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





 
               21ST CENTURY CURES: THE PRESIDENT'S COUNCIL 
                  OF ADVISORS ON SCIENCE AND TECHNOLOGY  
                    (PCAST) REPORT ON DRUG INNOVATION

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON HEALTH

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                    ONE HUNDRED THIRTEENTH CONGRESS

                             SECOND SESSION

                               __________

                              MAY 20, 2014

                               __________

                           Serial No. 113-145
                           
                           
                           
                           
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]




      Printed for the use of the Committee on Energy and Commerce

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                    COMMITTEE ON ENERGY AND COMMERCE

                          FRED UPTON, Michigan
                                 Chairman

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

                                 7_____

                         Subcommittee on Health

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

                                  (ii)
                             C O N T E N T S

                              ----------                              
                                                                   Page
Hon. Joseph R. Pitts, a Representative in Congress from the 
  Commonwealth of Pennsylvania, opening statement................     1
    Prepared statement...........................................     2
Hon. Michael C. Burgess, a Representative in Congress from the 
  State of Texas, opening statement..............................    13
Hon. Frank Pallone, Jr., a Representative in Congress from the 
  State of New Jersey, opening statement.........................    13
Hon. Gene Green, a Representative in Congress from the State of 
  Texas, opening statement.......................................    15
Hon. Fred Upton, a Representative in Congress from the State of 
  Michigan, opening statement....................................    15
    Prepared statement...........................................    16
Hon. Henry A. Waxman, a Representative in Congress from the State 
  of California, opening statement...............................    17
Hon. Diane DeGette, a Representative in Congress from the State 
  of Colorado, opening statement.................................    18

                               Witnesses

Garry A. Neil, Global Head of Research and Development, 
  Medgenics, Inc.................................................    19
    Prepared statement...........................................    22
    Answers to submitted questions...............................   153
Sara Radcliffe, Executive Vice President for Health, 
  Biotechnology Industry Organization............................    35
    Prepared statement...........................................    37
    Answers to submitted questions...............................   161
Frank J. Sasinowski, Director, Hyman, Phelps & McNamara, P.C.....    48
    Prepared statement...........................................    50
    Additional material \1\
    Answers to submitted questions...............................   169
Jeff Allen, Executive Director, Friends of Cancer Research.......    75
    Prepared statement...........................................    77
    Answers to submitted questions...............................   176
Sean R. Tunis, President and Chief Executive Officer, Center for 
  Medical Technology Policy......................................    89
    Prepared statement...........................................    91
    Answers to submitted questions \2\...........................   185

                           Submitted Material

Statement of May 20, 2014, from Raymond L. Woosley, President, 
  AZCERT, submitted by Mr. Pitts.................................     4
Report of May 20, 2014, ``Progress on the 2012 Drug Innovation 
  Report by PCAST (President's Council of Advisors on Science and 
  Technology),'' by Janet Woodcock, submitted by Mr. Pitts.......     9

----------
\1\ Supporting documents submitted by Mr. Sasinowski are available at 
http://docs.house.gov/Committee/Calendar/ByEvent.aspx?EventID=102237.
\2\ Mr. Tunis did not answer submitted questions for the record by the 
time of printing.
Article of May 16, 2014, ```Right to Try' laws spur debate over 
  dying patients' access to experimental drugs,'' by Brady Dennis 
  and Ariana Eunjung Cha, The Washington Post, submitted by Mr. 
  Shimkus........................................................   120
Article of April 5, 2014, ``Even Small Medical Advances Can Mean 
  Big Jumps in Bills,'' by Elisabeth Rosenthal, The New York 
  Times, submitted by Mr. Waxman.................................   127


21ST CENTURY CURES: THE PRESIDENT'S COUNCIL OF ADVISORS ON SCIENCE AND 
              TECHNOLOGY (PCAST) REPORT ON DRUG INNOVATION

                              ----------                              


                         TUESDAY, MAY 20, 2014

                  House of Representatives,
                            Subcommittee on Health,
                          Committee on Energy and Commerce,
                                                    Washington, DC.
    The subcommittee met, pursuant to call, at 10:00 a.m., in 
room 2322 of the Rayburn House Office Building, Hon. Joseph R. 
Pitts (chairman of the subcommittee) presiding.
    Members present: Representatives Pitts, Burgess, Shimkus, 
Blackburn, McMorris Rodgers, Lance, Cassidy, Griffith, 
Bilirakis, Ellmers, Barton, Upton (ex officio), Pallone, Engel, 
Schakowsky, Green, Barrow, Sarbanes, and Waxman (ex officio).
    Also present: Representative DeGette.
    Staff present: Clay Alspach, Chief Counsel, Health; Gary 
Andres, Staff Director; Mike Bloomquist, General Counsel; Matt 
Bravo, Professional Staff Member; Noelle Clemente, Press 
Secretary; Paul Edattel, Professional Staff Member, Health; 
Sydne Harwick, Legislative Clerk; Robert Horne, Professional 
Staff Member, Health; Carly McWilliams, Professional Staff 
Member, Health; Katie Novaria, Professional Staff Member, 
Health; Krista Rosenthall, Counsel to Chairman Emeritus; Chris 
Sarley, Policy Coordinator, Environment and the Economy; Heidi 
Stirrup, Policy Coordinator, Health; John Stone, Counsel, 
Health; Ziky Ababiya, Democratic Staff Assistant; Phil Barnett, 
Democratic Staff Director; Eric Flamm, Democratic FDA Detailee; 
Elizabeth Letter, Democratic Press Secretary; Karen Lightfoot, 
Democratic Communications Director and Senior Policy Advisor; 
Karen Nelson, Democratic Deputy Committee Staff Director, 
Health; Anne Morris Reid, Democratic Senior Professional Staff 
Member; and Rachel Sher, Democratic Senior Counsel.
    Mr. Pitts. The subcommittee will come to order. The Chair 
will recognize himself for an opening statement.

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

    Today's hearing relates to the 21st Century Cures 
Initiative announced by the Energy and Commerce Committee on 
April 30, 2014. This Cures effort is envisioned to explore ways 
to accelerate the discovery, development and delivery cycle for 
new medical breakthroughs. Through this effort, Congress hopes 
to clear a path to find more cures and treatments, while also 
creating jobs, and keeping America as the innovation center of 
the world.
    Shortly following the announcement of the Cures Initiative, 
the committee issued a white paper on May 1, 2014, entitled 
21st Century Cures: Call for Action, which more fully discusses 
the ideas behind the Cures project and issues of call to 
action, call for ideas. The first goal of this project is to 
solicit ideas. Congress does not have all the answers, but we 
do have a role to play in ensuring our Nation's laws and 
regulations, keep pace and compliment the biomedical research 
and innovation that is happening at lightning speed.
    Earlier this month, we heard from the NIH, FDA, patient 
advocates, university leaders, and other scientific pioneers 
about their ideas, challenges and successes. Today, we will 
hear from experts who contributed to the President's Council of 
Advisor on Science and Technology, PCAST, report on propelling 
innovation in drug discovery, development and evaluation. This 
important report hits on a number of topics that we will have 
to explore if we are to truly advance Cures. These ideas 
include, among others, making sure incentives are in place to 
ensure capital is flowing towards research and development of 
new cures, and designing clinical trials to the appropriate 
size and scale, given the growth of targeted personalized 
medicine.
    Today, we hope to learn more about these proposals and 
others put forth by PCAST, and determine which ideas or 
recommendations could potentially advance the 21st Century 
Cures Initiative.
    Excitingly, the fight for faster cures in the 21st century 
will not only foster medical innovations, but it can also make 
our healthcare system more efficient, and can save lives.
    I want to welcome our witnesses today. I look forward to 
learning more about the advancements in biomedical research and 
innovation.
    [The prepared statement of Mr. Pitts follows:]

               Prepared statement of Hon. Joseph R. Pitts

    Today's hearing relates to the 21st Century Cures 
Initiative announced by the Energy and Commerce Committee on 
April 30, 2014. This Cures effort is envisioned to explore ways 
to accelerate the discovery, development, and delivery cycle 
for new medical breakthroughs. Through this effort, Congress 
hopes to clear a path to find more cures and treatments while 
also creating jobs and keeping America as the innovation center 
of the world.
    Shortly following the announcement of the Cures initiative, 
the committee issued a white paper on May 1, 2014 entitled 
``21st Century Cures: A Call to Action'' which more fully 
discusses the ideas behind the Cures project and issues a call 
to action--a call for ideas.
    The first goal of this project is to solicit ideas. 
Congress does not have all the answers, but we do have a role 
to play in ensuring our Nation's laws and regulations keep pace 
and complement the biomedical research and innovation that is 
happening at lightning speed.
    Earlier this month, we heard from the NIH, FDA, patient 
advocates, university leaders and other scientific pioneers 
about their ideas, challenges and successes. Today, we will 
hear from experts who contributed to the President's Council of 
Advisors on Science and Technology (PCAST) report on Propelling 
Innovation in Drug Discovery, Development, and Evaluation.
    This important report hits on a number of topics that we 
will have to explore if we are to truly advance cures. These 
ideas include, among others, making sure incentives are in 
place to ensure capital is flowing toward research and 
development of new cures and designing clinical trials to the 
appropriate size and scale given the growth of targeted, 
personalized medicine.
    Today we hope to learn more about these proposals and 
others put forth by PCAST, and determine which ideas or 
recommendations could potentially advance the 21st Century 
Cures Initiative. Excitingly, the fight for faster cures in the 
21st century will not only foster medical innovations, but it 
can also make our health care system more efficient, and can 
save lives.
    I want to welcome our witnesses today and look forward to 
learning more about the advancements in biomedical research and 
innovation.

    Mr. Pitts. And I ask for unanimous consent to include the 
following statements for today's hearing record from Dr. 
Raymond Woosley, former president of the Critical Path 
Institute and one of the experts that participated in the 
development of the PCAST report, and Dr. Janet Woodcock, 
Director of FDA Center for Drug Evaluation Research Blog Post, 
``Progress on the 2012 Drug Innovation report by PCAST'' from 
May 20, 2014.
    Without objection, so ordered.
    [The information follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    Mr. Pitts. Thank you. I yield the remainder of my time to 
Dr. Burgess.

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

    Mr. Burgess. Thank you, Mr. Chairman. Thank you for 
yielding. Thank you for having this hearing, and especially 
thanks to the chairman and ranking member of the full committee 
for pursuing the 21st Century Cures Agenda.
    So this is an accompanying bipartisan effort to listen to 
you, the scientists, to listen to doctors, listen to 
researchers, listen to patients, and, yes, we will listen to 
government agencies to find out how we can continue to lead the 
world in scientific discovery that ultimately leads to cures, 
treatments, medical devices that will improve human health, 
and, most importantly, alleviate human suffering.
    In September 2012, the President's Council of Advisors on 
Science and Technology issued a report to the President on 
propelling innovation in drug discovery, development and 
evaluation. The report provided recommendations on how to 
ensure we are doing everything we can to capture the 
significant amount of knowledge that has been gained in the 
last few decades, and to ensure that the knowledge is 
translated into cures and actually make it into the lives of 
patients. The report found many of the same themes that we have 
heard for the last 10 years in this committee. While our 
scientific knowledge has significantly grown, the promise of 
that knowledge has not been realized. The recommendations of 
the President's council also mirror familiar suggestions, 
including building off existing authorities to accelerate 
therapeutics and ensure management of regulatory agencies 
appropriately balances the benefits and risk. With this--when 
this effort was launched, we said we wanted to hear from 
everyone, and I am pleased that we are evaluating the advice 
that is being given to the President in this area.
    I certainly look forward to this hearing. I look forward to 
your testimony. I look forward to all of the participation of 
our witnesses.
    Thank you, Mr. Chairman. I will yield back.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the ranking member, Mr. Pallone, 5 minutes 
for an opening statement.

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

    Mr. Pallone. Thank you, Chairman Pitts, and thank you for 
calling this hearing.
    I wanted to initially ask unanimous consent to enter into 
the record a--an article on the progress of the 2012 Drug 
Innovation report by PCAST, if I could. I believe you have it, 
Mr. Chairman.
    Mr. Pitts. Yes, we just did that.
    Mr. Pallone. All right, thank you.
    Let me also thank Chairman Upton for convening the 21st 
Century Cures Initiative, and also Ms. DeGette, who was very 
much involved with that.
    We all agree that the Federal Government and Congress can 
play a role to help accelerate the discovery, development and 
delivery of promising new treatments to patients, and the 
question remains how to best advance those goals. I look 
forward to engaging this process as we meet with stakeholders, 
and gather ideas and input from experts on what, if any, 
policies Congress can consider moving forward. And most 
importantly, I look forward to working with my colleagues in a 
bipartisan way to ensure that promising new medicines get to 
patients in a timely manner, and they are safe and effective.
    The committee already has a great record on that effort, 
most recently with the passage of the FDA Safety and Innovation 
Act of 2012, or FDASIA. That law reformed and revitalized many 
FDA programs to improve its regulatory scheme, to facilitate a 
more efficient and predictable review process. Specifically, we 
updated the regulatory pathways under which FDA provides for 
expedited reviews of drugs. WE also aided for the first time 
the breakthrough therapy, Pathway, and all of these programs 
served a goal of helping drug sponsors and the FDA work 
together to cut development time.
    In addition, I am currently working with Chairman Pitts on 
a Bill that would streamline the DEA's scheduling process as it 
relates to improved drug therapies. If we are going to have a 
comprehensive discussion about how to promote innovation and 
medical advancements, we can't simply focus on the FDA. The 
work being done at NIH and through the country at research 
universities like my hometown school of Rutgers University, has 
to be properly funded. Discovering cures and developing 
effective treatments are complex, difficult and expensive 
endeavors. NIH is the premiere biomedical research institution 
in the world, and I hope this committee can find ways to ensure 
that NEH--NIH has the necessary tools to maintain that 
designation.
    When we talk about the delivery of therapies, we have got 
to address access. Medical advances and cures at the earliest 
possible time is our shared goal, but we all must work together 
to ensure that when discovered, those cures can get to all 
patients, and not just those who can afford them.
    So, Mr. Chairman, based on your comments and actions to 
date, I am hopeful we will have these conversations as we move 
forward. Today, the committee will examine the President's 
Council of Advisor on Science and Technology, or PCAST, Report 
on Drug Innovation. That report issued in September of 2012, 
only a couple of months following the passage of FDASIA, puts 
forth a number of proposals across a large spectrum of 
policies, from funding basic biomedical research, to developing 
economic initiatives. And there are a number of ideas in this 
report, so I look forward to flushing out their relevance, and 
thank everyone for their input today in moving forward.
    And I have about a minute and a half. I would like to yield 
to my colleague from Texas, Mr. Green.

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

    Mr. Green. Thank you to our ranking member and the Chair 
for having this hearing, and our witnesses for testifying, and 
yielding the time.
    I applaud the committee for its 21st Century Cures 
Initiative to examine what steps are needed to harness 
scientific knowledge, and accelerate the pace of the new Cures. 
The--in 2012, this committee took an important first step in 
addressing the lack of new drug development to treat drug-
resistant infections. Our committee colleague, Congressman 
Gingrey, and I were the lead sponsors of that legislation, 
along with a number of our other colleagues on the committee, 
but I fear our work is far from finished. According to the 
report recently by the WHO last month, the antibiotic crisis is 
bigger and more urgent than the AIDS epidemic of the 1980s, and 
without swift and significant action, the implications will be 
devastating. The GAIN Act was an important step to address--
addressing a lack of new drug development, but it must not be 
the last. Weekly reports of new global threats and cases 
identified here at home are a stark reminder our ability to 
meet this threat relies in no small part upon a robust pipeline 
and new therapies. PCAST, scientists, physicians and global 
health leaders have sounded the alarm. We need new incentives 
and approaches to continue fighting drug-resistant bacteria and 
build on the work of getting it started. It would be wrong to 
let this opportunity for action pass us by.
    I urge the committee to address this crisis head-on, and 
encourage meaningful development in the antibiotic space. I 
stand ready to work with you to achieve this worthy goal, and 
we do not have a moment to waste.
    And I yield back my time. Thank you.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the chairman of the full committee, Mr. 
Upton, 5 minutes for an opening statement.

   OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF MICHIGAN

    Mr. Upton. Well, thank you, Mr. Chairman.
    So today marks our first 21st Century Cures hearing at the 
Health Subcommittee. We launched this bipartisan initiative 
earlier this month with one primary goal: accelerate the pace 
of the discovery, development and delivery cycle so that we can 
get innovative new cures and treatments to patients more 
quickly.
    Today, we continue this important conversation with several 
of the distinguished experts who contributed to the President's 
Council of Advisors on Science and Tech Report on Drug 
Innovation. The President, in soliciting recommendations on 
this very important topic, decided propelling drug innovation 
is a policy worthy of exploring and advancing, and I couldn't 
agree more.
    In their report, the President's advisors found that the 
Nation's biomedical innovation ecosystem is under significant 
stress, citing the patient--citing the patent cliff facing the 
pharmaceutical industry, declining investment from venture 
capital, and decreasing research and development in critical 
area, including Alzheimer's. We have heard similar concern in 
our discussion with patients, innovators and thought leaders.
    So in order to address these issues facing our biomedical 
innovation ecosystem, the experts who contributed to the report 
recommended closing scientific knowledge gaps, addressing 
inefficiencies in clinical trials, considering more economic 
initiatives to decrease investment--to increase investment, and 
encouraging even more innovation at the FDA. The President's 
advisors put forth the following goal for our Nation. ``Double 
the current annual output of innovative new medicines for 
patients with important unmet medical needs, while increasing 
drug efficacy and safety, through industry academia and 
Government working together to double the efficiency of drug 
development by decreasing clinical failure, clinical trial 
cost, time to market, and regulatory uncertainty.'' I know that 
we can all agree to join the President and his advisors to meet 
that goal.
    As the President's advisors so rightly said, we must work 
together to achieve the goal. This has to be a collaborative 
effort.
    The committee recently put out a call for feedback on the 
PCAST report. We also asked for input from our Nation's 
patients on the discovery of treatment and cures for their 
diseases. The 21st Century Cures Initiative ultimately touches 
everybody, every family, patients, doctors, loved ones, 
researchers, thought leaders, everyone, and we want input from 
all of those involved. Folks can email their ideas to 
[email protected], and contribute to the conversation on 
Twitter and Facebook using hashtag #Pathtocures. Together, I 
know that we can provide hope to patients and families across 
our great country, and keep America at the forefront of 
innovation, and, by the way, create lots more jobs too.
    Mr. Chairman, I yield back my balance of my time.
    [The prepared statement of Mr. Upton follows:]

                 Prepared statement of Hon. Fred Upton

    Today marks our first 21st Century Cures hearing at the 
Health Subcommittee. We launched this bipartisan initiative 
earlier this month with one primary goal: accelerate the pace 
of the discovery, development, and delivery cycle so we can get 
innovative new cures and treatments to patients more quickly. 
Today, we continue this important conversation with several of 
the distinguished experts who contributed to the President's 
Council of Advisors on Science and Technology report on drug 
innovation.
    The President, in soliciting recommendations on this 
important topic, decided propelling drug innovation is a policy 
worthy of exploring and advancing. I could not agree more.
    In their report, the President's advisors found that the 
Nation's biomedical innovation ecosystem is under significant 
stress, citing the patent cliff facing the pharmaceutical 
industry, declining investment from venture capital and 
decreasing research and development in critical areas, 
including Alzheimer's. We have heard similar concerns in our 
discussions with patients, innovators, and thoughts leaders.
    In order to address these issues facing our biomedical 
innovation ecosystem, the experts who contributed to the report 
recommended closing scientific knowledge gaps, addressing 
inefficiencies in clinical trials, considering new economic 
incentives to increase investment, and encouraging even more 
innovation at the Food and Drug Administration.
    The President's advisors put forth the following goal for 
our Nation:
    ``Double the current annual output of innovative new 
medicines forpatients with important unmet medical needs, while 
increasing drug efficacy and safety, through industry, 
academia, and Government working together to double the 
efficiency of drug development, by decreasing clinical failure, 
clinical trial costs, time to market, and regulatory 
uncertainty.''
    I think we can all agree to join the President and his 
advisors in meeting this goal.
    As the President's advisors so rightly said, we must work 
together to achieve this goal. This must be a collaborative 
effort. The committee recently put out a call for feedback on 
the PCAST report. We also asked for input from our Nation's 
patients on the discovery of treatments and cures for their 
diseases. The 21st Century Cures Initiative ultimately touches 
everyone--patients, doctors, loved ones, researchers, thought 
leaders--and we want input from all those involved. Email your 
ideas to [email protected] and contribute to the 
conversation on Twitter and Facebook using the hashtag 
#Path2Cures. Together we can provide hope to patients and 
families all across the country and keep America at the 
forefront of innovation.

    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the ranking member of the full committee, Mr. 
Waxman, 5 minutes for an opening statement.

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

    Mr. Waxman. Thank you, Mr. Chairman.
    Today, we continue our work on the 21st Century Cures 
Initiative. These hearings are important. We need to ensure 
that patients gain access to new treatment and cures at the 
earliest possible time. At the same time, we need to recognize 
the strengths of our current system which has led to enormous 
breakthroughs in drugs and devices. FDA reviews and approves 
drugs faster than any other regulatory agency in the world. NIH 
and FDA are world leaders in clinical trial design, and in 
integrating the newest science into their policies and 
approaches, and our system protects the health of patients.
    It is critical that we avoid any attempt to fix things that 
aren't broken, and, in the process, do harm to a system that is 
already working very well. We should create policies that 
foster scientific advances, but we should do so in a way that 
does not jeopardize public health.
    Across the board, when we have an informal meeting, 
participants at the roundtable 2 weeks ago said that we need to 
assure that NIH has the resources necessary to maintain its 
national and international leadership in biomedical research, 
and I would welcome an opportunity to work with Chairman Upton, 
and all of our colleagues on both sides of the aisle, on 
accomplishing that goal.
    The participants at that roundtable also indicated that FDA 
was generally excelling in drug and device oversight, and I was 
glad to hear that investment in the life sciences was booming. 
Mr. Left, one of the people there, attributed that success, at 
least in part, to some of the reforms we put into place in the 
2012 FDA Safety and Innovation Act.
    The PCAST report makes several recommendations relating to 
FDA. There are two I would particularly like to learn more 
about. One is the recommendation that FDA or Congress develop 
new voluntary pathway to facilitate the approval of drugs for 
special medical uses based on smaller clinical trials that 
would be needed for broader uses. A bipartisan Bill is 
introduced that would create such a pathway for antibiotics for 
serious or life-threatening infections for which there are few, 
if any other, options. This is an area of increasingly dire 
need, and I think this Bill warrants serious consideration. As 
written, however, it does not achieve what PCAST described as 
an essential component of the pathway that the drug's labeling 
send a clear and effective signal that it should be reserved 
for use in the specific subgroup of patients for which it was 
approved. I would be interested in our witnesses telling us 
their views on this issue.
    The other recommendation is the FDA undertake pilot 
projects to explore certain kinds of provisional approval 
pathways. These so-called adaptive approval pathways shift more 
of the data requirements to post-market studies, however, PCAST 
recommended that Congress not legislate in this area yet 
because serious questions still need to be addressed. These 
include appropriate evidentiary standards, protection of 
patients, and the ability to ensure that drugs are withdrawn if 
their effectiveness is not subsequently demonstrated. I would 
like to hear more about that.
    I was disappointed that FDA and NIH were not invited to 
participate in today's hearing. I appreciate it, Mr. Chairman, 
that you entered the FDA blog into the record. It shows the 
significant progress FDA has made in meeting the 
recommendations of the PCAST report.
    And I would like to now yield the balance of my time to our 
colleague, Ms. DeGette, from the State of Colorado.

 OPENING STATEMENT OF HON. DIANE DEGETTE, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF COLORADO

    Ms. DeGette. Thank you very much, Mr. Waxman. And thanks, 
Mr. Chairman, for holding this hearing on the President's 
Council of Advisors on Science and Technology Report on Drug 
Innovation.
    As has been mentioned, I joined with Chairman Upton to 
launch the 21st Century Cures Initiative about a month ago. We 
had a very successful kickoff roundtable with other members of 
this committee, where we heard from a number of experts, top 
leaders from the administration, academia, research and 
industry, to dig deep into how we can effectively and 
efficiently tackle some of the more complex challenges in 
medicine.
    As the next step in this endeavor, it was important to 
consider what types of recommendations relating to research and 
innovation have already been proposed. The report that we will 
discuss today, as has been mentioned, provides 8 
recommendations, ranging from Federal funding for basic 
biomedical research, to improved drug evaluation. The report 
also highlighted what can happen when lawmakers work together 
on a bipartisan basis to pass legislation that addresses 
emerging medical needs.
    There are several Bills that I support, which have been 
mentioned both by the witnesses in their testimony, as well as 
the other Members today. A couple of them that have not been 
mentioned are the Antibiotic Development to Advance Patient 
Treatment, or ADAPT Act, and the Regenerative Medicine 
Promotion Act of 2014, of which I am the prime sponsor.
    So there is a lot going on. I think the testimony today 
will be a good step along our path to figure out how we can 
work together toward improving research and innovation.
    Thank you very much, Mr. Chairman.
    Mr. Pitts. The Chair thanks the gentlelady.
    That concludes the opening statements, but opening 
statement of all the other Members will be made a part of the 
record.
    We have one panel with us today, five witnesses, and I will 
introduce them in the order that they speak.
    Dr. Garry Neil, Global Head of Research and Development for 
Medgenics; Ms. Sara Radcliffe, Executive Vice President, 
Biotechnology Industry Organiation; Mr. Frank Sasinowski, 
Director, Hyman, Phelps and McNamara; Mr. Jeff Allen, Executive 
Director, Friends of Cancer Research; Dr. Sean Tunis, Found and 
CEO, Center for Medical Technology Policy.
    Thank you for coming. Your written testimony will be made a 
part of the record. You will be each given 5 minutes to 
summarize your testimony.
    And, Dr. Neil, we will start with you. You are recognized 
for 5 minutes for your opening statement. Push the button, yes.

   STATEMENTS OF GARRY A. NEIL, GLOBAL HEAD OF RESEARCH AND 
 DEVELOPMENT, MEDGENICS, INC.; SARA RADCLIFFE, EXECUTIVE VICE 
  PRESIDENT FOR HEALTH, BIOTECHNOLOGY INDUSTRY ORGANIZATION; 
FRANK J. SASINOWSKI, DIRECTOR, HYMAN, PHELPS & MCNAMARA, P.C., 
  ON BEHALF OF NATIONAL ORGANIZATION FOR RARE DISORDERS; JEFF 
ALLEN, EXECUTIVE DIRECTOR, FRIENDS OF CANCER RESEARCH; AND SEAN 
  R. TUNIS, PRESIDENT AND CHIEF EXECUTIVE OFFICER, CENTER FOR 
                   MEDICAL TECHNOLOGY POLICY

                   STATEMENT OF GARRY A. NEIL

    Mr. Neil. Sorry. Chairman Pitts, Ranking Member Pallone, 
Ranking Member Waxman, and Members of the committee, thank you 
for the opportunity to testify before you this morning.
    My name is Garry Neil and I head research and development 
in Medgenics, a small biotechnology company in Wayne, 
Pennsylvania, with operations in the U.S. and in Israel. My 
colleagues and I are working to bring novel ex vivo gene 
therapies to patients with serious, rare and orphan diseases. I 
am a physician, and have spent the past 30 years in biomedical 
research and academia in industry, where I have worked in both 
large and small companies. I have also spent time in venture 
capital, and I have been engaged with a number of nonprofit 
organizations in support of the missions of FDA, NIH, and 
industrial research and development, and these include the 
Foundation for the NIH, the Reagan-Udall Foundation for the 
FDA, the Biomarkers Consortium, and TranCelerate Biomedical, an 
industry collaboration I helped found in 2012. I provided 
expert input into the 2012 PCAST report, and I am here today 
representing myself.
    The American Biomedical Research and Development Ecosystem 
remains the envy of the world. Its value is immense, and I am 
sure that all of us in this room have benefitted from medical 
innovation driven by that system in some way or other. 
Biomedical innovation employs nearly 1 million people in the 
U.S., and exports from the biopharmaceutical industry reached 
nearly $47 billion in 2010, but beyond the economic impact, it 
provides increasingly effective treatments and hope for 
patients everywhere.
    The PCAST report identified a series of challenges and 
obstacles that continue to raise cost, lengthen timelines, and 
increase risk, including difficulties in translating basic 
scientific discoveries into therapies, inefficiency of clinical 
trials, and the need to streamline the regulatory process, as 
well as the need to ensure that appropriate incentives are in 
place to encourage investment in U.S. biomedical research. But 
since the release of that report, a number of important 
developments have occurred demonstrating the resilience of the 
system. The FDA Safety and Innovation Act of 2012 expanded the 
use of accelerated approval, and introduced a new breakthrough 
designation, both very helpful. TranCelerate Biomedical, as I 
mentioned, was launched as an industry collaboration to improve 
the efficiency of clinical trials. It currently has 16 member 
companies, and has embarked on a number of projects aimed at 
reducing operational bottlenecks faced by all sponsors. Early 
results are extremely encouraging. The accelerating medicines 
partnership, a public-private partnership between NIH, the 
pharmaceutical industry and patient advocacy groups, was 
established and will address Alzheimer's Disease, diabetes and 
others.
    At the Reagan-Udall Foundation, a public-private 
partnership created by Congress to support regulatory science, 
post-marketing safety surveillance is being advanced by the 
Innovation in Medical Evidence Development and Surveillance 
Project. And as Mr. Waxman noted, venture capital investment of 
biomedical research has started to increase again. 
Biotechnology investment dollars rose 8 percent in 2013 to $4.5 
billion. These are encouraging signs, but much more needs to be 
done if we are going to reach the ambitious goals set in the 
PCAST report, and maintain our global leadership and life 
sciences, as well as address the healthcare challenges that 
confront the country now.
    Additional help and leadership from Congress on this would 
be tremendously beneficial, and areas for Congress to target 
include facilitating the creation of clinical trial networks, 
investing in new biomarkers and clinical trial endpoints, 
increasing and sustaining funding for both FDA and NIH, 
expansion of public-private partnerships to support the 
scientific missions of both FDA and NIH, providing FDA with 
increased flexibility to accelerate programs for lifesaving 
medicines, and examining existing incentives for capital 
investment of biomedical research.
    Our company, like hundreds of other small innovative 
companies, faces many of these challenges every day. Our 
scientists, like virtually all industry scientists, are 
incredibly dedicated, driven and focused. Their ingenuity and 
problem-solving amazes me every day, and we are making rapid 
progress. We rely heavily upon collaboration with academic 
scientists who advise us, and also upon the regulators who help 
us to find the path forward. We also rely upon our investors. 
They risk their capital because they believe we will succeed. 
Clearly, there is no time or resource to spare. We lay every 
decision, every experiment with the utmost care. We understand 
the implications for our people, our investors, the country, 
but most importantly for the patients and their parents who are 
desperately waiting for cures.
    I applaud the committee for undertaking this effort, and 
the sincere belief that it can result in positive change. 
Enlightened, science-driven policy will allow companies like 
Medgenics to succeed, put the next generation of 
transformational therapies in the hands of caregivers around 
the world, and increase the competitiveness and prosperity of 
our country. Thank you.
    [The prepared statement of Mr. Neil follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize Ms. Radcliffe, 5 minutes for an opening 
statement.

                  STATEMENT OF SARA RADCLIFFE

    Ms. Radcliffe. Chairman Pitts, Ranking Member Pallone, and 
Members of the committee, my name is Sara Radcliffe, and I am 
the executive vice president for health of the Biotechnology 
Industry Organization, BIO. I thank you for the opportunity to 
testify here today.
    BIO is the world's largest trade association, representing 
over 1,000 biotechnology companies, academic institutions, and 
State biotechnology centers across the United States. BIO 
applauds Chairman Upton, Representative Diana DeGette, and the 
committee members for undertaking the 21st Century Cures 
Initiative to examine what steps Congress can take to 
accelerate the pace of discovering and developing cures. We are 
excited to work with you to keep America the innovation capital 
of the world.
    We also applaud the committee for holding a hearing on the 
PCAST report on drug innovation. It is critical that even in an 
environment of budgetary constraint, we do not yield to global 
competition and lose the next generation of discoveries that 
could treat or cure the myriad of chronic and life-threatening 
diseases. From an emotional point of view, we have a duty to 
work to end the suffering these diseases cause. From an 
economic point of view, the U.S. can't afford to lose these 
advancements. Medicare spent over $100 billion in 2012 caring 
for individuals suffering from Alzheimer's Disease, and the 
expense is only going to increase. By 2030, almost one out of 
every five Americans, some 72 million people, will be 65 years 
or older. If we could delay the onset of Alzheimer's by just 5 
years, we would save $50 billion per year. We have a national 
imperative to find new solutions, and this can only be 
accomplished if we all work together to create and defend 
policies that protect intellectual property, empower regulatory 
agencies to keep pace with science, encourage the development 
and adoption of modern approaches to drug development, promote 
a robust reimbursement environment, and continue to incentivize 
investment in scientific research.
    The PCAST report noted that the overall efficiency of 
pharmaceutical R&D efforts has been declining steadily for more 
than 50 years. While there are many contributing factors, it is 
widely recognized that increasing timelines and costs 
associated with clinical trials are key issues. More efficient 
clinical trials will reduce barriers to market for safe, 
innovative medicines.
    In 2012, BIO launched our clinical modernization initiative 
to address four priority clinical research-related issues, some 
of which were also highlighted in the PCAST report. First, the 
use of centralized institutional review boards to promote 
greater efficiency, consistency and qualify of ethical 
oversight for multicenter clinical trials. Next, improving the 
FDA qualification process for drug development tools, including 
biomarkers. Additionally, advancing efforts by patient advocacy 
networks, medical centers, healthcare providers and other 
stakeholders to develop clinical trial networks and 
collaborative partnerships that could realize greater 
efficiency, consistency and quality in the conduct of clinical 
research. Finally, implementing a risk-based approach to 
clinical trial monitoring that leverages centralized data 
monitoring through electronic data capture systems can lead to 
significant efficiencies for clinical trial sponsors.
    We would also like to applaud Congress for already having 
taken action of several of the PCAST recommendations with the 
passage of the Food and Drug Safety Innovation Act, FDASIA. For 
example, PCAST urged the FDA to expand the use of the 
accelerated approval pathway beyond the traditional areas of 
HIV, AIDS and oncology, and to be more open to the use of 
surrogate endpoints and intermediate clinical endpoints that 
are reasonably likely to predict clinical benefit, and that can 
be measured earlier in drug development, pending post-market 
confirmation. FDASIA encourages FDA to utilize the accelerated 
approval program more broadly, which may result in fewer, 
smaller or shorter clinical trials without compromising or 
altering the high standards of the FDA for the approval of 
drugs.
    FDA's draft guidance on expedited programs will be very 
useful to sponsors, however, we encourage the Agency to further 
clarify the process for validating a novel endpoint, and for 
FDA to--and sponsors to discuss potential surrogate or clinical 
endpoints earlier in drug development. The PCAST report notes 
the drug developers have expressed frustration that it is 
difficult to get clear and timely answers concerning the 
accessibility of specific predictors for accelerated approval. 
Without such clarity, the risk of employing such predictors 
during the lengthy drug development process is often too great 
to justify a significant investment.
    Finally, there has been interest in an expedited approval 
process for medicines used for small populations. We look 
forward to continuing discussions with the committee on this 
issue.
    Thank you for the opportunity to share with you our ideas.
    [The prepared statement of Ms. Radcliffe follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    Mr. Pitts. The Chair thanks the gentlelady.
    Now recognizes Mr. Sasinowski, 5 minutes for his opening 
statement.

                STATEMENT OF FRANK J. SASINOWSKI

    Mr. Sasinowski. Thank you for inviting me to testify.
    I would like to introduce my colleagues, Alex Verone and 
James Valentine, who helped me prepare this testimony.
    My testimony draws on 31 years of aiding new medicines get 
to patients in need. My career started at FDA in 1983, and I 
have a special passion for helping on therapies for rare 
diseases, because both my son and I have rare diseases. And I 
have been on the Board of Directors of NORD for the past 14 
years. I am here today representing both myself and NORD. NORD, 
for over 40 years, has been the voice for the 30 million 
Americans with rare diseases.
    I will be presenting 4 proposals for you to consider. My 
first proposal is for FDA to adopt a practice of considering 
the appropriateness of accelerated approval for each new 
therapy. Both PCAST and FDASIA exhort FDA to use its 
accelerated approval authority more. Last September, Alex 
Verone and I submitted to FDA our 65-page analysis of FDA's 
accelerated approvals. Our analysis shows that FDA knows how to 
use this authority, and even how to use it flexibly, creatively 
and nimbly. In my view, what is needed now is simply to give 
this accelerated approval pathway greater visibility, so that 
it will be used more frequently for the benefit of patients, as 
was recommended by both PCAST and FDASIA.
    So my first proposal is for this committee to encourage FDA 
to consider whether accelerated approval is appropriate for 
every new drug therapy that is brought by sponsors to the FDA.
    My second proposal is for sponsors and FDA to use 
intermediate clinical endpoints, also known by its acronym of 
ICE, more often to secure accelerated approval. Alex and I 
analyzed the FDA accelerated approval precedents according to 
the 3 major factors that FDA described in the document that Ms. 
Radcliffe just mentioned, its June 2013 FDA guidance on 
expedited approvals. We analyzed the FDA approvals according to 
these three factors, and we found that two of these three 
factors are far less relevant to accelerated approvals, when 
accelerated approvals based on intermediate clinical endpoints 
or ICE, rather than surrogate endpoints. Therefore, the 
quantity of evidence that sponsors must acquire and present to 
FDA, and that FDA then must review, may be substantially 
reduced if more accelerated approvals are based on intermediate 
clinical endpoints or ICE.
    So to get more medicines to patients faster, this committee 
should encourage both sponsors and FDA simply to use more ICE.
    My third proposal is to tap into the statutory authority 
for approving drugs that Congress created and gave to FDA in 
the 1997 FDAMA Law. This authority stated that FDA could 
approve a drug based on a single study with confirmatory 
evidence. Congress created this as an alternative to the 
standard Congress created in 1962, which has generally been 
interpreted to require two studies. This 1997 alternatives 
authority has been almost universally overlooked by all 
stakeholders, academia, sponsors, patients and even largely by 
the FDA as well.
    I now ask my colleagues to hold up a chart. This chart is 
in my written testimony in greater detail, but this committee 
could propose that this simple chart be used at FDA Advisory 
Committee, and other FDA sponsor meetings and at other forums 
to ensure that all the existing authorities are considered by 
every stakeholder for every new drug. Notice that the second 
line identifies that 1997 statutory authority or standard of a 
single study with confirmatory evidence, and the fourth line 
ensures that all recognize the potential of accelerated 
approval. So this one simple chart could help accomplish both 
of my first and third proposals.
    Thank you, James and Alex.
    My fourth proposal is for the committee to encourage FDA to 
issue guidance on cumulative distribution analyses of clinical 
study results. This could help understand the clinical 
meaningfulness of a new therapy. PCAST recommended that FDA 
issue more guidances to communicate innovative advances and 
regulatory science just like this one of cumulative 
distribution analyses.
    So I am deeply honored by you to have been asked to appear 
before you today. Thank you.
    [The prepared statement of Mr. Sasinowski follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    [Supporting documents submitted by Mr. Sasinowski are 
available at http://docs.house.gov/Committee/Calendar/
ByEvent.aspx?EventID=102237.]
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize Mr. Allen, 5 minutes for an opening 
statement.

                    STATEMENT OF JEFF ALLEN

    Mr. Allen. Good morning, Chairman Pitts, Ranking Member 
Pallone, and members of the subcommittee.
    I am Jeff Allen, Executive Director of Friends of Cancer 
Research, a think-tank and advocacy organization dedicated to 
accelerating science and technology from bench to bedside.
    It is an honor to be here, and I would also like to thank 
our founder and driving force, Ellen Sigal, who is here today 
as well.
    Today, I would like to focus on a few of the key items 
identified within the report to the President, by describing 
areas in which there has been significant progress, and areas 
to which the committee might turn its attention and resources.
    One key challenge that the working group explored was 
improving drug regulation at FDA. The authority and tools to 
fill FDA's monumental responsibility continues to evolve to 
keep pace with current science. I would like to provide a few 
examples that demonstrate this.
    In collaboration with our expert colleagues from FDA, NIH, 
patient advocacy industry, and academia, we at Friends of 
Cancer Research proposed a series of approaches of how clinical 
testing could be modified to expedite the development of new 
targeted therapies that show dramatic clinical activity early 
in development. With the leadership of this committee, and your 
colleagues in the Senate, the creation of the new FDA program 
called the Breakthrough Therapies Designation was codified into 
law as part of the FDA Safety and Innovation Act.
    FDA has been rapidly implementing the program in many 
serious disease settings, and, Mr. Chairman, I am happy to 
report that in just 2 years, 178 requests for breakthrough 
designation have been submitted, 44 have been granted, and 6 
breakthrough therapies have been approved.
    It has been estimated by some of the sponsors of the drugs 
that the breakthrough therapy program accelerated the 
development process by several years, without compromising the 
long-held standards for safety and efficacy. The all-hands-on-
deck approach demonstrates the importance of the public-private 
collaboration that the designation brings to enhanced science-
based regulation, translating to reduced development times, 
increased investment in the biotech sector, and the improved 
health of patients that previously had few treatment options. 
This is an incredible example of Congress putting partisan 
politics aside, and acting deliberately to address one of our 
country's most pressing health issues.
    Another key component of the report to the President 
explored ways of addressing inefficiencies in clinical trial 
conduct. There is no doubt that our antiquated patchwork 
clinical trial system makes developing new treatments a 
cumbersome, expensive and protracted process.
    To being to address this issue directly, and truly change 
the course of how trials are done, Friends of Cancer Research 
is spearheading a project working with a large diverse set of 
partners from academia, industry, Government and advocacy, to 
develop a modern-day clinical trial as innovative as the 
therapies it seeks to test. In this project, called Lung Map, a 
master protocol will govern how multiple drugs, each targeting 
a different biomarker, will be tested as a potential treatment 
for lung cancer. Each arm of the study will test a different 
drug, and utilize cutting-edge screening technology to identify 
which patient is a molecular match to each arm. This will 
create a rapidly evolving infrastructure that can 
simultaneously examine the safety and efficacy of multiple new 
drugs. Lung Map has the ability to reinvigorate the research 
enterprise, and rapidly facilitate the development of 
molecularly targeted medicine. This approach has the ability to 
improve enrollment, enhance consistency, increase efficiency, 
reduce cost, and most importantly, improve patient lives.
    One way that the FDA communicates to researchers and 
developers about new approaches or changes to current policy is 
through guidance documents, an interchange that is vital to 
modernizing the enterprise. The report recommends that external 
partnerships could be beneficial in providing input on 
scientific subjects that would be fit for guidance. Neutral 
public venues that can facilitate the exchange of ideas can 
greatly inform the topics and approaches that FDA may take when 
considering best practices and guidance development. Much like 
FDA benefits from hearing the challenges faced by the research 
community, the external community gains from hearing from FDA. 
Processes and adequate funding levels need to be established to 
increase FDA's ability to gain external input and develop new 
guidance. This has the ability to greatly enhance the success 
of research endeavors, encourage innovation--innovative 
collaborations, and can inform by the legislation.
    In addition to the elements raised in the report, we at 
Friends of Cancer Research believe that consideration should 
also be given to opportunities in the development of companion 
diagnostics. Building on the foundation that FDA has provided 
through recent guidance, this committee could facilitate new 
policies to advance how novel technologies can inform the use 
of new drugs to ensure that the right patients have access to 
the right treatments at the right time.
    The examples that I have provided today are case studies 
that can be learned from, and are steppingstones upon which 
more work can be done. Innovation is incremental, but with 
better understanding of the disease processes, these 
incremental steps toward improving health can and will be 
transformational. The regulatory framework has been put into 
place, and enhanced collaborations will be needed to uncover 
new breakthroughs and alleviate inefficiencies. Aligning 
policies with the current state of science can enhance 
biomedical research and improve the lives of patients. The 21st 
Center Cures Initiative can be the next step toward that goal.
    [The prepared statement of Mr. Allen follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognizes Dr. Tunis, 5 minutes for an opening 
statement.

                   STATEMENT OF SEAN R. TUNIS

    Mr. Tunis. Well, I would also like to thank Chairman Pitts, 
Mr. Pallone, and the members of the subcommittee for the chance 
to testify today.
    Again, my name is Sean Tunis, and I am currently the CEO 
for the Center for Medical Technology Policy. It is a nonprofit 
that works on bringing together stakeholders to improve the 
quality and efficiency of clinical research.
    I did serve as one of the invited experts to the PCAST 
council members and staff, and because of my former role as 
chief medical officer for the Medicare Program, I thought it 
would be most useful to reflect on these recommendations in the 
report from the perspective of the payer and the health system. 
It wasn't directly addressed in the report, but a number of the 
recommendations have implications for the health delivery 
system that I think need to be thought through more carefully 
in order to ensure that the recommendations can be implemented 
successful.
    And I really think the--kind of the key message I wanted to 
deliver and what it comes down to is that because many of the 
recommendations in the report essentially shift evidence 
requirements and data development from the pre-market space to 
the post-market space, in other words, the delivery system, it 
is going to be important to think about how it is going to be 
possible to efficiently conduct clinical research in the post-
market environment, in other words, how do we embed the 
evidence development that is not generated preapproval in the 
context of delivering clinical care. And so I am going to offer 
3 recommendations or suggestions about how that kind of 
evidence can be produced.
    Just to briefly highlight the recommendations in the PCAST 
report that sort of have this effect, essentially, of shifting 
clinical research and evidence development to the post-market 
space, of course, there is the increased use of accelerated 
approval, depends more on intermediate and surrogate markers, 
and, therefore, the expectation is that more of the evidence of 
safety, effectiveness and even value are going to be generated 
while these products are in use in the delivery system. The 
special medical use as well as the adaptive licensing 
mechanisms also have the same effect, which is, again, to 
require the ability to do efficient clinical research and data 
collection in the post-market space.
    So in order for the PCAST recommendations, I think, to have 
the desired impact, which is to speed innovation, and to do 
that in a way that doesn't in some way compromise the 
expectation of safe, effective and high-value medications in 
clinical use, we are going to need, again, to think about how 
do we get that kind of data out of the delivery system.
    As members of the subcommittee know very well, what is 
simultaneously going on to these innovation discussions is a 
lot of health systems reform that is increasingly pushing 
payers and the health systems to be looking for improved 
effectiveness, real-world effectiveness, and even the value of 
new medications. So at the same time as we are hoping to 
introduce new drugs into the healthcare system with less 
information about safety and efficacy, we are also putting 
pressure on payers and providers and health systems to demand 
more evidence of comparative effectiveness and value in order 
to be able to deliver high quality and efficient care. So we 
have got some tension between what we are trying to do on each 
ends of this policy spectrum.
    So, again, I think the solution to this is to think about 
ways in which we can be more efficient about data development 
in post-market studies. And basically, I will mention three 
kinds of components that I think are important to this. The 
first one is developing more clarity about what constitutes 
adequate evidence of effectiveness and value from the 
perspective of payers, clinicians and patients. And what I 
really mean by this is, in the same way that regulators produce 
guidance to explain what kinds of studies are necessary to 
achieve regulatory approval, there is currently nothing that 
provides guidance to product developers on what meets 
expectations of real-world effectiveness and value. And so, in 
a sense, the whole world of regulatory science, which is all 
about giving product developers clear guidance on clinical 
development, I think needs to be kind of mirrored in something 
you might call reimbursement science, which is how do you 
develop evidence for reimbursement decisions.
    The second recommendation is, and some people might think 
reimbursement science is an oxymoron, but, you know, possibly 
we will make some progress.
    The second and third recommendation, since I am running out 
of time, is--one is that we need to build infrastructure in the 
healthcare system to do better research. The NIH is working on 
that. And, finally, we are going to need to find reimbursement 
mechanisms that are actually conditional on collecting 
additional data. Medicare has used coverage with evidence 
development. There are other forms, but if we are actually 
going to be shifting these data collection requirements to 
post-approval, we need the payers to be willing to pay for 
things while they are being evaluated, much like the FDA has 
post-approval authority. I think the payers need to implement 
post-reimbursement authorities for--to collect the additional 
data on safety and effectiveness.
    So thanks again for the opportunity to testify.
    [The prepared statement of Mr. Tunis follows:]
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT] 
    
    Mr. Pitts. The Chair thanks the gentleman. Thanks all the 
witnesses for their prepared testimony. We will now begin 
questions and answers. I will begin the questioning and 
recognize myself 5 minutes for that purpose.
    Dr. Neil, the PCAST report notes that the pharmaceutical 
industry is facing the largest patent cliff in its history. As 
a result, many companies are adopting more conservative 
approaches to research and development, particularly in areas 
with growing healthcare and economic burden, such as 
neurodegenerative diseases such as Alzheimer's and psychiatric 
diseases. What role could additional economic incentives play 
in driving R&D into these areas where there is a critical 
public health need, Dr. Neil?
    Mr. Neil. I think they could be extremely valuable in 
helping to offset some of the cost associated with the risk, 
and the length of time these programs require. I do think 
though that it may be as productive or more productive to 
invest additional resources in things like endpoints, 
intermediate clinical endpoints, clinical endpoints. Often, we 
have found that as we try to study some of these 
neurodegenerative diseases, they--it is a very long time 
between onset and ultimate disability, and if that is what 
needs to be used as an endpoint, it makes the feasibility of 
these trials much lower. So we haven't done enough to really 
invest, I think, in creating such endpoints, and I am thinking 
about Alzheimer's Disease, I am thinking about stroke as a 
couple of those, but there are many others, and some of the 
rarer neurodegenerative diseases have been inadequately studied 
with respect to their natural history as well. So I think some 
targeted efforts there would also be very helpful, as well as 
accelerating the pace of discovery work where diseases like 
schizophrenia, we have been out of really promising targets for 
some time.
    Mr. Pitts. OK. Ms. Radcliffe, what challenges do drug 
sponsors and the FDA face today in the use of surrogate 
endpoints and biomarkers, and what are the current barriers to 
their more widespread adoption and use? And maybe you want to, 
just for the general public, tell us what biomarkers, 
endpoints, define them for us too briefly.
    Ms. Radcliffe. Sure. Absolutely. So biomarkers, and the 
terms biomarkers and endpoints are used in various different 
ways in the scientific community, so I am going to tell you the 
way in which I urge that we understand those terms. A biomarker 
is really a signal of--it is a biological signal of another 
biological process. It is really that simple. A biomarker can 
be used in many different ways in research and development. For 
it to be used in the regulatory context, all parties have to 
have a great confidence in the relationship between the 
biological signal and the biological process that it is 
signaling. An endpoint in regulatory terms, a clinical 
endpoint, is something that affects how a patient feels, 
functions or survives. So in relatively simple terms, it is 
something that the patient will actually recognize. A surrogate 
endpoint is a marker that can point toward the ultimate 
clinical benefit for a patient. So an example of that would be 
viral load is a surrogate endpoint for a treatment effect for 
HIV and AIDS drugs. An intermediate clinical endpoint is a 
clinical endpoint that can be measured earlier on in the 
disease process. And so an example of an intermediate clinical 
endpoint would be something that is called forced vital 
capacity, that is the ability for a patient to expel a large 
amount of air, and it can be a good marker of progression and 
possibly treatment effect in neurodegenerative disorders. And 
so the use of intermediate clinical endpoints can expedite drug 
development because you are now working toward treatment of an 
endpoint that you are seeing earlier on in the disease process, 
and that may enable you to ward off further--effects further 
down the line in the disease process. So why is it important 
for our companies? The use of surrogate endpoints and 
intermediate clinical endpoints can expedite drug development, 
and enable us to get a product to patients earlier with smaller 
and shorter clinical trials. In terms of the obstacles that we 
face, as I said, there is not the kind of clarity that we would 
like around what FDA will accept as a surrogate endpoint, and 
what FDA will accept as an intermediate clinical endpoint. The 
evidentiary standards that FDA is likely to require at this 
time really require a lot more discussion with the Agency, and 
also just in terms of process, as I said in my testimony, there 
isn't at this time a good practice of companies and sponsors 
talking about intermediate clinical endpoints earlier on in the 
drug development process, so that you can really work toward 
the use of those endpoints as you develop your submission to 
the FDA.
    Mr. Pitts. The Chair thanks the gentlelady.
    My time has expired. Recognize the ranking member 5 minutes 
for questions.
    Mr. Pallone. Thank you, Mr. Chairman.
    I wanted to explore in some detail one of the 
recommendations from the PCAST report, specifically, 
recommendation number three, which states that FDA should 
expand the use of its existing authorities for accelerated 
approval, and for confirmatory evidence. And as I understand 
it, there are already a few pathways in the current law and 
regulations for the expedited review of drugs, including fast 
track, breakthrough therapy, accelerated approval and priority 
review, and the goal of all these pathways is to speed the 
development and availability of new treatments to patients at 
the earliest possible time. Just a couple of years ago in the 
2012 FDA Safety Innovation Act, we updated the fast track 
approval mechanism and established the breakthrough therapy 
path. And then, of course, the 21st Century Cures Initiative 
seems to have been promoted at least in part by what has been 
described as a regulatory system that is a relic of the past, 
but this is confusing to me because we just finished updating 
the system, and providing FDA with new tools. So I also didn't 
hear anyone at this--the first roundtable with the 21st Century 
Cures Initiative who would describe FDA's drug regulatory 
program as somehow out-of-date.
    So I would like to hear more from our experts here today on 
how effectively FDA has been using these current authorities, 
and where there might be room for improvement.
    First, let me ask Dr. Allen. Your testimony describes FDA's 
use of the breakthrough therapy pathway, which sounds like it 
has been a real success. Can you say a little more about that, 
and describe how FDA has used any of the other expedited review 
authorities with respect to cancer drugs, and have you 
identified any problems or issues in its application of these 
authorities?
    Mr. Allen. Sure. Well, I again want to thank the committee 
for their leadership in creating such a designation.
    The tools that FDA currently has, based on the 2012 law and 
others, have been widely used in cancer. I think well over a 
third of all anticancer drugs have utilized the accelerated 
approval process, for example. So it certainly is valuable. The 
purpose of the breakthrough therapy designation was to, as you 
say, Mr. Pallone, too, advance and give the flexibility for FDA 
to respond to the current state of science, because what we are 
seeing in oncology and many other genetically driven diseases 
is the ability to target different genetic alterations, and 
stop the progression of the disease. And this calls for a 
different way of doing business, and we believe that is what 
the FDA is doing, and they have robustly implemented the new 
breakthrough therapies provision and are excising it regularly.
    I think it is worth noting the resource intensity of this 
program. It certainly is serving its purpose of getting the 
most promising therapies to patients, but the resources 
required to do so are not insignificant, and I know there is a 
hearing elsewhere today considering the funding for FDA, and I 
would encourage them to do what they can to support that.
    I think the historic basis of speaking to those regulations 
is because there were laws in 1960 that established the safety 
and efficacy standard, and those are extremely important that 
we continue to optimize regulation and drug development within 
those important standards.
    Mr. Pallone. All right, thanks.
    Mr. Sasinowski, your testimony also describes the ways in 
which FDA has used these authorities over the years, and it 
sounds like you would also say that FDA uses them frequently 
and prudently. Is that correct?
    Mr. Sasinowski. Mr. Pallone, prudently but not frequently. 
The analysis that my colleague, Alex Verone, and I did, we 
looked at all of the FDA accelerated approvals for therapies 
other than cancer, and Mr. Allen is right, it is often used in 
cancer. I was at FDA during the AIDS crisis, and so I was part 
of the group that helped create Subpart H, which was very 
useful for stemming the AIDS crisis. So accelerated approval 
has been used, but you will notice in our PCAST report that you 
cite, Mr. Pallone, that 87--we say in the PCAST report 87 
percent of all the accelerated approvals have been for cancer 
and for AIDS. And so what Mr. Verone and I did is we looked at 
every accelerated approval from the mid-'80s through June 2013. 
We found only 19 drugs that had been approved, not for cancer, 
not for AIDS, under accelerated approval. We found that the FDA 
did use accelerated approval appropriately in those 19 cases, 
but it was only 19 cases, Mr. Pallone, and that is why I think 
PCAST said we should use it more. I think that is why this 
committee and Congress said in FDASIA, FDA, use it more. That 
is why there are 2 women who I was surprised to see here, who 
are in this room, who have between the 2 of them, 3 boys with 
DMD; Christine McSherry and Jane McNeary, and I know that they 
represent, as a member of NORD, they represent the kind of 
Americans who are suffering and who are looking for FDA to use 
accelerated approval more often for conditions that are not 
AIDS, not cancer.
    So I think appropriately they used it, and that is why I 
suggest this chart, because I have been to thousands of FDA 
meetings since I left the FDA, with sponsors seldom does the 
word Subpart H, accelerated approval or fast track ever get 
mentioned. People are not focused on it, that is why I urge you 
to consider exhorting the FDA through some simple mechanisms 
like a chart, like at every advisory committee when the chair 
of an advisory committee turns to the FDA and says, ``What are 
we supposed to do with this date? We know what the Congress' 
standard was in 1962: two adequate and well-controlled studies. 
This is a rare disease. Something like Duchenne Muscular 
Dystrophy. We don't have two adequate and well-controlled 
studies, so what are we supposed to do?''
    Well, there is a lot of hemming and hawing, and I think 
that if we had a chart like this that was proposed, that would 
summarize in a clear way that there are alternate authorities 
like the 1997 authority that Congress created, which was the 
single study with confirmatory evidence, and I have explained 
that in great detail in my written testimony, that that would 
be very useful, as well as to remind everybody of accelerated 
approval.
    Mr. Pallone, I was at a hearing just last summer, in August 
2013, for a drug for autosomal dominant polycystic kidney 
disease. My spiritual director had his nephew die of this 
disease. I know people who have died of this rare disease. It 
is a terrible disease, and yet not once did anyone ever mention 
at that hearing the possibility of accelerated approval, even 
though it is a serious disease, it is for a situation where 
there are no approved therapies, it is ripe for consideration 
under accelerated approval, just like PCAST, just like you and 
FDASIA said FDA should do, and yet it was never considered.
    So I am struggling to think of ways, Mr. Pallone and the 
committee, to try to bring this forward in practical ways, and 
that is why I come up with something as simple as a chart. It 
might seem pedantic, it might seem trite, but I think sometimes 
simple things work. And so I think you are right when my 
analysis shows that the FDA has used this authority 
appropriately and prudently, but not frequently. And the other 
thing that has been completely overlooked is that single study 
with confirmatory evidence standard, which Congress created in 
1997 and FDA seldom used.
    Mr. Pallone. Thank you.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the vice chair of the subcommittee, Dr. 
Burgess, 5 minutes for questions.
    Mr. Burgess. Thank you, Mr. Chairman. And I actually 
appreciate that last part of your discussion, Mr. Sasinowski. 
You started at the FDA just a couple of years after I started 
in private practice, and I can recall back in the '80s being 
frustrated by the fact that it seemed like there were new 
therapies that were available in Europe, and it took us forever 
to get them in this country. Of course, Chairman Waxman, or 
Ranking Member Waxman, deserves a lot of credit for starting 
the user fee agreements, which we reauthorized in the last 
Congress.
    Dr. Neil, I wanted to ask you just very quickly if you 
could--you mentioned that your company was involved in novel ex 
vivo gene therapies. Could you give us a synopsis or a summary 
of--without violating, obviously, propriety interests, but can 
you tell us some of the directions that you are--in which you 
are working?
    Mr. Neil. Yes. The core of our technology is something 
called the bio pump. So we remove a small piece of dermis, the 
layer just below the skin, about half the size of a toothpick, 
and we transduce that with a viral vector to express a 
transgene, a protein that a patient with a rare and orphan 
disease might not express at all, or might express in too low a 
quantity, and it is causing their disease, and they could 
benefit from having this restored. And after the transduction, 
all of the viral antigens are washed away and we re-implant 
this small piece of tissue back into the patient, so the 
patient effectively manufactures their own protein that they 
could not manufacture before, or in a sufficient quantity, and 
that then addresses, we hope, the disease in question.
    And we are aiming this technology at a number of rare and 
orphan diseases that could benefit.
    Mr. Burgess. And in addition to rare diseases, are there 
more common diseases that you are also working toward?
    Mr. Neil. Yes, that is very likely, but I think that we 
shouldn't overlook the fact that very often we can learn so 
much by studying a rare and orphan disease initially because 
the population is enriched, we understand the mechanisms much 
better, and then we can apply the lessons that we have learned 
to the larger syndromic diseases.
    Mr. Burgess. Since a lot of this panel, or a this hearing 
today, deals with the regulatory aspects, how is that--how has 
your experience been then when you take this information back 
to the FDA for regulatory approval? Do they understand what you 
are doing, are they able to give you the proper direction about 
how to structure your studies so that regulatory approval can 
be achieved?
    Mr. Neil. Yes, our interactions with FDA have been a little 
bit earlier than approval, because we are just embarking on 
some of these programs in the clinic, but those interactions 
have been very positive, and they seem very helpful and very 
interested in the technology, but we and other companies are 
now bringing to FDA very novel therapies which incorporate many 
different elements, such as medical devices, gene therapy, 
tissue transplant and so on, and I think that, and I directed 
some of my testimony toward that, the increasing complexity of 
these types of treatments, something that FDA is going to need 
to invest in expertise in----
    Mr. Burgess. That is----
    Mr. Neil [continuing]. Culture.
    Mr. Burgess. That is correct. I don't mean to interrupt you 
because I am going to run out of time, but that is correct, 
they don't have the----
    Mr. Neil. Right.
    Mr. Burgess [continuing]. Expertise currently. They do have 
to develop it.
    Dr. Tunis, I really appreciated your end of the discussion. 
You talked about from the payer aspect to the CMS aspect. 
Certainly we want to avoid the public relations disasters that 
were of Asten and Provenge from a year or two ago, and one of 
my concerns through a lot of the hearings that we have had here 
is anyone looking at the end use of this, I mean, OK, we have 
got NIH developing, we have got the FDA which is going to 
regulate and/or approve, but we also need to involve the payer 
at some point to let them know what is coming so that they can 
appropriately adjust. So I do appreciate you bringing that up, 
and I think oftentimes we overlook that aspect of the 
regulatory pathway.
    Mr. Neil. Yes, and, you know, I think, just to point out, I 
think, you know, the payers are often viewed collectively as, 
you know, not in favor of innovation or somehow resistant to, 
you know, new technologies, and while, you know, there are 
certain ways in which that is true, I think it is also true 
that the health system understands that innovation is 
potentially a way to get better outcomes at even lost costs, 
you know. Treating disease is obviously, you know, cheaper than 
treating a--you know, treating it forever is cheaper than 
having to continue to treat it in an ongoing way.
    So the challenge really is that--and as I said, I do think 
the payers get left out of these conversations. There were a 
couple of payers on the PCAST committee, and again, most of the 
discussion about the--is about regulatory issues, but, you 
know, a metaphor I use is you don't want to create this 
superhighway of innovation in the regulatory space, and then 
have a gravel road, you know----
    Mr. Burgess. Um-hum.
    Mr. Neil [continuing]. In the reimbursement space for 
those----
    Mr. Burgess. And I have been down that gravel road. You 
know, when I was in medical school, we learned about the 
treatment of peptic ulcer disease. It was a surgery, a highly 
selective vagotomy of removal of part of your body, but I also 
remember going to a luncheon meeting back in the '70's where 
Dr. Fordtran from Dallas came down and talked about this new 
idea he had of a histamine blocker to deal with ulcer disease. 
And, of course, now half the country is on proton pump 
inhibitors, and the highly selective vagotomy is in the 
Smithsonian Institution. No one does them anymore. You would 
have to go--it itself is a rare disease because you--no one has 
to have that anymore. It is hard to get the same, you know, to 
be able to account for the savings that Dr. Fordtran created 
with the development of his product, because all of the baby 
boomers who at that point were in medical school, but were on 
their way to developing ulcer disease, would have required that 
surgery at some point in their future.
    Mr. Neil. To say nothing of them cured of antibiotic 
therapy for helicobacter pylori, which----
    Mr. Burgess. Sure.
    Mr. Neil. Yes.
    Mr. Burgess. Thank you, Mr. Chairman. He--his gavel is the 
surrogate endpoint for my questioning.
    Mr. Pitts. We will have a second round.
    The Chair thanks the gentleman. Now recognize the gentleman 
from Texas, Mr. Green, 5 minutes for questions.
    Mr. Green. Thank you, Mr. Chairman. And, again, thank our 
witnesses for your testimony today.
    Without greater investment in antibiotics, we will face a 
future that resembles the days before these miracle drugs were 
developed, one in which people died of common infections, and 
many medical advances that we take for granted today will 
become impossible, including surgery, chemotherapy and organ 
transplantation.
    Dr. Neil, you mentioned in your statement, in 2012, PCAST 
recommended a limited population drug approval pathway in order 
to facilitate drug development. PCAST specifically identified 
antibiotics as an area where this pathway would be important, 
and as we know, the need for new antibiotics is urgent. The 
World Health Organization reiterated this just this month in a 
report of antibiotic resistance which said it is a very real 
potential for post-antibiotic era here in the near future.
    My colleague, Dr. Gingrey, and I introduced the ADAPT Act 
which would create the pathway PCAST described. FDA officials 
from the Commissioner down have talked about the Agency's 
desire to work with Congress to get this done. We are eager for 
Congress to act quickly and given the urgency of the situation.
    Dr. Neil, could you explain how this pathway would benefit 
antibiotic development?
    Mr. Neil. I think that--yes, it is on. I think it would 
benefit it tremendously, not only the development of it, but 
also the appropriate use of these new drugs once they get into 
clinical use. But the idea that one can identify very easily 
through surrogate markers the appropriate population with a 
serious infection, and be able to address that much more 
quickly, speed these antibiotics to the market, I think is a 
terrific one. And not only that, I think what we learn from 
this and how to implement it can be applied to other serious 
diseases later on, potentially.
    Mr. Green. OK. Dr. Allen, cancer patients are particularly 
at risk for serious bacterial infections. Patients undergoing 
chemotherapy have suppressed immune systems, making it more 
difficult for them to fight off other diseases. Without 
antibiotics, chemotherapy would be significantly more 
dangerous.
    Dr. Allen, you talk about a limited population pathway for 
antibiotics. Could--this could be important to cancer patients. 
Can you talk to us about that?
    Mr. Allen. Sure. Well, as you mentioned, and thank you for 
your leadership in this area, risk of infection for cancer 
patients is certainly increased, and it has the potential to 
interrupt their treatment on a chemotherapy or other anticancer 
drug, that they may have to stop that treatment, and it could 
have a detrimental effect toward harnessing the growth of the 
cancer. Even more detrimentally is if a cancer patient who is 
immune-compromised is infected with microbial infection, it 
poses them at risk for serious adverse events and fatality. So 
it is not insignificant here both in the treatment of the 
cancer, but also in the survival of the patient.
    Mr. Green. OK. In 1990, there were almost 20 pharmaceutical 
companies with large antibiotic research and development 
programs. Today, there are only two or three large companies 
with strong active programs, and only a small number of 
companies that have more limited programs.
    Ms. Radcliffe, in your testimony, you mentioned that the 
ADAPT Act and the importance of the voluntary pathway that can 
help foster novel drug development. Can you elaborate on how 
this kind of pathway would address some of the economic 
challenges, particularly the size, the cost and time it takes 
to complete clinical trials that may be hindering antibiotic--
investment in antibiotics?
    Ms. Radcliffe. Yes, certainly. BIO supports the ADAPT Act, 
and we thank you very much as well as Representative Gingrey 
for your work on developing this pathway. It has to walk a very 
fine line.
    Mr. Green. Yes.
    Ms. Radcliffe. It is important that sponsors be able to 
seek the designation early, or follow the pathway early on in 
development so that they can gain the benefits of being able to 
design a clinical pathway in a smaller population, and with 
attention from FDA as to the greatest clinical efficiency in 
those trials. This Bill would permit that to happen. It is also 
important that the pathway not infringe on the pathway--on the 
practice of medicine, and that is an important protection for 
patients. Physicians have to be able to use a product that they 
believe to be the best for their patient and the circumstances 
where the patient finds him or herself. And so, therefore, it 
is very important that such a pathway not infringe on the 
path--on the practice of medicine, and the Bill that you have 
introduced does that. So we think that it will be a very 
great--of very great assistance to sponsors in terms of 
incentivizing work in this incredibly important area for 
antibiotic resistance.
    Mr. Green. Thank you, Mr. Chairman. I know I am out of 
time. To meet this crisis, we need a multi-prong approach that 
includes enhanced monitoring, better use of antibiotics, and 
investment in new therapies, and we can no longer ignore the 
risk of antibiotic resistance, the epidemic and the growing 
number of lives these superbugs claim.
    And I thank you for having the hearing today.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the gentleman from Illinois, Mr. Shimkus, 5 
minutes for questions.
    Mr. Shimkus. Thank you, Mr. Chairman. It is great to have 
you all here.
    I have been interested, there is a Washington Post story 
published May 16 on the movement by States on right-to-try 
laws. The one column--part of the end of the article, and, Mr. 
Chairman, if we could submit it for the record. I----
    Mr. Pitts. Without objection, so ordered.
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    Mr. Shimkus. There is a story about the spouse, Amy Auden, 
from Lone Tree, Colorado, who had--her husband had melanoma, 2-
year battle, the last year they tried to get a promising drug, 
couldn't get it, and he has since passed. And her comment is, 
of course there was a chance Nick would have been in the 52 
percent of the people who are responding to the drug, however, 
a 52 percent chance of life is better than a 0 percent chance 
of life, which was the dilemma that this family was placed in. 
And, hence, you see States moving to address this. It is not--
what--a brief comment on this movement by States on--to right-
to-try laws, and that is probably symptomatic of a slow process 
of getting drug therapies quickly to the market. Is that true? 
Let us just go from left to right, if you want? And if you 
don't want to answer, that is fine. I mean it is----
    Mr. Neil. Well, in my experience, FDA has always been very 
compliant in getting patients, you know, into small trials or 
compassionate use trials. To me, the issue has always been for 
smaller companies, having the resources to be able to provide 
that, and I think mechanisms----
    Mr. Shimkus. This wasn't a small company that she had to 
deal with----
    Mr. Neil. Yes.
    Mr. Shimkus [continuing]. So----
    Mr. Neil. Well, yes, I think that there should be some way 
for companies to recover their cost, and to get patients into 
trials, and to be able to collect the information that you need 
to make that----
    Mr. Shimkus. Right.
    Mr. Neil [continuing]. Usable.
    Mr. Shimkus. And please kind of go quickly. I have got--
actually my two official questions that I need to get to.
    Ms. Radcliffe. So this is a very, very difficult issue. BIO 
has a board-level Biothics Committee which is currently 
involved in taking a deep look at the issues around expanded 
access. I think everyone understands that if somebody in their 
own family were in such a situation that they needed an 
investigational product, I think most of us would do everything 
that we could to----
    Ms. Shimkus. But is the statement----
    Ms. Radcliffe [continuing]. Ensure----
    Mr. Shimkus [continuing]. About the process----
    Ms. Radcliffe. Yes.
    Mr. Shimkus [continuing]. And how slow and methodical, and 
people who--it is happening, I mean these are--there are three 
States I think, there is Colorado, one is going to be signed 
into law on Saturday, from what I am reading, and that is a 
response to people feel that they are not getting a chance to 
fight for their life, and they are being held up either in 
the--let me move forward. I--because I need to move on on these 
two other questions. On the presence counsel raises the fact 
that in recent years there has been a regulatory uncertainty 
about a variety of important issues that has hindered 
investment and innovation. One such issue is combination of 
therapies and studies that are required for their approval.
    Has FDA since provided sufficient clarity in this area, or 
is there need to ensure greater regulatory certainty for 
companies to spur further innovation in this increasingly 
important area of drug development? Anyone want to try it?
    Mr. Neil. I think there is further need, particularly 
outside of cancer, to echo Mr. Sasinowski's comments earlier.
    Mr. Shimkus. Great, thank you. Anyone else?
    Mr. Tunis. Yes, you know, and I would just add again, sort 
of related to some of the comments I made in my testimony, that 
the better equipped, you know, we are in the context of 
delivering healthcare to get the additional information about, 
you know, products that are approved through an accelerated 
pathway, I think the more the FDA can count on some of the 
unanswered questions about safety, you know, safety and 
effectiveness to be efficient--to be answered at least at some 
point, and then the opportunity to accelerate--to use the 
accelerated authorities more frequently, I think, is enhanced 
as the delivery system gets better at filling in what is not 
studied pre-market.
    Mr. Shimkus. Let me finish with this last question, and the 
rest I will submit for the record.
    A second distinct area that report highlights which is of 
particular interest to me is the issue surrounding the 
certainty and the regulatory pathway when it comes to therapies 
for which patients are picked based upon companion diagnostics. 
The companion diagnostic may or may not be approved already, 
adding an additional layer of complexity for the sponsor.
    Do any of you witnesses have experience in this area to 
comment on what needs to be done to encourage investment and 
innovation for these personalized approaches?
    Mr. Allen. So the trial that I mentioned with regards to 
lung cancer is working to try and advance these technologies 
through the regulatory process, by using new technologies that 
have the ability within a single test to monitor the activity 
and presence of different genetic alterations. So it has the 
ability to really reform the current single test paradigm with 
a single drug. But I think the FDA has been proactive in 
issuing guidance documents both from the drug and diagnostic 
side, to begin to lay out what their feelings are on how to 
generate this evidence, but some of this is also an artifact of 
making sure that there is a robust research enterprise to 
really understand which are those true alterations that are 
driving different diseases.
    Mr. Shimkus. Great, thank you.
    My time has expired. Thank you, Mr. Chairman.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the ranking member of the full committee, Mr. 
Waxman, 5 minutes for questions.
    Mr. Waxman. Thank you, Mr. Chairman.
    The PCAST report's fourth recommendation is the creation of 
a new pathway that manufacturers could choose to use for 
initial approval of drugs shown to be safe and effective in a 
specific subgroup of patients. The report notes that such 
approvals could sometimes be based on relatively small and 
rapid clinical trials showing a favorable safety and 
effectiveness risk benefit ratio for the narrow population most 
in need of the drug, however, it notes that for such a pathway 
to work, FDA would have to be confident that the drug generally 
would not be used beyond the limited population for which it 
was evaluated and intended.
    Dr. Allen, do you think the pathway makes sense if FDA does 
not have adequate authority to ensure that the designation is 
used to inform potential users and payers of the special 
standing and circumstances surrounding approval of the drug?
    Mr. Allen. I think it is important to state that the 
intention of the limited population pathway is to still operate 
within the confines of safety and efficacy, and that is not 
altered. I think that ensuring appropriate use of these types 
of products will require a great deal of interaction with the 
medical community, and make sure--in making sure that the 
appropriate lines of communications are present, to make sure 
that the benefit risk profile within that subset is maintained, 
and communicating clearly that the benefit risk for the 
entirety of the population may not be known yet, but those 
patients with the most life-threatening version of that disease 
don't have the time to wait. So this allows for access for 
those with the most severe form of a relatively common illness.
    Mr. Waxman. So you think that if a--if they have adequate 
authority to designate this information, that that would be 
important if they are going to release this drug before it is 
approved for the general population?
    Mr. Allen. Yes, certainly, and having the ability to 
communicate is largely based on the label, as it is with all 
prescription drugs----
    Mr. Waxman. Um-hum.
    Mr. Allen [continuing]. But in this case, it would be 
important to indicate if there is--if this has only been tested 
in the most severely ill patients, through use of some sort of 
symbol----
    Mr. Waxman. Um-hum.
    Mr. Allen [continuing]. Or logo to communicate it, but also 
the ability to pre-review marketing material, and that has been 
an effective strategy in other areas such as accelerated 
approval.
    Mr. Waxman. Let me turn to another recommendation in the 
report. Recommendation five has to do with another new 
potential mechanism for more quickly making new therapies 
available to patients, a so-called adaptive approval. As I 
understand it, adaptive approval refers to the concept that 
there would be a series of approval stages that would gradually 
allow a new therapy to be marketed for broader patient 
population, so as more is learned about a drug, the use of it 
could be expanded.
    The PCAST apparently explored this concept extensively, 
however, in its final recommendation, it said that Congress 
should not legislate this new pathway, instead, any use of this 
approach should instead be tested in pilot projects.
    Dr. Allen, can you say more about why PCAST was hesitant to 
have any legislation on this pathway at this point?
    Mr. Allen. Well, I don't want to speak on behalf of the 
entire work group, but, you know, from my perspective, it is 
very difficult to have one set of rules that governs a very 
diverse set of products----
    Mr. Waxman. Um-hum.
    Mr. Allen [continuing]. And given the pace at which science 
is accelerating, I think many of the other witnesses on the 
panel today have talked about some really innovative approaches 
to different diseases, and it is hard to really kind of draw a 
single line in the sand. A drug for prevention is very 
different than a drug for late-stage pancreatic cancer, and the 
benefit risk profile of that is very different----
    Mr. Waxman. Um-hum.
    Mr. Allen [continuing]. And so it is hard to codify that 
into law.
    Mr. Waxman. Mr. Sasinowski, do you have anything to add on 
this? Why did PCAST recommend against legislation?
    Mr. Sasinowski. I cannot speak for PCAST, just as Mr. Allen 
can't, but for my own perspective, and that from NORD, is our 
perspective is that it was premature. It merits exploration, 
but at this time, you know, trying to integrate that and come 
up with a system, we didn't have a program in front of us that 
had enough granularity for us to speak to it with any 
confidence. So I think that this is in the exploratory world.
    Mr. Waxman. And I appreciate that.
    Let me, Mr. Chairman, just briefly mention one other 
critical issue that deserves a hearing in and of itself. We 
need new therapies to be marketed but we have got to address 
high prices for these therapies. They are no good for anyone if 
we can't afford them. And I have a recent article from the New 
York Times that describes the hardships faced by patients with 
chronic diseases who can't afford the price of their 
treatments. It notes that the high prices of treatments for 
diabetes and other chronic diseases are a major contributor to 
the U.S.'s $2.7 trillion annual health bill. This is an issue 
we will have to address at some point. And I would ask 
unanimous consent this article be made part of the record.
    Mr. Pitts. Without objection, so ordered.
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    Mr. Waxman. Thank you.
    Mr. Pitts. The Chair thanks the gentleman.
    And now recognize the gentleman from New Jersey, Mr. Lance, 
5 minutes for questions.
    Mr. Lance. Thank you, Mr. Chairman. And good morning to you 
all.
    The State I represent, New Jersey, represented as well by 
Ranking Member Pallone, is certainly among the medicine chests 
of the world, and a center of significant biomedical 
innovation. We are the proud home to tens of thousands of jobs 
in these life-saving industries. These companies reinvest 
hundreds of millions of dollars each year back into R&D in 
order to bring much-needed therapies to patients, to market.
    I am deeply concerned about the slashing of R&D budgets 
that may look good on a financial spreadsheet, but I think 
would be tragic for patients moving forward. I ask this out of 
a concern regarding recent news on certain potential acquiring 
companies' intentions to slash R&D spending, for example, in 
the case of Allergan, a company that provides hundreds of jobs 
in the congressional district I serve. A potential buyer of 
Allergan has stated that it can achieve cost synergies by 
cutting approximately $1 billion in investment in R&D, and 
eliminate 5,000 high-quality U.S. jobs, as well as lower its 
tax rate from 26 percent to low single digits. Companies like 
Allergan invest significant capital in R&D in order to continue 
to development treatments for unmet medical needs. These 
investments not only support high-skilled, well-paying jobs, 
but also continue to deliver new, potentially life-saving 
products in the development pipeline. I am concerned that this 
could become the model for other such mergers, and we would 
lose the engine for innovation and growth here in the United 
States.
    To you, Ms. Radcliffe, how dependent are future cures on 
robust commitments in the private sector to research and 
development?
    Ms. Radcliffe. Thank you. So BIO is unable to comment on 
any particular companies----
    Mr. Lance. Yes, I realize that but----
    Ms. Radcliffe [continuing]. Businesses and things----
    Mr. Lance [continuing]. In general, please.
    Ms. Radcliffe. We are not familiar with that. I personally 
am not familiar with the situation, specifically in the case 
that you mentioned, to make any comment whatsoever. Obviously, 
the mission of BIO is to ensure that there is a research--a 
robust research and development pipeline in the United States 
for the development of new cures that will help patients and 
meet unmet medical needs.
    Mr. Lance. And do you believe that the level of research 
and development now in this country, in private companies, 
that, in general, that is the level that should continue and 
perhaps even increase?
    Ms. Radcliffe. Again, not commenting on any specific 
company, because there--every individual company may have its 
own situation with respect to exactly the level of research and 
development that it is conducting, as opposed to research and 
development that it licenses in or that are conducted in 
partnerships and so forth, however, I think that it--for BIO, 
again, the level of research and development in the United 
States is extremely important, as I said in my testimony, it is 
very important that we as a Nation continue to elevate our 
research and development for the purposes of meeting unmet 
medical needs for patients, and also in terms of global 
competitiveness.
    Mr. Lance. So in general, you favor more research 
development funding as opposed to fewer funds in that portion 
of the larger whole?
    Ms. Radcliffe. As a general principle, yes.
    Mr. Lance. Yes.
    Ms. Radcliffe. And, of course, it would matter as to how 
that research and development funding were specifically spent.
    Mr. Lance. Thank you.
    To the panel in general, the President's Council of 
Advisors on Science and Technology states that one of the most 
powerful incentives for drug development is granting periods of 
exclusivity to new drugs. It also mentions the economic 
disincentives created by long clinical trials required for 
conditions such as Alzheimer's Disease. The President's council 
acknowledges that engaging in the economic analyses required to 
provide potential policy changes is beyond the scope of the 
report and outside core experience. That being said, Hatch-
Waxman was enacted in 1984, and it is indisputable that the 
time and cost it takes to develop a drug has significantly 
increased over the course of the last 3 decades. There are many 
potential therapies that would address other unmet medical 
needs, such as rare diseases and mental health, areas in which 
I am involved; I am the Republican chair of the Rare Disease 
Caucus, that lack sufficient patent protection.
    To the panel in general, what are your thoughts on using 
data exclusivity to address these issues?
    Mr. Sasinowski. You know, first, on behalf of NORD, I want 
to acknowledge Congressman Lance's leadership in the 
congressional caucus on rare diseases.
    Mr. Lance. Thank you very much.
    Mr. Sasinowski. We have so awarded you, you know, on behalf 
of your leadership in that area, and we believe that the 
ability of all--let us say the Orphan Drug Exclusivity Act had 
a tremendous incentive that has sparked a great deal of 
research and development for rare diseases. You heard even Dr. 
Neil mention that his company is moving in the area of rare 
diseases, maybe in part because of the economic incentive that 
is provided by the Orphan Drug Act. So these kind of incentives 
have been powerful. Every person or every organization that has 
examined it has found their utility. The question though that 
is sometimes raised, Congressman Lance, is should we, for 
instance, expand the exclusivity, should we enter into the 
orphan drug exclusivity now that we have other forms of 
protections that exceed 7 years, perhaps in order to re-
establish the primacy of orphan drug exclusivity that should be 
extended beyond 7 years. So these questions have been raised, 
and they are serious questions that I think that merit further 
discussion.
    Mr. Lance. Thank you.
    I yield back the balance of my time.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the gentleman from Virginia, Mr. Griffith, 5 
minutes for questions.
    Mr. Griffith. Mr. Allen, you indicated it is hard to 
legislate or to come up with a good legislative model when you 
have all these different diseases, and you have some which are 
fatal and quickly fatal, others which are chronic. Don't you 
think simpler might be better, and that maybe Mr. Sasinowski's 
chart might be of some help in that regard?
    Mr. Allen. Absolutely, and I think that was what was 
intended and what the committee enacted through the 
breakthrough therapies designation; a very simple requirement 
of early clinical activities showing a substantial improvement 
that results in a very flexible, intensive collaboration to get 
that drug through the process.
    Mr. Griffith. And sometimes we get fancy. We like to do 
things that are more complicated.
    Mr. Sasinowski, you want to talk about your chart again for 
a minute? Somebody might not have been watching earlier.
    Mr. Sasinowski. Well, thank you, Congressman Griffith. As a 
fellow Virginian, I appreciate that.
    I am holding up a paperclip. Sometimes a paperclip can do 
an awful lot of good. And so I have been involved in this area 
of drug innovation, like I said, for more than 3 decades, and I 
have wrestled with this question of what can we do as--to 
achieve what we all want to achieve, like to accelerate 
approvals. And when I have been involved in this process, I see 
how often, shockingly, these very simple concepts that the 
Congress has created, such as fast track, you know, are not 
considered, and if we just give them more visibility, it sounds 
so simple, but if we required that at every new therapy that 
were to come before the FDA, there would be a simple question 
put, is this therapy one that would be a candidate for 
accelerated approval, it wouldn't take hardly any resources to 
consider that, it wouldn't delay at all the review of it, but 
it might spark the very kind of thing that others around the 
table here have talked to, that if we are going to engage in 
accelerated approval, we have to start that engagement early in 
order to identify intermediate clinical endpoints, and identify 
surrogates that can be used. And so since we are not 
recognizing the utility of it until, at all, very late in the 
process, we lose that--we forfeit that opportunity.
    So thank you, Congressman, for recognizing that.
    Mr. Griffith. All right, I appreciate that. I would ask you 
to put on your thinking caps. I don't necessarily expect an 
answer today, but if you can think of what other legal barriers 
are out there that are currently limiting the potential for 
doctors, researchers, drug companies, to communicate on how 
therapies are working for patients in the real world, and what 
can we do to break down some of those legal barriers that are 
preventing reasonable and valuable treatments from getting to 
the patients. And if you have an answer today, I would be glad 
to hear it. Got about 2 minutes of my time left, if you want to 
use it. If not, if you could submit ideas for the record, I 
would greatly appreciate that.
    Mr. Sasinowski. Well, Congressman----
    Mr. Griffith. Yes, sir?
    Mr. Sasinowski [continuing]. One thing I am not sure about 
the legal--even though I am a lawyer, I am not sure about the 
legal impediment. I will have to think about this further, but 
many of the members of this committee have suggested issues 
that where natural histories or registries could be a very 
valuable tool. If we understood more about the natural history, 
progression of a disease, we could better understand how it 
might work in a small population. We could be able to discern 
what is the treatment benefit, versus what is the natural 
course of disease, and in the same way, we can tell, separate 
what is a safety signal that is a true safety signal that might 
be due to the therapy, from just a signal that is part of the 
natural course of the progression of the disease.
    So these natural histories and registries are very 
important. We, on behalf of NORD, have been encouraging the 
development of them in every area, and there are difficulties 
in trying to get physicians and trying to get medical 
institutions to be able to share information, and to be able to 
have uniform information so that we are not talking about 
apples and oranges. We need some sort of common lexicon in 
these areas.
    So I don't have the specific answer of what are the legal 
aspects of that----
    Mr. Griffith. Right.
    Mr. Sasinowski [continuing]. But I know what the target 
should be.
    Mr. Griffith. I appreciate that.
    Mr. Chairman, if anyone would like my time. If not, I yield 
back.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the gentlelady from North Carolina, Mrs. 
Ellmers, 5 minutes for questions.
    Mrs. Ellmers. Thank you, Mr. Chairman, and thank you to our 
panel for being here today on this very important issue.
    I represent the Second District of North Carolina, and in 
our district we have 70,000 veterans, and I am very proud to 
represent them. Many of them are returning home from 
Afghanistan, and certainly have come home from Iraq, and are 
living in our communities with PTSD, and I know that is 
something that you are all aware of. I understand that new 
path-breaking technologies are emerging in treating veterans 
with PTSD, specifically, the use of magnetic resonance therapy.
    Dr. Neil, this is a question for you: Do you know if the 
Department of Veterans Affairs has looked into any of these new 
technologies, in particular, into the magnetic resonance 
therapy treatment?
    Mr. Neil. Thanks, Mrs. Ellmers. No, I do not know that.
    Mrs. Ellmers. OK. Getting into the issue of how we need to 
move forward on many of these treatments, such as PTSD. You 
know, there is broad agreement that the present system that we 
have with clinical trials is ineffective and costly. There was 
an expert that participated in the PCAST report that estimated 
a more efficient clinical trial system could cut the cost in 
half across the industry.
    Dr. Neil, do you have any thoughts on what we can do to 
make trials more efficient and less expensive, and what would 
this mean to the R&D budgets across the industry?
    Mr. Neil. Well, thank you again. First of all, I would just 
say that it would have a huge impact because more than 40 
percent of industrial R&D expenditure is in the area of 
clinical trials.
    Mrs. Ellmers. Um-hum.
    Mr. Neil. And one of the reasons that we formed 
TranCelerate Biomedical as an industry collaboration was to 
address clinical trials' inefficiency, and there, we looked at 
this and said these are areas where we do not have, cannot 
really realize any competitive advantage, and we are all 
spending the same money over and over again to basically 
reconstruct a clinical trial's----
    Mrs. Ellmers. Um-hum.
    Mr. Neil [continuing]. Infrastructure every time. We are 
all using the same investigators, we are all training the 
investigators, and then we are not recognizing each other's 
training. We all have our own Web site to communicate with--so 
on and so forth. And so we took that on, and the early results 
are very promising as a way to be able to increase a lot of 
efficiency, reduce the burden on clinical investigators----
    Mrs. Ellmers. Um-hum.
    Mr. Neil [continuing]. And reduce the cost. I think there 
are a lot of other great examples, the cystic fibrosis example 
being one of them, with their clinical trials network where 
specific--or disease-specific networks could be created, so you 
become plug-and-play by being able to start these trials very 
quickly, and this new lung cancer master protocol, I think, is 
a great innovation in that direction.
    So taken all together, I believe there is an enormous 
amount of efficiency on the table. There are a lot of things in 
my testimony that I specifically recommended around IRB's, 
safety monitoring boards, clinical trial networks, and new 
innovative approaches to this like, again, in your State, the 
Duke Clinical Research Institute, their collaboration with the 
NIH----
    Mrs. Ellmers. Um-hum.
    Mr. Neil [continuing]. With the collaboratory. So they are 
exploring ways to be able to randomize using electronic health 
records and test different therapies. I think we need to 
explore all of that, and there is no doubt that we will have 
the greatest impact on accelerating these cures to patients, 
reducing costs, and making the whole system work better if we 
could take that on. And I think Congress could do a lot here.
    Mrs. Ellmers. Thank you, Dr. Neil.
    Let me see, time. About a minute left.
    Dr. Tunis, I have a question, and it gets back to the issue 
that has been asked a number of times on how much of the 
patient involvement is taken into account, especially in the 
FDA, when it comes to moving forward in an accelerated fashion. 
How does the FDA view the patient input on some of these 
issues?
    Mr. Tunis. Certainly aware that there is a, you know, a 
couple of focused initiatives going on at the FDA that are 
really trying to enhance the degree to which patient 
perspectives are taken into account. There is the patient focus 
drug development that I believe came out of the FDAMA was--and 
FDASIA was--OK. And then on--in the--actually, in the Center 
for Devices, there is a medical device innovation collaborative 
that is very much focusing on patient perspectives on benefit 
risk, very much with the notion that, you know, one of the 
potential delays in product development is what level of 
concern, or what willingness patients have to tolerate risk, 
and whether the regulatories and the regulator's perspective on 
that is different from the patient's. And I think there is a 
view that the patients are probably--are--maybe, in many cases, 
willing to tolerate more risk, particularly in serious and 
life-threatening illnesses.
    So it seems to me, you know, from my observations, that 
there is a lot of recognition that the patient perspective is 
important, and the difficulty is, you know, capturing it both, 
you know, individually and aggregately, and how do you make a 
regulatory process that might even have to be adjustable based 
on individual patient preferences for balancing benefits and 
risks. So their interest is there, but I think it is 
complicated.
    Mrs. Ellmers. It is complicated, and certainly liability 
plays into all of this as well.
    It looks to me, you really want to comment on this.
    Mr. Sasinowski. I do. I do, because----
    Mrs. Ellmers. I would like----
    Mr. Sasinowski. Because Congress deserves a great deal of 
credit, and as the lawyer understands the drug law, a 1906 drug 
law was created, it never mentioned--no law until FDASIA ever 
mentioned patient. It was assumed that laws could be created in 
order to enable a regulator to look at what the medical 
industry and the drug industry produced in some sort of 
paternalistic way for patients.
    Mrs. Ellmers. Um-hum.
    Mr. Sasinowski. Now I am speaking on behalf of NORD, who 
represents 30 million Americans with rare diseases. And so we 
are so pleased that this Congress in FDASIA introduced the 
concept for the first time that the patient voice is 
meaningful, has a role in drug development, and that is why you 
had the patient focus drug development, the structured benefit 
risk ratio. The FDA said we can now empanel--the FDASIA law 
said empanel patients in part of the FDA internal review team 
as special Government employees. Tiffany House with Pompe 
Disease did that for a drug for Pompe, and the FDA reviewers, 
later when I talked to them, I said what did you learn from 
having a patient for the first time as part of your internal 
review team? They said we learned that for a patient with a 
relentlessly progressive deteriorating disease, that for that 
patient to be stable was a huge win.
    So the role of the patient is now emergent, and it is due 
to this Congress. So I just couldn't avoid taking the time to 
say thank you.
    Mrs. Ellmers. Thank you to the panel. And thank you, Mr. 
Chairman, I know we went over our time, but I really could not 
avoid hearing those thanks and appreciative words. So much of 
what we typically do not hear. So thank you.
    Mr. Pitts. The Chair thanks the gentlelady. And thank you 
for your remarks.
    The Chair recognizes Mrs. McMorris Rodgers 5 minutes for 
questions.
    Mrs. McMorris Rodgers. Thank you, Mr. Chairman.
    Would any of you, and maybe specifically Ms. Radcliffe or 
Dr. Neil, speak to the bureaucratic or regulatory burdens faced 
in starting or conducting clinical trials? And when was the 
last time that we, as a Nation, or Congress addressed the 
regulatory framework which governs how clinical trials are 
conducted, and do you think it is time for an update, given new 
technologies we can now bring to bear?
    Mr. Neil. Yes, I do think that this is an important issue, 
as I said previously, which is impacting the speed of 
development and its cost, especially, and also its 
effectiveness. So I do think this is worth a re-examination. I 
think there are a lot of things that we could potentially do at 
the statutory level. And here, I am thinking about standardized 
contracts for investigators, institutional review boards, 
safety monitoring boards which could be set up at the national 
or regional level, rather than the inefficiencies of having to 
establish these at every institution, and not having people who 
are necessarily as professionally qualified and experienced in 
monitoring these types of studies as they could be, as 
examples. And I think that working through public-private 
partnerships, or possibly authorizing additional money through 
the NIH to allow these trial networks to be established would 
also be a great help.
    Ms. Radcliffe. Yes, I recommend Dr. Neil's testimony as a 
fairly comprehensive list of some of the things that could be 
done to expedite clinical trials. For BIO specifically, we have 
launched an initiative to look at 4 things. One is central 
IRB's, that is to streamline the review of protocols when they 
extend over multiple academic centers. The qualification 
process for drug development tools, such as biomarkers, and we 
have talked a little bit about that earlier in this hearing. 
Clinical trial networks. One of the great advantages of 
establishing clinical trial networks is to speed up the patient 
recruitment process which, today, is very much longer than it 
has been in the past. And so we could really make great inroads 
to addressing that issue. And finally, adopting a risk-based 
approach to clinical trial monitoring using centralized 
monitoring mechanisms. So those are 4 areas where we really 
want to make some progress at BIO over the coming years.
    Mrs. McMorris Rodgers. Thank you. Thank you.
    Like many, I have been following the story of an innovative 
company, 23andMe, which developed a DNA testing kit that allows 
individuals to see which diseases or conditions they may have a 
predisposition to. And it seems to me that alerting individuals 
that they are more likely to have a certain disease or 
condition is a good thing, and it could be something that aids 
the development of new and innovative cures. For example, the 
genetic make-up of an individual who carries the gene for 
Huntington's Disease but does not suffer from the symptoms 
could be analyzed to determine what is his specific biology 
that stunts the development of that awful disease.
    So the question, are products like this making a major step 
towards personalized medicine and tailor-made cures, and what 
does it mean for millions of people to be able to have crowd 
source--to be able to crowd source their genetic information? 
Anyone that may want to answer.
    Ms. Radcliffe. All right, I will answer. We are--in the 
biotechnology industry, we are extremely excited about the 
potential for the use of genetic information in the design of 
clinical trials, and the expediting of those clinical trials, 
and also in healthcare delivery to help physicians and patients 
understand the best course of action. I think it is also 
important to understand though that information needs to be 
delivered in a way that enables the best decision-making by 
patients. A very specific example is that a patient might 
receive information about a risk of a certain type of cancer, 
and take action on that in a way that really would be 
detrimental to that person's health. And so as all of this 
wonderful information comes out, and as it is made available 
more broadly, we also have to put a great deal of thought 
toward the context for delivering that health information in a 
way that is helpful and not harmful.
    Mrs. McMorris Rodgers. Then would you speak to the role 
that FDA is playing in the process, and has FDA promoted the 
development of these kinds of diagnostic test? Is the FDA 
approval process adequately equipped to consider these types of 
products?
    Ms. Radcliffe. This is an area where BIO has worked for a 
long time with FDA. The products that are coming out are so 
novel and so different from those that have been reviewed by 
FDA in the past, that they really require a different kind of 
scrutiny and different expertise. FDA has done a lot to improve 
that regulatory process, and to ensure that it has the 
expertise internally to manage these new technologies. I think 
that in the future, there will be a need for FDA to continue 
evolving to make sure that it is keeping up with the pace of 
scientific advances.
    Mrs. McMorris Rodgers. Thank you. And I too want to thank 
the panel and for everyone for participating. I am very excited 
about this 21st Century Cures Initiative, like everyone.
    Thank you, Mr. Chairman.
    Mr. Pitts. The Chair thanks the gentlelady.
    Now recognize the gentlelady from Tennessee, Mrs. 
Blackburn, 5 minutes for questions.
    Mrs. Blackburn. Thank you, Mr. Chairman. And I want to 
thank each of you for taking the time to be here, and I 
apologize that we have been jumping up and down from the first 
floor where we have Chairman Wheeler with the FCC with a 
hearing going on, and I know for some of your groups, having 
access to broadband for some of the new medical apps, for 
telemedicine concepts, things of that nature, is very 
important. It is important to us also. So we have been in and 
out of that hearing.
    I have been pleased to catch some of the comments about 
clinical trials and looking at those meaningful outcomes of 
bringing patients into that process, and we were discussing 
this in our office this morning. Dr. Summer, who is--does our 
health policy in the office, and I were talking about how 
important that is to have that impact. And my experience, you 
know, you have health professionals like Mrs. Ellmers and Dr. 
Cassidy and Dr. Burgess that are on this panel, but I come from 
the other side as a community volunteer who was chairman of the 
board for the Lung Association, on the Heart Board, the 
Arthritis Board, Children's Hospital, those components there in 
Nashville. And realizing as we put the emphasis on different 
participation for managing disease like asthma and the outreach 
we did with the Lung Association, how important it was to hear 
from those patents and those patients of how different 
protocols and therapies affected them, and what the outcome 
was, and the importance of finding something that worked.
    And, Dr. Radcliffe, I think it is the reason it was so--
when I went to the State Senate in Tennessee, I took the 
initiative of working with a colleague, and we pulled together 
a biotechnology task force to begin to look for some of those 
personalizations that can come about in the medical field for 
treating these--the diseases that impact us. So I have enjoyed 
hearing your comments today, and appreciate that you all would 
take your time.
    Just more one question I want to add to the mix here. And, 
Dr. Allen, I am going to come to you on this. We have had a 
little bit of discussion this morning as we have looked at 
Section 903 in FDASIA, and being able to pull those external 
experts into the process, and, of course, the conflict of 
interest, things of that nature, always has been such a 
problem, but I think that for those of you who are medical 
professionals, and for those like me who want to find answers 
and find a way to cure some of these diseases, having that 
participation is vitally important. And so I would just ask 
you, how is the FDA doing as it comes to the involvement and 
making it possible for some of these experts to openly 
participate, be full participants, in this process, which is 
what we are going to have to have if we get to some of these 
answers?
    Mr. Allen. Right, so I think some of the panelists have 
already commented on bringing the FDA's efforts, and bringing 
patient expertise to the process and how important that is, in 
addition to Section 903 that you mentioned, bringing subject 
matter experts into the review process. And I think that was a 
very important component of FDASIA to expand on activities that 
the FDA was already doing, and might be able to even enhance 
through 903, and making sure that there were diverse experts in 
really subsets of specialties like rare diseases, or in 
different genetic diseases, to make sure that they had access 
to them.
    You know, again, this goes back to resource-constrained 
agency. They simply will never have all of these experts, and 
particularly, as medical therapy becomes more and more diverse 
and specialized. So I think the--Section 903 provides one way 
to allow experts to be more involved in review, and I think we 
all can agree that we would like to see the FDA continue to 
implement that as rapidly as possible. I think even there is 
opportunity beyond just Section 903, which is really focused on 
involving expertise in the review process, but even things with 
not just the specific review, for things like developing best 
practices and guidance documents, there is a real opportunity 
to also call on those experts and those patients to make sure 
that they are able to contribute to the many diverse and 
important things that the FDA is charged with carrying out. And 
they continue to have more and more responsibility, and, 
unfortunately, not the resources to go along with that, so this 
is one way to help open those doors.
    Mrs. Blackburn. We will continue to hold them accountable. 
Thank you, sir.
    Mr. Pitts. The Chair thanks the gentlelady.
    Now recognize the gentleman from New York, Mr. Engel, 5 
minutes for questions.
    Mr. Engel. Thank you, Chairman Pitts, and thank you, 
Ranking Member Pallone, for holding today's hearing. I am 
pleased that this committee is focusing its efforts on the 21st 
Century Cures Initiative, and the President's Council of 
Advisors on Science and Technology, PCAST, Report, on Drug 
Innovation.
    I believe that some of the best work that this Congress did 
during the 112th Congress was in working together to pass 
FDASIA. I have always been proud to serve on this committee 
because of the tremendous impact laws that originate within 
this committee can have on medical research and disease 
treatments.
    The 21st Century Cures Initiative proves that this 
committee's commitment to getting new treatments into the hands 
of patients as quickly and safely as possible remains strong.
    So let me ask you, Dr. Neil, in your written testimony, you 
suggested that Congress target its efforts in several different 
ways; one of which, and I quote you, was ``to ensure that the 
FDA has adequate resources to do their job.'' I think it is 
critical the FDA--that the FDA does have adequate funding and 
staff resources in place in order to meet the demands of 
increasingly complicated and advanced medical therapies. I know 
there was significant frustration last year when sequestration 
caused $85 million in pharmaceutical and medical device company 
paid user fees to be unavailable to the FDA. Fortunately, the 
fiscal year 2014 Omnibus Appropriations Act restored the 
ability and the availability of these funds to the FDA. 
However, beyond funding, Dr. Neil, you mentioned that, and 
again, I am quoting you, ``new trial designs and clinical 
endpoints will require collaborative efforts with academics and 
patient advocacy groups.''
    So could you elaborate on how academics and patient 
advocacy groups can better assist the FDA with the resources 
they need to meet the demands of 21st century medical 
treatments?
    Mr. Neil. Yes, thank you very much, Mr. Engel. I believe 
that FDA should be given more resources so that they can engage 
consultants, convene meetings with outside experts and also 
with patient advocacy groups to a greater extent. And I also 
think part of their--this new resources allocation that they 
might get beyond their base budget funding could allow them to 
hire more staff that could engage with small companies along 
the way to be able to guide them through the process more 
efficiently. I think they don't have enough money right now to 
be able to support the sort of scientific work that they need 
to do, in other words, there could be a lot more scholarship 
and original research in the areas of regulatory science that 
impinges on all of this inside the FDA, both an intramural and 
extramural program, and also the ability, just simple things 
like being able to travel to scientific meetings, I know that 
that is constrained right now too. And all of these things 
would help them to be able to create a more scientific culture 
internally, to be apprised of the latest advances in science, 
and to be able to incorporate that as they need to in their 
review process.
    Mr. Engel. Well, thank you.
    I mentioned to Dr. Woodcock during our last FDASIA hearing 
in November 2013, but I am particularly interested in the 
development and approval of drugs for rare diseases. I am a co-
author of the Paul D. Wellstone muscular dystrophy community 
assistance, research and education amendments of 2008 and 2013. 
I did it in conjunction with our colleague, Representative 
Burgess, and one of the aspects of FDASIA I am most interested 
in is the improvements made to the various expedited approval 
pathways, and the establishment of the breakthrough therapy 
pathway. To me, diseases like muscular dystrophy are why the 
expedited approval pathways are so important. One type of 
muscular dystrophy, Duchenne Muscular Dystrophy, is the most 
commonly lethal genetic disorder of children worldwide, 
affecting 1 in every 3,500 live male births. There is no cure, 
it is always fatal, and often at a young age, so the best hope 
for those with Duchenne is to treat the symptoms and delay its 
progression. However, in recent years, the muscular dystrophy 
research pipeline has held much promises, potentially life-
saving therapies appear on the horizon, some of which are a 
result of Congress' efforts to improve research into this 
spectrum of muscle-weakening diseases through the MD Care Act, 
which was first passed and signed into law in 2001.
    So it would appear to me that establishing quality 
intermediate endpoints that can add value to future trials is 
vital for experimental medications to be considered under the 
various expedited approval pathways.
    So my question is recognizing the significant challenges 
that exist in developing therapies within the rare disease 
space, how can the FDA, NIH, drug companies and patient 
advocacy organizations better work together to ensure proper 
parameters for success and failure, being established through 
the critical trial process? Anybody want to comment on that?
    Mr. Sasinowski. Well, Congressman Engel, I couldn't applaud 
you more for your work in the area, and with the MD Care Act 
and others, for reaching out to these communities of patients 
with rare diseases. So thank you for your work in that area.
    I think that my testimony--my written testimony, I tried to 
describe what I thought would be four proposals that would 
advance the interests of those with rare diseases. I think 
number one is, you know, to again have FDA use accelerated 
approval more often. As I noted in my written testimony and my 
oral statement earlier, that when we looked at all of the use 
of accelerated approvals since FDA started it for the AIDS 
crisis in the mid-'80s through June 2013, there were only 19 
drug therapies that the FDA had approved with that pathway that 
were not for cancer and not for AIDS. So it has to be used for 
these rare diseases, because in these rare diseases, we are 
looking, just as you said, Congressman, we are looking for 
something--an endpoint in a trial design that is something 
short of the ultimate clinical benefit. We don't want to have a 
clinical trial that is going to follow DMD boys all the time 
until they lose ambulation. And that is the ultimate clinical 
benefit, and we don't have the luxury to design clinical trials 
because we don't have enough boys and we don't have enough 
time. So we need to establish these other endpoints, and I 
think accelerated approval would help us do it, and I think 
this committee has done a great deal in FDASIA, and I think 
that there is more though that can be done.
    Mr. Engel. Thank you.
    Thank you, Mr. Chairman.
    Mr. Pitts. The Chair thanks the gentleman.
    Now recognize the gentleman from Louisiana, Dr. Cassidy, 5 
minutes for questions.
    Mr. Cassidy. I am sorry, I came in late, so if someone has 
already answered this. Several of you, and I think the PCAST 
recommendations speak of increased NIH funding, and decry the 
fact that since '03, there has been some decline. And reality 
is we have constrained Federal resources.
    So with that context, there was an IOM report or GAO, I 
can't recall, from about 20 years ago suggesting that the NIH 
should reprioritize its funding priorities, and better reflect 
current needs. Frankly, I think when I looked at it a couple of 
years ago, they had not done so.
    Now, do you have any thoughts on whether or not the NIH is 
appropriately allocating its resources to our current funding 
needs? I look at Alzheimer's, I think it may be getting $600 
million, but the cost of future Alzheimer's is huge.
    Ms. Radcliffe, do you have any thoughts, just to call upon 
you?
    Ms. Radcliffe. First, thank you for highlighting the 
importance of continuing to fund the NIH. As you noted, the 
real----
    Mr. Cassidy. Yes, I got that, but----
    Ms. Radcliffe. Yes.
    Mr. Cassidy [continuing]. Frankly, we don't have enough 
money. So my real question is, my pointed question is, does the 
NIH need to reallocate some of its assets, because, again, the 
IOM suggested this 20 years ago, I am not sure it has been done 
since.
    Ms. Radcliffe. Yes, so we have been extremely supportive of 
a new center at NIH called the National Center for Advancing 
Translational Sciences, NCATS, and we are extremely interested 
in supporting the work of that center----
    Mr. Cassidy. I----
    Ms. Radcliffe [continuing]. Because it will more directly 
lead to----
    Mr. Cassidy. I hear what you are saying. I have limited 
time so that is not really what I am asking.
    Dr. Neil, any comments upon what I just suggested?
    Mr. Neil. I think they are doing a very good job, actually, 
in prioritizing at the moment. One wishes that one could 
predict where important discoveries were going to come from, 
but----
    Mr. Cassidy. Now, let me ask you, it isn't so much to 
predict important discoveries, it is the fact that we have this 
incredible challenge of neurodegenerative diseases. I mean that 
is just out there.
    Mr. Neil. Right.
    Mr. Cassidy. And if you look at what we are funding that 
with relative to other diseases and their future cost, which is 
easily predicted, it seems perhaps, again, a different priority 
than others would select if you could just start over. So any 
specific--again, people may be hesitant to criticize NIH, but 
if we are asking for more funding, we have to also know they 
are using their funding wisely.
    Mr. Neil. Yes. I just wish that one could, again, really 
think about how to prioritize and manage it, but we don't know 
where a discovery in a completely different area that affects 
mitochondria or who knows what may be the breakthrough that we 
need in neurodegenerative diseases.
    Mr. Cassidy. You are suggesting that we need to have no 
direction whatsoever, I think I am--I think is what I am 
hearing from you, but rather rely upon kind of basic research 
to produce.
    Mr. Neil. Well, I don't think it is just that, but I think 
that the most promising basic research needs to be funded if we 
are going to continue to advance.
    Mr. Cassidy. Mr. Sasinowski, any thoughts?
    Mr. Sasinowski. Yes, it--with your particular concern about 
neurological, neurodegenerative diseases, yes, a large swath of 
the rare diseases in this country fit into that category. And 
as, you know, Dr. Neil just mentioned, you know, the 
underpinnings, the pathophysiology of many of those go back to 
mitochondrial energy production. So if we could have 
reallocation of NIH funds that would redirect it to some of 
these areas that have the promise of being able to address a 
lot of diseases, that might be a worthwhile endeavor.
    Mr. Cassidy. It seems like we should have some metric; what 
is the future cost, what is the current morbidity, and have it 
reflect that.
    Dr. Tunis, you know, I used to do medical research. My 
nurse who I worked with, who basically told me what to do when 
I showed up, said, man, the paperwork has increased 
dramatically over the years. Now, one of the recommendations, I 
think number seven, suggests that maybe FDA could be more 
efficient in terms of how it does it process. I am asking you 
just to ask, it could be anyone, how would you grade what FDA 
has done in terms of, is the monitoring process thoroughly 
useful, or is some of it kind of, oh, my gosh, why in the heck 
are we doing this? It is just driving up cost. Any kind of a--
any kind of grade you would give the FDA for their current 
efforts?
    Mr. Tunis. Well, I think--I would hate to grade FDA, but I 
think FDA actually recognizes that there are a lot of this 
excessive activities and cost embedded in clinical trials, and 
one of the things, again, Garry and others know a lot about is 
they do have this partnership with Duke called the Clinical 
Trials Transformation Initiative which is systematically trying 
to identify where there are, you know, excessive regulatory 
burdens, things that contribute to the inefficiency of clinical 
research, and, you know, doing--you know, exploring how those 
things could be minimized. So I would give the FDA an A grade 
in terms of identifying that there are opportunities to 
improve, and having at least that forum to, you know, to look 
for solutions. And I don't know if, Garry, you wanted to add 
anything to that.
    Mr. Neil. Well, the--monitoring is a particular issue that 
we took on with TranCelerate, and FDA provided input into that, 
and we know that we are overdoing this in ways that are not 
really adding value, maybe subtracting value and driving cost, 
so moving to a more risk-based monitoring approach, again, with 
FDA----
    Mr. Cassidy. Any sense of how much cost that adds? Five 
percent, 10 percent, marginal cost of----
    Mr. Neil. It----
    Mr. Cassidy [continuing]. Monitoring which may be 
inefficient?
    Mr. Neil. It depends on the trial, obviously, but--and I 
can't give you a precise estimate, but it is very substantial.
    Mr. Cassidy. Very substantial.
    Mr. Neil. Very substantial.
    Mr. Cassidy. OK. That was kind of my impression from being 
frontline way back when.
    Thank you very much. I yield back.
    Mr. Pitts. The Chair thanks the gentleman.
    That concludes the first round of questioning. We are going 
to go to one follow-up per side now.
    I will recognize Dr. Burgess 5 minutes for his follow-up.
    Mr. Burgess. Thank you, Mr. Chairman, and again, I want to 
thank the panel for being here. It has been a long morning but 
a very informative morning. I would be remiss if I did not 
acknowledge, I guess, my co-sponsor, Eliot Engel, has left, but 
the MD Care Act, Mr. Chairman, that is a good Bill and one that 
I hope we can have a legislative hearing and a markup on before 
we get too deep in the political season, because it is one that 
needs to occur, and, in fact, the last reauthorization--we 
haven't addressed the problem that occurs that we are doing 
such a good job, some of these patients are now living until 
early adulthood when they didn't before, and the current Act 
does not address young adults with the illness, and we need to 
do that. So I hope we can have that legislative hearing.
    I also, Mr. Sasinowski, I don't want to correct you, but it 
was actually the last Congress that passed FDASIA, but it was 
this committee that did the work, and I just wanted to 
acknowledge the work of Brian Bilbray, who is no longer with 
us, and really it was his--I mean he was a bulldog on the 
surrogate endpoints when FDA was in testifying before this 
committee. And without Brian Bilbray's contribution, I don't 
think FDASIA would have been as effective, and, of course, 
the--I certainly--I appreciate the hearing this morning about 
the conflicts, the trying to improve the status of the 
conflicts language so that we could improve the advisory panels 
that we empanel to advise the FDA on approvals.
    Look, one of the things that the President's council did 
come up with and talk about was the woeful state of the 
information technology at the Food and Drug Administration. You 
hear the urban legends about the warehouses of new drug 
applications that are in boxes on paper applications in the 
basement somewhere. I don't know whether it is true or not 
because I have never seen it, but can anyone speak to--I guess 
there has been the hiring of a new chief information officer. 
Does anybody see any daylight on the horizon there? Apparently 
not.
    Let me just tell you what is so frustrating. This 
committee, for the last--I have been on the committee for 10 
years, and we have had this discussion over and over and over 
again. As a practicing physician, I have received the slings 
and arrows because doctors' offices are not coming into the 
information age rapidly enough, and here we have the FDA which 
is just stumbling all over itself. I mean surely there is 
something we can do about that to digitize the data. I mean if 
this were a class action lawsuit, the large litigation firms 
around the country would get together, digitize the data and 
analyze it in a weekend, and we can't do it as a Federal 
agency. I don't know, surely somebody has some thoughts on how 
to improve this system. Again, let the--for the clerk's 
benefit, no one volunteered an answer. I just--I acknowledge 
this is something that needs to be fixed. I appreciate Dr. 
Cassidy's comments about the funding constraints, but if we 
don't fix this, we are not getting out of this problem.
    I do want to ask Mr. Sasinowski, probably the one thing I 
have heard this morning that I am going to take with me out of 
this hearing is that perhaps the default position that the FDA 
ought to be the accelerated pathway. And the FDA historically 
has been risk averse, but you are talking about a new world 
order where the FDA now defaults to the accelerated pathway. So 
can you speak to accelerated approval as the default in the 
future?
    Mr. Sasinowski. Yes, Dr. Burgess, that the--I don't see it 
as a default. I don't see most of the therapies coming through 
the FDA's gauntlet, being approved under accelerated approval 
because it only fits for those which are serious diseases where 
there is an unmet medical need, but what I am saying is that 
those twin criteria could apply to many diseases, especially 
the rare diseases, the 7,000 rare diseases that affect 
Americans, and so for those, you know, that should be part of 
the discussion at the beginning, at the pre-IND meeting, when 
we are first coming into the FDA, that should be part of that 
engagement, because you have heard several other witnesses, and 
it was also in FDASIA and PCAST, that said if you are going to 
go forward with accelerated approval, you have to start that 
discussion early because you have to be able to identify the 
surrogate endpoints, and the intermediary clinical endpoints so 
that you can run the studies in the proper way. And so that 
discussion is not going on. So what I was suggesting, Dr. 
Burgess, is that every time that a new therapy is proposed to 
the Agency, one of the first questions always be, as part of 
their checkbox, is this a candidate for accelerated--would this 
fit, is this a serious disease for which there is an unmet 
medical need, and then the system can integrate that. And it is 
currently just not being considered.
    Mr. Burgess. Not only is it not being considered, but I 
will just tell you, not a month goes by that someone is not in 
my office with a tale of woe----
    Voice. Yes.
    Mr. Burgess [continuing]. About getting their drug or 
device approved, and I for one, in this committee, I am just 
tired of hitting my head against that wall, and it is time for 
us to break through or break out of that modality and move into 
the 21st century.
    Thank you, Mr. Chairman, for holding the hearing. I will 
yield back.
    Mr. Pitts. The Chair thanks the gentleman.
    That concludes the questions at this point.
    The Members will have follow-up questions. We ask that you 
please respond promptly.
    This has been a very informative hearing. We appreciate you 
sharing your expertise with us and the practical 
recommendations.
    I remind Members that they will have 10 business days to 
submit questions for the record. Members should submit their 
questions by the close of business on Tuesday, June 3.
    Without objection, the subcommittee is adjourned.
    [Whereupon, at 12:12 p.m., the subcommittee was adjourned.]
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