    [House Hearing, 113 Congress]
    [From the U.S. Government Publishing Office]

           21ST CENTURY CURES: INCORPORATING THE PATIENT PERSPECTIVE

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

                                    HEARING

                                   BEFORE THE

                             SUBCOMMITTEE ON HEALTH

                                     OF THE

                        COMMITTEE ON ENERGY AND COMMERCE
                            HOUSE OF REPRESENTATIVES

                        ONE HUNDRED THIRTEENTH CONGRESS

                                 SECOND SESSION

                                   __________

                                 JULY 11, 2014

                                   __________

                               Serial No. 113-158

          Printed for the use of the Committee on Energy and Commerce

                            energycommerce.house.gov

                                   ________

                         U.S. GOVERNMENT PUBLISHING OFFICE

    91-848 PDF                   WASHINGTON : 2015
    -----------------------------------------------------------------------
      For sale by the Superintendent of Documents, U.S. Government Publishing
      Office Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800;
             DC area (202) 512-1800 Fax: (202) 512-2104 Mail: Stop IDCC,
                              Washington, DC 20402-0001

                        COMMITTEE ON ENERGY AND COMMERCE

                              FRED UPTON, Michigan
                                     Chairman
    RALPH M. HALL, Texas                 HENRY A. WAXMAN, California
    JOE BARTON, Texas                      Ranking Member
      Chairman Emeritus                  JOHN D. DINGELL, Michigan
    ED WHITFIELD, Kentucky                 Chairman Emeritus
    JOHN SHIMKUS, Illinois               FRANK PALLONE, Jr., New Jersey
    JOSEPH R. PITTS, Pennsylvania        BOBBY L. RUSH, Illinois
    GREG WALDEN, Oregon                  ANNA G. ESHOO, California
    LEE TERRY, Nebraska                  ELIOT L. ENGEL, New York
    MIKE ROGERS, Michigan                GENE GREEN, Texas
    TIM MURPHY, Pennsylvania             DIANA DeGETTE, Colorado
    MICHAEL C. BURGESS, Texas            LOIS CAPPS, California
    MARSHA BLACKBURN, Tennessee          MICHAEL F. DOYLE, Pennsylvania
      Vice Chairman                      JANICE D. SCHAKOWSKY, Illinois
    PHIL GINGREY, Georgia                JIM MATHESON, Utah
    STEVE SCALISE, Louisiana             G.K. BUTTERFIELD, North Carolina
    ROBERT E. LATTA, Ohio                JOHN BARROW, Georgia
    CATHY McMORRIS RODGERS, Washington   DORIS O. MATSUI, California
    GREGG HARPER, Mississippi            DONNA M. CHRISTENSEN, Virgin
    LEONARD LANCE, New Jersey                Islands
    BILL CASSIDY, Louisiana              KATHY CASTOR, Florida
    BRETT GUTHRIE, Kentucky              JOHN P. SARBANES, Maryland
    PETE OLSON, Texas                    JERRY McNERNEY, California
    DAVID B. McKINLEY, West Virginia     BRUCE L. BRALEY, Iowa
    CORY GARDNER, Colorado               PETER WELCH, Vermont
    MIKE POMPEO, Kansas                  BEN RAY LUJAN, New Mexico
    ADAM KINZINGER, Illinois             PAUL TONKO, New York
    H. MORGAN GRIFFITH, Virginia         JOHN A. YARMUTH, Kentucky
    GUS M. BILIRAKIS, Florida
    BILL JOHNSON, Missouri
    BILLY LONG, Missouri
    RENEE L. ELLMERS, North Carolina

                             Subcommittee on Health

                         JOSEPH R. PITTS, Pennsylvania
                                     Chairman
    MICHAEL C. BURGESS, Texas            FRANK PALLONE, Jr., New Jersey
      Vice Chairman                        Ranking Member
    ED WHITFIELD, Kentucky               JOHN D. DINGELL, Michigan
    JOHN SHIMKUS, Illinois               ELIOT L. ENGEL, New York
    MIKE ROGERS, Michigan                LOIS CAPPS, California
    TIM MURPHY, Pennsylvania             JANICE D. SCHAKOWSKY, Illinois
    MARSHA BLACKBURN, Tennessee          JIM MATHESON, Utah
    PHIL GINGREY, Georgia                GENE GREEN, Texas
    CATHY McMORRIS RODGERS, Washington   G.K. BUTTERFIELD, North Carolina
    LEONARD LANCE, New Jersey            JOHN BARROW, Georgia
    BILL CASSIDY, Louisiana              DONNA M. CHRISTENSEN, Virgin
    BRETT GUTHRIE, Kentucky                  Islands
    H. MORGAN GRIFFITH, Virginia         KATHY CASTOR, Florida
    GUS M. BILIRAKIS, Florida            JOHN P. SARBANES, Maryland
    RENEE L. ELLMERS, North Carolina     HENRY A. WAXMAN, California (ex
    JOE BARTON, Texas                        officio)
    FRED UPTON, Michigan (ex officio)

                                 C O N T E N T S

                                  ----------
                                                                       Page
    Hon. Joseph R. Pitts, a Representative in Congress from the
      Commonwealth of Pennsylvania, opening statement................     1
        Prepared statement...........................................     2
    Hon. Henry A. Waxman, a Representative in Congress from the State
      of California, opening statement...............................     3
    Hon. Fred Upton, a Representative in Congress from the State of
      Michigan, prepared statement...................................     5

                                   Witnesses

    Janet Woodcock, M.D., Director, Center for Drug Evaluation and
      Research, U.S. Food and Drug Administration....................     6
        Prepared statement...........................................     8
        Answers to submitted questions...............................   123
    Pat Furlong, Founding President and CEO, Parent Project Muscular
      Dystrophy......................................................    53
        Prepared statement...........................................    55
        Answers to submitted questions...............................   132
    Robert J. Beall, Ph.D., President and CEO, Cystic Fibrosis
      Foundation.....................................................    58
        Prepared statement...........................................    60
        Answers to submitted questions...............................   137
    Richard F. Pops, Chairman and CEO, Alkermes......................    68
        Prepared statement...........................................    70
    J. Leonard Lichtenfeld, M.D., Deputy Chief Medical Officer,
      American Cancer Society........................................    77
        Prepared statement...........................................    79
    Marshall Summar, M.D., Director, Scientific Advisory Committee,
      National Organization for Rare Disorders.......................    85
        Prepared statement...........................................    88

                               Submitted Material

    Statement of the National Health Council, submitted by Mr. Pitts.   114

           21ST CENTURY CURES: INCORPORATING THE PATIENT PERSPECTIVE

                                  ----------

                             FRIDAY, JULY 11, 2014

                      House of Representatives,
                                Subcommittee on Health,
                              Committee on Energy and Commerce,
                                                        Washington, DC.
        The subcommittee met, pursuant to call, at 9:00 a.m., in
    room 2322, Rayburn House Office Building, Hon. Joseph R. Pitts
    (chairman of the subcommittee) presiding.
        Present: Representatives Pitts, Burgess, Shimkus, Murphy,
    Blackburn, Gingrey, Lance, Cassidy, Guthrie, Griffith,
    Bilirakis, Ellmers, Upton (ex officio), Pallone, Engel, Capps,
    Schakowsky, Green, Barrow, Castor, Sarbanes, and Waxman (ex
    officio).
        Also present: Representative DeGette.
        Staff Present: Clay Alspach, Chief Counsel, Health; Gary
    Andres, Staff Director; Mike Bloomquist, General Counsel; Sean
    Bonyun, Communications Director; Leighton Brown, Press
    Assistant; Paul Edattel, Professional Staff Member, Health;
    Brad Grantz, Policy Coordinator, O&I; Sydne Harwick,
    Legislative Clerk; Robert Horne, Professional Staff Member,
    Health; Carly McWilliams, Professional Staff Member, Health;
    Macey Sevcik, Press Assistant; Heidi Stirrup, Health Policy
    Coordinator; John Stone, Counsel, Health; Jean Woodrow,
    Director, Information Technology; Ziky Ababiya, Minority Staff
    Assistant; Eric Flamm, Minority FDA Detailee; Karen Lightfoot,
    Minority Communications Director and Senior Policy Advisor; and
    Rachel Sher, Minority Senior Counsel.

    OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
             CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA

        Mr. Pitts. The subcommittee will come to order. We are
    going to have early votes, so we are going to have to start. We
    understand the minority members are on their way.
        The chair will recognize himself for an opening statement.
    Today's hearing provides us with an opportunity to examine
    perhaps one of the most important aspects of the 21st Century
    Cures Initiative. What does medical innovation or faster cures
    mean for patients? Keeping our work centered on the patient and
    understanding the patient perspective will bring much needed
    focus on results for patients who may lack adequate treatment
    options. Remember, there are only effective treatments for 500
    of the 7,000 known diseases impacting patients today.
        While FDA has developed an enhanced structured approach to
    benefit risk assessment in regulatory decisionmaking for human
    drug device and biologic products, the committee recognizes the
    value of considering patients in decisionmaking about therapy
    development and access. Assessment of a drug or device's
    benefits and risk includes an analysis of the severity of the
    condition treated and the current treatment options available,
    and getting the patient's unique perspective should be a part
    of that assessment.
        One of our witnesses today, Pat Furlong of the Parent
    Project Muscular Dystrophy, PPMD--and I must say Pat is
    accompanied by Mary Bono Mack, a distinguished former member of
    this committee. Welcome, Mary. And Pat will explain how this
    organization was founded to create opportunities for families
    waiting for therapies to stop Duchenne muscular dystrophy from
    claiming young lives. To quote Pat Furlong, ``Patient-focused
    drug development acknowledges the need to gather input from
    patients and their caregivers to create a more complete
    assessment of the benefit-risk equation, encouraging
    predictability, and increased flexibility within the review
    process. The clock is ticking for patients who need and deserve
    access to promising therapies.''
        I would like to applaud her tireless work drafting guidance
    PPMD recently released that actually quantifies patient
    priorities and preferences. This guidance will serve the
    Duchenne community and every other patient community because it
    provides a path for other patient groups to follow. This was an
    enormous undertaking, and I am confident it will make a
    substantial contribution to the entire medical community.
        I would like to welcome our witnesses today and look
    forward to learning more about the assessment of benefits and
    risks central to medical product development, regulations, and
    healthcare decisionmaking and the tradeoffs between desired
    benefits and tolerable risk. Thank you.
        Any member on the majority side seeking recognition?

        [The prepared statement of Mr. Pitts follows:]

                   Prepared statement of Hon. Joseph R. Pitts

        The Subcommittee will come to order.
        The Chair will recognize himself for an opening statement.
        Today's hearing provides us with an opportunity to examine
    perhaps one of the most important aspects of the 21st Century
    Cures Initiative: what does medical innovation or faster cures
    mean for patients. Keeping our work centered on the patient and
    understanding the patient perspective will bring much needed
    focus on results for patients who may lack adequate treatment
    options. Remember, there are only effective treatments for 500
    of the 7,000 known diseases impacting patients today.
        While FDA has developed an enhanced structured approach to
    benefit-risk assessment in regulatory decision-making for human
    drug, device and biologic products, the Committee recognizes
    the value of considering patients in decision-making about
    therapy development and access. Assessment of a drug or
    device's benefits and risks includes an analysis of the
    severity of the condition treated and the current treatment
    options available and getting the patient's unique perspective
    should be a part of that assessment.
        One of our witnesses today, Pat Furlong of Parent Project
    Muscular Dystrophy--PPMD--will explain how this organization
    was founded to create opportunities for families waiting for
    therapies to stop Duchene muscular dystrophy from claiming
    young lives. To quote Pat Furlong, ``Patient focused drug
    development acknowledges the need to gather input from patients
    and their caregivers to create a more complete assessment of
    the benefit-risk equation, encouraging predictability and
    increased flexibility within the review process. The clock is
    ticking for patients who need and deserve access to promising
    therapies.'' I would like to applaud her tireless work drafting
    guidance PPMD recently released that actually quantifies
    patient priorities and preferences. This guidance will serve
    the Duchene community and every other patient community because
    it provides a path for other patient groups to follow. This was
    an enormous undertaking, and I am confident it will make a
    substantial contribution to the entire medical community.
        I want to welcome our witnesses today and look forward to
    learning more about the assessment of benefits and risks
    central to medical product development, regulations, and
    healthcare decision-making, and the tradeoffs between desired
    benefits and tolerable risks.
        Thank you, and I yield the remainder of my time to --------
    ------------------------------------.

        Mr. Pitts. The chair recognizes the vice chairman, Dr.
    Burgess for the remainder of time.
        Mr. Burgess. And thank you, Mr. Chairman.
        And Dr. Woodcock, thank you for joining us again. It is
    always good to see you, always good to have you as a witness.
    You always provide valuable testimony. And our second panel
    representatives. I also want to acknowledge just as the
    chairman did, many of the patient organizations that you
    represent have worked well with our office and myself over the
    last several years.
        Mr. Chairman, the laudable goals of the 21st Century Cures
    Initiative, and they are indeed laudable, but we got to
    remember, at the end of the day, it is all about patients.
    Doctors want to heal. We want to cure. That is why we entered
    the profession. No doctor ever wants to tell a patient there is
    nothing more we can do. The good news is that the golden age of
    medicine is really right around the corner. The doctors of
    tomorrow will have tools at their disposal unlike any before in
    human history. The ability of tomorrow's doctor to alleviate
    human suffering is going to be unparalleled and unmatched in
    history. Yet every day that goes by where these tools are not
    realized is a day that patients and their families have to
    struggle through the pain and suffering of their condition.
        Every day counts for these Americans and for their
    families. For those who struggle with rare diseases, their
    struggle is only compounded by the lack of biomedical research.
    For those patients, it is difficult to see over the horizon. We
    have much work to do on this committee, and we have done a lot
    in the past. We particularly celebrate the 2-year anniversary
    of the Food and Drug Reauthorization Act that was just a few
    days ago. That was a good template. It was a good method for
    moving forward, and I appreciate that the Cures initiative is
    following that template, but there is no doubt that we can do
    much more.
        I welcome the testimony of our witnesses, and I will yield
    back my time.
        Mr. Pitts. The chair thanks the gentleman.
        And I now recognize the ranking member of the full
    committee, Mr. Waxman, 5 minutes for opening statement.

    OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN
                 CONGRESS FROM THE STATE OF CALIFORNIA

        Mr. Waxman. Thank you very much, Mr. Chairman.
        This hearing is a fitting followup to Wednesday's hearing
    on clinical trials. After all, it is patients who live with the
    diseases and conditions for which treatments are being sought,
    and this hearing, which is called ``21st Century Cures:
    Incorporating the Patient Perspective,'' illustrates that we
    should take every opportunity to understand their experience.
        Congress has a long history of listening to concerns of
    patients. That is what I did in 1983 when I wrote the Orphan
    Drug Act. That law came up when I heard from a constituent,
    Adam Seligman, who had a rare disease called Tourette's
    Syndrome. Adam was forced to take a drug that he could only get
    from Canada because, at that time, there were no effective
    treatments available in the United States. When his drugs were
    ceased at the border, his mother made a desperate call to my
    office begging me to do something.
        I set out to figure out why there were no drugs in the U.S.
    for Adam's condition. We discovered that Adam was not alone.
    There are 134 drugs for rare diseases but only 10 had come to
    market solely as a result of industry. We knew we had a problem
    on our hands, and we set out to solve it.
        The Orphan Drug Act has been a resounding success. Today,
    there are over 400 drugs for rare diseases, and I want to
    welcome the National Organization for Rare Disorders here today
    and look forward to their testimony.
        I am telling this story about the Orphan Drug Act not only
    as an example of how Congress has listened to the concerns of
    patients and acted on them, I tell it because it is an example
    of appropriate use of legislation. In the case of rare diseases
    in the early 1980s, there was very clear evidence of a market
    failure in need of congressional action.
        In the context of the 21st Century Cures Initiative, we
    need to assure that both FDA and the drug and device companies
    are listening to the concerns of the patients. FDA has a long
    history of engaging with patients, both in the context of
    advisory committees and in its review of drugs and devices. In
    the 2012 FDA Safety and Innovation Act, Congress pushed FDA to
    do even more to hear patients' concerns, and I look forward to
    hearing more from FDA today.
        From what I can tell, the agency has taken that mandate
    seriously and is engaged extensively with the patient
    community. We should ask today whether FDA has adequate
    resources to continue to do this work.
        As I mentioned on Wednesday when we had our last hearing,
    when it comes to legislating in complicated scientific areas,
    like the conduct of clinical trials, we need to proceed with
    great caution. For example, one issue in the area of clinical
    trials that is likely to come up today is how to incorporate
    so-called patient reported outcomes. As I understand it, this
    is an area that is multifaceted and scientifically complex.
    Congress should ensure that FDA has the flexibility and
    authority to make use of these outcomes but not dictate how and
    when that occurs.
        I hope FDA will tell us about how it is applying other
    novel approaches to clinical trials in their regulation of
    drugs and devices. I would also like to know whether the agency
    believes it has the authorities necessary to adopt new
    approaches and whether other new statutory powers are
    necessary.
        Mr. Chairman, thank you for holding this hearing. I look
    forward to the witnesses' testimony. I must say in advance that
    there is another subcommittee scheduled at the very same time
    as this one, so I will try to be back and forth to participate
    in both of them.
        Thank you, and yield back my time.
        Mr. Pitts. The chair thanks the gentleman.
        I now recognize the chairman of the full committee, Mr.
    Upton, 5 minutes for opening statement.
        Mr. Upton. I yield back my time. I will just submit my
    statement in order to----

        [The prepared statement of Mr. Upton follows:]

                     Prepared statement of Hon. Fred Upton

        The entire purpose of our 21st Century Cures initiative is
    to accelerate the discovery, development, and delivery of safe
    and effective treatments to America's patients. We are here
    today to better understand how we can incorporate the most
    important perspective--that of patients and their families--
    into the conversation.
        Patients should and need to play a key part of this process
    if we are to be successful. As one of our witnesses, Dr. Beall
    has noted, ``Congress should work to ensure patients have a
    seat at the table, because no one understands a disease better
    than the people who suffer and fight every day.''
        I would like to issue a special welcome to Pat Furlong who
    has continued to fight after losing her two boys, Christopher
    and Patrick, to Duchene. We are very humbled that you are here
    to help with the cures initiative. I'd also like to welcome to
    Dr. Marshall Summer--a parent of a child with Down's Syndrome.
    Parents are tireless advocates of their children and we are
    pleased that you are here today. Thank you and all of our
    witnesses for being here today.
        I also would like to thank Dr. Woodcock for testifying
    today. Unfortunately, prior obligations prevented her from
    coming to Wednesday's hearing so today she will provide her
    expertise on both modernizing clinical trials and incorporating
    the perspective of patients.
        As I'm sure Dr. Woodcock will explain, FDA has taken steps
    to incorporate the perspective of patients in the drug
    development process. FDA's work with Parents Project Muscular
    Dystrophy is a good example of collaboration, and we look
    forward to hearing about next steps on the guidance they put
    together.
        However, much work remains. We would like to learn how we
    can leverage the successful examples of agency-patient
    collaboration and what other steps we can take to ensure the
    patient's perspective on the benefit-risk framework is
    thoroughly considered and incorporated throughout the cycle of
    the drug review process.
        At our first 21st Century Cures roundtable, we learned that
    there are treatments for only 500 of the more than 7,000 known
    diseases affecting our nation's patients. Our work will not be
    done until we can close this gap in cures. I look forward to
    hearing how we can incorporate the voice of patients in this
    process.
        I yield the balance of my time to ------------------------
    --------.

        Mr. Pitts. The chair thanks the gentleman.
        We have two panels today.
        On our first panel, we have Dr. Janet Woodcock, director,
    Center for Drug Evaluation and Research, U.S. Food and Drug
    Administration.
        Thank you for coming again today. And you will have 5
    minutes to summarize your testimony. Written testimony will be
    placed in the record.
        So, at this time, the chair recognizes Dr. Woodcock 5
    minutes for opening statement.

     STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
       EVALUATION AND RESEARCH, U.S. FOOD AND DRUG ADMINISTRATION

        Dr. Woodcock. Thank you. We are here to discuss how drug
    development better meets the needs of patients. Decades ago,
    healthcare was very physician-centric and actually very
    paternalistic. We all recognize that today. It was kind of
    ``The doctor knows best; don't ask any questions.''
        Today, the model is collaboration between the patient and
    the healthcare team. These changes, though, have evolved slowly
    in our society, and the thinking and drug development has
    slowly changed in parallel.
        The FDA Safety and Innovation Act of 2 years ago took
    significant steps in this direction of patient-centric
    development. It contained agreements under PDUFA that FDA would
    sponsor at least 20 patient-focused disease-focused meetings
    over 5 years. Eight of these meetings have been held to date,
    and they have been very impactful. The first one we held on
    chronic fatigue syndrome, we have issued a draft guidance on
    drug development in this area of very serious unmet medical
    need. Also, under PDUFA, were agreements to advance the
    development and use of patient-reported outcome measures. These
    are measures that the patient can fill out to say from their
    point of view how well they are feeling, how well the treatment
    is working, what adverse events they are experiencing.
        We are having an expert meeting next week and will continue
    to work in collaboration consortiums to try and advance the
    science of patient reported outcomes. This is very important to
    really scientifically incorporate the patient's perspective
    into clinical trials.
        Additionally, under FDASIA, FDA was to advance the
    development and use of a structured benefit risk framework in
    drug approval decision, and this work is under way, and it
    really explicitly provides for considering the burden of
    disease, the impact of current therapies, both for good and for
    ill, and the tolerance of risk from the patient's point of
    view, and this is an extremely important set of factors that
    need to go into the benefit-risk decision, but we need to do
    this in a scientific manner and a structured manner and we are
    rolling out the structured benefit risk framework.
        Now, we know that for people with very serious diseases who
    may lack good therapy or actually lack any therapy, access to
    new treatments is their number one priority, and that is why
    expediting drug development programs in these areas is so
    important. If you look at the diagram that we have here that
    was provided, these data and the diagram were actually
    developed by the Pharma organization, talks about, shows the
    drug development process, and it is starting on the left, it
    shows you start with many thousands of compounds, up to 10,000
    compounds at one end, the beginning, and after 9 to 13 years,
    you may end up with one safe and effective drug on the market.
        The clinical development phase, which is the gray phase,
    the middle phase on this diagram, is the longest and by far the
    most expensive phase.
        In contrast, the FDA review phase, of which much attention
    has been paid to, is actually the very small slice there, the
    white slice toward the end of the process, right before the
    drug gets on the market and is typically at this time less than
    a year in duration.
        So FDA has made strenuous efforts, really, to help reform
    and modernize the clinical development phase of drug
    development because that is the major bottleneck. Not only is
    it expensive and long, many products fail in this phase, and
    there is a tremendous opportunity cost there where other
    treatments could have been developed.
        Now, the FDASIA included several innovations to this
    process and the most striking being the breakthrough therapy
    designation program, so if we could have the next diagram.
    Thank you. This was mandated by Congress and was specifically
    directed at that clinical development phase, so that we could
    help when therapies were particularly promising and were
    designated, we could help move them through that phase more
    quickly. The BT designation has been enthusiastically
    subscribed. We have had over 160 requests in the 2 years since
    the legislation was passed. We have actually--and this is the
    really surprising part, we have granted 52 designations. So
    what Dr. Burgess said about we are on the verge of a new era in
    therapeutics, I think, is reflected by this. We would not have
    seen this a decade ago, and we have approved six products: four
    new products and two new indications.
        Now, it is too early to judge really the impact of the
    breakthrough designation program; is it really going to be able
    to speed up drug development? However, I will say the four
    products we approved, their clinical development time was 4.5
    years, so much shorter than what I showed in the earlier
    diagram.
        Also, in FDASIA were clarifications of the application
    accelerated approval, and we issued a final expedited draft
    guidance in May that includes, in response to stakeholders'
    requests, examples of rare diseases and includes more
    information on the use in rare disease. However, it is clear
    much more needs to be done to modernize the clinical trial
    process. That is the big bottleneck now in getting discoveries
    to patients. This can't be done, though, by FDA alone. We don't
    execute this process. All the stakeholders need to participate,
    and I think the series of hearings that have been held and the
    21st Century Initiative can help provide the framework for
    significant reform in this process.
        Mr. Pitts. The chair thanks the gentlelady.

        [The prepared statement of Dr. Woodcock follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. I will begin the questioning, recognize myself 5
    minutes for that purpose.
        Dr. Woodcock, what is FDA's plan to advance biomarkers and
    the use of patient reported outcomes data during the drug
    development process and post-market setting?
        Dr. Woodcock. Many years ago, a decade ago, we recognized
    that there was no structured scientific process to provide the
    evidentiary basis for use of a biomarker in decisionmaking, and
    so doctors and biomedical researchers would float new
    biomarkers, but there was no rigorous process by which they
    could be evaluated to see if they were really useful. So we
    actually established a process for this. It is not really in
    our mission, but we established it, and it is called the
    Biomarker Qualification Process. And we also work with the
    European medicine agencies and the Japanese regulators so that
    this would be a worldwide activity. And consortia can come into
    the FDA and propose a biomarker, a new biomarker, and we give
    them advice on what needs to be done, and then--and also for
    patient-reported outcomes. And if, in fact, that evidence is
    developed, then we will publish a letter that is public, and so
    will the EMA if they accept it and so forth, and then any
    developer can use that biomarker or measure in a development
    program and will rely on it for the context of use.
        We have 79 projects by different consortia in different
    phases of this process right now.
        Mr. Pitts. Good. Describe your plans for implementation of
    the structured benefit-risk framework you mentioned that--
    transparent to the public and the sponsor so that the
    assessment of data from clinicals trials and other studies by
    FDA reviewers can be better understood and acted upon.
        Dr. Woodcock. Yes. Well, this is an iterative process. We
    have had public meetings. Then we went back, and we are
    piloting this in the different drug review divisions and having
    the medical officers work through this framework that we have
    developed and see what the results are. Then when we have those
    results, we will go back through a public discussion and get
    input on how this can be improved, so this is not something
    that can happen overnight.
        It is a scientific process, and actually, we feel that we
    don't have the tools right now. They exist out in society in
    science, but we haven't applied them, these rigorous analytical
    tools to the benefit-risk decision, and so we have had
    workshops on this, various scientists come in and advise us, so
    we will have a public process once we have gathered more
    experience.
        Mr. Pitts. I have been hearing a lot about FDA's efforts to
    improve the quality of pharmaceutical manufacturing. Where do
    U.S. drug manufacturers currently stand when it comes to
    producing quality medicines? Can you tell me a little bit about
    your plans in this area?
        Dr. Woodcock. Well, I think the major problem here is that
    many of our essential drugs are not made in the United States,
    and they are made all around the world, and sometimes they may
    only come from a single source, and this is, I think, a real
    vulnerability to medicine. And in addition, we used to be a
    manufacturing powerhouse in drug manufacturing, but those jobs
    have moved offshore. And I think now we have an opportunity,
    with new modern manufacturing methods, such as continuous
    manufacturing, to actually build a high-tech industry in the
    United States that actually will make the drugs we need here in
    this country. And FDA has been collaborating with this
    manufacturing community to help bring this about, and we are
    very interested in seeing this happen.
        Mr. Pitts. Now, we have recently heard a lot about Lung-
    MAP, the Lung Cancer Master Protocol trial. There are other
    examples of similar innovative trial designs, like I-SPY for
    breast cancer. What else needs to happen before these types of
    trials are no longer front-page stories?
        Dr. Woodcock. That is a good question. We also have been
    advocating for this for many years, and it is wonderful to see
    it start to become a reality. The concept, I think, in drug
    development needs to be turned on its head in clinical drug
    development, and instead of, for each investigational drug,
    there is a whole clinical trial program developed with
    different clinical trials that take a very long time, as you
    heard on Wednesday, to get started and so forth, that there are
    networks that are available that investigational drugs can be
    plugged into. This will provide independence of an assessment
    but also really decrease the time and expense of assessing
    whether these drugs are safe and effective.
        But what needs to happen, I think, is we need to expand
    this to more diseases. The NIH is very interested in
    antimicrobials in setting up a network, and other groups are
    looking into this, and I think you may hear today from some
    patient groups say Cystic Fibrosis has really successfully set
    up the infrastructure to have cystic fibrosis drugs rapidly
    evaluated once they reach the clinic.
        Mr. Pitts. The chair thanks the gentlelady.
        Now recognizes the ranking member of the subcommittee, Mr.
    Pallone, 5 minutes for questions.
        Mr. Pallone. I am going to have to--since I just got here.
        Mr. Pitts. OK. You want to yield to Green?
        Mr. Pallone. Yes.
        Mr. Pitts. All right. Mr. Green.
        Mr. Green. Thank you, Mr. Chairman.
        Dr. Woodcock, welcome back. I want to thank our chairman,
    ranking member, and Dr. Woodcock for testifying. In a time
    where revolutionary science and technological development, we
    have an opportunity to target specific patient populations,
    advance personalized medicine, and transform how we approach
    the prevention and treatment of disease, one of the goals I
    think is particularly worthy of exploration is the idea of
    personalized medicine, in which a patient may be able to
    receive more tailored drugs and treatment suited to his or her
    specific condition.
        Our understanding of the human genome is the key to that
    goal. Academics and researchers tell me, another piece is the
    potential for researchers and developers to discuss these drug
    and device innovations with patients during the development
    phase.
        Dr. Woodcock, can you give us your views on the upsides and
    downsides of any increasing permissibility of communication
    between patients and developers during the clinical trial phase
    of development?
        Dr. Woodcock. It is a very interesting question. We have
    seen from the 1990s, where only 5 percent of drugs were
    targeted; in 2013, 45 percent of the drugs we approved were
    targeted in some way. There are barriers to locating patients
    and joining up patients who have specific conditions, subsets
    with appropriate investigational therapy, and these diseases
    are fragmented into smaller and smaller subsets. It is harder
    and harder to find these people who might be eligible for a
    given therapy.
        The Lung-MAP trial is one way of doing that where it has
    multiple investigational arms in one trial, so people can come
    in, and they can be spread out. But there is great interest, of
    course, with more patient activism in using social media and
    other ways to actually match up the right patients with the
    right investigational drugs, and I think this is one of the
    challenges right now of the clinical trial enterprise.
        Mr. Green. Well, increasing patient involvement in FDA's
    decisionmaking surrounding drugs, devices is a significant yet
    challenging endeavor. Can you provide your suggestions on how
    mechanisms need to be developed to accurately measure what
    meaningful outcomes for patients are, both in the clinical
    outcomes and the quality of life? Can we do that?
        Dr. Woodcock. Yes. That is what I was referring to with
    Chairman Pitts is that there is a science of measurement, and
    patient-reported outcomes is one science. How do you measure
    how a patient feels from their point of view? And there are
    ways to do this, but these measurements have to be developed.
    We approved many drugs based on their impact on quality of
    life, so that is completely possible, but what needs to be done
    is this science needs to be developed, and we are participating
    in that. As I said, we have an expert meeting next week on
    patient-reported outcomes.
        Mr. Green. Well, and the patient involvement process has to
    be data driven and improve the overall efficiency of drug
    development and maintain FDA standards of safety and
    effectiveness. How can Congress support the FDA in
    incorporating patient perspectives in regulatory decisionmaking
    in a way that helps deliver that innovative, safe, and
    effective medicines to the patients sooner?
        Dr. Woodcock. Well----
        Mr. Green. Do you need statutory authority, or do you think
    you already have it?
        Dr. Woodcock. To my knowledge, we have the authority to do
    this, and I think you will hear from the next panel, for
    example, how patient groups can develop draft guidance, submit
    it to the FDA. They can run processes that actually incorporate
    all their points of view and those of the expert scientists, so
    more of that needs to be done, but I don't know that it needs
    more statutory authority.
        Mr. Green. Can you do it within current resources, because
    again, you are specializing, instead of a broad brush--and I
    assume it costs more when you do an individual?
        Dr. Woodcock. Yes. Well, when you have 7,000 diseases that
    need good treatments and most of them don't have them, it would
    be very difficult for FDA alone to develop the standards for
    patient reported outcomes in each one of those diseases, much
    less the clinical outcomes. So much more participation of the
    medical and patient community is needed in drug development,
    and we need to find better ways to do that, but I am not sure
    that is through legislation.
        Mr. Green. OK. And without a doubt, our greater resources,
    but again, our committee has worked over the years to try and
    provide those resources----
        Dr. Woodcock. Yes.
        Mr. Green [continuing]. To the FDA and look forward to
    working with you.
        Thank you, Mr. Chairman. I yield back.
        Mr. Burgess [presiding]. The gentleman yields back.
        I recognize myself for 5 minutes for the purposes of
    question.
        Dr. Woodcock, again, good to see you, good to have you back
    in the committee. So you have talked about how the FDA
    routinely works with sponsors to apply flexibility, including
    the use of biomarkers, surrogate endpoints, and nontraditional
    trial designs, and other available tools to expedite the
    development of products to treat both common and rare diseases.
        With respect to the common diseases, how is the FDA working
    with sponsors to apply these innovative development and review
    methods?
        Dr. Woodcock. Well, for example, hypertension is a common
    disease. We approve drugs for hypertension based on a surrogate
    measure, blood pressure, that is very well accepted, and for a
    number of years ago, we looked at automated blood pressure
    monitoring, and we decided it was unbiased, and so we decided
    that you really didn't need a control group in the same way
    that you would for most other diseases because you have an
    unbiased measure, and so we issued new approaches to studying
    hypertensive medicines. So that is an example.
        Mr. Burgess. What could happen so that the FDA could use
    this more frequently?
        Dr. Woodcock. Well, 45 percent of the drugs that we
    approved over the last several years used a surrogate endpoint.
    So we do use that when it is appropriate and it is available.
    For many diseases, we don't know what the right surrogate is,
    and that is why many of the accelerated approvals have been
    confined say to cancer and HIV is because the science, a great
    deal of science has been driven in those conditions, and we
    understand the biomarkers. But for other diseases, there needs
    to be more scientific development, and that is why we are using
    this, for example, biomarker qualification process to try and
    get more biomarkers developed that we can use, but we can't
    just dream them up and use them.
        Mr. Burgess. I thought that was your job. Well, let me ask
    you this. Are there situations where a majority of the
    scientific or research community believes that a certain
    biomarker sufficiently predicts the clinical outcome, but the
    FDA has yet to accept that?
        Dr. Woodcock. There may be. I think there is a lot of
    controversy around use of these. You heard some of that on
    Wednesday. There are two sides to this. If you rely upon a
    surrogate, often, especially when it isn't well validated,
    there is more uncertainty about whether or not the drug is
    actually going to work or not, and so there are different
    points of view. And as we have all been saying, the community,
    the patient community really ought to have--and treating
    community ought to have--a lot of input into how much
    uncertainty should be tolerated, given the circumstances of
    that disease.
        So there are situations where there is disagreement amongst
    various parties, external and internal, about the use of a
    surrogate.
        Mr. Burgess. Are you able to give us any examples of that,
    of a surrogate that the FDA may not right now be willing to
    accept?
        Dr. Woodcock. Well, for example, raising good cholesterol,
    all right. We had a series of trials on that. Everybody thought
    raising good cholesterol would be really good, and in fact, it
    turned out to be either neutral, or in one case, it actually
    increased mortality, so we no longer accept that surrogate.
    That is the kind of example where--and there are many others
    like that.
        In bone density, for osteoporosis, estrogens do a very good
    job and they decrease fractures. Although they have other
    liabilities. But some other agents were tried, and actually,
    they increased bone density, but they also increased fractures,
    and so we have to be careful when we use these surrogates to
    make sure that we are getting the intended results, clinical
    results.
        Mr. Burgess. Thank you for that.
        Let me ask you a question that is a follow-up from when we
    visited in April.
        Do you have an update on the status of the FDA's guidance
    on biosimilars naming and when that guidance will become final?
        Dr. Woodcock. Well, I certainly would like to get that
    guidance out as soon as possible. We are working diligently on
    that, and I don't have any further update.
        Mr. Burgess. But that was submitted as a question in April,
    and we are awaiting an answer.
        Now, also, along with that, I asked if anyone in the
    administration, outside of the FDA, had provided the agency
    with suggestions or recommendations with respect to this
    guidance.
        Can you, if the answer to that is yes, can you provide us
    with the name or names of those individuals?
        Dr. Woodcock. We would have to get back to you on that.
        Mr. Burgess. And again, we anxiously await your answer.
        My time is expired.
        I will recognize the gentleman from New Jersey, the ranking
    member, 5 minutes for questions.
        Mr. Pallone. Thank you.
        Mr. Chairman, you asked a lot of my questions, so I am
    going to have to move on to other things.
        But Dr. Woodcock, we heard a lot at Wednesday's hearing
    about the accelerated approval program at FDA, and as you know,
    the program allows for earlier approval of drugs that treat
    serious conditions and fill an unmet medical need, and the
    drugs are approved on the basis of surrogate endpoints which we
    also learned about on Wednesday, and of course, a critical
    requirement of the system is that companies conduct studies to
    confirm the clinical benefits suggested by the surrogate
    endpoint, and these studies are called phase 4 confirmatory
    trials. So a critical part--I want to ask about the phase 4
    trials. What challenges has FDA faced with respect to phase 4
    trials? Do sponsors complete in a timely manner?
        Dr. Woodcock. Well, it is sometimes difficult to complete
    these trials, and the reason is that if you had a serious and
    life-threatening disease and we approved a treatment for it,
    you probably would be somewhat reluctant to enter a trial where
    you had a maybe 50 percent chance of not getting the treatment.
    So what we often do is ask that trials be conducted in a
    different stage of disease or something where it actually
    hasn't been studied yet, so then we can get the results since
    that might take time.
        So I think in the early years of the program, we didn't
    track this as well as we should, and we did have a lot of
    trouble getting these trials completed. But in the current era,
    we are on top of this, and generally speaking, the sponsors are
    diligent in trying to get them completed, generally, but they
    have difficulty sometimes enrolling patients in these trials.
        Mr. Pallone. Another important component of the program is
    that when the surrogate endpoints do not ultimately show the
    anticipated clinical benefit, FDA could be faced with needing
    to remove the indication or take the drug off the market, and I
    imagine that is also no easy task.
        Can you describe what is involved with removing the
    indication or taking a drug off the market and what challenges
    does the FDA face there?
        Dr. Woodcock. Yes. Generally, if the confirmatory trial
    failed to show benefit, the first thing we ask is the sponsor
    to voluntarily withdraw the drug or the indication from the
    market. It is only if the sponsor does not agree to do that,
    then we go into a long administrative process, which includes
    hearings and formal findings and so forth, and this can take a
    long time if the sponsor can test our finding that the drug
    isn't effective.
        Mr. Pallone. Now, just a couple of years ago, we included
    some provisions to improve upon the accelerated approval
    program, and the FDA Safety Innovation Act of 2012. For
    example, the law made it clear that FDA could rely upon
    evidence developed using biomarkers or other scientific methods
    or tools when assessing surrogate endpoints. Can you describe
    what impact those legislative changes had on the program, and
    are there any other changes that you feel are necessary to
    allow you to make full use of the most recent scientific
    developments with respect to surrogate endpoints?
        Dr. Woodcock. I think the legislation was very helpful. We
    have taken it quite seriously. We have issued guidance, final
    guidance on expedited programs, and probably the biggest change
    that the legislation brought about was its focus on
    intermediate clinical end points, and we had to have quite an
    internal discussion about what that means, and I think you will
    see us approving more products under accelerated approval based
    on these intermediate clinical endpoints.
        Mr. Pallone. All right. Well, thanks.
        Again, it is clear to me that this is an extremely
    complicated area and one that is not necessarily conducive to
    further legislation, but I wanted to ask last about the master
    protocol.
        At the hearing on Wednesday, some panelists described some
    of the inefficiencies that exist in the way that clinical
    trials are currently conducted, and one of the suggestions for
    addressing those inefficiencies is to create a master protocol.
    So I just wanted to ask, first, can you tell us more about
    this, what is a master protocol? How would it help to improve
    the way we conduct clinical trials? Has FDA been involved in
    the development of a master protocol, and are there particular
    diseases that the master protocol is more appropriate for than
    others, and if so, which ones, and are there other areas where
    it might be expanded?
        Dr. Woodcock. Well, master protocol is one version of using
    clinical trial networks or standing clinical trials to evaluate
    investigational therapies where the drug development program
    isn't just for one therapy. It is for any therapy for that
    disease. So master protocol, though, has to be somewhat disease
    specific. You can't just have a general overall master
    protocol, right. It has to be focused on one disease.
        For example, the Lung-MAP trial is on squamous cell cancer
    of the lung that is advanced but five different agents right
    now are being studied all at once within that protocol, and
    that is a huge efficiency. But there are other versions of
    standing trials or trial networks that also could be used in
    other diseases. And as I said, the Cystic Fibrosis Foundation
    has a kind of network of clinical excellence where they
    actually sequenced the genome of all their patients, and so
    they are ready when a targeted therapy comes along. They are
    ready. They can put those patients into the protocol, and that
    tremendously improves the efficiency.
        So it is a long conversation that probably can't be had in
    5 minutes, but I have long advanced this concept and tried to
    push this concept because the current clinical trial paradigm
    is not sustainable.
        Mr. Pallone. All right. Thank you very much.
        Thank you.
        Mr. Burgess. The gentleman's time is expired.
        The chair recognizes the gentleman from Pennsylvania, Dr.
    Murphy, 5 minutes for questions, please.
        Mr. Murphy. Thank you.
        And good morning, Doctor. It is always good to have you
    here.
        Let me start out by asking about it is important for the
    medications and research to advance those but also for those
    that are already approved, and so let me ask you, we had passed
    the PDUFA laws a while ago, certainly that was supposed to help
    us get more generic drugs in the queue, but what has happened
    is we got 1.5 billion authorized over 5 years, what has
    happened is approval times have gone up, and there are fewer
    approvals, even though the law was supposed to reduce all
    those.
        Can you give me some indication of what is going on and
    what FDA is going to do about that?
        Dr. Woodcock. Certainly. We are well aware of these issues.
    In June, we received 625, I believe, generic drug applications,
    so the rate of submission is well above what was projected in
    the negotiations that we held.
        However, on October 1, the deadlines kick in for timelines
    for review of generic drugs, and we are fully prepared to meet
    those timelines as well as deal with this large backlog of
    pending.
        We had to hire a large number of people and totally revise
    our processes, reorganize the generic drug review offices and
    conduct many other changes, and that is what we have done over
    the past 2 years in preparation for the deadlines coming into
    effect on October 1.
        Mr. Murphy. Thank you. Another question here about some
    labeling issues. The abbreviated new drug application that
    would allow generic manufacturers--this is a proposal for FDA
    to change a label without FDA's prior approval but then come
    back later on, and the FDA itself has recognized, and say,
    quote, ``consistent labeling will assure physicians help
    professionals and consumers that a generic drug is as safe and
    effective as its brand name counterpart,'' unquote. But there
    is a concern out there that allowing these changes take place
    and then go backfill them later on can cause a lot of confusion
    in studies that have asked pharmacists and physicians this, so
    I am wondering where this issue stands in clarifying this.
        Dr. Woodcock. Well, we have received comments on the
    proposed rule. It was a proposed rule, and we received many
    comments. We are analyzing the comments, and subsequent to
    that, we will have to go forward with a rulemaking process.
        The proposed rule contemplated that we would actually have
    less disparities of labels in the marketplace on this because
    of this proposal because we would put up a Web site, and we
    would also require conformance of labels, which we cannot carry
    through right now, given the current systems.
        Mr. Murphy. A lot of us back in January asked to meet with
    Commissioner Hamburg and others about this, and I am not sure
    those things have taken place yet, so I hope this gets
    expedited and that these issues are addressed because I think
    it still leads to some confusion. So I am not clear yet in
    understanding even why this proposed rule was set up there to
    allow individuals to change the label and then come back later
    and ask permission.
        Dr. Woodcock. Well, currently, generic labels do not always
    match the innovator and they do not change their label in a
    timely manner, and so there will be labels out there for quite
    a bit of time, even with serious safety issues like new box
    warnings that don't conform to the innovator label, so we are
    trying to address this situation. And also, as generics are now
    85 percent of all drugs dispensed to consumers--that they
    should have the opportunity, since their drugs are the ones
    that people are being exposed to, to submit their findings of
    adverse events and suggest label changes, proposed label
    changes and actually execute them.
        Mr. Murphy. Well, I just hope that you will meet with the
    committee staff members and the companies to help clarify this
    because it still is not clear to me why this would be allowed,
    and I think it would end up confusing.
        I want to bring up one last thing just while you are here.
    I had sent a letter a few weeks ago to Dr. Hamburg. I am sure
    you didn't see this, but one of the things that is out there,
    too, is complications that are oftentimes reported in the media
    about caffeine, whether it is--and sometimes toxic levels
    people take.
        Dr. Woodcock. Yes.
        Mr. Murphy. Through over-the-counter things, pure caffeine
    or some of these supplements out there for athletes, et cetera,
    and yet it is also in everything from chocolate to coffee and
    other things we promote all the time, so I am hoping, at some
    point, FDA can also give some recommendations in terms of
    individual levels per drink, per dose, per day, per male,
    female, the genders, for weight, age, whatever that is.
        Dr. Woodcock. Yes.
        Mr. Murphy. Because it is still pretty confusing, whatever
    those products are that they can be beneficial, but I hope you
    will expedite that.
        Dr. Woodcock. Thank you.
        Mr. Murphy. Thank you.
        I yield back.
        Mr. Burgess. The gentleman's time is expired.
        The chair recognizes the gentlelady from California, Mrs.
    Capps for 5 minutes for questions, please.
        Mrs. Capps. Thank you for holding this hearing, to our
    chairman and ranking member.
        Thank you, Dr. Woodcock, for your testimony.
        This is an issue very dear to me, and as you know, I am
    incredibly concerned about our Nation's history of excluding
    minority groups, especially women, from all levels of medical
    research, from the lab rats to the most advanced clinical
    trials. And reports have shown that even when these groups are
    included in trials, there are often too few participants in the
    groups to analyze the effects on them or the analyses are
    simply not run or reported.
        I am sure you are familiar with the case of Ambien,
    commonly prescribed medication that recently had its label
    changed because it metabolizes differently in women than men,
    meaning that women had been receiving an inappropriately high
    does of this drug for over 20 years.
        In addition, in spring, a report entitled ``Sex-Specific
    Medical Research Why Women's Health Can't Wait'' was released,
    which provides evidence for the further inclusion of sex and
    gender in scientific research. And the FDA's own August 2013
    report, which was initiated by the inclusion of My Heart for
    Women Act in the FDASIA legislation, showed that there is still
    much work to be done to make sure that women are fully
    represented in clinical trials and that the safety and
    effectiveness of the information is readily available.
        I know the FDA is continuing to work on an action plan to
    address these disparities, so Dr. Woodcock, can you give us an
    update on where the agency is on this?
        Dr. Woodcock. Certainly. I would expect that that would be
    released, we would be timely in its release. I believe there
    was a statutory deadline or not, or there is some expectation,
    so we are working diligently on the action plan, yes.
        But I will say for drug development, which is what I am
    discussing here, that we did a study, for example, the class of
    2010, the product that we approved, we found that about 45
    percent of the participants were male, all right.
        And we found that almost all the submissions included the
    required gender analysis, which has been required for drugs for
    20 years, because I oversaw that when I first joined the Center
    for Drugs in 1994. So it is by regulation, so we do have these,
    but I think the transparency of the information is the problem,
    and we are working on that, and I really am committed to making
    that information more transparent so people understand what we
    know and what we don't know.
        Mrs. Capps. I think you put your finger on something, and I
    want to highlight a bipartisan letter I led, signed by the
    women of the House of Representatives, urging this agency to
    include clear and actionable strategies. And I think what you
    said about transparency and the reporting in the action plan is
    a way to address this issue once and for all.
        At Wednesday's hearing this week, I also asked the panel
    about the tools FDA is developing that could supplement our
    knowledge base, especially in the light of less robust clinical
    trial designs. The FDA Sentinel system, which I understand is
    making progress, if slowly, to conduct post-market passage
    surveillance of drugs and devices, could help spot issues like
    adverse drug interactions more quickly. I believe the Sentinel
    program holds great promise, and that is why I worked to get
    the Sentinel Assurance for Effective Devices Act included in
    FDASIA to continue progress on the program and ensure the
    design for both drugs and devices. Could you update us on the
    development of the Sentinel program, please, and what other
    resources or authorities do you need to get the system up and
    running to protect consumers more effectively and
    expeditiously.
        Dr. Woodcock. Well, I think use of electronic health data,
    which is rapidly becoming available, and the electronic health
    records and so forth, has tremendous promise for actually
    finding out what happens in the real world for medical
    products, both that are approved recently and those that have
    been on the market a long time, and that is what the Sentinel
    system is intended to do.
        We have run a mini-Sentinel network for 5 years, and that
    was between drugs and biologics. We paid for that out of our
    money that we have, and we are recompeting that to put up the
    Sentinel system, so that contract proposal is out on the
    street, and we hope to establish the real Sentinel system,
    which will be a large-scale system for surveillance.
        Now, as far as medical devices, we require a unique
    identifier or some kind of identifier in the medical record
    electronically so that we are able to capture that because the
    Sentinel system uses those electronic records to get the
    information, and I will repeat for everyone that it does not
    take any personnel information and move it to some central
    database. It strictly runs those analyses within the healthcare
    system and then the results only are combined.
        So that has tremendous promise. We feel very good about
    that. We actually are piloting running active surveillance on
    there, so when we approve a drug and we have a question about
    it, we can watch over time and see what actually happens. And
    as more and more people get on electronic health records, we
    can really have more insight in what is happening.
        So that is where we are with that, and it is resource
    limited. I have to pull resources from other activities to fund
    that, but I believe very strongly that this is the future.
        Mrs. Capps. Thank you. I appreciate that.
        Mr. Pitts [presiding]. The chair thanks the gentlelady.
        Now recognizes the gentleman from Georgia, Dr. Gingrey, 5
    minutes for questions.
        Mr. Gingrey. Mr. Chairman, thank you.
        Dr. Woodcock, thank you for appearing. It is always good to
    see you.
        I understand that a number of the challenges that have led
    to the duration and cost of conducting clinical trials in the
    U.S. to increase essentially are outside of FDA's purview. That
    being said, clinical trials are conducted to generate evidence
    used in the application for FDA approval, so my first question,
    how early do you typically communicate with these
    pharmaceutical companies, to discuss their trial design before
    the investigational new drug application is submitted?
        Dr. Woodcock. Well, we have agreements under PDUFA, that
    prescription drug user fee program, and for novel products or
    novel indications, say they are testing a disease that really
    doesn't have any treatment, companies can come in and have a
    pre-IND meeting. That meeting is before they start their
    clinical trials, their first in human studies, and we talk
    about that development program so they can start thinking about
    how that is going to be done.
        We do have information, it is preliminary, but looking at
    our information, it seems that companies that have more
    interactions with the FDA are able to get their products
    through more quickly, through the entire clinical trial process
    than companies that haven't had interaction with the FDA during
    the development process. But there are formal meetings that are
    held at different times under the user fee program, and those
    minutes are tracked, and we track the meetings and so forth, so
    there is quite a process for interaction during drug
    development.
        Mr. Gingrey. So you, as a manager, would be, maybe at that
    particular time, you make sure that your reviewers are not
    requesting overly burdensome data that really is not necessary
    so that the process can be speeded up?
        Dr. Woodcock. Well, there is always a push and pull.
    Scientists of all stripes always want more data, and that is
    scientists in the companies and scientists in the FDA, and so
    we have to walk that path between getting more data and
    actually the cost that is generated. And we have made a number
    of efforts under the CITI collaboration that we do with Duke
    University and many, many, many other partners to try and
    figure out how to streamline clinical trials as far as data
    collection, for example. But it is difficult.
        We have 1,600 meetings a year under the PDUFA, and when we
    meet with companies, the supervisors are there, the senior
    medical officials are also at these meetings.
        Mr. Gingrey. Well, that is the whole purpose of 21st
    Century Cures, of course, and as we get to the second panel and
    we hear about the associations and from the families, I am sure
    they are going to talk about how we can speed this process up.
        The last question. At our first 21st Century Cures hearing,
    we heard that only 19 drugs, outside of cancer and HIV space,
    have been approved by the accelerated approval pathway since
    1992, and I understand that you wrote a blog post after that
    hearing about how a number of drugs that were being considered
    under accelerated approval ultimately received traditional
    approval, so these statistics, according to your blog, were
    somewhat misleading. Can you provide some examples of when that
    occurred as well as the process involved?
        Dr. Woodcock. Certainly. Well, for certain rare diseases,
    we may decide, for example, that the surrogate is fine, OK, and
    it correlates with clinical benefit. Then the term
    ``accelerated approval'' is a little misleading. It sounds like
    it is faster than regular approval, but actually, if we give
    regular approval on a surrogate, it is just as fast as
    accelerated approval, but you don't have to do confirmatory
    studies afterward because we already believe the surrogate.
        So, for a lot of, say, rare deficiency diseases where there
    is something missing, you may be able to show that you
    actually, when you replace that protein in the body, you give
    the activity back to the person, right, and so you may not have
    to show clinical outcomes. It is still a surrogate, but we feel
    it is good enough because we understand the problem that
    something is missing, and you deliver an active drug to the
    site of action of where the problem is, and that would be
    enough.
        So, in many cases, we are able to do traditional approval
    with the surrogate; that means that the patients and the
    sponsor don't have to go through all these confirmatory trials.
    I described the difficulties of that when you have a serious
    disease; you have approved a drug; and then you ask people to
    be randomized after approval.
        Mr. Gingrey. Dr. Woodcock, thank you.
        And my time is expired. Mr. Chairman, thank you, and I
    yield back.
        Mr. Pitts. The chair thanks the gentleman.
        I recognize the gentlelady from Florida, Ms. Castor, 5
    minutes for questions.
        Ms. Castor. Well, thank you very much.
        Thank you, Dr. Woodcock, for everything you are doing to
    ensure safe and effective drugs are available for the American
    public and those with health challenges.
        This is a hearing about the patient involvement in FDA drug
    approvals, and I think we can agree, they deserve a seat at the
    table when companies are developing drugs and medical devices
    within the clinical trial process. I have long been a supporter
    of the Department of Defense's Congressionally Directed Medical
    Research Programs known as the CDMRP. CDMRP funds peer-reviewed
    research into breast cancer, autism, ovarian cancer, prostate
    cancer, and other diseases. And since 1993, the patients have
    been involved and have been a part of CDMRP, and they have a
    consumer reviewer as part of a peer-review panel to represent
    the stakeholder community, and it has been very successful in
    combining patient perspectives and needs with scientific
    research and bringing those perspectives together.
        Has FDA, as you begin to consider improving patient
    involvement, have you looked at CDMRP to see if there is
    anything you can borrow from that in the drug approval process?
        Dr. Woodcock. We have not, and that is a good suggestion,
    so we would be happy to do that.
        Ms. Castor. OK. You mentioned previously that the Patient-
    Focused Drug Development Initiative that was included in PDUFA
    was designed to allow FDA to hear from patients on how a
    disease impacts their life, and I understand you are scheduled
    to hold 20 public hearings. Share with us who FDA has met with
    so far. Have you started those hearings? If so, what have you
    learned already?
        Dr. Woodcock. Well, we have learned the devastating impact,
    I think, of the diseases, of these different diseases on
    people's lives it just incredible. We had one on chronic
    fatigue syndrome--that was our first one--HIV, lung cancer,
    narcolepsy, sickle-cell disease, fibromyalgia, pulmonary
    arterial hypertension, and inborn errors of metabolism, and we
    plan to have 16 of these meetings completed by the end of 2015,
    but we recognize this is just a drop in the bucket of what
    people suffer from.
        So what we are trying to do is really model how people can
    do this, and hopefully, it could be done more--not put on by
    the FDA but by the patient groups themselves in the medical
    community that serves them so that they can assemble more of
    this information and kind of multiply the effect of this, and
    we are already seeing some of that. NORD, for example, has
    offered to help with rare diseases, for example, to have more
    input that way because our resources are limited. We are not
    going to be able to cover all the different diseases.
        Ms. Castor. Good. So I expect we will hear from the patient
    organizations later today and their view on how they can be
    helpful and we can be effective.
        I think the wave of the future really is the information we
    will be able to gather through the electronic health record, so
    it is interesting to hear what you have done already with the
    Sentinel initiative. I heard from research institutes back home
    that are doing so much in genomics and personalized medicine
    that they think these larger networks are the wave of the
    future. You say you don't need additional legislation to
    continue, but you are having to borrow resources from this and
    that.
        Dr. Woodcock. Yes.
        Ms. Castor. So is your advice to the committee that we need
    to do more in technology when it comes to improving timelines
    on clinical trials by focusing on these networks and the
    electronic health record?
        Dr. Woodcock. The electronic networks have much promise in
    doing clinical trials.
        If we could move clinical trials more out into the
    community and have people out in the community, like most
    cancer patients in the U.S. who have diseases that are
    untreatable don't get into trials because they are being
    treated at places that aren't running trials. So we need to
    move this out into the community, make those folks eligible.
        And I am on the Steering Committee of the Lung-MAP trial,
    and I really urged that we make sure that we are out there in
    the community so that anyone who has lung cancer has an
    opportunity to participate in this research and perhaps have a
    more effective therapy.
        So I think the electronic health records, that is a huge
    different area that we are working on in how to do clinical
    trials utilizing that infrastructure that is emerging.
        Ms. Castor. Great. Thank you very much.
        Mr. Pitts. The chair thanks the gentlelady.
        I now recognize the gentleman from New Jersey, Mr. Lance, 5
    minutes for questions.
        Mr. Lance. Thank you very much, Mr. Chairman.
        A portion of your testimony has focused on the FDA's
    efforts on patient engagement. It is my understanding that
    ClinicalTrials.gov was intended to be a resource that provides
    clinical study information for patients, for healthcare
    providers, and for researchers. But it seems to me that the
    site lacks considerable information and has proven to be
    difficult to navigate.
        Dr. Woodcock, would you please comment on the current
    utility of the ClinicalTrials.gov.
        Dr. Woodcock. Well, I think that it has provided, along
    with the requirement of the medical editors of the journals
    that things be registered before they are going to be
    published--provided tremendously more transparency into what
    clinical trials are ongoing in the United States.
        And that has been a big achievement. All right? So we know,
    the issue of publication bias and everything is minimized
    because we know what trials have been done.
        However, I agree that, certainly for patients, I think that
    initiation of trials and understanding where there might be a
    trial that might be ongoing that might be available to them has
    also been effective, although, as you said, there are
    technological issues that remain. So it has made tremendous
    progress in transparency.
        Mr. Lance. Is there a way that you and we can work together
    to improve it? And I am not suggesting that you are in any way
    responsible for the challenges that remain. But moving forward
    for the better health of the American people, how together can
    we improve it?
        Dr. Woodcock. Well, the FDA Amendment Act required that
    regulations be issued around the results----
        Mr. Lance. Yes.
        Dr. Woodcock [continuing]. Section of this and that they
    consider whether to require the submission of clinical trial
    results for unapproved products, because much of the lag in
    getting results in there is that the products still are not on
    the market.
        So NIH is the lead for this rulemaking and I think they
    would be in the best position, and, also, they operate the
    infrastructure for this database.
        Mr. Lance. Thank you.
        In another area, in the past several hearings, we have
    discussed the difficulty of various institutions communicating
    one with another and a lack of coordination often leads to
    inefficiencies.
        What methods are currently in place to reduce redundancies
    in clinical trials? And what steps can we take together to
    ensure that we are not doubling up on research or making the
    same mistakes over and over?
        Dr. Woodcock. Hopefully, most things would eventually come
    out and be published. But certainly in the drug development
    area, there is interest in more sharing of earlier data and
    sharing of failures.
        But this has proven to be very a intractable area----
        Mr. Lance. Yes.
        Dr. Woodcock [continuing]. For transparency. All right?
        Mr. Lance. Yes.
        Dr. Woodcock. But we have continued to work on that.
        Mr. Lance. Yes.
        Dr. Woodcock. As far as some of the things that were
    referred to in the prior hearing, which I was able to listen to
    some of, they were talking about some of the inefficiencies,
    say, of IRBs, where you might have to have 100 IRBs that looked
    at----
        Mr. Lance. Yes.
        Dr. Woodcock. And I believe that there are efforts to try
    and address this. It is not an FDA issue. But, really, we came
    out a number of years ago in saying that central IRBs would
    really be preferable in these large multi-center trials.
        And then the contractual agreements that take so long to
    set up with each specific site is something that has been taken
    on. They have tried to develop model agreements and so forth.
        But that is something that the standing trial addresses
    because you sign this contractual agreement once and then you
    can do multiple investigational agents.
        Mr. Lance. Are we moving in the direction of central IRBs,
    in your judgment?
        Dr. Woodcock. Yes. There is certainly a consensus, I think,
    in the clinical trial investigator community that that is
    desirable, but various universities, naturally, are legally
    concerned about their own----
        Mr. Lance. Of course.
        Dr. Woodcock [continuing]. Liabilities and so forth. And so
    there is a push and pull about that.
        Mr. Lance. I think this is an area that we should engage in
    further investigation to make sure that we move forward in a
    manner that does not result in redundancies.
        Thank you, Mr. Chairman. I yield back the balance of my
    time.
        Mr. Pitts. Chair thanks the gentleman.
        Now recognize the gentlelady from Illinois, Ms. Schakowsky,
    for 5 minutes for questions.
        Ms. Schakowsky. Thank you, Mr. Chairman.
        Thank you, Dr. Woodcock. I think you are really an
    excellent witness. I appreciate your answers.
        Dr. Woodcock. Thank you.
        Ms. Schakowsky. I wanted to go a little bit further on the
    problem that Congresswoman Capps raised about the
    underrepresentation of women.
        I know you said that you found that, actually, women were
    overrepresented, but recently the Congressional Caucus for
    Women's Issues sponsored a meeting with leading women heart
    experts--both clinical and research experts, physicians.
        Those experts raised concerns that the lack of
    representation from women in clinical trials is limiting our
    ability to effectively treat women with heart disease. They
    were focusing in on heart disease.
        And according to those experts, for the last 50 years,
    women's heart treatment has largely been based on medical
    research about men.
        And even today, despite that fact, what they said is that
    women make up more than 50 percent of the U.S. population, that
    women comprise only 24 percent of participants in all heart-
    related studies.
        And, additionally, scientists from the Women's Health
    Research Institute at Northwestern--that is in my district--
    have raised concerns about the disproportionate number of
    adverse drug effects that occur in women due to the lack of
    sex-based clinical research.
        And, as you know, the biological, physiological, hormonal
    differences in males and females impact the rate of drug
    absorption, distribution, metabolism, elimination and,
    ultimately, affect the drug's effectiveness.
        According to those experts, the lack of requirement for
    drug manufacturers to take this into account and document any
    sex variability early in the drug development pipeline before a
    drug has been released places consumers, especially female
    patients, at an increased risk of adverse drug effects.
        So I want you to respond to that.
        Dr. Woodcock. Certainly.
        Ms. Schakowsky. Many of us were really left with a very
    disturbing feeling because heart disease is the major killer of
    women right now.
        Dr. Woodcock. Right. Well, I think we have to--what are the
    facts on the ground. All right? One of the reasons for the
    disparities that they are mentioning is actually the fact that
    men suffer heart disease earlier in life than women.
        Ms. Schakowsky. Although, let me just point out, they also
    said that the growing number, even though it is lower----
        Dr. Woodcock. Yes.
        Ms. Schakowsky [continuing]. Is younger women getting heart
    attacks and heart diseases.
        Dr. Woodcock. Yes. Yes. So that the reason for maybe
    maldistribution in the trials is because there is an age
    cutoff, and there always has been.
        In our survey, we found that there were--19 percent of the
    people in the trial in these 147 studies we looked at were over
    65, which is more than in the general population, obviously,
    but of sick people, that is still low representation, right--to
    save people with heart disease.
        Generally speaking, there is often a cutoff--age 75--and we
    are trying to eliminate those cutoffs for age and concomitant
    conditions so that the population will be more representative.
        But to your original point, we have always required male
    and female animals in the toxicology studies. All right? We
    require what we call population pharmacokinetics, PK/PD, early
    in drug development.
        And our clinical pharmacologists look at blood levels and
    exposure in men and women and we understand that, usually, and
    that is modern drug development.
        So there are multiple trials that are done that look at
    exposures, in other words, achieve blood level by gender and
    other factors, liver failure, kidney failure and so forth.
        And we can look at the phase 3 trials to see if they are--
    there has been a requirement in the regulations since, I think,
    1994 that sponsors submit a gender analysis with their
    application.
        Ms. Schakowsky. Is this incorrect, then? It says women
    comprise only 24 percent of participants in all heart-related
    studies.
        Dr. Woodcock. Well, that may be true. And that may also
    include medical devices. It also may have to do with this age
    disparity when onset of disease.
        Ms. Schakowsky. I really hope that you will look at that
    because it is a great concern. It is a growing problem for
    women.
        And let me just give you an example of what--she said
    women, because we have different symptoms of heart disease--she
    said, if you have some of these symptoms of nausea, dizziness,
    go to the emergency room, but say, ``I am having chest pains''
    because, without that, you may not get an electrocardiogram and
    you may be misdiagnosed. We need to help women.
        Thank you. I yield back.
        Mr. Pitts. Chair thanks the gentlelady.
        Now recognize the gentleman from Louisiana, Dr. Cassidy, 5
    minutes for questions.
        Mr. Cassidy. Hello, Dr. Woodcock. I always enjoy your
    testimony.
        Dr. Woodcock. Thank you.
        Mr. Cassidy. I mean that as a big compliment.
        So, next, real quickly--because I want to talk about
    something else--but does FDA--you mentioned that some
    institutions may be nervous about their liability if they refer
    their IRB activity to a centralized IRB.
        Dr. Woodcock. Correct.
        Mr. Cassidy. Except so many do, we know that is a false
    argument.
        Is there any way FDA can reassure those institutions?
    Because the gentleman from Mayo suggested it is a cultural
    issue. He didn't mention anything about legal. Thoughts?
        Dr. Woodcock. Right. Yes. I heard his testimony.
        In my experience, that there are legal--there are concerns
    of the--counsel of the various----
        Mr. Cassidy. Attorneys are always nervous. Right? I mean,
    they don't make money if they are not nervous. I hate to be
    cynical, but----
        Dr. Woodcock. Yes.
        Mr. Cassidy. Is there any way FDA can send reassurances
    regarding that?
        Dr. Woodcock. Well, we have tried. In guidance and so
    forth, we have encouraged this. And in the city initiative, we
    had a whole discussion and dissemination of information about
    central IRBs. But possibly there is more that we can do to
    encourage this.
        Mr. Cassidy. OK. Let me then bring on--you mentioned
    something intriguing earlier, that there may be some at high
    risk for disease; so, therefore they will be more risk-
    tolerant.
        Dr. Woodcock. Yes.
        Mr. Cassidy. Now, I have a family member, a nephew, with
    Down syndrome. And I am looking on the alzheimers.org Web site,
    and they mention how virtually 100 percent of adults with Down
    syndrome by age 40 will have evidence of the tangles associated
    with Alzheimer's.
        Dr. Woodcock. Yes.
        Mr. Cassidy. Now, what are the issues regarding--wow. This
    is a group of adults who are 100 percent at risk for a terrible
    condition.
        Dr. Woodcock. Right.
        Mr. Cassidy. But there are other issues involved as well.
        What are your thoughts about this? How do we make stuff
    available for folks incredibly at risk for such a terrible
    disease?
        Dr. Woodcock. Yes. Well, with Alzheimer's, there are a
    number of problems. The basic problem is we still don't
    understand the disease well enough and the interventions that
    have been tried, which have been in late-stage disease when
    people are already demented, have failed to work.
        Mr. Cassidy. Now, as I gather, though, the problem is
    predicting at an earlier stage those at risk. Correct?
        Dr. Woodcock. That is correct. If you want to intervene
    early. We recently issued a draft guidance saying that, OK, if
    you want to intervene earlier, we would accept an end point
    that is subtle cognitive testing.
        Mr. Cassidy. I accept that.
        But how do you decide which population is at such high
    risk? Because, if you have a control group--you follow what I
    am saying--only 10 percent are really going to be at risk.
        Dr. Woodcock. Right.
        Mr. Cassidy. You with me? This is a really expensive study.
        Dr. Woodcock. That is right. And so we advocate techniques
    called enrichment, which you try to use biomarkers or other
    tests to figure out. There are genetic conditions that increase
    your risk for Alzheimer's disease.
        Mr. Cassidy. So speaking of Down syndrome as one example?
        Dr. Woodcock. That would be one example. Yes. There are
    others.
        Mr. Cassidy. And can you give us the progress of that. So
    if you accept these, are people now using these?
        Dr. Woodcock. Well, we need agents to use them in. So that
    is part----
        Mr. Cassidy. And I am sorry. ``Agents,'' you mean as in----
        Dr. Woodcock. I am sorry. Investigational interventions
    that we can test in the people.
        And that is part of the problem. The science of
    understanding what causes Alzheimer's and what you can
    intervene in that would actually delay or prevent the disease
    is not mature enough.
        And we have approved a couple imaging agents for
    Alzheimer's, but they aren't 100 percent. And you would maybe
    be kind of advanced----
        Mr. Cassidy. But, for example, I know hyperinsulinemia is
    thought to be a potential risk factor.
        Dr. Woodcock. Yes. I know that.
        Mr. Cassidy. And I think there are some studies suggesting
    that Actos might give some benefit.
        Dr. Woodcock. Yes.
        Mr. Cassidy. Presumably, it would be at an earlier stage,
    not a later stage, would be a non-metabolic syndrome indication
    for the use of Actos. Fair statement?
        Dr. Woodcock. Yes.
        Mr. Cassidy. So there is at least some of that. I guess I
    pose that to ask the degree to which that has been, again, the
    current state. I will go back to what is the current state of
    using that sort of thing?
        Dr. Woodcock. Right. So the current state, if someone
    decided to do a trial--and I believe there have been some
    intervention trials, not of Actos, but an earlier intervention
    at high-risk--in higher-risk people--they might identify people
    they felt were high risk for one reason or another, randomize
    them to this intervention or not, and then we would allow use
    of neurocognitive testing even before they had symptoms, if
    they had subtle changes, and if the treatment group did better
    than the placebo group, we could give accelerated approval.
        Mr. Cassidy. So I guess you have got the framework. It is
    just a question of someone coming forward to take advantage of
    it.
        But how long would such a study, do you imagine, take to
    complete its course? Twenty years?
        Dr. Woodcock. No. No. But we need to have better
    measurements that stick to these biomarkers and other
    measurements, like of subtle cognitive function, where we--the
    NIH and us and others are working on this.
        Because the earlier you can intervene--if you have a very
    targeted test that can identify people early, they don't have
    any symptoms, but you can tell their brain isn't working as
    well as it should, and then it will decrease over time. So that
    is kind of the rate-limiting step.
        But I agree. Prevention is very difficult because there you
    want to intervene on people who are well and treat them for a
    long time and expose them to something with the hope that, at
    the end of the day, they are not going to get whatever bad
    outcome.
        Mr. Cassidy. We are out of time. Thank you very much.
        Mr. Pitts. Chair thanks the gentleman.
        Now recognize the gentleman from Virginia, Mr. Griffith, 5
    minutes for questioning.
        Mr. Griffith. Thank you very much, Mr. Chairman.
        Dr. Woodcock, as others have said today and, also, what I
    have heard in some of our informal conversations is that you
    not only do a good job as a witness, but that you are doing a
    good job overall.
        Dr. Woodcock. Thank you.
        Mr. Griffith. And so I appreciate that, and thank you so
    much for being here today.
        You and Dr. Cassidy had a little conversation about
    lawyers. Some lawyers are always nervous. Other lawyers are
    always looking for a way to solve the problem.
        And so maybe we need to get some of those lawyers on your
    team and some of the corporate teams to solve the problem,
    figure out how we can make these things work, because I do
    think it is important.
        As you probably know, I am one of those who advocates that
    we try to move a little quicker in those areas where we have
    problems that we don't have solutions for currently and, also,
    favor what is known in some State laws as right to try when you
    have a situation where doctors have tried everything and folks
    are given a diagnosis they have got months to live or their
    condition is going to be fatal.
        I am one of those people who believes that we ought to let
    them go ahead and try whatever it is they are willing to pay to
    do because the FDA can't protect you if you are going to die
    from something that might kill you.
        Dr. Woodcock. Right.
        Mr. Griffith. I mean, it is going to happen one way or the
    other. You might as well have the right to try something.
        That being said, I know there are a lot of issues
    surrounding that. I am not sure we have time for for that
    discussion today.
        And I know that there is another panel, and I want to hear
    from the patients as well because they are involved in this
    process.
        So respecting you greatly, I yield back my time.
        Mr. Pitts. Chair thanks the gentleman.
        Now recognizes gentlelady from North Carolina, Mrs.
    Ellmers, 5 minutes for questions.
        Mrs. Ellmers. Thank you, Mr. Chairman.
        And thank you, Dr. Woodcock, for being with us again today.
        This is such an important issue. As you know, we had our
    panel on Wednesday. And it seemed to me that it was a general
    consensus that everyone is looking for ways to expedite this
    and to make it more efficient and get those drugs to market
    sooner so that we can be taking care of our patients more
    effectively.
        In your testimony and in the discussions that we have had
    today, you have touched on the biomarkers and targeted drug
    development to benefit disease populations, obviously.
        As all of our representatives here, we all have
    constituents with rare diseases, heart-breaking. Especially
    right now in my community, I have a very good friend with ALS.
    And as I am learning more and realizing, we have had a number
    of members of our community diagnosed with ALS. So this is
    something that is very important to me right now.
        And I am just looking at the idea--as far as the target
    approval process being appropriated and applied through the
    FDA, it seems to be that we are looking at cancer and HIV.
    Where do some of those rare diseases fall within that?
        And you had mentioned and there was discussion about the
    master protocol and that seems to be applied more to cancer or
    HIV. Where can some of the rare diseases fall in there? And
    what can we do to help make that happen?
        Dr. Woodcock. Well, any rare disease would be a great
    candidate for a standing network, a network of experts--and I
    think you may hear more about this from the next panel--where
    they are ready to evaluate any therapy that advances through
    the early, the nonhuman, stages.
        So they could pick that up right away and test it quickly.
    In the meantime, until that happens, they can get what we call
    natural history, which I know sounds very wonky.
        But people are asking--just now Mr. Cassidy--like how long
    does Alzheimer's progress from presymptomatic to symptomatic.
    Well, we need to know that so that we can design the trial
    correctly.
        In rare diseases, even more difficult because nobody knows.
    And, usually, they get experts together and say, ``Well, in my
    opinion, it takes this long.'' Right? And they are usually
    wrong because they have only seen a few people.
        So we are encouraging these natural history studies, these
    networks. First, they look at the people and they can look at
    the biomarkers, too.
        So what changes in ALS? What can we measure? Could we
    measure something that gives us indication that treatment might
    be working? Right?
        And then, as soon as a therapy becomes available, then you
    can rapidly get people into a trial and there would be no
    delays because there is no delaying an ALS.
        Mrs. Ellmers. Right. Exactly.
        And that is obviously part of the concern. And certainly I
    agree with my colleague in talking about right to try. This
    would be a perfect example of decisions that families and
    patients can make.
        I do want to talk about--you had also mentioned listening
    carefully to patients and families.
        Dr. Woodcock. Yes.
        Mrs. Ellmers. And do you consider and give more weight--
    that is one of our questions, is how much weight are you giving
    to the patients and families? And there again, from our
    perspective in Congress, what can we do?
        You know, as we have heard everyone agreeing that we need
    to make a difference here and we can move things forward, how
    open is the FDA to this possibility? And what can we do right
    now to make this happen?
        Dr. Woodcock. Well, as I said in my testimony in the
    beginning, medical culture has changed over the years. It used
    to be very doctor-centric and now it is patient-centric. And
    the FDA culture and drugs is a medical culture. And so that has
    changed at the same time, but slowly.
        So we have been working, though, very diligently with
    patient groups and so forth to try to get the patient point of
    view more central to the evaluation of benefit and risk and
    what it means to the person who actually has the disease, is
    going to take the drug.
        To answer your question what can be done, I think a lot of
    this needs to be done out in the community. The patient groups
    need to get organized and develop these. Some of them are
    working with PCORI and trying to use that mechanism to get more
    information available and so forth.
        We have gotten draft guidances from different groups,
    including Muscular Dystrophy, that really are a statement of,
    ``This is what we care about. This is what we value. This is
    what we want you to look at.'' And we will pay extremely close
    attention to those, and those are extremely valuable.
        Mrs. Ellmers. Thank you, Dr. Woodcock.
        And I yield back the remainder of my time.
        Mr. Pitts. The chair thanks the gentlelady.
        We are voting on the floor. We have 10 minutes left in the
    vote. We have three more questioners.
        Mr. Guthrie recognized for 5 minutes for questioning.
        Mr. Guthrie. Thank you, Mr. Chairman. I will try to be
    brief.
        I will echo what the others said about your testimony.
    Appreciate it.
        But since we started this 21st Century Cures and--
    everybody's excited. Both sides are trying to see how we can do
    this better.
        And I have heard from a lot of groups and I have heard
    several times that the oncology division seems to be one people
    really like to work with and it works well. Some of the other
    divisions in expedition is not as well to work with.
        And I have always believed--Jack Kemp used to say, ``Don't
    study failures and point out the problems. Let's look at
    successes and see how it can be replicated.''
        So within your own agency, you are having wonderfully
    successful programs, at least according to the feedback I have
    gotten, and some not as fun as the ability to work with.
        So I guess my question is: Is there any impediment to
    saying, ``Hey, this''--the oncology is what we hear about more,
    not that the others aren't, but we hear more--is there any
    impediment to taking what is happening there and transferring
    to other agencies? Is there something Congress can do to make
    it easier or is it just learning and moving forward?
        Dr. Woodcock. Let me tell you that 10 years ago, I heard a
    lot of negative comments about our oncology group. All right?
    And now we have therapies that are so effective. They are
    really on fire.
        They see that, for their patients they took care of--they
    are all oncologists, hem onc doctors--that these new treatments
    would really have made a difference for those people. And so
    they are doing everything they can to get those treatments out.
        And I think what we need, we need the same kind of
    inspiring therapies in these other areas. And I do think the
    doctors--they are doctors. They are physicians. They care about
    patients in their disease area.
        And this breakthrough--I don't know whether you can see it
    here, but you see that other disease areas are coming up and we
    are designating--in neurology and anti-infectives and
    psychiatry, we are designating potential breakthroughs. And so
    this type of thing will really help.
        But, also, of course, we try to have a management
    structure, multiple mechanisms whereby we have consistency and
    uniformity of our approach and our procedures, and I think we
    do quite well in our procedures.
        But I think the attitude may have something to do with the
    underlying science. We had a war on cancer. It is starting to
    pay off. And we need to really expedite that.
        Mr. Guthrie. Well, thanks.
        And I have a bill particularly to put the same professional
    budget judgment status for Alzheimer's, which we are going to
    spend in 2050 $1 trillion. This is not loss of income, loss of
    productivity.
        Dr. Woodcock. Right.
        Mr. Guthrie. That is $1 trillion spent on that disease.
        That is when I am 86. So that is when my children and our
    grandchildren will be taking care of us. So, hopefully, we can
    have the same inspiration and do that, particularly in
    Alzheimer's.
        Dr. Woodcock. I can assure you that, if they were promising
    treatments for Alzheimer's, we would jump right on them.
        Mr. Guthrie. Appreciate that. Thank you very much.
        And I will yield back.
        Mr. Pitts. Chair thanks the gentleman.
        Recognizes the gentlelady from Tennessee, Mrs. Blackburn, 5
    minutes for questions.
        Mrs. Blackburn. Thank you so much, Dr. Woodcock. I have
    basically one question that I do want to get to.
        Looking at the QIDP and the moving forward of that, it can
    give up to 5 years of additional data exclusivity. Bipartisan
    effort. We were all for it.
        What I want to know from you is: How many QIDPs has the FDA
    designated to date? How many products have actually been
    approved to date? And do you believe that the QIDP is an
    important designation?
        Dr. Woodcock. It is absolutely important.
        Mrs. Blackburn. OK.
        Dr. Woodcock. We have granted 50 designations for 34 unique
    molecules. And in the last several weeks, we have approved the
    first two medications that are designated, the first two
    antimicrobials.
        Mrs. Blackburn. Excellent.
        Dr. Woodcock. So that is making a difference. We do feel,
    though, that probably more needs to be done.
        Mrs. Blackburn. And in that ``more needs to be done,'' give
    me a couple of examples of what you think the next step should
    be. I would be interested in that.
        Dr. Woodcock. Well, we are very interested in the pathway
    that people call limited population antibacterial drugs or
    other streamlined pathways for development that would be
    matched with some sort of symbol or logo that would enable
    doctors and other prescribers to recognize that it was from a
    limited program. We think that would also allow us to
    streamline the development program.
        Mrs. Blackburn. Excellent.
        And for the second panel, I want to welcome a fellow
    Tennesseean, Dr. Marshall Summar, who is going to be speaking
    on behalf of the National Organization of Rare Diseases.
        So welcome. We are delighted you are here.
        And I would yield back.
        Mr. Pitts. Chair thanks the gentlelady.
        Now recognizes the gentleman from Florida, Mr. Bilirakis, 5
    minutes for questions.
        Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
        And thank you for your testimony, Dr. Woodcock.
        I asked these questions a few months ago and I didn't get a
    response. So I am going to see if I can get a response this
    time. Appreciate it if you can answer.
        Can you tell me how many treatments were approved with
    novel biomarkers used for the first time?
        Dr. Woodcock. No. I don't have that in the----
        Mr. Bilirakis. Can you get that information to me as soon
    as possible?
        Dr. Woodcock. I would be happy to. It is a very interesting
    question. Yes.
        Mr. Bilirakis. And then next question: Have any accelerated
    approval occurred within novel biomarker in never-before-
    treated disease?
        Dr. Woodcock. Oh, yes. All the time. And I can get that for
    you. I don't have it, again.
        Mr. Bilirakis. Please.
        How many new biomarkers did the FDA accept for a first-time
    use in the last 5 years?
        Dr. Woodcock. Certainly.
        Mr. Bilirakis. Can you get that for me?
        Dr. Woodcock. Absolutely.
        Mr. Bilirakis. OK. Very good. Thank you very much.
        I know we don't have a lot of time; so, I will yield back.
    Thank you, Mr. Chairman.
        Mr. Pitts. Thank you.
        There is 2 minutes left in the vote on the floor; so, we
    are going to recess. There are two votes. As soon as we have
    the second vote, we will come back and reconvene with our
    second panel.
        Again, Dr. Woodcock, thank you for coming. You have been a
    terrific witness.
        Dr. Woodcock. Thank you.
        Mr. Pitts. Members will have follow-up questions. We will
    send them to you. We would ask that you please respond.
        Thank you. And thank you for your patience.
        The subcommittee stands in recess.
        [Recess.]
        Mr. Pitts. Time of recess having expired, we will reconvene
    the subcommittee on Health and introduce our second panel.
        In our second panel, we have five witnesses. I will
    introduce them in order of their presentation. First, Ms. Pat
    Furlong, Founding President and CEO of the Parent Project
    Muscular Dystrophy; second one, Mr. Robert Beall, President and
    CEO of Cystic Fibrosis Foundation; third, Mr. Richard Pops,
    Chairman and CEO of Alkermes; fourthly, Dr. Leonard
    Lichtenfeld, Deputy Chief Medical Officer of American Cancer
    Society; finally, Dr. Marshall Summar, Director of Scientific
    Advisory Committee, National Organization for Rare Disorders.
        Thank you all for coming. You will each be given 5 minutes
    to summarize your testimony. Your written testimony will be
    placed in the record.
        Ms. Furlong, we will start with you. You are recognized for
    5 minutes for your opening statement.

     STATEMENTS OF PAT FURLONG, FOUNDING PRESIDENT AND CEO, PARENT
    PROJECT MUSCULAR DYSTROPHY; RICHARD F. POPS, CHAIRMAN AND CEO,
    ALKERMES; MARSHALL SUMMAR, M.D., DIRECTOR, SCIENTIFIC ADVISORY
    COMMITTEE, NATIONAL ORGANIZATION FOR RARE DISORDERS; ROBERT J.
     BEALL, PH.D., PRESIDENT AND CEO, CYSTIC FIBROSIS FOUNDATION;
    AND J. LEONARD LICHTENFELD, M.D., DEPUTY CHIEF MEDICAL OFFICER,
                        AMERICAN CANCER SOCIETY

                        STATEMENT OF PAT FURLONG

        Ms. Furlong. Thank you.
        Good morning, Chairman Pitts and members of the committee.
        My name is Pat Furlong. Twenty years ago I joined other
    parents to form Parent Project Muscular Dystrophy to end
    Duchenne, one of the many forms of muscular dystrophy and the
    most common lethal genetic disorder diagnosed in childhood.
        In 1984, I received the horrific diagnosis on my two sons,
    Christopher and Patrick, and both of my sons are gone now. I
    wage this crusade in their honor.
        Much has happened over the past 15 years to transform the
    Duchenne clinical and research landscapes, and much of this is
    a direct result of the actions by Congress and this committee,
    notably the enactment of the Childs' Health Act in 2000, and
    the Muscular Dystrophy CARE Act 1 year later. Since the MD CARE
    Act was enacted, we have seen about 10 years added to the
    lifespan of patients with Duchenne.
        There has been an improvement in quality of life driven
    largely by the development and dissemination of care standards
    so that all patients can be diagnosed accurately and as early
    as possible and provided with the highest quality of care.
        The MD CARE Act also transformed the Duchenne research
    landscape. What was just 12 years ago a near-barren field has
    evolved into a robust area of research where multiple potential
    therapies are in clinical testing and several others are in
    early stages of development.
        Despite these advancements, Duchenne remains a fatal
    disease without any FDA-approved therapies. Most boys end up in
    wheelchairs by their mid-teens, and only a few live beyond
    their late 20s.
        Our community needs therapies and we need them fast to. To
    achieve this goal, PPMD has led groundbreaking efforts over the
    past year to address two major impediments in our request to
    end Duchenne.
        One is a lack of regulatory understanding of patient and
    parent perspectives on benefit-risk; and, two, a lack of clear
    guidance or direction to the biopharmaceutical companies
    designing these clinical trials.
        PPMD partnered with Johns Hopkins University to conduct the
    first-ever scientific survey on benefit-risk perspectives. The
    survey involved 120 parents of Duchenne children. It validated
    what we have known anecdotally for years.
        Because Duchenne is 100 percent fatal at a young age, many
    patients and families are willing to accept higher levels of
    risk in return for the prospect of potential benefit.
        The data has been shared with the FDA and was recently
    published in an academic journal. Now the FDA must ensure its
    reviewers apply this evidence to their decisionmaking process.
        Another impediment to drug development, particularly in
    rare diseases, is the absence of a clear guidance from FDA when
    it comes to designing clinical trials. Small patient
    populations, limited knowledge about the condition and a lack
    of accepted or validated biomarkers are some of these
    challenges.
        At the invitation of the FDA, PPMD led a comprehensive 6-
    month effort to convene key stakeholders--patients, parents,
    clinicians, researchers and industry--to write a draft guidance
    document that would address trial design and many other issues.
    This was submitted to the FDA last month, marking the first
    time a patient group has led the development of such a product.
        Now the FDA must step up promptly to review the draft,
    gather stakeholder input and issue a guidance document under
    the Agency's name.
        While each of these projects is focused on Duchenne, each
    also offers a template or a model that could be applied to
    other diseases or other conditions, particularly rare diseases,
    and I hope other organizations will take on similar programs.
        So what can Congress and Federal agencies do moving ahead?
    First, you can make sure that the patient perspective on
    benefit-risk and other issues is considered by reviewers of the
    FDA.
        One way to do so could be by establishing a nonburdensome
    step where reviewers would disclose how they did or did not
    take such information into account making their decisions on a
    drug application. This would shed light on for what many
    considered a mysterious process and could be done in a very
    simple manner.
        Second, I suggest an even greater focus on regulatory
    science so the FDA keeps pace with the breakneck speed of
    innovation. Specifically, NIH could bolster support for
    regulatory science research and infuse that into clinical and
    translational awards. Incorporating a regulatory perspective
    earlier in the pipeline can maximize the likelihood that
    candidate therapies will be ready for the rigor of the FDA.
        Finally, I would encourage greater flexibility in clinical
    trials, particularly rare fatal conditions like Duchenne that
    have small populations. Business-as-usual trial designs simply
    do not hit the mark when working with these populations.
        The Duchenne community has traveled a great distance over
    the past 15 years, thanks in significant part to the leadership
    of this very committee, leadership that will continue on Monday
    with action by the full committee on the MD CARE Act
    amendments.
        For far too many families, my own included, this journey
    has not been fast enough. We stand ready to work with your
    committee to make sure the 21st Century Cures Initiative ends
    Duchenne and so many other rare diseases.
        Thank you.
        Mr. Pitts. Chair thanks the gentlelady.
        [The statement of Ms. Furlong follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. Mr. Beall, you are recognized for 5 minutes for
    your opening statement.

                  STATEMENT OF ROBERT J. BEALL, PH.D.

        Mr. Beall. Thank you very much for this invitation to
    present this testimony.
        The story of cystic fibrosis is clearly a story of
    determination of hope and optimism. The progress that we have
    documented in our submission really shows what is possible when
    a system works well, when patients, when stakeholders and the
    regulatory agencies collaborate to develop life-changing
    treatments.
        Cystic fibrosis is clearly a life-threatening genetic
    disease that affects about 30,000 individuals in the United
    States. There has been tremendous progress in life expectancy
    over the decades.
        In the 1950s, people with cystic fibrosis barely lived to
    elementary school. But there are people that are living today
    with cystic fibrosis in their 30s and 40s, and some are even
    going beyond.
        But we still lose too many patients at very young ages. The
    increase in life expectancy is due in large part to
    groundbreaking advancements and treatments made possible
    because of the Cystic Fibrosis Foundation, our patient
    community and our industry collaborators.
        Two years ago the FDA approved Kalydeco, the first drug to
    treat the underlying causes of cystic fibrosis in a small
    subset of people with the disease. Hailed as a game-changer, it
    has transformed the lives of those taking this drug.
        It is a perfect example of personalized medicine. I might
    mention that the FDA approved this drug in near record time, 3
    months before the prescribed PDUFA date and months before the
    EMEA.
        Just 2 weeks ago we saw another breakthrough in cystic
    fibrosis. It happened when--the positive data from a phase 3
    clinical trial for a new therapy that is targeted at 40 percent
    of the CF population.
        This data was released by Vertex Pharmaceuticals Company.
    These products would not have been possible without the
    breakthroughs that have taken place in basic research, in all
    the efforts that our foundation has made over the years.
        The CF community was thrilled to learn that the trial
    participants showed a significant improvement in lung function,
    weight gain, and 30 to 40 percent reduction in exacerbations.
    That is the time that they would have to go to the hospitals or
    have IV infections.
        So this is clearly a game-changer for these patients.
    Obviously, Vertex plans to submit the new drug application to
    the FDA by the end of the year for this treatment.
        What is exciting about this progress is that these drugs
    would not have been possible were it not for the Foundation and
    our patient community. Our commitment to scientific discovery
    and drug development is at the root of our success, but it
    hasn't been easy and it hasn't occurred overnight.
        In 1965, we created the first patient registry in the
    United States, now a model for chronic disease. Because of this
    registry, we have a documented natural history of cystic
    fibrosis.
        We have the mutation analysis on most of these patients, as
    Dr. Woodcock referred to this morning, and we have the ability
    to have post-marketing phase 4 follow-up on these new drugs as
    they are introduced to the community.
        The same year, 1965, we created a care center network. 90
    percent of all patients seen in the United States are seen at
    these CFF-accredited and funded care centers.
        In 1989, through our support, the CF gene was discovered,
    12 years before the human genome was completed.
        In 1998, we established a Clinical Trials Network, the
    first Clinical Trials Network founded solely by a nonprofit
    organization like the Foundation. It is a critical component of
    our ability to conduct CF clinical trials efficiently and
    effectively.
        In 1999, the CF Foundation pioneered a successful venture
    philanthropy model to derisk companies from investing in CF
    research drug development.
        It was our initial investment of $42 million in a small
    biotech company in San Diego that ultimately led to Kalydeco.
    Vertex would not have had Kalydeco and the other drugs
    announced last week were it not for the Cystic Fibrosis
    Foundation.
        The CF Foundation spearheads collaboration across all
    sectors, and this same collaborative spirit extends to the
    Foundation's strong partnership with the Food and Drug
    Administration.
        With the FDA, we are committed to collaboration and
    bringing strong data to the table. As often has been stated,
    the CF Foundation comes with data, not demands.
        Just last week we met with FDA officials to discuss
    strategies for clinical research design that may not occur
    until 5 years from now.
        However, curing a disease is never easy, and even more
    risky is the approval of drugs without sufficient data to
    assure efficacy and safety.
        If this happens, you place patients immediately at risk and
    you risk losing the opportunity to test drugs that could have a
    real impact and beneficial effect.
        So, in closing, what can Congress do for us? Congress
    should make sure that patients have a seat at the table, as was
    just referred to.
        Congress must provide the necessary resources so that the
    FDA can attract the best and the brightest. And Congress must
    provide the NIH and FDA sufficient resources for regulatory
    sciences, as also mentioned.
        But, finally, Congress may also encourage that they look at
    the CTSA program, a network of care centers that are funded by
    the NIH, and see how they might use these to be able to
    facilitate Clinical Trial Network and the development of
    patient registries in other rare diseases.
        So, once again, thank you for this opportunity to add the
    CF community's perspective to this important discussion.
        Mr. Pitts. Chair thanks the gentleman.

        [The statement of Mr. Beall follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. Mr. Pops is recognized 5 minutes for an opening
    statement.

                      STATEMENT OF RICHARD F. POPS

        Mr. Pops. Thank you very much.
        I would like to thank you, Mr. Chairman, Ranking Member
    Pallone and all the members of the committee for inviting me to
    testify.
        I just want to thank Chairman Upton and Congressman DeGette
    for spearheading the 21st Century Cures Initiative.
        I would also like to express my respect for and
    appreciation for the folks on this panel and for Dr. Woodcock.
    We are all partners in this together, and it is an credibly
    important mission.
        The simple and powerful concept of incorporating insights
    from patients is centrally important to the future of the
    Nation's healthcare system. And it is also one of the great
    opportunities for us all to have a transformative impact.
        I have served as the CEO of Alkermes for over 20 years. Our
    company develops medicines for people living with chronic
    debilitating diseases, such as opioid addiction, schizophrenia,
    and depression. Our approach is entirely dependent upon
    considering the patient perspective early and consistently
    throughout the drug development process.
        I also serve on the Boards of both BIO and PhRMA and was
    deeply involved in the PDUFA V negotiations, as well as the
    preparations ongoing for PDUFA VI, where elevating the patient
    voice has already emerged as a key theme for that initiative.
        Today I would like to propose a new framework for patient
    involvement in developing new medicines, which requires
    engagement from all three of the major parties involved,
    innovative biopharmaceutical companies like ours, FDA, and the
    patients who stand to benefit from these medicines.
        And the framework is based on three core principles.
        First is that interactions must be data-driven, based on
    science and separate from powerful and passionate advocacy
    messages that patient groups otherwise deliver.
        Second, the engagement framework should be actionable, not
    theoretical. It should improve the overall efficiency of the
    process rather than adding new steps in a process that is
    already incredibly complicated. This is particularly important
    for young biotechnology companies who are developing their
    first drugs on limited resources.
        Third, the approach should preserve and enhance FDA's gold
    standard of safety and efficacy, which is really one of our
    great national treasures. I believe deeply, personally, that
    increased patient input can coexist with efficiency and the
    highest level of scientific rigor.
        So from industry's perspective, there is clearly no
    consistent way to incorporate patient-generated input. This
    input would have a really meaningful impact on a range of
    critical decisions we and our researchers make specific to
    particular product candidates and certainly to the way we
    design clinical trials and implement them around the world.
    This is an important missing link.
        As Dr. Woodcock mentioned and the FDA, patient engagement
    is not a new concept. Several provisions included in PDUFA as
    well as FDASIA have resulted in meaningful new expansions in
    patient engagement.
        FDA has also been open to and has taken initial steps to
    include patient input into their reviews, and we can build on
    this. The proposed framework I am considering would build on
    all of these things.
        The historical paradigm of drug regulation as a bilateral
    process between FDA and the industry is outdated. Science and
    society have continued to advance. Patients are organizing in
    new ways, and their critical role in driving innovation is
    becoming more the rule than the exception. We have 20th-century
    regulatory framework for 21st-century drug development.
        To tackle these increasingly complex scientific and
    regulatory issues as we look to treat and cure complex
    diseases, all three parties can work together to develop
    improvements to their existing regulatory framework.
        These would include new clinical trial designs, more
    efficient clinical trial enrollment methods, advancing FDA's
    evaluation of risk and benefit, and more sophisticated post-
    market data collection. These are incredibly exciting areas for
    future consideration.
        We would need to evolve the way we work together, all the
    different parties, recognizing our shared responsibility to
    improve the efficiency of the development process and our
    accountability to assure the medicines are safe and efficacious
    for patients.
        There will be a number of challenges to this as we move in,
    and these could include establishing a common threshold for
    data and scientific rigor that is shared by patient industry
    groups and FDA, modifying existing regulations to accommodate
    this new framework, protecting intellectual property and data,
    which is essential to enabling innovation and maintaining this
    gold standard of safety and efficacy.
        As next steps, I propose that Congress, industry, FDA and
    patient groups come together to develop and implement this new
    framework, building on existing patient-focused provisions of
    PDUFA and FDASIA. We should also analyze existing statues and
    regulations to identify impediments and opportunities.
        In conclusion, the concept of a new and comprehensive
    patient-inclusive framework is both ambitious and, at the same
    time, it is quite modest.
        It is ambitious as it could result in a dramatic change in
    the way we discover and develop medicines. It is modest because
    it is not a new regulatory pathway or authority, but it builds
    on an existing foundation.
        And we at Alkermes and all of our colleagues in the
    biopharmaceutical industry are standing by to help you in that
    effort. We really thank you very much for your leadership.
        Mr. Pitts. Chair thanks the gentleman.
        [The statement of Mr. Pops follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. Dr. Lichtenfeld, you are recognized for 5
    minutes for your opening statement.

               STATEMENT OF J. LEONARD LICHTENFELD, M.D.

        Dr, Lichtenfeld. Good morning, Chairman Pitts, Ranking
    Member Pallone, and members of the subcommittee.
        I am Dr. Len Lichtenfeld, and I am Deputy Chief Medical
    Officer for the American Cancer Society and truly appreciate
    the opportunity to be with you today to testify. The American
    Cancer Society is pleased to contribute to the dialogue around
    the committee's 21st Century Cures Initiative.
        Today I would like to focus on three critical areas for the
    committee's consideration. One is the need for greater
    investment in research; secondly, expedited approval processes
    that continue to ensure safety and efficacy of approved drugs;
    and, third, making patients active partners in all aspects of
    research development and regulation of new therapies.
        We are fortunate and blessed that today we have 14 million
    cancer survivors in the United States. It is a remarkable
    number, and it is due to more effective treatments and improved
    screening tools that have been made possible through research.
        We must continue and expand our steadfast commitment to
    research, and we must continue to support researchers working
    on finding the next generation of cures.
        Just as important, we must ensure that expedited approval
    processes for drugs and devices are appropriately safe,
    effective and accessible to patients. The goal of the 21st
    Century Cures Initiative is to accelerate the development and
    approval of new medical treatments.
        There are a few other areas that can match the research and
    development activity in the field of cancer. It is, in fact,
    and has been a model of innovation.
        The FDA's Office of Hematology Oncology Products has
    aggressively used the tools provided by Congress to speed new
    drugs to patients and has encouraged drug companies to be
    innovative in clinical trials.
        In the past 8 months, three cancer drugs have been approved
    using the accelerated pathway. One approval was based on a
    trial of 111 patients, an example of research approvals
    happening faster and with smaller clinical trials as has been
    the case in the past.
        Small-sized trials and accelerated approval do have
    drawbacks. They may not include a diverse population, which may
    yield an incomplete picture of how a drug might work in a
    broader population. Small trials and accelerated approvals also
    tend to be seen in deadlier cancers where there are no other
    good therapeutic options.
        And I want to stress that the risk-benefit tolerance of a
    cancer patient facing a poor prognosis may be much different
    than for those with other available treatment options.
        And, therefore, the same acceptance of reduced data on
    which to base FDA approval may not be appropriate in other
    fields or for other diseases.
        Finally, I want to stress the importance of researchers,
    pharmaceutical companies and the FDA in engaging widely and
    meaningfully with patients.
        The Food and Drug Administration Safety and Innovation Act
    requires greater patient involvement throughout the drug and
    device approval process. ACS CAN championed provisions to
    expand the FDA's patient representative program to maximize
    patient input during the drug development process.
        We need to continue to build on that progress. Patients can
    provide important perspectives at various stages of medical
    product development and regulation.
        They know more than anyone what is most important to
    patients, to themselves: Symptom reduction, risk tolerance and
    design elements that might affect trial recruitment or
    retention.
        This kind of patient involvement should be reinforced and
    supported and, to this end, the FDASIA provisions requiring FDA
    to address challenges that have hindered patient involvement
    must be fully implemented.
        We urge the committee to consider examining opportunities
    for providing greater funding to support the FDA patient
    representative program as well as broader continued engagement
    with the patient community.
        Another important way patients' perspectives can inform
    development of therapies is through the design and use of
    patient-reported outcomes.
        Measures of cancer therapy effectiveness sometimes include
    functional status, pain or quality-of-life measures, but these
    may be reported by the physician rather than by the patient.
        Quality-of-life measures like pain or nausea should come
    from patients themselves, and patients should help prioritize
    the importance of these side effects in the overall response to
    a disease and the associated treatments.
        When quality-of-life outcomes are vigorously measured and
    supported by the FDA, they should be included in a drug's
    labeling and they should be considered for a drug's approval.
        The FDA should also be encouraged to work with industry and
    researchers to incorporate self-reported symptom measurements
    as a regular part of clinical trials.
        In closing, we appreciate the opportunity to contribute to
    the dialogue around the committee's 21st Century Cures
    Initiative and look forward to working with the subcommittee
    and its staff. I am happy to take any questions.
        Thank you very much for this opportunity.
        Mr. Pitts. Chair thanks the gentleman.

        [The statement of Dr. Lichtenfeld follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. Dr. Summar, you are recognized for 5 minutes for
    your opening statement.

                   STATEMENT OF MARSHALL SUMMAR, M.D.

        Dr. Summar. Thank you, sir.
        Good morning, Chairman Pitts, Ranking Member Pallone and
    members of the subcommittee. And thank you for inviting me
    today.
        My name is Marshall Summar. I have the good fortune to be
    the Chief of Genetics and Metabolism at Children's National
    Medical Center here in Washington, D.C.
        I have been working in the field of rare diseases for the
    last 29 years, and I am here today in my capacity as a member
    of the Board of Directors of the National Organization of Rare
    Disease and Chair of the Scientific Advisory Committee of NORD.
        On behalf of the estimated 30 million individuals with rare
    diseases, NORD thanks you in the Energy and Commerce Committee
    for your continued strong support of the rare disease
    community. You have made a huge difference for us.
        NORD's a unique federation of over 200 patient advocacy
    groups, clinicians, researchers, dedicated to helping people
    with rare diseases.
        NORD provides resources, research advocacy, education,
    community and infrastructure support to the rare-disease
    community that small individual organizations cannot. It is the
    nature of rare diseases. They are small.
        NORD was founded in 1983 and played an active role in the
    passage of the Orphan Drug Act, which is a successful model of
    how to incentivize the development of treatment that saves
    lives.
        Data show that years of life lost to rare diseases declined
    at an annual rate of 3.3 percent after the Orphan Drug Act due
    to the development of new treatments.
        Without these new drugs, if you take them out of the
    equation, the number of years of lives lost should have
    increased at about a 1 percent rate per year. So it has made a
    real impact on our patients.
        Speaking personally, without these treatments, many of my
    patients would not be here. I thank you for what you have
    already done.
        These efforts represent a good beginning, but there is much
    more we can do to improve the lives of our patients, and NORD
    views the 21st Century Cures Initiative as a great way to do
    this.
        NORD's long advocated increased involvement of patients in
    the drug development process. We appreciate the commitment by
    many at the FDA to increase patient involvement, but believe
    much more needs to be done to make patients feel they are
    partners in the process. NORD will continue to work with the
    FDA to advance the patient role in the development and approval
    process.
        We have developed a series of recommendations that we
    believe will advance not only the development of new orphan
    drugs and devices, but non-orphan ones as well. We look forward
    to discussing these ideas with the committee as the 21st
    Century Cures Initiative continues.
        Permit me to focus on two of our recommendations.
        First, we support the establishment of a commission and
    national plan to determine priorities, methods, resource needs
    and a consistent agenda on rare-disease registries and natural
    history studies.
        They have got a lot of variation. They tend to be all over
    the map. To assess the drug's efficacy, we need the information
    on the existence, frequency, and severity of clinical findings.
    This information is needed before a clinical trial can begin.
        We encourage the creation and maintenance of programs to
    create, curate, and standardize registries and national history
    studies which can generate this needed data.
        This could be one of the most important accelerators of the
    treatment development and monitoring process. These registries
    can also be used in the post-approval process as well.
        This is an area where patients can have a major and cost-
    saving impact on the process. Patient-entered data has been
    shown to be accurate and useful when collected properly.
        Creative hybrids using physician-, patient- and other
    health professional-collected data can greatly speed the
    understanding, discovery, approval and monitoring process.
        In collaboration with the NIH and FDA, NORD has built and
    is in the process of testing a rare-disease patient-driven
    registry national history program. The NIH's Rare Disease
    Clinical Research Network has already demonstrated the benefits
    of this approach.
        In a registry I have been involved with, we have had
    approval of three drugs over a 10-year period with only 700
    patients. So it definitely has accelerated the approval process
    for us.
        The Patient Centered Outcomes Research Institute is
    developing these statistical methods and models to use data
    from rare-disease patient studies that will further refine this
    process.
        They are also involved in patient-driven registries through
    PCORnet and will begin working with NORD on our rare disease-
    focused registry program. So we should have good input from
    multiple agencies.
        All of these efforts will help our patients, but a national
    plan and standards would help prevent duplicated effort and
    resources. This is what we truly need.
        The other thing we advocate is significant reform to the
    Institutional Review Board system. I have been working with
    this system for the last 30 years; so, I am pretty familiar
    with all of its manifestations.
        Currently, all clinical trials for new treatments, whether
    a drug, biologic or medical device, must receive approval from
    an IRB.
        Each institution and study site typically requires approval
    and protocol adjustment by its own IRB. With a large number of
    sites needed for rare-disease study, this is one of the
    greatest impediments and cost to clinical trials.
        NORD recommends that Congress develop legislation that
    would de-risk the process and foster the creation of an IRB
    system that is portable across institutions.
        The de-risking of the IRB process and the encouragement
    requirement of reliance agreements between institutions
    receiving Federal funding would save cost and time while
    accelerating the clinical trials and clinical research process
    greatly. This will significantly increase the pool of study
    sites and allow greater patient participation.
        These are just two of our recommendations. My written
    testimony includes the rest.
        And I on behalf of NORD, I thank the committee for allowing
    us to testify today.
        Mr. Pitts. Chair thanks the gentleman.

        [The statement of Dr. Summar follows:]

        [GRAPHIC] [TIFF OMITTED]

        Mr. Pitts. Thanks to all the witnesses for your opening
    statements. And we will now begin questioning.
        I will recognize myself 5 minutes for that purpose.
        Ms. Furlong, we will start with you.
        Do you believe your guidance collaboration with industry is
    a scaleable model that can be used in other conditions,
    specifically, where there are unique factors that make Duchenne
    muscular dystrophy guidance a special case in the multi-
    stakeholder effort that you led with encouragement from the
    FDA?
        Ms. Furlong. Thank you, Chairman Pitts, for the question.
        I certainly think that this methodology and process is
    exportable to other rare conditions. How we started the
    guidance or initiated the guidance was to develop a steering
    committee that was representative of the stakeholders, which
    included patients, academia, as well as industry.
        From there, the steering committee identified several
    areas, seven working groups, actually, of things that they felt
    were relevant, to include diagnosis, biomarkers, clinical trial
    design, natural history, and benefit-risk.
        And then we further developed a CAB, which is the Community
    Advisory Board, so that would be--incorporate the entire
    patient voice and any individual or patient group that wanted
    to contribute to the development of the guidance.
        The standardization for the guidance was that it would be a
    reference document and that it would include documented
    evidence that was published or accepted for publication by the
    end of July.
        So we felt--and we are writing up the methodology--that
    this methodology is exportable. It was certainly an
    investigation and a thorough, thoughtful, reasoned look at the
    community and the nuances of Duchenne.
        But I believe that most rare diseases could do the same.
    Their issues may be slightly different and their progress to
    date might be slightly different, but it is certainly
    exportable.
        Mr. Pitts. Thank you.
        Dr. Beall, communication with patients to make sure they
    can make informed decisions about clinical trial participation
    is critical.
        How does the cystic fibrosis community communicate with
    patients about the various options? And how do you think we can
    best translate your good practices into the Cures Initiative?
        Mr. Beall. Thank you very much.
        First of all, because 90 percent of all of our CF patients
    are seen in a network of care centers and that we also have a
    Clinical Trials Network, there is a very close relationship
    between our physicians and the patients that are involved.
        And that is critical for the recruitment of patients in the
    clinical trials. It is critically important for showing them
    the value and the risk of participating in clinical trials.
        And it is that close association between the physician and
    the patient and the recruitment process in a very closed
    network that is critical. That is why I think Clinical Trials
    Networks are critically important.
        So we also have established within our Clinical Trials
    Network a data safety monitoring board independent of the
    Cystic Fibrosis Foundation, but it is made up of experts.
        And that provides a degree of assurance to every single
    patient that there is somebody looking out for their continuing
    interest and for any risk that may be inherent in any single
    trial.
        So I think all of these things, plus we have worked very
    hard to try to create a culture of participation and a
    responsibility that each patient, when you have a small patient
    population, needs to participate in the process. So I think it
    is that reassurance that is so important.
        Mr. Pitts. Thank you.
        Mr. Pops, what stage of drug development could most use the
    assistance of patient insight about benefit expectations and
    risk tolerance?
        Mr. Pops. Thank you for the question.
        It is actually the most exciting part of the whole
    opportunity, that it is every stage, actually from
    identification of new drug candidates, all the way through to
    determination of the value of the medicine after the completion
    of the pivotal clinical trials.
        And I think that is the whole idea of this framework, is
    creating a structure where we can get that input on a
    continuous basis, and I think it could fundamentally transform
    the way we approach these development programs.
        Mr. Pitts. Thank you.
        Dr. Lichtenfeld, you have discussed examples of cancer
    drugs that have recently been successfully approved by FDA
    through an accelerated approval process.
        Are there best practices that we can learn from cancer and
    how FDA is expediting the approval process for particular
    drugs?
        Dr. Lichtenfeld. Thank you, Mr. Chairman.
        When we talk about best practices, I think the question
    really came up with Dr. Woodcock earlier today: What is the
    oncology community doing that is different than other
    communities?
        Let's understand it is a complex process in the sense that
    we have research that has been building literally for decades
    that has produced very exciting results that is actionable and
    companies are standing up to create drugs for the targets that
    we are finding for the new immunotherapies for genetic disease,
    what have you, genetic markers. So we are, in a sense, at an
    interesting and turning-point kind of place.
        But important, relevant to your question, the Office of
    Hematology Oncology Products has also stepped up to the plate.
    And as was mentioned earlier, the oncology community
    appreciates the efforts of the FDA staff to reach out to the
    patient community, to reach out to the pharmaceutical
    community, to reach out to those who do clinical trials, to be
    active participants, to be at the table.
        Lung-MAP was cited several times. The American Cancer
    Society was grateful to be able to have contributed to that
    effort, among many other organizations.
        But the FDA has become an active partner with the process.
    And so I don't know if that is a best practice or a best
    example. But it is that source of communication.
        But let's not forget it is also the opportunity because we
    are now in a place that we only dreamed of just a short while
    ago.
        Mr. Pitts. The chair thanks the gentleman.
        My time has expired.
        The chair recognizes the ranking member, Mr. Pallone, 5
    minutes for questions.
        Mr. Pallone. Thank you, Mr. Chairman.
        My questions are of Mr. Beall.
        The Cystic Fibrosis Foundation has done some great
    collaborative work that has resulted not only in successful
    marketing of Kalydeco, but also the recent positive test
    results of a complementary drug that may extend treatment to
    nearly half of all patients with CF. And, of course, I commend
    you for your efforts.
        But I wanted to ask you about a couple of points in your
    testimony. In your remarks, you spoke about the CF Foundation's
    strong relationship with the FDA and the importance of bringing
    good data to the table when consulting with the FDA, which I
    know is true. And I would like to hear more about that
    relationship.
        Obviously, we are hearing a lot today about the need for
    FDA to do more to seek and incorporate patient input into its
    review process.
        So the basic question, Mr. Beall, is: Can you tell us more
    about the CF Foundation's interaction with the FDA? And are
    there any lessons that can be learned by other disease groups?
        Mr. Beall. Well, I can give you a perfect example because,
    on Wednesday of this week, we had three officials, including
    Dr. Robert Temple, who is in the drug division at our offices,
    talking about the development of clinical trial protocols of
    drugs that might not enter into clinical trials until 3 to 5
    years from now.
        So that is a perfect example of this open discussion.
    Because we have a natural history of the disease. We know that
    the drugs that we have tested are treating the basic defect. We
    know the mechanism of action. We have a safety profile.
        And now we can start to talk about the future. And I think
    it is that kind of example. And that goes back many, many
    years.
        Soon after we discovered the CF gene, we talked about gene
    therapy and we had extensive dialogues with the FDA, not only
    with manufacturers, but with the FDA and the Foundation.
        So I could just say that we have always had a wonderful
    collaboration. We have data. We have natural history of the
    disease because of the patient registry.
        And, again, we come with data and we come with experience
    and we come with the networks that can make these things
    happen.
        So I just gave you an example. That was the example.
        Mr. Pallone. No. That is fine.
        We are hearing a lot about the various expedited drug
    review processes at FDA, and it is clearly a push by many to
    get the Agency to use these pathways more frequently and in
    more disease areas. And I share the goal of speeding the
    therapies to patient at the earliest possible time.
        But I think we need to be cognizant of the risks that could
    accompany that speed, and we especially need to be concerned
    about such risks if we are ultimately thinking about somehow
    requiring more frequent use of these expedited pathways through
    legislation. And I know you share that concern.
        Your testimony mentions the health risk that could result
    from approving therapies based on early data that needs more
    vigorous study, but you also describe the possibility that
    these kinds of approvals could endanger progress toward the
    development of other treatments.
        Can you just elaborate on both of those concerns, if you
    would.
        Mr. Beall. Well, certainly, one of the things when you are
    dealing with a small population--and now we are talking about
    personalized medicine where you may only have 25 patients with
    a certain genotype that may be approachable or therapeutic
    opportunities for that particular drug--if those patients were
    introduced to a drug that was less than effective, what happens
    when the next drug that could be effective--how do you do the
    clinical trial?
        So I think that is really very critical because we want to
    make sure that our first introduction is drugs that are
    efficacious, and then we move forward to the next level.
    Because then you really are depriving, if you don't have safe
    drugs, of developing good drugs and effective drugs that could
    move us above the therapeutic options that we have.
        So I think that that is the critical thing that we always
    face. There is always the risk. But now we are dealing with
    small populations, personalized medicine. Maybe there is only
    going to be 6, 10, 1,000 patients.
        So I think you have to be particularly critical on that
    issue with rare diseases.
        Mr. Pallone. OK. Yes. I just wanted to echo another point
    you made in your testimony about the importance of resources.
        And I couldn't agree more, that, as you say, FDA needs
    resources to ensure that they can rely on the best regulatory
    science available and they need adequate resources to enable
    them basically to meaningfully engage with the patient
    community.
        And we have this 21st Century Cures Initiative, which is
    progressing now. We have had some sort of larger meetings and
    now some hearings. And my colleagues always ask what can
    Congress do.
        And I think that the most effective thing we can do is
    provide adequate resources to make sure that FDA, as well as
    NIH, have the resources to fulfill the expectations we have for
    both agencies.
        And I hear not only from the agencies, but, also, from my
    constituents, that they don't have enough resources. So I just
    wanted to echo again what you said.
        Thank you, Mr. Chairman.
        Mr. Pitts. The chair thanks the gentleman.
        I now recognize the vice chairman of the subcommittee, Dr.
    Burgess, 5 minutes for questions.
        Mr. Burgess. Just before my time starts to run, could I
    make a unanimous consent request?
        Mr. Pitts. You may proceed.
        Mr. Burgess. I would like to move that the committee make
    people aware that, if someone wishes to contact or communicate
    with the Cures Initiative, it is cures@mail.house.gov.
        I know there are many people watching who think, ``I would
    like to interact with the committee staff.'' So that is the way
    to do it.
        Mr. Pitts. Thank you.
        Without objection, so ordered.
        Mr. Burgess. Very well. I knew they wouldn't deny me.
        Let me ask Ms. Furlong. You were kind enough to mention the
    work on the MD CARE Act, and thank you for that. As you know,
    we will likely be marking that up next week. So that is a big
    milestone.
        Can you talk about how the MD CARE Act needs updating and
    the type of updating that this committee has pursued?
        Ms. Furlong. Certainly. And thank you for the question, Dr.
    Burgess.
        The MD CARE Act was the solid foundation that set Duchenne
    and the muscular dystrophies--really galvanized their progress.
        So the MD CARE Act was enacted in 2001 and reauthorized in
    2008. And right now the amendments are really to look at what
    we have learned in the meantime.
        So the cardiac issues in Duchenne muscular dystrophy are
    real and they have to be tackled in order to answer the
    question. As you look at these potential therapies that were
    hopeful to be approved in the next months and years, they
    extend function. Will they protect or have a negative effect on
    the heart?
        So it is the gaps that we need to really look at with the
    amendments, in addition to the fact that, when this legislation
    was enacted in 2001, young boys with Duchenne didn't live to be
    adults.
        So now we have an adult population and we need to really
    address those adults in terms of their medical care and, also,
    to incentivize and understand how to treat them, how to
    encourage them to have long and independent lives as they
    become adults and reach for their dreams.
        So I think that the MD CARE Act is now looking with the
    muscular dystrophy committee from the NIH and other agencies.
    Their research plan has to be updated and these amendments to
    be incorporated so that we are really achieving the full effect
    that the MD CARE Act was initiated for.
        Mr. Burgess. Thank you.
        And of course, Mr. Beall will also acknowledge that the
    population of patients is changing because of some of the
    successes that have happened over the past several years.
        And in both of those illnesses, both cystic fibrosis and
    muscular dystrophy, it is important that we keep pace with the
    way the patient population is changing.
        We want people to live longer and fuller lives with their
    conditions and, at the same time, we don't want the legislation
    then to stymie that. So it is, in my opinion, an important step
    forward.
        Dr. Beall, we talked--or you talked about the development
    of mutation-specific therapies and the next evolution in
    precision medicine and you could see the cystic fibrosis
    example impacting the way we address other serious illnesses.
        Is there something more you would like to add to that?
        Mr. Beall. Well, again, we are clearly in the age of
    personalized medicine. Fortunately, with the completion of the
    human genome, we understand the genetics of so many more
    diseases and genetic diseases that it is a very critical time
    for us.
        Mr. Pitts. Microphone.
        Mr. Beall. Not on? OK.
        I just saw Dr. Collins downstairs, and he is excited
    because he was one of the discoverers of our CF gene.
        So we live in a very unique age, and I think more and more
    therapies are going to be directed towards specific mutations.
        And that is one of the reasons that we have to have these
    kinds of patient registries, so we can start to identify those
    mutations.
        When Vertex felt that they had a drug that might work on a
    certain mutation, the small drug that came out, G551D, we were
    willing--we were able to tell them in the United States we have
    1,100 of those patients within 5 minutes after they asked us
    because of a patient registry, because we have a documented
    history of the disease.
        So I think that is why it is very important to have
    personalized medicine, therapies and the options for that, but
    it is also--we have to be able to document the patients that
    can participate in the trials.
        Mr. Burgess. Yes. It is very powerful.
        And, of course, you referenced to the 1965 registry. In
    1965, you didn't know that we were going to know about the
    sequence of the human genome 30 years later.
        Mr. Beall. Well, but we have been able to document it.
    Today we have 26,000 patients whose data is provided to our
    patient registry every single year.
        Mr. Burgess. Let me ask you a question. I am going to run
    out of time pretty quickly. But--and this is either for Mr.
    Beall or Mr. Pops.
        The world is different now and you have people that are
    perhaps lucky enough to enter into a clinical trial and they
    are likely to perhaps have friends with the same condition.
        So in the old days, a randomized clinical trial, you
    wouldn't know which arm to which you were randomized, who was
    getting the target or study drug, who was getting either an
    older therapy or no therapy. But now people communicate.
    Facebook. Twitter. They are likely to be Facebook friends.
        How is that going to impact the ability to have a blind and
    randomized clinical trial? Are people likely to communicate
    with each other, I mean, look, ``I am getting a lot better on
    this stuff. How about you?'' ``Wait a minute. I haven't seen a
    darn thing''?
        Mr. Pops. I think it is a real question. It is a real issue
    because--and you can't pretend that it is not going to happen.
        This is already happening, particularly as you get large
    cohorts of patients in randomized studies in multiple
    countries. They are all communicating.
        So I think it is very important that we be really rigorous
    in maintaining the blind to the extent that we can.
        Mr. Burgess. To the extent that we can. But, also, we
    probably need to embrace the fact that the information is out
    there and being communicated and, to the extent that it can
    further enhance what we are doing----
        Mr. Pops. So let's take advantage of it.
        Mr. Burgess. Yes.
        Mr. Pops. Let's do more in the aftermarket. Let's approve
    drugs and collect this information and get a more nuanced view
    of the drugs' use in the real world and turn it to our
    advantage.
        Mr. Beall. And, in some cases, it is going to make it
    easier to do clinical trials when you can have large networks
    that exist out there, when they can report patient-reported
    outcomes and things like that.
        So I think sometimes it is looked at as a disadvantage, but
    we ought to turn it--as Mr. Pops just said, we ought to turn it
    to an advantage because I think it can expedite the ability to
    do clinical trials as we move forward with the technology.
        Mr. Burgess. Great. Thank you.
        Ms. Furlong. And it should expedite post-hoc analysis so
    that we can see the long-term effects. Because in a clinical
    trial of 12 months, for instance, plus or minus, you might not
    see the full effect of a drug that is multisystemic. So it will
    enable us to understand the full impact on the patients' lives.
        Mr. Burgess. Thank you, Mr. Chairman. I yield back.
        Mr. Pitts. The chair thanks the gentleman.
        Now recognize the gentlelady from Illinois, Ms. Schakowsky,
    5 minutes for questions.
        Ms. Schakowsky. Thank you very much.
        I had a question for Dr. Lichtenfeld--actually, for anyone
    on the panel that wants to comment on this.
        This is about quality-of-life outcomes. I mean, obviously,
    if this is a known life-threatening disease, you want to do
    everything you can to make sure that the therapies match the
    disease.
        But there are--you would say, when these quality-of-life
    outcomes are rigorously measured and supported by the FDA, they
    can and should be included in drugs' labeling and can by
    themselves be a basis for a drug's approval.
        I certainly know people who have suffered so much from side
    effects of drugs. And I just wonder, in the whole process of
    drug approvals, how much are these quality-of-life issues
    really looked at? As a basis for approval or just as a basis of
    whether or not they are used?
        Dr. Lichtenfeld. Thank you for your question.
        In fact, it is a work in progress. Let's understand that
    quality of life is a buzzword today, but it wasn't a buzzword
    very recently.
        So as we look at the issues, shall we say, of palliative
    care, of supportive care, quality of life, issues that the
    American Cancer Society and many others have been involved in,
    it is relatively new to the table.
        Having said that, there have been issues recently with one
    particular drug where, had the question really centered around
    was the--even though the drug may not have met the FDA
    standard--and this was about 2 years ago--even though it had
    not met the FDA standard, did it meet the quality-of-life
    standard? Did it improve the quality of life of the--it
    happened to be a breast cancer drug--for the women who took it?
        Because that would have been an important consideration.
    And, unfortunately, the quality of the data measuring quality
    of life was inadequate.
        So going forward, cancer patients have enough on their
    plates, as do everyone represented at this table, as do
    patients throughout this country. We need to be aware that
    quality of life is an important part of the treatment process,
    and we need to have tools in place.
        They are not uniform yet. They are not as good as we would
    like. But they have to be in place to measure quality of life,
    and that has to be considered. And patient-reported outcomes
    are very much a part of that process.
        Ms. Schakowsky. Yes. Go ahead, Doctor.
        Mr. Pops. I just wanted to make a comment as it relates to
    patients with chronic disease as well. We talked a lot about
    cancer and orphan, small diseases.
        We work in the field of chronic disease--schizophrenia,
    depression, addiction--where patients are taking medicines for
    long, long periods of time.
        And simple things that may seem prosaic to the researcher,
    like nausea----
        Ms. Schakowsky. Sure.
        Mr. Pops [continuing]. Fatigue, propensity to get addicted
    or dependent on the drug, these are really important inputs
    that we want to hear from patients about.
        Ms. Schakowsky. And is that part of the process?
        Mr. Pops. It is less part of the approval process today
    than I think it will be in the future. It is certainly part of
    the utilization process as patients make a determination,
    ``Which medicine do I want to stay on for years and months?'' I
    think that is a critical part of it, but it is not really
    incorporated in the consideration of the approval.
        Ms. Schakowsky. Especially where all things might be equal
    in effectiveness, whether or not something causes nausea,
    fatigue, could be really important.
        Mr. Pops. That is right. Particularly if you are launching
    a new medicine into a large category where there might be an
    abundance of generic drugs that are safe and effective, but
    might not hit all of those parameters for certain subsets of
    patients for long periods of time.
        And we just want people to be sensitive to the fact that,
    from the patient perspective, there are differences between the
    medicines.
        Ms. Schakowsky. Right.
        And then, also, Dr. Lichtenfeld, I wanted to ask you about
    small-sized trials. And you mentioned one of the drawbacks.
        I had talked about the extent to which women aren't
    considered. And I would just be concerned--I understand the
    plus. I do. But if we rely too heavily on them, isn't there the
    real risk of excluding important populations?
        Dr. Lichtenfeld. Well, the answer is yes, there is a real
    risk of excluding important populations.
        In fact, when you talked about women and heart disease, I
    remember back in the early 1990s when the article came out
    talking about the absence of women in clinical trials for the
    treatment of hypertension and heart disease. So this is an
    issue I am aware of.
        But let's talk about the other side of the coin, and that
    is, when you are sitting--I have sat in the presentations at
    ASCO, at oncology meetings--and you see a presentation of 80
    patients and you see what we call waterfall plots--basically,
    the responses in survival that occur--and suddenly, 70 percent
    of those patients are having significant responses, In a
    disease where there was no treatment before, I don't think one
    asks the question--they ask the question in followup, but not
    at the moment.
        And what has happened and what has been exciting to me is I
    am now sitting in those presentations every June and I see--I
    wrote about it--it took a year for one of the drugs to go from
    clinical trial to approval because it was that effective in the
    disease where there was no other treatment available. That is
    pretty spectacular. That is new thinking. That is a new
    approach.
        Now, we have learned more as time has gone on. Yes. Doesn't
    mean we have stopped learning, as was mentioned before about
    cystic fibrosis. But when you suddenly see moments like that,
    no one would want to hold back. Develop the data, yes, but
    don't hold back the opportunity.
        In fact, even a phase 1 trial that was presented at this
    ASCO meeting in June, the company, actually--well, not the
    company, but ASCO in the press release indicated the company
    was willing after a phase 1 trial to put it into compassionate
    use. And that is pretty amazing, a major change in the way that
    traditionally we have seen cancer drugs move through the
    pipeline.
        Ms. Schakowsky. Thank you.
        I have overstayed my time. Thank you.
        Mr. Pitts. Sure. Thanks to the gentlelady.
        I now recognize the gentleman from Virginia, Mr. Griffith,
    5 minutes for questions.
        Mr. Griffith. Dr. Lichtenfeld, let's pick up there, because
    I think that that compassionate use is something that--we
    really need to be figuring out how we can make it more
    effective and how we can do it faster at the Federal level.
        You talked about in your testimony that patients needed to
    be involved both on saying what kind of nausea they had and
    what the pain levels were and so forth, and I agree with that.
        But I also think that, particularly when you have no
    treatment, that patients need to be involved in that, too. And
    as Ms. Furlong said earlier, when there isn't a treatment, you
    are much more willing to take those risks than you would be if
    there is some other treatment out there that might work, but
    this might be a little more comfortable.
        And I want to give both you and Ms. Furlong an opportunity
    just to address that further.
        Dr. Lichtenfeld. Well, thank you. And I appreciate the
    question, and I know you mentioned it earlier.
        It is a complex issue. It is not a new issue. As you may
    well be aware, it has been around for some time with the number
    of drugs that have gone through the pipeline, which seem to
    show some opportunities. Various state legislatures are
    involved.
        And I am sitting here today both as a representative of the
    Society, but also as an individual, and understand that there
    are discussions on both sides of that issue and they are
    complicated.
        Bottom line is that we need to understand what drugs work
    when they work. We need to understand that patients need to
    have access to promising drugs as soon as possible.
        Companies make those decisions as to how they are going to
    handle that process. The FDA, as a matter of fact, has approved
    almost all of the applications they received. And we need to
    have those discussions to come to a better resolution about how
    to address that issue.
        Mr. Griffith. And what I would say is that whatever we can
    do--I think I speak for a lot of the members of the committee--
    I am probably a little more out there than some--but whatever
    we can do to help by changing the law to expedite that process,
    we will do.
        Dr. Lichtenfeld. We would be glad to have those discussions
    on behalf of the Society, sir.
        Mr. Griffith. Ms. Furlong, did you want to make another
    comment about risk assessment? Because, obviously, when your
    boys were sick, you probably would have taken anything that had
    any promise of hope.
        Ms. Furlong. I think I could tell you stories about looking
    in China to see some tea that you might be appalled about, but
    that was long ago.
        I think it really is up to the companies. FDA has always,
    to my knowledge, at least in the Duchenne and other fields,
    been willing to entertain and talk about compassionate use.
        I think for the rare disease community this really talks
    about and gets us back to trial design.
        In general, trials are designed to test a small subset of
    patients. In the Duchenne community, the 6-minute walk test is
    the standard primary outcome measure.
        So that means, as a child with Duchenne, you have to walk 6
    minutes and even further, as we learn more about the testing.
    It is a very narrow subset of people within a certain framework
    of that 6-minute walk test, which, as you can imagine, leaves a
    great number of people outside the trial.
        So I think trials have to be designed that are inclusive
    and welcoming of people that live with the spectrum of the
    illness, both very young as well as adults with very limited
    functional ability.
        That way, we can test those in those populations. We can
    have labels that are broad and then provide access to all. So I
    think that might be a better solution.
        Mr. Griffith. Thank you.
        I look forward to working with you all.
        And, with that, I yield the remainder of my time to Dr.
    Burgess.
        Mr. Burgess. I thank the gentleman.
        Dr. Lichtenfeld, I just wanted to follow up with you
    because your specialty has been involved in this type of
    activity probably longer than any other branch of clinical
    medicine, going back to 1955 when the developmental
    therapeutics program was put into place at the National Cancer
    Institute.
        So with that breadth of experience within your specialty,
    are there things that you want to share with others about what
    that experience has taught you?
        Dr. Lichtenfeld. Well, what we did back in 1965 or whenever
    was a lot different than what we are doing today. I don't want
    to take the time to really go into it. You may be aware of it.
        But here is the message. It didn't happen overnight. It
    took 40 years of research to get us to the tipping point where
    we understood the genome and had the opportunity to take
    advantage of that and move forward.
        Immunotherapy, the same story. It has taken us 40 years.
    That was a substantial amount--I don't want to underestimate
    the value of research investment to get us to the point where
    we are, where suddenly we look like we have so much to offer
    and to do.
        I also comment, with regard to my co-panelists, that they
    have populations and they have demonstrated that finding the
    patients where they are is critically important.
        We have a substantial amount of work to do to understand
    not only the clinical trial mechanism, but also the medical
    practice system, so we can make sure that patients and
    communities--I live in a small town in south Georgia--that my
    friends have opportunities to get these drugs in clinical
    trials and be part of that process. There is a lot of work to
    do.
        Mr. Burgess. Thank you, Mr. Chairman. I yield back.
        Mr. Pitts. The chair thanks the gentleman.
        Now recognize the gentleman from New York, Mr. Engel, 5
    minutes for questions.
        Mr. Engel. Thank you, Mr. Chairman and Mr. Pallone, for
    holding this hearing. I am pleased to have this opportunity to
    further consider how patient perspectives can best be
    incorporated into the therapeutic development process.
        As the author of the ALS Registry Act and the Paul D.
    Wellstone Muscular Dystrophy Community Assistance Research
    Education Amendments of 2008 and 2013, along with my colleague,
    Dr. Burgess, I have worked to be a voice with those with rare
    and orphan diseases.
        I am encouraged by the advances we have made into the
    causes and mechanisms of these diseases, as well as our
    progress toward treatments, but, obviously, we still have a
    long way to go.
        One of the most striking gains we have made is for
    individuals with Duchenne muscular dystrophy. As Ms. Furlong
    mentioned, our efforts have added an average of 10 years to the
    life expectancy of boys with Duchenne. And now, as life
    expectancy increases, we face new challenges in finding
    effective therapies.
        The patient community brings an important perspective and
    understanding to this process, and I am interested to see how
    we can best use that knowledge to assist medical researchers
    with therapy developments.
        So, Ms. Furlong, let me ask you this. I am particularly
    interested in the way the Duchenne patient community is engaged
    with the FDA to help inform the benefit-risk determinations
    made by agency reviewers, as well as the Duchenne community
    guidance document you referred to in your prepared testimony.
        Could you please comment on how you hope to see these
    efforts affect the therapeutic pipeline and the various
    stakeholders who are part of that pipeline.
        Ms. Furlong. Yes. Thank you, Mr. Engel, for the question.
        The benefit-risk really originated out of discussions with
    the FDA because, in our early discussions, it was known that we
    were telling anecdotal stories that the equation of benefit-
    risk was different in, for instance, Duchenne muscular
    dystrophy than perhaps some more common disease.
        And in that the FDA suggested to us that they agreed, but
    they didn't have anything they could rely on, any quantified
    evidence-based document that could help them make those
    decisions.
        So we agreed to go out on benefit-risk and did the pilot
    with 120 parents. We learned that their priority is disease
    stabilization and they were willing to accept a great deal of
    risk. In fact, they are living with a great deal of risk, as
    they know that their child has a fatal illness.
        So the FDA has now asked us to expand that study to a
    greater number of patients than 120 patients and, also, to ask
    these questions of the young men with Duchenne. Our hope is
    that they will incorporate it into the review process and they
    will demonstrate to us how and when they use it and when they
    don't and what makes sense for them as they make their
    decisions.
        Mr. Engel. Thank you. And thank you for your advocacy and
    hard work. It is very much appreciated.
        Dr. Summar, can you talk about the role you think the
    patient perspectives should play in developing therapies for
    diseases like ALS and muscular dystrophy that have limited
    treatment options and for which quality of life is, obviously,
    an especially important factor to patients.
        How can the FDA best consider the views of patients and
    families when examining the benefit-risk calculus for these
    diseases?
        Dr. Summar. Thank you for that question, Mr. Engel.
        This really kind of expands across the entire field of rare
    diseases, but your question is particularly relevant for those
    two groups.
        Patients often tell us about things that they wish were
    better that we never thought of. One of the things I have run
    across time and time again is, when we go and ask our patients,
    ``What is the worst part of this disease?''--a lot of times it
    is parents in the case of pediatric patients--they will list
    some things. And sometimes the things we thought were most
    important are number nine or ten on the list.
        So I think, when we look at what our therapeutic targets
    are, what our quality-of-life targets are for these diseases,
    patient and family input is a huge factor, and I think it is
    something we can incorporate a lot better than we have.
        I think during the early stages, particularly when we are
    designing our pivotal trials, clinical trials, looking at what
    end points are--I think that those are going to become more and
    more important.
        And the other thing, of course, is the small group sizes
    with these. Many times it is hard to pick one single outcome
    variable that you are going to be able to achieve.
        The smallest study I have been involved with was five
    patients for an approval process. Getting one exact target for
    that--fortunately, the effect of the drug was massive; so, we
    were able to do it. But if it had been milder, I might have
    needed more than one outcome variable.
        So I think families can help us determine what is important
    there. They can help us, also, as we talked about with some of
    what risk is tolerable in those situations. It is different.
    And there are 7,000 different rare diseases. Each one of these
    is unique in its own regard. But there are some commonalities
    like that.
        Mr. Engel. Well, thank you. And thank you for your
    comments, and also thank you for your interest.
        And I want to thank the panel for a very interesting
    discussion.
        Thank you, Mr. Chairman.
        Mr. Pitts. The chair thanks the gentleman.
        Now 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.
        I know we have been talking about this and you have had an
    opportunity. I want to give you more of an opportunity to
    respond on this.
        On Wednesday, I asked one of the witnesses about his
    statement in including patients in the clinical trial process,
    but I want to make sure that you all have every opportunity to
    respond to this.
        If patients had a greater role in clinical trial design--
    and I know you have touched upon this--if trials measured
    qualitative data from patients like, ``How do you feel?'', ``Is
    it less painful?'', what have you; ``How would things be
    different?'' and ``What would you like to see?''
        We will start with the----
        Mr. Beall. I would like to start.
        First of all, the patient-reported outcomes I think has
    been part of every clinical trial in cystic fibrosis for the
    last 10 or 15 years. Some of the tools are not the best at this
    point, but we are working to refine them.
        We have just spent as a Foundation a large effort to look
    at the patient-reported outcomes as a kind of specific
    validated tool for CF, and it is going to be submitted to the
    FDA and go through a validation process. In the past, we have
    used one that was generally for lung disease, but it may not be
    specific.
        So this is a science that is evolving. A decade ago or 15
    years ago, 20 years ago, PROs were not really incorporated.
        So it is a science that is evolving, and it has to be
    evolved not only with the FDA, it has to be evolved with the
    sponsors, too, because they have got to be willing to
    incorporate those into the clinical-trial process.
        So I am encouraged by the process, but I will tell you
    the--just in this last trial we had where their lung function
    went up and the exacerbations went down, we didn't have a
    statistically significant improvement in the patient-reported
    outcomes.
        Because when you are starting to treat the basic defect,
    you are treating the whole disease process and you are looking
    at extending lives.
        And the patients may not feel that from day to day, but
    over years, you may have a tremendous impact on those patients.
    So it is a tool that can be used, but it shouldn't be used
    exclusively.
        Mr. Bilirakis. Thank you very much.
        Ms. Furlong, do you have a response?
        Ms. Furlong. Sure.
        So I agree with Dr. Beall. And patient-reported outcomes
    are incredibly important, but I think this is where involving
    the patients in the design and conduct of clinical trials is
    really going to be important.
        Because, for instance, how do we measure energy and
    endurance? How do we know that turning over in bed is important
    to patients as opposed to an outcome measure such as the 6-
    minute walk test?
        So I think things are important to patients that have a
    real effect on their lives. For instance, as you can imagine,
    if a boy can still text at the age of 18, that gives him
    independence. If a child can walk up a single step, they can
    enter buildings. If a child can roll over in bed, that makes
    the families' quality of life overall, in general, much, much
    better.
        So I think the use of patient-reported outcomes and
    including the patient voice in the discussion about what the
    clinical trial looks like and what the measurements are, both
    primary and secondary, is going to be incredibly important.
        Mr. Bilirakis. Thank you so much.
        Mr. Pops, do you have a comment or----
        Mr. Pops. I think these outcomes are so critical. In the
    world that we are developing drugs in, which is in psychiatry
    often, in schizophrenia, depression, addiction, the end point
    of the clinical trial--the hard end point is asking people
    essentially how they feel.
        And so how you feel is typically embodied in the set of
    validated scales, but those often don't capture some of the
    most important parts of how they actually feel over time.
        A perfect example might be an opioid dependence or an
    alcohol dependence, where a critical question the patients ask
    us when they take our medicine is, ``Is my craving going to go
    down? Am I going to crave this less? It may block the receptor
    and keep me from drinking, but is my craving going to change?''
        That was not a validated end point. That was something we
    couldn't incorporate in the label, but it is essential to the
    patient's perception of the disease.
        Mr. Bilirakis. Good point.
        Doctor?
        Dr. Lichtenfeld. About 4 weeks ago at ASCO, the oncology
    meeting, they showed a picture of a lady who was 96 years old
    who had received a phase 1 drug--that in itself is a
    fascinating point--whose cancer completely resolved.
        And on the bottom end of the before and after picture--on
    the after picture, you saw a trace of a little smile. And I
    noticed that smile and I tweeted it, actually. I took a picture
    and tweeted it and it got re-tweeted quite a bit. And then the
    lecturer said, ``Yes. That really is a smile'' in front of
    2,000 people.
        What I am trying to say by that example is that is what we
    have to be able to measure and aggregate in a scientific way to
    show that the treatments make a difference.
        One example of one lady in an unusual situation, but
    something that I think all of us agree--I would echo the
    comments that were already made--is so critical to
    understanding, particularly in the oncology world, what we do
    and how we do it and the goal that we have to have of improving
    quality of life.
        Mr. Bilirakis. Thank you.
        Dr. Summar?
        Dr. Summar. Yes. I will just use another example, too.
        We had a new medication we were looking at. Most of the
    patients with rare diseases are on the medicines they take for
    life. So it is every day, day in and day out. And these care
    plans are often complex and they really affect the whole
    family.
        So the new drug looked like it was promising from the
    standpoint of maybe a little bit better efficacy, a little bit
    better control, but it was five times a day instead of two or
    three times a day compared to the old one.
        And the families were like, ``Why would we add three more
    times a day of dosing for the small effect?'' And no one had
    really bothered to ask them that before we started.
        So I think there is all of these things that really getting
    the patient input early on is going to make a difference.
        Mr. Bilirakis. Thank you so much. Appreciate it.
        Mr. Chairman, can I ask one more question?
        Mr. Pitts. You may proceed.
        Mr. Bilirakis. OK. Thank you so much. Appreciate it.
        Dr. Beall, the CF Foundation's venture philanthropy model
    has produced incredible results. Congratulations. Your
    foundation found your breakthrough drug when it helped
    translate some of the early research through the valley of
    death, and now you have the Kalydeco.
        How are you able to establish this program? And how can
    other groups adopt this similar model?
        Mr. Beall. Well, it is a willingness to take risks. That is
    what you have to do in drug discovery. And we were frustrated
    by the fact that companies were not getting involved in the
    orphan diseases.
        So the whole concept here was to say, ``Take some of the
    risk out of biotech companies or pharmaceutical companies to
    get engaged in CF research.'' And, as I said, we spent $42
    million initially to start a high-throughput screening that led
    to Kalydeco.
        I think what is the most important and gratifying thing for
    the Cystic Fibrosis Foundation--and I know Ms. Furlong was in
    my office a number of years ago--and what we are seeing is so
    many other organizations are feeling the same impatience that
    our foundation felt 14 years ago in adopting this.
        One of the first times I talked about venture philanthropy
    at the bio meetings, we had 10 people in the audience. And now
    it is really becoming really inherent in what many voluntary
    health organizations are doing.
        In fact, FasterCures has been an organization that has been
    central to making some of that happen. There are law firms that
    specialize in it.
        So we love to share our ideas. We share our ideas all the
    time. And it has been very gratifying to our community that we
    happen to be fortunate enough to be able to start it because we
    had the resources. Bill and Melinda Gates gave us $20 million
    to start our program. We had other dollars to really make that
    initial investment.
        Mr. Bilirakis. Can you tell us how you successfully
    established the CF registry?
        Mr. Beall. As I say, it goes back a long time. But Dr.
    Zerhouni was here several years ago when he was the head of the
    NIH, and he says one thing about the CF community, it is a
    community with a culture of research.
        And every patient who goes to one of our care centers is
    asked, ``Do you want to participate in a patient registry?''
    And I think it is 99.5 percent of the patients that say, ``Yes,
    I do'' and then signs the informed consent.
        So it is all part of the culture. It is part of the culture
    the organization creates. It is the physicians and it is the
    relationships and the recognition that it is an important part
    of having a disease because we can't cure this disease without
    their involvement.
        Mr. Bilirakis. Very good. Thank you very much. Appreciate
    it.
        I yield back, Mr. Chairman.
        Mr. Pitts. The chair thanks the gentleman.
        Dr. Summar, I didn't get to you in my round.
        On Wednesday, we heard an idea thrown out there that there
    are vast amounts of data available that are not being utilized.
    And we all know what an organ donor is. The idea was that we
    have data donors.
        Now, how would this play--and you mentioned the IRB system,
    the risk enterprise. What is your reaction to that?
        Dr. Summar. This is something we talk about when we are
    having coffee a lot.
        There are data sets all over the place. In fact, most of
    them end up usually lost when someone's computer gets recycled.
    We had a physician lose 15 years of data because his Excel
    spreadsheet didn't update.
        I think a way--find a way that balances, obviously,
    people's desire for confidentiality versus the irreplaceable
    and oftentimes irreproducible amounts of data that are out
    there. We really do need to find that balance.
        My reaction to that would be I would love to find a way
    forward with that. That one is going to--you can see a lot of
    sides to that question. But I definitely think it is worth
    looking at.
        And I think what we find is a lot of patients are like,
    ``Yes. I will put it out there. I am fine with that.'' There
    will be a small core that won't. You can take a count for that.
    But I think most folks, if you ask them, saying, ``Would you
    feel OK if your data is out there so everybody can take a look
    at it?'' would be fine.
        You see people opening up their genomes, who had their
    genomes sequenced, saying, ``I will publicly post it along with
    my medical health history.'' A lot of folks want to help.
        Mr. Pitts. Thank you. Thank you.
        Mr. Burgess. I did that. We did that. I mean, that is a
    real thing that is happening right now. And, yes, privacy is
    something we all value, but it also is a voluntary
    relinquishing of a portion of that for the greater good.
        I think that is something we ought to not encourage--well,
    not encourage, but we certainly shouldn't stand in the way if
    that is an activity that----
        Dr. Summar. Right.
        Mr. Burgess. And unfortunately, I can't say that we don't
    always respect that, that we shouldn't stand in the way. But
    enough about that.
        Mr. Pitts. All right. The chair thanks the gentleman.
        That concludes the questions of the Members who are here.
    Another exciting, informative, very important hearing. Thank
    you so much for coming.
        Members will have followup questions, and we will send
    those to you. We ask that you please respond promptly. I remind
    Members they have 10 business days to submit questions for the
    record, and that means Members should submit their questions by
    the close of business on Friday, July 25th.
        I have a UC request, a statement for the record, from the
    National Health Council. Without objection, that will be
    inserted into the record.
        [The information appears at the conclusion of the hearing.]
        Mr. Pitts. Without objection, the subcommittee is
    adjourned.
        [Whereupon, at 12:19 p.m., the subcommittee was adjourned.]

        [Material submitted for inclusion in the record follows:]

        [GRAPHIC] [TIFF OMITTED]
                                     [all]