[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
                           
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      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:]
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    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:]
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    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:]
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    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:]
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    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:]
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    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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