    [House Hearing, 115 Congress]
    [From the U.S. Government Publishing Office]

          21ST CENTURY CURES IMPLEMENTATION: UPDATES FROM FDA AND NIH

    =======================================================================

                                    HEARING

                                   BEFORE THE

                             SUBCOMMITTEE ON HEALTH

                                     OF THE

                        COMMITTEE ON ENERGY AND COMMERCE
                            HOUSE OF REPRESENTATIVES

                         ONE HUNDRED FIFTEENTH CONGRESS

                                 SECOND SESSION

                                   __________

                                 JULY 25, 2018

                                   __________

                               Serial No. 115-157

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

          Printed for the use of the Committee on Energy and Commerce

                            energycommerce.house.gov

                             _________

                  U.S. GOVERNMENT PUBLISHING OFFICE

    35-866                WASHINGTON : 2019

                        COMMITTEE ON ENERGY AND COMMERCE

                              GREG WALDEN, Oregon
                                     Chairman
    JOE BARTON, Texas                    FRANK PALLONE, Jr., New Jersey
      Vice Chairman                        Ranking Member
    FRED UPTON, Michigan                 BOBBY L. RUSH, Illinois
    JOHN SHIMKUS, Illinois               ANNA G. ESHOO, California
    MICHAEL C. BURGESS, Texas            ELIOT L. ENGEL, New York
    MARSHA BLACKBURN, Tennessee          GENE GREEN, Texas
    STEVE SCALISE, Louisiana             DIANA DeGETTE, Colorado
    ROBERT E. LATTA, Ohio                MICHAEL F. DOYLE, Pennsylvania
    CATHY McMORRIS RODGERS, Washington   JANICE D. SCHAKOWSKY, Illinois
    GREGG HARPER, Mississippi            G.K. BUTTERFIELD, North Carolina
    LEONARD LANCE, New Jersey            DORIS O. MATSUI, California
    BRETT GUTHRIE, Kentucky              KATHY CASTOR, Florida
    PETE OLSON, Texas                    JOHN P. SARBANES, Maryland
    DAVID B. McKINLEY, West Virginia     JERRY McNERNEY, California
    ADAM KINZINGER, Illinois             PETER WELCH, Vermont
    H. MORGAN GRIFFITH, Virginia         BEN RAY LUJAN, New Mexico
    GUS M. BILIRAKIS, Florida            PAUL TONKO, New York
    BILL JOHNSON, Ohio                   YVETTE D. CLARKE, New York
    BILLY LONG, Missouri                 DAVID LOEBSACK, Iowa
    LARRY BUCSHON, Indiana               KURT SCHRADER, Oregon
    BILL FLORES, Texas                   JOSEPH P. KENNEDY, III,
    SUSAN W. BROOKS, Indiana                 Massachusetts
    MARKWAYNE MULLIN, Oklahoma           TONY CARDENAS, California
    RICHARD HUDSON, North Carolina       RAUL RUIZ, California
    CHRIS COLLINS, New York              SCOTT H. PETERS, California
    KEVIN CRAMER, North Dakota           DEBBIE DINGELL, Michigan
    TIM WALBERG, Michigan
    MIMI WALTERS, California
    RYAN A. COSTELLO, Pennsylvania
    EARL L. ``BUDDY'' CARTER, Georgia
    JEFF DUNCAN, South Carolina
                             Subcommittee on Health

                           MICHAEL C. BURGESS, Texas
                                     Chairman
    BRETT GUTHRIE, Kentucky              GENE GREEN, Texas
      Vice Chairman                        Ranking Member
    JOE BARTON, Texas                    ELIOT L. ENGEL, New York
    FRED UPTON, Michigan                 JANICE D. SCHAKOWSKY, Illinois
    JOHN SHIMKUS, Illinois               G.K. BUTTERFIELD, North Carolina
    MARSHA BLACKBURN, Tennessee          DORIS O. MATSUI, California
    ROBERT E. LATTA, Ohio                KATHY CASTOR, Florida
    CATHY McMORRIS RODGERS, Washington   JOHN P. SARBANES, Maryland
    LEONARD LANCE, New Jersey            BEN RAY LUJAN, New Mexico
    H. MORGAN GRIFFITH, Virginia         KURT SCHRADER, Oregon
    GUS M. BILIRAKIS, Florida            JOSEPH P. KENNEDY, III,
    BILLY LONG, Missouri                     Massachusetts
    LARRY BUCSHON, Indiana               TONY CARDENAS, California
    SUSAN W. BROOKS, Indiana             ANNA G. ESHOO, California
    MARKWAYNE MULLIN, Oklahoma           DIANA DeGETTE, Colorado
    RICHARD HUDSON, North Carolina       FRANK PALLONE, Jr., New Jersey (ex
    CHRIS COLLINS, New York                  officio)
    EARL L. ``BUDDY'' CARTER, Georgia
    GREG WALDEN, Oregon (ex officio)

                                 C O N T E N T S

                                  ----------
                                                                       Page
    Hon. Michael C. Burgess, a Representative in Congress from the
      State of Texas, opening statement..............................     1
        Prepared statement...........................................     3
    Hon. Gene Green, a Representative in Congress from the State of
      Texas, opening statement.......................................     4
        Prepared statement...........................................     5
    Hon. Frank Pallone, Jr., a Representative in Congress from the
      State of New Jersey, opening statement.........................     6
        Prepared statement...........................................     7

                                   Witnesses

    Francis Collins, Director, National Institutes of Health;
      accompanied by Stephanie Devaney, Deputy Director, All Of Us
      Research Program and Norman Sharpless, Director, National
      Cancer Institute...............................................     8
        Prepared statement...........................................    11
    Scott Gottlieb, Commissioner, Food And Drug Administration.......    29
        Prepared statement...........................................    31

          21ST CENTURY CURES IMPLEMENTATION: UPDATES FROM FDA AND NIH

                                  ----------

                            WEDNESDAY, JULY 25, 2018

                      House of Representatives,
                                Subcommittee on Health,
                              Committee on Energy and Commerce,
                                                        Washington, DC.
        The subcommittee met, pursuant to call, at 9:04 a.m., in
    room 2123, Rayburn House Office Building, Hon. Michael Burgess,
    M.D. (chairman of the subcommittee) presiding.
        Present: Representatives Burgess, Guthrie, Barton, Upton,
    Blackburn, Latta, Lance, Griffith, Bilirakis, Long, Bucshon,
    Brooks, Mullin, Hudson, Collins, Carter, Walden (ex officio),
    Green, Schakowsky, Matsui, Castor, Sarbanes, Kennedy, Cardenas,
    Eshoo, DeGette, and Pallone (ex officio).
        Staff Present: Daniel Butler, Legislative Clerk, Health;
    Jordan Davis, Senior Advisor; Adam Fromm, Director of Outreach
    and Coalitions; Caleb Graff, Professional Staff Member, Health;
    Ed Kim, Policy Coordinator, Health; Ryan Long, Deputy Staff
    Director; Brannon Rains, Staff Assistant; Mark Ratner, Policy
    Coordinator; Kristen Shatynski, Professional Staff Member,
    Health; Danielle Steele, Counsel, Health; Austin Stonebraker,
    Press Assistant; Josh Trent, Chief Health Counsel, Health;
    Hamlin Wade, Special Advisor, External Affairs; Waverly Gordon,
    Minority Health Counsel; Tiffany Guarascio, Minority Deputy
    Staff Director and Chief Health Advisor; Samantha Satchell,
    Minority Senior Policy Analyst; Andrew Souvall, Minority
    Director of Communications, Outreach and Member Services;
    Kimberlee Trzeciak, Minority Senior Health Policy Advisor; and
    C.J. Young, Minority Press Secretary.

    OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
                  IN CONGRESS FROM THE STATE OF TEXAS

        Mr. Burgess. The Subcommittee on Health will now come to
    order. I recognize myself 5 minutes for an opening statement.
        This morning, I certainly want to welcome our witnesses. We
    are here to conduct oversight and receive updates on the
    implementation on one of the most substantial legislative
    accomplishments in the space of biomedical innovation, the 21st
    Century Cures Act. Cures passed both the House and the Senate
    with wide bipartisan support. It was signed into law December,
    2016. As with all landmark laws, I think it is critical that
    the Congress, especially the relevant authorizing committee,
    engage in oversight to ensure that the agencies are
    implementing the law according with legislative intent, based
    upon the active leadership and robust activities of both the
    National Institutes of Health and the Food and Drug
    Administration.
        I look forward to hearing from Dr. Francis Collins,
    Director of National Institutes of Health, and Dr. Scott
    Gottlieb, the Commissioner of the Food and Drug Administration,
    regarding progress in implementing Cures. I thank our witnesses
    for their willingness to testify on such an important topic.
        The 21st Century Cures Act provides hope to those who need
    it the most, individuals and families suffering from life-
    altering, often life-threatening illnesses, whether it is
    cancer, or a rare disease, or Alzheimer's. There are conditions
    that are costly to Americans of all ages and their families.
    Sadly, we each know too well the financial and the human toll
    that diseases place on our friends and our communities.
        One of the most impactful positions of the 21st Century
    Cures created the NIH Innovation Account in Treasury. This
    account funds projects like those related to Precision Medicine
    Initiative, the Brain Research Through Advancing Innovative
    Neurotechnologies Initiative, cancer research and regenerative
    medicine. The pace and breadth of biomedical research continues
    to accelerate, as we now have treatments to cure diseases, such
    as Hepatitis C, which was once unimaginable. Yet there is still
    much we do not know, especially regarding the neurodegenerative
    diseases.
        21st Century Cures included a provision to establish a
    National Neurological Conditions Surveillance System. Prior to
    Cures, there was no requirement or authorization to provide
    surveillance of neurologic disease, but this changed, thanks to
    Cures. Specifically, this section of law requires the Secretary
    of the Department of Health and Human Services to create such a
    system by expanding surveillance, infrastructure, and
    activities, including data collection, to determine prevalence,
    risk factors, and diagnostic and progression markers.
        Preliminary results from an ongoing Multiple Sclerosis
    Society study show that there are nearly 1 million Americans
    living with MS, more than twice the previously reported number.
    The surveillance system included in Cures will provide us
    better information so that we can further our understanding of,
    and eventually cure these diseases. I am especially grateful to
    see progress on this important policy. This began as a
    standalone bill introduced in the previous Congress.
        Additionally, Cures advanced precision medicine, which
    allows physicians to offer their patients truly personalized
    treatment. Achieving the full potential of precision medicine
    will require effort to collect health data in addition to the
    research done by our nation's best research investigators. The
    law codifies the Precision Medicine Initiative, and encourages
    the Secretary of Health and Human Services to carry out the
    goals of the initiative while ensuring confidentiality of the
    patient's information. The All of Us Research Program is a
    major piece of the Precision Medicine Initiative, and has
    already engaged over 1 million volunteers in the United States.
    I think you are to be congratulated for that.
        Clinical trials play a crucial and necessary role in the
    drug approval process. While the Food and Drug Administration's
    traditional clinical trial methods have proven successful, they
    are not always timely or applicable to new types of drugs.
    Cures requires the Food and Drug Administration to evaluate its
    trial designs and issue guidance for the purposes of
    ``incorporating complex adaptive and other novel trial
    designs.''
        The innovation and promising results of efforts included in
    Cures will provide Americans suffering from cancer and other
    diseases with the opportunity to undergo successful treatments,
    and to, in some cases, be cured.
        So our thanks to Dr. Collins, Dr. Gottlieb, for giving us
    the updates on the implementation of this new law.
        I will yield the balance of my time to the gentlelady from
    Tennessee, Mrs. Blackburn, for a statement.
        [The prepared statement of Mr. Burgess follows:]

                 Prepared statement of Hon. Michael C. Burgess

        Today, we are here to conduct oversight and receive updates
    on implementation of one of the most substantial legislative
    accomplishments in the space of biomedical innovation--the 21st
    Century Cures Act. Cures passed both the House and the Senate
    with wide bipartisan support and was signed into law in
    December of 2016. As with all landmark laws, I think it is
    critical that the Congress, especially the relevant authorizing
    Committee, engage in oversight to ensure that the agencies are
    implementing the law successfully.
        Based on the active leadership and robust activities of
    both the National Institutes of Health and the Food and Drug
    Administration, I look forward to hearing from Dr. Francis
    Collins, Director of the National Institutes of Health (NIH),
    and Dr. Scott Gottlieb, Commissioner of the Food and Drug
    Administration (FDA), regarding progress in implementing
    provisions of Cures. I thank both of our witnesses for their
    willingness to testify on such an important topic.
        The 21st Century Cures Act provides hope to those who need
    it the most--individuals and families suffering from life-
    altering, often life-threatening illnesses. Whether it be
    cancer, a rare disease, or Alzheimer's, there are countless
    conditions that are costly to Americans of all ages and their
    families. Sadly, we each know too well the financial and human
    toll that diseases place on our friends and communities.
        One of the most impactful provisions in 21st Century Cures
    created the NIH Innovation Account in the Treasury. This
    account funds projects related to the Precision Medicine
    Initiative (PMI), the Brain Research through Advancing
    Innovative Neurotechnologies (BRAIN) Initiative, cancer
    research, and regenerative medicine. The pace and breadth of
    biomedical research continues to accelerate, as we now have
    treatments to cure diseases such as Hepatitis C, which was once
    unthinkable. Yet, there is still much we do not know,
    especially regarding neurodegenerative diseases.
        21st Century Cures also included a provision to establish a
    National Neurological Conditions Surveillance System. Prior to
    Cures, there was no requirement or authorization to provide
    surveillance of neurological diseases. But this has changed
    thanks to the Cures law.
        Specifically, this section of the law requires the
    Secretary of the Department of Health and Human Services to
    create such a system by expanding surveillance infrastructure
    and activities, including data collection to determine
    prevalence, risk factors, and diagnostic and progression
    markers. Preliminary results from an ongoing MS Society study
    show that there are nearly one million Americans living with
    MS, more than twice the previously reported number. The
    surveillance system included in Cures will provide us with
    better information so that we can further our understanding of,
    and eventually cure, these diseases. I am especially grateful
    to see progress on this important policy, as this part of the
    law began as a standalone bill that I introduced last Congress.
        Additionally, Cures advanced precision medicine, which
    allows physicians to offer their patients truly personalized
    treatment. Achieving the full potential of precision medicine
    will require immense efforts to collect health care data in
    addition to research done by our nation's best research
    investigators. This law codifies the Precision Medicine
    Initiative and encourages the Secretary of HHS to carry out the
    goals of the initiative while ensuring confidentiality of
    patients' information. The All of Us Research Program is a
    major piece of the PMI and has already engaged over 1 million
    volunteers in the U.S.
        Clinical trials play a crucial, and necessary, role in the
    drug approval process. While FDA's traditional clinical trial
    methods have proven successful, they are not always timely or
    applicable to new types of drugs. Cures requires the FDA to
    evaluate its trial designs and issue guidance for the purpose
    of ``incorporating complex adaptive and other novel trial
    designs.''
        The innovation and promising results of efforts included in
    Cures will certainly provide Americans suffering from cancer
    and other diseases with the opportunity to undergo successful
    treatments, and in some cases, to be cured.
        Thank you to Drs. Collins and Gottlieb for giving us
    updates on the implementation of this important law. I look
    forward to hearing your testimony.
        I yield the balance of my time to the gentlelady from
    Tennessee, Ms. Blackburn, for a statement.

        Mrs. Blackburn. Thank you, Mr. Chairman.
        And Dr. Collins and Dr. Gottlieb, we are delighted that you
    are here. Two things that I am going to want to discuss with
    you all. Dr. Collins, the All of Us Research project, and
    making certain that we anonymize, and that we protect the data
    that is in that program, and that the privacy of the patients
    with data is respected as we move forward with this.
        And, Dr. Gottlieb, following up on the SOFTWARE Act and
    making certain that the implementation is going well. And we
    welcome you both. We look forward to the hearing.
        I yield back.
        Mr. Burgess. The chair thanks the gentlelady. The chair
    yields back.
        The chair now recognizes the gentleman from Texas, the
    ranking member of the subcommittee, Mr. Green, 5 minutes for an
    opening statement, please.

       OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
                    CONGRESS FROM THE STATE OF TEXAS

        Mr. Green. Mr. Chairman, thank you for holding today's
    hearing on the Implementation of the 21st Century Cures Act. I
    want to thank all our witnesses for being here today,
    especially Dr. Collins from NIH and Dr. Gottlieb from FDA--you
    are pretty regulars at that table--for being here.
        This December will mark the 2-year anniversary of the 21st
    Century Cures Act being signed into law by President Obama in
    his last public signing ceremony. The promise of the 21st
    Century Cures is to advance the discovery and development of
    new treatments, cures, through increased research and improved
    drug approval process.
        This important law dedicated $6.3 billion in new
    investments to support medical research initiatives, like the
    Beau Biden Cancer Moonshot, the BRAIN Initiative, the Precision
    Medicine Initiative within the National Institutes of Health.
    It also provides money to the Food and Drug Administration to
    advance the agency's mission and implement the policies in the
    underlying bill.
        I hope, our committee and Congress, that these investments
    are being put toward finding a cure for many of our nation's
    greatest medical priorities and ensuring the infrastructure is
    in place so the new therapies are accessible to all Americans.
        The NIH was provided $4.8 billion in new funding and
    advanced cutting-edge research initiatives. The FDA was
    provided $500 million over 10 years to improve the agency's
    medical product review process and expedite patient access to
    drugs and devices without compromising standards of safety and
    effectiveness.
        In addition to this much-needed funding, there are many
    provisions in this package worthy of support, from facilitating
    the development of new antibiotics to fight against superbugs
    through advancing the use of modern clinical trial designs to
    investing in the next generation of medical researchers. While
    some of the provisions are technical in nature, the real-world
    impact could not be abstract.
        Patients and families deserve to have their elected
    officials respond to their needs. The 21st Century Cures was
    written to do just that. This morning is an opportunity to hear
    from the heads of the FDA and NIH on implementation of the many
    provisions of this law, from patient-focused drug development,
    medical device innovation, and improving scientific expertise
    and hiring capacity. Many members of our committee were
    instrumental in getting Cures developed and signed into law.
    Most notably, Representative Diana DeGette and Representative
    Fred Upton.
        The 21st Century Cures Act demonstrates what we can
    accomplish when we work across the aisle. I look forward to
    hearing from our witnesses about the oncoming implementation of
    21st Century Cures.
        Mr. Chairman, I yield the remainder of my time to my
    colleague, Congressman Diana DeGette.
        [The prepared statement of Mr. Green follows:]

                     Prepared statement of Hon. Gene Green

        Mr. Chairman, thank you for holding today's hearing on the
    implementation of the 21st Century Cures Act.
        I thank Dr. Collins and Dr. Gottlieb for being here this
    morning.
        This December will mark the 2 year anniversary of the 21st
    Century Cures Act being signed into law by President Obama in
    his last public signing ceremony.
        The promise of the 21st Century Cures Act is to advance the
    discovery and development of new treatments and cures through
    increased research and an improved drug approval process.
        This important law dedicated $6.3 billion in new
    investments to support medical research initiatives like the
    Beau Biden Cancer Moonshot, the BRAIN Initiative and the
    Precision Medicine Initiative within the National Institutes of
    Health (NIH).
        It also provides money to the Food and Drug Administration
    (FDA) to advance the agency's mission and implement the
    policies in the underlying bill.
        It is the hope of our committee and Congress that these
    investments are being put towards finding a cure for many of
    our nation's biggest medical priorities and ensuring the
    infrastructure is in place so new therapies are accessible to
    all Americans.
        The NIH was provided $4.8 billion in new funding to advance
    cutting-edge research initiatives.
        The FDA was provided $500 million over 10 years to improve
    the agency's medical product review process and expedite
    patient access to drugs and devices without compromising
    standards of safety and effectiveness.
        In addition to this much needed funding, there were many
    provisions in this package worthy of support: From facilitating
    the development of new antibiotics to fight against superbugs
    to advancing the use of modern clinical trial designs, to
    investing in the next generation of medical researchers.
        While some of the provisions are technical in nature, the
    real-world impact they could have is not abstract.
        Patients and families deserve to have their elected
    officials respond to their needs. The 21st Century Cures Act
    was written to do just that.
        This morning is an opportunity to hear from the heads of
    the FDA and the NIH on implementation of the many provisions of
    this law, from patient-focused drug development, medical device
    innovation, and improving scientific expertise and hiring
    capacity.
        Many Members of our committee were instrumental in getting
    Cures developed and signed into law, most notably
    Representatives Diana DeGette and Fred Upton.
        The 21st Century Cures Act demonstrates what we can
    accomplish when we work across the aisle.
        I look forward to hearing from our witnesses about the
    ongoing implementation of the 21st Century Cures Act.
        Thank you Mr. Chairman, and I yield the remainder of my
    time to Congresswoman DeGette.

        Ms. DeGette. Thank you so much, Mr. Chairman, or Mr.
    Ranking Member, for yielding.
        And I just want to add my thanks to everybody here, in
    particular, Dr. Collins and Dr. Gottlieb, and all of their
    staff who helped us develop this bill, most especially my
    compadre, Fred Upton, who is sitting over there, who really
    worked with us every day.
        But this really was a work product of this entire
    committee, and it shows the greatness of the Energy and
    Commerce Committee and what we can do when we decide to work
    together to tackle a serious problem.
        Mr. Chairman, I also want to thank you for having this
    series of hearings. It is about a year and a half since the
    bill has been signed, and it is almost exactly 2 years since we
    originally passed it through this committee. We need to make
    sure that everything we intended to do in Cures is happening,
    and if the agencies need modifications or changes or additional
    resources that we give that all due consideration. And the only
    way we can do that is to have hearings like this.
        I do want to say I have been concerned lately reading some
    media accounts that say that some of the Cures money may be
    reprogrammed for other purposes, including for the ORR issues
    of the kids at the border. We should be able to find the money
    to do that without taking money away from important biomedical
    research and drug and device approval at the FDA.
        So I hope that is not the case; and if it is, I hope this
    committee acts swiftly and in a bipartisan way to make sure
    that the intended moneys that we authorized in this committee
    remain, because we still have so many bridges to cross and we
    are going to need every penny that we authorized.
        With that, thank you very much, Mr. Green, for yielding,
    and I yield back.
        Mr. Green. Mr. Chairman, I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. Pending the arrival of the chairman of the full
    committee, the chair now recognizes the ranking member of the
    full committee, Mr. Pallone of New Jersey, 5 minutes for an
    opening statement, please.

    OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
                IN CONGRESS FROM THE STATE OF NEW JERSEY

        Mr. Pallone. Thank you, Mr. Chairman. I want to thank Dr.
    Collins, Dr. Gottlieb, Dr. Sharpless, and Dr. Devaney for
    joining us to discuss the ongoing work at NIH and FDA to
    implement the 21st Century Cures Act. And, of course, I also
    want to thank our colleagues Diana DeGette and Fred Upton,
    without which the Cures Act would never have become law.
        The Cures Act tasks both of your agencies with implementing
    critical provisions aimed at improving the discovery and
    development of new treatments and cures. At NIH, the law
    provided significant funding for the Beau Biden Cancer Moonshot
    Initiative, the All of Us Research Program, and the BRAIN
    Initiative; and at FDA, the law included provisions to improve
    the medical product review process, as well as new authorities
    and funding to ensure the agency has the resources to recruit
    the best talent.
        At our hearing on this topic last November, you both
    provided promising updates, and I look forward to your
    continued work. As I said before, it is important to hold
    oversight hearings like these that allow us to learn directly
    from the administration how policies are being implemented.
        While I am pleased that the subcommittee has decided to
    conduct continued oversight of the Cures Act, there are several
    topics within the subcommittee's jurisdiction that also deserve
    hearings and oversight. For example, I have asked the majority
    to schedule hearings on a number of issues that are priorities
    for Democratic members of the committee. I have asked for
    hearings on maternal mortality, health disparities, gun
    violence, the Indian Health Service, cosmetics reform, the
    Office of Refugee Resettlement, drug pricing, abuse of the REMS
    program, and marketplace stabilization.
        These are all different issues within the subcommittee's
    jurisdiction, and we may have different opinions on many of
    them. That is exactly why we should at least have a hearing.
    And these are critical issues that this committee should be
    discussing in an effort to find potential solutions.
        So I hope in the coming weeks, after the August recess,
    that the chairman will respond and select a few of these issues
    to hold hearings on in the short time we have left for this
    Congress.
        And unless someone else wants my time, I yield back, Mr.
    Chairman.
        [The prepared statement of Mr. Pallone follows:]

                 Prepared statement of Hon. Frank Pallone, Jr.

        I want to thank Dr. Collins, Dr. Gottlieb, Dr. Sharpless,
    and Dr. Devaney for all joining us to discuss the ongoing work
    at NIH and FDA to implement the 21st Century Cures Act.
        The Cures Act tasked both of your agencies with
    implementing critical provisions aimed at improving the
    discovery and development of new treatments and cures. At NIH
    the law provided significant funding for the Beau Biden Cancer
    Moonshot Initiative, the All of Us Research Program, and the
    BRAIN Initiative. And at FDA, the law included provisions to
    improve the medical product review process, as well as new
    authorities and funding to ensure the agency has the resources
    to recruit the best talent.
        At our hearing on this topic last November you both
    provided promising updates and I look forward to your continued
    work. As I've said before, it's important to hold oversight
    hearings like these that allow us to learn directly from the
    Administration how policies are being implemented.
        While I'm pleased that the Subcommittee has decided to
    conduct continued oversight of the Cures Act, there are several
    topics within this Subcommittee's jurisdiction that also
    deserve hearings and oversight. For example, I've asked the
    Majority to schedule hearings on a number of issues that are
    priorities for Democratic Members of the Committee. I've asked
    for hearings on maternal mortality, health disparities, gun
    violence, the Indian Health Service, cosmetics reform, the
    Office of Refugee Resettlement, drug pricing, abuse of the REMS
    program, and marketplace stabilization.
        These are all different issues within this Subcommittee's
    jurisdiction, and we may have different opinions on many of
    them, but that's exactly why we should at least have a hearing.
    These are critical issues that this Committee should be
    discussing in an effort to find potential solutions.
        I hope that in the coming weeks the Chairman will respond
    to my requests and select a few of these issues to hold
    hearings on in the short time we have left this Congress.
        I yield back.

        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. The chair will hold the time for the opening
    statement of the chairman of the full committee, pending his
    arrival.
        We thank our witnesses for being here today and taking time
    to testify before the subcommittee. I am going to give our
    witnesses an opportunity to give an opening statement. That
    will be followed by questions from members.
        Today, we are going to hear from the Honorable Francis
    Collins, the Director of the National Institutes of Health; and
    the Honorable Scott Gottlieb, Commissioner of the Food and Drug
    Administration. And Dr. Collins, it is my understanding you
    have brought a supporting cast of Dr. Norman Sharpless, the
    15th Director of the National Cancer Institute; and Dr.
    Stephanie Devaney, who is the Deputy Director of the All of Us
    Research Program. I don't know if it is the intention for all
    of you to give an opening statement, but we will start with you
    then, Dr. Collins, and you are recognized for 5 minutes for an
    opening statement, please.

        STATEMENTS OF HON. FRANCIS COLLINS, DIRECTOR, NATIONAL
      INSTITUTES OF HEALTH, ACCOMPANIED BY DR. STEPHANIE DEVANEY,
        DEPUTY DIRECTOR, ALL OF US RESEARCH PROGRAM, DR. NORMAN
    SHARPLESS, DIRECTOR, NATIONAL CANCER INSTITUTE; AND HON. SCOTT
         GOTTLIEB, COMMISSIONER, FOOD AND DRUG ADMINISTRATION.

                    STATEMENT OF DR. FRANCIS COLLINS

        Dr. Collins. Thank you and good morning, Chairman Burgess,
    Ranking Member Green, and other distinguished committee
    members. It is a great honor to appear before you again today,
    along with my colleague, FDA Commissioner Dr. Scott Gottlieb,
    to give you a progress report on our implementation of the 21st
    Century Cures Act. Also joining me, as you have just
    introduced, the head of the Cancer Institute, Ned Sharpless;
    and Deputy Director of the All of Us Program, Dr. Stephanie
    Devaney.
        I can't emphasize enough for this subcommittee how much we
    appreciate your bipartisan leadership in passing this Act--51
    to nothing, as I recall, out of Energy and Commerce--which aims
    to speed the translation of scientific discoveries into life-
    saving treatments and cures. In the written statement I have
    submitted, I have outlined a comprehensive report on how NIH is
    working swiftly to implement the Act's provisions one by one.
        That most especially includes multiyear support for four
    specific areas of scientific opportunity supported by the Act's
    Innovation Fund. Today, I would like to highlight two of these:
    The Cancer Moonshot, and the bold new Precision Medicine
    Initiative, called All of Us.
        The Cancer Moonshot is aggressively pursuing a very
    ambitious goal to accelerate advances in cancer prevention,
    diagnosis, treatment and care. Such advances include
    immunotherapy, in which a person's own immune system is taught
    to recognize and attack cancer cells. After years of research
    supported by NIH, immunotherapy is leading to dramatic cures of
    some cancers, like leukemia, lymphoma, and melanoma. But some
    other cancers, particularly solid tumors, like colon, pancreas,
    breast and prostate, have proven much less responsive.
        Thank you. The slides are now up there.
        I am thrilled to tell you that some of those barriers seem
    ready to come down. Just last month, a team led by NIH's Dr.
    Steven Rosenberg announced a novel modification of an
    immunotherapy approach that led to a complete regression, most
    likely a cure, of widely metastatic breast cancer in a woman
    with previously, universally fatal form of the disease. As
    always, I have to counsel patients this success story for solid
    tumors, like breast cancer, involves very few cases right now,
    and must be replicated in further studies; but without doubt,
    this woman's life-saving experience represents hope for
    millions more.
        As exciting as potential cures like this can be, in
    authorizing and funding the Cancer Moonshot, you wisely tasked
    NIH with advancing not just cancer therapies, but also cancer
    care. Let me tell you about an NIH-funded trial that
    beautifully illustrates the progress we are making in this
    area. Each year, as many as 135,000 American women who have
    undergone surgery for the most common form of early stage
    breast cancer, face a very difficult decision, whether or not
    to also undergo chemotherapy to improve their odds. Now, thanks
    to a large NIH-funded clinical trial called TAILORx, we finally
    have some answers, and they are good answers. It turns out that
    about 70 percent of such women actually do not benefit from
    chemotherapy, and a genomic test of tumor tissue can identify
    them quite reliably.
        Clearly, it is ideal to spare women from the potential
    toxic side effects of chemotherapy, if that is possible, and
    still have a good outcome. On top of that, and this will
    probably warm your heart, because it certainly does mine, this
    move, basically making it not necessary to go through
    chemotherapy for many of those women, will produce a
    significant cost savings for our healthcare system, maybe up to
    $1 billion a year.
        Figuring out what health approaches work best for each
    individual and why brings me to the goal of another important
    investment of the Cures Innovation Fund, and that is, the
    Precision Medicine Initiative. The centerpiece of this
    initiative, the All of Us Research Program, will enroll 1
    million or more people, and we are off to a very strong start.
    On May 6, just 2 months ago, the day we launched national
    enrollment in seven sites across the Nation, we reached more
    than 10,000 people just that day at community events, and
    almost four times that number online.
        As of this week, over 86,000 volunteers have signed up to
    contribute their health data in many ways over many years. Some
    are enrolled through health provider organizations, ten of them
    that are part of our enterprise, and that includes community
    health centers and the Department of Veterans Affairs. Others
    enroll as direct volunteers, who sign up over the internet.
    Altogether, I am happy to tell you that almost half are from
    historically underrepresented racial and ethnic groups, which
    is one of our goals, so that we can utilize this to look at
    health disparities.
        Right now, anyone who is 18 and older, including Members of
    Congress--note the URL if you are interested in learning more
    about how to sign up--you can join. Next year, we will begin
    enrolling children. We decided to first start with adults, but
    next year, children will be added in. And in 2019, we plan to
    open a secure portal to give researchers access to All of Us
    data in a deidentified format with exceptional security.
        With every new person enrolled, every biological sample
    preserved, every electronic health record collected, every
    survey filled out, this data will hold more and more promise
    for advancing human health. And with every new scientist mining
    this data in search of answers to the important biomedical
    questions, the more that promise will be realized. This is
    groundbreaking.
        This exciting progress, along with many other advances in
    biomedical research, is being made possible because of the
    vision of you and your colleagues. So thank you for your
    investment in the 21st Century Cures Act, as well as your
    ongoing support of NIH. We could not do this without you.
        My colleagues and I really look forward to your questions.
    Thank you.
        [The prepared statement of Dr. Collins follows:]

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        Mr. Burgess. Thank you, Dr. Collins.
        Dr. Gottlieb, you are recognized for 5 minutes for an
    opening statement, please.

                    STATEMENT OF DR. SCOTT GOTTLIEB

        Dr. Gottlieb. Thank you, Mr. Chairman, Mr. Ranking Member,
    and members of the subcommittee. Almost 2 years ago, the
    members of this committee hailed the passage of Cures as a
    potential game-changer for patients. I agree. I have provided a
    comprehensive list of our Cures activities in my written
    statement, but I would like to focus my remarks on one
    crosscutting priority under Cures, and that is modernizing
    clinical trials.
        FDA has embraced innovative trial designs and novel
    endpoints in the patient-centered trials envisioned by the
    Cures Act. Our aim is simple: Innovative, advanced, evidence
    generation, to assure the timely availability of safe and
    effective therapies. The Cures Act is catalyzing these
    approaches and catalyzing the development of new precision
    medical technologies that are enabling us to target, arrest,
    and cure intractable conditions. These advances aren't cheap.
    Access and cost is a big issue.
        And I know some question whether our market base system for
    medical innovation is financially sustainable. They ask if we
    can afford this coming wave of precision-guided therapies. I
    would say, we couldn't sustain our system without them. New
    advances, like regenerative medicine and gene therapy, can
    displace costs associated with serious illness by restoring
    function and reducing reliance on costly medical care delivered
    in hospitals and nursing homes. The best solution isn't to
    reduce market incentives for innovation, but to make it easier
    to bring new innovations and competition to the market, all
    without compromising one bit FDA's rigorous gold standard for
    product regulation.
        That brings me back to modernizing clinical trials. Rising
    trial costs and complexity undoubtedly impacts market
    competition and drug pricing. It can be a barrier to getting
    timely competition to newly approved branded innovative drugs.
    One reason we may be seeing higher costs is because it is
    taking longer for competition to emerge in some of these
    categories where specialty drugs are targeting unmet medical
    needs. We studied this question at FDA, and the data confirms
    these trends. I want to share a snapshot today of what we
    found. We plan to publish the full results really soon.
        For nonorphan drugs that treat conditions affecting larger
    patient populations, 41 percent of the first-in-class drugs
    approved between the years of 1991 and 2000 had at least one
    competitor in the same class within 5 years. This rate dropped
    sharply over the next decade. For the same kind of drugs
    approved between 2001 and 2010, only 18 percent had a within-
    class competitor after 5 years.
        Another way of interpreting the data is to describe the lag
    in competition. For the drugs approved in 1991 to 2000, nearly
    a quarter had a competitor within 2 years. For the cohort of
    drugs where the first-in-class medicine was approved between
    2001 and 2010, it took an additional 5 years for there to be
    nearly as much competition; and by year 7, competition still
    lagged, with only 22 percent of the newer cohort of drugs
    having any competitor.
        We see similar patterns in most rare disease treatments as
    well. These trends mean that costlier branded drugs may enjoy
    longer periods without facing competition from products in the
    same class. And this may increase their pricing power. We need
    to understand why. Part of this has to do with the difficulty
    of running clinical trials with a second-in-market drug,
    especially if there is available therapy for a significant
    unmet need. It is becoming harder and harder to be second, and
    that is a problem.
        Efficient, modern approaches to designing and conducting
    trials can address some of these challenges and help us get
    more information about safety and effectiveness at the same
    time. To advance these and complementary goals, the FDA is
    pioneering a number of critical advances in clinical trial
    design.
        First, our master clinical trial protocols. These include
    basket trials, umbrella trials, and platform trials. These
    approaches can sharply increase trial efficiency and lower
    costs. They move away from one-drug/one-disease trials and
    allow the testing of multiple drugs against one or more
    diseases, or disease subtypes, using a common clinical trial
    infrastructure.
        Another approach is seamless trial designs that compress
    the traditional three phases of trials into one continuous
    trial. Through these approaches, you run one continuous trial;
    and as you enroll new patients, you expand subsequent cohorts
    of enrolled patients, using the information you learn about the
    features that help predict benefit from a new treatment.
        We are going to be publishing a guidance very soon that
    lays out how product developers can conduct these seamless
    trials and how to expand cohorts as trials progress, and a
    clinical criteria that can be used to expand cohorts as these
    trials advance. A lot of time and cost of clinical development
    is spent waiting in between the starting and stopping of the
    three phases of trials, and seamless trials can compress this.
        Every American has already, or will one day, face a serious
    medical diagnosis, either personally or through a loved one. We
    need to reduce the burden and the cost of advancing care. The
    clinical trial reforms we are making today will help ensure
    more patients who find themselves in these hard circumstances
    have a better chance of finding a cure, and that market
    competition helps make these treatments accessible to everyone.
    Thanks a lot.
        [The prepared statement of Dr. Gottlieb follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

            Mr. Burgess. Thank you, Dr. Gottlieb.
        And, again, thanks to all of our witnesses for agreeing to
    be here. We will now proceed to the member question-and-answer
    part of the hearing, and we will still yield to Chairman Walden
    when he comes in for an opening statement. But let me recognize
    myself 5 minutes for questions.
        Dr. Collins, thanks for being here. Thanks for bringing
    your backup. So let me ask you a question. On the 21st Century
    Cures, we tried to identify ways to get regulations and
    policies that were inconsistent, and to give you some
    flexibility to move past some of these that are overlapping and
    unnecessarily duplicative to relieve some of the administrative
    burden. I think the Act asked you to review that.
        So can you, perhaps, share with us where you are in the
    review and how NIH has identified some opportunities to relieve
    the burden on investigators?
        Dr. Collins. Yes, I am happy to do so. And, again, thanks
    to the committee for making all of those changes part of this
    bill. Some of them may seem kind of bureaucratic and
    administrative, but they make a huge difference to us in terms
    of the ability to carry out our mission.
        We have been asked, for instance, to look at the way in
    which we have asked our grantees to deal with financial
    conflicts of interest, which we think are very important for us
    to track, but where the mechanisms for doing that tracking were
    seen as unduly onerous. And we are in the process of going
    through that with our colleagues at HHS, and I think there will
    be some changes that will make that a more efficient process.
        Another thing, again, that sounds pretty down in the weeds,
    but it mattered a lot to us, is the degree to which we need to
    do monitoring of what you would call a subrecipient, where you
    give a grant to a particular institution, and then they have a
    subpart of that to another individual. And in the past, our
    need to reach through and do very detailed monitoring, even of
    subrecipients, was something that we were required to do
    without a whole lot of reason for that. And so we have already
    moved to simplify that process.
        Financial expenditure reporting, a lot of the reports that
    have been done in the past produce data that not very many
    people look at, and yet at the same time, we need to be sure
    that we are being good stewards; and that is also being
    simplified.
        We are looking right now at animal care and use, and the
    oversight that is necessary, of course, to be sure that we are
    dealing with animals in an ethical way. But some of those
    particular oversight mechanisms are now being reviewed, and we
    put out an RFI and got 19,000 comments back from people who
    have opinions about how we might streamline this process.
        Those are a few of the examples. Again, it was really
    helpful having those features into 21st Century Cures to give
    us the authority to do those things.
        Mr. Burgess. And obviously, ongoing, it is going to be
    important for us to communicate on this, and if there are ways
    where we can provide additional legislative help on that, I
    think you would find the committee willing to have those
    discussions.
        Dr. Collins. Thank you.
        Mr. Burgess. Dr. Gottlieb, thank you for your comments on
    the clinical trial reform. And I always felt while we were
    doing the roundtables for Cures, that that is likely where the
    big money was. If we could reduce the time in trial, if a
    product was going to fail, allow it to be identified and fail
    early so we didn't spend a lot of time chasing something that
    was not going to pan out.
        So I really like the concept that you just elucidated about
    the seamless trial concept and condensing the time between
    Phase I, Phase II, and Phase III clinical trials. I think that
    is likely to have a significant impact.
        One of the things that has always concerned me is that we
    have had some legislation, there has been a little controversy,
    but the ability for all--we don't have a payer here, we don't
    have CMS, but for the researcher, the regulator, and the payer
    to communicate before something comes.
        I always got the impression that when Hepatitis C, when
    SOVALDI came down the pike, that the payers at the State level,
    certainly the Medicaid payers, were not ready for what was
    happening, but they had been prohibited from having those
    discussions because of current law.
        So I am hopeful that we are able to do something, because
    particularly in gene therapy or gene editing, rather, where you
    have one shot that is going to cure something that is a
    lifelong problem, that is huge, but it is likely to be priced
    out of the range of most average people's budgets.
        Can you comment on that, on our ability to communicate
    prior to approval?
        Dr. Gottlieb. Thank you, Mr. Chairman. I think we, I would
    say, fully addressed this issue. And your points are well-made,
    and I share your concerns and have shared your concerns in the
    past. I think we have fully addressed this issue with the
    guidance that we issued earlier this year. That was, in part,
    built off of a Cures provision related to payer communications
    with product developers for purposes of engaging in value-based
    contracting and other economic kinds of discussions, where we
    have essentially established a safe harbor for those kinds of
    communications where the FDA isn't opining on whether or not it
    has the legal authority to provide any regulation to that
    context, and some would argue we don't on First Amendment
    grounds. But even if we did, we would not choose to exercise
    that authority because, as a matter of public health, we
    believe there should be robust discussions between product
    developers and payers for the purposes that you suggest, so
    they can engage in value-based contracting, other novel ways to
    try to pay for these very novel therapies.
        Mr. Burgess. Great. Thank you. Thank you for that answer.
        I yield back my time and recognize Mr. Green, 5 minutes for
    questions, please.
        Mr. Green. Thank you, Mr. Chairman. And, again, I welcome
    our whole panel here.
        Let me give an example of what has happened in the last 4
    years. In 2014, we had an outbreak of Ebola in West Africa.
    There was no treatment for it. And today, what we are seeing in
    the Democratic Republic of Congo, we have a vaccine. What has
    happened in those 4 years? Now, Cures came on in 2016. But can
    Dr. Collins or Dr. Gottlieb share that? How did that become? I
    know Merck actually has the vaccine now, but how did we get
    there? Because back in 2014, there was no vaccine.
        Dr. Gottlieb. I will let Francis talk, because the vaccine
    came from him, and I will comment on where it is now.
        Mr. Green. It has to be approved.
        Dr. Gottlieb. Exactly.
        Dr. Collins. So NIH actually began working on an Ebola
    vaccine back in the 1990s, when nobody had really paid that
    much attention to this, but we were concerned that this might,
    at some point, become important. So there was already a
    fundamental amount of basic science and work toward a vaccine
    happening for a good 15 to 18 years before the crisis that
    struck in West Africa in 2014.
        That being the case, this was, in fact, a program that
    developed a vaccine in record time, but still not, in fact, for
    West Africa in time to have much of an impact on the actual
    outbreak, because by the time the vaccine was being
    distributed, good public health measures were already resulting
    in the epidemic waning rather quickly, which was a good thing.
        With the DRC, this vaccine, which is manufactured by Merck,
    but based upon a close collaboration with NIH--in fact, the
    Phase I trials for this very vaccine were done in the NIH
    Clinical Center up here in Bethesda, showing that it was, in
    fact, safe and seemed to generate good antibody titers. That
    was distributed in DRC in a ring vaccination strategy, and also
    giving them to healthcare workers.
        And we were very happy to see yesterday, the declaration
    that this epidemic is now over. Did the vaccine contribute to
    that? It is a little hard to tell, because, fortunately, this
    was a limited outbreak. DRC moved quickly with traditional
    measures. But I think, again, we are very well-situated now to
    deal with an Ebola outbreak in the future. In this instance, it
    was great to see how quickly the vaccine was available, got
    distributed, and was made available to those who needed it.
        Dr. Gottlieb. I will comment just to build off Dr. Collins'
    comments. I make two points up front: First, I think it is hard
    to understate what a game-changer this is. This is the first
    time that we now have a technology available in the setting of
    Ebola to intervene to stop the spread with something other than
    just traditional public health tools of isolation.
        I also think we should make note of the efforts of the
    manufacturer in this case, Merck; the doses that were deployed
    in the DRC were donated. They shipped about 13,000 doses to
    WHO. WHO handled the transport to the DRC. It was delivered
    under an expanded access protocol that was administered by the
    WHO. So this was very much an altruistic effort that helped in
    that setting.
        I will say that we are working efficiently to try to move
    toward a licensed product here in the U.S. Obviously, I need to
    be cautious what I say, but I feel optimistic that this will be
    something that we can accomplish in the near term, and we can
    have a fully licensed vaccine.
        Mr. Green. Well, and that is just an example, because we
    had a gentleman from West Africa come to Dallas, Texas, and the
    protocols weren't followed, and so it impacted our own country.
    But using this as a paradigm on what we can do for other
    terrible illnesses that are developing, and I tell people on
    any given day, we have tuberculosis in the city of Houston,
    because it is an international city, and you just don't check
    everybody. So we have to be on our toes to be able to do that.
        And the 21st Century Cures, I think, gives you some focus.
    But looking at the Ebola vaccine, in 4 years, we went from
    people worried it is going to get--and I was trying to explain
    to folks, more of my constituents will die of the flu because
    they didn't get a flu shot than will ever be exposed to Ebola.
    And we want to keep it that way, though.
        But I am concerned about the growing threat of the
    antibiotic resistance, and that is why I sponsored a provision
    in 21st Century Cures to create a pathway for these antibiotics
    that would meet unmet medical needs. The provisions directed
    FDA and CDC to coordinate efforts with respect to monitoring
    antibiotic resistance, and any other drugs approved under the
    limited population pathway for antibiotic and antifungal drugs.
        Dr. Gottlieb, what steps has the FDA taken to coordinate
    with the CDC to support policy that promotes judicious
    antibiotic use and antibiotic stewardship?
        Dr. Gottlieb. We have taken a number of steps. We are going
    to be taking some additional steps to look at antibiotic use in
    animal feed, the length, the duration of use and the
    indications in which they are used, and plan to have some
    additional policy steps that we should be announcing within the
    next couple of months to continue to advance what we have
    already done in that regard to reduce the use of antibiotics in
    animal feed and limit one route by which we are seeing the
    resistance develop.
        And as well, with both the provisions in FDASIA, the QIDP,
    Qualified Infectious Disease Product provisions, as well as the
    LPAD that was also enabled in legislation passed by this
    committee, we have been able to create new pathways to try to
    provide additional incentives and additional efficient pathways
    to get new drugs to the market that attack some of these
    multidrug resistant pathogens.
        I would just close by saying I think it is still important
    that we focus on trying to develop new pull incentives and new
    ways to potentially reimburse some of these limited-use anti-
    infectives as a way to create additional incentives for the
    development of these products.
        And we are working on one such idea in conjunction with our
    colleagues at CMS to try to move towards a different
    reimbursement paradigm for drugs that are the kinds that you
    want to just put on the shelf and never have to use, moving
    toward a site licensing model as opposed to a pay-per-use
    model, which has been the traditional way that we have paid for
    drugs.
        Mr. Green. Thank you, Mr. Chairman. I know I am way over
    time and I will yield back the time I don't have.
        Mr. Burgess. The chair thanks the gentleman.
        The chair recognizes the gentleman from Kentucky, Mr.
    Guthrie, the vice chairman of the subcommittee, 5 minutes for
    questions please.
        Mr. Guthrie. Thank you, Mr. Chairman.
        I have a couple of questions, but first I want to say I
    know there is a lot going on in this great city and this great
    country moving forward. And a lot of times what is happening in
    this hearing--a lot of hearings make television. This one
    probably doesn't make a lot of prime time television, but it is
    important. It is extremely important what happened when a bill
    like the 21st Century Cures passed, I think got a voice vote
    out of this committee, overwhelmingly bipartisan, and really
    makes a difference in people's lives.
        And, Dr. Collins, you and I had a meeting the other day
    with a member of the band, U2. I only point that out because he
    was talking about somebody that was close to him that had had
    childhood cancer. And I remember walking away, because I had a
    friend of mine that passed away when I was about 11 or 12, and
    she would be alive today if she had the same disease this time,
    or probably would be alive today. And the reason I point out
    U2, because I think they, being Irish, really love this country
    and they really point out why America inspires the world and
    does things throughout the world.
        And people throughout the world do research, but nobody
    compares to what you are doing at NIH, what we are doing as a
    country, what our healthcare system, what our industry, public-
    private partnerships. And it is just a shame that--the old
    Annie Murray song, We Could Use a Little Good News Today. There
    is a lot of good news, and a lot of it is happening in what
    people and this panel is doing. We really appreciate it very
    much.
        But I do have a couple questions for Dr. Gottlieb. One is
    specific on the Cures Act. It codified many practices in the
    Office of Combination Products, but also included provisions to
    clarify regulatory requirements, improve processes. Can you
    explain how the FDA is delivering on these efforts in the
    complex area of regulation?
        Dr. Gottlieb. We have put forward a number of additional
    guidances as well as staff manual guidances on how we approach
    combination products in the agency. Historically, it has been
    challenging for the agency. I think we have made a lot of
    progress in recent years. I think we have made a lot of
    progress owing to some of the provisions that flow out of the
    Cures Act as well.
        We set up a Combinations Council to try to adjudicate who
    has primary jurisdiction over these products, and we will be
    putting out a guidance sometime probably this fall, end of the
    summer, early fall, that is going to make some further process
    reforms that I think is going to make it more efficient for
    products that sit on that cusp to move into the device realm,
    which I think is the preferred route for a lot of product
    developers, if they can get there.
        So we are going to look for ways to find the most efficient
    route while being mindful of our public health obligations in
    these circumstances.
        Mr. Guthrie. Well, thank you. And also, you and I talked
    just recently on the telephone, and several of us here sent a
    letter concerning drug shortages, drug supply shortages. I know
    I have had an emergency room physician from my district say
    that sometimes they don't have just the simple things they
    need. They have to be more creative. They have to figure out
    other things to move forward.
        I know some of it was tied to the natural disaster in
    Puerto Rico. I think you guys really went in and handled it.
    That is what people need to know. There are people in
    government that are trying to make things work. We have issues
    we need to address. But what happened in Puerto Rico to get
    pharmaceuticals moving again, what you guys have done. But I
    know there are still issues with drug shortages. I hear from
    EMS, emergency room physicians, anesthesiologists, just basic
    things.
        Could you just talk to me about a minute and a half what
    you explained to me on the phone and what you are doing with
    your Drug Task Force and what is pressing and what is moving
    forward?
        Dr. Gottlieb. So the challenges here are structural in my
    view, Congressman. If it is not one thing in shortage today, it
    is going to be another thing tomorrow. And we are dealing
    specifically with sterile parenteral drugs, the sterile
    injectable drugs, and those are the ones that seem to be
    chronically in shortage.
        I think there are structural problems in that. Frankly,
    reimbursement has been driven down so low. Many of these drugs
    are manufactured slightly above cost of goods. So the only way
    to profitably manufacture them is to do it at tremendous scale.
    So we have seen a lot of consolidation in the space, but we
    have also seen underinvestment in manufacturing, because there
    aren't a lot of margins to reinvest in manufacturing.
        And I will say manufacturing these isn't trivial. It is one
    thing to manufacture a small-molecule drug and have a margin
    that is slightly above cost of goods. It is quite different
    when you are trying to manufacture a sterile, injectable drug.
    So things go wrong, and when things do go wrong, since this
    space is consolidated, if one facility gets shuttered it could
    take down 30, 40 percent of the market.
        We think there are things we can do, apply an additional
    regulatory touch to some of these critical drugs, if we could
    define sort of a category of what we would say are critical
    access drugs that we don't want to go into shortage. But, quite
    frankly, I am concerned that my regulatory touch is only going
    to exacerbate the problem insofar as it will increase cost.
        So what we are trying to do with our shortages task force
    is look at this holistically, and bring in our colleagues from
    the VA and CMS and look at how we might couple some additional
    regulatory steps that we could take to mitigate shortages, or
    try to prevent them with some potential changes in the
    reimbursement structure for certain of these drugs.
        We talk a lot about drugs that are priced too high. And
    there are drugs that are very costly, and probably exceed the
    value that they are delivering. But there are drugs also that
    probably are priced too low relative to their importance and
    the cost of manufacturing them. And I think we need to take
    another look at how we reimburse these old sterile, parenteral
    generic drugs, off-patent drugs.
        Mr. Guthrie. Well, thank you very much. And my time is
    expired and I yield back. Thank you all for being here.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back.
        The chair recognizes the gentleman from New Jersey, Mr.
    Pallone, the ranking member of the full committee, 5 minutes
    for questions, please.
        Mr. Pallone. Thank you, Mr. Chairman.
        First, I have a question for Dr. Gottlieb, and then I want
    to go to Dr. Collins for a second one.
        Last week, FDA announced the release of its biosimilar
    action plan, which strives to encourage more innovation and
    competition in the biologics market. And I believe such action
    is critical and necessary if patients are to realize the full
    benefits of biosimilars. While 8 years have passed since the
    Biologics Price Competition and Innovation Act, only three
    biosimilars are marketed in the U.S., despite FDA having
    approved 11 of them. So as you noted yourself, Dr. Gottlieb,
    competition in this space is anemic.
        So I have two questions: First, you are well-aware that the
    high cost of prescription drugs, including biologics, continues
    to be a barrier for many patients. As a part of the Biosimilars
    Action Plan release, you revealed that a recent FDA analysis
    that found that if all FDA-approved biosimilars were available
    to American consumers, that significant savings could be
    realized.
        Could you discuss further FDA's analysis and the savings
    potential that biosimilars could offer?
        Dr. Gottlieb. I appreciate the question. We are going to be
    publishing the full results of that analysis soon, but
    essentially what we did is, we looked at the experience in the
    European market where we saw product introductions, and
    extrapolated that experience to what could have happened in the
    U.S. market if the same product had been introduced in the U.S.
    market.
        So we effectively took the competitive landscape from
    Europe, made some corrections for the fact that the dynamic in
    the European market is slightly different than the dynamic in
    the U.S. market, but looked at the percentage price reductions
    when one, two, three, four biosimilars entered the market. And
    when we extrapolated those findings back to the U.S. market,
    and then assumed that if every biosimilar that was approved in
    the U.S. market had launched, we extracted that an additional
    $4.5 billion would have been saved in 2017.
        So the savings are quite significant, and I think, if
    anything, we probably erred on the side of underestimating them
    by being very conservative in how we did our analysis.
        When you look at the European experience, the savings
    aren't of the same magnitude that you see in the small molecule
    world, but they are quite significant. They start to approach
    the small molecule type of savings once you see four or five
    product introductions.
        Mr. Pallone. Thanks a lot, really.
        The second question, I always want to commend you for your
    continued dedication to curbing gaming tactics used by certain
    manufacturers to delay or impede competition, but a question
    is, how can Congress work with the FDA as you implement the
    Biosimilars Action Plan to help facilitate greater competition
    in the biosimilar space?
        Dr. Gottlieb. I appreciate the question, Congressman. Yes,
    we are going to look at some of these more difficult scientific
    questions that I think could facilitate more competition, like
    interchangeability.
        But one of them, in particular, that we are going to be
    looking very hard at is being able to use the European product
    as a reference standard. We have situations where a biosimilar
    might be manufactured in the same facility and distributed in
    both the U.S. and Europe. We know that, but our knowledge of
    that constitutes commercial confidential information. So we
    have to require a biosimilar entrant to run the study against
    the U.S.-referenced product, even though the European product
    is the same thing, and the European product might be cheaper
    and easier for them to source.
        So that there are opportunities, I think, to have cost
    savings if you could source a reference product globally. And I
    will add that about half the cost right now of developing a
    biosimilar--it is highly variable, but, on average, about half
    the cost of developing a biosimilar are the costs of acquiring
    the branded biologic to run the trial, to run the comparative
    trial. So the savings could be significant.
        Mr. Pallone. Thank you.
        Let me quickly get to Dr. Collins. You mention in your
    testimony that NIH is currently building the All of Us data
    resource, which ultimately help researchers study the data
    collected from participants and connect to other large
    datasets. Making this data available to a broad range of
    researchers obviously has pros and cons, and the two major
    issues that come to mind are data security and participant
    privacy.
        So let me quickly put two questions into one. Given that
    NIH is asking participants to share intimate details about
    their health and lifestyle, how do you plan to ensure data
    privacy and data security, and are there protocols in place to
    share updates or study results with participants?
        Dr. Collins. I am going to ask Dr. Devaney, the Deputy
    Director, who is all over these issues, to respond to your
    question.
        Mr. Pallone. Thank you.
        Ms. Devaney. Thank you for the question and thank you for
    having us here today.
        So we are thrilled about where we have come with the All of
    Us Research Program. We have over 86,000 participants. Of
    course, we know, as we try to engage a community of diverse
    participants, up to a million, or maybe even more, we need to
    gain their trust. And so privacy is one of our most important
    priorities.
        All of the data that comes into the database source is
    encrypted and deidentified, and goes into a secure cloud
    environment. And once we open up access to researchers next
    year, they will have to abide by a code of conduct, and no data
    will be allowed to be downloaded from that environment.
        In addition, and just really briefly, I want to thank the
    committee here for giving us really strong privacy protections
    within the Cures Act, including certificates of
    confidentiality, which cover all of our data and allow us to
    really provide robust protections to our participants'
    confidentiality.
        Mr. Pallone. Thank you. Thank you, Mr. Chairman.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back.
        The chair recognizes the gentleman from Michigan, Mr.
    Upton, the author of the Cures legislation, 5 minutes for
    questions, please.
        Mr. Upton. Well, thank you, Mr. Chairman.
        I just want to remind everyone here that this was a great
    committee process that passed 51 to nothing. And I want to say
    that everybody that was on the committee in the last Congress
    actually had a piece of this, because we listened to everybody
    here. Staff was terrific, that is for sure, but so were the
    agencies, because you helped lead us to where we wanted to go.
    The administration. The Senate. We had all the disease groups.
    We had lots of players, and we appreciated that input.
        And I think, based on the hearing today and what we really
    thought was going to happen, it has fulfilled our expectations,
    and we have got a lot of time left to play. It is a game-
    changer. And I got to say, way back when, I was one of the
    participants with John McCain and Paul Wellstone and Henry
    Waxman, who doubled the money for the NIH back in the 1990s.
    The four of us were the sponsors of that bill to get it done.
    And it was a very important element that we actually increased
    the money for the NIH, knowing that we had a terrific steward
    in Dr. Collins, who was going to be able to lead us there.
        And I can remember sitting upstairs with Mr. Pallone and
    Ms. DeGette, my partner, and a few others to talk about how
    much money we wanted to add to that baseline. And we got it up
    to a $45 billion increase over a 10-year span. And the
    leadership demanded that we have pay-fors for it, and we came
    up with those not once, but twice, as they were stolen the
    first time.
        And a comment that was made earlier, and it might be more
    important to have maybe someone from HHS here, but I was too
    alarmed last week when I read a story that HHS was perhaps
    reprogramming some of the money that we had done a dollar-for-
    dollar, year-by-year table to make sure that that money went
    for the NIH.
        And I don't know, Dr. Collins, if you have knowledge if
    there is some truth to the published reports that money was
    being taken away from what we were able to do and put to
    something else. I don't know if that is happening. And if it is
    happening, how do we get it back?
        Dr. Collins. So I am not aware of the published report you
    are mentioning. There is, I believe--and we should probably
    check this--language in 21st Century Cures that prohibits
    transfer of the funds that are allocated in the Innovation Fund
    by the Secretary for any other purposes. So I think this is
    nicely designed so that those funds are intended to go for your
    original plan.
        Mr. Upton. That is good to hear. I want to talk a little
    bit about All of Us. And I think privacy protections are
    important, and it is very important people know about them and
    that they don't have to worry about that data being stolen.
    And, as we found, particularly from our roundtables,
    individuals were more than willing to share what their own
    experience was, knowing that it was going to protect someone
    else from maybe having that same ailment.
        So it is exciting to hear that 87,000 people have already
    signed up, really, just in a couple weeks. I know for me,
    particularly with the privacy protections, we would like to
    maybe set up a caucus here, and All of Us caucus that can be
    bipartisan to encourage members and staff to participate. We
    have got about, oh, like 25,000 people that work here on the
    Hill. Maybe we can get a good percentage that will come down to
    the Gold Room around the corner to figure that out.
        I know that researchers are going to have access to this
    information in about a year or so. How quickly do you think
    some of that data might be able to be utilized and figure out
    the right pathway for some real important research to be
    promising?
        Obviously, the news in the last couple weeks about the
    chemo, and not having chemo for breast cancer was very
    important, heralded around the country nicely. But how fast do
    we expect that maybe some of this All of Us information might
    be able to be used by the researchers with some concrete result
    of positive?
        Dr. Collins. Ms. Devaney.
        Ms. Devaney. Sure. Yes, it is a great question. We are
    really excited to get some of the brightest minds around the
    country actually accessing the data. And as you mentioned,
    86,000 participants, that data is just going to get richer and
    richer as we add more participants, and as we get more
    electronic health record data in on all the participants.
        I would imagine that once we give access to researchers,
    that we would pretty shortly start to see some pretty
    significant findings. And, of course, the data gets richer with
    more participants, but over the long term as well, as we get to
    see people who are healthy, stay healthy, get disease, how they
    respond to therapies. All of that will be----
        Mr. Upton. Just real quickly, because my time is expiring,
    how long does it take for someone, if they sign up to do this,
    what is the time element for them to participate?
        Ms. Devaney. Sure. So the online enrollment process takes
    about 45 minutes to go through the consent and to authorize
    your electronic health record. And then we have the in-person
    visit where people donate blood and undergo a physical
    measurement. That takes somewhere between 45 minutes and an
    hour as well. And then over time, we will be asking
    participants to continue to fill out surveys and do other
    things digitally, and maybe even come back for in-person visits
    over the years.
        Mr. Upton. I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back.
        The chair recognizes the gentlelady from California, Ms.
    Eshoo, 5 minutes for questions, please.
        Ms. Eshoo. Thank you, Mr. Chairman.
        Good morning, Doctors. It is an honor to have you here. And
    I can't help but think that while most people in the country
    don't know our names or what we do, they are all counting on
    you. So thank you for what you do. I think that you represent
    part of the real genius of our country. And I always say, NIH
    stands for our National Institutes of Hope. And you gave us
    even more hope with your report, Dr. Collins.
        Dr. Gottlieb, I know that you are aware that the
    legislation that my wonderful colleague, Congresswoman Susan
    Brooks and I wrote, the Strengthening Public Health Emergency
    Response Act, was included in the 21st Century Cures Act. And
    among other provisions, the bill established a priority review
    voucher to encourage the development of medical countermeasure
    drugs and vaccines at FDA.
        Now, when we developed the bill, the FDA, at that time,
    expressed concerns that allowing biodefense medical
    countermeasures to qualify for the PRV, would dramatically
    increase the number of PRVs awarded. The first product was just
    approved earlier this month. So does the FDA still have
    concerns about the number of products that will qualify for the
    PRV under the legislation? Can you tell us if there has been
    good interest on the part of companies to apply for it? Can you
    just maybe briefly inform us about that?
        Dr. Gottlieb. I appreciate the question, Congresswoman. And
    I think we all appreciate the effort of this committee to try
    to provide incentives to these important products. As you
    noted, the first product that qualified for one of these PRVs
    was just approved by the FDA. And it is potentially a very
    important product, a treatment rather than just purely a
    vaccine for smallpox. The Holy Grail was always to have a
    treatment in the event of smallpox being used as a bioweapon.
        I don't know the position of my colleagues who were here
    before me, but I certainly wouldn't argue that we have too many
    medical countermeasures coming into the agency and too many
    PRVs being issued in this context. I think, if anything, it is
    probably quite the opposite. We would still like to see more
    drug development in this realm, and there are still economic
    challenges to developing these kinds of medicines.
        Ms. Eshoo. I appreciate that.
        I don't know whether it is Dr. Collins or Dr. Sharpless.
    Pancreatic cancer is still a death sentence. I did legislation
    some years ago regarding it. Can you give us an update of if
    the needle has actually moved? I know when I did the
    legislation--I can't remember the year--that the needle really
    hadn't moved in about 40 years. So can you give us just a quick
    update on that? And then I would like to go to Dr. Devaney for
    a question.
        Dr. Sharpless. Sure. I think the answer is yes, the needle
    has begun to tick ever so slightly up in pancreatic cancer. I
    was speaking recently at the PanCAN, one of the leading
    advocacy groups in this space on this topic.
        Ms. Eshoo. Marvelous advocates.
        Dr. Sharpless. They do great work. And I think we have seen
    some really good stuff. So if you can resect pancreatic cancer,
    so you get a so-called R zero resection, those patients are
    doing pretty well. So resectable pancreatic cancer is a
    minority of those patients, but that group is growing. And we
    just had a positive trial, a randomized trial announced at ASCO
    with a significant survival rate for adjuvant chemotherapy in
    those patients.
        Other patients who do not have the RAS mutation, so the so-
    called RAS wild-type patients, which may be about 10 percent,
    some of those patients are responding to novel kinase
    inhibitors, for example, that----
        Ms. Eshoo. I think I would like to follow up with you----
        Dr. Sharpless. Sure.
        Ms. Eshoo [continuing]. Because I am not a doctor, so I
    don't understand everything you just said. But I know that you
    can break it down for me if we have a conversation or a
    meeting. I would appreciate it.
        Dr. Devaney, thank you for your wonderful report. One of
    the places where the program is taking place is in my
    congressional district at the Palo Alto VA. Can you give me
    just a quick update if you know about the veterans that signed
    up to participate, how your experience working with the Palo
    Alto VA? I am very proud of it. It is quite an enterprise
    there. I have heard from many constituents who were interested,
    who are interested in participating in All of Us. And I would
    also like to know how you are advertising to the general
    public?
        Ms. Devaney. Sure, yes. I will start with the VA, and--
    thank you for that by the way--we have a really great
    partnership with the VA and have for years. And of course they
    have been running the Million Veteran Program and they have
    670,000 veterans or more already enrolled. So we have learned a
    lot from them.
        Dr. Phil Tsao, who is the P.I. at Palo Alto, has been a
    great partner. They launched a few months ago and have had
    great success getting veterans enrolled into our program, which
    has been--it is a really important population for us, because
    of course the health outcomes that are so important there. And
    we have also a VA site in Boston. So we are excited to get even
    more VA sites launched around the country.
        Ms. Eshoo. Great and how are you advertising to the
    public----
        Ms. Devaney. Sure. Yes. We are using a number of different
    tactics, learning over time, how do we actually engage across a
    study that is trying to be national. So we are using different
    marketing techniques, digital marketing, we are also doing in-
    person engagement. The healthcare provider organizations,
    including the VA site, are really critical for us because they
    have those direct relationships with their patients.
        Ms. Eshoo. Thank you very much.
        Thank you, Mr. Chairman. I yield back. Thank you again to
    all of you.
        Mr. Burgess. The chair recognizes the gentleman from Ohio,
    Mr. Latta, for 5 minutes for your questions, please.
        Mr. Latta. Thank you, Mr. Chairman. And thank you very much
    to our panel for being here. I really appreciate it and the
    testimony you have provided. It is important for this country.
    And also the gentleman from Michigan's not here right now, but
    I also want to thank him for his leadership on 21st Century
    Cures and getting us to this point where we are today.
        Dr. Collins, if I could start with a question for you in
    your testimony you talked in regards to the brain initiative.
    And especially at the end of testimony talking about where it
    will lead to increased understanding for brain health and a
    means of preventing brain disorders such as Alzheimer's
    disease, Parkinson's, Schizophrenia, autism, drug addiction and
    traumatic brain injury. And I know I also see that there has
    been about $1.5 billion that has been allocated over the next
    10 years for the studies that is going on, but I know that when
    I have been at Ohio State and seeing what they are doing with
    Parkinson's in their studies. But the one area I would like to
    focus in on today is on Alzheimer's, because as we look across
    the Nation today and we are seeing what is happening, and the
    reports especially from what Alzheimer's association's reports
    that you are looking at that the cost could rise as high as
    $1.1 trillion by the year 2050.
        The sixth leading cause of death in the United States
    today. One in ten Americans over 65 will have it. We have about
    5 million Americans living with Alzheimer's today. One-third of
    Americans over 85 are afflicted with it. But unfortunately,
    start looking down the road over the next almost 30 years,
    people over the age of 65 there will be about 14 million people
    afflicted. Where do you see this going right now with
    Alzheimer's?
        Dr. Collins. This is an area of intense interest as a major
    challenge for the world and certainly that is very true of the
    United States. You have quoted the frightening numbers of
    individuals that are projected to be affected and the cost that
    that is going to apply to our healthcare system.
        And even more than that, the personal tragedies that happen
    every time a diagnosis of this sort appears, it affects not
    only the individual but their family and the caregivers. We are
    all in on trying to come up with an aggressive strategy to
    identify a pathway toward prevention and treatment of the
    disease. And we are grateful to the Congress because over the
    course of the last 3 years, Congress has been progressively
    giving us greater resources to work specifically on
    Alzheimer's. We are also doing that in a very I think visionary
    productive partnership with industry in something called the
    Accelerating Medicines Partnership to try to be sure that the
    basic science that we are doing on the brain, trying to tell
    what are the earliest signs of Alzheimer's gets translated
    quickly into therapeutics.
        One of the things we are learning is that Alzheimer's
    begins long before the first symptom, in terms of cognitive
    function. And if we are really going to be successful in
    delaying or preventing it, we need to find people at risk at
    the earliest possible moment and not wait until they are
    already in a circumstance of having lost a lot of neurons,
    because they will be hard to get back at that point.
        I am a guardedly optimistic that we are on the right path
    with some of the trials that are underway right now where we
    have the opportunity to treat people before they have any
    symptoms, but we know they are on a dangerous pathway and can
    watch and see what is happening.
        We are also learning a lot more about roles that play a
    significant hand in what happens with Alzheimer's and the
    immune system which we hadn't really realized before. And
    inflammation seems to be important in this condition. And all
    of the focus that we have had on amyloid and tau, the two
    proteins that build up in the brain are important, but that may
    not be the whole story. I could give you a long lecture on
    this, and I will stop now because of the timetable. But I do
    want to reassure you that between NIH basic and clinical
    science working with industry and with close collaborations
    with the advocates, we are pushing this as fast as we possibly
    can.
        Dr. Gottlieb. And I would just add if I may, we work
    closely with Dr. Collins in these efforts and we recently
    issued a new guidance document updating the agency's guidance
    on clinical trial end points in this setting, in this
    particular disease setting.
        Historically there was a perception that you had to show
    improvement in both functional status and cognition to win
    approval or at least show that you slowed the decline in
    functional status and cognition. That is challenging because by
    the time your functional status declines as an Alzheimer's
    patient, you probably had a pretty significant decline in
    cognition.
        And now that we are able to identify patients earlier with
    more sensitive tools to detect changes in cognition, also
    process prespecify patients who are at high risk of developing
    Alzheimer's, what we want to do is intervene earlier when there
    are slight changes in cognition, try to arrest that process.
    And so what the agency has said is in the right circumstances
    if you can show an improvement of cognition alone, that could
    potentially qualify for approval for a drug that would slow the
    progression of Alzheimer's disease in the right prespecified
    population that properly identify patients. So we are trying to
    work closely with NIH as well to help facilitate this
    innovation.
        Mr. Latta. Thanks Scott.
        Dr. Collins. That is really important to have that as an
    endpoint.
        Mr. Latta. Well again, thank you very much for our panel.
    And Mr. Chairman, I yield back.
        Mr. Burgess. The chair thanks the gentleman.
        Mr. Green. Mr. Chairman, could I ask for the next Member of
    Congress, Ms. Diana DeGette, could come up and sit in the
    ranking chair as a cosponsor of the bill.
        Mr. Burgess. No objection.
        The gentlelady is recognized for 5 minutes for questions.
        Ms. DeGette. Thank you so much. I just thought Mr. Green
    wanted a break. That was very nice of him to recognize me.
        And again, I want to add my thanks to all four of our
    witnesses up here for their extraordinary help, not just in
    passing this bill, but also in implementing it. It really warms
    our hearts to see how much progress we have made in such a
    relatively short time. And it also encourages us to think how
    much more we can make.
        So I just have a few questions for each of our agencies
    that are here today. I think I will start with the FDA. So Dr.
    Gottlieb, the biomedical community has really made great
    strides in developing clinical therapies from a marking of the
    potential system cells, to creating therapies tailored to the
    unique genetic fabric of a patient.
        And one of the things we have been concerned about for a
    long time is that overseeing and regulating these cutting edge
    therapies really requires an experienced, well trained, robust
    public health workforce.
        And so in 21st Century Cures we had a provision for new
    hiring authorities known as HR Cures. I am wondering if you can
    talk to us about how the HR Cures authority has helped the
    agency recruit and retain its talent.
        Dr. Gottlieb. Thank you, Congresswoman. We are in the
    process of implementing that. I think it is going to be
    transformative for the agency in terms of our ability to
    recruit people with specialized skills. We have identified 38
    occupations that meet the requirement for the alternative pay
    system. We have made the first two hires under the new cures
    authority, both deputy center directors, but I think this is
    going to be very important for the agency.
        And just to briefly pick up on your point, when we are
    talking about new treatments like gene therapy and cell base
    regenerative medicine and even things we are seeing on the
    medical device side of the house, the clinical characteristics
    of the products relate very closely to the product features.
    And the product features change very quickly. The underlying
    technology of the product itself, these aren't all pills
    anymore.
        Ms. DeGette. Right.
        Dr. Gottlieb. And so it used to be that if you had
    expertise in the scientific field or the clinical field you
    could adjudicate all the different kinds of drugs. But now it
    requires expertise also in the products themselves. The gene
    therapy platforms, there are regenerative medicine platforms.
    And we see this a lot on the medical device side of the house
    where there is a lot of novel technology. You have to have
    engineering skills on that specific technology. That is where
    this is going to be particularly helpful, trying to find those
    people with the very discrete, specialized----
        Ms. DeGette. These are people you just can't hire someone
    out of grad school. These are people with really specialized
    areas of knowledge.
        Dr. Gottlieb. That is right. And they are people who are
    often employed in endeavors in the private sector where they
    are highly paid, highly skilled so we are competing against
    others for the same small pool of talent.
        Ms. DeGette. In the FDA June 2018 report called 21st
    Century Cures Workforce Planning you talk about this patchwork
    of hiring authorities that have created challenges. Are you
    beginning to be able to address that?
        Dr. Gottlieb. We have had historical challenges with the
    overall hiring framework at FDA going back 15 years or longer.
    Some of the same challenges that I am grappling with now I saw
    commissioners grappling with when I was at the agency in 2003
    and again in 2007.
        We are addressing it very directly. We are trying to do it
    top down, wholesale change of the hiring process to make it far
    more efficient. We started a pilot which dramatically
    streamlined the on boarding process, the hiring process. And we
    focused that pilot on the PDUFA slots, on the user fee slots.
    What we have decided to do is basically take that structure of
    that pilot and apply it to the whole hiring process and not
    just sort of bifurcate off one set of hiring----
        Ms. DeGette. I hate to cut you off, but I can't ignore Dr.
    Collins. And I have about 10 minutes of questions for you, but
    you are going to have 1 minute to answer them.
        Let me just ask you what kind of research is going on over
    in your agency on alternatives to opioids for pain management?
    Because the opioid crisis is one of the big issues that has
    really been facing this committee for the last 1 year or 2.
        Dr. Collins. Thank you for raising this. This is an
    incredibly important issue. We are grateful to the Congress
    that in the omnibus an additional $500 million was put into our
    budget to work on the opioid crisis. And a significant fraction
    of that is being devoted to just the thing you are raising
    here, the need to develop affective and nonaddictive pain
    medicines for those 25 million Americans who suffer from
    chronic pain every day and for whom opioids is not the answer.
        Ms. DeGette. Right.
        Dr. Collins. And actually it is quite harmful in many
    instances. This goes all the way from basic science, to
    discovering new targets, to working with industry to help
    actually free up some ideas that had been on the slow boat and
    now can be speeded up. Working in a collaborative way. And
    setting up a clinical trials network so that we can quickly
    test and see whether new therapeutics that are not addictive
    work, and in what setting did they work, because all pain it
    not the same. Low back pain may not be the same as the pain you
    get from trigeminal neuralgia, and we need to have all ready to
    go the kind of clinical trial networks that currently doesn't
    exist.
        Ms. DeGette. I think, Mr. Chairman, this might be a good
    subject for a whole separate hearing. Thank you.
        Just one last thing, Dr. Gottlieb, I had some questions
    about some rules that have been pending about shock therapy in
    the FDA. We don't have time to have you answer those questions
    right now, but I am going to be contacting your agency to find
    out why those rules haven't been approved. They have been
    pending since 2016. And I promised my constituents I would ask
    you about this so we----
        Dr. Gottlieb. I would be happy to discuss that with you
    moving forward thank you.
        Ms. DeGette. Thank you, very much. Mr. Chairman.
        Mr. Upton. Thank you, Mr. Chairman. I appreciate your
    holding this hearing. And I want to thank all of our witnesses
    today and the very talented men and women that you are speaking
    on behalf of your agencies who do amazing work in the area of
    healthcare in America Cures. The legislation was passed,
    medical innovation, reforms to America's and mental health
    services.
        And this is why I thought today was really an important
    day, an important hearing to continue our work to legislate and
    evaluate and legislate and evaluate and see what else we need
    to do going forward. What is working, what is not, and what do
    we need to change.
        I know I have had a lot of roundtable discussions, and
    hospital board rooms, community centers townhalls with people
    in my district who are very pleased with the investments we
    have made in medical research and in turn the work that your
    scientists are doing.
        To turn that money and research into reality, and medicine,
    and cures that goes from one end of this table to the other.
    And so we appreciate the work you are doing. A friend in Bend
    say Carol, who is an MS advocate, has said Cures was a great
    step toward making it possible to find a cure to MS. And I know
    you all hear that every day. People are pretty excited about
    precision medicine, the cures that are out there waiting to be
    found and the work that you are doing.
        Dr. Gottlieb, in your testimony today you suggested there
    is a correlation between lowering medical product costs and
    promoting modern clinical trial designs. Can you elaborate on
    that, because we are all very concerned about the costs of
    healthcare, the cost of medicines. And clinical research isn't
    always as efficient as it could be, and how biomarkers and
    other drug development tools help to make that more efficient
    in patient centers.
        Dr. Gottlieb. I appreciate the question, Mr. Chairman. I
    think while clinical trial costs don't directly translate into
    how a product is priced, we know that. People price products
    based on what the market's going to bear and the value that it
    is delivering. We know that clinical trial costs, cost
    development costs do factor into the rising costs of the
    overall development and competitive nature of this landscape.
    What I talked about in particular today is the complexity of
    clinical trials, especially in areas of unmet medical need when
    there is already available therapy is in my view delaying to
    market the second and third in class drugs.
        So these specialty drugs that target unmet medical needs
    are enjoying monopolies for longer periods of time. And if you
    believe that subsequent competition and the data shows this is
    when competition market prices come down, that competition
    isn't entering and the prices aren't coming down. And we now
    have data to demonstrate this. We will be publishing that soon.
    I gave a snapshot of it here today.
        I think there are things we can do to try to facilitate
    more efficient routes to market the second in class drugs and
    third in class drugs while at the same time increasing our
    assurance in safety and effectiveness, not sacrificing it one
    bit. And those are the kinds of development reforms that we are
    focused on.
        Mr. Upton. And trials for rare diseases can be difficult to
    conduct, especially if there is already a first FDA approved
    treatment. How do you spur additional innovation and greater
    market competition for rare diseases?
        Dr. Gottlieb. And this gets to some of the changes in the
    clinical trial designs. One thing in particular is in very rare
    diseases looking at natural history models to model the
    behavior of the control arm, or using modeling as simulation,
    so you don't have to droll placebo trials in those settings,
    because if there is already available therapy, patients aren't
    going to want to go on to a placebo if they can otherwise use
    the available therapy. They are going to want to use an active
    drug.
        So this is a place where we could benefit from more disease
    models. We should be able to create those. There is a request
    in the President's budget for about $20 million which would
    help facilitate that. I know we have support from this
    committee and others in Congress for some of those resources so
    we are very grateful for that. But I think there are things we
    can do working together.
        Mr. Upton. I appreciate that and a good reminder. The
    promotion for the President's budget, well done, well played.
    Send that to the White House.
        Drs. Collins, and Devaney, and Sharpless, I saw the NIH
    recently announced an effort called respond or research on
    prostate cancer in men of African ancestry defining the roles
    of genetics, tumor markers and social stress. So that study
    funded in part by 21st Century Cures Cancer Moon Shot
    initiative will investigate the environmental and genetic
    factors of prostate cancer in African-American men. Can you
    tell us more about this important study and how it will combine
    molecular approaches in environmental science?
        Dr. Sharpless.
        Dr. Sharpless. Thank you for the question. This is alluding
    to a trial just announced from the NCI. That will be the
    largest trial on this topic in our history, so it is going to
    take 10,000 patients newly collected and 10,000 historical
    patients and try to analyze the genomes and social factors that
    contributes to this important disparity. African-American men
    are likely to be diagnosed with advanced and prostate cancer
    and are more likely to die of prostate cancer. So understanding
    this important disparity in our country is really a crucial
    question and the response trial are exciting.
        Mr. Upton. All right. Anything else anybody want to add?
        Dr. Collins.
        Dr. Collins. I think I just have to point again to the All
    of Us study as a platform that we will be able to utilize going
    forward for answering many of that sort. We have this goal and
    we aim to reach it that about 50 percent of the participants in
    All of Us are going to come from traditionally underrepresented
    groups, racial and ethic groups.
        And so if you want to really examine health disparity
    circumstance, you are going have a million participants who are
    highly motivated to take part and research on whom we collected
    a great deal of data. We are going to learn a lot about this
    kind of health disparity, about all diseases once we have that
    platform up and going.
        Mr. Upton. Excellent. Excellent. Thank you all. Appreciate
    your continuing involvement with our committee. It has been
    positive and effective I think for the American people. And we
    look forward to doing more together.
        And Mr. Chairman, I yield back.
        Mr. Burgess. The chairman thanks the gentleman. The
    gentleman yields back. The chair recognizes the gentlelady from
    Florida for 5 minutes for questions, please.
        Ms. Castor. Thank you, Mr. Chairman. And welcome to all of
    our witnesses today.
        Dr. Collins, I share your enthusiasm over the future of the
    Cancer Moon Shot in precision medicine. Part of my enthusiasm
    stems from the fact that back home in Tampa I represent the
    Moffitt Cancer Center community, the only NCI designated
    comprehensive cancer center in the State of Florida.
        And I love meeting routinely with the young scientists and
    researchers who now feel like we have given them a new
    commitment where they were very concerned in the past on the
    future of NIH funding as it competes with all the other needs.
    Now they feel like, OK, 21st Century Cures, these new
    investments for the Cancer Moon Shot, gives them hope for all
    of their research and the care they are providing.
        Dr. Duvaney, the Moffitt Cancer Center has been a national
    leader in building large datasets, tissue samples before and
    working with other institutions, especially for those in
    underrepresented communities.
        You have now given us a bit of an outline on the importance
    of protecting privacy for the people who participate. Can you
    tell us a little bit about the protocols going forward for
    researchers? Will they be required to share their research?
    When would that happen? Will those research results be
    available to all for other researchers to build upon?
        Ms. Devaney. Great question, thank you for that. So, we
    have been thinking a lot about the--to your point about young
    investigators, the diversity of researchers also that can
    access the data, making sure that the platform we are building
    is open to everyone, and feel responsible for ensuring that the
    things that we learn on the data, that is so generously
    provided by our participants, is returned to the scientific
    community and to our participants in fact.
        So we are developing policies around ensuring that
    researchers who access the data required to follow code of
    conduct and share their results within a specific amount of
    time. And we are still finalizing those policies in
    anticipation of opening up the data next year, and policies
    around returning results back to participants who participate
    in the study as well.
        Mr. Costello. Because Dr. Collins, in the past it has been
    kind of siloed. If certain researchers had kind of kept it,
    held it close, and didn't make all the data available, what
    does the future hold do you think?
        Dr. Collins. I appreciate the question. And I appreciate
    21st Century Cures gave me, as the NIH director, authority,
    that I did not have before, to require data access for studies
    that we support. I could cajole in the past. I could try to
    embarrass people, but I didn't really have the clout to say,
    this is a requirement. If you are getting a grant from NIH, you
    are required to make your data accessible.
        You all gave me that and that has been a very useful tool.
    And we are very engaged in the process of trying to establish
    exactly what that needs to look like for a wide variety of
    studies. We have done it particularly for genomics where we
    have a very well worked out genomic data sharing policy, and we
    are in the process of working that out for things like imaging
    and electronic health record information and so on. But this is
    a very high priority. We hate those silos too and we have been
    having a good time knocking them down.
        Ms. Castor. Great. We look forward to that.
        Dr. Sharpless, your predecessor at NCI, Dr. Doug Lowy was
    well-known for his research on HPV and the HPV vaccine. Part of
    the Cancer Moon Shot isn't just the cancer research, but it is
    what NCI can do to help prevent cancers and protect them. Over
    the past few years, there has been new NCI focus on making sure
    that there is greater uptake of the HPV vaccine across the
    country.
        Do you intend to continue with that? If we discovered the
    cure for cancer, there would be parades in the streets, but
    here is an actual vaccine that prevents cervical and a whole
    host of other cancers, I think it is important. Are you
    committed to continuing those initiatives?
        Dr. Sharpless. Very much. I should mention that Dr. Lowy
    continues as my deputy director. He has been incredibly
    invaluable in that regard, because entering the Federal
    processes as an academic is challenging so I really appreciate
    Doug and his work in this area is wonderful.
        Yes, we have a robust, huge portfolio in this area. I think
    one of the most important studies is a trial of one versus two
    doses of the vaccine. Right now the recommended is three doses.
    That is a big issue in terms of implementation in the
    community. So if one dose worked well, that could be game
    changing for subjects in the United States as well as globally
    with cervical cancer is a bigger problem.
        Ms. Castor. I guess it is a good reminder, it is back to
    school time. This is a vaccine that is appropriate. It is
    important for boys and girls, middle schoolers to get the HPV
    vaccine to prevent cancer in the future. Is that correct?
        Dr. Sharpless. Yes, right. A number of vaccines that
    prevent cancer HPV, Hepatitis B, for example, the dissemination
    of those things that work into the community is a real
    challenge for us in terms of the inflammation science to make
    these effective therapies more available.
        Ms. Castor. Thank you very much. I yield back.
        Mr. Burgess. The chair thanks the gentlelady. The chair
    recognizes the gentleman from New Jersey, Mr. Lance 5 minutes
    for questions, please.
        Mr. Lance. Thank you, Mr. Chairman. Good morning to you
    both and thank you for your enormous public service.
        For Dr. Gottlieb, the Orphan Drug Act has helped to create
    a market based system, to encourage the development of new
    medicines for people living with rare diseases, most of whom
    are children. As you know, I am the chair of the Rare Disease
    Caucus in the House.
        In exchange innovators are granted 7 year monopolies in a
    specific disease area. Since the act was established in 1984,
    medicines have been brought to market for only some rare
    diseases, and there are many rare diseases as you both know
    where there are no medicines at all.
        For many of these diseases, however, there has been zero
    second generation, newly innovative medicines brought to market
    for patients. In the field of Lysosomal storage disorders, for
    example there have been enzyme replacement therapies for eight
    different rare diseases. The cost on average is nearly $500,000
    per patient per year. However, with the exception of Gaucher
    disease, not a single second generation therapy has been
    approved for any of these diseases, since these first
    generation ERT approvals, and most of those approvals date back
    at least a decade.
        In your view, Dr. Gottlieb, have we created perpetual
    monopolies in many rare diseases, especially in the areas I
    have discussed? And what are the barriers to moving innovation
    forward to spur competition and innovation and to bring newer,
    better medicines to patients with rare diseases as rapidly as
    possible?
        Dr. Gottlieb. Thank you for the question, Congressman. I
    think this cuts to some of the other issues we discussed here
    today so it is a very relevant question.
        I do believe that there are settings where it is harder to
    bring second to market competition into certain categories. I
    would argue this is one of them. It is particularly the case
    when you have drugs that target degenerative diseases,
    significant unmet medical needs, small populations. It is hard
    to run clinical trials with new drugs once one therapy is
    available. Typically, the subsequent drugs will have to be
    studied on top of the available therapy and you will have to
    show improved efficacy, with combination therapy, as opposed to
    just monotherapy. It is hard to run head-to-head comparative
    studies when already effective therapy is available. People
    don't want to forego an effective treatment, especially when
    you are dealing with a child with a degenerative disease.
        I think there are a lot of things we can do. Earlier this
    year we published it in conjunction with our counterparts in
    Europe, our regulatory counterparts in Europe, a master
    protocol, if you will, for Gaucher's disease and how you can
    study multiple drugs within the context of the same clinical
    trial. Structure for Gaucher's, we have talked earlier about
    trying to develop natural history models to model. The behavior
    of patients who go untreated. We know how these diseases
    progress.
        We know how they affect patients. We should have really
    robust natural history models to model be able to model that
    affect so we don't have to enroll patients on placebo trials.
    It relies much on placebo and that would make trials easier to
    conduct.
        So there is a whole host of clinical trial reforms that I
    think we can pursue to try to facilitate second to market
    innovation, which I agree with you is critical in these areas.
        Mr. Lance. Is there something more we should be doing
    statutorily here in the legislative branch of government,
    Doctor?
        Dr. Gottlieb. I would be happy to have that discussion with
    you. I think there is a lot of things that we can do, that we
    are trying to do, and will do. I think one thing that I would
    just affirm--and I had this discussion with the chairman about
    the natural history models--we allocated $6 million earlier
    this year to develop six natural history models, Myotonic
    dystrophy 1, a natural history model for the affects of sickle
    cell disease on the kidney, but we did in our budget this year
    request additional funds to develop up to an additional 20
    natural history models, and those would be focused on these
    diseases areas, these very orphaned, if you will, super
    orphaned diseases we would focus on the resources there.
        Mr. Lance. Thank you, I look forward to working with you as
    we have in the past. I have been the chair of the Rare Disease
    Caucus for quite some time. And this is completely bipartisan
    in nature. And we look forward to continuing the discussion.
    Dr. Collins, it is always a pleasure to see you.
        I note in the audience John Crowley who has been very much
    involved in the rare disease space and his daughter Megan, and
    they are residents of New Jersey. And there is no one who is
    fighting for progress in the rare disease space more than my
    friend Mr. Crowley.
        Thank you, Mr. Chairman. I yield back the balance of my
    time.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. The chair recognizes the gentleman from Virginia,
    Mr. Griffith, 5 minutes for questions, please.
        Mr. Griffith. Thank you very much, Mr. Chairman. I do
    appreciate it. I appreciate you all being here today.
        On June 8, 2018, Dr. Gottlieb, the committee sent FDA
    bipartisan oversight requests for information about the FDA
    increasing criminal enforcement at ports of entry to combat the
    opioid epidemic, an initiative that you have championed and we
    support. The letter has only six requests, some of the requests
    were first posed by an email to the FDA Office of Legislation
    on January 30th of year. It is now late July and the FDA
    continues to tell the committee staff of letters in clearance.
        Commissioner, could you help expedite the clearance of this
    letter so the committee has the FDA's response before the end
    of July?
        Dr. Gottlieb. I absolutely will. It is in clearance. And we
    in an effort to try to improve transparency and get the
    information out publicly, I did make a lot of the information,
    if not most of the information that is going to be in that
    letter, available publicly in some remarks I gave at a forum we
    had to try to work with internet stakeholders to address opioid
    sales online. So I have made the information public. I can make
    those remarks available to you. I think we have made them
    widely available. But I recognize the importance of getting the
    formal response back to Congress and I am on it. I have some of
    my own challenges up my line.
        Mr. Griffith. I appreciate it. Well, and you have so much
    to do and I really thank you for the good work that you are
    doing. And there is a lot of different areas that we have been
    working on together.
        Dr. Gottlieb. Thank you.
        Mr. Griffith. And I appreciate that very much.
        What further improvements will FDA make to the expanded
    access program to ensure the process is effective and efficient
    for providers and patients, particularly now that the Federal
    rights to trial legislation has passed? And while I like the
    House version better than the Senate version, we have got the
    Senate version. Give me an update on that.
        Dr. Gottlieb. Well, we have a process underway right now, a
    working group that is looking at what steps, if any, we ought
    to take to facilitate the proper implementation of the right to
    try measure. It is going to be a pathway that sits alongside
    our extended access program. We are still going to operate our
    extended access program.
        We did bring in an outside group, an expert group to take a
    top down look at our expanded access program and make some
    recommendations to the agency on how we can improve it. I am
    going to make that public soon to provide some transparency
    around what they found.
        But we think that there are additional process steps that
    we can take to make it easier for people who aren't as
    sophisticated or physicians who haven't done this before to
    access that. We are also working with Friends of Cancer
    Research and the Reagan-Udall Foundation to create a platform
    to have sort of a one site of entry, if you will, to get
    information about what expanded access programs exist.
        I think the challenge still remains that the difficulty,
    sometimes reluctance, but a lot of times difficulty of sponsors
    to actually make drugs available especially when we are dealing
    with things like some of these cell based therapies or
    biologics cost aren't trivial, when you are a small company you
    barely have enough product for the clinical trials. And I have
    been on the other side of this, so I know how that is. And so I
    think we still need to look for ways to provide proper
    incentives to try to make sure that when we have really really
    promising therapies we might be able to have supply available
    too to make that available to patients.
        Mr. Griffith. Well I appreciate that. I have been an active
    proponent for right to try for many years. And if people are
    facing death, they will take that Hail Mary pass and take
    whatever they need to, if they can. Let us know what we can do
    to assist you on that as well.
        Dr. Collins, I am going to ask you a couple of questions
    just to give me update. I have a partial answer that I already
    found on the internet and that is with Lou Gehrig's ALS, I
    understand you all had a breakthrough this spring. But I also
    am interested in Huntington's chorea, and I obviously ask about
    these because I have friends who have been afflicted with both
    of those.
        Dr. Collins. Those are both terribly important and often
    tragic neurological diseases that result in neurodegeneration.
    With ALS, as you mentioned, there has been encouraging
    development of a new therapeutic approach this spring still
    very much in the process of being evaluated.
        Huntington's disease I will actually reflect a bit on, this
    was 25 years ago that my own laboratory was involved in the
    discovery of gene that is responsible for that condition. And
    it has been very gratifying to see in the course of just the
    last year or two, a still and a mouse model, very encouraging
    information about using a genetic approach to try to block the
    production of the toxic protein.
        And now in human clinical trial, which we are waiting for
    the full data to be rolled out, but sounding encouraging, a
    similar possibility that utilizing a molecular therapy injected
    into spinal fluid, which then gets into the brain, may very
    well be able to provide benefit.
        And goodness knows, we have waited a long time for that
    kind of thing to happen. So it is pretty exciting to see. We
    have a long way to go I think before we can say really have the
    answers, but this is a lot different than saying we have
    nothing to offer.
        Mr. Griffith. I appreciate that very much and yield back.
        Thank you, Mr. Chairman.
        Mr. Burgess. The chair thanks the gentleman, the gentleman
    yields back. The chair recognizes the gentleman from
    California, Mr. Cardenas, for 5 minutes for questions please.
        Mr. Cardenas. Thank you very much, Mr. Chairman and ranking
    member. I appreciate the opportunity to openly discuss with the
    witnesses the progress that we have made. And not every day do
    we as United States Congress actually pass laws that we can
    actually look at and say, I think we did something good. And so
    I want to thank all of the implementers for doing good work.
        My first question has to do with the diversity in research
    of subjects. So thank you for testifying today. I was excited
    to read in your testimony, Dr. Collins, that about 85,000
    individuals have already started the enrollment process for the
    All of Us Research Program; ``70 to 75 percent are from
    communities who have been historically unrepresented in
    biomedical research and almost 50 percent are specifically from
    racial and ethic groups who have not been included in previous
    research.''
        As you all know, diversity in medical research has long
    been an issue. I believe one way to decrease health disparities
    in this country is to ensure that we are including individuals
    of all races and ethnicities in medical research.
        So with that, my question is what is NIH doing to ensure
    that All of Us research program recruits a diverse group of
    participants that is racially and ethnically diverse?
        Dr. Collins. Well we track that week by week. I personally
    am asking for that information every week to see how the
    enrollment is going. But I am going to ask Dr. Duvaney to say
    how this is being done because this is unprecedented to have
    this level of diversity.
        Ms. Devaney. Yes. And thank you for the question. This is
    perhaps our strongest priority as a program, understanding that
    ultimately a lot of the data scientists are using today is not
    reflective of the diversity of the country and that what we are
    learning is not applicable to all communities.
        We have a number of different ways in which we are
    attempting to reach out to diverse communities. And just go
    into it with the understanding that we are going to try things,
    and it is not going to work, and we are going to go have to
    shift and try new things.
        One of the things I would just like to highlight is working
    with community partners. We have a number of community
    engagement partners across the country who are helping us to
    build trusted relationships with their communities at a local
    level. And our chief engagement officer, Dr. Dara Richardson-
    Heron at the NIH has been really working with those groups in a
    very robust way. And beyond our first foreign inaugural
    partners we have about 30 plus partners that are national that
    are helping us to build awareness within our communities.
        Mr. Cardenas. So you are talking about groups that are more
    local and actually might have a propensity for working with a
    particular population, whether it is an immigrant population,
    or a Hispanic population, or a Black population, et cetera. So
    working with local groups who already have relationships with
    those communities?
        Ms. Devaney. That is right, exactly. Yes.
        Dr. Collins. When we did the launch on May 6 in seven
    different places I was in New York at the Abyssinian Baptist
    Church with an African-American community that was totally
    revved up about the opportunity to be included this time.
        And I have to give credit to 21st Century Cures about this
    focus on inclusion. You have given us some additional tools
    there in many different projects across the board, but All of
    Us is really turning out to be a flagship here about how to do
    this in the most visionary way.
        Mr. Cardenas. OK. So this opportunity for us to remind
    ourselves that diversity and research when it comes to subjects
    in particular communities, et cetera, because we all
    genetically have different reactions, et cetera, and different
    propensities when it comes to certain diseases and cause and
    effect, correct?
        Dr. Collins. Absolutely. And one should not assume that
    when you see a health disparity that that is something that is
    readily understandable on the basis of looking at one thing.
    Usually these are a combination of environmental exposures, of
    stress levels, of some genetics in there. But one shouldn't
    overinterpret that part because we are awfully similar at the
    DNA level. And if you really want to understand the health
    disparities, you need to have these comprehensive studies that
    collect data from all those perspectives and then figure out
    how to intervene.
        Mr. Cardenas. So it is better to have good research rather
    than having to force yourself to extrapolate out, and then that
    is more guesswork and that is not necessarily scientific.
        Dr. Collins. You want to have the data on the people for
    whom you are going to then offer some answers. We just heard
    from Dr. Sharpless a few moments ago about this big study they
    are just starting with African-American prostate cancer.
    Another example, where we don't understand, why men who have
    prostate cancer, who are Black, have a higher likelihood of
    dying and a higher likelihood of aggressive disease. We need to
    know that.
        Mr. Cardenas. OK. So what are some of the challenges
    associated with building a cohort that is racially and
    ethnically diverse? Do we have some findings or things that we
    are hoping to tackle in the near future that maybe you learn by
    venturing further into this diversity effort than ever before?
        Ms. Devaney. Yes. Well, we are just at the beginning of
    this journey. So we would love to follow up with your office
    and talk about this more. I will say we have community advocacy
    groups and participant advisory boards, at all of the health
    care organizations that are part of our program that are
    helping us understand what is working, and what is not working,
    messaging what is not working as part of--even things like your
    parking isn't close enough to the clinic, and therefore it is
    too hard for me to make the appointment time to come in and
    donate my samples. So we have been learning a lot just from
    participant feedback and would be happy to share as we learn
    more.
        Mr. Cardenas. So as an engineer myself, having a good
    feedback system and adjusting all the way is important so you
    are doing that.
        Ms. Devaney. Yes.
        Mr. Cardenas. OK. Thank you very much Mr. Chairman and
    thank you for the generosity of time.
        Mr. Burgess. The gentleman yields back. The chair
    recognizes the gentleman from Missouri, Billy Long, for 5
    minutes for questions, please.
        Mr. Long. Thank you, Mr. Chairman.
        And I would like to get one more shout out to Diana
    DeGette. Diana is my co-chair on a congressional study group on
    Japan. We travel to Japan together every year. And also to Fred
    Upton for their tireless work on this 21st Century Cures and
    they just did yeoman's work as a lot of you know. So I want to
    give one more shout out to them.
        My youngest daughter when she was 25 years old diagnosed
    with Hodgkin's lymphoma. Today she is 29 years old, she is 3
    years past chemo. So the developments over the years as Dr.
    Collins was talking earlier have been phenomenal. And I want to
    thank everyone.
        Dr. Sharpless, we were happy to support the Cancer Moon
    Shot funding in the 21st Century Cures and are looking forward
    to hearing about progress for patients. Can you tell us about
    the most exciting thing that is being supported in the Cancer
    Moon Shot?
        Dr. Sharpless. Well, that is really tough. There is so much
    good stuff. I think this is a very meaningful law for patients
    with cancer. And I think it is impacting in many ways. We
    already talked about the response studies, maybe I will talk
    about the rare tumor initiative, which is also a very exciting
    initiative. We mention rare diseases, many rare cancers
    actually are hard to study for some of the reasons that came
    up. They are rare, they are hard to do clinical trials.
        And the NCI is a good place to study those things. We can
    have patients with a certain rare disease come to the NCI and
    get their care here. And this paradigm works and the Moon Shot
    trying to build on that experience. So for example, in the area
    of a disease called RASopathies where different mutations that
    activate RAS, a driver protein in cancer, those patients
    generally present with childhood tumors.
        And the NCI now has a recent trial that we just had
    presented at ASCO shown here on the left is a slide of Andrea
    Gross showing, one of our scientists--showing results of
    selumetinib trial in this RASopathy patients.
        So this is a patient with NF1 deficiency. And my executive
    summary was the tumors shrink, the kids feel better and the
    drugs seem safe. Yay. And then a few parents contacted me and
    said, my child was on this trial, actually and the responses
    have been marvelous.
        And so shown is the picture of the child pretreatment on
    the left. This is Phillip after treatment. And you can see his
    windpipe, his airway is not being compressed by the tumor
    anymore, and he has not the social stress of going to school
    with a big lesion like that. So this is a sort of a precancer
    syndrome. This is mutation that activates RAS, this cancer
    gene. And this kind of study is a really great thing for the
    NCI to take on because of our integral program.
        Mr. Long. OK. And in the testimony it says we must
    transform the way we conduct research, the way we share
    results, and the way we get discoveries into patient's care.
    Could you discuss how NIH is helping transform infrastructures
    needed to help meet these goals?
        Dr. Sharpless. For junior scientist you mean?
        Mr. Long. Yes.
        Dr. Sharpless. Yes. Yes. So the new funding from Congress
    has made it possible to increase the success rates for new
    scientists applying for their first grants, so it is called R01
    grant. So in NCI for example has set aside enough funds to
    increase that amount by 25 percent. We similarly are trying to
    link in the period of the award. We think that that will allow
    the scientists to concentrate on their science and not much
    bureaucracy in terms of writing grants.
        So we are testing out a 7-year award as opposed to a 5-year
    award. And one of the things we are really doing is thinking
    about the training opportunities we are providing for young
    scientists, both in the postdoctoral setting and in the faculty
    setting, to make sure they get the right skills, for example in
    big data, which is something that we really need more training
    for.
        Dr. Collins. If I may, just across all of NIH, and again
    thanks to the 21st Century Cures and Next Generation researcher
    initiative, which is part of this bill, we have put into place
    efforts to provide a better chance for early stage
    investigators coming to NIH with their first major grant
    application to get funded, and then to have sustainable support
    so they know they have a career.
        This year, fiscal year 2018, we are predicting we will fund
    the largest number of first time investigators ever at NIH
    because we have made this shift in priorities and you helped us
    with that, with 21st Century Cures.
        Mr. Long. Thank you. I had a chance to meet with two early
    career scientists from the American Association of Cancer
    Research. And I was very impressed with the excitement and
    passion they have for careers in cancer research and helping
    cancer patients. And once again as a father of a cancer patient
    survivor it really means a lot to me.
        Thank you all for being here, and thank you for being here
    today, you all too.
        So I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. The chair now recognizes the gentleman from
    Maryland, Mr. Sarbanes, for 5 minutes of questions, please.
        Mr. Sarbanes. Thank you, Mr. Chairman. Thank you all for
    coming today. Whenever you testify I am reminded of the
    tremendous responsibility that you have heading the
    organizations that you do. And I am going to thank you for your
    work to implement 21st Century Cures, which obviously as you
    know is a point of real pride for this committee. So thank you
    for that.
        Commissioner Gottlieb, I wanted to ask, I know there have
    been some discussions already about the biosimilars action
    plans that you released. I commend you for that. I have just
    introduced in the last few days something we are calling the
    biosimilars competition act, which is try to get to some of
    these pay for delay agreements that are operating in the
    biologic, biosimilar space in the same way that we have given
    authority to the FTC to kind of police that conduct with
    respect to brand name drugs and in generics where it has been
    consequential for sure. That the authority is there, that they
    can look at these agreements, they can judge whether they are
    fair and appropriate, vis a vis the consumer or not--there are
    tremendous savings to be had there.
        I think maybe the figure is that brand names occupy about
    20 percent of the drugs that are produced every year, but it is
    still 75 percent of the cost that is out there. And I think
    that includes the sort of biologics, biosimilar distinction as
    well. Can you just speak to anything that is a good idea for
    the FTC to have this authority?
        And also, I think you understand from the plan that you put
    forward in your comments generally that you look for ways to
    cooperate with an agency like the FTC around this kind of thing
    to make sure that we are getting these drugs at the price point
    that they should be at.
        Dr. Gottlieb. I thank you for the question, Congressman. I
    haven't looked specifically at the measure, but I will. It is a
    little bit outside the scope of my authorities. I have my own
    equities with FTC in trying to work with them to try to see how
    we can facilitate their interests and potentially bring in
    cases related to delaying tactics it might involve for example
    the REMS where we can help provide information that could
    prompt them to take a look at whether those practices are
    anticompetitive and that has been a big bugaboo of mine as
    well.
        Generally speaking, we like to approve safety biosimilars
    and we like to see them marketed and we like to see patients
    benefiting from them.
        So culturally we like to see drugs marketed. It is the fact
    that most of the biosimilars that have been approved have not
    been marketed for various reasons. The biggest reason is in
    patent delays. It is also a fact that a growing number of small
    molecule generic drugs end as being approved but the drugs are
    never being marketed because of the changing economic dynamic
    to that market as well as. And I think we need to keep a close
    eye on that as well, because competition may be declining in
    the small molecule generic world as well.
        Mr. Sarbanes. Thank you. And we will try to get this tool
    into the toolkit that the government has broadly to make sure
    that we are protecting consumers in that space.
        Let me switch gears real quick. To you, Dr. Collins. And I
    know you got a question earlier I believe about Alzheimer's
    research generally and some of the clinical trials associated
    therewith. But there was an article in The New York Times
    yesterday that pointed specifically to the challenge that is
    presented by trying to find sufficient people to participate in
    these trials.
        There are a lot of trials that are underway or are on deck
    that would suggest the need for up to 25,000 participants in
    these trials. And some of them could be really breakthrough,
    but I gather that this is a real problem, challenge, trying to
    find enough participants.
        Can you speak to what you know about that and what can be
    done about it?
        Dr. Collins. Yes, thank you. That was based upon comments
    made by Dr. Marie Bernard who is the deputy director on the
    National Institute on Aging at the major Alzheimer's meeting
    that was held in Chicago.
        This is a challenge because we are now at the point where
    we are trying to recruit individuals who don't yet have
    cognitive decline, but who are at high risk for Alzheimer's by
    increasingly accurate means that we have, some of them using
    imaging, some using genetics, and we need a lot of participants
    in order to do that. But now we are reaching out to people who
    may not be that motivated to take part in research because they
    are fine, right now.
        We are arguing that that is the best time to intervene, but
    it is not so easy to enroll. I will say one of dreams I have of
    the All of Us program that we have been talking about there
    program where you have a million participants who are
    preconsented for recontact for reach protocols that that would
    be a fantastic group to be able to enroll participants in
    studies like this for common disease, whether it is diabetes,
    or hypertension, or Alzheimer's.
        But right at the moment where we don't have that platform,
    we really have a challenge trying to convince people that this
    is going to be something they want to take part in. We are
    pulling out all the stops. And again the Congress having made
    Alzheimer's such a high priority for us. We have resources in
    order to do that kind of recruitment, but it is not simple
    because it is a different model than what people are used to
    where you get approached about a clinical trial when you
    already have the diagnosis. Here we are approaching people who
    don't have that diagnosis trying to figure out how to prevent
    it.
        Mr. Sarbanes. Thank you very much. I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. The chair recognizes the gentleman from Indiana,
    Dr. Buschon, for 5 minutes of questions, please.
        Mr. Buschon. Thank you, Mr. Chairman. Thank you all for
    being here. Honestly it is pleasure for me to be here. As a
    physician, I never thought I would get to talk to you all. And
    I was at an event with Dr. Sharpless with Steve Rosenberg and
    Diana DeGette recently. And the work that he has done over the
    years. I can't even express how much of an impact he has had.
        Dr. Collins, you just said high risk. Who is high risk for
    Alzheimer's?
        Dr. Collins. Well, anyone who gets to be 85 or 90 is at
    high risk.
        Mr. Buschon. No, I am saying that people who don't know
    they have it, if your mom has it, your dad has it, your
    grandma? Maybe if one of your family members has it, you are
    high risk. I don't know.
        Dr. Collins. So there are there ways in which we are
    currently identifying such folks. One is we that you have a
    very strong family history, almost inherited in a dominant
    fashion. In fact, it is a dominant fashion. And there are those
    families that if you are in one of those circumstances we can
    track the gene in the family and figure out who has it long
    before any symptoms.
        Another way is to look at a genetic risk factor called
    ApoE4. If you have one copy of that, your risk goes up
    threefold. If you have two copies, one from each parent, it
    goes up 15 fold so those people are very high risk. And the
    third way is scanning using a PET scan that picks up amyloid,
    because amyloid starts depositing in your brain probably 20
    years before the first cognitive decline symptoms. So if people
    who are worried about this are willing to do a scan, we may be
    able to say, hey, you are one of those that ought to get into
    this clinical trial.
        Mr. Buschon. So if somebody out there is watching C-SPAN
    right now and they are sitting there going, hmm, I wonder if I
    am high risk. I understand the technical tests and things that
    you do, but people need to say well, my mom had it so I am high
    risk. You know what I am saying?
        Dr. Collins. And indeed that is one.
        Mr. Buschon. That is one of them, right?
        Dr. Collins. There are other ways to try to be more precise
    about it. If people are watching C-SPAN out there and are
    wondering hey should I take part in this? We just heard how
    difficult it has been sometimes to get the word out there. The
    place to go is clinicaltrials.gov which posts the trials on
    Alzheimer's disease and everything else where you can find out
    who is doing a trial, what are the enrollment criteria, who do
    you contact to learn more about it? All of this we do very
    closely with the FDA as a partner.
        Mr. Buschon. Great, thank you.
        Dr. Gottlieb, my wife's an anesthesiologist she is out in
    the field today practicing medicine. She just texted me. She
    didn't even know you guys were here. And she says, hey, can you
    check into the fentanyl shortage, because--no, I am not kidding
    she just texted me.
        Mr. Long. She is watching C-SPAN.
        Mr. Buschon. No, she doesn't. She is actually practicing
    medicine. And we have demonized Fentanyl, the illicit forms of
    Fentanyl, but this is a very, very common anesthetic agent. And
    apparently there is going to be a long term back order on
    Fentanyl. Which is honestly going to be a huge problem.
        You don't need to answer the question, I just want to point
    out that what you are doing on drug shortages has real
    everyday, and you know this, but for everyone else out there,
    clinical implications in the practice of medicine. She says
    Zofran, other common paralytic agents that she uses daily in
    her anesthesia practice are really in short supply. Fentanyl is
    a new one on me though, she just texted me that.
        So thank you for work on that and your response earlier on
    what you all are doing on that. If you have any other further
    comments. Because I have one other question for you.
        Mr. Gottlieb. I will just say these are structural
    problems, as I mentioned before, and whatever is in shortage
    say 6 months from now I guarantee it is going to be something
    different. I have grappled personally with these as well, as a
    hospital based physician, so this impacts patient care. We are
    working very hard on this.
        Mr. Buschon. I know you are. So 21st Century Cures sought
    to implement personalized medicine and seek cures. This is a
    little proprietary question here, for diseases such as cancer
    which rely on diagnostics, and I know your staff probably has
    told you I might ask about this, unfortunately the current
    diagnostic frameworks for laboratory developed tests, LDTS in
    vitro diagnostic test kits haven't been updated since 1988,
    1976, and 1988. That is why Diana DeGette and I and other
    members of the committee have released the Diagnostic Accuracy
    and Innovation Act, DAIA, so to speak, to update how
    diagnostics are regulated.
        We have had a discussion draft out there for a long time
    you all have had that and we really appreciate your input. And
    we have talked to laboratories, patient groups providers and
    others and we really need reform now.
        And so I know you are familiar with the issue and I brought
    it in the past, as well as the committee's last hearing. You
    recently gave us a narrative on what the FDA provided us
    earlier this year in response to DAIA, but I want to get
    diagnostic reform done this Congress hopefully.
        So we are waiting for the red line of the bill from FDA and
    I wanted to know if you have any insight in that progress?
        Dr. Gottlieb. It is very close, Congressman. We have
    completed most of our work and I hope to have it to you very
    soon. I would be happy to come into your office and brief you
    on it as well, but I think we are very close.
        Mr. Buschon. Great. I just want to reiterate you have been
    very helpful and I am very appreciative of that. And we are
    hopeful to get this accomplished this Congress.
        Thank you, Mr. Chairman. I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back. The chair recognizes the gentlelady from Indiana,
    Ms. Brooks, 5 minutes for questions, please.
        Mrs. Brooks. Thank you, Mr. Chairman and thank you all for
    your service to our country and for all of the incredible
    medical innovation. I just want to thank you, because you all
    could probably be doing very, very different things in our
    country and yet you are here, working on behalf of all
    citizens, not just here but actually around the globe.
        Dr. Collins, I would like to ask in your testimony you
    mention that there are provisions that provide direction from
    Congress to ensure specific subgroups of patients are
    specifically included in research in clinical trials. I am
    particularly interested in childhood disease and cancers.
        And having heard from constituents who have lost a child to
    cancer and are currently fighting the disease, we know that NIH
    is focused on improvements for children. That is an area that
    has been lacking in the past. Can you elaborate on the
    implementation of the recently passed Childhood Cancer STAR
    Act, which was signed into law in June and what kind of
    innovation are we focused on for childhood cancers and disease?
        Dr. Collins. I ask Dr. Sharpless to respond to that.
        Dr. Sharpless. I thank you for the question on childhood
    cancer. It is important to say two things about childhood
    cancer. While it is true we have made tremendous progress,
    fewer children are dying of cancer than ever, we are still
    having, also true, too many children die of cancer.
        And in particular, even when we are able to cure kids of
    cancer, we often leave them with lifelong toxicity, so they
    have survivorship issues. And I think that is one of the
    principal issues the STAR Act tried to address is the issues of
    novel therapies for kids with cancer, and then also, the burden
    of survivorship that some of these patients incur through their
    curative therapy.
        And so the NCI is really interested in this topic. This was
    a personal research interest of mine when I was in academics,
    so I know firsthand the pain that many of these patients go
    through or the suffering that this entails.
        And I think we have a focus on new research efforts related
    to survivorship, biospecimen acquisition, and then getting new
    advices and new voices into the NCI, to make sure that we are
    adequately advised from the expert community on pressing issues
    in survivorship.
        So thank you for the leadership on that important act.
        Mrs. Brooks. Thank you very much.
        Dr. Gottlieb, as my colleague, Anna Eshoo, talked about, in
    our focus on PAHPA reauthorization, which it is critically
    important we get that reauthorized by the end of September, one
    of the things that has come up in various discussions with Dr.
    Kadlec and others is the importance of platform technology, the
    use of platform technology when it comes to innovation with
    vaccine.
        Can you talk about that to some extent, because there has
    been frustration on this committee about egg-based vaccines
    versus platform technology? Or if anyone would like to comment.
    I am starting with you, but----
        Dr. Gottlieb. I would like to start, if I can. I appreciate
    the question very much. And we have a proposal in the
    President's budget for some additional funding for the agency
    to try to support continuous manufacturing, alternative
    manufacturing. And we think this is really the direction that
    we want to head in, where you have closed, continuous
    manufacturing platforms, particularly with recombinant
    technologies, where you can effectively have, like, cassettes
    that you basically plug into the platform and can allow
    continuous manufacturing of a vaccine.
        And if you want to modify the vaccine, you can literally
    plug in another cassette that codes for a different permutation
    of the same vaccine, same recombinant vaccine.
        We think that this is really the solution or a solution for
    influenza seasonal flu, the ability to scale up manufacturing
    more quickly andproduce vaccines closer to the flu season so
    you can guess the strain better as well as have a platform
    available in the event of a pandemic flu. And these same
    technologies can be used to try to scale up manufacturing of
    other vaccines.
        In an ideal circumstance, what we would have isn't
    mothballed vaccine that degrades over time if it is not stored
    correctly and takes up a lot of space and is costly, but
    platforms that allow quick manufacturing of vaccines should we
    need it.
        Mrs. Brooks. I am assuming, Dr. Collins.
        Dr. Collins. NIH works very closely with FDA in this space.
    If Tony Fauci was here, he would go into this in some detail,
    that the idea of having to build things in eggs is so much
    yesterday's technology.
        And the concrete example this past year, with the flu
    vaccine having been surprisingly ineffective. It turns out that
    the virus mutated in the process of being grown in the eggs;
    and so, therefore, it turned out not to be a particularly
    effective vaccine for something that we didn't have control
    over.
        These new platforms, which allow you to build vaccines in a
    much more rapid fashion, and much more directed fashion, DNA-
    based vaccines, RNA-based vaccines. Once you have that platform
    going, you can, very quickly, adapt it to many different
    pathogens. And that is certainly something we are working on
    now, to develop this universal influenza vaccine, which is a
    very high priority, and Congress has given us some additional
    funds for that, so that we wouldn't have to have the yearly
    effort to try to guess right. You would have a vaccine that
    works against virtually all strains and would also be effective
    against that next 1918-style pandemic, which we are all worried
    about and which is overdue.
        Mrs. Brooks. Thank you. And we did include a Pan Flu
    provision in the PAHPA legislation passed out of this
    committee.
        With that, I yield back. Thank you for your work.
        Dr. Collins. Thank you for that.
        Mr. Burgess. The chair thanks the gentlelady. The
    gentlelady yields back.
        The chair recognizes the gentleman from Florida, Mr.
    Bilirakis, 5 minutes for questions.
        Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
    And I thank the panel for their testimony today as well.
        Well, the first question I wanted to ask is, we talked
    about Alzheimer's disease, of course, and what about
    Parkinson's? We are talking maybe how do you know if you are a
    candidate for Parkinson's disease to participate in these
    clinical trials, if there are no symptoms? It may be in the
    early stages. And if you could answer that question, sir, I
    would appreciate it.
        Dr. Collins. There are parallels here that are notable.
    There are genetic risk factors for Parkinson's disease, which
    is interesting, because when I was in training and I asked my
    professor, ``Are there any diseases that don't have genetic
    contributions?'' And he said, ``Oh yes, everybody knows
    Parkinson's is always totally random and sporadic.'' Well, he
    was really wrong.
        So if you have a variant, for instance, in a gene called
    LRRK2, your risk of Parkinson's goes up. If you have a variant
    in a gene alpha-synuclein, your risk goes up. We are beginning
    to, therefore, be able to identify people at high risk and
    invite them to take part in prevention trials.
        Another big thing that has happened in Parkinson's disease
    in just the last 6 months is the formation of a partnership
    with industry called the Accelerating Medicines Partnership for
    Parkinson's Disease with FDA as a critical partner in this as
    well, and really, now, figuring out how we could learn from a
    very large amount of data that is out there, but hadn't been
    brought together, what are the next generation of drug targets
    for Parkinson's disease and how do we accelerate the process of
    getting there? Because we have treatments, L-dopa has been
    around a long time, but we certainly don't have things that
    actually prevent progression. They more treat the symptoms. And
    we believe we could do better with that.
        I should also say the BRAIN Initiative, which is this very
    bold effort supported by 21st Century Cures and the Innovation
    Fund, is learning things about the wiring diagram of the brain
    that is going to be very relevant to some of the things that
    are being done for Parkinson's disease, with direct brain
    stimulation, where you actually put an electrode into the brain
    to try to take care of some of the motor problems. What we do
    right now is kind of clunky. As we learn the wiring diagram, we
    could be much more precise and effective about that.
        Mr. Bilirakis. Well, thank you very much. Anyone else want
    to add something with regard to that? OK. Thank you.
        Dr. Gottlieb, Section 3088 clarifies that FDA has the
    authority to grant emergency use authorization for animal
    drugs, allowing the agency to approve the GMO mosquitoes for,
    again, Florida's Zika problem. We are planning ahead.
        Would you provide an update on the implementation of
    Section 3088, specifically as it relates to approval of the GMO
    mosquitoes?
        Dr. Gottlieb. I can get back to you with a more detailed
    update on that, Congressman. But I will tell you, there has
    been some discussion about the nexus of authority with EPA for
    some of these products. But we did provide a guidance earlier
    this year, I believe, that addressed some of these issues. So I
    can get back to you with more specifics about where that
    stands.
        Mr. Bilirakis. I appreciate that very much.
        Dr. Gottlieb, a second question: As a long-time champion
    and supporter of policies that seek to promote a deeper level
    of patient engagement in the therapy development processes, I
    am pleased with the progress the agency has made under your
    leadership--so congratulations, and we appreciate all you do--
    including the FDA's moving ahead to implement the Patient-
    Focused Impact Assessment Act provision of Cures that requires
    the FDA to disclose how patient engagement data informed a
    review of any approved product.
        Where is the agency presently in implementing this
    provision, particularly efforts to standardize the inclusion of
    such information in the record of approved drugs so that it is
    accessible and understandable?
        Dr. Gottlieb. We have issued one of four guidances that we
    intend to relay to patient-focused drug development, and we
    have standardized a format for the presentation of patient-
    related information in clinical trials.
        So when a clinical trial is submitted to us, there is a
    discrete, a very explicit section for patient-focused
    information. And on the medical device side of our house, we
    have done some similar things: We are seeing a very high rate
    of the use of patient-focused information, and PROs, in the
    development of medical devices as well. So this is a cross-
    agency effort across all of our Medical Product Centers. We
    also just stood up a Patient Affairs Office inside the Office
    of the Commissioner reporting in to the principal deputy that
    is going to help advance some of these policies, really, a
    coordinating office to provide a focus of access for patient
    groups, but also, a focus of policymaking when it is cross-
    agency policymaking around these issues.
        Mr. Bilirakis. OK. Thank you very much.
        I yield back, Mr. Chairman.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back.
        The chair recognizes the gentleman from Georgia, Mr.
    Carter, 5 minutes for questions, please.
        Mr. Carter. Thank you, Mr. Chairman. And thank all of you
    for being here and thank you for your efforts in implementing
    21st Century Cures, legislation that I personally feel like is
    some of the best legislation we have passed in Congress in
    quite a while, so we are very proud of, particularly coming out
    of this committee.
        Dr. Collins, I will start with you. I wanted to ask you
    particularly about one of the initiatives of 21st Century
    Cures, and that was to, really, review the regulations and
    policies with respect to research in laboratory animals. And as
    I understand it, you are working with USDA now and the FDA to
    try to complete a review of that. And I just wanted to ask you
    if you could tell us the current status of that review, and
    when do you anticipate the completion of that review?
        Dr. Collins. I appreciate the question. We are very
    seriously engaged in this. And, again, 21st Century Cures gave
    us some clear guidance about what we ought to engage in. We did
    put out an RFI back in March to ask for comments in this area,
    in terms of whether the oversight that we currently apply to
    animal experimentation is sufficient or whether it has areas
    that are overly bureaucratic, which has been a concern.
        Obviously, we are deeply concerned about maintaining our
    ethical responsibilities, in terms of how we take care of
    animals that are subjected to various experimental approaches,
    from which we learn a great deal that has led to many medical
    advances.
        We got 19,000 responses to that request, and they are
    currently being sorted at the moment. We would expect,
    therefore, to have, based upon those, a draft set of
    recommendations about animal care and use, sometime probably in
    September. We will then need to have responses to that. And so
    we would hope to have a final version of this by December or
    early in 2019.
        Mr. Carter. Great, great. Any opportunities that you have
    identified thus far that may help you?
        Dr. Collins. I think there are concerns that some of the
    requirements we put on grant applicants in terms of animal care
    and use could be delayed until the award is actually made as
    opposed to asking them to have all of those things in place
    when they submit an application, because that can add a lot of
    time and effort.
        And obviously, our concern is, if we are going to actually
    make the award, we want to be sure that the animal care is
    being done in the best possible way. That is one area.
    Obviously, there are differences of opinion here.
        Mr. Carter. Yes.
        Dr. Collins. And we are seeing those in those 19,000
    responses. And at some point, we have to try to come down in
    what we think is a fair and balanced approach.
        Mr. Carter. And I am sure you will reach that. I am very
    confident. Let me switch gears here and talk about something
    that is very exciting to me as a pharmacist, and that is
    precision medicine. And that is something that I see in genomic
    testing and everything is something I see as the wave of the
    future, and great opportunities for us in healthcare.
        But I am concerned, when we get all this data in, we are
    struggling already with our electronic health records. How are
    we going to handle this? I want to ask you that, and then I
    would like to ask Dr. Gottlieb as well.
        Dr. Collins. Well, I will say a word, and then I will ask
    Dr. Devaney to say a little more, as the Deputy Director of the
    All of Us Program. We are very invested in looking at this in
    the fashion that is cutting-edge, as far as dealing with very
    large datasets, putting the data into the cloud.
        We just had a very interesting all-day workshop on Monday
    on artificial intelligence and machine learning and how that
    can be applied to these unprecedented datasets to glean the
    maximum amount of information out of there while, at the same
    time, maintaining the confidentiality, the security systems
    that the participants in this are going to expect about their
    deidentified data.
        But maybe, Dr. Devaney, you want to say a little more?
        Mr. Carter. Sure, please.
        Ms. Devaney. I would love to add to that. So one of the
    data types that is going to be, I think, the most essential to
    precision medicine, or one of is information from electronic
    health records. And this is one of the largest challenges for
    our program.
        We have direct partnerships with many healthcare
    organizations, and we are getting those data continuously from
    those partnerships, but we are also working on other
    strategies, including one in partnership with four of the
    largest her vendors right now, to work on making the data
    transmission much more seamless across provider lines and into
    the program when a participant authorizes it.
        Mr. Carter. Great. Dr. Gottlieb, I know this is important
    in drug data development as well.
        Dr. Gottlieb. I appreciate the question. I would just take
    a step up the continuum to try to make effective use of the
    data. Because there is so much information, how can we make
    effective use of the data in a way that it can translate to
    clinical benefits to patients. And I think this is where some
    of the issues we talked about earlier around clinical trial
    innovation comes in where you have the ability now, with a
    seamless clinical trial design, to effectively buy us
    enrollment in the trial for some of the genomic information and
    predictive information that is likely to predict who is more
    likely to benefit from a treatment, and who is less likely to
    experience a side effect.
        And so if we can use this information in that way to
    structure trials and enrollment, we can end up with much more
    information about who is likely to benefit from a drug and more
    tools to make sure the right drug gets to the right patient at
    the right time. We have talked about this for decades. We now
    have that technology at hand.
        Mr. Carter. And I can sense the excitement in your voice.
    And it is exciting for me, as a healthcare professional as
    well. I just look into the future of this and just think, Wow,
    what we have got to look forward to. Thank you.
        And I yield back.
        Mr. Burgess. The chair thanks the gentleman. The gentleman
    yields back.
        The chair needs to state that, without objection, all
    members' opening statements will be made part of the record.
        The chair asks if the gentleman from Texas has a unanimous
    consent request concerning Alzheimer's. Were you going to ask
    that additional information be forwarded to the committee about
    Alzheimer's?
        Mr. Green. If you could just send it to the committee on
    some of the information you couldn't have given us today
    because of the time limits.
        Dr. Collins. Happy to do that.
        Mr. Green. Thank you. I forgot what I was going to ask.
        Mr. Burgess. And also, the chair would like to make the
    observation that, Dr. Collins, you started out this hearing
    with the remark about the immunotherapy and some of the
    dramatic things that have occurred. And it predated our work,
    our passage of the Cures bill, but a former President of the
    United States, in July of 2015, went public with the
    information that he had metastatic melanoma to the brain and
    the liver. And remembering my time in medical school, my
    initial thought was, we will not have this individual with us
    by Labor Day. But it has really been dramatic to see him a year
    later deliver a speech at the Democratic Convention. A year and
    a half, then he was present at the inauguration in January
    2017. I don't know what his clinical status is now, but it was
    truly dramatic.
        And, again, all of you are to be congratulated for making
    that possible. And hats off to former President Carter for
    going public with the information and entering a clinical
    trial, because that is the way information is gathered and
    learned. So, again, I felt obligated to make mention of that
    milestone.
        Seeing that there are no further members wishing to ask
    questions, I do want to thank our witnesses for being here
    today. Pursuant to committee rules, I remind members they have
    10 business days to submit additional questions for the record.
    I ask the witnesses to submit their responses in receipt of
    those questions.
        Without objection, the subcommittee is adjourned.
        [Whereupon, at 11:17 a.m., the subcommittee was adjourned.]