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

             EXAMINING MEDICAL PRODUCT MANUFACTURER COMMUNICATIONS

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

                                    HEARING

                                   BEFORE THE

                             SUBCOMMITTEE ON HEALTH

                                     OF THE

                        COMMITTEE ON ENERGY AND COMMERCE
                            HOUSE OF REPRESENTATIVES

                         ONE HUNDRED FIFTEENTH CONGRESS

                                 FIRST SESSION

                                   __________

                                 JULY 12, 2017

                                   __________

                               Serial No. 115-44

     [GRAPHIC NOT AVAILABLE IN TIFF FORMAT]

          Printed for the use of the Committee on Energy and Commerce

                            energycommerce.house.gov

                                   __________

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                        COMMITTEE ON ENERGY AND COMMERCE

                              GREG WALDEN, Oregon
                                     Chairman

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

                             Subcommittee on Health

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

                                      (ii)

                                 C O N T E N T S

                                  ----------
                                                                       Page
    Hon. Michael C. Burgess, a Representative in Congress from the
      State of Texas, opening statement..............................     1
        Prepared statement...........................................     2
    Hon. Gene Green, a Representative in Congress from the State of
      Texas, opening statement.......................................     4
    Hon. Greg Walden, a Representative in Congress from the State of
      Oregon, opening statement......................................     5
        Prepared statement...........................................     6
    Hon. Frank Pallone, Jr., a Representative in Congress from the
      State of New Jersey, opening statement.........................     7
        Prepared statement...........................................     9

                                   Witnesses

    Coleen Klasmeier, Partner, Sidley Austin, LLP....................    10
        Prepared statement...........................................    13
        Answers to submitted questions...............................   154
    R. Alta Charo, Warren P. Knowles Professor of Law, University of
      Wisconsin......................................................    23
        Prepared statement...........................................    26
        Answers to submitted questions...............................   164
    George Van Hare, M.D., President, Heart Rhythm Society...........    28
        Prepared statement...........................................    30
        Answers to submitted questions...............................   169
    Aaron S. Kesselheim, Associate Professor of Medicine, Harvard
      Medical School and Brigham and Women's Hospital................    36
        Prepared statement...........................................    38
        Answers to submitted questions \1\...........................   174
    Linda House, President, Cancer Support Community.................    46
        Prepared statement...........................................    49
        Answers to submitted questions...............................   178
    Katherine Wolf Khachatourian, Vice President, Delegation
      Oversight, Pharmacy Services, and Strategy, Qualchoice Health
      Plan Services, Inc.............................................    55
        Prepared statement...........................................    57
        Answers to submitted questions \1\...........................   183

                               Submitted Material

    Discussion Draft, H.R. ___, Facilitating exchange of information
      prior to approval..............................................   108
    Discussion Draft, H.R. ___, Communications regarding intended
      uses of drugs and devices; scientific exchange.................   112
    Letter of July 10, 2017, from Academy of Managed Care Pharmacy,
      et al., to Mr. Guthrie, submitted by Mr. Guthrie...............   115
    Letter of May 2, 2017, from the Alliance of Specialty Medicine,
      to Mr. Griffith, submitted by Mr. Griffith.....................   117
    Letter of May 16, 2017, from Dystrophic Epidermolysis Bullosa
      Research Association of America, Inc., et al., to Mr. Griffith,
      submitted by Mr. Griffith......................................   118
    Letter of May 5, 2017, from Mary R. Grealy, President, Healthcare
      Leadership Council, to subcommittee leadership, submitted by
      Mr. Griffith...................................................   120

    ----------
    \1\ Dr. Kesselheim and Ms. Khachatourian did not answer submitted
      questions for the record by the time of printing.
    Letter of July 11, 2017, from Michael Carome, M.D., Director,
      Public Citizen's Health Research Group, to Mr. Burgess and Mr.
      Green, submitted by Mr. Green..................................   122
    Statement of John Rother, Executive Director, The Campaign for
      Sustainable Rx Pricing, July 12, 2017, submitted by Mr. Green..   143
    Statement of America's Health Insurance Plans, July 12, 2017,
      submitted by Mr. Green.........................................   147

             EXAMINING MEDICAL PRODUCT MANUFACTURER COMMUNICATIONS

                                  ----------

                            WEDNESDAY, JULY 12, 2017

                      House of Representatives,
                                Subcommittee on Health,
                              Committee on Energy and Commerce,
                                                        Washington, DC.
        The subcommittee met, pursuant to call, at 10:18 a.m., in
    Room 2322, Rayburn House Office Building, Hon. Michael C.
    Burgess (chairman of the subcommittee) presiding.
        Members present: Representatives Burgess, Guthrie, Barton,
    Upton, Shimkus, Blackburn, Lance, Griffith, Bilirakis, Bucshon,
    Brooks, Mullin, Hudson, Collins, Carter, Walden (ex officio),
    Green, Engel, Schakowsky, Butterfield, Matsui, Castor,
    Sarbanes, Kennedy, Cardenas, Eshoo, and Pallone (ex officio).
        Staff present: Adam Buckalew, Professional Staff Member,
    Health; Daryll Dykes, Health Fellow; Paul Edattel, Chief
    Counsel, Health; Adam Fromm, Director of Outreach and
    Coalitions; Jay Gulshen, Legislative Clerk, Health; Alex
    Miller, Video Production Aide and Press Assistant; Jennifer
    Sherman, Press Secretary; Danielle Steele, Policy Coordinator,
    Health; John Stone, Senior Counsel, Health; Hamlin Wade,
    Special Advisor for External Affairs; Jeff Carroll, Minority
    Staff Director; Samantha Satchell, Minority Policy Analyst;
    Andrew Souvall, Minority Director of Communications, Member
    Services, and Outreach; Kimberlee Trzeciak, Minority Senior
    Health Policy Advisor; and C.J. Young, Minority Press
    Secretary.
        Mr. Burgess. The Subcommittee on Health will now come to
    order. I will recognize myself for 5 minutes for the purpose of
    an opening statement.

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

        From last year's 21st Century Cures Act to this year's Food
    and Drug Administration reauthorization, this subcommittee has
    been committed to bringing Federal regulation into the modern
    era of medicine. Today, we continue that work by examining
    legislation to update the regulatory framework affecting the
    dissemination of truthful and nonmisleading information about
    products approved by the Food and Drug Administration.
        I practiced medicine for several decades. I know firsthand
    how challenging it is it and how challenging it can be for
    providers to stay up to the minute with cutting-edge
    information in both medicine and science. Following the Food
    and Drug Administration's approval of a product, the use of
    that product rapidly evolves based on patient and provider
    experience. Frequently, the standard of care for a condition is
    outside of the Food and Drug Administration-approved labeling.
    Ensuring that healthcare providers have access to new
    information generated by real-world evidence is critical to
    optimizing patient care and outcomes. Particularly in medicine,
    the old adage holds true, knowledge is power.
        Our legal framework for the regulation of manufacturer
    communications sometimes prevents healthcare professionals from
    receiving the most current scientific information available
    about the benefits and risks of FDA-approved medicines. A lack
    of relevant information can lead to physicians making patient
    care decisions with incomplete information. This is both unfair
    to the physician and unsafe for the patient.
        We owe it to the patient and medical communities to ensure
    that there is free and full dissemination of truthful and
    nonmisleading scientific and medical information for healthcare
    professionals.
        I certainly want to thank two of our committee members, the
    vice chairman of the committee, Brett Guthrie, and
    Representative Morgan Griffith from Virginia for offering the
    bills that will be under discussion today. I feel they offer a
    targeted approached to addressing the problems presented by our
    regulatory framework for medical product communication. And, if
    he would like time, I am prepared to yield to the gentleman
    from Kentucky, if he would like time for an opening statement.
        [The prepared statement of Mr. Burgess follows:]

                 Prepared statement of Hon. Michael C. Burgess

        From last year's 21st Century Cures Act, to this year's FDA
    Reauthorization, this subcommittee has been steadfast in its
    commitment to bring Federal regulation into the modern era of
    medicine. Today we will continue that work by examining
    legislation to update the regulatory framework affecting
    dissemination of truthful and nonmisleading information about
    FDA-approved products.
        I practiced as a physician for several decades, and so I
    know firsthand how challenging it can be for providers to stay
    abreast of cutting-edge information in medicine and science.
    Following FDA-approval of a product, the use of that product
    rapidly evolves based on patient and provider experience.
    Frequently the standard of care for a condition is outside of
    the FDA-approved labeling. Ensuring that healthcare providers
    are able to access new information generated by real-world
    evidence is critical to optimizing patient care and outcomes.
    Particularly in medicine, the old adage holds true-knowledge is
    power.
        Unfortunately, our legal framework for the regulation of
    manufacturer communication prevents healthcare professionals
    from receiving the most current scientific information
    available about the benefits and risks of FDA-approved
    medicines. A lack of relevant information can lead to
    physicians making patient care decisions with incomplete
    information. This is both unfair to the physician and unsafe
    for the patient.
        We owe it to the patient and medical communities to ensure
    that there is free and full dissemination of truthful and
    nonmisleading scientific and medical information to healthcare
    professionals.
        I would like to yield the balance of my time to Vice
    Chairman Guthrie and Representative Griffith to discuss their
    bills--each of which is a targeted approach to addressing the
    problems presented by our outdated regulatory framework for
    medical product communication.

        Mr. Guthrie. Thank you, Mr. Chairman. There is another very
    important hearing on opioids going on downstairs, and we have
    our Kentucky Justice Secretary there.
        Mr. Chairman, I want to thank you for holding this hearing
    today to examine communications between manufacturers and
    healthcare payers which I addressed in my bill, H.R. 2026, the
    Pharmaceutical Information Exchange Act. My bill will enable
    greater information exchange in order to guide health plans,
    pharmacy benefit managers, and others who develop prescription
    drug formularies and medical devices to make well-informed
    decisions about the benefits and costs of medications and
    medical devices for the populations they cover.
        Patients benefit when these formulary decisions are
    informed by the most recent and reliable scientific evidence on
    drugs and devices beyond just what we learn from the clinical
    trials conducted by FDA approval. Our committee has addressed
    post-approval information exchange. We should take the next
    logical step by addressing what information can and should be
    exchanged preapproval by considering the updated discussion
    draft we are examining today.
        I would like to submit for the record a letter of support
    for my bill by a number of organizations, including the Academy
    of Managed Care Pharmacy, Humana, Sanofi, and Mayo Clinic.
        Mr. Burgess. Without objection, so ordered.
        [The information appears at the conclusion of the hearing.]
        Mr. Guthrie. Thank you, Mr. Chairman. I yield back.
        Mr. Burgess. The Chair thanks the gentleman. The Chair
    would like to recognize the gentleman from Virginia, Mr.
    Griffith, if he would seek time for an opening statement.
        Mr. Griffith. Thank you very much, Mr. Chairman, I do
    appreciate it. Mr. Guthrie and I were both downstairs
    introducing former colleagues from the House of Delegates, so
    we apologize that we came rushing in, but we got that done.
        The draft version of my bill that we are discussing today
    will responsibly set the rules of the road so that
    manufacturers have the most accurate and up-to-date information
    about their products that can provide doctors and researchers
    with that information, and in the appropriate context, to
    improve patient care and facilitate additional research.
        Not only does the lack of clear rules have a public health
    ramification, but also it has legal consequences. There have
    been a number of court decisions that raise significant First
    Amendment questions about the FDA's authority to restrict a
    drug or device manufacturer from communicating truthful and
    nonmisleading off-label information about their products.
        The Judiciary Branch should not be turned into de facto
    policy makers because of FDA's misunderstanding of the law or
    our inaction here in Congress.
        I remain open to any and all suggestions from both sides of
    the aisle and from stakeholders as to how this legislation may
    be improved, but I am glad we are continuing the dialogue.
    Also, I also forward to hear from witnesses today about how the
    FDA's vague policies hinder the facilitation of information to
    healthcare providers and how this legislation could be a first
    step in addressing some of the challenges that we will hear
    about. Thank you. I yield back.
        Mr. Burgess. The gentleman yields back, and the Chair yield
    back. The Chair recognizes the ranking member of the
    subcommittee, Mr. Green, 5 minutes for an opening statement,
    please.

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

        Mr. Green. Thank you, Mr. Chairman. Today, we are
    considering two draft bills addressing pharmaceutical
    manufacturer communications on medical products. The Medical
    Product Communications Act and the Pharmaceutical Information
    Exchange Act suggest the changes of the rules surrounding the
    communications from medical product manufacturers will likely
    have far-reaching implications for decisions made by healthcare
    providers about which therapies are appropriate for their
    patients. It is critically important for us to fully consider
    and appreciate the impact those proposed changes could have on
    patient safety, health outcomes, and the promotion of value in
    our healthcare system.
        My concern with the two bills we are considering today is
    that as drafted they would undermine public health, discourage
    pharmaceutical research, and undermine the FDA's central
    capacity to ensure medical products used on patients have
    demonstrated safety and efficiency. Opening the floodgates for
    off-label communication puts patients at risk, puts a dent in
    the armor that ensures patients get effective therapies, and
    not snake oil.
        Broadening off-label communications could erode FDA's
    approval standard as it would enable the uses of products never
    found to be safe or effective in patients and weaken consumer
    confidence in the FDA approval process. FDA's approval standard
    of safety and efficiency is considered to be the gold standard
    globally. As the FDA Commissioner Dr. Scott Gottlieb has said,
    the most important incentive to developing useful information
    remains the ability for companies to market drugs based on what
    has been proven scientifically. There is an incentive currently
    for companies to seek FDA's approval for all uses of a drug
    product if they wish to market the product for those uses and
    gain coverage for these uses.
        Allowing manufacturers to communicate about unproven uses
    of their products reduces the incentive to go through the FDA's
    approval process as clinical trials are the most expensive part
    of the development. Thus, it is not hard to imagine a scenario
    where a company seeks the narrowest indication for their
    product, gets on the market, and forgoes on continuing large,
    well controlled, randomized clinical trials that would prove a
    product is both safe and effective for broader populations or
    indications. Patients and doctors should fully be empowered to
    make joint decisions about their care. This includes the
    efficiency, risk, and cost of their options.
        Information is key, however, and the best decisions are
    based on accurate, evidence-based information, not just for
    information that may be incomplete, inconclusive, or at worst
    inaccurate. The discussion draft of the Medical Product
    Communications Act would not provide or ensure that patients
    and care providers have access to better research and evidence.
    Rather, it would allow drug manufacturers to communicate
    information about prescription drugs that have not been
    approved by the FDA. The lack of approval may be due to
    contradictory evidence or the lack of any evidence at all, or
    the need for additional research.
        While I have concerns with both discussion drafts as
    written, I do appreciate that our audience matters. The
    discussion draft of the Pharmaceutical Information Exchange Act
    would expand the ability of drug and device manufacturers to
    communicate healthcare economic information, and scientific
    information to payers, formularies, technology review
    committees, or other entities about unapproved uses of
    products. These audiences are sophisticated and have an
    inherent interest in being skeptical of claims made outside a
    product's label. Therefore, it is less problematic in its
    premise than the other bill we are considering.
        While I am willing to work with my colleagues on the
    proposal, it is critical that these communications promote
    patient safety, public health, and the appropriate safeguards
    are in place to avoid damaging unintended consequences. As we
    consider the issue of off-label communication, we must always
    keep in mind that the way to truly help patients get the most
    effective treatments is to maintain the highest standards of
    safety and evidence and appropriate risk of benefit balance.
        Scientifically validated safety and efficiency and the
    incentives for manufacturers to seek FDA approval are clear and
    should be preserved. I look forward to hearing from our
    witnesses and if anybody wants time, I will yield my 45 seconds
    back. Thank you, Mr. Chairman.
        Mr. Burgess. The gentleman yields back. The Chair thanks
    the gentleman. The Chair recognizes the gentleman from Oregon,
    the chairman of the full committee, Mr. Walden, 5 minutes for
    an opening statement, please.

      OPENING STATEMENT OF HON. GREG WALDEN, A REPRESENTATIVE IN
                   CONGRESS FROM THE STATE OF OREGON

        Mr. Walden. I thank the subcommittee chairman, Chairman
    Burgess. Thanks for this holding this hearing. It is a really
    important topic, and it is a topic that has been important for
    our Members for some time.
        Approximately 40 percent, 40 percent of prescriptions in
    the United States are for indications or uses not included in
    the FDA-approved product labeling. Although off-label uses of
    drugs and devices are often the recognized standard for care
    for treating many conditions, the lack of clarity in the
    statute and implementing regulations has stifled important
    information about such uses for being communicated in a
    responsible and nonpromotional manner by manufacturers.
        The FDA has attempted to address this issue, but it has
    been in a piecemeal fashion or the last 2 decades with various
    nonbinding guidance documents and policy statements that
    frankly fall woefully short, particularly given the criminal
    penalties in play.
        As the Supreme Court affirmed in 2011 that First Amendment
    commercial speech protections extend to medical product
    manufacturers, every subsequent judicial decision, every
    decision, has raised significant questions about the extent of
    FDA's authority to restrict truthful and nonmisleading off-
    label communications.
        So where are we today? The regulators and the courts have
    spoken. Everyone is left with a vast amount of uncertainty that
    does nothing to protect or benefit patients. So it is time for
    Congress to act. And as FDA's authorizing committee, it is our
    job to clarify this statute and get it right which brings us to
    this hearing. Neither of these bills are new to my fellow
    committee members. We discussed an earlier version of both
    bills during a markup in this subcommittee back in May and we
    reviewed these updated versions of the full committee markup of
    the FDA Reauthorization Act last month. Both bills were
    ultimately withdrawn as amendments to FDARA with a commitment
    from our colleagues on the other side of the aisle to work with
    us together to iron out a compromise so we could move these
    important policies forward and speak as the Congress and not
    leave this up to a mishmash of court decisions.
        So I look forward to continuing that work today.
        I believe Morgan Griffith's bill, H.R. 1703, is a serious,
    well-thought-out policy proposal that responsibly sets the
    rules of the road in a constitutionally sound manner. I greatly
    appreciate his willingness to continue to address concerns. He
    has heard about the legislative language.
        I also appreciate Ranking Member Pallone's commitment at
    the user fee markup to work with us in good faith on this issue
    through regular order which starts with this important hearing.
        In addition. Representative Guthrie's amended version of
    H.R. 2026 would clarify how drug and medical device companies
    can share healthcare, economic, or scientific information
    related to investigational uses of their products with payers
    and similar entities. These bills do not provide manufacturers
    with free reign to communicate any and all information about
    their products. They establish targeted, statutory boundaries
    within which manufacturers may responsibly disseminate accurate
    and up-to-date information about medical products. These
    clarifications will lead to a better informed healthcare
    system. They will ensure that patients receive high-quality
    care based on current sound, scientific, and clinical
    information.
        Today, we continue the dialogue. I look forward to a
    productive discussion and I appreciate the input of our
    witnesses who are before us today, and with that, unless there
    are other Members who would like to use the balance of my time,
    I will yield back the balance of my time.
        Mr. Burgess. The Chair thanks the gentleman. The gentleman
    yields back. The Chair recognizes the gentleman from New
    Jersey, the ranking member of the full committee, 5 minutes for
    an opening statement, please.
        [The prepared statement of Mr. Walden follows:]

                     Prepared statement of Hon. Greg Walden

        Thank you, Chairman Burgess, for holding today's hearing on
    an increasingly important topic--one that has been a topic
    amongst our Members for some time.
        Approximately 40 percent of prescriptions in this country
    are for indications or uses not included in the FDA-approved
    product labeling. Although ``off-label'' uses of drugs and
    devices are often the recognized standard of care for treating
    many conditions, the lack of clarity in the statute and
    implementing regulations has stifled important information
    about such uses from being communicated in a responsible,
    nonpromotional manner by manufacturers.
        FDA has attempted to address this issue in a piecemeal
    fashion over the last two decades with various nonbinding
    guidance documents and policy statements that fall woefully
    short, particularly given the criminal penalties in play.
        Since the Supreme Court affirmed in 2011 that First
    Amendment commercial speech protections extend to medical
    product manufacturers, every subsequent judicial decision has
    raised significant questions about the extent of FDA's
    authority to restrict truthful and nonmisleading off-label
    communications.
        So, where are we today? The regulators and the courts have
    spoken. Everyone is left with a vast amount of uncertainty that
    does nothing to protect or benefit patients.
        It is past time for Congress to act, and as FDA's
    authorizing committee it is our job to clarify the statute.
        Which brings us to this hearing. Neither of these bills are
    new to my fellow committee members. We discussed an earlier
    version of both bills during a markup in this subcommittee back
    in May, and we reviewed these updated versions at the full
    committee markup of the FDA Reauthorization Act (FDARA) last
    month.
        Both bills were ultimately withdrawn as amendments to
    FDARA, with a commitment from our Democrat colleagues to
    continue to work together to iron out a compromise on moving
    these important policies forward. I look forward to continuing
    that work today.
        I believe Morgan Griffith's bill, H.R. 1703, is a serious,
    well-thought-out policy proposal that responsibly sets the
    rules of the road in a constitutionally sound manner. I greatly
    appreciate his willingness to continue to address concerns he
    has heard about the legislative language. I am also
    appreciative of Ranking Member Pallone's commitment at the user
    fee markup to work with us on this issue through regular order,
    which starts with this important hearing.
        In addition, Rep. Guthrie's amended version of H.R. 2026
    would clarify how drug and medical device companies can share
    healthcare, economic, or scientific information related to
    investigational uses of their products with payers and similar
    entities.
        These bills do not provide manufacturers with free rein to
    communicate any and all information about their products. They
    establish targeted statutory boundaries within which
    manufacturers may responsibly disseminate accurate, and up-to-
    date information about medical products. These clarifications
    will lead to a betterinformed health care system and will
    ensure that patients receive high-quality care based on
    current, sound scientific and clinical information.
        Today we continue the dialogue, and I look forward to a
    productive discussion.

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

        Mr. Pallone. Thank you, Mr. Chairman. I want to thank you
    for holding today's hearing. The issue before us today is an
    important one and I hope that our discussion today will help to
    inform whether or not it would be appropriate for this
    committee to take further action.
        Today, under current law, medical product manufacturers are
    required to demonstrate the safety and effectiveness of each
    intended use of their medical product. This review process has
    been critical to protecting and promoting public health by
    ensuring that the benefits of medical products that are
    prescribed to patients outweigh the risk. It also is common
    sense. Just because a medical product approved for one use may
    be found to be safe and effective for that use, doesn't
    necessarily mean that it will be safe and effective for another
    use or for another population.
        Recognizing that physicians may prescribe treatments off-
    label in response to individual patient needs, FDA allows the
    communication of truthful and nonmisleading scientific or
    medical information regarding unapproved uses of medical
    products that may assist physicians in making treatment
    decisions. In those instances, FDA has allowed for
    manufacturers to respond to requests from physicians about
    unapproved uses and provide peer reviewed journal articles,
    scientific or medical texts, and clinical practice guidelines.
        Following 21st Century Cures, manufacturers are also now
    able to share healthcare economic information with payers to
    help them better understand the economic benefits of an
    approved treatment.
        These are commonsense approaches that allow doctors to
    address the individual needs of a patient, but also ensure that
    patients are not unnecessarily exposed to unproven or harmful
    medical products.
        Now today, we are here to examine discussion drafts from
    Representatives Griffith and Guthrie that would greatly expand
    the types of scientific information that manufacturers could
    share without any FDA oversight. While I understand that
    medical product manufacturers have voiced concerns about their
    ability to communicate with doctors about their products, I am
    concerned that these drafts would severely undermine the
    current protections against marketing unsafe and ineffective
    medical products.
        During this hearing, I hope to hear what materials
    manufacturers want to share with healthcare professionals and
    payers that they feel they can't under current law.
        The scientific exchange discussion draft would severely
    restrict the types of evidence the FDA has always relied on to
    determine the intended use of a medical product. It would also
    hamstring the Agency from holding bad actors who distribute
    dangerous drugs or medical devices accountable.
        The preapproval communication discussion draft will blow a
    hole in the current approval process by allowing the
    communication of any scientific evidence or healthcare economic
    information to payers or formularies without any recourse to
    the FDA to prevent bad actors from communicating false or
    misleading information. Allowing manufacturers to communicate
    about unapproved products and unapproved uses of their products
    reduces the incentive of those through FDA's approval process
    and that is grossly irresponsible in my opinion.
        For example, the proposed discussion draft would allow for
    a manufacturer to publish a biased, scientific study in any
    medium to constitute scientific exchange. This could simply
    include posting results of a nonpeer-reviewed study on a
    company's website, and there is no requirement that this
    information be truthful.
        I am also concerned that these two discussion drafts could
    expose more patients to medical products that have never been
    proven to be safe or effective. One study found that 81 percent
    of medications prescribed for off-label purposes had poor or no
    scientific support, while another found that patients who
    received off-label prescriptions were 54 percent more likely to
    experience an adverse event, as compared to on-label use. And
    these are risks that we simply cannot ignore.
        So Mr. Chairman, if there is a need for greater certainty
    and clarity on the types of communications that manufacturers
    are permitted to use under current law, I am willing to have
    that discussion. However, broadening communication in the way
    it is proposed under these discussion drafts would, in my
    opinion, undermine FDA's regulatory review process and the
    safety and effectiveness approval standard.
        I have about a minute. I don't know if anybody wants it. If
    not, I yield back, Mr. Chairman.
        [The prepared statement of Mr. Pallone follows:]

                 Prepared statement of Hon. Frank Pallone, Jr.

        Mr. Chairman, I want to thank you for holding today's
    hearing. The issue before us today is an important one, and I
    hope that our discussion will help to inform whether or not it
    would be appropriate for this committee to take further action
    at this time.
        Today, under current law, medical product manufacturers are
    required to demonstrate the safety and effectiveness of each
    intended use of their medical product. This review process has
    been critical to protecting and promoting public health by
    ensuring that the benefits of medical products that are
    prescribed to patients outweigh the risks. It is also
    commonsense--just because a medical product approved for one
    use may be found to be safe and effective for that use, does
    not necessarily mean that it will be safe and effective for
    another use or for another population.
        Recognizing that physicians may prescribe treatments off-
    label in response to individual patient needs, FDA allows the
    communication of truthful and nonmisleading scientific or
    medical information regarding unapproved uses of medical
    products that may assist physicians in making treatment
    decisions. In these instances, FDA has allowed for
    manufacturers to respond to requests from physicians about
    unapproved uses and provide peer-reviewed journal articles,
    scientific or medical texts, and clinical practice guidelines.
    Following 21st Century Cures, manufacturers are also now able
    to share health care economic information with payors to help
    them better understand the economic benefits of an approved
    treatment.
        These are commonsense approaches that allow doctors to
    address the individual needs of a patient, but also ensure that
    patients are not unnecessarily exposed to unproven or harmful
    medical products.
        Today, we are here to examine discussion drafts from
    Representatives Griffith and Guthrie that would greatly expand
    the types of scientific information that manufacturers could
    share without any FDA oversight. While I understand that
    medical product manufacturers have voiced concern about their
    ability to communicate with doctors about their products, I am
    concerned that these drafts would severely undermine the
    current protections against marketing unsafe and ineffective
    medical products. During this hearing, I hope to hear what
    materials manufacturers want to share with health care
    professionals and payors today that they feel they cannot under
    current law.
        The scientific exchange discussion draft would severely
    restrict the types of evidence the FDA has always relied on to
    determine the intended use of a medical product. It would also
    hamstring the agency from holding bad-actors who distribute
    dangerous drugs or medical devices accountable.
        The preapproval communication discussion draft would blow a
    hole in the current approval process by allowing the
    communication of any scientific evidence or health care
    economic information to payors or formularies without any
    recourse for the FDA to prevent bad actors from communicating
    false or misleading information. Allowing manufacturers to
    communicate about unapproved products and unapproved uses of
    their products, reduces the incentive to go through FDA's
    approval process. This is grossly irresponsible.
        For example, the proposed discussion draft would allow for
    a manufacturer to publish a biased scientific study in any
    medium to constitute ``scientific exchange.'' This could
    include simply posting results of a nonpeer reviewed study on a
    company's own website, and there is no requirement that this
    information be truthful.
        I am concerned these two discussion drafts could expose
    more patients to medical products that have never been proven
    to be safe or effective. One study found that 81 percent of
    medications prescribed for off-label purposes had poor or no
    scientific support, while another found that patients who
    received off-label prescriptions were 54 percent more likely to
    experience an adverse event as compared to on-label use. These
    are risks that we simply cannot ignore.
        If there is a need for greater certainty and clarity on the
    types of communications that manufacturers are permitted to use
    under current law, I am willing to have that discussion.
    However, broadening communication in the ways proposed under
    these discussion drafts would undermine FDA's regulatory review
    process and the safety and effectiveness approval standard.
        Thank you.

        Mr. Burgess. The gentleman yields back. The Chair thanks
    the gentleman. This concludes Member opening statements, and I
    would like to remind Members that, pursuant to committee rules,
    all Members' opening statements will be made part of the
    record.
        And we want to thank our witnesses for being here with us
    this morning, for taking time to testify before the
    subcommittee. Each witness will have the opportunity to give a
    summary of their opening statement, followed by questions from
    Members.
        This morning, we are going to hear from Coleen Klasmeier, a
    partner of Sidley Austin, LLP; Alta Charo, the Warren Knowles
    Professor of Law at the University of Wisconsin; Dr. George Van
    Hare, the Division Chief, Pediatric Cardiology; Louis Larrick
    Ward, Professor of Pediatrics at Washington University School
    of Pediatrics; and Co-Director of the St. Louis Children's and
    Washington University Heart Center; Aaron Kesselheim, Associate
    Professor of Medicine, Harvard Medical School, Director of
    Program on Regulation, Therapeutics and Law from the Division
    of Pharmacoepidemiology and Pharmacoeconomics at the Brigham
    and Women's Hospital; Linda House, President of the Cancer
    Support Community; and Katherine Wolf Khachatourian, Vice
    President, Delegation Oversight, Pharmacy Services of
    QualchoiceHealth Plan Services.
        We appreciate all of you being here today and Ms.
    Klasmeier, you are recognized for 5 minutes for the purpose of
    an opening statement. Thank you for being here.

    STATEMENTS OF COLEEN KLASMEIER, PARTNER, SIDLEY AUSTIN, LLP; R.
     ALTA CHARO, WARREN P. KNOWLES PROFESSOR OF LAW, UNIVERSITY OF
       WISCONSIN; GEORGE VAN HARE, M.D., PRESIDENT, HEART RHYTHM
    SOCIETY; AARON S. KESSELHEIM, ASSOCIATE PROFESSOR OF MEDICINE,
    HARVARD MEDICAL SCHOOL AND BRIGHAM AND WOMEN'S HOSPITAL; LINDA
    HOUSE, PRESIDENT, CANCER SUPPORT COMMUNITY; AND KATHERINE WOLF
     KHACHATOURIAN, VICE PRESIDENT, DELEGATION OVERSIGHT, PHARMACY
     SERVICES, AND STRATEGY, QUALCHOICE HEALTH PLAN SERVICES, INC.

                     STATEMENT OF COLEEN KLASMEIER

        Ms. Klasmeier. Thank you, Mr. Chairman. Chairman Burgess,
    Vice Chairman Guthrie, Ranking Member Green, Chairman Walden,
    members of the subcommittee, my name is Coleen Klasmeier. I am
    a partner and the head of the FDA Regulatory Practice at Sidley
    Austin in Washington, DC. I am appearing today on behalf of the
    Medical Information Working Group.
        Today, I would like to make three points. First, FDA's
    rules governing manufacturer communications are neither clear
    nor precise. Decisions to prescribe and use lawfully marketed
    drugs and medical devices in ways that differ from the FDA
    authorized labeling, so-called off-label use, are a constituent
    part of medical and surgical practice and can also be the
    standard of care. FDA has long recognized the need for
    prescribers to receive and for manufacturers to have some
    ability to provide information outside of product labeling to
    help support clinical decision making. As a result, although a
    manufacturer is prohibited from promoting its product for new
    uses, it can lawfully provide information about off-label uses
    within defined circumstances.
        Currently, there are four safe harbors. Only one is set
    forth in a binding regulation. The others are in nonbinding
    documents. They therefore lack the force of law. Moreover, two
    of the four safe harbors have been the subject of ongoing FDA
    proceedings since 2011. Under these policies, a manufacturer
    can provide off-label information ostensibly without fear of
    enforcement in four scenarios involving scientific exchange,
    responses to unsolicited requests, continuing education, and
    reprints of journal articles, reference texts, and clinical
    practice guidelines. Each safe harbor is subject to a number of
    qualifying criteria and additional requirements which are
    unclear in many key respects.
        Moreover, FDA has been unable to complete its process of
    revising the safe harbor policies, so questions frequently
    arise regarding the relationship between the old policies and
    the new policies.
        In addition, there is a lack of symmetry between the safe
    harbors that apply to drugs and those that apply to medical
    devices. In short, the safe harbors are a mess. As a result,
    manufacturers cannot confidently rely on the safe harbors and
    that has public health consequences. For example, it is common
    for the Advisory Committee on Immunization Practices, a Federal
    statutory advisory committee to the CDC, to make
    recommendations for vaccines that are arguably off-label. ACIP
    recommendations might vary the dosing schedule or recommend use
    of a vaccine in a new patient population. The vaccine
    manufacturer would reasonably fear that communicating about the
    ACIP recommendation to physicians or payers could be
    characterized by Government as unlawful, off-label promotion.
    Ultimately, the public health would not be advanced because
    physicians would not receive manufacturer communications
    reinforcing that recommendation.
        The regulatory scheme also has legal consequences. The
    First Amendment case law makes clear that FDA is limited in its
    power to prohibit drug and device manufacturers from engaging
    in accurate communications about their product. FDA's
    regulatory scheme also implicates the due process laws of the
    Fifth Amendment which requires Government agencies to establish
    rules that are clear and to give fair notice of what is
    prohibited, particularly in the context of free expression.
        Second, the existing FDA regulatory scheme for manufacturer
    communication is highly unstable. The lack of clear rules to
    allow manufacturers an appropriate measure of latitude to
    communicate about their products is only a part of the problem.
    FDA and the Justice Department impose aggressive restraints on
    manufacturers' speech. Although manufacturers have indeed
    settled many cases involving off-label promotion allegations in
    recent years, in some instances individuals and firms have
    raised First Amendment arguments in court and those arguments
    have succeeded. FDA's regulatory scheme continues to burden
    constitutionally protected speech and is therefore at risk from
    additional lawsuits.
        The Medical Information Working Group has for more than 10
    years and across more than 20 submissions, requested targeted
    clarifications to the existing FDA safe harbors and to key
    statutory terms such as labeling and intended use. We have not
    asked for and we do not want a healthcare system in which
    manufacturers can market their product based on spurious or
    unsubstantiated claims of safety or efficacy.
        Third, legislation could dramatically improve the
    regulatory scheme. Although the MIWG has been dedicated to
    direct engagement with FDA on manufacturer communication issues
    since 2006, we also recognize the paramount role of Congress
    and we believe that legislation may be necessary for several
    reasons.
        For one thing, FDA action has been slow and ineffectual. It
    has been almost 6 years, for example, since FDA published a
    notice in the Federal Register asking for comment on scientific
    exchange and responses to unsolicited requests. Where FDA has
    taken action, the policy has tacked in the wrong direction
    becoming less clear and even more speech restrictive. For these
    reasons, it would be helpful for Congress to step in and set
    the overall policy direction for FDA to implement.
        Legislation is also more durable than unilateral FDA
    action. Statutory law is not subject to the same variability as
    agency pronouncements and cannot be undone in a future
    administration. Legislation would be less susceptible to legal
    challenge than a regulation or an FDA guidance document.
    Regulations have the force of law, but the Administrative
    Procedure Act creates a vehicle for challenge in court, whereas
    a statutory change could only be challenge successfully in
    court on constitutional grounds.
        Legislation may also be necessary given the likelihood of
    continued judicial involvement in this area. Although we value
    the contributions that recent judicial decisions have made to
    the body of relevant law, we also believe that litigation is
    not the best way to make law on important public health issues
    where there is little room for error. We are especially
    concerned that some future lawsuit might eviscerate the FDA
    regulatory scheme.
        We see great value in congressional engagement with FDA on
    manufacturer communication issues to help assure the regulatory
    scheme is put on to a more stable and sustainable footing.
    Thank you very much for the opportunity to testify today and I
    look forward to your questions.
        [The prepared statement of Ms. Klasmeier follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. I thank the gentlelady for her testimony.
        Ms. Charo, you are recognized for 5 minutes, please.

                       STATEMENT OF R. ALTA CHARO

        Ms. Charo. Chairman Burgess, Vice Chairman Guthrie,
    Congressman Green, and members of the committee, thank you for
    the opportunity to address you on issues surrounding
    communication and marketing of off-label uses.
        My name is Alta Charo. I am the Warren P. Knowles Professor
    of Law at the University of Wisconsin. I am an elected member
    of National Academy of Medicine, formerly known as the
    Institute of Medicine, where I have served on a number of
    committees including the one that produced a report on ensuring
    the safety of the U.S. drug system. I also served as an advisor
    in the Office of the Commissioner at FDA from 2009 to 2011, but
    I would like to note for the record that I speak for myself
    only and not for FDA and not for the National Academies.
        There are two possible reasons to expand communication
    about off-label uses. One is to ensure that the law is
    consistent with the requirements of the First Amendment. The
    other is to protect public health by increasing patient access
    to safe and effective drugs. And I share those two goals. I
    don't, however, believe that the two amendments under
    discussion are necessary to achieve those goals. Indeed, I fear
    the unintended consequence of adopting the language in these
    amendments would be to undermine public health, to discourage
    pharmaceutical research, and to set pharmaceutical regulation
    back by more than 100 years.
        As noted in an article I co-authored with Josh Sharfstein,
    formerly the principal deputy at FDA, our drug regulation
    system has prohibited false or misleading advertising since
    1906. And in 1962, broad marketing for secondary uses of
    thalidomide caused thousands of severe birth defects worldwide,
    and Congress then recognized that a product can be ``safe and
    effective'' for one intended use where the benefits exceed the
    risks, but not ``safe and effective'' for another which why
    approval of a drug for a labeled indication does not mean it
    will be safe and effective for off-label uses and precisely why
    additional studies are needed.
        This requirement to demonstrate safety and effectiveness
    for an intended use applies both to the first approval of a new
    compound or a new drug, as well as to any supplemental
    indication. And while it is true there have been a handful of
    cases narrowing constraints on commercial speech regarding
    unapproved ``off-label'' uses, the courts have consistently
    upheld commercial speech restriction with respect to the first
    approval of a new product. If the First Amendment means that
    off-label promotion must be permitted, then promotion of
    entirely untested, never-approved drugs should also garner the
    same protection. In both cases, the majority of drugs will fail
    to show that they are safe and effective when the testing has
    been completed and the substantial public interest in achieving
    that certainty is the same regardless of whether it is an
    entirely new drug or a supplemental indication for an existing
    drug.
        If we were to eliminate the restrictions on commercial
    speech for entirely unapproved drugs, it would return us to the
    1906 law where prosecution for false and misleading marketing
    took place only after people had been harmed.
        Scientific journals and conferences are already allowed to
    present information about off-label uses. Sponsors can answer
    questions from physicians and provide reprints of peer-reviewed
    articles, even if related to off-label uses. And in April 2017,
    the FDA further clarified these rules and used guidances as a
    more flexible mechanism to provide that information.
    Legislation, regulation, and court decisions have not the kind
    of flexibility that guidances have. We have entered an era in
    which communication takes on many new forms ranging from tweets
    to Facebook to any number of internet sources and it is
    important to maintain flexibility in how we regard
    communication and its influence and its intended purpose,
    rather than solidifying it in legislation which can be
    difficult to change over time.
        Now the proposed amendment of Section 201 muddies the
    exceptions that FDA has outlined and I fear it risks
    eviscerating the general rule against off-label promotion even
    if that is not its intent. It also has the effect of immunizing
    sponsors from responsibility even if they know and take
    advantage of the now blurry line between legitimate scientific
    exchange and illegal marketing.
        The proposed amendment of Section 502, I fear, will
    exacerbate this problem, by allowing premature information to
    be delivered to formularies and payers with the probable effect
    of increasing patient use of unproven and unsafe therapies. And
    as has been noted already by Members here on the committee,
    studies have repeatedly shown that even products that look
    promising in early trials will usually be shown to be unsafe or
    ineffective when larger trials are completed. And indeed,
    overall only about one in five compounds, only one in five,
    will successfully move from Phase 2 to Phase 3 trial, with lack
    of efficacy as the most common reason for failure.
        In a series of articles recently produced by Professor
    Christopher Robinson at the University of Arizona, we can also
    see that multiple studies show that the majority of off-label
    uses also will turn out to be either unsafe or ineffective.
    Encouraging coverage before approval is to encourage expanded
    use before approval of treatments that we now know empirically
    are likely to fail. And I fear that the effect would be to
    increase use that will harm more patients than it helps.
        History amply demonstrates there is a compelling public
    interest in unbiased evaluation of evidence; in clear, accurate
    communication; in maintaining incentives for research. The
    combined effect of these amendments is to expand promotion and
    payment for unproven uses of drugs. It undercuts the marketing
    advantages that the law now uses as an incentive for sponsors
    to complete the research needed to see which uses are, in fact,
    safe and effective. And in turn, it leaves physicians,
    patients, formularies, and payers without independently
    verified information. For complex products like drugs, the
    marketplace of ideas cannot work properly with unvetted
    information from necessarily self-interested sources. And when
    using the wrong drug can injure patients or cause them to miss
    out on effective treatment, it is an invitation to another
    tragedy when we prevent FDA from doing its job to protect the
    public.
        Thank you very much.
        [The prepared statement of Ms. Charo follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. The Chair thanks the gentlelady.
        The Chair recognizes Dr. Van Hare, 5 minutes for your
    opening statement, please.

                      STATEMENT OF GEORGE VAN HARE

        Dr. Van Hare. Good morning, Chairman Burgess, Ranking
    Member Green, and members of the subcommittee. Thank you for
    holding this hearing and for inviting me to testify on this
    important topic. My name is George Van Hare. I am Chief of
    Pediatric Cardiology at St. Louis Children's Hospital in St.
    Louis, Missouri. My clinical practice is focused on caring for
    children with heart rhythm disorders. This year I have the
    honor of serving as the president of the Heart Rhythm Society.
    The Heart Rhythm Society is the international leader in
    science, education, and advocacy for cardiac arrhythmia
    professionals. Its members include 6,100 physicians,
    scientists, nurses, and other allied health professionals in
    more than 90 countries.
        Sharing comprehensive, scientifically valid data is
    critical to the practice of medicine generally, and it is even
    more critical for particular specialties. It is sometimes
    claimed that the use of drugs or devices off-label is the
    result of a choice by physicians. Sometimes this is
        true. However, for pediatric sub-specialists, this is
    usually not the case. This is due to the fact that very few of
    the medications for arrhythmias that are on the market are
    formally approved for use in children. Thus, using treatments
    off-label is often our main method of
        treatment of children. Similarly, catheters that we use for
    catheter ablation procedures are labeled for a limited number
    of specific arrhythmias, but are used for treating and curing
    all types of arrhythmias in adults and children.
        By way of example, I would like to cite the specific drug,
    amiodarone, brand name Cordarone. This is one of our most
    important medications for the treatment of potentially life-
    threatening arrhythmias, particularly in patients who have
    undergone successful surgical repair of complex
        congenital heart defects. The FDA-approved label simply
    states ``The safety and efficacy of Cordarone Tablets in
    pediatric patients have not been established.'' This means that
    the manufacturer is not allowed to share prospectively any data
    that they may have concerning experience with this drug in
    children.
        Another example, not specific to children, is a labeling of
    ablation catheters. These devices are used in performing
    catheterization procedures to cure arrhythmias. In the last 25
    years, these procedures have essentially replaced open heart
    surgery as the best option for a curative procedure. Their
    labeling is limited to only certain arrhythmias. For example,
    the Cryocath, a cryoablation catheter manufactured by
    Medtronic, is only labeled for treating one common arrhythmia,
    AVNRT, despite the fact that it is ideal for treating other,
    more dangerous arrhythmias. It would be absurd to use a
    different catheter for these other arrhythmias on the basis of
    the labeling, and even more absurd if you consider open heart
    surgery. However, because of the labeling, technical support
    representatives of the manufacturer are not allowed to discuss
    other indications directions and prospectively, despite the
    fact that the use of this catheter for these other indication
    sis widely agreed to be the standard of care.
        There is an important way in which information sharing
    among physicians may also be adversely affected. When a medical
    conference is directly sponsored by a manufacturer, these
    conferences do not qualify as official continuing medical
    education events. Consequently, physician speakers are
    considered to be ``agents'' of the manufacturer sponsoring the
    event, and they are also limited to discussing only the labeled
    indications. Any discussion between physicians regarding
    experiences with drugs or devices that are off-label at such
    events must occur informally, rather than as part of the
    program, and thus these discussions do not benefit from the
    great potential for information sharing among physician
    attendees.
        The good news is that it doesn't have to be this way. It is
    likely that there is a large amount of data maintained by
    manufacturers, which under the current rules they are not
    allowed to proactively share with clinicians. I urge the
    committee to explore ways to define acceptable types of real-
    world evidence that manufacturers might proactively share with
    medical decision makers. These types of data might include
    observational studies, pharmacokinetic studies, and information
    on particular sub-populations. The data must be truthful,
    presented in context, and scientifically valid.
        There is some concern that manufacturers might overwhelm
    physicians with data taken out of context or data that are
    misleading and skewed to present a more favorable picture than
    is realistic. However, physicians are trained to analyze data.
    We know how to evaluate the validity of studies. If regulatory
    restrictions provide guard rails to ensure that data are
    truthful and presented in context, physicians are fully capable
    of analyzing such data effectively.
        In my opinion, a reasonable regulatory paradigm lies
    somewhere between no communication and completely unrestricted
    communication. The current structure is not optimal for
    fostering the advancement of medical knowledge, and it leaves
    many patients and their physicians at an unnecessary
    disadvantage. Additionally, it seems incongruous to me that the
    manufacturer, the entity with the most robust data related to a
    product, cannot share information they hold proactively while
    any lay person with an internet connection can freely
    disseminate whatever information they like about that same
    product however biased and unreliable.
        In closing, I hope that my testimony has provided the
    committee with a real-world perspective on how the current
    rules often prevent physicians from receiving valuable,
    clinical information in a timely fashion. I respectfully
    suggest that Congress should establish ways to unlock
        data maintained by manufacturers related to off-label use
    of drugs and devices. I thank the committee for its time. The
    Heart Rhythm Society would welcome the opportunity to work with
    you on policy proposals related to this topic. Thank you.
        [The prepared statement of Dr. Van Hare follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. The Chair thanks the gentleman for his
    testimony.
        Dr. Kesselheim, you are recognized for 5 minutes for your
    statement, please.

                    STATEMENT OF AARON S. KESSELHEIM

        Dr. Kesselheim. Good morning, Chairman Burgess, Ranking
    Member Green, and other members of the committee, thank you for
    the opportunity to join you today. In my time I want to make
    four main points.
        First, the current restrictions on manufacturers' ability
    to market their drugs for non-FDA-approved indications is not a
    bureaucratic or paternalistic effort to prevent manufacturers
    from communicating. These rules were developed in response to
    major public health problems caused by the lack of such
    regulation. Evidence of the public health dangers that arise
    from widespread off-label marketing can be seen in the drug
    paroxetine or Paxil, an antidepressant that was promoted off-
    label for use in children leading to at its peak over two
    million prescriptions per year for use in children until it was
    ultimately linked to self-injury and suicide in that
    population. Or, the off-label promotion of anti-psychotic
    medications to control behavioral symptoms in elderly patients
    with dementia, uses that are not only generally ineffective,
    but that also increase the risk of death by 60 to 70 percent.
        At one point, due to off-label promotion approximately one
    in seven elderly nursing home residents reportedly received
    these drugs.
        Over and over again, these episodes show us, as former
    Chief Justice William Rehnquist originally put it that ``there
    are sufficient dangers attending [the] widespread use [of
    pharmaceuticals] that they simply may not be promoted in the
    same manner as hair creams, deodorants, and toothpaste.''
        Second, the dangers from off-label promotion do not come
    simply from the spread of false information about these
    products, although that does happen on occasion of course.
    Rather, in one study that I led, we found that off-label
    promotion most commonly involved presenting reports of
    individual cases or poorly designed studies as definitive
    evidence supporting an off-label use, while de-emphasizing data
    that didn't fit the narrative the manufacturers were creating.
    In each of these particular cases, the words themselves may not
    have been false or strictly misleading, but the benefits of the
    drug overstated and the risks down played in ways that the
    physicians might have needed advanced training in epidemiology
    or access to the underlying clinical trial data to understand
    which they simply do not have. This is why we need the
    diligent, independent assessment of safety and efficacy
    provided by the FDA. The complexity of the assessment that is
    required, along with the high stakes of getting that assessment
    wrong provides the rationale for having a formal drug approval
    process in the first place.
        Third, the Griffith and Guthrie discussion drafts directly
    risk these outcomes. The Guthrie discussion draft, for example,
    defines scientific information that could support an off-label
    marketing claim as including preclinical data in petri dishes
    or in mice, and all it requires is a study that was conducted
    that the manufacturer anticipates could be sufficient to
    support FDA approval.
        The Griffith draft, in creating a so-called safe harbor for
    scientific exchange, purports to require manufacturers to
    disclose appropriate contextual information for their
    statements, but it would be highly risky to give a manufacturer
    with a strong financial and intellectual stake in the product's
    success free reign to determine what is or isn't proper context
    or what is or isn't contradictory for its product. At the same
    time, it is unrealistic to expect each individual physician to
    have the time and expertise to subject such claims to the same
    kind of scrutiny that the FDA would exercise when it reviews a
    drug application or a request for a new indication.
        The drafts also purport to protect the public health by
    attaching disclaimers to these off-label communications, but I
    led a systematic review of the evidence about the impact of
    such disclaimers, most of which currently come in the context
    of promotional statements for herbal remedies and dietary
    supplements for which Congress eliminated FDA oversight of
    promotion more than 20 years ago. Many of these products
    advertise health-enhancing effects despite no legitimate
    evidence that they work with disclaimers that the FDA has not
    evaluated the promotional claims, but the massive collective
    evidence reveals that such disclaimers fail to adequately
    inform or modify consumer behavior. So when anybody proposes a
    disclaimer, I suggest that there be a disclaimer, that
    disclaimers don't actually work.
        Finally, I want to emphasize that the current system helps
    protect patients from widespread promotion of drugs and devices
    for potentially unsafe and ineffective off-label uses, while
    still permitting off-label prescribing at the discretion of
    physician and patients and providing well-circumscribed avenues
    for manufacturer communication about these issues such as in
    response to bona fide questions arising from physicians. By
    contrast, the Griffith and Guthrie discussion drafts would
    reduce manufacturers' incentives to conduct well-controlled
    trials of potential off-label uses in the first place. Instead,
    as Representative Green mentioned, manufacturers would be
    incentivized to seek approval of drugs and devices for the
    narrowest indication possible, and then conduct ``studies'' of
    variable quality showing the utility of these products for
    unapproved indications that would not meet current FDA
    standards for scientific rigor.
        I strongly recommend that the committee not pursue these
    drafts and instead consider how we can give the FDA the proper
    resources and authorities to continue to review emerging data
    efficiently so that evidence that does support new uses of
    drugs and devices can be incorporated into their labels and
    clinical practice while uses that the totality of the data show
    are unsafe can be identified for the benefits of patients.
    Thank you very much.
        [The prepared statement of Dr. Kesselheim follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. The Chair thanks the gentleman.
        Ms. House, you are recognized for 5 minutes for an opening
    statement, please.

                        STATEMENT OF LINDA HOUSE

        Ms. House. Good morning. My name is Linda House, and I am
    the president of the Cancer Support Community. I would like to
    thank the committee for allowing us to be here and share this
    testimony today.
        The Cancer Support Community is an international nonprofit
    organization whose mission is to ensure that all people
    impacted by cancer are empowered by knowledge, strengthened by
    action, and sustained by community. Our organization sees over
    100,000 patients and families each year through a network of
    affiliates around the world. We also have a Cancer Support
    Helpline where we administer through both of those properties,
    over $50 million of evidenced-based care and support each year
    free of charge to patients and their families. Importantly, CSC
    is also home to the only Research and Training Institute of its
    kind whose mission is to collect and analyze information from
    patients to elevate the voice of the patient and the caregiver
    as it relates to their cancer experience.
        I am here today to bring you what I feel is the most
    important voice to this conversation and that is the voice of
    the patient.
        The last 20 years have delivered unprecedented growth in
    innovation across all aspects of health care. Never before has
    a patient had so many options for diagnosis, treatment, and
    follow-up care as they do now. Patients are more educated. They
    are more engaged. They are more empowered consumers of health
    care than ever before. Yet, despite the emergence of patients
    as important players, and even leaders of their care teams,
    accessibility to comprehensive information continues to be
    elusive.
        We will be releasing data next week from our Cancer
    Experience Registry where we have learned that 50 percent of
    patients engage in shared treatment decision making with their
    healthcare professionals. Only about eight percent report
    allowing healthcare professionals to make decisions without
    their input. Yet, only 25 percent indicate that they feel like
    they are prepared to have those treatment decisions.
        Importantly, our data reflects a growing concern about
    inadequate collection, reporting, and label updating of
    endpoints that are meaningful to patients. In our research, 93
    percent of respondents considered quality of life as very
    important when making treatment decisions. Quality of life
    measured higher than length of life, and these are people with
    cancer, yet product labels continue to focus very little on
    fully measuring comprehensive quality of life metrics. Further,
    product labels almost never reflect updates when there are
    findings beyond the clinical trial setting including findings
    about long-term effects which would be meaningful for patients.
    A system that does not proactively collet, publish, and share
    data poses a significant risk to patient care.
        There are a few issues I would like to raise as current
    limitations and we do support the work that the FDA does and we
    do support the work of the clinical trial systems and we do
    support accurate, meaningful, nonpromotional communication.
        Preapproval information, as you know, is when clinical data
    is available on a product prior to the product having an FDA
    label. According to PhRMA, it takes an average of 10 to 15
    years for a drug to make it to market. And during that time,
    much is learned about the way in which the drug works in the
    body, how the body works with the drug, what is the accurate
    dose, what is the toxic dose, and what are the side effects
    associated with that drug. Yet, this treasure trove of
    information remains out of reach from individuals other than
    the sponsor or potential trial investigators.
        Number two, limiting communication of information to only
    that which is reflected in the label poses a significant
    challenge to patients. CSC appreciates the work of the FDA and
    sponsors of phase IV studies, in particular, but recognizes
    that these studies do not capture comprehensive data for the
    use of the product as was mentioned in the real world. Also, it
    is a rare occurrence for the label to be updated in a manner
    that would allow for proactive communications of findings
    outside of the controlled clinical trial setting. And as we
    know, once trials go into broader, less controlled situations,
    they perform differently in those patients.
        Number three, data accumulated through Investigator
    Initiated Trials on diseases that would never reach the
    investment potential for registration in a label is extremely
    important to clinical care. This information may never be
    communicated to clinicians and will almost certainly not be
    made available to patients who may benefit from the findings
    and this is particularly important in patients with rare
    disease.
        Number four, information learned outside of the clinical
    trial setting and not captured in the label can also have a
    true impact on the patient experience. And as I submitted in my
    written testimony, this could be things like burning at the
    injection site, a reduction in fatigue by understanding how to
    better supplement the treatment. That information is not in the
    label and cannot be shared in a proactive way.
        Number five, there are several elements in general clinical
    practice that are continuing to contribute to the limitation
    that patients have to access comprehensive medical information
    through their healthcare team. And in particular, as there is
    an active evolution of the care delivery systems from volume to
    value, it has brought with it efficiency and cost containment
    strategies that focus on limiting treatment decisions. And I am
    talking about hospital-based formularies and clinical pathways
    that are currently being used in physician practices.
        Number six, there is an inconsistent practice and
    reinforcement of publishing clinical trial data results in
    scientific journals and other databases. This information has
    to be published and as mentioned in my written comments, the
    ratio of trials that have been opened, closed, and published,
    the compliance rate with that abysmal and there must not only
    be requirements, but also enforcement of the requirements to
    ensure that all results of trials be posted whether those
    results are positive or negative.
        Finally, industry interpretation of the current regulations
    is applied inconsistently across companies. This impacts the
    way in which industry communicates with all stakeholders and
    most certainly the way in which industry communicates with
    patients and families forcing them only through the direct-to-
    consumer marketing channel.
        So in conclusion, while the comments that I have made have
    simply scratched the surface on what is a much broader and
    deeper issue, it is my hope that I have highlighted in your
    mind the perspective of patients who are living with chronic
    and life-threatening illness across the United States.
        And to summarize in specific areas where we would like to
    continue to work with the committee and the FDA, patients and
    healthcare providers must have access to medical research
    findings in a comprehensive and real-time manner. Product
    labels should be updated in a timely manner and include data
    from endpoints that matter most to patients and/or there must
    be another mechanism by which to capture and proactively
    communicate findings that are clinically meaningful and
    relevant. Scientifically sound communications about safe and
    effective uses of a product are essential and should be made
    available to all stakeholders. Clinical trial results, positive
    and negative, should be published by the trial sponsor in a
    period of time that is reasonable to allow full and meaningful
    data review while ensuring timely access to information. Data,
    positive and negative, collected outside of the clinical trial
    process, inclusive of real-world evidence that is collected and
    analyzed with appropriate scientific rigor should be published
    and made available to stakeholders. And finally, proactive
    medical communication should be tailored to meet the needs and
    literacy levels of specific stakeholders and should not, for
    any stakeholder, be limited only to the product label which may
    not yet exist or be outdated.
        Thank you for allowing us to be here.
        [The prepared statement of Ms. House follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. Thank you. Thank you for your testimony.
        Ms. Khachatourian, you are recognized for 5 minutes,
    please.

               STATEMENT OF KATHERINE WOLF KHACHATOURIAN

        Ms. Khachatourian. Thank you to Chairman Burgess, Ranking
    Member Green, and members of the Subcommittee on Health for
    providing me the opportunity to speak before you today.
        I am Katherine Khachatourian, a pharmacist working in
    Medicare health insurance and a member of the AMCP Professional
    Practice Committee.
        Imagine a world where you are required by Federal and State
    laws to determine a budget and coverage criteria for all drugs
    8 to 12 months in advance of the coverage year using limited
    available information while knowing there is information that
    could help you make more accurate and informed decisions. You
    just don't have the key to unlock the consistent release of
    that information. This is the world we live in as payers and
    population health decision makers.
        The limitations on information we are able to obtain
    results in a hindrance to patience access to novel and emerging
    therapies, limits our ability to accurately forecast, plan, and
    budget for anticipated expenditures, and it precludes our
    ability to contract on value rather than volume. This is the
    reason I am here before you today, to demonstrate the need for
    a legislative framework in support of House Bill 2026 which
    will provide the key to unlock additional information needed
    for us to make informed benefit decisions for better patient
    access to treatment. These concepts have been discussed in
    depth with a diverse group of stakeholders including payers,
    manufacturers, clinicians, and patient advocacy groups who
    provide consensus recommendations for how, who, and what
    information should be exchanged prior to FDA approval. This
    information should be limited to a narrow audience inclusive of
    payers and population health decision makers. This scope does
    not include manufacturer communications with patients or
    prescribers prior to FDA approval.
        Let me share a few personal examples where lack of
    information has decreased patients' timely access to treatment.
    In December of 2013 and October of 2014, the FDA-approved
    breakthrough treatments for the treatment of hepatitis C. These
    drugs had novel mechanisms of action which changed the
    landscape for patients with this diagnosis. Note, these
    approval dates were several months after we had already--one of
    the payers had already analyzed costs and planned benefit. Had
    we been able to discuss in advance of the approval of these
    treatments, we would have had a better understanding of the
    landscape, timing of approval of multiple products, the
    relevant patients for each treatment, and any clinical
    information that would help us to make better decisions and
    ultimately been able to treat more patients in a more effective
    manner without the subsequent criteria revisions that proceeded
    after the approval of these products.
        More importantly, the lack of needed information can impede
    patient access as seen in the new treatments for Duchenne's
    Muscular Dystrophy. In this instance, the level of evidence
    required to deem products safe and effective met the
    requirements for FDA approval. However, due to the inability of
    payers and manufacturers to openly discuss the level of
    evidence required for coverage, payers are not covering these
    therapies at this time. This is why the bi-directional
    information exchange is important to understand the level of
    evidence available and necessary for coverage. This example has
    left patients in a situation where they cannot access therapy.
    Had payers been able to convey the level of evidence required
    for coverage, could we have avoided this situation? Perhaps.
        Another patient access issue was one I experienced in the
    past year for a request for oncology. On September 21, 2016, we
    received a coverage request for a treatment of a patient
    diagnosed with inoperable lip cancer that had recently spread
    to their tongue. The FDA granted accelerated approval to expand
    the indications of an existing chemotherapy treatment on August
    5, 2016 to include head and neck cancer. However, when we
    received the request for coverage, the labeled indications and
    data supporting the expanded indication were not publicly
    available. In this situation, had I had the ability to discuss
    the data in advance with the manufacturer, I could have been
    better prepared to discuss the requested treatment with the
    provider, rather than scrambling through clinicaltrials.gov and
    requesting a copy of the clinical trial from the manufacturer
    while the insured patient awaited my coverage decision.
        Because we can only estimate when therapies will be
    approved, if we receive a coverage request shortly after FDA
    approval, the landscape still remains one of chaos and special
    requests to manufacturers until the data is published,
    compendia and guidelines are updated, and coverage criteria
    reflect these new and novel treatments.
        I have demonstrated in the previous examples each of these
    breakthrough therapies represent innovations and the potential
    to change a patient's life, if they are able to gain access to
    treatment. The barrier to access to novel therapies is a
    population health decision maker's ability to have sufficient
    data and sophisticated discussions with those most informed
    about the utility of the products in a timely enough fashion to
    budget, plan and forecast it for the therapies coming to
    market.
        In conclusion, this is an issue of great importance for
    patient access to emerging therapies where a diverse group of
    stakeholders have come together to develop consensus
    recommendations. This includes a very narrow audience and scope
    of exchange between manufacturers and payers only. We need your
    legislative support to better care for our patients. Thank you.
        [The prepared statement of Ms. Khachatourian follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

        Mr. Burgess. I thank you for your testimony. I want to
    thank all of our witnesses. It has certainly been compelling
    testimony this morning. People will note that I allowed the
    clock to run over because you had important information to
    provide us. I guess we will underscore that I will not be so
    generous with Members, so try to confine your time to the 5
    minutes allotted to these products that have not been evaluated
    by the FDA. This product is not intended to diagnose or prevent
    any condition, just to get through the appropriate label
    disclaimer.
        Let me begin the questioning and I will recognize myself
    for 5 minutes. And Ms. House and Ms. Khachatourian, thank you
    so much for your testimony.
        Ms. House, while you were talking and I actually wrote down
    a note to myself about when you mentioned about clinical trials
    and I was going to ask you about the utility of getting the
    information off of clinicaltrials.gov and then Ms.
    Khachatourian actually referenced that as well. So this is a
    real-world phenomenon where payer decisions are unable to be
    made, but the data is sort of accumulating on the data side of
    the docket, but it is not coming up to the payer's side. So it
    sounds like both of you have dealt with that.
        And Ms. Khachatourian, I thank you for bringing up the
    issue with the new hepatitis C drugs, because we were sitting
    on these panels in 2012 and 2013. And I would suggest it is not
    just an issue of commercial payers. Our State Medicaid
    directors, our State prison directors, our Federal prison
    directors were going to have to deal with this information in
    very short order and they did not have it available to them.
        And I would be happy to listen to what both of you have to
    say, particularly on the clinicaltrials.gov. Are we doing a
    good enough job getting that information out there in a usable
    way so that you can actually begin the process of what are we
    going to have to do as far as on the payer's side?
        Ms. House, we will start with you, and then I would like to
    hear Ms. Khachatourian's thoughts on that.
        Ms. House. Thank you, but I didn't share my comments that I
    have in my written testimony. I included two studies that were
    done on the clinicaltrials.gov database where there was a
    random sampling of 600 trials originally. And 50 percent of
    those trials did not have a corresponding article. The second
    study was even more alarming in that there was a look at 13,327
    trials and 1-year post-data closure, only 13 percent of those
    has posted clinical trials information. And even when they gave
    a bit of a grace period and extended that for another couple of
    years, only 38 percent had clinical trials posted there. So not
    only is the system extremely difficult to sort of use and find
    and especially as we are moving into the age of personalized
    medicine to get to trials that are relevant for me, the data
    results aren't there.
        And I will give you an example that happened to me just
    last week, is that a patient of ours reached out and he has a
    certain type of lung cancer, ALK positive lung, in which there
    are a number of solutions and options available for him. His
    physician wanted to put him on a phase 2 trial with a new
    product and he said, ``What do you think about this?'' And so I
    went online to try to find information because I was trying to
    decide why would they put him on a phase 2 trial instead of the
    phase 3 trial, and I am an educated consumer and I have worked
    in clinical trials for a long time. After about an hour and a
    half, I could find two sources online to your point. One of
    them was with a reputable medical society and the other was an
    opinion piece on the way in which this product worked.
        They are in a phase 3 setting already, so there is a lot of
    evidence on this particular drug and not available to even
    educated consumers.
        Mr. Burgess. OK. Ms. Khachatourian.
        Ms. Khachatourian. Thank you, Mr. Burgess. I actually
    pulled some dates more relevant to some recently approved
    therapies. In the hepatitis space, the products Zepatier and
    Epclusa were approved January 28, 2016, and June 28, 2016, per
    the FDA website. However, results on clinicaltrials.gov were
    not published until September 27, 2016 and April 26, 2017
    respectively. So just to give perspective regarding when data
    is available and results are published, those are key dates
    that I was able to glean. I have some oncology examples as
    well, but I think that proves the point regarding the delay in
    access to information that is necessary for coverage decisions.
        Mr. Burgess. Dr. Van Hare, you referenced the rich data
    sets that would be available by a drug or device manufacturer,
    but that data is sort of locked away from the clinician. I
    guess you have to go the bar to have those discussions? You
    can't have those discussions in the hearing room or the
    continuing education room? You have to go offsite?
        Dr. Van Hare. On the stairwell.
        Mr. Burgess. On the stairwell, OK. Very well. And you see
    what we are talking about today as a way of unlocking those
    data sets being available to the clinicians?
        Dr. Van Hare. I think so. I think it is really pretty
    simple for allowing off-label use. A physician who prescribes
    something off-label is responsible for ensuring that they have
    evaluated the most appropriate clinical data before they make a
    decision about prescribing something off-label and some of that
    data is actually held by the manufacturers.
        They are allowed, as I understand it, to provide it to us
    privately and in response to an unsolicited request, but you
    know, there is 300 of me in the country, the pediatric
    cardiologists who do what I do in the country. Every single one
    of us has to independently call up the drug company to get the
    information. It is not particularly efficient.
        Mr. Burgess. No. I think my time is expired. I want to be
    respectful of everyone's time.
        Mr. Green, you are recognized for 5 minutes for questions,
    please.
        Mr. Green. Thank you, Mr. Chairman. Long ago, Congress
    recognized the importance of requiring manufacturers to provide
    evidence demonstrating the safety and efficiency of the
    product. In marketing under current law, drug and medical
    device manufacturers can disseminate certain medical and
    scientific information about unapproved uses of approved or
    cleared products to health care professionals and other
    entities.
        Recent court cases cited as a source of uncertainty around
    the types of communication about these unapproved uses are
    permissible.
        Ms. Charo, in your written testimony, you said if the First
    Amendment means that the off-label promotion must be permitted,
    then the promotion of entirely untested, unproved drugs should
    also garner the same protection. Is that true?
        Ms. Charo. I fear that the logic would be the same in both
    cases. Now it is true that for things that have been approved
    at least once, one does have some, at least, early information
    that the drug is not highly toxic because that is what we are
    going to get from the early Phase 1 or 2 trials. But the
    reality is over time, both the drugs that have never been
    approved before or the off-label indications for things that
    have been approved turn out to fail which means that one begins
    with a presumption that any unapproved use or any unapproved
    drug is probably not safe or not effective until it is proven
    to be so.
        Mr. Green. Well, this is an issue that this subcommittee
    and our committee has wrestled with for a number of years. Can
    you help us understand what restrictions the Constitution does
    and does not allow? Does the First Amendment prohibit the FDA
    from restricting promotion of unapproved uses?
        Ms. Charo. No, there are a number of Federal cases that
    have upheld the FDA's authority to do just that. There is
    constitutional protection for commercial speech and there are
    standards for that protection and in the area of commercial
    speech it is a fair amount of protection although not the same
    degree of protection as you would get for political speech or
    other forms of speech. And those restrictions on commercial
    speech are permitted when there is a substantial public
    interest in doing so. In this case, by restricting off-label
    promotion, one is able to create both a stick and a carrot that
    drives the pharmaceutical industry toward the research needed
    to actually figure out which things are safe and which things
    are effective. If one is able to simply promote without
    restriction and gets no market advantage by going in and
    investing in the research, one loses that system entirely and
    we really do risk having an absence of information for people
    like Dr. Van Hare to solicit or to develop on his own, let
    alone to share with his colleagues.
        Mr. Green. Ms. House, I note in your focus on your
    testimony the fact that so much clinical trial data is
    unpublished. One thing that concerns me is the bias in what is
    published. Multiple studies have shown that positive trial
    results are more likely to be published than negative results.
    And in particular, industry sponsorship has been demonstrated
    to be a factor contributing to the biased publication. Industry
    has no incentive to publish or promote negative findings.
        My question is if industry is more likely to publish
    positive than negative results, do you also worry that positive
    results will be promoted more than negative results, even if
    there is a particular research being communicated is truthful
    and not misleading? Doesn't selected provocation create a
    distorted view of the safety and effectiveness of the unproven
    use?
        Ms. House. I am going to answer this very carefully because
    I have not seen the data that you re referencing that would
    suggest that there is more positive data than negative data.
    What I would say is that our position is is that both positive
    and negative data needs to be published in an equal manner and
    should be available for communication because we do know that
    there are patient harms as well as benefits.
        Mr. Green. And I think that is what we want to get to. If I
    am a pharmaceutical or if I am advertising anything else, I am
    going to talk about how great it is. If we are running for
    office, I am not going to talk about our bad side. We are going
    to talk about the good side. So we need to have it, but we need
    some agency to be able to say this is what you are doing and
    the FDA is what we have. That is my frustration, I guess.
        Dr. Van Hare, in your testimony you note that Pediatric
    Research Equity Act has not been sufficient in producing the
    amount of shareable data we might like particularly in the
    older drugs and clinical decisions are often made. I think you
    raised an important point about the need for the robust data to
    allow clinicians to make the best decisions they can. My
    concern is there is nothing in this legislation we are talking
    about today would actually encourage drug companies to conduct
    those clinical trials that could answer important questions for
    pediatric populations. And again, our subcommittee for decades
    has wrestled around what may be appropriate for an adult is
    just not appropriate for children and we need to do a lot more
    work on that to make sure that we don't leave out the pediatric
    population.
        Mr. Chairman, I know I am over time, so I yield back my
    time, unless you want to give it Dr. Van Hare?
        Mr. Burgess. Dr. Van Hare, did you want to comment?
        Dr. Van Hare. I think that legislation has actually helped
    children in terms of getting a lot more information about
    drugs. And certainly in the pediatric world, originally for
    some companies or actually enticed some companies to actually
    do some trials. For the most part though companies are not
    really interested in the pediatric market. We are very, very
    small market and sort of thinking about the carrot and stick
    sort of approach, none of the carrots are really going to help
    us in pediatrics because it is a fairly small market. So we are
    left in a situation where no one is going to do the type of
    clinical trial that was actually going to allow labeling for
    pediatric application for a lot of the things that we actually
    use.
        Despite that, we are talking care of our children, and we
    need the best available data to make those decisions.
        Mr. Burgess. Thank you. The Chair recognizes the gentleman
    from Illinois, Mr. Shimkus, 5 minutes for questions, please.
        Mr. Shimkus. Well, thank you. I am going to follow up with
    Dr. Van Hare first of all saying for my colleagues that the
    Washington University School of Medicine is one of the
    preeminent institutions in our country. And VJC which they are
    affiliated with, that is the go-to for major deals. So welcome.
        Dr. Van Hare. Thank you.
        Mr. Shimkus. And I know that because--please extend my
    hello to Dr. Braverman and Dr. Damiano, who I know personally
    from personal medical stuff. I am a Homer for these folks and I
    have great confidence in your testimony and your word. But I
    would like to follow up on the question in that how often do
    you assess the various information to try to treat kids? I mean
    so we are talking about FDA approval, but you have given
    testimony about outside information to make sure you can best
    care for kids. How often do you go and search outside
    information to try to bring the best medical care to the kids
    in the cardiology aspects?
        Dr. Van Hare. It really depends on what the condition is
    that we are actually trying to treat. I would say that we do
    have the process of developing consensus documents that
    actually summarize the medical evidence, the clinical trials
    and things like that that actually sort of express and
    certainly our society, the Heart Rhythm Society does this all
    the time to create these consensus documents to give physicians
    guidance. But you know, I guess pediatrics and also really sub-
    specialty medicine in general, we take care of a lot of very
    unusual types of conditions that don't really fall under the
    labels and the recommended uses. And so I guess for those less
    common, more unusual types of situations, we are often looking
    to our colleagues. We are calling around. We are finding what
    has your experience been with this? What has your experience
    been with that?
        Interestingly, I am a real proponent of the concept of
    partnership between industry and physicians. We often work
    elbow to elbow when we put pacemakers in and when we do
    different kinds of procedures. They have a lot of information
    just from their experience and it is an important source for
    us.
        Mr. Shimkus. Great. Thank you. Let me go to Ms. Klasmeier.
    In your testimony you talked about, and I quote, ``strict
    scrutiny'' the test. What does that mean, strict scrutiny in a
    test in court?
        Ms. Klasmeier. As a practical matter, Congressman, it means
    the goverment loses. So strict scrutiny is a bit of a legal
    fiction that we indulgence. It reflects the notion that when
    you examine Government regulation that affects core speech such
    as political speech, it is very, very hard for the Government
    to sustain its burden of justifying that speech regulatory
    provision against First Amendment is solvent. So as a practical
    matter, if the court concludes the applicable standard is
    strict scrutiny, the Government loses.
        Mr. Shimkus. Maybe my colleague, Mr. Griffith, will follow
    up on that. He is our legal mind here on the committee and does
    a good job.
        Let me finish with Dr. Kesselheim. I am somewhat confused
    in your testimony because you used numerous times the term
    promotion over and over again in your testimony. But on page 2
    of the Griffith draft, it explicitly excludes promotional
    communications. Am I missing something?
        Dr. Kesselheim. Well, no. I mean I think this is part of an
    example of how the Griffith draft actually makes something that
    is fairly clear a lot less clear because, you know, if the
    pharmaceutical company defines something as promotion
    determines whether or not they fall into this safe harbor.
        Mr. Shimkus. What do you mean by promotion? You used it
    numerous times.
        Dr. Kesselheim. Sure. When a pharmaceutical company
    promotes a drug, it goes out and it tells people about the use
    of the----
        Mr. Shimkus. For their ability to sell it?
        Dr. Kesselheim. Yes. It goes out and it tells physicians
    about how to use the product and it sort of promotes the use of
    the drug through one of the various advertising----
        Mr. Shimkus. I am reclaiming my time. I will let
    Congressman Griffith kind of hash this out more, but again, on
    page 2, it is pretty clear. It says communication is not
    advertising or otherwise promotional in nature. So I just had a
    concern with your statements in your opening statement because
    you said it over and over again. I think it gives the wrong
    indication of what my colleague is trying to do. With that, I
    yield back my time.
        Mr. Burgess. The Chair thanks the gentleman. The gentleman
    yields back. The Chair recognizes the gentlelady from Illinois,
    Ms. Schakowsky, 5 minutes for questions, please.
        Ms. Schakowsky. Thank you. I think it is really important
    that we step back and remember that the FDA approval process
    really is the gold standard, the universal gold standard to
    determine safety and efficacy. And efforts to undermine that
    standard are very worrisome to me and I think that is what
    happens in these drafts. I think that Ms. Charo put it best in
    her testimony when she stated ``for complex products like
    drugs, the marketplace of ideas cannot work properly with
    unvetted information from a self-interested source.''
        I mean I think that often this committee is inclined to say
    whatever PhRMA wants, PhRMA gets. But I want to ask Dr.
    Kesselheim, we have heard compelling testimony, I think, about
    access for patients to drugs. And so it is very important, I
    think, for you to explain what---does access trump safety or
    does it have to by having these kind of off-label procedures?
    It seems to me that safety ought to come first, but are there
    ways to guarantee that safety without the process of approval
    by the FDA?
        Dr. Kesselheim. Well, I mean so sure and I think that part
    of some of the testimony that we heard was a little bit
    disingenuous because the access to the products was not defined
    necessarily by the communications that occurred. The access in
    the case of the hepatitis C drugs, the effectiveness of the
    hepatitis C drugs is not a secret. Everybody knew how well they
    worked. Access to them was determined by the high cost of the
    product, not the evaluation, not whether or not there could
    have been communication in the few months before the drug was
    approved. So I mean I think the issue is really about getting
    high quality evidence or high quality communications out to
    help inform the market so that patients can make well-informed
    decisions based on the highest quality information that is out
    there possible. And the way to do that is to make sure that a
    neutral, third party body of experts like the FDA is able to
    vet the information. And I think what we should be doing is
    talking about how to make sure that more information is
    published, more trials are published, more trials are
    available, open access, and that the FDA has more power and
    more authority to review information so that they can make
    those kinds of determinations so patients can benefit.
        Ms. Schakowsky. Is there a way for the FDA to move more
    quickly? We heard about 9, 10 years, or whatever?
        Dr. Kesselheim. I think if the FDA had more resources, it
    would be able to move more quickly. There are plenty of
    examples where the FDA has gone out and has been concerned
    about new safety issues that emerge, about off-label uses and
    ultimately goes through the process of revising the label to
    try to integrate those kinds of changes. If the FDA had more
    resources added and more people doing that kind of post-market
    surveillance, label updating kind of work, then I think we
    would get that information out to patients and vetted
    information out to patients more efficiently and more quickly.
        Ms. Schakowsky. Ms. Charo, one of the most compelling
    things I heard from you saying that, in fact, when you look at
    these drugs, the majority of them, in fact, would probably not
    meet the test. Am I hearing you right?
        Ms. Charo. You are hearing me correctly, and I believe, in
    fact, it was Ranking Member Green who referenced some of those
    studies in his opening comments.
        You know, scientific research is often somewhat equivocal
    for a very long time. I think what we are discussing here is
    really what to do in that interim period where the evidence is
    shifting around. Do we presume everything is going to work and
    therefore everything people want to say is likely to be true
    and should be allowed or are we going to presume that it
    probably isn't going to work out and we should restrain the
    speech until we have actually proved it will.
        From my perspective, given that the risk of incorrect
    information is that people will actually be harmed, or they
    won't go for the effective treatment, they will go for the
    ineffective one, we need to err on the side of caution here and
    protect the larger population.
        That said, there are certainly going to be some occasions
    in which it turns out that something does work and it would
    have been wonderful if we could have seen it earlier and talked
    about it earlier, but those incidents will be fewer than those
    in which it would be damaging.
        Ms. Schakowsky. In the last 30 seconds, Dr. Kesselheim,
    what does history tell us about off-label promotion? Are there
    some things we should be recognizing here?
        Dr. Kesselheim. Sure, I mean over and over and over again
    throughout history and you don't even have to go back to the
    thalidomides 50 years ago, more recent history tells us that
    off-label promotion drives physician practices in ways that
    favor the drug being promoted, not in ways that favor the
    overall state of the evidence and the overall state of
    practice. I think that we need to be very wary about efforts to
    try to expand that promotion when it covers nonevidenced
    based--potentially nonevidenced based communications.
        Ms. Schakowsky. I think we need to, when it comes to
    patient access, discuss more about the cost. Thank you.
        Mr. Burgess. The gentlelady yields back. The Chair thanks
    the gentlelady. The Chair recognizes the gentleman from New
    Jersey, Mr. Lance, 5 minutes for questions, please.
        Mr. Lance. Thank you, Mr. Chairman. Let me state that I
    don't believe any of the testimony has been disingenuous, in my
    judgment. This is a very difficult issue, and we are trying to
    balance the equities on this committee, and I am pleased that
    every member of the panel is here, and I do not question the
    integrity of any member of the panel.
        Counselor Klasmeier, do you believe that the standard will
    be strict scrutiny, or will it be rational basis, or will it be
    some intermediate standard, based upon your professional
    judgment as a distinguished member of the bar?
        Ms. Klasmeier. Congressman, my judgment is that the
    standard will be some variation of intermediate scrutiny.
        Mr. Lance. Intermediate scrutiny, yes.
        Ms. Klasmeier. And it will be most likely the Central
    Hudson standard with a garnish of heightened scrutiny as a
    result of the Supreme Court's decision in Sorrell in 2011.
        Mr. Lance. Yes, that is my judgment as well, and I think
    that there is a history of decisions in this regard that would
    indicate that that is probably where we would be eventually as
    a matter of legal analysis. Thank you.
        Dr. Van Hare, we have all heard that some off-label uses
    are well established in clinical practice, and supported by
    high-quality evidence, and are the standard of cure for many
    conditions. From your perspective, based upon your
    distinguished history, how does the pieces of legislation
    before this committee stand to improve care for patients?
        Dr. Van Hare. Well, to the extent that the legislation
    proposed by Congressman Griffith allows or improves the
    efficiency of sharing data that the device companies and
    pharmaceutical companies actually have, for physicians who are
    prescribing off-label, I think it will actually help.
        Mr. Lance. Thank you, and other members of the panel are
    certainly welcome to comment.
        Ds. Khachatourian, what are the odds that if we pass
    legislation we are considering today, sophisticated population
    health decision makers like payers, provider sponsored health
    plans, pharmacy-benefit managers, and other organizations would
    be misled by unscrupulous drug and device manufacturers who
    make unfounded claims about their products?
        Ms. Khachatourian. So first let me acknowledge my testimony
    by no means disingenuous.
        Mr. Lance. I am sure and that is why I raised it. And if I
    might interrupt you, I try to lead by example in the Congress,
    both on the floor and in committee, and I enjoy the testimony
    of every witness who comes before us. Those who know me know
    that disingenuous is not a word that I find attractive in
    vocabulary here on Capitol Hill. Yes, please continue.
        Ms. Khachatourian. Thank you. So population health decision
    makers and clinicians that we are discussing here are well
    trained to look at things with scrutiny and to determine what
    level of evidence is acceptable. And during the multi-
    stakeholder discussions that we have had, we did address the
    need to determine a level of evidence and to have an agreement
    on what is acceptable and nonmisleading. And as evidence
    continues to evolve and as new therapies continue to emerge,
    that is the goal, is to develop strict criteria that will be
    used to apply to any level of evidence in order to ensure that
    it is high level and with the patient's best interest in mind.
        Mr. Lance. Certainly, and that is what we are attempting to
    get to a place where we can make sure that always there is the
    greatest standard of care. It is the jurisdiction of the
    subcommittee and ultimately of the full committee to promote
    the better health of the American Nation, and we recognize this
    is a difficult issue and I certainly commend my colleagues,
    including the gentleman to my immediate right, the
    distinguished Member from Virginia, as we undertake an analysis
    of how best to protect the American people recognizing that
    that is the goal of this subcommittee in a bipartisan nature. I
    yield back 22 seconds, Mr. Chairman.
        Mr. Burgess. The Chair thanks the gentleman. The Chair
    recognizes the gentlelady from California, 5 minutes for
    questions, please, Ms. Matsui.
        Ms. Matsui. Thank you very much, Mr. Chairman. This
    committee recognizes the important role that FDA plays to
    ensure public health and safety as evidenced by the bipartisan
    User Fee Reauthorization that we intend to pass out of the
    House this afternoon.
        Now we can't tolerate efforts to jeopardize that role as
    patients across America who take drugs to treat or cure
    conditions rely upon the FDA to monitor the safety of these
    drugs and devices.
        I am really glad that we are holding this hearing today to
    examine issues that arise around information sharing,
    particularly for those so-called off-label use and what could
    be done to alleviate those issues without detracting from FDA's
    ability to regulate safety.
        I am particularly interested in the situation that many
    rare disease and cancer patients find themselves in. As many as
    one in five prescriptions are written for drugs off-label,
    meaning that they are prescribed for a condition or population
    that has not been FDA-approved as safe and effective.
    Oftentimes, off-label drugs are the only treatment available
    and even the standard of care for rare disease patients with
    limited options.
        Ms. House, thank you very much for your advocacy on behalf
    of cancer patients. Can you please discuss prevalence of off-
    label use in cancer patients?
        Ms. House. So there was a physician posted by the Friends
    of Cancer Research just yesterday that indicated that the use
    in cancer off-label was close to 80 percent. And part of--one
    of the problems that I just wanted to raise is I was looking at
    some other discussion is I am going to give you an example. It
    is an older example, but it really talks about how the current
    labels are out of date. There was a time around 2000 where this
    is the time prior to personalized medicine, so it was still in
    the era of poisons for cancer, that there was a combination
    being used off-label as standard of care for the treatment of
    lung cancer. That particular combination failed at that time 13
    Phase 3 trials which is the gold standard for the evaluation
    for the FDA, yet it continued to be used standard of care for
    many, many, many years beyond that.
        This morning, I went on the FDA website and pulled up the
    label for the lead drug in that and today in 2017, still has
    not been updated to reflect the use of that combination which
    is a problem.
        Ms. Matsui. It is a problem, right. Now, you know when a
    family gets a cancer diagnosis, I think the world stops. And
    you are sort of grasping at what can we do? And I think we all
    go to the internet. That is where we go right now.
        What types of information is generally available to
    patients and their providers when a drug is used off-label and
    even when you are an educated consumer, you really kind of hit
    a brick wall. What kinds of solutions might you recommend to
    address these challenges?
        Ms. House. I think creating solutions that again are
    tailored to the stakeholder, to their literacy level, to their
    educational level. There is really no reason why we can't
    create forums that would be peer reviewed, scientifically sound
    analysis, and presentation of clinical data. What it does
    prevent then is people going to the internet and getting into a
    chat room that may be facilitated out of another country or by
    somebody who has absolutely no medical background. And we see
    that happening all the time. And furthermore, if a patient
    calls a pharmaceutical company and says I am a patient, can you
    give me information about XYZ, the response will almost
    uniformly be, I cannot answer your question. You will have to
    go speak with your doctor.
        Ms. Matsui. Thank you very much. Ms. Charo, I know you have
    concerns about the legislation that we are discussing today.
    Are there ways that we can refine the legislation to reach our
    shared goal of promoting public safety by increasing patient
    access to safe and effective drugs? I think there is
    information out there and you know, we are in a time now where
    there is much more research and innovation and I would hate to
    just have a hard and fast rule regarding this.
        Ms. Charo. Thank you. I completely agree with you that
    there are other avenues that need to be explored. For one
    thing, it may make sense to try to distinguish those areas
    where off-label use really is a necessary and important part of
    medical care as we just heard in the area of cancer, and some
    other areas there it really is not as prevalent and is not as
    needed. And I would suggest that pediatrics may be another good
    example.
        And the Congress has made great strides in trying to create
    new systems for both incentives and even possibly rewards for
    continuing the necessary research to find what really is safe
    and effective, for example, in the pediatric population.
    Working on making sure that there is a proper incentive and
    reward to fill in the gaps in those areas would be a good step
    forward and might accomplish many of these goals without some
    of the risks that are intended upon some of the ambiguities and
    what constitutes promotional marketing or what constitutes
    accurate information.
        Ms. Matsui. Thank you. I have run out of time. I yield
    back.
        Mr. Burgess. The Chair thanks the gentlelady. The
    gentlelady yields back. The Chair recognizes the gentleman from
    Indiana, Dr. Bucshon, for 5 minutes for questions, please.
        Mr. Bucshon. Thank you, Mr. Chairman. I was a practicing
    cardiothoracic surgeon prior to coming to Congress and I just
    have a comment, not a question, but the medical community is
    relatively small and I think Dr. Van Hare said there is 300
    pediatric cardiologists. There is about 4,500 to 5,000 cardiac
    surgeons. Information travels quickly. Physicians are always
    looking for better ways or effective ways to treat their
    patients whether it is on label or off-label and information
    passes quickly.
        Frustration with labeling can be really high amongst
    different physician communities because of the delay in
    updating what may or may not be FDA-approved. Patients are
    desperate and are getting information potentially from
    incorrect sources including the internet as has been pointed
    out and so I would suggest that we definitely need reform so
    that patients have the opportunity to get more accurate
    information.
        With that, I am going to yield the remainder of my time to
    Mr. Griffith.
        Mr. Griffith. Thank you very much. I appreciate it greatly.
    Let me first say that I appreciate everybody being here today
    and appreciate all of your testimony. I am open to continue to
    work on the language to make sure that we get it right. So that
    is something that I would invite you all, if you have issues
    with the language that we currently have, please get those
    suggestions to us because we want to try to do this in the best
    way that we can. We do believe that we need to do something on
    a legislative side.
        Also, Mr. Chairman, I have some letters in support of the
    bill and a draft language, and, if I could have unanimous
    consent to enter those into the record, I would appreciate it.
        Mr. Burgess. If the gentleman will share those with us, I
    will seek unanimous consent in a moment.
        Mr. Griffith. I also want to make sure that we are all
    working on the language that we currently have. And so what the
    bill says is, when we are talking about communication, if you
    look on page 2 it says, ``(a) the communication is not
    advertising or otherwise promotional in nature; (b) the
    communication is supported by competent and reliable scientific
    evidence.'' And then (c) and this was to address some of the
    concerns that have been raised here today, we put this language
    in: ``The communication clearly discloses appropriate
    contextual information about the data presented including
    information about limitations.'' And I probably should put
    numbers in front of these. ``(1) Limitations of the data; (2)
    the scientific and analytical methodologies used; and (3)''--
    and I think very importantly--``any contradictory data or
    information known to the manufacturer or sponsor.''
        We are never going to solve all of the problems if somebody
    is not doing what they are supposed to do, but our intent is to
    try to make sure that both sides are presented. I think
    somebody mentioned that earlier in their testimony, that both
    sides are presented and that the negative evidence is out there
    as well.
        And then we talk about situations related to the rare
    diseases. Cancer has been mentioned today and the children
    because one of the problems you have in those situations and
    Dr. Van Hare, you touched on this is that there may not be a
    sufficient number of patients to actually warrant doing a
    clinical study. Nothing compared to what you deal with your
    families Dr. Van Hare, but my son who is now 11 had \2/3\ of
    his body covered with eczema when he was about 3 months old. I
    kept telling my wife because of the history in the family we
    have allergy problems, honey. We got him to an allergist.
    Between the cream that worked for me that my pharmacist knew,
    between the steroid creams, between the antihistamines that
    they gave him, we were able to control that situation. We still
    have issues there. But for a child under the age of 2, there
    were no--some of that might have been on-label, but most of
    that treatment was off-label, so I appreciated Ms. Charo saying
    that we ought to take a look at that, because I think those are
    the two hot-button areas. But that doesn't mean we should
    exclude others.
        I was very curious, too, about this whole agent concept
    that is going on where you can't go and tell the 300 other
    doctors, Dr. Van Hare. Could you speak on that briefly, and I
    have only got a minute left of this time period.
        Dr. Van Hare. Yes. It has to do with how CME or Continuing
    Medical Education is defined. CME is actually a safe harbor. If
    I am speaking at a conference that is sponsored by an
    accredited CME provider, like the Heart Rhythm Society or the
    American College of Cardiology or some other group, I can say
    whatever I want and I can talk about off-label indications as
    much as I want. If I am actually speaking at a conference that
    is actually sponsored by the pharmaceutical company or the
    manufacturer, then I basically am an agent, or considered an
    agent.
        Mr. Griffith. So if on the podium somebody asks you about a
    catheter to be used in a child that might be off-label, you
    could then be deemed and the company could be deemed that you
    are their agent and then be in trouble under the current rules
    of the FDA. Is that correct?
        Dr. Van Hare. That is my understanding.
        Mr. Griffith. That is my understanding also. All right, Ms.
    Klasmeier, my friend and colleague from New Jersey, Mr. Lance,
    did a great job of going through the intellectual. Let us
    translate that into human regular English. That means that if
    you bring that example to the courts, FDA is most likely going
    to lose, wouldn't you agree?
        Ms. Klasmeier. I would agree and I would go one further.
    FDA did lose that case. That was the Washington Legal
    Foundation decision in 1998 and the upshot of that is that the
    court found it unconstitutional for the Government to purport
    to restrict the identity of the speakers that could participate
    in those kinds of continuing education events that Dr. Van Hare
    described.
        Mr. Griffith. Thank you very much. I yield back to my
    colleague. Thank you.
        Mr. Bucshon. I yield back.
        Mr. Burgess. The gentleman had a unanimous consent request
    and I sought counsel from the other side of the dais, so
    without objection, so ordered if that unanimous consent request
    still stands.
        [The information appears at the conclusion of the hearing.]
        Mr. Griffith. It does, and I apologize. I just saw my time
    taken away.
        Mr. Burgess. Very well. The Chair recognizes the gentlelady
    from Florida, Ms. Castor, for 5 minutes for questions.
        Ms. Castor. Well, thank you very much, Mr. Chairman, for
    calling this hearing. I think allowing drug companies and
    manufacturers to market their drugs and devices for unapproved
    uses would be very dangerous for American families, American
    consumers. It would reduce the incentive for them to go through
    FDA's approval process and reduce the incentive to go through
    clinical trials that really just test whether or not a product
    is safe and it is effective. FDA's approval process right now
    is the gold standard for safety and efficacy.
        The FDA Commissioner, Dr. Gottlieb, has said the most
    important incentive to developing useful information remains
    the ability for companies to market drugs based on what can be
    proven scientifically. Now this is not a hard and fast rule
    because I have learned today and reviewing your testimony,
    there are safe harbors, but nevertheless, Professor Charo, some
    contend that we must revisit this regulation of off-label
    promotion because the trend in the courts is that restrictions
    on off-label promotion run afoul of the First Amendment. I
    think this is a stretch. Does the First Amendment limit FDA's
    responsibility for scientific review? Does it limit FDA from
    restricting promotion of unapproved uses? If not, what avenues
    do medical product manufacturers have to communicate about such
    uses?
        Ms. Charo. Well, we have seen some cases that have touched
    on these things from the fringes, but you don't actually get
    cases that touch on it directly. For example, in one case that
    is frequently cited for the suggestion that the Constitution
    prevents the FDA from restricting truthful speech, at issue at
    the time was not truthful speech, but simply off-label speech
    and the FDA premised its entire case on the fact that the
    speaker had been discussing an off-label use and never really
    talked to the issue about whether or not the speaker's comments
    had been true.
        The problem here has simply been that it is really and I
    hope that Mr. Griffith's staff is still around for this, the
    problem is that no company is going to have all the information
    about all the studies that are being done at that time
    including those that have negative results because of various
    rules about confidentiality of information. The FDA may be in
    possession of all the information, but not necessarily every
    company. So even with the best of intentions to be conveying
    what they believe to be truthful and contextualized
    information, there is the risk that that actually is missing
    large areas of data that would suggest that the studies they
    are discussing are not, in fact, going to be indicative of a
    truly safe and effective drug at the end of the day. This is
    why there really is a substantial public interest which is one
    of the key elements in the restriction of speech to the current
    system.
        And the alternatives that have been presented,
    unfortunately, I believe offer risks to public health that
    dwarf their benefits which is why the second rung, the second
    prong of these tests which have to do with whether or not the
    Government can find an alternative way of achieving its goals I
    think show that really the current system is probably the best
    way, tweaking, yes, but the removal of many of these
    restrictions, I don't believe is necessary in order to meet the
    Constitution test.
        Ms. Castor. And there seems to be debate on whetherthe
    Griffith proposal would restrict scientific exchange under the
    safe harbor. What is your view of this and the Griffith
    discussion draft?
        Ms. Charo. You know, I think that the text does attempt
    does attempt to isolate what is nonpromotional and protect that
    while continuing the prohibit promotional language. I think
    that the difficulty here is that the very notion of what is
    promotional is actually somewhat ambiguous. We now know, for
    example, that it is possible to tweak how various results come
    up on the internet, whether or not it is the first, second, or
    third thing you see on the page. If there is a tweaking
    algorithm, does that constitute promotional if all it does is
    raise your particular data to the front of the page? These are
    the kinds of subtle questions that can both make the language
    ambiguous despite our efforts and also from my perspective,
    suggest that it is better to have the flexible tools of
    guidances that can be negotiated over time with the constantly
    changing nature of communication rather than the somewhat more
    rigid tools of regulation and legislation, let alone having
    courts do it 17 years after the fact and leave everybody
    uncertain for that long period in between.
        Ms. Castor. Dr. Kesselheim, do you have a comment on this
    topic as well?
        Dr. Kesselheim. I mean I also agree that the way that this
    discussion draft is written provides substantial leeway for
    companies to interpret these various provisions in ways that
    are favorable to their particular advertising strategy.
        Ms. Castor. And at the cost to public safety.
        Dr. Kesselheim. And at the cost to public safety.
        Ms. Castor. Thank you. I yield back. I am out of time.
        Mr. Burgess. The gentleman yields back. The Chair thanks
    the gentlelady. The Chair recognizes the gentleman from
    Georgia, Mr. Carter, 5 minutes for questions, please.
        Mr. Carter. Thank you, Mr. Chairman. And thank all of you
    for being here. Certainly, an important subject.
        Dr. Khachatourian, you are a pharmacist, as am I. And I can
    tell you that after 30 years of practicing pharmacy, certainly
    side effects are--we call them side effects. And you know, it
    has always been interesting to me why we call them side effects
    because essentially they are effects of the drug, but they are
    not what we want it to do, so we kind of label them as side
    effects.
        I noticed in your statement, in your testimony, in your
    written testimony that you feel like the Pharmaceutical
    Information Exchange would be helpful and useful and there is
    some debate on whether it should be evidenced based or whether
    it should be information based. And I noticed that you said
    that it should be based on information only, well, not only,
    but basically. Can you kind of elaborate on that?
        Ms. Khachatourian. Absolutely, thank you. So when we think
    about evidence, there are established criteria for evidence as
    far as what constitutes a clinical trial and the acceptable
    level of evidence for FDA approval. When I talk about
    information, information may include financial models, may
    include other information that does not quite meet the level of
    evidence that one might traditionally think. So when we talk
    about information, if I am able to discuss with my clinical
    colleagues at a manufacturer what models might be available,
    what sub-populations were studied and what level of information
    might be available that can help me to make more effective
    decisions, that is what I mean by information.
        And again, I will reference the multi-stakeholder forum
    where we discuss developing criteria that will set the
    foundation for what that information might entail and what
    level of quality of information could be deemed acceptable.
        Mr. Carter. You also mentioned in your testimony that a
    very proactive pharmaceutical information exchange would lead
    cost savings. It could lead to cost savings for patients. So in
    that respect, how can we assure that the cost savings are going
    to be passed on to the patients if we don't have transparency
    within the prescription benefit managers and the other middle
    men that are included so often in these scenarios?
        Ms. Khachatourian. Sure. While cost is an aspect of
    evolving and emerging therapies and treatments that are coming,
    cost is an aspect that needs to be discussed. However, with the
    exchange of information it makes us more effective in the use
    of the funds that we have available to make benefit decisions.
    So when we are structuring a benefit based on value, that is
    what value will be conveyed to both us as the payer as well as
    the patient. So ultimately from a cost discussion, that is, in
    turn, outside of the transparency which is a little bit of a
    different discussion.
        Mr. Carter. I am not sure I understand how it can be a
    little bit of a different discussion. Because I believe truly
    that it can have cost savings to the patient if we have
    transparency within the system and I don't see how it can be if
    we don't have transparency.
        Ms. Khachatourian. So I absolutely acknowledge transparency
    is an important factor. However, the information exchange
    between a payer, as well as the manufacturer, will help us to
    make better decisions and with a limited pool of money that we
    are able to allocate to benefit design. We try to make the most
    cost-effective decisions on behalf of those patients that we
    serve, so in turn, the cost savings are passed to the patient
    as the ultimate user of our benefit design.
        Mr. Carter. OK. I will move on. Dr. Van Hare--and thank you
    very much for being here, Dr. Khachatourian.
        Dr. Van Hare, I have seen in my practice over the years,
    particularly with prescription drugs, a lot of off-label uses,
    if you will, in pediatric patients. And I just want to get your
    feeling on the value of that? Because I have seen it first hand
    that it has been very valuable.
        Dr. Van Hare. Yes, well, so I would say it is essential, in
    fact, for most of what we do, particularly in the pediatric
    cardiology area. But I mean I do think we have reservations
    about it. When people make decisions based on information they
    get from like one other colleague who used it once on some
    patient, that is very, very sort of limited. But I would say
    that certainly we have to do it. We have no choice but to do
    off-label prescribing in a lot of situations. And we would
    prefer to have the best possible information.
        We also use what is known about the use of these
    medications in other age groups, particularly adults, or other
    particular conditions and basically extend to these particular
    populations. That may or may not be valid as some other members
    of the panel here have talked about. But absent better data, it
    is all we actually have.
        Mr. Carter. Great. Thank you all very much for your
    participation here today. A very important subject I can tell
    you. Many years of practice in pharmacy, we have used many
    drugs that were not indicated or at least not approved for
    certain therapies that have been very, very beneficial to
    patients.
        Thank you, Mr. Chairman. I yield back.
        Mr. Burgess. The Chair thanks the gentleman, the gentleman
    yields back. The chair recognizes the gentlelady from
    California, Ms. Eshoo, 5 minutes for questions, please.
        Ms. Eshoo. Thank you, Mr. Chairman. And thank you to all of
    the witnesses. I also want to thank our colleagues who are
    offering the drafts and to Mr. Griffith, I especially
    appreciate your openness to suggestions and I think that that
    is very important.
        Over all the years I have been in Congress, this is my 25th
    year, and have worked with medical device manufacturers, worked
    with the biotechnology industry, done legislation that has
    reformed how medical devices are approved, passed legislation
    signed into law, but I can't remember which President relative
    to pediatric medications, and improved that system for
    children. This issue, the issues that are being discussed here
    today, no one has ever raised with me. So this is the first
    time I am hearing about it. But it is good. It is a discussion,
    but it still says something to me that no one has contacted me
    about this. So I don't think it is exactly a burning issue.
        Number two, it is my understanding that what is being
    offered by our two colleagues today were supposed to be a part
    of the overall approval for the FDA, but were pulled because
    they were controversial. I can hear today where the controversy
    is coming from. That is legitimate and I am glad that it wasn't
    in the larger bill, because they really didn't belong there.
    This cake has not been baked yet.
        Now it is my understanding that in one of the discussion
    drafts, that there is no clear list of what qualifies as
    scientific information. Now that is foundational to me,
    scientific information. Not who is gabbing and saying what from
    a given industry. That is always interesting and those
    discussions take place. But we are dealing with over 200
    million people in our country and these words are going to walk
    into their life. This is a huge responsibility. They don't know
    that we are here today. They don't know any of our names, but
    we have the public interest in the safety and the efficacy of
    what takes place on their behalf.
        To Ms. House, I am not sure, are you in favor of the two
    discussion drafts? Yes or no?
        Ms. House. We have not taken a formal position on either.
        Ms. Eshoo. That is fine.
        Ms. House. Neither of them are perfect.
        Ms. Eshoo. Yes, well, but I couldn't tell from your
    testimony whether you were for or against or where you were.
        Ms. Charo, thank you for your testimony. I think that you
    have set down the importance of where the information comes
    from and that it can't be haphazard. There has to be a final
    kind of resting place that has all of the information for
    people in our country that can be used.
        I don't think anyone has really made the case here to take
    it outside of the FDA. Maybe I am missing something, but I
    haven't heard that.
        To Ms. Khachatourian--I love the I-A 09N; I share either
    your husband's heritage or yours--when you spoke about hep C,
    how many patients were excluded from treatment?
        Ms. Khachatourian. So while I can't speak for all payers
    and all----
        Ms. Eshoo. No, but you used that as an example, hep C. So
    we know, it is a company I am very familiar with in my
    district. I have worked with them. They have presented a cure
    which we are not accustomed to. It is expensive. But who was
    left out, according to your testimony?
        Ms. Khachatourian. Sure. So in the initial approval, we
    approved treatments according to the label. So for the first
    time in hepatitis C, we saw the criteria, the approval criteria
    change multiple times. So initially it excluded patients that
    might have cirrhosis. It initially excluded patients that
    according to the FDA label----
        Ms. Eshoo. How do these drafts fix that?
        Ms. Khachatourian. So with the drafts, we could understand
    that there would be evidence published that would add
    additional clinical evidence to indicate effectiveness of
    treatment in those sub-populations although at the time of the
    initial approval, that evidence was not available for decision
    making.
        So in my medical space----
        Ms. Eshoo. You are saying people were excluded, but you
    don't know how many?
        Ms. Khachatourian. I can't speak to the exact number
    globally. However, within our population, Medicare is who
    defines our coverage criteria. So when we submit our criteria
    to CMS for approval, it has to be according to the Part D
    coverage, what is listed in the FDA-approved label. So we
    cannot cover off-label unless it is within the oncology space.
    When we are talking about a Part D indication.
        Ms. Eshoo. I still don't know who has been injured in this
    according to your testimony. That is why I am asking you, and I
    still don't know. But I appreciate your trying.
        Thank you, Mr. Chairman.
        Ms. Khachatourian. If we expand the discussion to
    commercial payer outside of Part D, the additional patients
    that were denied treatment.
        Ms. Eshoo. But you don't know how many.
        Ms. Khachatourian. I don't coverage commercial insurance,
    however, that is something I would be happy to look into for
    you.
        Ms. Eshoo. Thank you.
        Mr. Burgess. The gentlelady yields back. The Chair thanks
    the gentleman. The Chair recognizes the gentleman from
    Virginia, Mr. Griffith, 5 minutes for questions, please.
        Mr. Griffith. Thank you very much. I appreciate it. Ms.
    Klasmeier, we have had some discussions and I know this is not
    the Judiciary Committee, but this is where the law touches
    everything. And so as we consider legislation in this area,
    just so the committee knows as a whole and that I am better
    educated, what points should we be taking away from the various
    judicial cases in considering First Amendment challenges to the
    FDA's regulations? And what should we be looking out for? So
    that is Part A and Part B. What should we be looking out for to
    make sure that we get it right and that we do it where it is
    constitutional as we draft this?
        Ms. Klasmeier. Thank you very much for the question,
    Congressman. I think a very important take away from the case
    law is the need for clarity and that point arises out of the
    intersection of the Fifth Amendment case law and the First
    Amendment case law. I think there is a lot of discussion about
    the First Amendment, but the due process laws requires clarity
    and precision, requires rules that give regulated entities
    clear notice on an a priori basis of what conduct is prohibited
    versus permitted.
        Mr. Griffith. And let me, I don't want to cut the rest of
    the answer off, but let me interrupt up there because that is
    one of my pet peeves. So many times people think that means we
    have to define every word in the bill, but if there is no
    definition in the bill, then the courts use the normal usage of
    the English language or if it is a term of art, the term of art
    in this case from the medical community. Is that not correct?
        Ms. Klasmeier. It is absolutely correct, sir. And just to
    augment your observation, there was a conversation earlier this
    morning about the definition of claim and promotion and where
    do we draw the line. And I understand why there may be some
    misunderstanding around that, but I have to say as a
    practitioner in this area--and I also have to say I suffer from
    a little bit of an existential crisis because the news that
    this is not a hot-button issue or something that needs to be
    resolved makes me question what I have spent the last 20 years
    of my life doing. But that is an aside.
        Mr. Griffith. No worry, her phones will be lit up before
    the day is done, I am sure.
        Ms. Khachatourian. But there is among those of us who
    practice in this area day in and day out a very well-understood
    line between promotional speech and nonpromotional speech. So I
    think the legislative measures that we have been talking about
    this morning would just under foundational interpretive
    principles be examined against those background legal norms. So
    there is a very rich body of administrative precedent from FDA
    in addition to case law and the statutory foundation of the
    measures that you are talking about. We know what these words
    mean. So I agree to the extent that you are saying we ought not
    to feel overly anxious about those two or three words. I think
    folks who are battle tested in this area know the difference
    between promotional speech and nonpromotional speech and can
    advise clients accordingly.
        Mr. Griffith. And I kind of got you off track there for a
    second. You were talking about the First and the Fifth. I am
    going to let you go back to is there anything else on that you
    wanted to touch base on that I distracted----
        Ms. Khachatourian. Many things, but I will try to limit it
    to a big-ticket item, which is it is increasingly obvious from
    the case law, which goes back to at least to 1976, that it is
    very hard for the Government to defend any speech regulation
    that affects accurate communication regarding lawful activity.
    I think we tend to get hung up on the kind of Central Hudson
    test and prongs and that sort of thing. But just to sort of
    bring it down to its essence, if the Government wants to
    restrain accurate speech about conduct that is permitted--and
    off-label use is not only permitted in almost all cases, it is
    by Federal law, it is also the standard of care in many
    instances--it has really got an uphill battle.
        I think there is probably a way for all of these very
    challenging and complex policy considerations to be balanced in
    a smart way that takes account of the First Amendment backdrop,
    and I think the measures that we are talking about today have
    done an admirable job of strengthening that balance. But there
    is a little bit of a thumb on the scale, if you like, as a
    result of years and years of case law going back to at least
    1976 against anything that would purport to prohibit accurate
    speech about lawful activity.
        Mr. Griffith. And while I wasn't as concerned about the
    freedom of speech, per se, although it is very important to me,
    when I put in that clause that they have to put in the
    contradictory information, as well, and the contextual
    information, that actually shores that up from a free speech
    standpoint as well, because we are saying you have to present--
    if you are going to present--you have to present both sides of
    the data. Isn't that accurate?
        Ms. Khachatourian. Absolutely accurate, yes, sir.
        Mr. Griffith. I appreciate that. And it does make me worry
    and I know it is not their field of expertise either, but you
    indicated there was a late '90s case that clarified some of
    this. I think the bill clarifies it more, but I am just curious
    why the FDA keeps going down this pathway when they have lost a
    number of cases over the years, if not in this circle of the
    three-ring circus, in another circle of that same circus under
    the same tent.
        Ms. Khachatourian. Yes, well, it is concerning because you
    have not only the cases that we have been talking about here,
    Caronia and Amarin and Pacira, but also on the dietary
    supplement side of the house, a great many cases from the DC
    Circuit, a lot of other sources of precedent that draw into
    question the constitutionality of the current scheme. That
    said, I think there are a lot of undeveloped arguments that we
    have been, in industry, waiting with bated breath for FDA to
    articulate and there was a memoranda that FDA lodged in one of
    its administrative dockets in January, right before the
    inauguration that purported to explain for all the world to see
    how the agency thought through these constitutional issues and
    it was a little more than a defense of the status quo.
        I think there is a lot of room for optimism in the coming
    months, particularly with the involvement of this subcommittee
    and the Congress, generally, that FDA will do a better job of
    explaining and including stakeholders in a conversation about
    the constitutionality and constitutional issues associated with
    this current regulatory scheme.
        Mr. Griffith. I appreciate it and yield back. Thank you,
    Mr. Chairman.
        Mr. Burgess. The Chair thanks the gentleman. The Chair
    thanks Ms. Khachatourian for her optimism. We always welcome
    optimism on this subcommittee.
        The Chair now recognizes the gentleman from Maryland, Mr.
    Sarbanes, 5 minutes for questions.
        Mr. Sarbanes. Thank you, Mr. Chairman. I want to thank the
    panel. This is a really complicated issue, I am finding. I sat
    here through the entire testimony. And certainly the ability
    and the internet is kind of at the center of this now for
    people to get hold of information about beneficial off-label
    use of drugs and medical devices much more readily than
    obviously they ever could before, is creating some pressure to
    figure out a way to make that opportunity more available to
    people. The fast distribution of information can also allow for
    the fast distribution of bad information and lead to poor
    decision making. But I understand that Congressmen Griffith,
    Guthrie, and others are trying to respond to pressure and often
    it comes from patients that are seeking a solution.
        What I am concerned about is that you could solve the way
    they are proposing for this pressure, or you could solve
    perhaps by building more capacity inside the FDA. So what I am
    interested in hearing about, I don't want us to take a
    shortcut. I don't want the reason we are reaching for the
    proposed solution here to be that we have overlooked the
    opportunity to build more capacity in FDA as a way of solving
    for this, and perhaps solving for in a way that protects public
    safety better than taking the alternative route.
        So I wonder, Ms. Charo, maybe you could begin here. Speak
    to that issue. How do we explore fully the opportunity to build
    capacity in FDA to respond to the pressure we are talking
    about? Can that be done? If so, what are the ways in which it
    can be done, et cetera?
        Ms. Charo. Well, first, I am going to second what has been
    said by others here which is that FDA, just in terms of sure
    personnel, would certainly benefit from having more people able
    to act on data as it is coming in and everything would move
    more rapidly with no question. But we shouldn't restrict
    ourselves only to FDA. I mean one of the things we have been
    struggling with here is that there are areas in which the
    incentive systems that currently exist are inadequate for
    driving the research that we all agree would be ideal to figure
    out what really works and what does not. Pediatrics, rare
    diseases are two very good examples.
        Now we have some new tools. Congress have given things like
    priority reviews and extended patent periods as incentives, but
    we have yet to completely explore the full range of tools.
    Antibiotics is another example where the Infectious Disease
    Society of America has been pointing out for years we could use
    rewards, milestone rewards. We have not talked about NIHI
    funding for direction of studies that would look at things like
    off-label uses that are hinted at already and that need to be
    confirmed.
        In other words, we need not restrict ourselves to only one
    tool which is to pull the industry slowly to do the research
    under the threat of not being able to market. But we could
    bring to bear a combination of tools to get the information
    developed more rapidly. And ideally, then everybody would
    benefit because we would have a wider range of applications,
    but we would have more confidence that they have been tested in
    a way that is comprehensive and objective and has been vetted
    by independent eyes.
        Mr. Sarbanes. I appreciate that. I mean, I worry a little
    bit that I don't completely trust the industries we are talking
    about here to restrain themselves if they get--if there is an
    avenue for aggressively pursuing a particular product's appeal
    out there in ways that may compromise public safety, and I
    worry about a bunch of camels starting to get their noses under
    the tent. So I understand the desire to try to accommodate
    people's interest in pursuing this, but if there are other ways
    we can respond to that, without sacrificing some of these
    concerns about public safety, then I think that we ought to
    pursue those and explore some of the additional tools that you
    have suggested, perhaps. With that, I yield back. Thank you.
        Mr. Burgess. The gentleman yields back. The Chair thanks
    the gentleman. The Chair recognizes the gentleman from Florida,
    Mr. Bilirakis, 5 minutes for questions.
        Mr. Bilirakis. Thank you, Mr. Chairman. I thank the panel
    as well. I have a question for Ms. House. Again, thank you for
    your testimony. Throughout my time on the Energy and Commerce
    Committee, I have been involved with the rare disease
    community. There are about 30 million Americans--and there are
    7,000 rare diseases--30 million Americans have a rare disease,
    which includes pediatric cancers. And I understand there are
    about 500 FDA-approved treatments. Correct me if I am wrong.
        Do you think that many of these 30 million Americans are
    taking medications off-label? For Ms. House, please.
        Ms. House. Yes. Yes, I do. I do. In my written comments, I
    have referenced in particular lupus, and if you look at the FDA
    site right now, there are only four drugs that are approved for
    lupus. And the approvals of those go back into the mid-1900s.
    So when you look at the drugs, aspirin was approved first in
    1948, followed by steroids, and there was no drug listed. There
    was an antimalarial that was approved in 1955. And finally, a
    new drug approved in 2011. So if you are a patient living with
    lupus, you are likely not getting aspirin as a therapeutic
    option for your particular disease. And certainly when you look
    at cancer, there is a reason why there is such a high rate of
    pediatrics in cancer clinical trials, and it is because they
    don't have a lot of other options available to them.
        Mr. Bilirakis. Thank you, so there are other examples out
    there. So a large percentage of the 30 million are taking
    medication off-label.
        Ms. House. Arthritis is another good sample. If you look at
    the label of methotrexate, for example, you will see that the
    label doesn't reflect the broad use of that particular product
    and you can probably speak to that better than I could.
        Mr. Bilirakis. Thank you. I am here with a young Floridian
    from the Miami area who told me about how she came down with
    ITP, a condition where her body destroyed her platelets. And I
    have conversed with her over a long period of time on these
    particular issues. I have sponsored the Open Act and we are
    working together.
        She had to become an expert. She became an expert on ITP,
    and she really became her own doctor and found a treatment,
    really extraordinary. She was able to find a drug that could
    treat her condition. The drug was FDA-approved for non-
    Hodgkin's lymphoma and rheumatoid arthritis, but not for ITP.
        After a long conversation with her physician, we were able
    to pursue that course, the off-label treatment, and it was very
    successful. She comes to DC on a regular basis as an advocate
    for cures and treatments for rare diseases.
        Ms. House, does it make sense to withhold information from
    physicians and not share truthful medical information that
    could say a person's life? And who should be in charge of a
    patient's treatment? The patient working with her physician or
    again, a bureaucrat? If you could answer that question, I would
    appreciate that.
         Ms. House. Well, you know, we have spent 35 years trying
    to assist patients to become equal participants and empower
    participants in their care, so I am going to answer that as the
    patient needs to be quarterback of their care, working with
    their particular physician.
        I will say that it is incredibly important though that the
    information that is provided, both to patients and to
    physicians, is fair balanced. I worked in the pharmaceutical
    industry for a period of time, so I also understand the bright
    white lines between what is promotional and what is
    nonpromotional and we are not talking about shipping patients
    or physicians glossy pieces of information on off-label uses or
    other additional information, but we have to provide for them
    and whether that is, I do agree that there are alternative
    solutions, whether it is through the FDA, whether it is through
    a professional society, whether it is through a third party
    peer reviewed entity, we have to get to a point where we are
    providing that data set to people who are making decisions,
    including patients who are making more and more of their care
    decisions as you have referenced.
        Mr. Bilirakis. Thank you. Agreed. Dr. Van Hare, in your
    practice, you deal with children and adults who suffer from a
    heart condition such as the congenital heart and some are
    congenital heart in nature. I sponsored a bill to reauthorize a
    congenital heart program and it went through this committee and
    hopefully on the floor as soon as possible.
        If you have a child who comes to the hospital with a heart
    condition, you might need to do a surgical procedure. How
    common is it for medical devices to be approved for use in
    children?
        Mr. Bilirakis. Well, as I understand, most medical devices,
    at least that I use in the cardiology sphere are not specific
    to children or adults. They are more specific to actual
    specific arrhythmias. And as I talked about in my oral
    testimony, a lot of what we take care of, the devices, in fact,
    are not labeled for those particular sort of conditions.
        I will say that you sort of raise the issue of surgery for
    congenital heart disease. We often think about surgery as
    basically correcting a problem. But those patients need to have
    a cardiologist for the rest of their life and one of the
    biggest problems if they develop heart rhythm issues and those
    heart rhythm issues are often very, very difficult to take care
    of and so we are reaching for whatever we can find to treat
    those things most effectively. And we use technology and we use
    devices that have been approved for other indications for this
    particular situation.
        I just want to emphasize that we keep talking about
    pediatrics as sort of being an important issue and I am a proud
    pediatrician and I believe that. But I think pediatrics is a
    special case of a larger issue which is there are a lot of
    patients that devices and drugs have been developed for other
    indications. We have to find a way to take care of our
    patients. I think pediatric diseases, but also rare diseases,
    and anything that is kind of on a cutting edge of what we are
    doing medically to treat things are going to fall into this
    discussion.
        Mr. Bilirakis. Thank you very much. I yield back, Mr.
    Chairman.
        Mr. Burgess. The Chair thanks the gentleman. The gentleman
    yields back. The Chair recognizes the gentleman from New York,
    Mr. Engel, 5 minutes for questions, please.
        Mr. Engel. Thank you very much, Mr. Chairman. I have long
    been an advocate for those suffering from rare diseases. I was
    an author of the ALS Registry Act and the two most recent
    Muscular Dystrophy Care Act reauthorizations and I know how
    much relief and encouragement new therapies can bring to rare
    disease patients. And I think I speak for everyone on this
    subcommittee when I say that all of us want to do what we can
    to bring effective and potentially life-saving treatments to
    patients as quickly as possible, but it is absolutely critical
    that we ensure our actions do not compromise patient safety.
        Efficiency is a worthwhile goal that we all share, but as
    we strive to hasten the delivery of new treatments, safety and
    effectiveness must always be paramount and that is why this
    hearing is so important. Any action by this committee needs to
    take into account the input of expert witnesses who can speak
    to the potential implications of our actions. And that is what
    we have, Mr. Chairman, in our panel. And so I want to thank
    today's witnesses for being here and sharing your insights.
        Let me start with Ms. Charo. During your testimony, you
    noted that ``approval of a drug for labeled''--I am quoting
    you--``indication does not mean it will be safe and effective
    for off-label uses.'' And that ``additional studies are needed
    to explore them.''
        Now it would seem to me that if a manufacturer wished to
    communicate about an off-label use for a product that
    manufacturer must already have reason to believe that this
    product is safe and effective for the given off-label use. So
    if there is already evidence supporting an off-label use, can
    you explain why additional studies would be necessary?
        Ms. Charo. Of course. And I think other people on this
    panel are even more expert than I in research trial design, but
    the reality is that evidence comes in many forms and often it
    is based on small numbers of people with very homogenous kinds
    of situations. But in the real world, you need larger numbers
    of people with a wider variety of background conditions and
    complexities in order to detect both the areas in which it will
    or will not be effective. It might depend upon co-morbidity,
    and also to detect some of the less common kinds of side
    effects or adverse events.
        And those things are relevant to deciding whether or not
    the benefit that some people get will be sufficient to outweigh
    the kinds of risks or failures to work for other people.
        So initial evidence often can look extremely promising.
    Preclinical evidence, particularly we have cured cancer in mice
    countless times, but also early human evidence is often very,
    very promising and then when we move into larger trials with
    more complicated and more diverse populations we discover that,
    unfortunately, it was misleading. And it is just a matter of
    basic statistics as well as medicine. That is why there is such
    an emphasis on properly controlled trials of sufficient size
    and statistical power and the ability, too, to look at the
    possibility of inherent biases and how you structure the
    trials. It is very easy to structure trials in a way that
    subtly lead to one conclusion or another without even intending
    to do so. That is the value of the independent expert eyes that
    the agency brings.
        Mr. Engel. Thank you very much. Dr. Kesselheim, you also
    touched on the need for additional studies in your testimony.
    So I would like to ask you the same question. If there is
    already evidence supporting an off-label use, can you explain
    why additional studies would be necessary?
        Dr. Kesselheim. Sure. I mean if there is evidence
    supporting an off-label use and there are certainly plenty of
    ways that that evidence can already be communicated under the
    current rules. I think the rules are fairly clear about what
    types of communications are, where there are opportunities to
    communicate that information. And if there are additional
    studies and again, I think the importance is what is the nature
    of that evidence. How is that evidence defined? What are the
    statistical methods that were used in testing? How is the
    population defined? And these are details that, you know,
    average physicians don't know a lot, don't have a lot of
    training in and don't know a lot about it and these are the
    details that the FDA has expertise in. And so if there are
    nuances that might not be caught in initial examination of the
    information, additional studies that are necessary, then the
    numerous dozens of experts at the FDA with training in various
    different fields can identify that and pick up on that and
    determine whether or not what might initially be seen in the
    data, turns out to be legitimate.
        Mr. Engel. Thank you. Ms. Charo, I have one final question
    for you. It is my understanding that in January the FDA
    released draft guidance regarding which manufacturer
    communications are consistent with the FDA required labeling in
    which are not. And I understand also that this guidance has not
    yet been finalized.
        So do you feel that draft guidance strikes the right
    balance between enabling potentially helpful communications to
    take place and protecting patient safety and why shouldn't we
    legislate in this space to provide even greater clarity for
    manufacturers?
        Ms. Charo. I do think the FDA is moving in the right
    direction. I agree that draft guidances would be better off if
    they were finalized guidances, although it is worth noting that
    a tremendous amount is already done through draft guidances at
    the FDA without any Fifth Amendment due process questions being
    raised about it.
        The thing that I think is most important about what the FDA
    has been doing is its insistence that actual knowledge about
    how your product is being used can be in some instances
    considered to be evidence that you actually intended for the
    product to be used that way. I think a lot of the debate has
    been around that phenomenon. But we have seen that phenomenon
    in other contexts. We have seen it in areas having to do with
    constructive knowledge in tort law where if you know something
    is about to happen and you actually go ahead and do all the
    things that are necessary for it to come about, you are
    actually going to be considered to have intended that to happen
    in many cases.
        On the other hand, we have seen in the area of gun law, a
    lot of resistance to the idea that actual knowledge constitute
    intent. I do think that is an area where we have to have some
    more discussion to clarify, but I also think that it is risky
    to simply allow for an expansion of communication while
    simultaneously saying but now that I have communicated more,
    the fact that I know that it is having an effect doesn't mean
    that I intended that particular outcome. I think to have both
    of those things at once I think is particularly risky. Choosing
    one or the other at least would be the right direction.
        Mr. Engel. Thank you very much. Thank you, Mr. Chairman.
        Mr. Burgess. The gentleman yields back. The Chair thanks
    the gentleman. Does the gentleman from Texas have a unanimous
    consent request?
        Mr. Green. Yes, Mr. Chairman, I have a consent request.
        Mr. Burgess. I will yield for a unanimous consent request.
        Mr. Green. I move that we have statements in the record
    from the American Health Insurance Plans, the Campaign for
    Sustainable Drug Pricing, and also Public Citizen Action be
    placed into the record.
        Mr. Burgess. Without objection, so ordered. Seeing no other
    Members wishing to ask questions, I once again want to thank
    our witnesses for being here today.
        [The information appears at the conclusion of the hearing.]
        Mr. Burgess. Pursuant to committee rules, I remind Members
    they have 10 business days to submit additional questions for
    the record. I ask the witnesses to submit their responses
    within 10 business days upon receipt of those questions. And
    without objection, the subcommittee stands adjourned.
        [Whereupon, at 12:37 p.m., the subcommittee was adjourned.]
        [Material submitted for inclusion in the record follows:]
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