, chromophobe kidney cancer, adult soft
    tissue sarcomas, thymomas, and uterine carcinosarcoma.
    ---------------------------------------------------------------------------
        Finally, the proposed fiscal year 2020 Childhood Cancer Data
    Initiative seeks to create a federated data system for pediatric cancer
    research to increase the number of cases represented, and all pediatric
    cancers are considered rare diseases. The data federation will include
    clinical records, genomic information, pathology and outcomes data and
    will build upon existing initiatives at NIH and NCI including the GDC
    and TARGET.
                   cancer research and the deadliest cancers
        Question. While Congress has been providing the NIH, including the
    National Cancer Institute, with more funding each of the past 4 years,
    the odds of securing a grant from NCI have actually been getting more
    difficult.
        (A) What's driving this trend, what's its significance, and do you
    expect it to continue?
        (B) How much of the progress that you're seeing is occurring in NCI
    Cancer Centers and Translational Research centers, is it
    disproportionate, and what accounts for their success?
        (C) While the progress in cancer research is very encouraging, it
    remains elusive for those like cancers of the pancreas, esophagus,
    ovary and stomach, where progress remains elusive. What is NCI doing to
    address that?
        Please provide the number of grants and total grant funding devoted
    to research related to cancers of the pancreas, esophagus, ovary,
    liver, brain, lung and stomach for each year from fiscal year 2013 to
    fiscal year 2018.
        Answer. NIH appreciates the additional resources Congress provided
    NCI each of the past 6 years (Fiscal Years 2013-2018) to support cancer
    research. As members are fully aware, cancer continues to be a leading
    cause of death and disability for the Nation, and thus scientists
    around the country are motivated to find strategies for combatting the
    issue. The additional funding resulted in an approximately 24 percent
    increase to NCI's appropriation to support essential research into
    understanding and treating what we now recognize as a multitude of
    cancer subtypes. Over that same period, NCI received a nearly 50
    percent increase in the number of investigator-initiated grant
    applications (R01s) indicating that the field continues to attract
    researchers to propose novel scientific proposals. Specifically, during
    fiscal year 2013, NCI received 4,175 investigator-initiated R01
    applications. During fiscal year 2018 NCI received 6,113 R01
    investigator-initiated applications, and experienced year-to-year
    annual growth in the number of applications throughout the period. We
    have also observed that the increases represent a growing number of
    unique investigators applying for awards, and only a small portion
    (approximately 10 percent) of the increase in applications is driven by
    individual investigators submitting multiple applications As a result,
    even during an era of significant budget increases, this dramatic
    growth in applications had increased competition for NCI funding, and
    NCI is taking affirmative steps to improve the chances for applicants
    to be funded. Of note, in fiscal year 2019, NCI expects to increase the
    investigator-initiated research grant pool by $100 million, an amount
    that is greater than the increase NCI received to its fiscal year 2019
    base appropriation.
        (A) Regarding the increase in applications to NCI, we suspect that
    the public health burden in combination with the scientific opportunity
    is the likely source of a surging biomedical research workforce in this
    area. We are reaping the benefits of decades of investment in basic
    science and rapid advances in technology that have resulted in a record
    number of oncology drug approvals. This includes significant progress
    in the development of cancer immunotherapies and molecularly targeted
    therapies. At the same time, we are making gains in cancer prevention
    and survivorship. Taking these advances into consideration with the
    increasingly interdisciplinary nature of cancer research, that is the
    intersection of genomics, data science, biology, and more, this
    progress continues to attract more interest and talent to the cancer
    research enterprise.
        (B) The 70 NCI-designated Cancer Centers serve as anchors of the
    United States cancer research enterprise, convening concentrations of
    expertise that are vital to rapidly advance progress against cancer.
    NCI strives to provide opportunities to participate in cutting edge,
    NCI-supported research to every patient across the country, not just
    those with easy access to an NCI-designated Cancer Center and thus two
    additional pillars of the NCI research infrastructure are the National
    Clinical Trials Network (NCTN) and the NCI Community Oncology Research
    Program (NCORP), which seek to enroll diverse patient populations from
    across the Nation in NCI-sponsored research.
        The NCTN is a collection of organizations and clinicians that
    coordinates and supports cancer clinical trials at more than 3,000
    sites across the U.S. and Canada. The NCTN provides the infrastructure
    for NCI-funded treatment, screening, and diagnosis trials, centralizing
    many administrative efforts to rapidly facilitate easier enrollment of
    patients in clinical trials. For physicians and their patients, a
    variety of significant, innovative trials are widely available
    throughout the country, in large and small communities alike.\93\
    ---------------------------------------------------------------------------
        \93\ https://www.cancer.gov/research/areas/clinical-trials/nctn.
    ---------------------------------------------------------------------------
        NCORP, which works closely with the NCTN, expands NCI's reach even
    further. In addition to designing and conducting cancer prevention,
    supportive care and symptom management, screening, and surveillance
    clinical trials, NCORP sites recruit patients and participants to NCI-
    supported treatment and imaging trials, most of which are conducted
    through the NCTN. NCORP is led by 7 research bases and 46 community
    sites, and there are over 900 NCORP component sites across the country.
    The sites represent collaborations between researchers, public
    hospitals, physician practices, academic medical centers, and other
    groups that provide healthcare services.\94\
    ---------------------------------------------------------------------------
        \94\ https://ncorp.cancer.gov/about/.
    ---------------------------------------------------------------------------
        Independent investigators fill out the robust research
    infrastructure supported by NCI. This includes principal investigators
    for NCI's Specialized Programs of Research Excellence (SPOREs),\95\
    which represent collaborative translational research projects focusing
    on more than twenty organ sites, systems, and pathway-specific themes.
    While large programs like NCI-designated cancer centers, clinical
    trials networks, data commons, and biorepositories constitute the
    backbone of the cancer research enterprise, the majority of research
    proposals received and funded by NCI are investigator-initiated,
    meaning that the studies are developed by researchers themselves. This
    process allows for the scientific ingenuity and intellectual autonomy
    that is essential to advance biomedical research. In fiscal year 2018,
    NCI supported research at more than 700 institutions across the United
    States.
    ---------------------------------------------------------------------------
        \95\ https://trp.cancer.gov/.
    ---------------------------------------------------------------------------
        (C) NCI is committed to making progress against all cancers,
    including those that have proved most difficult to treat. Indeed,
    recognizing that the incentives that encourage private industry
    investment in therapies for more common cancers do not exist for
    cancers that occur less frequently, NCI has a responsibility to
    encourage and support research on these diseases, and does this through
    a variety of mechanisms, including support for disease-specific
    steering groups and the convening of scientific meetings and relevant
    cross-cutting research areas that seek to identify new scientific
    directions and opportunities.
        One way in which NCI encourages scientific collaboration and
    interdisciplinary research on these disease areas is through the SPOREs
    program, mentioned above. These programs include basic and clinical/
    applied scientists working together to support projects that will
    result in new and diverse approaches to the prevent, detect, diagnose,
    and treat cancer. NCI currently supports SPOREs focused on pancreas,
    esophagus, ovary, liver, brain, lung and stomach cancers through the
    following awards:
      --Pancreatic SPOREs are located at the Mayo Clinic, University of
            Nebraska Medical Center, and Washington University in St.
            Louis.\96\
    ---------------------------------------------------------------------------
        \96\ https://trp.cancer.gov/spores/pancreatic.htm.
    ---------------------------------------------------------------------------
      --Gastrointestinal SPOREs, which include research on cancers of the
            esophagus and stomach, are located at Case Western Reserve
            University, Dana-Farber Harvard Cancer Institute, Johns Hopkins
            University, and Vanderbilt University.\97\
    ---------------------------------------------------------------------------
        \97\ https://trp.cancer.gov/spores/gi.htm.
    ---------------------------------------------------------------------------
      --Ovarian SPOREs are located at Johns Hopkins University, the Mayo
            Clinic, Roswell Park Cancer Institute, and University of TX/MD
            Anderson.\98\
    ---------------------------------------------------------------------------
        \98\ https://trp.cancer.gov/spores/ovarian.htm.
    ---------------------------------------------------------------------------
      --A hepatobiliary (liver) cancer SPORE is located at the Mayo
            Clinic.\99\
    ---------------------------------------------------------------------------
        \99\ https://trp.cancer.gov/spores/hepatobiliary.htm.
    ---------------------------------------------------------------------------
      --Brain SPOREs are located at Dana-Farber Harvard Cancer Institute,
            Duke University Medical Center, Northwestern University at
            Chicago, University of California, Los Angeles, University of
            California, San Francisco, and University of Texas/MD
            Anderson.\100\
    ---------------------------------------------------------------------------
        \100\ https://trp.cancer.gov/spores/brain.htm.
    ---------------------------------------------------------------------------
      --Lung SPOREs are located at the University of Colorado Cancer
            Center, University of Texas/Southwestern Medicine, and Yale
            University.\101\
    ---------------------------------------------------------------------------
        \101\ https://trp.cancer.gov/spores/lung.htm.
    ---------------------------------------------------------------------------
        Between June 2017 and May 2018, the FDA approved several therapies
    for cancers that are the focus of SPORE research, advances made
    possible through NCI or NIH-supported research.\102\ The approved
    treatments include: \103\
    ---------------------------------------------------------------------------
        \102\ https://www.ncbi.nlm.nih.gov/pubmed/29440428.
        \103\ https://www.ascopost.com/issues/june-3-2018-narratives-
    special-issue/fda-oncology-drug-
    approvals-granted-between-june-2017-and-may-16-2018/.
    ---------------------------------------------------------------------------
      --Rucaparib (Rubrical), a maintenance treatment for recurrent
            ovarian, fallopian tube, or primary peritoneal cancers;
      --Lutetium Lu 177 Dotatate (Lutathera) for gastroenteropancreatic
            neuroendocrine tumors;
      --Trastuzumab-DKST (Ogivri), a biosimilar, to treat patients with
            certain types of metastatic stomach cancer and breast cancer;
      --Pembrolizumab (Keytruda) for patients with recurrent locally
            advanced or metastatic, gastric or gastroesophageal junction
            adenocarcinoma whose tumors express a certain biomarker;
      --Olaparib tablets (Lynparza) for maintenance treatment of patients
            with recurrent ovarian, fallopian tube, or primary peritoneal
            cancer who responded to certain chemotherapies; and
      --Several approvals to treat various subtypes of non-small cell lung
            cancer (NSCLC):
        --Osimertinib (Tagrisso)
        --Durvalumab (Imfinzi)
        --Alectinib (Alecensa)
        --Dabrafenib (Tafinlar), in combination with Trametinib (Mekinist)
        As these approvals indicate, the scientific community recognizes
    that within each type of cancer, there are unique subtypes, and when
    possible, physicians should rely on genetic and molecular markers to
    guide treatment. NCI's investments in basic research--understanding the
    underlying mechanisms that give rise to cancer--enable rapid advances
    of precision medicine in cancer treatment. Investigators are continuing
    to identify disease subtypes, which often uncovers tumors with similar
    genetic profiles that occur in various sites throughout the body. Such
    advances led to the FDA approval of FoundationOne CDX Next Generation
    Sequencing, a genetic test to detect alterations in 324 genes and two
    genomic signatures in any solid tumor type.\104\ These developments
    benefit all cancer patients, including those with difficult to treat
    cancers.
    ---------------------------------------------------------------------------
        \104\ https://www.ascopost.com/issues/june-3-2018-narratives-
    special-issue/fda-oncology-drug-
    approvals-granted-between-june-2017-and-may-16-2018/.
    ---------------------------------------------------------------------------
        Precision medicine is the foundation for the NCI MATCH (Molecular
    Analysis for Therapy Choice) Trial, a precision medicine trial that is
    expected to provide new research ideas to advance treatments in all
    cancer types.\105\ This study is analyzing patients' tumors to
    determine whether they contain gene abnormalities for which a targeted
    drug exists, and with that information, the study assigns treatment
    based on the genetic abnormality. As of April 2019, 443 pancreatic
    cancer patients, 235 gastroesophageal cancer patients, 666 ovarian
    cancer patients, and 345 liver and hepatobiliary cancer patients, 131
    patients with brain and other central nervous system tumors, and 707
    patients with various types of lung cancers have been screened for this
    trial.
    ---------------------------------------------------------------------------
        \105\ https://www.cancer.gov/about-cancer/treatment/clinical-
    trials/nci-supported/nci-match.
    ---------------------------------------------------------------------------
        Patients who are not assigned to an NCI MATCH treatment arm may be
    eligible for the NCI DART, or the Dual Anti-CTLA-4 & Anti-PD-1 blockade
    in Rare Tumors Trial. This study will also assess whether their tumors
    respond to two cutting-edge immunotherapy agents. DART is the first
    federally funded immunotherapy trial devoted entirely to rare
    cancers.\106\
    ---------------------------------------------------------------------------
        \106\ https://www.swog.org/sites/default/files/docs/2017-11/
    DARTrelease.pdf.
    ---------------------------------------------------------------------------
        As this background demonstrates, NCI will continue to support
    research on cancers of the pancreas, esophagus, ovary, liver, brain,
    lung and stomach through multiple research mechanisms.
        Question. Please provide the number of grants and total grant
    funding devoted to research related to cancers of the pancreas,
    esophagus, ovary, liver, brain, lung and stomach for each year from
    fiscal year 2013 to fiscal year 2018.
        Answer. The information requested is provided in the tables below
    (Table 1--Fiscal Year 2018-2016 and Table 2--Fiscal Year 2015-2013).
    Brain cancer, liver cancer, lung cancer, ovarian cancer and pancreatic
    cancer are Research, Condition, and Disease Categories (RCDC) and the
    data provided include the total number of projects--grants (including
    subprojects and supplements), contracts, and intramural research--for
    the NIH for those cancer types. Total funding is broken out as total
    NIH and total NCI funding. The data are publicly available and can be
    found at: https://report.nih.gov/categorical_spending.aspx.
        Additionally, it is important to clarify that RCDC category
    listings are not budget line items. The category represents a list of
    projects selected for funding following the rigorous NIH peer review
    process. Each category list provides a look back at projects funded in
    a given fiscal year. NIH does not allocate funding prospectively by
    category, and the RCDC categories do not add up to the total NIH budget
    because projects can be applicable to more than one category, and
    categories are by their nature overlapping (e.g., neurosciences and
    brain cancer). RCDC is not intended to account for the entire NIH
    budget across thousands of research topics. More information is
    available on the RCDC FAQ page: https://report.nih.gov/rcdc/
    faqs.aspx#q18.
        Esophageal cancer and stomach cancer are not currently RCDC
    categories. Therefore, the data provided for those sites are estimated
    based on NCI data for grants and intramural research projects. Although
    every attempt was made to provide data that is closely matched to the
    method used to assemble RCDC data for the other cancer sites. However,
    it is not comparable because there are no esophageal or stomach cancer
    RCDC categories.
        [The information follows:]

                     down syndrome and the include project
        Question. As a part of the INCLUDE Project, NIH has hosted
    scientific workshops to solicit input from the Down syndrome community
    on research between Alzheimer's disease and Down syndrome. What other
    topics does NIH plan to cover in future workshops and how will NIH plan
    to engage the Down syndrome community to ensure their robust
    participation in these workshops?
        Answer. The new, trans-NIH effort, Investigating Co-occurring
    conditions across the Lifespan to Understand Down syndrome, or INCLUDE,
    was launched in summer 2018. As a key component of the INCLUDE project,
    the NIA is supplementing an Alzheimer's clinical trials network to
    include adults with Down syndrome to learn more about the development
    of commonly co-occurring conditions in individuals with Down syndrome
    that are also seen in the general population, such as dementia and
    Alzheimer's disease. In addition, working through its established
    Pediatric Trials Network, in fiscal year 2019 (NICHD will create a new
    pediatric clinical trials infrastructure for Down syndrome. Such a
    resource will also ensure that new therapies can be brought to trial as
    they emerge in the future. To bolster these efforts, NIH is planning
    two major scientific workshops within the year to address the
    development of a cohort in Down syndrome, and how to include people
    with Down syndrome in clinical trials. These efforts can take advantage
    of the research registry for Down syndrome, DS-Connect,\107\ a Web-
    based health registry that serves as a national health resource for
    people with Down syndrome and their families, researchers, and
    healthcare providers. Funded by NICHD since 2013, with over 4,400
    participants, the registry facilitates information sharing about
    research and upcoming trials for individuals with Down syndrome, their
    families, and researchers.
    ---------------------------------------------------------------------------
        \107\ https://dsconnect.nih.gov/.
    ---------------------------------------------------------------------------
        Question. How is NIH going to use the INCLUDE Project and other
    investments in Down syndrome research to support the pipeline of early
    investigators in this field?
        Answer. One of the immediate successes of INCLUDE was to attract
    new researchers and talent into the field. In fact, many of the
    recipients of awards in fiscal year 2018 were investigators who had not
    previously had a research focus on Down syndrome. Since the purpose of
    the INCLUDE project is to investigate conditions that affect both
    individuals with Down syndrome and the general population, researchers
    with subject matter expertise other than Down syndrome now have the
    opportunity to submit applications in response respond to one of
    INCLUDE's three major components: to conduct targeted, high-risk, high-
    reward basic science studies on chromosome 21; assemble large study
    populations (cohorts) of individuals with Down syndrome; and include
    individuals with Down syndrome in new and existing clinical trials.
    These opportunities are widely disseminated across the Down syndrome
    community through the public-private Down Syndrome Consortium that
    includes the Trans-NIH Working Group, 16 national and international
    organizations whose missions focus on Down syndrome, and individuals
    with Down syndrome and family members. The consortium also works toward
    implementing the NIH Research Plan on Down Syndrome,\108\ which set
    research goals for Down syndrome.
    ---------------------------------------------------------------------------
        \108\ https://www.nichd.nih.gov/publications/product/441.
    ---------------------------------------------------------------------------
        In addition, NIH continues to fund from its baseline a wide range
    of research related to Down syndrome, across many of the NIH institutes
    and centers, nearly tripling its total funding for Down syndrome-
    related research over the last few years. For example, NICHD is funding
    an early-stage investigator studying children with Down syndrome, to
    develop outcome measures for early childhood communication. In the
    future, we anticipate initiatives that will be focused on support for
    trainees to continue to build a pipeline of investigators studying Down
    syndrome.
        Question. People with Down syndrome have a unique disease spectrum
    that offers many opportunities for research. As the NIH works to set up
    a clinical trials network as a part of the INCLUDE Project, how do you
    plan to work with the Down syndrome community to encourage people with
    this condition to participate in clinical trials?
        Answer. Over the coming year, NICHD plans to work with NIA and
    other partners to coordinate building an infrastructure for a clinical
    trials network in Down syndrome across the lifespan. At the same time,
    full inclusion of individuals with Down syndrome into ongoing clinical
    studies that have been enrolling people without Down syndrome will
    ensure that they will reap the benefits of therapeutic agents already
    in development. Working through its established Pediatric Trials
    Network that has enrolled over 7,000 children, in fiscal year 2019
    NICHD will create a new pediatric clinical trials infrastructure for
    Down syndrome. This resource will also ensure that new therapies can be
    brought to trial quickly and efficiently as they emerge in the future.
    In parallel, NICHD will create and fund a training program, working
    with its pediatric trials experts, as well as specialists in Down
    syndrome, to help teach investigators how to recruit and work with
    individuals with Down syndrome and their families.
        Further, through the INCLUDE project, NIA is supplementing an
    Alzheimer's clinical trials network to include adults with Down
    syndrome to learn more about the development of dementia and
    Alzheimer's disease. To bolster these efforts, NIH is planning two
    major scientific workshops within the year to address the development
    of a cohort in Down syndrome, and how to include people with Down
    syndrome in clinical trials. These efforts will take advantage of the
    research registry for Down syndrome, DS-Connect,\109\ a Web-based
    health registry that serves as a national health resource for people
    with Down syndrome and their families, researchers, and healthcare
    providers. Funded by NICHD since 2013, the registry facilitates
    information sharing about research and upcoming studies for both
    individuals with Down syndrome and researchers.
    ---------------------------------------------------------------------------
        \109\ https://dsconnect.nih.gov/.
    ---------------------------------------------------------------------------
        Question. We are pleased to see so many NIH Institutes and Centers
    participating in the INCLUDE Project. What kind of feedback have you
    been getting from the Institutes on this project, particularly as it
    may offer lessons learned for other trans-NIH initiatives?
        Answer. INCLUDE involves research projects or programs funded by 14
    NIH Institutes and Centers. INCLUDE will investigate conditions that
    affect both individuals with Down syndrome and the general population,
    such as Alzheimer's disease/dementia, autism, cataracts, celiac
    disease, congenital heart disease, and diabetes. This approach is
    creating new synergies among the NIH institutes and centers that study
    these conditions. To give just two examples from the first round of
    awards, NICHD is funding a project that will sequence the genomes of
    children with Down syndrome who also have congenital heart defects or
    leukemia. The results will be publicly available, allowing researchers
    globally to test hypotheses and find new gene variants that are
    associated with both Down syndrome and these additional conditions. NIA
    is developing a Down syndrome module for its Alzheimer's disease
    research centers with the goal of learning more about the development
    of dementia that will lead to potential treatments.
        Question. I recently learned that people with Down syndrome rarely
    get solid tumor cancers. For example, women with Down syndrome most
    likely would not ever need to get a mammogram because they are highly
    unlikely to develop breast cancer. The connection between Down syndrome
    and cancer seems like a promising research opportunity. Can you tell us
    about some of the topics that NIH is prioritizing in the INCLUDE
    Project?
        Answer. NIH was grateful to have the opportunity to dedicate more
    resources in fiscal year 2018 toward research related to Down syndrome
    through the INCLUDE project. In its first year, over $22 million was
    spent on projects under this new initiative alone. This figure was in
    addition to the baseline funding of $37 million for Down syndrome for a
    total of approximately $60 million. Awards were made to a wide range of
    investigators across the country,\110\ covering all aspects of the
    INCLUDE project: research to improve the understanding of the biology
    of Down syndrome, research focused on connecting large study
    populations (or cohorts) of individuals with Down syndrome and
    enrolling new participants at different ages, and identifying existing
    clinical trials that seek to address conditions common in individuals
    with Down syndrome to bolster recruitment and inclusion in more
    clinical studies.
    ---------------------------------------------------------------------------
        \110\ https://www.nih.gov/include-project/funding.
    ---------------------------------------------------------------------------
        INCLUDE involves research projects or programs funded by 14 NIH
    Institutes and Centers, investigating conditions that affect both
    individuals with Down syndrome and the general population, such as
    Alzheimer's disease/dementia, autism, cataracts, celiac disease,
    congenital heart disease, and diabetes. This approach is creating new
    synergies among the NIH institutes and centers that study these
    conditions. To give just two examples from the first round of awards,
    NICHD is funding a project that will sequence the genomes of children
    with Down syndrome who also have congenital heart defects or leukemia.
    The results will be publicly available, allowing researchers globally
    to test hypotheses and find new gene variants that are associated with
    these conditions. NIA is developing a Down syndrome module for its
    Alzheimer's centers with the goal of learning more about the
    development of dementia and lead to potential treatments.
        Question. I was pleased to learn that one of the aims of the
    INCLUDE Project is to encourage scientists studying other topics like
    cancer, Alzheimer's, and autoimmune disease to add research on Down
    syndrome to their work. What kind of feedback have you gotten from the
    research community on these opportunities?
        Answer. One of its immediate successes of INCLUDE was to attract
    new researchers and talent into the field. In fact, many of the
    recipients of awards in fiscal year 2018 were investigators who had not
    previously had a research focus on Down syndrome. Since the purpose of
    the INCLUDE project is to investigate conditions that affect both
    individuals with DS and the general population, researchers with
    subject matter expertise other than Down syndrome now have the
    opportunity to submit applications. These opportunities are widely
    disseminated across the Down syndrome community through the public-
    private Down Syndrome Consortium that includes the Trans-NIH Working
    Group, 16 national and international organizations whose missions focus
    on Down syndrome, and individuals with Down syndrome and family
    members. The response has been robust, demonstrating excitement among
    investigators who previously have not been involved in Down syndrome
    research.
                             antibiotic resistance
        Question. We have been hearing warnings for decades that overuse of
    antimicrobials is reducing their effectiveness, and that appears to be
    borne out by reports of a new superbug, Candida Auris.
        Where does NIH see the greatest opportunities for medical research
    to provide solutions to the threat posed by antimicrobial resistance?
        Answer. NIAID is the lead institute for antimicrobial resistance
    (AMR) research at NIH. NIAID supports a comprehensive portfolio of
    basic, translational, and applied research on AMR to better understand
    pathogenicity and the mechanisms by which resistant pathogens overcome
    antimicrobials, and to develop novel diagnostics, therapeutics, and
    vaccines. Recent advances in AMR research have created a number of
    scientific opportunities, particularly to: (1) accelerate the
    development of new antimicrobials with novel mechanisms of action; (2)
    identify ways to enhance or target the body's immune system to better
    fight infection; (3) manipulate microbial communities to prevent or
    treat colonization by harmful pathogens; and (4) develop state-of-the-
    art antivirulence strategies and rapid diagnostics to help control the
    spread of AMR. NIAID is pursuing these opportunities for both bacterial
    and fungal pathogens.
        NIAID is supporting development of a number of novel antimicrobial
    agents, including a group of novel forms of a class of antibiotics
    (tetracyclines) that are not susceptible to existing resistance
    mechanisms in bacteria. One of these compounds, XERAVATM, recently
    received FDA approval to treat complicated intra-abdominal infections.
    NIAID funding also has led to the discovery of a new class of
    antibiotics, malacidins, that are being investigated for further
    therapeutic development. In addition, NIAID is providing CARB-X
    (Combating Antibiotic Resistant Bacteria-X), a public-private
    partnership led by BARDA within HHS with in kind and technical support.
    CARB-X is currently funding 35 innovative projects--including 13 that
    represent new classes of antibiotics.
        NIAID currently is exploring several alternatives to traditional
    antimicrobials that leverage advances in basic research on
    pathogenesis, drug resistance, immune system function, and the
    microbiome. NIAID-supported scientists are exploring the use of
    protective bacterial strains and fecal microbiota transplant to prevent
    and treat bacterial infections. NIAID grantees also are investigating
    ways to boost the ability of an individual's own immune system to fight
    infection. This includes the use of modified immune cells to control
    invasive fungal infections, and studies by NIAID investigators to boost
    the immune system's ability to fight the bacterial species Klebsiella
    pneumoniae infection using targeted antibodies. NIAID also is advancing
    the development of candidate vaccines against bacterial and fungal
    pathogens, including strains that exhibit drug resistance. One such
    experimental vaccine, NDV-3, exhibited protection in animal models
    against Staphylococcus and Candida species, including Candida auris (C.
    auris). NDV-3 also was shown to be safe and well-tolerated in a Phase 1
    clinical study. Vaccines that confer protection against bacterial and
    fungal pathogens have the added benefit of mitigating the use of
    antimicrobial drugs and potentially avoiding the development of AMR.
        NIAID also is supporting the development of novel diagnostic tools
    to help control the emergence and spread of drug-resistant pathogens.
    The NIAID Antibacterial Resistance Leadership Group (ARLG) oversees
    clinical research on antibiotic resistance, including antimicrobial
    stewardship, infection prevention, and improved diagnostics. ARLG
    efforts include the development of a master protocol for evaluating
    multiple diagnostic tests using samples from a single patient. NIAID
    support also has contributed to the development of several novel
    diagnostics capable of distinguishing between numerous infectious
    agents, including a sepsis diagnostic that simultaneously tests for 24
    bacterial and fungal species, and a pneumonia diagnostic that can
    detect a number of different bacterial and viral species as well as
    seven genetic markers of AMR. Both diagnostics have received FDA
    clearance. In addition, NIH, in partnership with BARDA, is supporting
    the AMR Diagnostic Challenge competition. The Diagnostics Challenge
    aims to accelerate the development of raid, point-of-need diagnostic
    tests that can help inform treatment and facilitate antibiotic
    stewardship. Submissions for Step 3 of the Challenge are due in January
    2020, and final results of the competition are anticipated in July
    2020.
        Question. There are already a number of superbugs like MRSA and C-
    R-E that pose challenges in hospitals and other healthcare settings,
    what is significant about Candida Auris?
        Answer. Candida are fungi that can be found on the skin, mucous
    membranes, and in the intestinal tract. For people with certain risk
    factors, excessive growth of these fungi can cause invasive
    candidiasis--a serious infection that can affect the blood, heart,
    brain, eyes, bones and other parts of the body. C. auris is a newly
    emerging fungal species that is challenging to diagnose and is often
    resistant to multiple antifungal drugs. While most C. auris infections
    are treatable with existing antifungal drugs, the presence of C. auris
    infections resistant to three of the main classes of antifungal drugs
    is extremely concerning. In addition, C. auris is extremely difficult
    to eliminate from contaminated surfaces, and it can spread from person-
    to-person. Drug development for fungal pathogens poses an especially
    challenging problem. Unlike antibacterial drugs, which mostly target
    bacterial pathways that are very different than those in humans, many
    fundamental biochemical and cellular processes are similar in fungi and
    humans. Thus, many fungal drug candidates may pose a safety risk to
    humans because they could also target the similar human pathways, with
    potentially toxic side effects.
        AMR research supported by NIAID is especially critical in light of
    the emergence of novel AMR pathogens such as C. auris, which exhibits a
    unique multidrug resistance that has not been seen in other species of
    Candida. A major component of NIAID-supported research on C. auris is
    focused on developing an improved understanding of resistance
    mechanisms to better inform therapeutic development efforts. This
    includes genomic analysis of C. auris--including isolates from two
    recent outbreaks--as well as efforts to better understand host-pathogen
    interactions and resistance mechanisms for particular antifungal drugs.
    NIAID also is screening antifungal compounds for in vitro effectiveness
    against C. auris. Of 15 compounds tested to date, 11 showed activity
    against C. auris. NIAID also supports studies of a broad-spectrum
    antifungal with activity against C. auris and other Candida species. In
    addition, NIAID scientists have developed animal models to study C.
    auris infection and to screen investigational therapeutics, three of
    which showed activity against C. auris. Two of these investigational
    therapeutics are currently in various stages of clinical development.
        Question. This is clearly a problem that goes far beyond the NIH or
    even the United States. How is NIH working its your other Federal and
    international partners?
        Answer. NIAID works closely with its Federal partners, including
    the Centers for Disease Control and Prevention (CDC), BARDA, and FDA to
    monitor the spread of drug-resistant pathogens and further the
    development of promising diagnostics, therapeutics, and vaccines for
    AMR pathogens. NIAID continues to support CARB-X, the BARDA-led public-
    private partnership to incentivize the early development of
    antibiotics, vaccines, and diagnostics to combat resistance to
    antimicrobials that also is supported by the United Kingdom and
    Germany. NIAID also participates in the Transatlantic Task Force for
    Antimicrobial Resistance (TATFAR), which was established in 2009 with
    the goal of enhancing communication and cooperation in: 1)
    antimicrobial stewardship; 2) prevention and control of AMR; and 3)
    enhancement of the antimicrobial drug development pipeline. NIAID,
    through TATFAR, has aligned clinical trial networks with the European
    Union to expand access to patients in a clinical trial to optimize the
    antibacterial drug colistin for carbapenem-resistant Enterobacteriaceae
    (CRE) and in a clinical trial to evaluate an antibody for use against
    Pseudomonas. These collaborative efforts are helpful in gathering a
    sufficient number of patients to conduct critical AMR clinical studies.
    In addition, the NIAID-supported ARLG has established collaborations in
    19 countries and has recently established a collaboration with the
    Combatting Bacterial Resistance in Europe (COMBACTE) consortium to
    enable joint design and implementation of clinical research on
    antibiotic resistance. NIAID will continue to build on recent progress
    in AMR research, including studies on C. auris, and is committed to
    supporting partnerships with academia, industry, and Federal and
    international partners to develop novel strategies to combat the spread
    of AMR in bacterial and fungal pathogens.
                           new kinds of investigators
        Question. How have the BRAIN initiative and efforts around
    Alzheimer's disease helped recruit new investigators from various
    disciplines with diverse skill sets and backgrounds to work in these
    areas, and what have been the results? Is this something that could and
    should be replicated in other parts of NIH?
        Answer. The challenge, allure, and importance of understanding the
    brain and its disorders have always attracted scientists and clinicians
    with diverse skills and backgrounds. The Brain Research through
    Advancing Innovative NeuroTechnologies (BRAIN) Initiative, which is
    advancing the frontiers of technology and of brain science, has
    attracted an even wider breadth of skill and talent. The Initiative has
    engaged the full spectrum of neuroscientists and clinicians, including
    neurologists, neurosurgeons, and psychiatrists, and recruited experts
    from disciplines that include behavior, chemistry, cell biology,
    mathematics, nanoscience, optics, and physics, as well as computer
    science and informatics. More than a quarter of researchers at the
    BRAIN Initiative Annual Investigators meeting this April were
    engineers, which reflects the strong emphasis on technology
    development. About a quarter of principal investigators are also early
    stage investigators, receiving their first independent NIH funding, and
    many other project leaders and members of research teams are entirely
    new to neuroscience.
        To recruit this broad spectrum of investigators, the Initiative has
    emphasized the importance of diverse expertise since its inception.
    Funding opportunity announcements explicitly call for innovative and
    diverse approaches, with integration of technology developers and
    neuroscientists, and of theorists, computational biologists, and
    experimentalists. Peer review panels are attuned to this priority of
    the Initiative. Extensive outreach has reinforced this emphasis.
        NIH has also been particularly successful in encouraging early-
    stage investigators as well as established investigators not previously
    focusing on Alzheimer's disease and related dementias (AD/ADRD) to
    apply for AD/ADRD-related research funding. An internal NIA analysis
    has shown that between 2015 and 2018, over a quarter of the Institute's
    Research Project Grant (R01) equivalent AD/ADRD awardees were either
    NIH-designated New Investigators (i.e., this was their first
    competitive NIH grant) or Early-Stage Investigators (not only was this
    their first competitive NIH grant, but they were also within 10 years
    of their terminal degree). Approximately one third of the R01 AD/ADRD
    awardees had not previously applied for AD/ADRD funding from NIH--just
    below half of whom were established investigators previously pursuing
    other lines of research. We anticipate that the success of these
    investigators in securing funding will ensure an active pipeline of
    energetic researchers looking at AD/ADRD from new perspectives for
    years to come.
        Recognizing the importance of bringing fresh perspectives, NIA also
    released a notice in 2018 inviting researchers holding non-AD/ADRD
    grants from other NIH Institutes and Offices to apply for supplemental
    funding for new research that was relevant to both AD/ADRD and the
    topic of their research grant. The response was robust. Over 300
    supplements were awarded to investigators representing some 25 NIH
    Institutes, Centers, and Offices, broadening the spectrum of research
    and inspiring investigators to think creatively about how their area of
    study could interface productively with research on AD/ADRD.
        Although each disease and field of medicine presents unique
    challenges, NIH is certainly learning from Alzheimer's disease research
    and the BRAIN Initiative on the value of bringing in diverse expertise
    and new investigators and the strategies to accomplish that. Just as
    the Human Genome Project stimulated many areas of science and medicine
    beyond genetics, we expect the knowledge, technology, and strategies
    stimulated by the BRAIN Initiative and the aggressive goals of
    Alzheimer's and related dementias research will have much broader
    implications. NIH will continue to track progress in multi-disciplinary
    collaborations to ensure best practices are promulgated.
                           methamphetamine treatment
        Question. Parts of the U.S. are seeing an alarming increase in
    methamphetamine overdoses over the past few years. As you know, there
    are currently no FDA-approved treatments for methamphetamine
    dependence. What can you tell me about NIDA's efforts to develop
    treatments methamphetamine addiction?
        Answer. NIH is committed to addressing the alarming increase in
    methamphetamine overdoses, which rose fivefold from 1999 to 2017. As
    mentioned, there are currently no FDA-approved treatments for
    methamphetamine dependence and the most effective treatments are
    behavioral therapies, such as cognitive behavioral therapy and
    contingency management. While drug targets exist for methamphetamine
    that are analogous to those used in treating opioid addiction, alcohol
    addiction, and nicotine addiction, targeting them has not been
    similarly successful, necessitating a novel drug development approach.
        NIH, primarily through NIDA, continues to invest in tackling
    methamphetamine addiction, investing roughly $49 million on
    methamphetamine research in fiscal year 2018. NIDA takes a multi-
    pronged approach to this challenge, balancing its portfolio across
    basic research on the health effects of use, epidemiology of use and
    addiction, and efforts aimed at developing new treatments. This
    strategy allows researchers to test promising treatments and to
    leverage our increasing understanding of methamphetamine's mechanism of
    action to devise new ones. Importantly, as part of this portfolio, NIDA
    supports clinical trials using a wide range of potential approaches,
    from targeting signaling pathways involved in building tolerance to
    methamphetamine, to exploring immunotherapy and anti-inflammatory
    approaches, to testing effective pharmacotherapies for opioid use
    disorder that might have potential to help in methamphetamine use.
        Much of the research in this area to date has involved testing
    drugs that are already approved for other conditions, such as
    antidepressants and medications for opioid use disorder. While none of
    the drugs tested to date were sufficiently effective to warrant use in
    routine treatment, one potentially promising therapy uses antibodies
    that bind to methamphetamine and block it from reaching the brain, thus
    preventing both the euphoric effects and the brain changes that lead to
    addiction. NIDA is also supporting the study of behavioral
    interventions using mobile apps that might help individuals with
    methamphetamine addiction adhere to treatment and remain abstinent.
    While many of the trials are still in the fairly early stages, some
    have yielded preliminary analyses that may offer hope for patients
    suffering from methamphetamine dependence.
                                     ______

                Questions Submitted by Senator Richard J. Durbin
                                   new funding
        Question. Over the past 4 years, this Committee has provided NIH
    with more than $9 billion in increased funding, a 30 percent increase.
    Dr. Collins, what has this 30 percent increase meant to NIH? What new
    initiatives or projects have you been able to establish as a result of
    the new funding? How many new and promising grants have you been able
    to fund with the additional funding?
        Answer. These resources have supported a broad range of research
    conducted both through NIH's intramural research program and through
    the tens of thousands of extramural researchers in institutions across
    the country. This truly exciting, world class science is leading to
    breakthroughs in multiple areas.
        More than two-thirds of the NIH budget supports extramural research
    grants, and funding for these grants grew 33 percent over the last 4
    years, slightly faster than the 30 percent overall budget increase.
    Funding for research project grants (RPGs), which are the classic
    mechanism of support for investigator-led research into specific
    biomedical research questions, grew by 37 percent over this period.
    This funding increase allowed NIH to increase the number of RPG awards,
    while also compensating researchers for the effects of biomedical
    research inflation. The total number of RPG awards grew by 7,010, or 20
    percent, from fiscal year 2015 through fiscal year 2019. Meanwhile, the
    number of new and competing awards grew by 2,135, or 22 percent. This
    increase allowed the RPG success rate to rise from 18.3 percent in
    fiscal year 2015 to an estimated 20.3 percent in fiscal year 2019 in
    spite of an increase of more than 10 percent in the number of
    applications. Increased resources have allowed NIH to initiate or
    expand a number of critical research programs. The following list
    highlights just a few examples:\111\
    ---------------------------------------------------------------------------
        \111\ Estimates for Alzheimer's Disease and antimicrobial
    resistance are from NIH estimates of support for research, condition,
    and disease categories (RCDC), available on the NIH website at https://
    report.nih.gov/. These estimates show research support for 288
    research, condition, and disease categories ranging alphabetically from
    Acquired Cognitive Impairment to Youth Violence Prevention, including
    project detail for completed years.
    ---------------------------------------------------------------------------
      --All of Us. Initiated in fiscal year 2016, the NIH All of Us
            Research Program is a historic effort to gather data from one
            million or more people living in the U.S. to accelerate
            research and improve health. All of Us, funded in part with
            amounts authorized by the 21st Century Cures Act, is a key
            element of the Precision Medicine Initiative (PMI), which seeks
            to take into account individual differences in lifestyle,
            environment, and biology to enable prevention and treatment
            strategies tailored to individuals. All of Us will serve as a
            national research resource to support thousands of studies,
            covering a wide variety of health conditions. As of early April
            2019, more than 212,000 people had begun the enrollment
            process, and more than 129,000 had completed all the steps in
            the protocol.
      --Cancer Moonshot. Resources authorized by the Cures Act for the Beau
            Biden Cancer Moonshot are catalyzing progress in a number of
            areas to improve diagnosis and treatment of a broad range of
            cancers. Investments in the rapidly advancing field of cancer
            immunotherapy are particularly promising in harnessing the
            body's own immune system to fight off the disease. Resources
            are also being used to create a national ecosystem for sharing
            and analyzing cancer data to facilitate efficient data
            analysis, to overcome drug resistance of cancer cells, and to
            minimize the debilitating side effects of some cancer
            treatments.
      --Brain Research through Advancing Innovative Neurotechnologies
            (BRAIN) Initiative. The BRAIN Initiative, which is also
            supported in part with Cures Act funding, seeks to develop and
            apply technologies that will revolutionize our understanding of
            the human brain in health and disease. The initiative has
            supported research identifying the gene expression patterns of
            different subtypes of brain cells that can identify what makes
            different types of cells unique, demonstrating the use of
            neurotechnologies with clinical applications, such as deep
            brain stimulation, and mapping functional circuits across the
            brain, paving the way for an unprecedented level of
            understanding of the human brain and improving human health.
      --Helping to End Addiction Long-Term (HEAL). The HEAL Initiative,
            first funded in fiscal year 2018, aims to bring scientific
            solutions to address the crisis of opioid addiction and to
            provide safe and effective options for the more than 25 million
            Americans who suffer from daily chronic pain. Through HEAL, NIH
            is building on basic science discoveries to accelerate the
            development of novel medications and devices to treat all
            aspects of the opioid addiction cycle, including chronic use,
            withdrawal symptoms, craving, relapse, and overdose. In
            addition, studies on integrating prevention and treatment
            approaches into practice, including the HEALing Communities
            study, will inform understanding of how the implementation of
            promising and evidence-based strategies and treatments can
            decrease opioid use disorder and overdose deaths.
      --Alzheimer's Disease. Overall NIH funding for research into
            Alzheimer's Disease and related dementias (AD/ADRD) has grown
            almost threefold over the last 4 years, from $631 million in
            fiscal year 2015 to $2,468 million in fiscal year 2019.1
            Approximately 70 funding opportunity announcements (FOAs)
            relating to AD/ADRD are currently active, including new
            clinical and preclinical studies. A new NIH-supported clinical
            trials consortium is expected to accelerate and expand studies
            for therapies in Alzheimer's Disease and related dementias. The
            Alzheimer's Clinical Trial Consortium (ACTC) will encompass 35
            sites across the United States, and will address the timeframe,
            complexity and expense of the recruitment process and site
            activation for Alzheimer's trials to find new and effective
            ways to treat or prevent these devastating disorders.
      --Combatting Antimicrobial Resistance. NIH-funded research to combat
            the rising public health problem of drug-resistant bacteria has
            nearly doubled since fiscal year 2015.1 Antibiotic resistant
            bacteria cause at least 2 million infections and 23,000 deaths
            each year in the United States, according to the CDC. These
            efforts include the Antimicrobial Resistance Diagnostic
            Challenge, a $20 million Federal prize competition seeking
            innovative, rapid point-of-care laboratory diagnostic tests to
            combat the development and spread of drug resistant bacteria.
            Five finalists in the competition were announced in December of
            2018.
        --The Challenge is a joint effort between the National Institutes
                of Health and the HHS Office of the Assistant Secretary for
                Preparedness and Response (ASPR) in support of the National
                Action Plan for Combating Antibiotic Resistant Bacteria.
                NIAID and ASPR's BARDA are each contributing $10 million to
                the Challenge. The Challenge also was developed with
                technical and regulatory expertise from the CDC, the FDA,
                and NIH Office of the Director.
      --Universal Flu Vaccine. In fiscal year 2018, NIH unveiled a
            strategic plan to guide future basic, translational, and
            clinical research investments in areas essential to creating a
            safe and effective universal influenza vaccine. Along this
            path, NIH is funding basic research to understand the
            transmission, natural history, and disease process of
            influenza. Several universal flu vaccine strategies are already
            being tested in NIH-supported clinical trials.
      --Down Syndrome. The INCLUDE (INvestigation of Co-occurring
            conditions across the Lifespan to Understand Down syndromE)
            project, launched in fiscal year 2018, is a new trans-NIH
            research initiative on critical health and quality-of-life
            needs for individuals with Down syndrome. INCLUDE will assemble
            a large study population of individuals with Down syndrome and
            include individuals with Down syndrome in existing clinical
            trials. Individuals with Down syndrome are at higher risk for
            certain diseases such as Alzheimer's Disease, but at lower risk
            for others such as coronary artery disease and solid tumors,
            raising the possibility that better understanding Down syndrome
            will yield health benefits for the general population as well.
                                  e-cigarettes
        Question. Big Tobacco says e-cigarettes are a ``safe'' alternative
    to cigarettes, a way to get people to stop smoking. They make this
    claim despite never having conducted a clinical trial in the U.S. to
    prove it. So, while we don't actually know if e-cigarettes help adults
    quit, we do know that they are causing kids to start vaping and
    smoking. In 2018, youth use of e-cigarettes increased by 78 percent
    among high school students, and 48 percent among middle-school
    students. Today, nearly 4 million children are using e-cigarettes. This
    dramatic uptick is due to products like JUUL and kid-friendly flavors--
    fruit medley, fruity pebbles, choco milkshake, smurf, gummy bear. 81
    percent of kids vaping started with a flavored product. What is even
    more alarming is that there's evidence to suggest that e-cigarettes are
    actually causing kids to start smoking cigarettes! Dr. Collins, Dr.
    Lowy, and Dr. Volkow, are you alarmed by what you've seen with the
    massive increase in youth use of e-cigarettes? Just last week, the FDA
    reported that some people were having seizures as a result of e-
    cigarette use. What do we know about the health effects of e-
    cigarettes, especially for children?
        Answer. Any increase in nicotine use among adolescents is alarming.
    While youth cigarette smoking is at an all-time low, overall nicotine
    use through vaping is rising and reversing these gains. There is a
    perception that vaping is harmless because it does not involve the
    burning of tobacco--the source of carcinogenic tar in combustible
    cigarette smoke. While the long-term health impacts of e-cigarette use
    are unknown, emerging data from toxicological, animal, and human
    studies point to some concerning precursors to disease endpoints and
    health effects. For example:
      --Chemicals that are known carcinogens--for example, formaldehyde--
            have been found in e-cigarette aerosol and are found in
            increasing amounts at higher heat levels.\112\
    ---------------------------------------------------------------------------
        \112\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954153/.
    ---------------------------------------------------------------------------
      --Primary exposure to e-cigarette aerosol may increase oxidative
            stress and inflammation, important risk factors for cancer,
            cardiovascular, and pulmonary health consequences.\113\ For
            example, earlier this year, NCI-supported researchers published
            findings that people who vaped were nearly twice as likely to
            experience wheezing compared to people who didn't regularly use
            tobacco products.\114\
    ---------------------------------------------------------------------------
        \113\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768608/.
        \114\ https://www.ncbi.nlm.nih.gov/pubmed/30760629.
    ---------------------------------------------------------------------------
      --E-cigarette use may cause lasting changes to gene expression.
            Preliminary results from a study of nearly 100 e-cigarette
            users led by NIEHS intramural investigators suggest that e-
            cigarette use may cause unique patterns of DNA modifications in
            blood cells which could alter gene expression in these cells.
      --Nicotine exposure during adolescence can cause addiction and harm
            the developing brain. NIDA, along with NCI, NIAAA, and other
            NIH Institutes and Centers, is leading the Adolescent Brain and
            Cognitive Development Study, which will examine the effects of
            environmental factors, including nicotine use, on the
            developing brains of adolescents.
        FDA recently reported on 35 cases of seizures among people who have
    used e-cigarettes, including youth and young adults, between 2010 and
    2019. Although seizure is a known potential consequence of nicotine
    poisoning, FDA cautioned that it does not know if there is a direct
    relationship between e-cigarette use and seizure risk, or how e-
    cigarette use behavior, use of other substances, or underlying
    conditions may have contributed to these seizures.\115\ Despite those
    unknowns, NIH agrees with the FDA that it is important to share
    information on potential serious risks with the public as it becomes
    evident.
    ---------------------------------------------------------------------------
        \115\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
    ucm635157.htm.
    ---------------------------------------------------------------------------
        Several studies, some funded by an FDA-NIH partnership, demonstrate
    that e-cigarette use among never-smoking youth is a risk factor for
    future cigarette smoking.\116\ One found that non-smoking youth who try
    e-cigarettes are more likely to use combustible tobacco products in the
    future than never users of e-cigarettes.\117\ This is particularly
    worrisome considering that viewing e-cigarette advertising is
    associated with initiating e-cigarette use among youth,\118\ and
    exposure to e-cigarette ads on social media sites increases the
    likelihood of subsequent e-cigarette use among youth who had never used
    e-cigarettes.\119\
    ---------------------------------------------------------------------------
        \116\ https://jamanetwork.com/journals/jamapediatrics/fullarticle/
    2634377;https://www.ncbi.
    nlm.nih.gov/pubmed/26348249;https://www.ncbi.nlm.nih.gov/pubmed/
    26811353;
    https://www.ncbi.nlm.nih.gov/pubmed/27296866.
        \117\ https://jamanetwork.com/journals/jama/fullarticle/
    2428954?resultClick=3,.
        \118\ https://www.ncbi.nlm.nih.gov/pubmed/29582078.
        \119\ https://www.ncbi.nlm.nih.gov/pubmed/29432916.
    ---------------------------------------------------------------------------
        Research regarding e-cigarettes and other electronic nicotine
    delivery systems (ENDS) (an umbrella term which includes JUUL), is of
    high interest to NIH. NIH recently developed and published two trans-
    NIH Funding Opportunity Announcements--one calling for research on the
    population, applied, and clinical impacts of ENDS \120\ and the other
    on basic science studies of the health effects from ENDS.\121\ NHLBI
    also organized a two-day meeting of scientific experts in 2015 that led
    to two grant solicitations, one in 2017 and one in 2018. Twenty
    research projects have been awarded through these programs, including
    animal studies on the effect of e-cigarettes on young versus old
    hearts,\122\ the susceptibility of adolescent airways to e-cigarette
    exposure,\123\ and the cardiopulmonary health of individuals in
    households where family members smoke e-cigarettes.\124\ In addition,
    NIH is studying how prevention and cessation approaches developed for
    combustible cigarettes might be adapted for similar purposes in e-
    cigarettes. By furthering our understanding of how they are used, how
    they affect the body, and how we can implement strategies to prevent
    and reduce their use, NIH aims to find ways to reverse this alarming
    trend and reduce the harms associated with it.
    ---------------------------------------------------------------------------
        \120\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-612.html.
        \121\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-476.html.
        \122\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9624711&icde=
    44343194&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
        \123\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9567413&icde=
    44343005&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
        \124\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9564974&icde=44342386.
    ---------------------------------------------------------------------------
                                infant mortality
        Question. Too often in our country, new moms and infants--
    especially women and babies of color--are dying from preventable health
    problems. The U.S. is one of only 13 countries where our maternal
    mortality rates are worse today than they were 25 years ago.
    Nationwide, more than 700 women die every year as a result of
    pregnancy--more than 70,000 others experience severe, near-fatal
    complications. In Illinois, 73 women die every year due to pregnancy-
    related complications--70 percent of these deaths are deemed
    preventable. We are also losing babies. Annually, more than 23,000
    babies die in the U.S., many due to preventable factors. Education and
    income offer no protection--a black woman with an advanced degree is
    more likely to lose her baby than a white woman with less than an
    eighth-grade education. Dr. Collins, why is this happening in the year
    2019? What research is NIH doing with respect to infant and maternal
    mortality, especially for women and babies of color?
        Answer. NIH supports a large and diverse portfolio of research in
    maternal health, pregnancy and pregnancy outcomes, and infant
    mortality, including stillbirth and Sudden Infant Death Syndrome
    (SIDS). For example, in fiscal year 2018, NIH funded approximately $303
    million on research related to maternal health.\125\ The NICHD is
    holding a number of workshops aimed at looking at the high rate of
    maternal mortality in the U.S., with a focus on the factors that are
    contributing to maternal deaths in black women. The first, in April
    2019, was a forum for members of community-based and healthcare
    provider groups about community engagement strategies to improve
    maternal health. Participants learned how patient-provider interactions
    and the process for making clinical care decisions affect maternal
    healthcare experiences at the local level. The second workshop, to be
    held May 2019, will bring scientific experts together to discuss
    research needed to address maternal mortality in the U.S. Participants
    will examine data quality and trends, the populations
    disproportionately affected, social determinants of maternal mortality,
    and clinical causes of this serious public health issue. Among the
    issues to be discussed are potential causes of the disparities in
    maternal mortality, such as medical mistrust, neighborhood environment,
    and the cultural frameworks needed to improve maternal health outcomes.
    A third workshop, to be held in early 2020, will focus on research
    needed by the medical community to address maternal mortality due to
    co-morbid conditions such as obesity, hypertension and diabetes,
    conditions prevalent in black women. Finally, as requested by Congress,
    NICHD has also contracted with the National Academies of Sciences,
    Engineering, and Medicine to conduct a study on the choice of birth
    setting, including risk factors, social determinants that influence
    risk, and maternal health outcomes.
    ---------------------------------------------------------------------------
        \125\ https://report.nih.gov/
    categorical_spending_project_listing.aspx?FY=2018&ARRA=
    N&DCat=Maternal Health.
    ---------------------------------------------------------------------------
        In the meantime, NICHD continues to fund investigator-initiated
    prevention research on the factors that promote healthy pregnancy,
    e.g., weight gain in pregnancy, lifestyle interventions, and efforts to
    reduce exposure of pregnant women to risk factors. For example, a
    recent NICHD-funded study showed that health outcomes associated with
    short interpregnancy intervals vary by age. Compared to younger
    mothers, mothers over 35 are at higher risk of death and serious
    illness if they conceive 6 months or less after the birth of a previous
    child.
        NICHD also supports a range of research projects related to
    pregnancy loss and other adverse pregnancy outcomes, determinants
    (e.g., biomarkers) of healthy pregnancies, and disparities among racial
    and ethnic groups and geographic regions. Among NICHD's research
    priorities are the development of specific algorithms that include
    physiological, biochemical, and genetic markers to predict pregnant
    women at risk for pregnancy loss and/or stillbirth, improving the
    chances for intervention. One NICHD-supported study published in 2018
    found that, in an animal model, Zika virus infection caused early loss
    of one-quarter of the pregnancies. Unfortunately, many causes of
    pregnancy loss are still unknown and could result from chromosomal
    factors, problems with the placenta, fetal infection, and maternal
    disorders. Environmental exposures also may influence pregnancy loss.
    For example, population-based research conducted in NICHD's intramural
    division found that excessive exposure to high ozone levels during the
    last week of pregnancy, and exposures to extremes in temperature,
    increased the risk of stillbirths.
        NICHD has a longstanding program of research on newborn screening,
    part of the highly successful, nationwide newborn screening public
    health effort that allows infants with serious or even fatal conditions
    to be identified for early treatment. The research component, The
    Hunter Kelly Newborn Screening Research Program, was originally
    established as a provision of The Newborn Screening Saves Lives Act of
    2007. Research under the program, led by NICHD, focuses on identifying,
    developing, and testing new newborn screening technologies in order to
    improve existing tests and develop new tests, and developing and
    testing innovative interventions and treatments for conditions that can
    be detected through screening, but which are not yet treatable. In the
    past year, a NICHD-funded study developed a newborn screening tool to
    detect Niemann-Pick Disease, a rare but fatal disorder. Niemann-Pick
    disease type C (NPC) is a rare but fatal disorder that is caused by
    defects in how the body stores cholesterol. Because NPC symptoms vary
    widely, the disease often goes undetected, causing the brain and body
    to degenerate beyond the point of treatment. NICHD-supported
    researchers found that one bile acid is increased 101-fold in patients
    with NPC, and quickly developed a method to detect this bile acid in
    dried blood spots; the method helps to detect Niemann-Pick disease in
    patients after birth, allowing doctors to treat them as soon as
    possible.
        In the meantime, NICHD continues to fund research to uncover the
    causes of SIDS. Among the many research grants that NICHD recently
    funded are hippocampus and brain stem studies in SIDS infants, cardiac
    channel mutations, and respiratory and autonomic mechanisms potentially
    underlying SIDS. In addition, NICHD's leadership of the Safe to Sleep
    public education campaign, working with its many collaborators, allows
    us to translate scientific findings on Sudden Unexpected Infant Death
    and Sudden Infant Deaths Syndrome (SUID-SIDS) into audience-tailored
    actionable messages. These efforts provide training, education, and
    support for parents and families, healthcare providers, and other
    infant caregivers in applying safe infant sleep practices. We
    collaborate closely with our Federal HHS partners to ensure consistent
    public communication. NICHD also supports focused activities with
    health departments in areas with high SUID-SIDS rates to train service
    providers and community leaders on effective risk-reduction practices
    and outreach tactics. For instance, one currently funded grant is
    exploring ways of enhancing safe sleep practices of urban low-income
    mothers.
                                   big pharma
        Question. All 210 drugs approved by the Food and Drug
    Administration (FDA) between 2010 and 2016 received NIH funding. But
    today, Americans are being hit twice by Big Pharma--we pay the highest
    prices in the world for many drugs, and we fund the development of them
    in the first place, mostly from NIH. On top of that, drug companies
    exploit another government-granted reward, the patent system. Two of
    the costliest cancer drugs are Rituxan and Revlimid. Both were
    developed with NIH funding, and both have received over 40 years of
    monopoly protection--because both of these medications has been issued
    more than 94 patents. The top 12 best-selling drugs in the United
    States each have an average of 71 patents, and their prices have
    increased by an average of 70 percent over the last 5 years. In fact,
    74 percent of all new drug patents are for drugs already on the
    market--extending monopolies well-past the 20-year patent term. In
    fiscal year 2017, the NIH executed 328 licensing agreements to transfer
    government- and taxpayer-funded intellectual property to industry to
    bring these inventions to market. Dr. Collins, do you believe drug
    companies are abusing the patent system? Do you believe that the
    practice of ``evergreening''--by which brand-name pharmaceutical
    companies obtain follow-on patents for often superficial or peripheral
    applications, such as a pill coating, to forestall generic
    competition--places a burden on the patient and societal benefits of
    innovative research?
        Answer. The mission of the NIH is to seek fundamental knowledge
    about the nature and behavior of living systems and the application of
    that knowledge to enhance health, lengthen life, and reduce illness and
    disability. Much of the research supported by the NIH is basic in
    nature, and the findings are published to inform the broader research
    community. The commercial sector may also use this information to
    inform their product discovery efforts. An analysis of 210 FDA approved
    drugs (2000-2016) and the published research associated with these
    drugs suggests that nearly 90 percent of the public sector funding
    underlying first-in-class drugs supported basic research of biological
    mechanisms, rather than drug-specific research (Cleary et al., PNAS,
    March 6, 2018). Every drug, whether first-in-class or a competing
    follow-on, was associated directly or indirectly with NIH-funded
    research. When the patent and regulatory exclusivity periods for these
    drugs end, they become generic.
        The NIH licenses technologies arising from the NIH intramural
    research program. Only 35 (11 percent) of the 328 license agreements
    executed by the NIH in fiscal year 2017 were exclusive licenses. In
    2018, NIH executed 329 license agreements, of which 26 (8 percent) were
    exclusive. The category of exclusive licenses often includes more than
    one exclusive license for a patented technology based on separate
    fields of use, e.g. a potential cancer therapy where one company
    develops it for blood cancers, another for solid tumors, and a third
    only in combination with its existing brand name drug. The category of
    non-exclusive license agreements includes commercial use of patented
    technologies and licenses for non-patented research materials such as
    cell lines, animal models and antibodies, which companies use in their
    research and development programs. NIH does not charge fees to transfer
    these non-patented research materials to non-profit researchers.
        Thus, NIH funding supports much basic research that is ultimately
    used by many for-profit researchers to develop new drugs for the
    prevention and treatment of disease conditions. Non-profit researchers
    make use of these published findings to further the understanding of
    biological processes and sometimes the development of new drugs. The
    innovative output of the US biomedical sector depends on this
    foundational government support. NIH manages the licensing of its own
    inventions in a manner that balances public health needs with
    incentives required by the private sector to bring new products to
    market. The NIH has no comment on the patent system because it is
    beyond the purview of NIH.
                        cost of specialty oncology drugs
        Question. The cost of specialty oncology drugs has increased more
    than 500 percent from 2006 to 2015, which is only expected to continue.
    Several studies and clinical trials, including those supported by NCI,
    have demonstrated significant cost savings from examination of de-
    escalation in dose, schedule, or duration of oncology medications, or
    simply by taking medication with or without food. Such trials can be
    self-financing, in that the relative savings from the optimized doses
    could be put toward the trial operation. For example, the NCI recently
    supported an international randomized study comparing a 75 percent dose
    reduction (with food) to standard dosing for the prostate cancer drug,
    abiraterone, which demonstrated no decline in efficacy with the lower
    dose. Separately, the National Eye Institute funded a study in 2011 to
    examine optimal dosing for ranibizumab.
        Does NIH believe that there may be a potential clinical benefit for
    patients to the study of optimal drug dosing and frequency regimens, in
    particular for oncology medications?
        Answer. The NCI conducts and supports research to identify when
    patients will benefit from treatment, and when multiple therapies will
    not provide patient outcomes. Reducing the frequency and number of
    therapies a patient receives during cancer treatment not only reduces
    healthcare costs but often minimizes the risk of side effects,
    complications, and long-term (late) effects. Researchers are
    capitalizing on advances in molecular and genetic profiling of cancers
    to develop clinical studies that will help to identify when it is
    appropriate to de-escalate doses, adjust treatment schedules, or
    shorten the duration of oncology therapies.
        The mission of the NCI clinical trials programs includes an
    emphasis on filling gaps in the national cancer research effort and
    avoiding duplicating on-going private sector efforts. Research
    questions focused on de-escalation of standard therapies, or
    distributing less therapy, are not likely to be answered by industry-
    sponsored trials--leaving a research gap that the NCI's clinical trials
    program seeks to fill. Removing or de-escalating well-accepted standard
    therapies in oncology requires significant care. Randomized trials are
    the gold standard, but require large numbers of patients and rigorous
    study design. NCI has supported several de-escalation studies through
    its National Clinical Trials Network, including recent trials in breast
    cancer and head and neck cancer.
        The Trial Assigning Individualized Options for Treatment (TAILORx)
    was a large phase 3 trial designed to evaluate the benefit of
    chemotherapy for patients with certain early stage breast cancers and
    an intermediate risk of recurrence based on the 21-gene breast cancer
    assay, Oncotype DX. Between 2006 and 2010, more than 10,000 patients
    were screened and more than 6,700 with a moderate risk of recurrence
    were randomized between hormonal therapy alone vs. hormonal therapy
    plus chemotherapy. The trial was designed to show that hormonal therapy
    alone is as effective at preventing recurrence, second cancers, or
    death as hormonal therapy plus chemotherapy. The trial results,
    published in the New England Journal of Medicine in July 2018,
    demonstrated that hormonal therapy alone and hormonal therapy with
    chemotherapy were similarly effective in this patient population,
    although some benefit of chemotherapy was found in some women over 50
    years old.\126\ This de-escalation trial demonstrated that chemotherapy
    could be safely dropped from therapy for this early stage breast cancer
    patient population--saving thousands of patients the burden and
    toxicity associated with chemotherapy treatment.
    ---------------------------------------------------------------------------
        \126\ https://www.ncbi.nlm.nih.gov/pubmed/29860917.
    ---------------------------------------------------------------------------
        Human papillomavirus (HPV)-driven head and neck (oropharyngeal)
    cancers have significantly better survival rates than tobacco and
    alcohol-induced head and neck cancers. HPV-positive (HPV+) patients are
    typically younger, healthier, and often likely to survive their
    disease. The goal of de-escalation trials for patients with HPV+
    oropharyngeal cancers is to see if short and long-term toxicity can be
    reduced while maintaining high survival rates. The Phase 3 NRG/RTOG-
    1016 trial was designed to see if the medication cetuximab therapy plus
    radiotherapy (RT) was as effective at controlling HPV+ oropharyngeal
    cancers as standard cisplatin therapy with RT, but with fewer side
    effects. The study opened in 2011 and closed in 2014, having screened
    987 patients for HPV+ tumors and randomizing 849 patients between the
    two therapeutic approaches. However, the trial's results, which were
    published in Lancet in January 2019, confirmed that cisplatin and
    radiation should remain the standard of care for HPV-related
    oropharyngeal cancers.\127\ This trial demonstrated the importance of
    testing such hypotheses to ensure that patients continue to receive the
    best care for their disease.
    ---------------------------------------------------------------------------
        \127\ https://www.ncbi.nlm.nih.gov/pubmed/30449625.
    ---------------------------------------------------------------------------
        In addition to de-escalating, investigators also seek to identify
    the optimal dosing schedule for cancer therapies. For example, a recent
    collaboration between NCI intramural investigators in the Center for
    Cancer Research (CCR) and the University of Chicago Comprehensive
    Cancer Center seeks to identify when the interval between cancer
    therapy doses can be safely increased. This research uses
    pharmacological modeling, which predicts the effect of different doses
    and timing based on knowledge of disease processes and the rate at
    which drugs are cleared from the body. Initial results suggest that,
    following the initial treatments, the interval between later doses of
    two cancer therapeutics can be increased without sacrificing efficacy
    in most patients. The treatment schedule identified by this work would
    result in a potential 70 percent cost savings for treatment with the
    medications Pembrolizumab, which is used to treat a number of cancers
    including melanoma and non-small cell lung cancer, and Nivolumab, which
    is approved for treatment of non-small cell lung cancer.\128\ Advances
    in precision medicine, or choosing a therapy based on a cancer's
    particular genetic and molecular profile, may also ultimately help to
    contain healthcare costs. Recent work by several researchers in NCI's
    CCR have focused on classifying several types of cancer, including
    melanoma,\129\ diffuse B-cell lymphoma,\130\ and liver cancer \131\
    into discrete subtypes based on gene expression patterns, as well as
    identifying molecular similarities between different tumor types.
    Identifying these different subtypes allows researchers and clinicians
    to better predict which treatments are likely to be effective for a
    patient and limit the use of expensive therapies with little hope of
    activity and potentially drive down costs.
    ---------------------------------------------------------------------------
        \128\ American Society for Clinical Oncology 2019 Annual Meeting,
    Poster #107, Abstract #3115: A modeling and simulation study of less
    frequent dosing of nivolumab 480 mg. Peer, Cody J.; Goldstein, Daniel
    A.; Figg, William D.; Ratain, Mark J.
        \129\ https://ccr.cancer.gov/news/milestones-2019/article/
    predicting-immunotherapy-responses.
        \130\ https://ccr.cancer.gov/news/milestones-2019/article/sorting-
    lymphoma-subtypes.
        \131\ https://ccr.cancer.gov/news/milestones-2018/article/
    different-and-the-same.
    ---------------------------------------------------------------------------
        As NCI leaders discussed in a recent article feature in the Journal
    of the American Medical Association (JAMA), the costs of conducting the
    clinical trials required for drug approvals contribute to the list
    prices of pharmaceutical products. The average per-patient costs have
    increased dramatically during the past two decades, an important factor
    in the total costs of drug discovery and development. Therefore, NCI is
    working to ensure that trials are appropriately sized to answer the
    scientific questions they pose, developing trials with fewer patients
    whenever possible. For example, in some trials of highly active agents,
    it may be possible to evaluate the drug without traditional control
    trials arms, instead relying on ``synthetic'' control groups created
    from data from previous trials. NCI is also considering the use of
    novel end points for clinical trials that are based on the agent's
    mechanisms of action and conducted through the aggregation of new and
    existing data.\132\
    ---------------------------------------------------------------------------
        \132\ https://jamanetwork.com/journals/jama/fullarticle/2723062.
    ---------------------------------------------------------------------------
        NCI will continue to work closely with the FDA and other Federal
    agencies and support research on the best therapeutic approaches for
    patients.
                                childhood trauma
        Question. So many children nationwide grow up in homes where they
    witness violence or drug misuse, or face abuse or neglect. I see this
    all over Chicago, but also in rural communities in my state. With the
    Adverse Childhood Experiences (ACEs) study, we now understand how this
    toxic stress from these situations can have serious, long-term impacts
    on the developing mind. Studies show that exposure to multiple ACEs or
    traumatic experiences increases the likelihood of chronic disease
    development, mental illness, drug use, poverty, and violence.
    Thankfully, there are interventions that can help children cope with
    this trauma, and process the experiences they have faced. This
    Subcommittee has included my language with Senator Capito each of the
    past 2 years to prioritize these trauma-informed best practices in more
    Federal grant programs. And Section 7132 of the SUPPORT for Patients
    and Communities Act established a Federal interagency task force to
    identify and disseminate such trauma-informed best practices. Dr.
    Collins, what research is NIH doing to study childhood trauma and its
    impact on long-term mental health and other outcomes, as well as
    interventions to mitigate the impact of such adversity? What more do we
    need to study?
        Answer. NIH, acting largely through NICHD, and NIMH, supports
    research on the mental and physical health effects of trauma, including
    funding investigator-initiated research related to improving our
    understanding of childhood trauma and its long-term impact and
    broadening the evidence-base needed to improve treatments,
    interventions, and mental health services for trauma survivors.
        The NICHD Pediatric Trauma and Critical Illness Branch was
    established in 2012 to coalesce the science in trauma, injury and
    critical illness across the Institute and to grow the field in these
    areas across the continuum of care.\133\ Of particular interest are
    studies that examine interactions between physical and psychological
    trauma, emergency medical services to children, injury prevention and
    the provision of critical care medicine to the most vulnerable
    children.\134\ The Branch's research portfolio on psychological trauma,
    traumatic stress, violence, and child maltreatment supports projects
    that examine the psychological processes that co-occur with physical
    trauma, which affect treatment, recovery, and well-being. To grow and
    maintain the pipeline of research experts in this area, NICHD also
    supports research training programs, such Career Development Awards,
    focused on training in child maltreatment research, and a national
    physician scientist training program for pediatric trauma surgeons and
    intensive care physicians.\135\
    ---------------------------------------------------------------------------
        \133\ https://www.nichd.nih.gov/sites/default/files/publications/
    pubs/Documents/Pediatric
    Trauma_Action_Agenda.pdf.
        \134\ https://injuryprevention.bmj.com/content/injuryprev/21/6/
    441.full.pdf.
        \135\ https://www.nichd.nih.gov/research/supported/pcctsdp.
    ---------------------------------------------------------------------------
        Recently, NICHD called for research resource-related projects on
    the epidemiology and prevention of injury, receiving an excellent
    response from the field. Among the projects funded is a study on the
    value of pediatric readiness in the emergency care of injured children.
    Its major goal is to construct a large, multi-State dataset to
    determine if pediatric readiness in emergency medicine will result in
    improved quality of care, patient health outcomes, and costs of care
    for injured children. This project will produce the largest population-
    based, pediatric trauma database, a unique research resource that would
    fill important knowledge gaps in pediatric trauma care and help to
    identify a re-engineered, high-value emergency care system for injured
    children that optimizes quality, outcomes, and costs. A second project
    was funded to provide a research and treatment resource for the
    management of psychological distress in children who have been
    hospitalized for a physical trauma. The researchers are developing
    multi-media therapeutic modules to ameliorate post-traumatic stress
    symptoms and associated psychological impairment in children after an
    injury to improve health related quality of life.
        NICHD's hallmark program is the Capstone Centers for Child
    Maltreatment Research and Training. In 2018, funding was awarded to
    three new centers (for a total of four) to serve as national resources
    for research on the prevention, screening and treatment of child abuse
    and neglect.\136\ This program has already been productive; findings
    recently released from the first center showed that adverse childhood
    experiences, including being abused and having parents with mental
    health issues, are associated with higher out-of-pocket healthcare
    costs later in life.
    ---------------------------------------------------------------------------
        \136\ https://www.nichd.nih.gov/newsroom/news/100418-child-
    maltreatment-research.
    ---------------------------------------------------------------------------
        NIMH recognizes that psychological trauma is an emotionally
    painful, shocking, stressful, and sometimes life-threatening
    experience. The cumulative nature of adverse childhood experiences can
    increase the risk for poor mental and physical health outcomes.\137\ To
    better understand trauma-related risk trajectories and how early life
    adversity shapes emotional, cognitive, and brain development, NIMH is
    supporting a landmark study on the developmental precursors of mental
    illnesses.\138\ Researchers are following mothers and their infants
    over the first 3 years of life to characterize development across
    multiple levels of analysis, from environmental risk to physiology to
    neural circuits to behavior. This research has the potential to define
    the contributions of modifiable factors (psychosocial adversity,
    inflammation, and early caregiver support) to the earliest indicators
    of risk for psychopathology, and may pave the way for innovative early
    interventions, and a greater understanding of childhood trauma.
    ---------------------------------------------------------------------------
        \137\ https://www.ncbi.nlm.nih.gov/pubmed/16311898.
        \138\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9518320.
    ---------------------------------------------------------------------------
        There remain many unanswered questions in the field of childhood
    trauma. Currently, NIMH supports over 120 human and animal research
    projects related to post-traumatic stress disorder (PTSD) across the
    lifespan. Through a robust traumatic stress research program that
    includes basic, translational, and services and intervention
    research,\139\ NIMH seeks to gain a deeper understanding of how
    exposure to traumatic stress affects individuals, and how to improve
    ways of identifying those at risk before adverse reactions develop.
    Current NIMH priorities also include testing preventive interventions
    to preempt PTSD, developing new treatments for PTSD, and making
    existing PTSD treatments more effective and accessible.
    ---------------------------------------------------------------------------
        \139\ https://www.nimh.nih.gov/about/organization/dtr/traumatic-
    stress-research-and-
    dimensional-measurement-and-intervention-program/index.shtml.
    ---------------------------------------------------------------------------
                                     ______

                    Questions Submitted by Senator Jack Reed
                                childhood cancer
        Question. As you know, there is strong bipartisan support for the
    Childhood Cancer STAR Act, which was signed into law last year. For
    fiscal year 2019, we provided $30 million to fund this law, the largest
    piece of which we anticipated would be dedicated to developing a
    national childhood cancer biorepository. What progress have you made in
    this area, and how much of the $30 million provided by Congress do you
    anticipate investing in the biorepositories this year?
        Answer. NCI appreciates the strong bipartisan support for childhood
    cancer research demonstrated through passage of the Childhood Cancer
    STAR Act, and NIH is committed to implementing its provisions. At NCI,
    efforts are underway to implement the childhood cancer survivorship
    research and biospecimen and biorepository research provisions, as well
    as other provisions focused on enhancing pediatric expertise on NCI
    advisory boards, and continued reporting on childhood cancer research
    activities.
        NCI continues to make progress in expanding and enhancing
    biospecimen collection and related research. For many years, NCI has
    supported the Children's Oncology Group (COG) and the COG
    Biorepository, and these efforts serve as NCI's central effort to bank
    biospecimens from children and adolescents with cancer for future
    research use. The Institute is hosting a scientific meeting in May 2019
    to bring together representatives from across the COG, including those
    involved in the COG Biorepository, and subject matter experts from
    across the childhood cancer research community who focus on specimen
    collection for cancer subtypes that are most refractory to treatment.
    NCI has invited colleagues from the Centers for Disease Control and
    Prevention's National Program of Cancer Registries to this meeting, as
    well as members of the childhood cancer advocacy community.
        This meeting will provide an opportunity to discuss specimen
    collection and biobanking challenges, particularly those related to
    specimen sharing across institutions, standardization of specimen
    annotation, and specimen quality control. The meeting will also focus
    on opportunities to further enhance specimen collection and storage, to
    encourage greater collaboration across institutions, to collect
    additional high-priority specimens outside the context of clinical
    trials, and to ensure that any new specimen collection efforts are
    complementary to those underway, such as ongoing collection and
    analysis of specimens at relapse through the NCI-COG Pediatric MATCH
    trial.\140\
    ---------------------------------------------------------------------------
        \140\ https://www.cancer.gov/about-cancer/treatment/clinical-
    trials/nci-supported/pediatric-match.
    ---------------------------------------------------------------------------
        We look forward to the valuable guidance and input this discussion
    will provide to the entire childhood cancer research community, which
    may inform any additional new biospecimen collection efforts or
    biorepository resource enhancements in fiscal year 2019, fiscal year
    2020, and beyond, to further implement these provisions of the STAR
    Act. While NCI is committed to making significant investments to
    advance this important work, we also recognize that the STAR Act
    authorization of $30 million per year covers all sections of the
    legislation, including aspects of the law that are directed at other
    entities within the Department of Health and Human Services.
        In fiscal year 2019, NCI is making several new investments to
    support biospecimen collection and analysis that align with STAR Act
    provisions. These include biospecimen analysis studies within NCI
    pediatric and the adolescent and young adult (AYA) clinical
    trials;\141\ the NCI Pediatric Oncology Branch MyPART (My Pediatric and
    Adult Rare Tumor) Network;\142\ and the Center for Pediatric Tumor Cell
    Atlas, part of the Cancer Moonshot Human Tumor Atlas Network. The
    Center, located at the Children's Hospital of Philadelphia, will focus
    on three high-risk cancer subtypes that combined, account for 50
    percent of all pediatric cancer deaths: high-grade glioma, high-risk
    neuroblastoma, and very high risk acute lymphoblastic B-cell precursor
    leukemia.\143\ NCI has also prioritized additional new funds in fiscal
    year 2019 for our National Clinical Trials Network Groups, including
    COG, to improve patient enrollment in clinical trials. Efforts are also
    underway through the Cancer Moonshot to perform retrospective analysis
    on pediatric biospecimens. The retrospective analysis involves
    additional sequencing of specimens from several completed COG trials,
    allowing for in-depth annotation of these specimens to support future
    research. These investments are all in addition to NCI's long-term
    commitment to supporting specimen collection through COG clinical
    trials, and specimen storage through the COG Biorepository.
    ---------------------------------------------------------------------------
        \141\ https://www.cancer.gov/about-nci/organization/ccct/funding/
    biqsfp.
        \142\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor.
        \143\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9627531&icde=0.
    ---------------------------------------------------------------------------
        There is a compelling need for the childhood cancer research and
    advocacy community to discuss opportunities specific to biospecimen
    collection and biorepository resources. Understanding these insights is
    best before we develop any new funding opportunity announcements to
    ensure that these rare and much needed research participant
    contributions are maximally impactful. With that principle in mind, NCI
    anticipates that fiscal year 2020 STAR Act implementation activities
    will expand emphasis on biorepositories, whereas fiscal year 2019 STAR
    Act implementation activities will include greater emphasis on
    survivorship research.
        Question. Can you provide additional details on the President's
    childhood cancer initiative and how it will coordinate with the STAR
    Act programs? Can you confirm that this $50 million request is in
    addition to the $30 million in funding that we secured in fiscal year
    2019 (and which we are seeking on a bipartisan basis to build on in
    fiscal year 2020)?
        Answer. There are approximately 16,000 children and adolescents
    diagnosed with cancer in the United States each year. The President's
    Budget proposes an additional $50 million in fiscal year 2020, to
    continue for 10 years and provide a total of $500 million to support
    the Childhood Cancer Data Initiative. This initiative focuses on the
    critical need to obtain and analyzing data to learn from children with
    cancer. This information, spanning the spectrum of tumor analysis to
    clinical care and outcomes of each child, will underpin our ability to
    develop new approaches to cure children with cancer.
        The additional resources of $50 million in fiscal year 2020 will
    allow the NCI to expand efforts to collect data, to make strides in
    federating existing sources of data, to ensure that data concerning
    childhood cancers are appropriately accessible and used, and to
    incentivize the cancer research community to develop new treatments for
    children with cancer. The initiative is a promising opportunity to
    enhance our ability to improve outcomes for children with cancer--first
    by learning from every one of these children in an intentional and
    organized manner and second by developing more efficient ways to share
    and use the information. We envision that it will aggregate the
    necessary information to foster essential research while also
    increasing available information about each child's illness. Such
    information will include extensive sequencing of tumors and additional
    clinical information regarding each child's response to treatment.
        NCI is hopeful that the Childhood Cancer Data Initiative will also
    serve as a force multiplier for efforts aligned with implementation of
    the Childhood Cancer STAR Act. NCI-supported biospecimen collection and
    associated data would all contribute to the aggregated data resources
    NCI plans to develop through the initiative. NCI would also aim to
    integrate data collected though new and continued childhood cancer
    survivorship research projects and ongoing longitudinal studies (e.g.,
    Childhood Cancer Survivor Study, St. Jude Lifetime Study) through the
    initiative. New data linkages and resources may also enable the cancer
    research community to establish additional cohorts to complement the
    Childhood Cancer Survivor Study, allowing NCI to study the long-term
    effects of new immunotherapy and targeted chemotherapy treatments. NCI
    is also exploring opportunities to leverage data collected through NCI
    and CDC cancer registries programs, including data collected though
    CDC's early case capture efforts for pediatric and young adult cancer
    cases. This program is a central piece of CDC's STAR Act
    implementation, and the Childhood Cancer Data Initiative has the
    potential to further build upon that work.
        In summary, NCI will continue these important research efforts with
    whatever resources are available to us. If appropriated, the
    President's Budget request envisions the $50 million proposed for the
    Childhood Cancer Data Initiative as additional new resources. In the
    current fiscal year, NCI is supporting implementation of the STAR Act
    provisions that are directed toward the Institute. For example, in
    addition to continuing to conduct and support childhood, AYA cancer
    survivorship research, NCI is expanding support in this area for new
    research projects. Specifically, NCI issued a new request for
    applications in fiscal year 2019. We estimate that we will allocate
    approximately $4.8 million per year for 5 years, to this survivorship
    research priority, subject to receiving meritorious applications and
    future fiscal year funding, among other considerations. NCI is also
    working to enhance biospecimen collection, biobanking, and related
    resources for childhood and AYA cancers, with an emphasis on those
    cancer types and subtypes for which treatments are least effective, as
    specifically encouraged in the STAR Act.
                                    suicide
        Question. CDC reported in June 2018 that the suicide rate has risen
    30 percent since 1999. Given this national crisis, can you discuss what
    research is being conducted on suicide prevention research at the NIMH
    and how does NIMH set research priorities specific to suicide and
    suicide prevention?
        Answer. Suicide prevention research continues to be a top priority
    for NIH.\144\ Over the past several years, NIH has steadily increased
    its support for suicide research. NIH spent approximately $46 million
    on suicide research in fiscal year 2015, $52 million in fiscal year
    2016, $68 million in fiscal year 2017, and $96 million in fiscal year
    2018.
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        \144\ https://www.nimh.nih.gov/about/director/messages/suicide-
    prevention.shtml.
    ---------------------------------------------------------------------------
        As the lead Federal agency for research on mental disorders, the
    National Institute of Mental Health (NIMH) within the NIH takes a
    central role in research aimed at identifying at-risk individuals and
    developing new treatments and interventions, ultimately to improve
    quality of life and prevent death. NIMH recognizes that comprehensive
    suicide prevention efforts require multiple approaches, with the
    following research projects exemplifying some of our most promising
    tools.
    Identifying At-Risk Individuals:
      --Implementing Universal Screening: The Emergency Department Safety
            Assessment and Follow-up Evaluation (ED-SAFE) study
            demonstrated that a three-item screening tool improved
            providers' ability to identify adults at risk for suicide.\145\
            This study showed that when screening was conducted for all
            patients--regardless of the reason for their emergency
            department (ED) visit--suicide risk detection increased nearly
            twofold. If these findings remain true when scaled up, the
            public health impact could be tremendous, because
            identification of risk is the first and necessary step for
            preventing suicide.
    ---------------------------------------------------------------------------
        \145\ https://www.ncbi.nlm.nih.gov/pubmed/26654691.
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      --Maximizing Electronic Health Records: Building on the Army Study to
            Assess Risk and Resilience in Servicemembers (Army
            STARRS),\146\ the largest study of mental health risk and
            resilience ever conducted among military personnel, researchers
            from NIMH partnered with the Department of Veterans Affairs
            (VA) and other collaborators to develop predictive models of
            suicide risk among veterans receiving VA healthcare. This
            research demonstrated the feasibility of developing algorithms
            to identify patients within the VA system whose predicted
            suicide risk was 20-30 times higher than average. Suicide
            prevention coordinators at each VA facility work with these
            patients and their clinicians on suicide-focused clinical
            assessment and ways to enhance treatment. Other healthcare
            systems are beginning to use data from electronic health
            records in novel ways to help identify people with suicide
            risk, including many of the 13 healthcare systems across the
            United States that are part of NIMH's Mental Health Research
            Network.\147\
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        \146\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286426/.
        \147\ https://www.ncbi.nlm.nih.gov/pubmed/29792051.
    ---------------------------------------------------------------------------
    Developing New Treatments and Interventions:
      --Strengthening Mental Health Support: NIMH continues to support
            research to identify effective interventions for individuals at
            risk for suicide. One such intervention is Safety Planning
            Intervention (SPI), in which a clinician collaborates with the
            patient to identify specific strategies to decrease the risk of
            suicidal behavior, such as ways to reduce the patients' access
            to lethal means during a time of crisis, and to identify
            personalized coping strategies. NIMH is supporting an
            evaluation of the implementation of the Zero Suicide approach,
            including SPI, in 145 community mental health clinics across
            New York.\148\ In addition, NIMH's ED-SAFE study, which focused
            on ED patients at risk for suicide, found that brief
            interventions in the ED, plus follow-up phone calls to the
            patient by a clinician, reduced suicide attempts by about 30
            percent during a 12-month period.\149\
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        \148\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9514242.
        \149\ https://www.ncbi.nlm.nih.gov/pubmed/28456130.
    ---------------------------------------------------------------------------
      --Deploying Fast-Acting Pharmacologic Interventions: NIMH research
            has also supported the study of fast-acting treatments for
            individuals with acute suicide risk. Ketamine, an anesthetic
            that has been around for decades, is emerging as a rapid onset
            intervention. NIMH researchers showed that suicidal ideation
            (in the context of major depressive disorder) was reduced
            within 40 minutes of a ketamine infusion and remained improved
            for up to four hours post-infusion.\150\ A subsequent meta-
            analysis reported that a single infusion of ketamine reduces
            suicidal ideation for up to one week.\151\ In March 2019, the
            FDA approved SpravatoTM, an esketamine nasal spray
            (a form of ketamine), in conjunction with an oral
            antidepressant, for treatment-resistant depression.\152\ This
            treatment is only available at a trained doctor's office or
            clinic to mitigate potential risks. The makers of
            SpravatoTM are also conducting clinical trials of
            intranasal esketamine in participants at imminent risk for
            suicide.\153\
    ---------------------------------------------------------------------------
        \150\ https://www.ncbi.nlm.nih.gov/pubmed/20673547.
        \151\ https://www.ncbi.nlm.nih.gov/pubmed/28969441.
        \152\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
    ucm632761.htm.
        \153\ https://www.ncbi.nlm.nih.gov/pubmed/29656663.
    ---------------------------------------------------------------------------
        NIMH's overall research priorities continue to be informed by
    strategic planning and include the input of stakeholders, advisory
    committees, and NIMH leadership. In developing these priorities, NIMH
    strives to balance public health needs and scientific opportunities,
    taking into consideration portfolio balance among other factors. For
    example, specific to suicide prevention, the stakeholder-informed
    Prioritized Research Agenda for Suicide Prevention is an available
    resource that can be used to help identify gaps in the NIMH suicide
    prevention portfolio.\154\ NIMH only funds research which is judged
    highly meritorious and follows a two-stage peer review process.
    ---------------------------------------------------------------------------
        \154\ https://theactionalliance.org/resource/prioritized-research-
    agenda-suicide-prevention-action-plan-save-lives.
    ---------------------------------------------------------------------------
        Question. The recently released action plan from the National
    Action Alliance for Suicide Prevention outlines the need to develop a
    prioritized approach for allocating funds and monitoring future suicide
    research to ensure that available resources are directed towards
    research with the greatest likelihood of reducing suicide deaths. Has
    NIH reviewed these recommendations and, if so, what does NIH plan to do
    with the recommendations?
        Answer. NIMH is working with scientists and stakeholders to address
    the increasing incidence of suicide across the country, focusing on
    identifying research gaps, challenges, and opportunities to inform how
    to make change now and in the longer-term. Under the leadership of
    former NIMH Director Thomas Insel, M.D., the Research Prioritization
    Task Force (RPTF) aimed to advance the efforts of the National Action
    Alliance for Suicide Prevention (NAASP), a public-private partnership
    among Federal agencies, State governments, private companies, and
    national suicide prevention advisory and advocacy groups. As part of
    the RPTF, NIMH helped to develop the Prioritized Research Agenda for
    Suicide Prevention.\155\ The Agenda identifies research gaps, such as
    limitations in understanding of the etiology and course of suicidal
    ideation and behavior, the need for new interventions specifically
    targeting suicide, better matching of existing treatments to individual
    needs, and implementation of effective suicide prevention practices.
    ---------------------------------------------------------------------------
        \155\ https://theactionalliance.org/resource/prioritized-research-
    agenda-suicide-prevention-action-plan-save-lives.
    ---------------------------------------------------------------------------
        NIMH has initiated research opportunities to address research gaps
    identified in the Agenda, such as studies to develop and test screening
    approaches for use in EDs to identify youth at risk for suicide, and
    develop methods to help assign youth who screen positive to appropriate
    interventions.\156\ NIMH also partnered with other NIH Institutes and
    Centers to support projects leveraging existing data sets to improve
    our understanding of risk trajectories and subgroups at risk for
    suicide, while addressing suicide research gaps in mortality
    outcomes.\157,158\ To further address gaps in the research workforce,
    NIMH issued a notice of special interest to expand the number of mental
    health researchers--both established scientists, as well as early
    career scientists--who engage in suicide research.\159\
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        \156\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
    070.html.
        \157\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
    400.html.
        \158\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
    410.html.
        \159\ https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-
    026.html.
    ---------------------------------------------------------------------------
        In addition, NIMH partners with NAASP to support their Zero Suicide
    initiative.\160\ Zero Suicide is a commitment, a goal, and a campaign
    to prevent suicide attempts and deaths among individuals receiving
    treatment within healthcare systems. NIMH is funding several projects
    aimed at Zero Suicide to create a stronger basis for dissemination and
    large-scale implementation of effective risk detection, intervention,
    and service delivery strategies for suicide prevention in real world
    settings.\161\ This effort is also consistent with the NIMH Strategic
    Plan for Research, Objective 4, improving public health through more
    practice-ready suicide prevention interventions.\162\
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        \160\ http://zerosuicide.sprc.org/.
        \161\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-
    800.html.
        \162\ https://www.nimh.nih.gov/about/strategic-planning-reports/
    strategic-objective-4.shtml.
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                                     ______

                Questions Submitted by Senator Patrick J. Leahy
                                   migraines
        Question. Migraine is currently the second leading cause of all
    global disability. Unfortunately, due in part to limited research and
    treatment, inappropriate opioid prescriptions for migraine present
    Americans with ongoing risks of opioid use disorders and have worsened
    outcomes in patients. The NIH website on disease burden shows
    ``migraine'' to have received by far the lowest level of research
    funding in 2015, among those diseases with the highest burden. In 2017,
    only 53 extramural investigators were funded for headache research,
    compared to 315 for epilepsy and 385 for schizophrenia, each of which
    has far lower burden than migraine. While migraine grant proposals are
    eligible for consideration under the HEAL RFAs recently issued for pain
    research, I am very concerned that these will fail to attract enough
    investigators to this historically under-funded research area.
        Does NIH have plans to issue specific RFA programs for headache
    disorders research, comparable in scope to the BACPAC group of RFAs for
    research on back pain?
        Answer. NIH recognizes the burden of headache disorders as
    prevalent and disabling conditions for patients around the country.
        NIH has identified priority areas of need unique to headache
    research, including fundamental mechanisms to guide new treatment
    development and advancing treatments through the clinical pipeline.
    Importantly, headache research is an area with trans-NIH interest for
    which funding has increased from $18 million in 2010 to $32 million in
    2018. NIH has supported important research that is providing exciting
    new therapies for headache. Basic research on potassium channels, delta
    or kappa opioid receptors, and TRP channels has fundamentally increased
    our understanding of trigeminal nociceptors and their involvement in
    initiating a migraine, giving us new targets for potential treatments.
    NIH investigators also provided the foundation for development of
    calcitonin gene receptor protein (CGRP) antibodies now used for
    migraine therapy. In addition, NIH sponsored research also led to
    efforts exploring the promising avenue of vagus nerve stimulation for
    headaches. Lastly, a pivotal trial on pediatric migraine is shifting
    clinical practice toward safer and more effective therapies. These
    exciting advances are all examples of NIH efforts toward relieving the
    burden of headache disorders.
        In addition, NIH's long-standing programs in these specific areas
    will be greatly enhanced by the recently launched HEAL (Helping to End
    Addiction Long-term) initiative and its efforts to advance the research
    agenda for pain and care across pain conditions. Through HEAL, NIH
    released many funding opportunity announcements for research on
    biomarker discovery, device and drug development, clinical trials on
    effectiveness of interventions and pragmatic trials for implementation
    of effective therapies for pain conditions. Headache research fits
    within the scope of all these initiatives and NIH has made strong
    efforts to network with and encourage the headache research community
    to submit applications to these solicitations. Furthermore, the
    infrastructure and resources being established through the HEAL
    initiative will be available to enhance pain research across all
    conditions which will greatly inform new areas of mechanisms for
    headache research.
        The HEAL BacPac Initiative was designed to fill a unique need for
    another highly prevalent pain condition for which much of the research
    framework is inadequate. Back pain is unique in that it lacks accurate
    diagnostic tools and assessments, a clear classification scheme based
    on causality, understating of the underlying mechanisms, and effective
    treatment approaches. Unlike the case for back pain, the diagnostics
    and classifications for headache disorders are better established and
    our understanding of the mechanisms of headaches is moving forward
    through existing programs and can be further advanced through HEAL with
    the participation of the headache research community.
                             cardiovascular disease
        Question. Over the past half-century, we have witnessed
    unprecedented progress in addressing cardiovascular disease, yet recent
    trends show that declines in heart disease and stroke mortality rates
    have slowed for all races and are increasing substantially among
    certain population groups such as rural, middle-aged white Americans.
    The American Heart Association recently announced new alarming data
    that shows that nearly half (48 percent) of U.S. adults have some form
    of cardiovascular disease.
        As our Nation's population ages, there is an urgent need for action
    to improve innovation in the treatment of cardiovascular disease. What
    is NIH doing to address the high rates of cardiovascular mortality,
    especially in rural areas like my home State of Vermont?
        Answer. The NIH is committed to ensuring that all Americans benefit
    from the life-saving advances made possible by federally funded
    research--regardless of their race, age, sex, income, or where they
    live. The National Heart, Lung, and Blood Institute (NHLBI) leads NIH's
    support for research on cardiovascular disease (CVD). Over the past 50
    years, research funded by the NHLBI has helped bring about a 71 percent
    decline in deaths from CVD nationwide. However, CVD remains the
    Nation's leading cause of death, with the highest mortality
    concentrated in certain groups, including African Americans, American
    Indian/Alaska Natives, and rural communities. We are supporting
    research to determine what causes these health disparities and how to
    correct them.
        High blood pressure is a leading risk factor for heart disease and
    stroke. Given that blood pressure medication dosing and adherence is a
    major challenge in rural and underserved communities, NHLBI is
    supporting innovative methods to help patients connect with
    pharmacists. For example, NHLBI's Collaboration Among Pharmacist and
    Physicians toto Improve Outcomes Now (CAPTION) study embedded
    pharmacists within 32 primary care physicians' offices in 15 states,
    serving high-risk socioeconomic and racial groups. After 9 months,
    patients treated through this physician-pharmacist team approach had
    sustained reductions in blood pressure, compared to patients who
    received usual care.\163\ Another recent NHLBI-funded study found that
    having blood pressure screenings and pharmacist consultations in
    barbershops helped men lower their blood pressure.\164\ Innovative
    programs like these could be adapted and used in rural settings to
    reduce hypertension and other cardiovascular risk factors.
    ---------------------------------------------------------------------------
        \163\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063695.
        \164\ https://www.ncbi.nlm.nih.gov/pubmed/29527973.
    ---------------------------------------------------------------------------
        A new NHLBI program launched in March 2019, Disparities Elimination
    through Coordinated Interventions to Prevent and Control Heart and Lung
    Disease Risk (DECIPHeR) will help bring evidence-based interventions
    like these to communities with a high burden of CVD. DECIPHeR
    researchers will form partnerships with local healthcare systems,
    government agencies, and community organizations so researchers and
    community members can work together to design, test, and sustain
    effective approaches to deliver proven treatments.\165\
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        \165\ https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-20-
    003.html.
    ---------------------------------------------------------------------------
        NHLBI also recently solicited proposals for new large cohort
    studies to address research on heart, lung, blood, and sleep disorders,
    with an emphasis on groups that are currently not well represented,
    including rural communities.\166\ We expect to fund three such cohorts
    later this year.
    ---------------------------------------------------------------------------
        \166\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-577.html.
    ---------------------------------------------------------------------------
        NHLBI also supports research to address CVD through telehealth.
    This could include the use of audiovisual technology to deliver remote
    care for patients who live in remote areas or have other challenges
    accessing primary healthcare centers. For example, an ongoing NHLBI-
    funded study is evaluating the effectiveness of traditional center-
    based cardiac rehabilitation combined with telemedicine-guided
    rehabilitation at home.\167\ NHLBI is also funding a study to collect
    national data on the use of telemedicine in intensive care units to
    identify best practices.\168\
    ---------------------------------------------------------------------------
        \167\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9588024.
        \168\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9061809.
    ---------------------------------------------------------------------------
        Rural patients have traditionally been underrepresented in
    cardiovascular clinical trials, yet have a higher burden of CVD than
    patients from metropolitan areas. We are working to increase enrollment
    of rural patients in NHLBI's Cardiothoracic Surgical Trials Network,
    which has made significant contributions in advancing the evidence base
    for cardiothoracic surgery. Dartmouth-Hitchcock Medical Center in New
    Hampshire and Maine Medical Center were recently linked to the network
    to expand its reach into rural communities of Northern New
    England.\169\
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        \169\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9755050.
    ---------------------------------------------------------------------------
                              nih pain consortium
        Question. Pain is a significant public health issue affecting an
    estimated 69.6 million Americans each year. According to the Institute
    of Medicine, the total incremental cost of healthcare due to pain
    management in the U.S. is estimated to range from $560 billion to $635
    billion, amounting to approximately 2.8 to 3.5 percent of our Nation's
    total GDP. This cost estimate combines the direct medical costs of pain
    management care as well as the economic costs related to lost
    productivity and disability programs. With little known about
    alternatives for treating and managing relief from pain, medical
    providers are often limited to prescribing highly addictive opioids or
    muscle relaxants to help patients mitigate symptoms from pain.
        Unfortunately, addiction to opioid painkillers has ravaged the
    Nation, and the number of opioid prescriptions has tripled in the past
    20 years alone. In 1996, the National Institutes of Health (NIH)
    established the NIH Pain Consortium to develop a strategy for research
    on pain. Since then, the NIH has worked to expand research in this
    area, while incorporating the work and expertise of stakeholders to
    find ways to better serve patients.
        Has the NIH Pain Consortium approached research on exploring opioid
    alternatives to treating and managing both acute and chronic pain? If
    so, please describe past, present, and ongoing projects in this area.
    If not, please describe if the NIH plans to develop more research
    focused on finding opioid alternatives to treating and managing acute
    and chronic pain.
        Answer. The NIH recognizes the significant public health crisis and
    individual burden of pain and supports research to better understand,
    manage and treat acute and chronic pain to relieve the burden of pain
    and reduce our reliance on prescription opioid medications.
        The NIH Pain Consortium is a collaboration of 27 Institutes,
    Centers, and Offices (ICOs) across the NIH charged with promoting and
    coordinating pain research across the agency. In 2018 the NIH Pain
    Consortium ICOs collectively spent $605 million on a wide range of
    research collectively aimed at understanding the mechanisms of pain,
    new targets for treatment, and more. NIH has existing programs to
    support development of novel and non-addictive treatments for acute and
    chronic pain, from early-stage drug target discovery of molecular
    pathways of pain signaling, exploration of receptors and channels as
    potential non-addictive analgesic targets, and testing of novel
    treatments in preclinical behavioral models. Through these programs,
    NIH researchers identified nerve growth factor receptor and pain-
    related ion channel targets, which have led to industry-sponsored
    clinical trials for safe pain treatments for musculoskeletal pain and
    other pain disorders. NINDS supported early development of calcitonin
    gene receptor protein, the precursor to a compound recently approved to
    treat migraine. NIH programs for discovery of new formulations,
    combinations of medicines, and re-purposing molecules developed for
    other disorders are being expanded rapidly to find new pain
    medications. Through the NIH Blueprint Neurotherapeutics Program, which
    provides support for small molecule drug discovery and development, NIH
    currently is funding research to develop a non-addictive treatment for
    headache and non-opioid analgesics for diabetic nerve pain.\170\
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        \170\ https://projectreporter.nih.gov/
    project_info_description.cfm?aid=9325694&icde=36528658
    &ddparam=&ddvalue=&ddsub=&cr=3&csb=default&cs=ASC&pball=.
    ---------------------------------------------------------------------------
        The NIH Pain Consortium worked with the Interagency Pain Research
    Coordinating Committee to develop the Federal Pain Research Strategy
    \171\ (FPRS), which outlines a long-term strategic plan to guide NIH
    and other Federal agencies in making their funding decisions to advance
    pain research. The development of safer opioids and new, non-opioid
    analgesics were considered high priority research areas in this
    strategy.
    ---------------------------------------------------------------------------
        \171\ Federal Pain Research Strategy: https://iprcc.nih.gov/sites/
    default/files/iprcc/FPRS_
    Research_Recommendations_Final_508C.pdf.
    ---------------------------------------------------------------------------
        The NIH Pain Consortium, with the FPRS as a guide, has been
    involved in developing and implementing the recently released NIH HEAL
    (Helping to End Addiction Long-term) Initiative,\172\ which aims to
    enhance research to better treat addiction and opioid overdose and to
    improve pain care, thereby reducing our reliance on opioids. HEAL
    supported projects will increase our understanding of pain, expand and
    accelerate the development of non-addictive treatments, and rapidly
    advance new treatments to the clinic. Through HEAL, NIH supports
    biomarker discovery and validation to inform early phase clinical
    testing of potential non-addictive pain therapies. To improve success
    in bringing medications to the clinic, HEAL will facilitate the sharing
    of data on past and future drug development efforts across the
    biopharmaceutical industry and academia. To accelerate testing of novel
    pain treatments in humans, NIH is establishing the HEAL Early Phase
    Pain Clinical Network to test new, non-addictive pain treatments
    through clinical trials. The HEAL initiative also is establishing a
    pain management effectiveness research network to support large
    clinical trials to test the effectiveness of pharmacological and non-
    pharmacological treatments across many pain conditions.
    ---------------------------------------------------------------------------
        \172\ The NIH HEAL Initiative: https://www.nih.gov/research-
    training/medical-research-initiatives/heal-initiative.
    ---------------------------------------------------------------------------
        NIH is working with Federal partners to provide the infrastructure
    through the NIH Health Care Systems Research Collaboratory for
    implementation of non-pharmacological treatments into healthcare
    systems, with the ultimate goal to embed evidence-based best pain
    management practices in clinics. These efforts represent unprecedented
    expansion of the NIH pain research portfolio.
                                     ______

                   Questions Submitted to Douglas Lowy, M.D.
              Questions Submitted by Senator Shelley Moore Capito
                                childhood cancer
        Question. There is strong bipartisan support for childhood cancer
    here in Congress, as evidenced by the overwhelming support for the
    Childhood Cancer STAR Act that was signed into law last year. I was
    very pleased to see the President highlight the vital need to invest
    more in childhood cancer during his State of the Union and in his
    Budget Submission to Congress.
        How does the President's childhood cancer initiative coordinate
    with the STAR Act programs? Is your $50 million request for increased
    childhood cancer funding in addition to the $30 million we are working
    to provide for the STAR Act?
        Answer. There are approximately 16,000 children and adolescents
    diagnosed with cancer in the United States each year. The President's
    Budget proposes an additional $50 million in fiscal year 2020, to
    continue for 10 years and provide a total of $500 million to support
    the Childhood Cancer Data Initiative. This initiative focuses on the
    critical need to obtain and analyze data to learn from children with
    cancer. This information, spanning the spectrum of tumor analysis to
    clinical care and outcomes of each child, will underpin our ability to
    develop new approaches to cure children with cancer.
        The additional resources of $50 million in fiscal year 2020 will
    allow the NCI to expand efforts to collect data, to make strides in
    federating existing sources of data, to ensure that data concerning
    childhood cancers is appropriately accessible and used, and to
    incentivize the cancer research community to develop new treatments for
    children with cancer. The initiative is a promising opportunity to
    enhance our ability to improve outcomes for children with cancer--first
    by learning from every one of these children in an intentional and
    organized manner and second by developing more efficient ways to share
    and use the information. We envision that it will aggregate the
    necessary information to foster essential research while also
    increasing available information about each child's illness. Such
    information will include extensive sequencing of tumors and additional
    clinical information regarding each child's response to treatment.
        The Childhood Cancer Data Initiative should also serve as a force
    multiplier for efforts aligned with implementation of the Childhood
    Cancer STAR Act. NCI-supported biospecimen collection and associated
    data would all contribute to the aggregated data resources NCI plans to
    develop through the initiative. NCI would also aim to integrate data
    collected though new and continued childhood cancer survivorship
    research projects and ongoing longitudinal studies (e.g., Childhood
    Cancer Survivor Study, St. Jude Lifetime Study) through the initiative.
    New data linkages and resources may also enable the cancer research
    community to establish additional cohorts to complement the Childhood
    Cancer Survivor Study, allowing NCI to study the long-term effects of
    new immunotherapy and targeted chemotherapy treatments. NCI is also
    exploring opportunities to leverage data collected through NCI and CDC
    cancer registries programs, including data collected though CDC's early
    case capture efforts for pediatric and young adult cancer cases. This
    program is a central piece of CDC's STAR Act implementation, and the
    Childhood Cancer Data Initiative has the potential to further build
    upon that work.
        In summary, NCI will continue these important research efforts with
    whatever resources are available to us. If appropriated, the
    President's Budget request envisions the $50 million proposed for the
    Childhood Cancer Data Initiative as additional new resources. In the
    current fiscal year, NCI is supporting implementation of the STAR Act
    provisions that are directed toward the Institute. For example, in
    addition to continuing to conduct and support childhood, adolescent,
    and young adult (AYA) cancer survivorship research, NCI is expanding
    support in this area for new research projects. Specifically, NCI
    issued a new request for applications in fiscal year 2019. We estimate
    that we will allocate approximately $4.8 million per year for 5 years,
    to this survivorship research priority, subject to receiving
    meritorious applications, among other considerations. NCI is also
    working to enhance biospecimen collection, biobanking, and related
    resources for childhood and AYA cancers, with an emphasis on those
    cancer types and subtypes for which treatments are least effective, as
    specifically encouraged in the STAR Act.
                                     ______

                Questions Submitted by Senator Richard J. Durbin
                                  ethyl oxide
        Question. I'd like to ask about Ethylene Oxide--or EtO--a gas that
    is widely used for the sterilization of certain medical devices. EtO is
    a carcinogen. The National Cancer Institute acknowledges that exposure
    to this gas has been linked to certain types of cancer, including
    lymphoma, leukemia, and breast cancer. Illinois has three large
    facilities that currently use EtO, including Sterigenics in
    Willowbrook, Illinois, which was recently ordered to stop using EtO,
    after the Environmental Protection Agency measured alarmingly high
    levels of the gas in neighboring communities. Late last month, the
    Illinois Department of Public Health issued a report which showed
    higher rates of certain types of cancers around the Sterigenics
    facility--including Hodgkins lymphoma and breast cancer in women, and
    pediatric lymphoma in young girls. While we do not know yet if these
    cancers are definitively linked to the Sterigenics EtO emissions, they
    are certainly cause for concern. Dr. Lowy, what do we know about
    exposure to EtO? What do you make of reports like the one released by
    the Illinois Department of Public Health?
        Answer. The NCI supports a wide range of research to understand
    associations between exposures and cancer risk, including environmental
    exposures like ethylene oxide (EtO). NCI is committed to supporting
    research to increase our understanding of the complexity of cancer risk
    factors and working with other government agencies responsible for
    regulating such environmental exposures.
        NCI-supported research has contributed to the body of knowledge
    that has led to the classification of EtO as a carcinogen. EtO is used
    primarily to produce other chemicals, including antifreeze, and in
    smaller amounts, EtO is used as a pesticide and a sterilizing agent.
    The ability of EtO to damage DNA makes it an effective sterilizing
    agent but also accounts for its cancer-causing activity. Because EtO is
    highly explosive and reactive, the equipment used for its processing
    generally consists of tightly closed and highly automated systems,
    which decreases the risk of occupational exposure. Despite these
    precautions, workers and people who live near industrial facilities
    that produce or use EtO may be exposed to EtO through uncontrolled
    industrial emissions. The general population may also be exposed
    through tobacco smoke and the use of products that have been sterilized
    with EtO, such as medical products, cosmetics, and beekeeping
    equipment.\173\
    ---------------------------------------------------------------------------
        \173\ https://www.cancer.gov/about-cancer/causes-prevention/risk/
    substances/ethylene-oxide.
    ---------------------------------------------------------------------------
        In 2000, the National Toxicology Program, part of the National
    Institute of Environmental Health Sciences, upgraded EtO from
    ``reasonability anticipated carcinogen'' to a ``known human
    carcinogen.'' \174\ As an analysis conducted by the EPA reaffirmed last
    year, lymphoma and leukemia are the cancers most frequently reported to
    be associated with occupational exposure to ethylene oxide. Stomach and
    breast cancers may also be associated with ethylene oxide
    exposure.\175\
    ---------------------------------------------------------------------------
        \174\ https://www.niehs.nih.gov/news/newsroom/releases/2000/may15/
    index.cfm.
        \175\ https://www.tandfonline.com/doi/full/10.1080/
    15376516.2017.1414343.
    ---------------------------------------------------------------------------
        Because the evidence indicating the carcinogenicity of EtO is well-
    established, NCI has a limited role in responses to suspected cases of
    EtO exposure. In these instances, NCI resources may provide data for
    investigators to determine whether EtO exposure may be contributing to
    high cancer rates. For example, those investigating such claims may use
    data collected by the NCI Surveillance, Epidemiology, and End Results
    (SEER) Program to inform conclusions about how EtO exposure has
    affected cancer incidence. The SEER Program collects information on
    cancer incidence, prevalence, and survival from specific geographic
    areas representing 34 percent of the U.S. population. The SEER research
    datasets, drawn primarily from State cancer registries, include SEER
    incidence and population data associated by age, sex, race, year of
    diagnosis, and geographic areas. SEER also provides analytical tools
    and methodological expertise in collecting, analyzing, interpreting,
    and disseminating population-based statistics.\176\ Another resource
    for those investigating instances of EtO exposure is the NCI Cancer
    Atlas, an exploratory tool that enables users to construct comparative
    maps, graphs, and charts of cancer statistics and risk factors. The NCI
    Cancer Atlas can help with the development of new methods of displaying
    geospatial data for clear communication to the public and for
    examination of complex multivariate data by researchers.\177\ Both the
    SEER Program and the NCI Atlas can act as resources to inform State and
    local health departments when assessing cancer incidence and
    surveillance.
    ---------------------------------------------------------------------------
        \176\ https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf.
        \177\ https://gis.cancer.gov/gis-nci/gis_nci.html.
    ---------------------------------------------------------------------------
        Federal agencies with the authority to research and monitor the
    effects of hazardous substances on human health are the U.S.
    Environmental Protection Agency (EPA), the CDC, and the Agency for
    Toxic Substances and Disease Registry (ATSDR). While the EPA identifies
    certain chemicals as hazardous air pollutants and regulates facilities
    with these emissions,\178\ the CDC is the lead Federal agency on
    addressing public health concerns about potential harmful exposures.
    ATSDR conducts research on the health impacts of specific sites and
    provides information and recommendations to Federal and State agencies,
    including CDC and EPA.\179\ The National Center for Environmental
    Health (NCEH), part of CDC, conducts research to investigate the
    effects of the environment on health by tracking and evaluating
    environment-related health problems through surveillance systems. NCEH
    partners with State, local, and tribal health State departments to
    conduct health surveillance, epidemiologic studies, communication and
    education, standard setting and guidelines, and technical support.\180\
    ---------------------------------------------------------------------------
        \178\ https://www.epa.gov/haps.
        \179\ https://www.atsdr.cdc.gov/about/index.html.
        \180\ https://www.cdc.gov/nceh/information/about.htm.
    ---------------------------------------------------------------------------
        With technical assistance from CDC, State and local health
    departments determine whether a particular exposure is responsible for
    certain cancer cases. NCI assists CDC by supporting epidemiological
    research on cancer surveillance and studies of cancer incidence,
    including those programs mentioned above.
        NCI will continue to work with other Federal agencies to provide
    epidemiological data and other research findings to inform their
    investigation of EtO exposure.
                                     ______

                   Questions Submitted to Anthony Fauci, M.D.
                    Questions Submitted by Senator Roy Blunt
                    antimicrobial and antibiotic resistance
        Question. Fauci, there was a New York Times article on April 7th
    describing the rise of drug-resistant germs. The article highlighted
    that just like bacteria, fungus is now becoming resistant to drugs
    developed to treat them. Over the past 4 years, the Labor/HHS bill has
    included specific funds to combat antibiotic resistance, most recently
    including $550 million in fiscal year 2019 for NIH, 50 percent more
    than you had in fiscal year 2016. Can you discuss the threat of
    antibiotic resistant germs and fungus and explain what research your
    Institute is focusing on in this area?
        Answer. The emergence of antimicrobial resistance (AMR) in a range
    of bacterial and fungal pathogens is a public health threat of great
    concern. Each year in the United States, there are more than 2 million
    infections with antibiotic-resistant bacteria and at least 23,000
    deaths as a direct result of these infections. Fungal infections also
    are a serious problem in healthcare settings, and infections with drug-
    resistant fungi are more difficult to treat. A drug-resistant form of a
    fungal pathogen, Candida auris (C. auris), recently has emerged in the
    United States and elsewhere, and has led to severe illness in
    hospitalized patients. The National Institute of Allergy and Infectious
    Diseases (NIAID) is the lead Institute of the NIH for basic,
    translational, and clinical research confronting the critical issue of
    AMR in bacterial and fungal pathogens.
        Advances in AMR research have created opportunities to develop
    state-of-the-art diagnostics to detect and help limit the spread of
    AMR, accelerate the development of new antimicrobials, identify ways to
    use the immune system to eradicate bacterial or fungal pathogens, and
    manipulate microbial communities to prevent or treat infections. NIAID
    has used recent funding increases provided by Congress to expand its
    comprehensive AMR research portfolio and accelerate research in each of
    these areas of scientific opportunity.
        NIAID supports research to develop rapid point-of-need diagnostics
    to inform appropriate treatment and identify resistance to commonly
    used drugs. NIAID research has led to the development of several novel
    diagnostics capable of distinguishing between numerous infectious
    agents. These include two Food and Drug Administration (FDA)-cleared
    diagnostics: one that tests for 24 bacterial and fungal species that
    cause sepsis, and another that can detect a number of different
    bacterial and viral species that cause pneumonia along with seven
    genetic markers of AMR. In addition, the NIAID Antibacterial Resistance
    Leadership Group, which oversees clinical research on antibiotic
    resistance, is developing a master protocol to allow for the evaluation
    of multiple diagnostic tests using samples from a single patient. NIH
    also is partnering with the Biomedical Advanced Research and
    Development Authority (BARDA) to support the Antimicrobial Resistance
    Diagnostic Challenge competition to identify innovative and rapid
    point-of-need diagnostic tests that inform appropriate antibiotic
    treatment and facilitate antimicrobial stewardship. Submissions for
    Step 3 of the Challenge are due in January 2020, and final results of
    the competition are anticipated in July 2020.
        NIAID's investments in AMR research are advancing the development
    of promising new therapeutic candidates for drug-resistant infections.
    NIAID-supported researchers have developed a method to synthesize novel
    forms of a class of antibiotics (tetracyclines) that are not
    susceptible to existing bacterial resistance mechanisms. One of these
    compounds, XERAVATM, recently received FDA approval to treat
    complicated intra-abdominal infections. NIAID funding also has led to
    the discovery of a new class of antibiotics, malacidins, that are being
    investigated for further therapeutic development. In addition, NIAID
    provides in-kind and technical support for CARB-X (Combating Antibiotic
    Resistant Bacteria-X), a public-private partnership led by BARDA. CARB-
    X is currently funding the development of 35 innovative projects,
    including 13 that represent new antibiotic classes.
        NIAID also supports the development of antifungal therapies,
    including those that may be effective against drug-resistant fungi. One
    fungal pathogen of particular concern is C. auris, which can cause
    serious infections that can affect the blood, heart, brain, eyes,
    bones, and other parts of the body. While most C. auris infections are
    treatable with existing antifungal drugs, the presence of C. auris
    infections resistant to the main classes of antifungal drugs is
    extremely concerning. NIAID is facilitating preclinical screening of
    candidate therapeutics for effectiveness against C. auris and has
    identified several lead candidates. NIAID also is supporting
    investigation of a broad-spectrum antifungal with activity against C.
    auris and other Candida species.
        NIAID-supported investigators are exploring approaches that
    leverage the immune system to combat drug-resistant infections. One
    novel approach uses antibodies to boost the ability of an infected
    individual's own immune system to fight infection. NIAID also is
    advancing the development of candidate vaccines against bacterial and
    fungal pathogens, including strains that exhibit drug resistance. This
    includes an experimental vaccine to protect against Staphylococcus and
    Candida species, including C. auris and Staphylococcus aureus (S.
    aureus). Vaccines against these bacterial and fungal pathogens could
    help prevent infections, thus avoiding the use of antibacterial or
    antifungal drugs and limiting the potential for development of AMR.
        NIAID also supports research investigating the use of beneficial
    bacteria to prevent or treat colonization with pathogenic AMR bacteria.
    NIAID funds studies on the use of fecal microbiota transplants to
    replenish beneficial gut microbiota and prevent and treat bacterial
    infections. This strategy may be particularly effective for difficult-
    to-eradicate infections such as the bacterial species Clostridium
    difficile. In addition, NIAID scientists discovered that the use of
    probiotic digestive supplements containing Bacillus bacteria prevented
    S. aureus bacteria from growing in the gut and nose of healthy
    individuals.
        NIAID recognizes that a multi-pronged, multi-disciplinary approach
    is necessary to address the serious threat posed by drug-resistant
    microbes. NIAID will continue to support the development of improved
    tools and strategies to identify, prevent, and treat infections with
    AMR pathogens.
                             ending hiv initiative
        Question. The President's budget proposes to end HIV transmission
    in the United States in 10 years. Dr. Fauci, can you discuss what is
    necessary to reach this goal, how an HIV vaccine could help achieve it,
    and where you are in the development of a vaccine?
        Answer. The fiscal year 2020 President's Budget has proposed a new
    initiative of the Department of Health and Human Services (HHS) on
    Ending the HIV Epidemic to address the ongoing public health crisis of
    HIV in this country. The goals of the initiative are first reducing
    numbers of new HIV infections in the United States by 75 percent within
    5 years, and then by 90 percent within 10 years. The initiative will
    leverage critical scientific advances in HIV prevention, diagnosis,
    treatment, and care by coordinating the highly successful programs,
    resources, and infrastructure of the NIH, the Centers for Disease
    Control and Prevention, the Health Resources and Services
    Administration, and the Indian Health Service.
        The initiative is coordinated by the HHS Office of the Assistant
    Secretary of Health. During the initial phase of the initiative, the
    focus will be on geographic areas and demographic groups in 19 States,
    Washington, DC, and Puerto Rico, where the majority of new HIV cases
    are reported, as well as in 7 States with a disproportionate occurrence
    of HIV in rural areas. The initiative includes four pillars to help
    reduce HIV infections:
      --Diagnose all individuals with HIV as early as possible after
            infection;
      --Treat HIV infection rapidly and effectively to achieve sustained
            viral suppression;
      --Prevent at-risk individuals from acquiring HIV, including through
            the use of pre-exposure prophylaxis (PrEP); and
      --Rapidly detect and respond to emerging local epidemics of HIV
            infection to further reduce new infections.
        Advances in HIV treatment and prevention research suggest that,
    theoretically, the HIV epidemic in this country could be ended by
    expanding access to treatment to all persons with HIV and PrEP to all
    those at high risk. The Administration has developed a practical,
    achievable plan to focus on the places and populations in the United
    States that are most affected by HIV. Lessons learned and effective
    strategies emanating from this initiative would ultimately be applied
    to profoundly reduce HIV incidence nationwide through Federal, State,
    and local health departments and nongovernmental organizations. NIH-
    supported research through the Centers for AIDS Research (CFARs) and
    AIDS Research Centers will play a critical role in developing best
    practices for the initiative by collecting and disseminating data on
    the effectiveness of approaches used to achieve the initiative's four
    pillars. The fiscal year 2020 President's Budget includes $6 million
    for NIH CFARs to support the HHS Ending the HIV Epidemic initiative.
        The development of a safe and effective HIV vaccine remains a key
    component to realizing an end to the HIV pandemic. If an HIV vaccine
    were to become available, it would add another key HIV prevention tool
    to complement the ongoing efforts on HIV diagnosis, treatment, and
    pharmaceutical-based prevention through this initiative. NIAID is the
    lead for HIV vaccine research at the NIH. Currently, NIAID-supported
    scientists around the world are following two complementary paths to
    accelerate the development of an HIV vaccine.
        The first approach to HIV vaccine development builds upon prior
    partial success of the RV144 vaccine regimen. In 2009, the findings of
    a large international clinical trial of the RV144 vaccine regimen
    showed for the first time that an HIV vaccine approach could confer
    modest protection against HIV. Today, NIH and our global partners are
    continuing to build upon the findings from the RV144 trial. Two large
    HIV vaccine efficacy clinical trials are now ongoing in southern
    Africa, one to evaluate an experimental vaccine regimen based on the
    one used in the RV144 trial, and another to assess an experimental
    ``mosaic'' vaccine candidate designed to induce immune responses
    against a wide variety of global HIV strains. Results from these trials
    are expected in 2022 and 2021, respectively.
        NIAID scientists also are pursuing a second, theoretical path that
    involves studying the body's immune response to HIV infection and
    finding various ways to generate and enhance that response through
    vaccination. One theoretical approach involves designing vaccine
    strategies to generate cellular immune responses capable of protecting
    against HIV infection. Another promising strategy seeks to identify
    potential HIV vaccine targets by uncovering the molecular structure of
    the virus. An additional theoretical approach involves the design of a
    vaccine that elicits broadly neutralizing antibodies, or antibodies to
    HIV that can target multiple different HIV strains. Studies are
    underway to determine whether delivery of such antibodies could provide
    long-acting protection against HIV infection, similar to the way a
    traditional vaccine approach would work. Two large clinical trials with
    sites in the Americas, Europe, and Africa are currently evaluating
    VRC01, a broadly neutralizing antibody developed by the NIAID Vaccine
    Research Center. In addition, planning is underway for early phase
    clinical trials of a three-pronged antibody capable of binding to three
    different critical sites on the surface of HIV. NIAID scientists and
    public-private partners are developing this ``tri-specific'' antibody
    with the expectation that it could eventually be used for long-acting
    HIV prevention and treatment. NIAID scientists also are conducting a
    Phase 1 clinical trial of a therapeutic HIV vaccine regimen that uses
    an adjuvanted DNA vaccine ``prime'' followed by a viral vector
    ``boost'' in participants with HIV. The goal of this vaccine strategy
    is to achieve prolonged undetectable levels of HIV, eliminating the
    need for lifelong anti-retroviral therapy.
        These scientific advances and ongoing investigations provide
    cautious optimism that the development of a safe and effective HIV
    vaccine is making headway. It is important to note that even a
    moderately effective HIV vaccine could substantially slow the HIV
    pandemic, if optimally implemented with current treatment and
    prevention modalities. NIAID is committed to the goal of developing a
    safe and effective HIV vaccine that would complement the HHS Ending the
    HIV Epidemic initiative and help end the HIV pandemic.
                                     ______

                 Questions Submitted to Richard J. Hodes, M.D.
                    Questions Submitted by Senator Roy Blunt
                              alzheimer's disease
        Question. Dr. Hodes, Dr. Randy Bateman, a researcher at Washington
    University in St. Louis, has developed a blood test that can detect the
    build-up of the Alzheimer's protein amyloid years before symptoms
    appear. This is a significant step toward predicting who will develop
    dementia. Further, another Washington University researcher, Dr.
    Gregory Van Stavern, has developed an eye scan that detects changes in
    the retina that may be able to predict Alzheimer's before dementia
    begins. These tools could ultimately save millions in healthcare costs
    because instead of paying thousands of dollars for a PET scan or a
    spinal tap, you will be able to detect the disease through only a blood
    test. Can you talk about the progress of this breakthrough as well as
    other potential ways to better detect Alzheimer's disease?
        Part of the issue with the recent drug failures is that may be
    targeting individuals too late in the disease progression process. Two
    years ago, you and I visited the Alzheimer's prevention trial in
    Medellin, Colombia that focuses on a family that is genetically
    predisposed to early-onset Alzheimer's disease. Can you discuss what
    research your Institute is supporting to prevent or delay Alzheimer's
    disease?
        Answer. Early detection of pathology consistent with Alzheimer's
    disease or a related form of dementia (AD/ADRD) opens a ``window of
    opportunity'' for us to target the disease before clinical symptoms
    appear. NIA supports studies exploring a variety of methods to detect
    AD/ADRD pathology prior to the appearance of symptoms, as well as to
    identify early, subtle signs of disease while cognitive abilities are
    still largely intact.
        The work of Dr. Bateman, who is affiliated with the NIA-supported
    Charles F. and Joanne Knight Alzheimer's Disease Research Center
    (Knight ADRC) at Washington University, uses subtypes of the amyloid
    beta protein in the blood to infer the presence of damaging amyloid
    buildup in the brain. Specifically, they have found that the ratio of
    two subtypes, amyloid beta 42 and 40, can indicate elevated brain
    amyloid. Multiple companies have now begun commercial development of
    diagnostic tests based on the amyloid beta 42/40 ratio.
        Other researchers are also working to identify blood-based
    biomarkers for early detection of AD/ADRD. For example, investigators
    with NIA's Intramural Research Program recently used advanced machine
    learning techniques to identify a panel of 26 blood and brain
    metabolites that were--when present in altered concentrations in
    blood--consistently associated with brain atrophy, cerebrospinal fluid
    measures of Alzheimer's pathology, cognitive performance, and disease
    risk before clinical symptoms appeared. Another team is using changes
    in autoantibodies--part of the body's immune response--as blood-based
    biomarkers to detect early AD/ADRD. Still another is testing special
    ``indicator cells'' as a biosensor for AD pathology.
        Dr. Van Stavern, also affiliated with the Knight ADRC, used a
    noninvasive eye scanning technique, optical coherence tomography (OCT)
    angiography, to detect thinning in the retina as well as alterations in
    retinal blood flow among older people without clinical symptoms of AD/
    ADRD. These findings correlated with elevated levels of amyloid and tau
    proteins as detected by PET scan and cerebrospinal fluid examination.
        Other ongoing, NIA-supported research using ocular biomarkers to
    detect early AD/ADRD includes a study correlating amyloid and tau
    levels in the fluid of the eye with OCT and cognitive testing for early
    detection of Alzheimer's disease. Elsewhere, NIA-supported
    investigators are using an innovative imaging method to detect
    Alzheimer's pathology, disease progression, and treatment response in
    people with Alzheimer's and in mouse models of the disease. In this
    study, individuals drink a solution made with curcumin, a component of
    the spice turmeric. The curcumin acts as a tracer, ``lighting up''
    amyloid in the eye and enabling its detection with a custom-built high-
    definition scanning instrument.
        In addition, NIA-supported investigators are exploring changes in
    smell, gait, personality, and even driving behaviors as early warning
    signs of incipient dementia. Ultimately, we hope to be able to
    intervene either with or prior to the earliest appearance of symptoms
    and thereby avoid progression to the later, devastating stages of
    disease.
        Research to prevent or delay AD/ADRD symptoms in at-risk and/or
    presymptomatic individuals remains a high priority at NIA. The
    Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's
    Disease Trial in Medellin, Colombia is one such study. Recruitment for
    this trial of the anti-amyloid agent Crenezumab among members of a
    family at very high genetic risk for developing the disease has been
    completed, and we anticipate reporting results in 2022. This study is
    one of several being conducted by the API, the goal of which is to
    identify pre-symptomatic interventions that will postpone, slow, or
    prevent the disease's progression.
        Another major initiative, the Dominantly Inherited Alzheimer's
    Network Trials Unit (DIAN-TU), is an international partnership
    dedicated to designing and managing clinical trials for individuals at
    high genetic risk of developing AD.
        The recently funded DIAN-TU Primary Prevention Trial is a 4-year
    study of two drugs, Solanezumab and Gantenerumab--antibodies that
    interact with different forms of amyloid--in 160 asymptomatic
    individuals at high genetic risk. Investigators will determine whether
    it is possible to prevent amyloid deposition in this population and if
    doing so will prevent the cascade of pathology associated with AD and,
    ultimately, dementia, in people who are otherwise certain to get the
    disease.
        In addition to these highly visible initiatives, NIA also supports
    studies of physical activity and exercise, diet, and cognitive training
    to prevent cognitive decline and dementia. Participants in many of
    these studies are at well-established risk of developing dementia but
    do not yet show evidence of cognitive decline.
        A new, NIA-funded Alzheimer's Clinical Trial Consortium (ACTC) will
    help investigators harness best practices and latest methods for both
    treatment and prevention trials. The ACTC includes 35 sites in the
    United States and will address the complexity, time, and expense of
    participant recruitment and site activation to find new and effective
    ways to treat or prevent these devastating disorders.
                                     ______

                    Questions Submitted to Nora Volkow, M.D.
                    Questions Submitted by Senator Roy Blunt
                opioid research and data collection from samhsa
        Question. Dr. Volkow, our Committee has invested significant
    resources into opioid treatment, prevention, education, and research.
    In particular, we now provide States with $1.5 billion in flexible
    State Opioid Response grants and require States to report to SAMHSA on
    how they are spending this funding. I believe it is incredibly
    important that we understand what opioid programs are working and how
    to replicate those programs across the country. Can you discuss (1)
    whether NIH researchers have access to this valuable State-by-State
    data; and (2) what research your Institute is undertaking to better
    understand what programs work and which do not in opioid prevention and
    treatment?
        Answer. (1) NIH researchers can gain access to data collected in
    conjunction with SAMHSA grants, such as the State Targeted Opioid
    Response and State Opioid Response (STR and SOR) grants, through State
    substance use agencies.
        (2) Determining which prevention and treatment approaches are most
    effective is central in addressing the opioid crisis, and this is
    precisely the goal of our HEALing Communities Study. Launched in
    partnership with SAMHSA on April 18, 2019, this multisite
    implementation research study tests the impact of an integrated set of
    evidence-based interventions across healthcare, behavioral health,
    justice, and other community-based settings. The ultimate goal is to
    generate the evidence needed to determine the most effective strategies
    for preventing and treating opioid misuse and opioid use disorder (OUD)
    within highly affected communities. This Study will examine the
    effectiveness of coordinated systems of care designed to reduce
    overdose fatalities and events; decrease the incidence of OUD; increase
    the number of individuals receiving medication to treat OUD, retained
    in treatment, and receiving recovery support services; and increase the
    distribution of naloxone.
        The HEALing Communities Study includes at least 15 communities in
    each of four participating States to measure the impact of these
    targeted strategies. The four institutions leading this research--
    University of Kentucky, Boston Medical Center, Columbia University, and
    The Ohio State University--were required to demonstrate their
    partnership with State governments, and specifically how they plan to
    leverage SAMHSA funding (such as STR and SOR funding) to provide
    evidence-based prevention and treatment services. RTI International,
    based in North Carolina, will serve as the study's coordinating center,
    and will be responsible for data analysis, health economics research,
    and widespread dissemination of research findings over the course of
    the study, under provisions that safeguard the privacy and
    confidentiality of respondents. The data generated by this Study will
    inform best practices for other States looking to maximize the impact
    of their SAMHSA grant funds.
        Question. What barriers exist for NIH and SAMSHA to partner on data
    sharing and how can we help make sure this data is available to the
    research community?
        Answer. NIH has benefitted from a long-standing partnership with
    SAMHSA that facilitates the translation of sound research into
    effective practice and policy. SAMHSA and NIH are in regular contact
    regarding the need for data to be available to researchers. Currently,
    researchers access data compiled for monitoring SAMHSA grants through
    State substance use agencies. This is occurring in a number of recently
    awarded NIH-funded studies. For example, there are currently five
    studies underway to test approaches for expanding medications for OUD
    in the context of SAMHSA STR and SOR grants issued under RFA-DA-18-005
    (with another three studies underway with support from the Arnold
    Foundation). In addition, NIH's National Center for Complementary and
    Integrative Health recently funded five projects examining the impact
    of behavioral and complementary health interventions within the context
    of States' plans for using SAMHSA's STR and SOR grant funds.
        NIH continues to be committed to working with SAMHSA to find
    innovative ways to mutually share data and to ensure the data are
    available to the research community in order to maximize the impact of
    the research.

                              SUBCOMMITTEE RECESS

        Senator Blunt. The subcommittee stands in recess.
        [Whereupon, at 11:45 a.m., Thursday, April 11, the
    subcommittee was recessed, to reconvene subject to the call of
    the Chair.]