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





       21ST CENTURY CURES: INCORPORATING THE PATIENT PERSPECTIVE

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON HEALTH

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                    ONE HUNDRED THIRTEENTH CONGRESS

                             SECOND SESSION

                               __________

                             JULY 11, 2014

                               __________

                           Serial No. 113-158


      Printed for the use of the Committee on Energy and Commerce

                        energycommerce.house.gov
                        
                               ________
 
                     U.S. GOVERNMENT PUBLISHING OFFICE 

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

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

                         Subcommittee on Health

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

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

                               Witnesses

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

                           Submitted Material

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

 
       21ST CENTURY CURES: INCORPORATING THE PATIENT PERSPECTIVE

                              ----------                              


                         FRIDAY, JULY 11, 2014

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

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

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

               Prepared statement of Hon. Joseph R. Pitts

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

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

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

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

    [The prepared statement of Mr. Upton follows:]

                 Prepared statement of Hon. Fred Upton

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

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

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

    Dr. Woodcock. Thank you. We are here to discuss how drug 
development better meets the needs of patients. Decades ago, 
healthcare was very physician-centric and actually very 
paternalistic. We all recognize that today. It was kind of 
``The doctor knows best; don't ask any questions.''
    Today, the model is collaboration between the patient and 
the healthcare team. These changes, though, have evolved slowly 
in our society, and the thinking and drug development has 
slowly changed in parallel.
    The FDA Safety and Innovation Act of 2 years ago took 
significant steps in this direction of patient-centric 
development. It contained agreements under PDUFA that FDA would 
sponsor at least 20 patient-focused disease-focused meetings 
over 5 years. Eight of these meetings have been held to date, 
and they have been very impactful. The first one we held on 
chronic fatigue syndrome, we have issued a draft guidance on 
drug development in this area of very serious unmet medical 
need. Also, under PDUFA, were agreements to advance the 
development and use of patient-reported outcome measures. These 
are measures that the patient can fill out to say from their 
point of view how well they are feeling, how well the treatment 
is working, what adverse events they are experiencing.
    We are having an expert meeting next week and will continue 
to work in collaboration consortiums to try and advance the 
science of patient reported outcomes. This is very important to 
really scientifically incorporate the patient's perspective 
into clinical trials.
    Additionally, under FDASIA, FDA was to advance the 
development and use of a structured benefit risk framework in 
drug approval decision, and this work is under way, and it 
really explicitly provides for considering the burden of 
disease, the impact of current therapies, both for good and for 
ill, and the tolerance of risk from the patient's point of 
view, and this is an extremely important set of factors that 
need to go into the benefit-risk decision, but we need to do 
this in a scientific manner and a structured manner and we are 
rolling out the structured benefit risk framework.
    Now, we know that for people with very serious diseases who 
may lack good therapy or actually lack any therapy, access to 
new treatments is their number one priority, and that is why 
expediting drug development programs in these areas is so 
important. If you look at the diagram that we have here that 
was provided, these data and the diagram were actually 
developed by the Pharma organization, talks about, shows the 
drug development process, and it is starting on the left, it 
shows you start with many thousands of compounds, up to 10,000 
compounds at one end, the beginning, and after 9 to 13 years, 
you may end up with one safe and effective drug on the market.
    The clinical development phase, which is the gray phase, 
the middle phase on this diagram, is the longest and by far the 
most expensive phase.
    In contrast, the FDA review phase, of which much attention 
has been paid to, is actually the very small slice there, the 
white slice toward the end of the process, right before the 
drug gets on the market and is typically at this time less than 
a year in duration.
    So FDA has made strenuous efforts, really, to help reform 
and modernize the clinical development phase of drug 
development because that is the major bottleneck. Not only is 
it expensive and long, many products fail in this phase, and 
there is a tremendous opportunity cost there where other 
treatments could have been developed.
    Now, the FDASIA included several innovations to this 
process and the most striking being the breakthrough therapy 
designation program, so if we could have the next diagram. 
Thank you. This was mandated by Congress and was specifically 
directed at that clinical development phase, so that we could 
help when therapies were particularly promising and were 
designated, we could help move them through that phase more 
quickly. The BT designation has been enthusiastically 
subscribed. We have had over 160 requests in the 2 years since 
the legislation was passed. We have actually--and this is the 
really surprising part, we have granted 52 designations. So 
what Dr. Burgess said about we are on the verge of a new era in 
therapeutics, I think, is reflected by this. We would not have 
seen this a decade ago, and we have approved six products: four 
new products and two new indications.
    Now, it is too early to judge really the impact of the 
breakthrough designation program; is it really going to be able 
to speed up drug development? However, I will say the four 
products we approved, their clinical development time was 4.5 
years, so much shorter than what I showed in the earlier 
diagram.
    Also, in FDASIA were clarifications of the application 
accelerated approval, and we issued a final expedited draft 
guidance in May that includes, in response to stakeholders' 
requests, examples of rare diseases and includes more 
information on the use in rare disease. However, it is clear 
much more needs to be done to modernize the clinical trial 
process. That is the big bottleneck now in getting discoveries 
to patients. This can't be done, though, by FDA alone. We don't 
execute this process. All the stakeholders need to participate, 
and I think the series of hearings that have been held and the 
21st Century Initiative can help provide the framework for 
significant reform in this process.
    Mr. Pitts. The chair thanks the gentlelady.
    
    [The prepared statement of Dr. Woodcock follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
    
    Mr. Pitts. I will begin the questioning, recognize myself 5 
minutes for that purpose.
    Dr. Woodcock, what is FDA's plan to advance biomarkers and 
the use of patient reported outcomes data during the drug 
development process and post-market setting?
    Dr. Woodcock. Many years ago, a decade ago, we recognized 
that there was no structured scientific process to provide the 
evidentiary basis for use of a biomarker in decisionmaking, and 
so doctors and biomedical researchers would float new 
biomarkers, but there was no rigorous process by which they 
could be evaluated to see if they were really useful. So we 
actually established a process for this. It is not really in 
our mission, but we established it, and it is called the 
Biomarker Qualification Process. And we also work with the 
European medicine agencies and the Japanese regulators so that 
this would be a worldwide activity. And consortia can come into 
the FDA and propose a biomarker, a new biomarker, and we give 
them advice on what needs to be done, and then--and also for 
patient-reported outcomes. And if, in fact, that evidence is 
developed, then we will publish a letter that is public, and so 
will the EMA if they accept it and so forth, and then any 
developer can use that biomarker or measure in a development 
program and will rely on it for the context of use.
    We have 79 projects by different consortia in different 
phases of this process right now.
    Mr. Pitts. Good. Describe your plans for implementation of 
the structured benefit-risk framework you mentioned that--
transparent to the public and the sponsor so that the 
assessment of data from clinicals trials and other studies by 
FDA reviewers can be better understood and acted upon.
    Dr. Woodcock. Yes. Well, this is an iterative process. We 
have had public meetings. Then we went back, and we are 
piloting this in the different drug review divisions and having 
the medical officers work through this framework that we have 
developed and see what the results are. Then when we have those 
results, we will go back through a public discussion and get 
input on how this can be improved, so this is not something 
that can happen overnight.
    It is a scientific process, and actually, we feel that we 
don't have the tools right now. They exist out in society in 
science, but we haven't applied them, these rigorous analytical 
tools to the benefit-risk decision, and so we have had 
workshops on this, various scientists come in and advise us, so 
we will have a public process once we have gathered more 
experience.
    Mr. Pitts. I have been hearing a lot about FDA's efforts to 
improve the quality of pharmaceutical manufacturing. Where do 
U.S. drug manufacturers currently stand when it comes to 
producing quality medicines? Can you tell me a little bit about 
your plans in this area?
    Dr. Woodcock. Well, I think the major problem here is that 
many of our essential drugs are not made in the United States, 
and they are made all around the world, and sometimes they may 
only come from a single source, and this is, I think, a real 
vulnerability to medicine. And in addition, we used to be a 
manufacturing powerhouse in drug manufacturing, but those jobs 
have moved offshore. And I think now we have an opportunity, 
with new modern manufacturing methods, such as continuous 
manufacturing, to actually build a high-tech industry in the 
United States that actually will make the drugs we need here in 
this country. And FDA has been collaborating with this 
manufacturing community to help bring this about, and we are 
very interested in seeing this happen.
    Mr. Pitts. Now, we have recently heard a lot about Lung-
MAP, the Lung Cancer Master Protocol trial. There are other 
examples of similar innovative trial designs, like I-SPY for 
breast cancer. What else needs to happen before these types of 
trials are no longer front-page stories?
    Dr. Woodcock. That is a good question. We also have been 
advocating for this for many years, and it is wonderful to see 
it start to become a reality. The concept, I think, in drug 
development needs to be turned on its head in clinical drug 
development, and instead of, for each investigational drug, 
there is a whole clinical trial program developed with 
different clinical trials that take a very long time, as you 
heard on Wednesday, to get started and so forth, that there are 
networks that are available that investigational drugs can be 
plugged into. This will provide independence of an assessment 
but also really decrease the time and expense of assessing 
whether these drugs are safe and effective.
    But what needs to happen, I think, is we need to expand 
this to more diseases. The NIH is very interested in 
antimicrobials in setting up a network, and other groups are 
looking into this, and I think you may hear today from some 
patient groups say Cystic Fibrosis has really successfully set 
up the infrastructure to have cystic fibrosis drugs rapidly 
evaluated once they reach the clinic.
    Mr. Pitts. The chair thanks the gentlelady.
    Now recognizes the ranking member of the subcommittee, Mr. 
Pallone, 5 minutes for questions.
    Mr. Pallone. I am going to have to--since I just got here.
    Mr. Pitts. OK. You want to yield to Green?
    Mr. Pallone. Yes.
    Mr. Pitts. All right. Mr. Green.
    Mr. Green. Thank you, Mr. Chairman.
    Dr. Woodcock, welcome back. I want to thank our chairman, 
ranking member, and Dr. Woodcock for testifying. In a time 
where revolutionary science and technological development, we 
have an opportunity to target specific patient populations, 
advance personalized medicine, and transform how we approach 
the prevention and treatment of disease, one of the goals I 
think is particularly worthy of exploration is the idea of 
personalized medicine, in which a patient may be able to 
receive more tailored drugs and treatment suited to his or her 
specific condition.
    Our understanding of the human genome is the key to that 
goal. Academics and researchers tell me, another piece is the 
potential for researchers and developers to discuss these drug 
and device innovations with patients during the development 
phase.
    Dr. Woodcock, can you give us your views on the upsides and 
downsides of any increasing permissibility of communication 
between patients and developers during the clinical trial phase 
of development?
    Dr. Woodcock. It is a very interesting question. We have 
seen from the 1990s, where only 5 percent of drugs were 
targeted; in 2013, 45 percent of the drugs we approved were 
targeted in some way. There are barriers to locating patients 
and joining up patients who have specific conditions, subsets 
with appropriate investigational therapy, and these diseases 
are fragmented into smaller and smaller subsets. It is harder 
and harder to find these people who might be eligible for a 
given therapy.
    The Lung-MAP trial is one way of doing that where it has 
multiple investigational arms in one trial, so people can come 
in, and they can be spread out. But there is great interest, of 
course, with more patient activism in using social media and 
other ways to actually match up the right patients with the 
right investigational drugs, and I think this is one of the 
challenges right now of the clinical trial enterprise.
    Mr. Green. Well, increasing patient involvement in FDA's 
decisionmaking surrounding drugs, devices is a significant yet 
challenging endeavor. Can you provide your suggestions on how 
mechanisms need to be developed to accurately measure what 
meaningful outcomes for patients are, both in the clinical 
outcomes and the quality of life? Can we do that?
    Dr. Woodcock. Yes. That is what I was referring to with 
Chairman Pitts is that there is a science of measurement, and 
patient-reported outcomes is one science. How do you measure 
how a patient feels from their point of view? And there are 
ways to do this, but these measurements have to be developed. 
We approved many drugs based on their impact on quality of 
life, so that is completely possible, but what needs to be done 
is this science needs to be developed, and we are participating 
in that. As I said, we have an expert meeting next week on 
patient-reported outcomes.
    Mr. Green. Well, and the patient involvement process has to 
be data driven and improve the overall efficiency of drug 
development and maintain FDA standards of safety and 
effectiveness. How can Congress support the FDA in 
incorporating patient perspectives in regulatory decisionmaking 
in a way that helps deliver that innovative, safe, and 
effective medicines to the patients sooner?
    Dr. Woodcock. Well----
    Mr. Green. Do you need statutory authority, or do you think 
you already have it?
    Dr. Woodcock. To my knowledge, we have the authority to do 
this, and I think you will hear from the next panel, for 
example, how patient groups can develop draft guidance, submit 
it to the FDA. They can run processes that actually incorporate 
all their points of view and those of the expert scientists, so 
more of that needs to be done, but I don't know that it needs 
more statutory authority.
    Mr. Green. Can you do it within current resources, because 
again, you are specializing, instead of a broad brush--and I 
assume it costs more when you do an individual?
    Dr. Woodcock. Yes. Well, when you have 7,000 diseases that 
need good treatments and most of them don't have them, it would 
be very difficult for FDA alone to develop the standards for 
patient reported outcomes in each one of those diseases, much 
less the clinical outcomes. So much more participation of the 
medical and patient community is needed in drug development, 
and we need to find better ways to do that, but I am not sure 
that is through legislation.
    Mr. Green. OK. And without a doubt, our greater resources, 
but again, our committee has worked over the years to try and 
provide those resources----
    Dr. Woodcock. Yes.
    Mr. Green [continuing]. To the FDA and look forward to 
working with you.
    Thank you, Mr. Chairman. I yield back.
    Mr. Burgess [presiding]. The gentleman yields back.
    I recognize myself for 5 minutes for the purposes of 
question.
    Dr. Woodcock, again, good to see you, good to have you back 
in the committee. So you have talked about how the FDA 
routinely works with sponsors to apply flexibility, including 
the use of biomarkers, surrogate endpoints, and nontraditional 
trial designs, and other available tools to expedite the 
development of products to treat both common and rare diseases.
    With respect to the common diseases, how is the FDA working 
with sponsors to apply these innovative development and review 
methods?
    Dr. Woodcock. Well, for example, hypertension is a common 
disease. We approve drugs for hypertension based on a surrogate 
measure, blood pressure, that is very well accepted, and for a 
number of years ago, we looked at automated blood pressure 
monitoring, and we decided it was unbiased, and so we decided 
that you really didn't need a control group in the same way 
that you would for most other diseases because you have an 
unbiased measure, and so we issued new approaches to studying 
hypertensive medicines. So that is an example.
    Mr. Burgess. What could happen so that the FDA could use 
this more frequently?
    Dr. Woodcock. Well, 45 percent of the drugs that we 
approved over the last several years used a surrogate endpoint. 
So we do use that when it is appropriate and it is available. 
For many diseases, we don't know what the right surrogate is, 
and that is why many of the accelerated approvals have been 
confined say to cancer and HIV is because the science, a great 
deal of science has been driven in those conditions, and we 
understand the biomarkers. But for other diseases, there needs 
to be more scientific development, and that is why we are using 
this, for example, biomarker qualification process to try and 
get more biomarkers developed that we can use, but we can't 
just dream them up and use them.
    Mr. Burgess. I thought that was your job. Well, let me ask 
you this. Are there situations where a majority of the 
scientific or research community believes that a certain 
biomarker sufficiently predicts the clinical outcome, but the 
FDA has yet to accept that?
    Dr. Woodcock. There may be. I think there is a lot of 
controversy around use of these. You heard some of that on 
Wednesday. There are two sides to this. If you rely upon a 
surrogate, often, especially when it isn't well validated, 
there is more uncertainty about whether or not the drug is 
actually going to work or not, and so there are different 
points of view. And as we have all been saying, the community, 
the patient community really ought to have--and treating 
community ought to have--a lot of input into how much 
uncertainty should be tolerated, given the circumstances of 
that disease.
    So there are situations where there is disagreement amongst 
various parties, external and internal, about the use of a 
surrogate.
    Mr. Burgess. Are you able to give us any examples of that, 
of a surrogate that the FDA may not right now be willing to 
accept?
    Dr. Woodcock. Well, for example, raising good cholesterol, 
all right. We had a series of trials on that. Everybody thought 
raising good cholesterol would be really good, and in fact, it 
turned out to be either neutral, or in one case, it actually 
increased mortality, so we no longer accept that surrogate. 
That is the kind of example where--and there are many others 
like that.
    In bone density, for osteoporosis, estrogens do a very good 
job and they decrease fractures. Although they have other 
liabilities. But some other agents were tried, and actually, 
they increased bone density, but they also increased fractures, 
and so we have to be careful when we use these surrogates to 
make sure that we are getting the intended results, clinical 
results.
    Mr. Burgess. Thank you for that.
    Let me ask you a question that is a follow-up from when we 
visited in April.
    Do you have an update on the status of the FDA's guidance 
on biosimilars naming and when that guidance will become final?
    Dr. Woodcock. Well, I certainly would like to get that 
guidance out as soon as possible. We are working diligently on 
that, and I don't have any further update.
    Mr. Burgess. But that was submitted as a question in April, 
and we are awaiting an answer.
    Now, also, along with that, I asked if anyone in the 
administration, outside of the FDA, had provided the agency 
with suggestions or recommendations with respect to this 
guidance.
    Can you, if the answer to that is yes, can you provide us 
with the name or names of those individuals?
    Dr. Woodcock. We would have to get back to you on that.
    Mr. Burgess. And again, we anxiously await your answer.
    My time is expired.
    I will recognize the gentleman from New Jersey, the ranking 
member, 5 minutes for questions.
    Mr. Pallone. Thank you.
    Mr. Chairman, you asked a lot of my questions, so I am 
going to have to move on to other things.
    But Dr. Woodcock, we heard a lot at Wednesday's hearing 
about the accelerated approval program at FDA, and as you know, 
the program allows for earlier approval of drugs that treat 
serious conditions and fill an unmet medical need, and the 
drugs are approved on the basis of surrogate endpoints which we 
also learned about on Wednesday, and of course, a critical 
requirement of the system is that companies conduct studies to 
confirm the clinical benefits suggested by the surrogate 
endpoint, and these studies are called phase 4 confirmatory 
trials. So a critical part--I want to ask about the phase 4 
trials. What challenges has FDA faced with respect to phase 4 
trials? Do sponsors complete in a timely manner?
    Dr. Woodcock. Well, it is sometimes difficult to complete 
these trials, and the reason is that if you had a serious and 
life-threatening disease and we approved a treatment for it, 
you probably would be somewhat reluctant to enter a trial where 
you had a maybe 50 percent chance of not getting the treatment. 
So what we often do is ask that trials be conducted in a 
different stage of disease or something where it actually 
hasn't been studied yet, so then we can get the results since 
that might take time.
    So I think in the early years of the program, we didn't 
track this as well as we should, and we did have a lot of 
trouble getting these trials completed. But in the current era, 
we are on top of this, and generally speaking, the sponsors are 
diligent in trying to get them completed, generally, but they 
have difficulty sometimes enrolling patients in these trials.
    Mr. Pallone. Another important component of the program is 
that when the surrogate endpoints do not ultimately show the 
anticipated clinical benefit, FDA could be faced with needing 
to remove the indication or take the drug off the market, and I 
imagine that is also no easy task.
    Can you describe what is involved with removing the 
indication or taking a drug off the market and what challenges 
does the FDA face there?
    Dr. Woodcock. Yes. Generally, if the confirmatory trial 
failed to show benefit, the first thing we ask is the sponsor 
to voluntarily withdraw the drug or the indication from the 
market. It is only if the sponsor does not agree to do that, 
then we go into a long administrative process, which includes 
hearings and formal findings and so forth, and this can take a 
long time if the sponsor can test our finding that the drug 
isn't effective.
    Mr. Pallone. Now, just a couple of years ago, we included 
some provisions to improve upon the accelerated approval 
program, and the FDA Safety Innovation Act of 2012. For 
example, the law made it clear that FDA could rely upon 
evidence developed using biomarkers or other scientific methods 
or tools when assessing surrogate endpoints. Can you describe 
what impact those legislative changes had on the program, and 
are there any other changes that you feel are necessary to 
allow you to make full use of the most recent scientific 
developments with respect to surrogate endpoints?
    Dr. Woodcock. I think the legislation was very helpful. We 
have taken it quite seriously. We have issued guidance, final 
guidance on expedited programs, and probably the biggest change 
that the legislation brought about was its focus on 
intermediate clinical end points, and we had to have quite an 
internal discussion about what that means, and I think you will 
see us approving more products under accelerated approval based 
on these intermediate clinical endpoints.
    Mr. Pallone. All right. Well, thanks.
    Again, it is clear to me that this is an extremely 
complicated area and one that is not necessarily conducive to 
further legislation, but I wanted to ask last about the master 
protocol.
    At the hearing on Wednesday, some panelists described some 
of the inefficiencies that exist in the way that clinical 
trials are currently conducted, and one of the suggestions for 
addressing those inefficiencies is to create a master protocol. 
So I just wanted to ask, first, can you tell us more about 
this, what is a master protocol? How would it help to improve 
the way we conduct clinical trials? Has FDA been involved in 
the development of a master protocol, and are there particular 
diseases that the master protocol is more appropriate for than 
others, and if so, which ones, and are there other areas where 
it might be expanded?
    Dr. Woodcock. Well, master protocol is one version of using 
clinical trial networks or standing clinical trials to evaluate 
investigational therapies where the drug development program 
isn't just for one therapy. It is for any therapy for that 
disease. So master protocol, though, has to be somewhat disease 
specific. You can't just have a general overall master 
protocol, right. It has to be focused on one disease.
    For example, the Lung-MAP trial is on squamous cell cancer 
of the lung that is advanced but five different agents right 
now are being studied all at once within that protocol, and 
that is a huge efficiency. But there are other versions of 
standing trials or trial networks that also could be used in 
other diseases. And as I said, the Cystic Fibrosis Foundation 
has a kind of network of clinical excellence where they 
actually sequenced the genome of all their patients, and so 
they are ready when a targeted therapy comes along. They are 
ready. They can put those patients into the protocol, and that 
tremendously improves the efficiency.
    So it is a long conversation that probably can't be had in 
5 minutes, but I have long advanced this concept and tried to 
push this concept because the current clinical trial paradigm 
is not sustainable.
    Mr. Pallone. All right. Thank you very much.
    Thank you.
    Mr. Burgess. The gentleman's time is expired.
    The chair recognizes the gentleman from Pennsylvania, Dr. 
Murphy, 5 minutes for questions, please.
    Mr. Murphy. Thank you.
    And good morning, Doctor. It is always good to have you 
here.
    Let me start out by asking about it is important for the 
medications and research to advance those but also for those 
that are already approved, and so let me ask you, we had passed 
the PDUFA laws a while ago, certainly that was supposed to help 
us get more generic drugs in the queue, but what has happened 
is we got 1.5 billion authorized over 5 years, what has 
happened is approval times have gone up, and there are fewer 
approvals, even though the law was supposed to reduce all 
those.
    Can you give me some indication of what is going on and 
what FDA is going to do about that?
    Dr. Woodcock. Certainly. We are well aware of these issues. 
In June, we received 625, I believe, generic drug applications, 
so the rate of submission is well above what was projected in 
the negotiations that we held.
    However, on October 1, the deadlines kick in for timelines 
for review of generic drugs, and we are fully prepared to meet 
those timelines as well as deal with this large backlog of 
pending.
    We had to hire a large number of people and totally revise 
our processes, reorganize the generic drug review offices and 
conduct many other changes, and that is what we have done over 
the past 2 years in preparation for the deadlines coming into 
effect on October 1.
    Mr. Murphy. Thank you. Another question here about some 
labeling issues. The abbreviated new drug application that 
would allow generic manufacturers--this is a proposal for FDA 
to change a label without FDA's prior approval but then come 
back later on, and the FDA itself has recognized, and say, 
quote, ``consistent labeling will assure physicians help 
professionals and consumers that a generic drug is as safe and 
effective as its brand name counterpart,'' unquote. But there 
is a concern out there that allowing these changes take place 
and then go backfill them later on can cause a lot of confusion 
in studies that have asked pharmacists and physicians this, so 
I am wondering where this issue stands in clarifying this.
    Dr. Woodcock. Well, we have received comments on the 
proposed rule. It was a proposed rule, and we received many 
comments. We are analyzing the comments, and subsequent to 
that, we will have to go forward with a rulemaking process.
    The proposed rule contemplated that we would actually have 
less disparities of labels in the marketplace on this because 
of this proposal because we would put up a Web site, and we 
would also require conformance of labels, which we cannot carry 
through right now, given the current systems.
    Mr. Murphy. A lot of us back in January asked to meet with 
Commissioner Hamburg and others about this, and I am not sure 
those things have taken place yet, so I hope this gets 
expedited and that these issues are addressed because I think 
it still leads to some confusion. So I am not clear yet in 
understanding even why this proposed rule was set up there to 
allow individuals to change the label and then come back later 
and ask permission.
    Dr. Woodcock. Well, currently, generic labels do not always 
match the innovator and they do not change their label in a 
timely manner, and so there will be labels out there for quite 
a bit of time, even with serious safety issues like new box 
warnings that don't conform to the innovator label, so we are 
trying to address this situation. And also, as generics are now 
85 percent of all drugs dispensed to consumers--that they 
should have the opportunity, since their drugs are the ones 
that people are being exposed to, to submit their findings of 
adverse events and suggest label changes, proposed label 
changes and actually execute them.
    Mr. Murphy. Well, I just hope that you will meet with the 
committee staff members and the companies to help clarify this 
because it still is not clear to me why this would be allowed, 
and I think it would end up confusing.
    I want to bring up one last thing just while you are here. 
I had sent a letter a few weeks ago to Dr. Hamburg. I am sure 
you didn't see this, but one of the things that is out there, 
too, is complications that are oftentimes reported in the media 
about caffeine, whether it is--and sometimes toxic levels 
people take.
    Dr. Woodcock. Yes.
    Mr. Murphy. Through over-the-counter things, pure caffeine 
or some of these supplements out there for athletes, et cetera, 
and yet it is also in everything from chocolate to coffee and 
other things we promote all the time, so I am hoping, at some 
point, FDA can also give some recommendations in terms of 
individual levels per drink, per dose, per day, per male, 
female, the genders, for weight, age, whatever that is.
    Dr. Woodcock. Yes.
    Mr. Murphy. Because it is still pretty confusing, whatever 
those products are that they can be beneficial, but I hope you 
will expedite that.
    Dr. Woodcock. Thank you.
    Mr. Murphy. Thank you.
    I yield back.
    Mr. Burgess. The gentleman's time is expired.
    The chair recognizes the gentlelady from California, Mrs. 
Capps for 5 minutes for questions, please.
    Mrs. Capps. Thank you for holding this hearing, to our 
chairman and ranking member.
    Thank you, Dr. Woodcock, for your testimony.
    This is an issue very dear to me, and as you know, I am 
incredibly concerned about our Nation's history of excluding 
minority groups, especially women, from all levels of medical 
research, from the lab rats to the most advanced clinical 
trials. And reports have shown that even when these groups are 
included in trials, there are often too few participants in the 
groups to analyze the effects on them or the analyses are 
simply not run or reported.
    I am sure you are familiar with the case of Ambien, 
commonly prescribed medication that recently had its label 
changed because it metabolizes differently in women than men, 
meaning that women had been receiving an inappropriately high 
does of this drug for over 20 years.
    In addition, in spring, a report entitled ``Sex-Specific 
Medical Research Why Women's Health Can't Wait'' was released, 
which provides evidence for the further inclusion of sex and 
gender in scientific research. And the FDA's own August 2013 
report, which was initiated by the inclusion of My Heart for 
Women Act in the FDASIA legislation, showed that there is still 
much work to be done to make sure that women are fully 
represented in clinical trials and that the safety and 
effectiveness of the information is readily available.
    I know the FDA is continuing to work on an action plan to 
address these disparities, so Dr. Woodcock, can you give us an 
update on where the agency is on this?
    Dr. Woodcock. Certainly. I would expect that that would be 
released, we would be timely in its release. I believe there 
was a statutory deadline or not, or there is some expectation, 
so we are working diligently on the action plan, yes.
    But I will say for drug development, which is what I am 
discussing here, that we did a study, for example, the class of 
2010, the product that we approved, we found that about 45 
percent of the participants were male, all right.
    And we found that almost all the submissions included the 
required gender analysis, which has been required for drugs for 
20 years, because I oversaw that when I first joined the Center 
for Drugs in 1994. So it is by regulation, so we do have these, 
but I think the transparency of the information is the problem, 
and we are working on that, and I really am committed to making 
that information more transparent so people understand what we 
know and what we don't know.
    Mrs. Capps. I think you put your finger on something, and I 
want to highlight a bipartisan letter I led, signed by the 
women of the House of Representatives, urging this agency to 
include clear and actionable strategies. And I think what you 
said about transparency and the reporting in the action plan is 
a way to address this issue once and for all.
    At Wednesday's hearing this week, I also asked the panel 
about the tools FDA is developing that could supplement our 
knowledge base, especially in the light of less robust clinical 
trial designs. The FDA Sentinel system, which I understand is 
making progress, if slowly, to conduct post-market passage 
surveillance of drugs and devices, could help spot issues like 
adverse drug interactions more quickly. I believe the Sentinel 
program holds great promise, and that is why I worked to get 
the Sentinel Assurance for Effective Devices Act included in 
FDASIA to continue progress on the program and ensure the 
design for both drugs and devices. Could you update us on the 
development of the Sentinel program, please, and what other 
resources or authorities do you need to get the system up and 
running to protect consumers more effectively and 
expeditiously.
    Dr. Woodcock. Well, I think use of electronic health data, 
which is rapidly becoming available, and the electronic health 
records and so forth, has tremendous promise for actually 
finding out what happens in the real world for medical 
products, both that are approved recently and those that have 
been on the market a long time, and that is what the Sentinel 
system is intended to do.
    We have run a mini-Sentinel network for 5 years, and that 
was between drugs and biologics. We paid for that out of our 
money that we have, and we are recompeting that to put up the 
Sentinel system, so that contract proposal is out on the 
street, and we hope to establish the real Sentinel system, 
which will be a large-scale system for surveillance.
    Now, as far as medical devices, we require a unique 
identifier or some kind of identifier in the medical record 
electronically so that we are able to capture that because the 
Sentinel system uses those electronic records to get the 
information, and I will repeat for everyone that it does not 
take any personnel information and move it to some central 
database. It strictly runs those analyses within the healthcare 
system and then the results only are combined.
    So that has tremendous promise. We feel very good about 
that. We actually are piloting running active surveillance on 
there, so when we approve a drug and we have a question about 
it, we can watch over time and see what actually happens. And 
as more and more people get on electronic health records, we 
can really have more insight in what is happening.
    So that is where we are with that, and it is resource 
limited. I have to pull resources from other activities to fund 
that, but I believe very strongly that this is the future.
    Mrs. Capps. Thank you. I appreciate that.
    Mr. Pitts [presiding]. The chair thanks the gentlelady.
    Now recognizes the gentleman from Georgia, Dr. Gingrey, 5 
minutes for questions.
    Mr. Gingrey. Mr. Chairman, thank you.
    Dr. Woodcock, thank you for appearing. It is always good to 
see you.
    I understand that a number of the challenges that have led 
to the duration and cost of conducting clinical trials in the 
U.S. to increase essentially are outside of FDA's purview. That 
being said, clinical trials are conducted to generate evidence 
used in the application for FDA approval, so my first question, 
how early do you typically communicate with these 
pharmaceutical companies, to discuss their trial design before 
the investigational new drug application is submitted?
    Dr. Woodcock. Well, we have agreements under PDUFA, that 
prescription drug user fee program, and for novel products or 
novel indications, say they are testing a disease that really 
doesn't have any treatment, companies can come in and have a 
pre-IND meeting. That meeting is before they start their 
clinical trials, their first in human studies, and we talk 
about that development program so they can start thinking about 
how that is going to be done.
    We do have information, it is preliminary, but looking at 
our information, it seems that companies that have more 
interactions with the FDA are able to get their products 
through more quickly, through the entire clinical trial process 
than companies that haven't had interaction with the FDA during 
the development process. But there are formal meetings that are 
held at different times under the user fee program, and those 
minutes are tracked, and we track the meetings and so forth, so 
there is quite a process for interaction during drug 
development.
    Mr. Gingrey. So you, as a manager, would be, maybe at that 
particular time, you make sure that your reviewers are not 
requesting overly burdensome data that really is not necessary 
so that the process can be speeded up?
    Dr. Woodcock. Well, there is always a push and pull. 
Scientists of all stripes always want more data, and that is 
scientists in the companies and scientists in the FDA, and so 
we have to walk that path between getting more data and 
actually the cost that is generated. And we have made a number 
of efforts under the CITI collaboration that we do with Duke 
University and many, many, many other partners to try and 
figure out how to streamline clinical trials as far as data 
collection, for example. But it is difficult.
    We have 1,600 meetings a year under the PDUFA, and when we 
meet with companies, the supervisors are there, the senior 
medical officials are also at these meetings.
    Mr. Gingrey. Well, that is the whole purpose of 21st 
Century Cures, of course, and as we get to the second panel and 
we hear about the associations and from the families, I am sure 
they are going to talk about how we can speed this process up.
    The last question. At our first 21st Century Cures hearing, 
we heard that only 19 drugs, outside of cancer and HIV space, 
have been approved by the accelerated approval pathway since 
1992, and I understand that you wrote a blog post after that 
hearing about how a number of drugs that were being considered 
under accelerated approval ultimately received traditional 
approval, so these statistics, according to your blog, were 
somewhat misleading. Can you provide some examples of when that 
occurred as well as the process involved?
    Dr. Woodcock. Certainly. Well, for certain rare diseases, 
we may decide, for example, that the surrogate is fine, OK, and 
it correlates with clinical benefit. Then the term 
``accelerated approval'' is a little misleading. It sounds like 
it is faster than regular approval, but actually, if we give 
regular approval on a surrogate, it is just as fast as 
accelerated approval, but you don't have to do confirmatory 
studies afterward because we already believe the surrogate.
    So, for a lot of, say, rare deficiency diseases where there 
is something missing, you may be able to show that you 
actually, when you replace that protein in the body, you give 
the activity back to the person, right, and so you may not have 
to show clinical outcomes. It is still a surrogate, but we feel 
it is good enough because we understand the problem that 
something is missing, and you deliver an active drug to the 
site of action of where the problem is, and that would be 
enough.
    So, in many cases, we are able to do traditional approval 
with the surrogate; that means that the patients and the 
sponsor don't have to go through all these confirmatory trials. 
I described the difficulties of that when you have a serious 
disease; you have approved a drug; and then you ask people to 
be randomized after approval.
    Mr. Gingrey. Dr. Woodcock, thank you.
    And my time is expired. Mr. Chairman, thank you, and I 
yield back.
    Mr. Pitts. The chair thanks the gentleman.
    I recognize the gentlelady from Florida, Ms. Castor, 5 
minutes for questions.
    Ms. Castor. Well, thank you very much.
    Thank you, Dr. Woodcock, for everything you are doing to 
ensure safe and effective drugs are available for the American 
public and those with health challenges.
    This is a hearing about the patient involvement in FDA drug 
approvals, and I think we can agree, they deserve a seat at the 
table when companies are developing drugs and medical devices 
within the clinical trial process. I have long been a supporter 
of the Department of Defense's Congressionally Directed Medical 
Research Programs known as the CDMRP. CDMRP funds peer-reviewed 
research into breast cancer, autism, ovarian cancer, prostate 
cancer, and other diseases. And since 1993, the patients have 
been involved and have been a part of CDMRP, and they have a 
consumer reviewer as part of a peer-review panel to represent 
the stakeholder community, and it has been very successful in 
combining patient perspectives and needs with scientific 
research and bringing those perspectives together.
    Has FDA, as you begin to consider improving patient 
involvement, have you looked at CDMRP to see if there is 
anything you can borrow from that in the drug approval process?
    Dr. Woodcock. We have not, and that is a good suggestion, 
so we would be happy to do that.
    Ms. Castor. OK. You mentioned previously that the Patient-
Focused Drug Development Initiative that was included in PDUFA 
was designed to allow FDA to hear from patients on how a 
disease impacts their life, and I understand you are scheduled 
to hold 20 public hearings. Share with us who FDA has met with 
so far. Have you started those hearings? If so, what have you 
learned already?
    Dr. Woodcock. Well, we have learned the devastating impact, 
I think, of the diseases, of these different diseases on 
people's lives it just incredible. We had one on chronic 
fatigue syndrome--that was our first one--HIV, lung cancer, 
narcolepsy, sickle-cell disease, fibromyalgia, pulmonary 
arterial hypertension, and inborn errors of metabolism, and we 
plan to have 16 of these meetings completed by the end of 2015, 
but we recognize this is just a drop in the bucket of what 
people suffer from.
    So what we are trying to do is really model how people can 
do this, and hopefully, it could be done more--not put on by 
the FDA but by the patient groups themselves in the medical 
community that serves them so that they can assemble more of 
this information and kind of multiply the effect of this, and 
we are already seeing some of that. NORD, for example, has 
offered to help with rare diseases, for example, to have more 
input that way because our resources are limited. We are not 
going to be able to cover all the different diseases.
    Ms. Castor. Good. So I expect we will hear from the patient 
organizations later today and their view on how they can be 
helpful and we can be effective.
    I think the wave of the future really is the information we 
will be able to gather through the electronic health record, so 
it is interesting to hear what you have done already with the 
Sentinel initiative. I heard from research institutes back home 
that are doing so much in genomics and personalized medicine 
that they think these larger networks are the wave of the 
future. You say you don't need additional legislation to 
continue, but you are having to borrow resources from this and 
that.
    Dr. Woodcock. Yes.
    Ms. Castor. So is your advice to the committee that we need 
to do more in technology when it comes to improving timelines 
on clinical trials by focusing on these networks and the 
electronic health record?
    Dr. Woodcock. The electronic networks have much promise in 
doing clinical trials.
    If we could move clinical trials more out into the 
community and have people out in the community, like most 
cancer patients in the U.S. who have diseases that are 
untreatable don't get into trials because they are being 
treated at places that aren't running trials. So we need to 
move this out into the community, make those folks eligible.
    And I am on the Steering Committee of the Lung-MAP trial, 
and I really urged that we make sure that we are out there in 
the community so that anyone who has lung cancer has an 
opportunity to participate in this research and perhaps have a 
more effective therapy.
    So I think the electronic health records, that is a huge 
different area that we are working on in how to do clinical 
trials utilizing that infrastructure that is emerging.
    Ms. Castor. Great. Thank you very much.
    Mr. Pitts. The chair thanks the gentlelady.
    I now recognize the gentleman from New Jersey, Mr. Lance, 5 
minutes for questions.
    Mr. Lance. Thank you very much, Mr. Chairman.
    A portion of your testimony has focused on the FDA's 
efforts on patient engagement. It is my understanding that 
ClinicalTrials.gov was intended to be a resource that provides 
clinical study information for patients, for healthcare 
providers, and for researchers. But it seems to me that the 
site lacks considerable information and has proven to be 
difficult to navigate.
    Dr. Woodcock, would you please comment on the current 
utility of the ClinicalTrials.gov.
    Dr. Woodcock. Well, I think that it has provided, along 
with the requirement of the medical editors of the journals 
that things be registered before they are going to be 
published--provided tremendously more transparency into what 
clinical trials are ongoing in the United States.
    And that has been a big achievement. All right? So we know, 
the issue of publication bias and everything is minimized 
because we know what trials have been done.
    However, I agree that, certainly for patients, I think that 
initiation of trials and understanding where there might be a 
trial that might be ongoing that might be available to them has 
also been effective, although, as you said, there are 
technological issues that remain. So it has made tremendous 
progress in transparency.
    Mr. Lance. Is there a way that you and we can work together 
to improve it? And I am not suggesting that you are in any way 
responsible for the challenges that remain. But moving forward 
for the better health of the American people, how together can 
we improve it?
    Dr. Woodcock. Well, the FDA Amendment Act required that 
regulations be issued around the results----
    Mr. Lance. Yes.
    Dr. Woodcock [continuing]. Section of this and that they 
consider whether to require the submission of clinical trial 
results for unapproved products, because much of the lag in 
getting results in there is that the products still are not on 
the market.
    So NIH is the lead for this rulemaking and I think they 
would be in the best position, and, also, they operate the 
infrastructure for this database.
    Mr. Lance. Thank you.
    In another area, in the past several hearings, we have 
discussed the difficulty of various institutions communicating 
one with another and a lack of coordination often leads to 
inefficiencies.
    What methods are currently in place to reduce redundancies 
in clinical trials? And what steps can we take together to 
ensure that we are not doubling up on research or making the 
same mistakes over and over?
    Dr. Woodcock. Hopefully, most things would eventually come 
out and be published. But certainly in the drug development 
area, there is interest in more sharing of earlier data and 
sharing of failures.
    But this has proven to be very a intractable area----
    Mr. Lance. Yes.
    Dr. Woodcock [continuing]. For transparency. All right?
    Mr. Lance. Yes.
    Dr. Woodcock. But we have continued to work on that.
    Mr. Lance. Yes.
    Dr. Woodcock. As far as some of the things that were 
referred to in the prior hearing, which I was able to listen to 
some of, they were talking about some of the inefficiencies, 
say, of IRBs, where you might have to have 100 IRBs that looked 
at----
    Mr. Lance. Yes.
    Dr. Woodcock. And I believe that there are efforts to try 
and address this. It is not an FDA issue. But, really, we came 
out a number of years ago in saying that central IRBs would 
really be preferable in these large multi-center trials.
    And then the contractual agreements that take so long to 
set up with each specific site is something that has been taken 
on. They have tried to develop model agreements and so forth.
    But that is something that the standing trial addresses 
because you sign this contractual agreement once and then you 
can do multiple investigational agents.
    Mr. Lance. Are we moving in the direction of central IRBs, 
in your judgment?
    Dr. Woodcock. Yes. There is certainly a consensus, I think, 
in the clinical trial investigator community that that is 
desirable, but various universities, naturally, are legally 
concerned about their own----
    Mr. Lance. Of course.
    Dr. Woodcock [continuing]. Liabilities and so forth. And so 
there is a push and pull about that.
    Mr. Lance. I think this is an area that we should engage in 
further investigation to make sure that we move forward in a 
manner that does not result in redundancies.
    Thank you, Mr. Chairman. I yield back the balance of my 
time.
    Mr. Pitts. Chair thanks the gentleman.
    Now recognize the gentlelady from Illinois, Ms. Schakowsky, 
for 5 minutes for questions.
    Ms. Schakowsky. Thank you, Mr. Chairman.
    Thank you, Dr. Woodcock. I think you are really an 
excellent witness. I appreciate your answers.
    Dr. Woodcock. Thank you.
    Ms. Schakowsky. I wanted to go a little bit further on the 
problem that Congresswoman Capps raised about the 
underrepresentation of women.
    I know you said that you found that, actually, women were 
overrepresented, but recently the Congressional Caucus for 
Women's Issues sponsored a meeting with leading women heart 
experts--both clinical and research experts, physicians.
    Those experts raised concerns that the lack of 
representation from women in clinical trials is limiting our 
ability to effectively treat women with heart disease. They 
were focusing in on heart disease.
    And according to those experts, for the last 50 years, 
women's heart treatment has largely been based on medical 
research about men.
    And even today, despite that fact, what they said is that 
women make up more than 50 percent of the U.S. population, that 
women comprise only 24 percent of participants in all heart-
related studies.
    And, additionally, scientists from the Women's Health 
Research Institute at Northwestern--that is in my district--
have raised concerns about the disproportionate number of 
adverse drug effects that occur in women due to the lack of 
sex-based clinical research.
    And, as you know, the biological, physiological, hormonal 
differences in males and females impact the rate of drug 
absorption, distribution, metabolism, elimination and, 
ultimately, affect the drug's effectiveness.
    According to those experts, the lack of requirement for 
drug manufacturers to take this into account and document any 
sex variability early in the drug development pipeline before a 
drug has been released places consumers, especially female 
patients, at an increased risk of adverse drug effects.
    So I want you to respond to that.
    Dr. Woodcock. Certainly.
    Ms. Schakowsky. Many of us were really left with a very 
disturbing feeling because heart disease is the major killer of 
women right now.
    Dr. Woodcock. Right. Well, I think we have to--what are the 
facts on the ground. All right? One of the reasons for the 
disparities that they are mentioning is actually the fact that 
men suffer heart disease earlier in life than women.
    Ms. Schakowsky. Although, let me just point out, they also 
said that the growing number, even though it is lower----
    Dr. Woodcock. Yes.
    Ms. Schakowsky [continuing]. Is younger women getting heart 
attacks and heart diseases.
    Dr. Woodcock. Yes. Yes. So that the reason for maybe 
maldistribution in the trials is because there is an age 
cutoff, and there always has been.
    In our survey, we found that there were--19 percent of the 
people in the trial in these 147 studies we looked at were over 
65, which is more than in the general population, obviously, 
but of sick people, that is still low representation, right--to 
save people with heart disease.
    Generally speaking, there is often a cutoff--age 75--and we 
are trying to eliminate those cutoffs for age and concomitant 
conditions so that the population will be more representative.
    But to your original point, we have always required male 
and female animals in the toxicology studies. All right? We 
require what we call population pharmacokinetics, PK/PD, early 
in drug development.
    And our clinical pharmacologists look at blood levels and 
exposure in men and women and we understand that, usually, and 
that is modern drug development.
    So there are multiple trials that are done that look at 
exposures, in other words, achieve blood level by gender and 
other factors, liver failure, kidney failure and so forth.
    And we can look at the phase 3 trials to see if they are--
there has been a requirement in the regulations since, I think, 
1994 that sponsors submit a gender analysis with their 
application.
    Ms. Schakowsky. Is this incorrect, then? It says women 
comprise only 24 percent of participants in all heart-related 
studies.
    Dr. Woodcock. Well, that may be true. And that may also 
include medical devices. It also may have to do with this age 
disparity when onset of disease.
    Ms. Schakowsky. I really hope that you will look at that 
because it is a great concern. It is a growing problem for 
women.
    And let me just give you an example of what--she said 
women, because we have different symptoms of heart disease--she 
said, if you have some of these symptoms of nausea, dizziness, 
go to the emergency room, but say, ``I am having chest pains'' 
because, without that, you may not get an electrocardiogram and 
you may be misdiagnosed. We need to help women.
    Thank you. I yield back.
    Mr. Pitts. Chair thanks the gentlelady.
    Now recognize the gentleman from Louisiana, Dr. Cassidy, 5 
minutes for questions.
    Mr. Cassidy. Hello, Dr. Woodcock. I always enjoy your 
testimony.
    Dr. Woodcock. Thank you.
    Mr. Cassidy. I mean that as a big compliment.
    So, next, real quickly--because I want to talk about 
something else--but does FDA--you mentioned that some 
institutions may be nervous about their liability if they refer 
their IRB activity to a centralized IRB.
    Dr. Woodcock. Correct.
    Mr. Cassidy. Except so many do, we know that is a false 
argument.
    Is there any way FDA can reassure those institutions? 
Because the gentleman from Mayo suggested it is a cultural 
issue. He didn't mention anything about legal. Thoughts?
    Dr. Woodcock. Right. Yes. I heard his testimony.
    In my experience, that there are legal--there are concerns 
of the--counsel of the various----
    Mr. Cassidy. Attorneys are always nervous. Right? I mean, 
they don't make money if they are not nervous. I hate to be 
cynical, but----
    Dr. Woodcock. Yes.
    Mr. Cassidy. Is there any way FDA can send reassurances 
regarding that?
    Dr. Woodcock. Well, we have tried. In guidance and so 
forth, we have encouraged this. And in the city initiative, we 
had a whole discussion and dissemination of information about 
central IRBs. But possibly there is more that we can do to 
encourage this.
    Mr. Cassidy. OK. Let me then bring on--you mentioned 
something intriguing earlier, that there may be some at high 
risk for disease; so, therefore they will be more risk-
tolerant.
    Dr. Woodcock. Yes.
    Mr. Cassidy. Now, I have a family member, a nephew, with 
Down syndrome. And I am looking on the alzheimers.org Web site, 
and they mention how virtually 100 percent of adults with Down 
syndrome by age 40 will have evidence of the tangles associated 
with Alzheimer's.
    Dr. Woodcock. Yes.
    Mr. Cassidy. Now, what are the issues regarding--wow. This 
is a group of adults who are 100 percent at risk for a terrible 
condition.
    Dr. Woodcock. Right.
    Mr. Cassidy. But there are other issues involved as well.
    What are your thoughts about this? How do we make stuff 
available for folks incredibly at risk for such a terrible 
disease?
    Dr. Woodcock. Yes. Well, with Alzheimer's, there are a 
number of problems. The basic problem is we still don't 
understand the disease well enough and the interventions that 
have been tried, which have been in late-stage disease when 
people are already demented, have failed to work.
    Mr. Cassidy. Now, as I gather, though, the problem is 
predicting at an earlier stage those at risk. Correct?
    Dr. Woodcock. That is correct. If you want to intervene 
early. We recently issued a draft guidance saying that, OK, if 
you want to intervene earlier, we would accept an end point 
that is subtle cognitive testing.
    Mr. Cassidy. I accept that.
    But how do you decide which population is at such high 
risk? Because, if you have a control group--you follow what I 
am saying--only 10 percent are really going to be at risk.
    Dr. Woodcock. Right.
    Mr. Cassidy. You with me? This is a really expensive study.
    Dr. Woodcock. That is right. And so we advocate techniques 
called enrichment, which you try to use biomarkers or other 
tests to figure out. There are genetic conditions that increase 
your risk for Alzheimer's disease.
    Mr. Cassidy. So speaking of Down syndrome as one example?
    Dr. Woodcock. That would be one example. Yes. There are 
others.
    Mr. Cassidy. And can you give us the progress of that. So 
if you accept these, are people now using these?
    Dr. Woodcock. Well, we need agents to use them in. So that 
is part----
    Mr. Cassidy. And I am sorry. ``Agents,'' you mean as in----
    Dr. Woodcock. I am sorry. Investigational interventions 
that we can test in the people.
    And that is part of the problem. The science of 
understanding what causes Alzheimer's and what you can 
intervene in that would actually delay or prevent the disease 
is not mature enough.
    And we have approved a couple imaging agents for 
Alzheimer's, but they aren't 100 percent. And you would maybe 
be kind of advanced----
    Mr. Cassidy. But, for example, I know hyperinsulinemia is 
thought to be a potential risk factor.
    Dr. Woodcock. Yes. I know that.
    Mr. Cassidy. And I think there are some studies suggesting 
that Actos might give some benefit.
    Dr. Woodcock. Yes.
    Mr. Cassidy. Presumably, it would be at an earlier stage, 
not a later stage, would be a non-metabolic syndrome indication 
for the use of Actos. Fair statement?
    Dr. Woodcock. Yes.
    Mr. Cassidy. So there is at least some of that. I guess I 
pose that to ask the degree to which that has been, again, the 
current state. I will go back to what is the current state of 
using that sort of thing?
    Dr. Woodcock. Right. So the current state, if someone 
decided to do a trial--and I believe there have been some 
intervention trials, not of Actos, but an earlier intervention 
at high-risk--in higher-risk people--they might identify people 
they felt were high risk for one reason or another, randomize 
them to this intervention or not, and then we would allow use 
of neurocognitive testing even before they had symptoms, if 
they had subtle changes, and if the treatment group did better 
than the placebo group, we could give accelerated approval.
    Mr. Cassidy. So I guess you have got the framework. It is 
just a question of someone coming forward to take advantage of 
it.
    But how long would such a study, do you imagine, take to 
complete its course? Twenty years?
    Dr. Woodcock. No. No. But we need to have better 
measurements that stick to these biomarkers and other 
measurements, like of subtle cognitive function, where we--the 
NIH and us and others are working on this.
    Because the earlier you can intervene--if you have a very 
targeted test that can identify people early, they don't have 
any symptoms, but you can tell their brain isn't working as 
well as it should, and then it will decrease over time. So that 
is kind of the rate-limiting step.
    But I agree. Prevention is very difficult because there you 
want to intervene on people who are well and treat them for a 
long time and expose them to something with the hope that, at 
the end of the day, they are not going to get whatever bad 
outcome.
    Mr. Cassidy. We are out of time. Thank you very much.
    Mr. Pitts. Chair thanks the gentleman.
    Now recognize the gentleman from Virginia, Mr. Griffith, 5 
minutes for questioning.
    Mr. Griffith. Thank you very much, Mr. Chairman.
    Dr. Woodcock, as others have said today and, also, what I 
have heard in some of our informal conversations is that you 
not only do a good job as a witness, but that you are doing a 
good job overall.
    Dr. Woodcock. Thank you.
    Mr. Griffith. And so I appreciate that, and thank you so 
much for being here today.
    You and Dr. Cassidy had a little conversation about 
lawyers. Some lawyers are always nervous. Other lawyers are 
always looking for a way to solve the problem.
    And so maybe we need to get some of those lawyers on your 
team and some of the corporate teams to solve the problem, 
figure out how we can make these things work, because I do 
think it is important.
    As you probably know, I am one of those who advocates that 
we try to move a little quicker in those areas where we have 
problems that we don't have solutions for currently and, also, 
favor what is known in some State laws as right to try when you 
have a situation where doctors have tried everything and folks 
are given a diagnosis they have got months to live or their 
condition is going to be fatal.
    I am one of those people who believes that we ought to let 
them go ahead and try whatever it is they are willing to pay to 
do because the FDA can't protect you if you are going to die 
from something that might kill you.
    Dr. Woodcock. Right.
    Mr. Griffith. I mean, it is going to happen one way or the 
other. You might as well have the right to try something.
    That being said, I know there are a lot of issues 
surrounding that. I am not sure we have time for for that 
discussion today.
    And I know that there is another panel, and I want to hear 
from the patients as well because they are involved in this 
process.
    So respecting you greatly, I yield back my time.
    Mr. Pitts. Chair thanks the gentleman.
    Now recognizes gentlelady from North Carolina, Mrs. 
Ellmers, 5 minutes for questions.
    Mrs. Ellmers. Thank you, Mr. Chairman.
    And thank you, Dr. Woodcock, for being with us again today.
    This is such an important issue. As you know, we had our 
panel on Wednesday. And it seemed to me that it was a general 
consensus that everyone is looking for ways to expedite this 
and to make it more efficient and get those drugs to market 
sooner so that we can be taking care of our patients more 
effectively.
    In your testimony and in the discussions that we have had 
today, you have touched on the biomarkers and targeted drug 
development to benefit disease populations, obviously.
    As all of our representatives here, we all have 
constituents with rare diseases, heart-breaking. Especially 
right now in my community, I have a very good friend with ALS. 
And as I am learning more and realizing, we have had a number 
of members of our community diagnosed with ALS. So this is 
something that is very important to me right now.
    And I am just looking at the idea--as far as the target 
approval process being appropriated and applied through the 
FDA, it seems to be that we are looking at cancer and HIV. 
Where do some of those rare diseases fall within that?
    And you had mentioned and there was discussion about the 
master protocol and that seems to be applied more to cancer or 
HIV. Where can some of the rare diseases fall in there? And 
what can we do to help make that happen?
    Dr. Woodcock. Well, any rare disease would be a great 
candidate for a standing network, a network of experts--and I 
think you may hear more about this from the next panel--where 
they are ready to evaluate any therapy that advances through 
the early, the nonhuman, stages.
    So they could pick that up right away and test it quickly. 
In the meantime, until that happens, they can get what we call 
natural history, which I know sounds very wonky.
    But people are asking--just now Mr. Cassidy--like how long 
does Alzheimer's progress from presymptomatic to symptomatic. 
Well, we need to know that so that we can design the trial 
correctly.
    In rare diseases, even more difficult because nobody knows. 
And, usually, they get experts together and say, ``Well, in my 
opinion, it takes this long.'' Right? And they are usually 
wrong because they have only seen a few people.
    So we are encouraging these natural history studies, these 
networks. First, they look at the people and they can look at 
the biomarkers, too.
    So what changes in ALS? What can we measure? Could we 
measure something that gives us indication that treatment might 
be working? Right?
    And then, as soon as a therapy becomes available, then you 
can rapidly get people into a trial and there would be no 
delays because there is no delaying an ALS.
    Mrs. Ellmers. Right. Exactly.
    And that is obviously part of the concern. And certainly I 
agree with my colleague in talking about right to try. This 
would be a perfect example of decisions that families and 
patients can make.
    I do want to talk about--you had also mentioned listening 
carefully to patients and families.
    Dr. Woodcock. Yes.
    Mrs. Ellmers. And do you consider and give more weight--
that is one of our questions, is how much weight are you giving 
to the patients and families? And there again, from our 
perspective in Congress, what can we do?
    You know, as we have heard everyone agreeing that we need 
to make a difference here and we can move things forward, how 
open is the FDA to this possibility? And what can we do right 
now to make this happen?
    Dr. Woodcock. Well, as I said in my testimony in the 
beginning, medical culture has changed over the years. It used 
to be very doctor-centric and now it is patient-centric. And 
the FDA culture and drugs is a medical culture. And so that has 
changed at the same time, but slowly.
    So we have been working, though, very diligently with 
patient groups and so forth to try to get the patient point of 
view more central to the evaluation of benefit and risk and 
what it means to the person who actually has the disease, is 
going to take the drug.
    To answer your question what can be done, I think a lot of 
this needs to be done out in the community. The patient groups 
need to get organized and develop these. Some of them are 
working with PCORI and trying to use that mechanism to get more 
information available and so forth.
    We have gotten draft guidances from different groups, 
including Muscular Dystrophy, that really are a statement of, 
``This is what we care about. This is what we value. This is 
what we want you to look at.'' And we will pay extremely close 
attention to those, and those are extremely valuable.
    Mrs. Ellmers. Thank you, Dr. Woodcock.
    And I yield back the remainder of my time.
    Mr. Pitts. The chair thanks the gentlelady.
    We are voting on the floor. We have 10 minutes left in the 
vote. We have three more questioners.
    Mr. Guthrie recognized for 5 minutes for questioning.
    Mr. Guthrie. Thank you, Mr. Chairman. I will try to be 
brief.
    I will echo what the others said about your testimony. 
Appreciate it.
    But since we started this 21st Century Cures and--
everybody's excited. Both sides are trying to see how we can do 
this better.
    And I have heard from a lot of groups and I have heard 
several times that the oncology division seems to be one people 
really like to work with and it works well. Some of the other 
divisions in expedition is not as well to work with.
    And I have always believed--Jack Kemp used to say, ``Don't 
study failures and point out the problems. Let's look at 
successes and see how it can be replicated.''
    So within your own agency, you are having wonderfully 
successful programs, at least according to the feedback I have 
gotten, and some not as fun as the ability to work with.
    So I guess my question is: Is there any impediment to 
saying, ``Hey, this''--the oncology is what we hear about more, 
not that the others aren't, but we hear more--is there any 
impediment to taking what is happening there and transferring 
to other agencies? Is there something Congress can do to make 
it easier or is it just learning and moving forward?
    Dr. Woodcock. Let me tell you that 10 years ago, I heard a 
lot of negative comments about our oncology group. All right? 
And now we have therapies that are so effective. They are 
really on fire.
    They see that, for their patients they took care of--they 
are all oncologists, hem onc doctors--that these new treatments 
would really have made a difference for those people. And so 
they are doing everything they can to get those treatments out.
    And I think what we need, we need the same kind of 
inspiring therapies in these other areas. And I do think the 
doctors--they are doctors. They are physicians. They care about 
patients in their disease area.
    And this breakthrough--I don't know whether you can see it 
here, but you see that other disease areas are coming up and we 
are designating--in neurology and anti-infectives and 
psychiatry, we are designating potential breakthroughs. And so 
this type of thing will really help.
    But, also, of course, we try to have a management 
structure, multiple mechanisms whereby we have consistency and 
uniformity of our approach and our procedures, and I think we 
do quite well in our procedures.
    But I think the attitude may have something to do with the 
underlying science. We had a war on cancer. It is starting to 
pay off. And we need to really expedite that.
    Mr. Guthrie. Well, thanks.
    And I have a bill particularly to put the same professional 
budget judgment status for Alzheimer's, which we are going to 
spend in 2050 $1 trillion. This is not loss of income, loss of 
productivity.
    Dr. Woodcock. Right.
    Mr. Guthrie. That is $1 trillion spent on that disease.
    That is when I am 86. So that is when my children and our 
grandchildren will be taking care of us. So, hopefully, we can 
have the same inspiration and do that, particularly in 
Alzheimer's.
    Dr. Woodcock. I can assure you that, if they were promising 
treatments for Alzheimer's, we would jump right on them.
    Mr. Guthrie. Appreciate that. Thank you very much.
    And I will yield back.
    Mr. Pitts. Chair thanks the gentleman.
    Recognizes the gentlelady from Tennessee, Mrs. Blackburn, 5 
minutes for questions.
    Mrs. Blackburn. Thank you so much, Dr. Woodcock. I have 
basically one question that I do want to get to.
    Looking at the QIDP and the moving forward of that, it can 
give up to 5 years of additional data exclusivity. Bipartisan 
effort. We were all for it.
    What I want to know from you is: How many QIDPs has the FDA 
designated to date? How many products have actually been 
approved to date? And do you believe that the QIDP is an 
important designation?
    Dr. Woodcock. It is absolutely important.
    Mrs. Blackburn. OK.
    Dr. Woodcock. We have granted 50 designations for 34 unique 
molecules. And in the last several weeks, we have approved the 
first two medications that are designated, the first two 
antimicrobials.
    Mrs. Blackburn. Excellent.
    Dr. Woodcock. So that is making a difference. We do feel, 
though, that probably more needs to be done.
    Mrs. Blackburn. And in that ``more needs to be done,'' give 
me a couple of examples of what you think the next step should 
be. I would be interested in that.
    Dr. Woodcock. Well, we are very interested in the pathway 
that people call limited population antibacterial drugs or 
other streamlined pathways for development that would be 
matched with some sort of symbol or logo that would enable 
doctors and other prescribers to recognize that it was from a 
limited program. We think that would also allow us to 
streamline the development program.
    Mrs. Blackburn. Excellent.
    And for the second panel, I want to welcome a fellow 
Tennesseean, Dr. Marshall Summar, who is going to be speaking 
on behalf of the National Organization of Rare Diseases.
    So welcome. We are delighted you are here.
    And I would yield back.
    Mr. Pitts. Chair thanks the gentlelady.
    Now recognizes the gentleman from Florida, Mr. Bilirakis, 5 
minutes for questions.
    Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
    And thank you for your testimony, Dr. Woodcock.
    I asked these questions a few months ago and I didn't get a 
response. So I am going to see if I can get a response this 
time. Appreciate it if you can answer.
    Can you tell me how many treatments were approved with 
novel biomarkers used for the first time?
    Dr. Woodcock. No. I don't have that in the----
    Mr. Bilirakis. Can you get that information to me as soon 
as possible?
    Dr. Woodcock. I would be happy to. It is a very interesting 
question. Yes.
    Mr. Bilirakis. And then next question: Have any accelerated 
approval occurred within novel biomarker in never-before-
treated disease?
    Dr. Woodcock. Oh, yes. All the time. And I can get that for 
you. I don't have it, again.
    Mr. Bilirakis. Please.
    How many new biomarkers did the FDA accept for a first-time 
use in the last 5 years?
    Dr. Woodcock. Certainly.
    Mr. Bilirakis. Can you get that for me?
    Dr. Woodcock. Absolutely.
    Mr. Bilirakis. OK. Very good. Thank you very much.
    I know we don't have a lot of time; so, I will yield back. 
Thank you, Mr. Chairman.
    Mr. Pitts. Thank you.
    There is 2 minutes left in the vote on the floor; so, we 
are going to recess. There are two votes. As soon as we have 
the second vote, we will come back and reconvene with our 
second panel.
    Again, Dr. Woodcock, thank you for coming. You have been a 
terrific witness.
    Dr. Woodcock. Thank you.
    Mr. Pitts. Members will have follow-up questions. We will 
send them to you. We would ask that you please respond.
    Thank you. And thank you for your patience.
    The subcommittee stands in recess.
    [Recess.]
    Mr. Pitts. Time of recess having expired, we will reconvene 
the subcommittee on Health and introduce our second panel.
    In our second panel, we have five witnesses. I will 
introduce them in order of their presentation. First, Ms. Pat 
Furlong, Founding President and CEO of the Parent Project 
Muscular Dystrophy; second one, Mr. Robert Beall, President and 
CEO of Cystic Fibrosis Foundation; third, Mr. Richard Pops, 
Chairman and CEO of Alkermes; fourthly, Dr. Leonard 
Lichtenfeld, Deputy Chief Medical Officer of American Cancer 
Society; finally, Dr. Marshall Summar, Director of Scientific 
Advisory Committee, National Organization for Rare Disorders.
    Thank you all for coming. You will each be given 5 minutes 
to summarize your testimony. Your written testimony will be 
placed in the record.
    Ms. Furlong, we will start with you. You are recognized for 
5 minutes for your opening statement.

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

                    STATEMENT OF PAT FURLONG

    Ms. Furlong. Thank you.
    Good morning, Chairman Pitts and members of the committee.
    My name is Pat Furlong. Twenty years ago I joined other 
parents to form Parent Project Muscular Dystrophy to end 
Duchenne, one of the many forms of muscular dystrophy and the 
most common lethal genetic disorder diagnosed in childhood.
    In 1984, I received the horrific diagnosis on my two sons, 
Christopher and Patrick, and both of my sons are gone now. I 
wage this crusade in their honor.
    Much has happened over the past 15 years to transform the 
Duchenne clinical and research landscapes, and much of this is 
a direct result of the actions by Congress and this committee, 
notably the enactment of the Childs' Health Act in 2000, and 
the Muscular Dystrophy CARE Act 1 year later. Since the MD CARE 
Act was enacted, we have seen about 10 years added to the 
lifespan of patients with Duchenne.
    There has been an improvement in quality of life driven 
largely by the development and dissemination of care standards 
so that all patients can be diagnosed accurately and as early 
as possible and provided with the highest quality of care.
    The MD CARE Act also transformed the Duchenne research 
landscape. What was just 12 years ago a near-barren field has 
evolved into a robust area of research where multiple potential 
therapies are in clinical testing and several others are in 
early stages of development.
    Despite these advancements, Duchenne remains a fatal 
disease without any FDA-approved therapies. Most boys end up in 
wheelchairs by their mid-teens, and only a few live beyond 
their late 20s.
    Our community needs therapies and we need them fast to. To 
achieve this goal, PPMD has led groundbreaking efforts over the 
past year to address two major impediments in our request to 
end Duchenne.
    One is a lack of regulatory understanding of patient and 
parent perspectives on benefit-risk; and, two, a lack of clear 
guidance or direction to the biopharmaceutical companies 
designing these clinical trials.
    PPMD partnered with Johns Hopkins University to conduct the 
first-ever scientific survey on benefit-risk perspectives. The 
survey involved 120 parents of Duchenne children. It validated 
what we have known anecdotally for years.
    Because Duchenne is 100 percent fatal at a young age, many 
patients and families are willing to accept higher levels of 
risk in return for the prospect of potential benefit.
    The data has been shared with the FDA and was recently 
published in an academic journal. Now the FDA must ensure its 
reviewers apply this evidence to their decisionmaking process.
    Another impediment to drug development, particularly in 
rare diseases, is the absence of a clear guidance from FDA when 
it comes to designing clinical trials. Small patient 
populations, limited knowledge about the condition and a lack 
of accepted or validated biomarkers are some of these 
challenges.
    At the invitation of the FDA, PPMD led a comprehensive 6-
month effort to convene key stakeholders--patients, parents, 
clinicians, researchers and industry--to write a draft guidance 
document that would address trial design and many other issues. 
This was submitted to the FDA last month, marking the first 
time a patient group has led the development of such a product.
    Now the FDA must step up promptly to review the draft, 
gather stakeholder input and issue a guidance document under 
the Agency's name.
    While each of these projects is focused on Duchenne, each 
also offers a template or a model that could be applied to 
other diseases or other conditions, particularly rare diseases, 
and I hope other organizations will take on similar programs.
    So what can Congress and Federal agencies do moving ahead? 
First, you can make sure that the patient perspective on 
benefit-risk and other issues is considered by reviewers of the 
FDA.
    One way to do so could be by establishing a nonburdensome 
step where reviewers would disclose how they did or did not 
take such information into account making their decisions on a 
drug application. This would shed light on for what many 
considered a mysterious process and could be done in a very 
simple manner.
    Second, I suggest an even greater focus on regulatory 
science so the FDA keeps pace with the breakneck speed of 
innovation. Specifically, NIH could bolster support for 
regulatory science research and infuse that into clinical and 
translational awards. Incorporating a regulatory perspective 
earlier in the pipeline can maximize the likelihood that 
candidate therapies will be ready for the rigor of the FDA.
    Finally, I would encourage greater flexibility in clinical 
trials, particularly rare fatal conditions like Duchenne that 
have small populations. Business-as-usual trial designs simply 
do not hit the mark when working with these populations.
    The Duchenne community has traveled a great distance over 
the past 15 years, thanks in significant part to the leadership 
of this very committee, leadership that will continue on Monday 
with action by the full committee on the MD CARE Act 
amendments.
    For far too many families, my own included, this journey 
has not been fast enough. We stand ready to work with your 
committee to make sure the 21st Century Cures Initiative ends 
Duchenne and so many other rare diseases.
    Thank you.
    Mr. Pitts. Chair thanks the gentlelady.
    [The statement of Ms. Furlong follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
    
    Mr. Pitts. Mr. Beall, you are recognized for 5 minutes for 
your opening statement.

              STATEMENT OF ROBERT J. BEALL, PH.D.

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

                  STATEMENT OF RICHARD F. POPS

    Mr. Pops. Thank you very much.
    I would like to thank you, Mr. Chairman, Ranking Member 
Pallone and all the members of the committee for inviting me to 
testify.
    I just want to thank Chairman Upton and Congressman DeGette 
for spearheading the 21st Century Cures Initiative.
    I would also like to express my respect for and 
appreciation for the folks on this panel and for Dr. Woodcock. 
We are all partners in this together, and it is an credibly 
important mission.
    The simple and powerful concept of incorporating insights 
from patients is centrally important to the future of the 
Nation's healthcare system. And it is also one of the great 
opportunities for us all to have a transformative impact.
    I have served as the CEO of Alkermes for over 20 years. Our 
company develops medicines for people living with chronic 
debilitating diseases, such as opioid addiction, schizophrenia, 
and depression. Our approach is entirely dependent upon 
considering the patient perspective early and consistently 
throughout the drug development process.
    I also serve on the Boards of both BIO and PhRMA and was 
deeply involved in the PDUFA V negotiations, as well as the 
preparations ongoing for PDUFA VI, where elevating the patient 
voice has already emerged as a key theme for that initiative.
    Today I would like to propose a new framework for patient 
involvement in developing new medicines, which requires 
engagement from all three of the major parties involved, 
innovative biopharmaceutical companies like ours, FDA, and the 
patients who stand to benefit from these medicines.
    And the framework is based on three core principles.
    First is that interactions must be data-driven, based on 
science and separate from powerful and passionate advocacy 
messages that patient groups otherwise deliver.
    Second, the engagement framework should be actionable, not 
theoretical. It should improve the overall efficiency of the 
process rather than adding new steps in a process that is 
already incredibly complicated. This is particularly important 
for young biotechnology companies who are developing their 
first drugs on limited resources.
    Third, the approach should preserve and enhance FDA's gold 
standard of safety and efficacy, which is really one of our 
great national treasures. I believe deeply, personally, that 
increased patient input can coexist with efficiency and the 
highest level of scientific rigor.
    So from industry's perspective, there is clearly no 
consistent way to incorporate patient-generated input. This 
input would have a really meaningful impact on a range of 
critical decisions we and our researchers make specific to 
particular product candidates and certainly to the way we 
design clinical trials and implement them around the world. 
This is an important missing link.
    As Dr. Woodcock mentioned and the FDA, patient engagement 
is not a new concept. Several provisions included in PDUFA as 
well as FDASIA have resulted in meaningful new expansions in 
patient engagement.
    FDA has also been open to and has taken initial steps to 
include patient input into their reviews, and we can build on 
this. The proposed framework I am considering would build on 
all of these things.
    The historical paradigm of drug regulation as a bilateral 
process between FDA and the industry is outdated. Science and 
society have continued to advance. Patients are organizing in 
new ways, and their critical role in driving innovation is 
becoming more the rule than the exception. We have 20th-century 
regulatory framework for 21st-century drug development.
    To tackle these increasingly complex scientific and 
regulatory issues as we look to treat and cure complex 
diseases, all three parties can work together to develop 
improvements to their existing regulatory framework.
    These would include new clinical trial designs, more 
efficient clinical trial enrollment methods, advancing FDA's 
evaluation of risk and benefit, and more sophisticated post-
market data collection. These are incredibly exciting areas for 
future consideration.
    We would need to evolve the way we work together, all the 
different parties, recognizing our shared responsibility to 
improve the efficiency of the development process and our 
accountability to assure the medicines are safe and efficacious 
for patients.
    There will be a number of challenges to this as we move in, 
and these could include establishing a common threshold for 
data and scientific rigor that is shared by patient industry 
groups and FDA, modifying existing regulations to accommodate 
this new framework, protecting intellectual property and data, 
which is essential to enabling innovation and maintaining this 
gold standard of safety and efficacy.
    As next steps, I propose that Congress, industry, FDA and 
patient groups come together to develop and implement this new 
framework, building on existing patient-focused provisions of 
PDUFA and FDASIA. We should also analyze existing statues and 
regulations to identify impediments and opportunities.
    In conclusion, the concept of a new and comprehensive 
patient-inclusive framework is both ambitious and, at the same 
time, it is quite modest.
    It is ambitious as it could result in a dramatic change in 
the way we discover and develop medicines. It is modest because 
it is not a new regulatory pathway or authority, but it builds 
on an existing foundation.
    And we at Alkermes and all of our colleagues in the 
biopharmaceutical industry are standing by to help you in that 
effort. We really thank you very much for your leadership.
    Mr. Pitts. Chair thanks the gentleman.
    [The statement of Mr. Pops follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
    
    Mr. Pitts. Dr. Lichtenfeld, you are recognized for 5 
minutes for your opening statement.

           STATEMENT OF J. LEONARD LICHTENFELD, M.D.

    Dr, Lichtenfeld. Good morning, Chairman Pitts, Ranking 
Member Pallone, and members of the subcommittee.
    I am Dr. Len Lichtenfeld, and I am Deputy Chief Medical 
Officer for the American Cancer Society and truly appreciate 
the opportunity to be with you today to testify. The American 
Cancer Society is pleased to contribute to the dialogue around 
the committee's 21st Century Cures Initiative.
    Today I would like to focus on three critical areas for the 
committee's consideration. One is the need for greater 
investment in research; secondly, expedited approval processes 
that continue to ensure safety and efficacy of approved drugs; 
and, third, making patients active partners in all aspects of 
research development and regulation of new therapies.
    We are fortunate and blessed that today we have 14 million 
cancer survivors in the United States. It is a remarkable 
number, and it is due to more effective treatments and improved 
screening tools that have been made possible through research.
    We must continue and expand our steadfast commitment to 
research, and we must continue to support researchers working 
on finding the next generation of cures.
    Just as important, we must ensure that expedited approval 
processes for drugs and devices are appropriately safe, 
effective and accessible to patients. The goal of the 21st 
Century Cures Initiative is to accelerate the development and 
approval of new medical treatments.
    There are a few other areas that can match the research and 
development activity in the field of cancer. It is, in fact, 
and has been a model of innovation.
    The FDA's Office of Hematology Oncology Products has 
aggressively used the tools provided by Congress to speed new 
drugs to patients and has encouraged drug companies to be 
innovative in clinical trials.
    In the past 8 months, three cancer drugs have been approved 
using the accelerated pathway. One approval was based on a 
trial of 111 patients, an example of research approvals 
happening faster and with smaller clinical trials as has been 
the case in the past.
    Small-sized trials and accelerated approval do have 
drawbacks. They may not include a diverse population, which may 
yield an incomplete picture of how a drug might work in a 
broader population. Small trials and accelerated approvals also 
tend to be seen in deadlier cancers where there are no other 
good therapeutic options.
    And I want to stress that the risk-benefit tolerance of a 
cancer patient facing a poor prognosis may be much different 
than for those with other available treatment options.
    And, therefore, the same acceptance of reduced data on 
which to base FDA approval may not be appropriate in other 
fields or for other diseases.
    Finally, I want to stress the importance of researchers, 
pharmaceutical companies and the FDA in engaging widely and 
meaningfully with patients.
    The Food and Drug Administration Safety and Innovation Act 
requires greater patient involvement throughout the drug and 
device approval process. ACS CAN championed provisions to 
expand the FDA's patient representative program to maximize 
patient input during the drug development process.
    We need to continue to build on that progress. Patients can 
provide important perspectives at various stages of medical 
product development and regulation.
    They know more than anyone what is most important to 
patients, to themselves: Symptom reduction, risk tolerance and 
design elements that might affect trial recruitment or 
retention.
    This kind of patient involvement should be reinforced and 
supported and, to this end, the FDASIA provisions requiring FDA 
to address challenges that have hindered patient involvement 
must be fully implemented.
    We urge the committee to consider examining opportunities 
for providing greater funding to support the FDA patient 
representative program as well as broader continued engagement 
with the patient community.
    Another important way patients' perspectives can inform 
development of therapies is through the design and use of 
patient-reported outcomes.
    Measures of cancer therapy effectiveness sometimes include 
functional status, pain or quality-of-life measures, but these 
may be reported by the physician rather than by the patient.
    Quality-of-life measures like pain or nausea should come 
from patients themselves, and patients should help prioritize 
the importance of these side effects in the overall response to 
a disease and the associated treatments.
    When quality-of-life outcomes are vigorously measured and 
supported by the FDA, they should be included in a drug's 
labeling and they should be considered for a drug's approval.
    The FDA should also be encouraged to work with industry and 
researchers to incorporate self-reported symptom measurements 
as a regular part of clinical trials.
    In closing, we appreciate the opportunity to contribute to 
the dialogue around the committee's 21st Century Cures 
Initiative and look forward to working with the subcommittee 
and its staff. I am happy to take any questions.
    Thank you very much for this opportunity.
    Mr. Pitts. Chair thanks the gentleman.
    
    [The statement of Dr. Lichtenfeld follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
    
    Mr. Pitts. Dr. Summar, you are recognized for 5 minutes for 
your opening statement.

               STATEMENT OF MARSHALL SUMMAR, M.D.

    Dr. Summar. Thank you, sir.
    Good morning, Chairman Pitts, Ranking Member Pallone and 
members of the subcommittee. And thank you for inviting me 
today.
    My name is Marshall Summar. I have the good fortune to be 
the Chief of Genetics and Metabolism at Children's National 
Medical Center here in Washington, D.C.
    I have been working in the field of rare diseases for the 
last 29 years, and I am here today in my capacity as a member 
of the Board of Directors of the National Organization of Rare 
Disease and Chair of the Scientific Advisory Committee of NORD.
    On behalf of the estimated 30 million individuals with rare 
diseases, NORD thanks you in the Energy and Commerce Committee 
for your continued strong support of the rare disease 
community. You have made a huge difference for us.
    NORD's a unique federation of over 200 patient advocacy 
groups, clinicians, researchers, dedicated to helping people 
with rare diseases.
    NORD provides resources, research advocacy, education, 
community and infrastructure support to the rare-disease 
community that small individual organizations cannot. It is the 
nature of rare diseases. They are small.
    NORD was founded in 1983 and played an active role in the 
passage of the Orphan Drug Act, which is a successful model of 
how to incentivize the development of treatment that saves 
lives.
    Data show that years of life lost to rare diseases declined 
at an annual rate of 3.3 percent after the Orphan Drug Act due 
to the development of new treatments.
    Without these new drugs, if you take them out of the 
equation, the number of years of lives lost should have 
increased at about a 1 percent rate per year. So it has made a 
real impact on our patients.
    Speaking personally, without these treatments, many of my 
patients would not be here. I thank you for what you have 
already done.
    These efforts represent a good beginning, but there is much 
more we can do to improve the lives of our patients, and NORD 
views the 21st Century Cures Initiative as a great way to do 
this.
    NORD's long advocated increased involvement of patients in 
the drug development process. We appreciate the commitment by 
many at the FDA to increase patient involvement, but believe 
much more needs to be done to make patients feel they are 
partners in the process. NORD will continue to work with the 
FDA to advance the patient role in the development and approval 
process.
    We have developed a series of recommendations that we 
believe will advance not only the development of new orphan 
drugs and devices, but non-orphan ones as well. We look forward 
to discussing these ideas with the committee as the 21st 
Century Cures Initiative continues.
    Permit me to focus on two of our recommendations.
    First, we support the establishment of a commission and 
national plan to determine priorities, methods, resource needs 
and a consistent agenda on rare-disease registries and natural 
history studies.
    They have got a lot of variation. They tend to be all over 
the map. To assess the drug's efficacy, we need the information 
on the existence, frequency, and severity of clinical findings. 
This information is needed before a clinical trial can begin.
    We encourage the creation and maintenance of programs to 
create, curate, and standardize registries and national history 
studies which can generate this needed data.
    This could be one of the most important accelerators of the 
treatment development and monitoring process. These registries 
can also be used in the post-approval process as well.
    This is an area where patients can have a major and cost-
saving impact on the process. Patient-entered data has been 
shown to be accurate and useful when collected properly.
    Creative hybrids using physician-, patient- and other 
health professional-collected data can greatly speed the 
understanding, discovery, approval and monitoring process.
    In collaboration with the NIH and FDA, NORD has built and 
is in the process of testing a rare-disease patient-driven 
registry national history program. The NIH's Rare Disease 
Clinical Research Network has already demonstrated the benefits 
of this approach.
    In a registry I have been involved with, we have had 
approval of three drugs over a 10-year period with only 700 
patients. So it definitely has accelerated the approval process 
for us.
    The Patient Centered Outcomes Research Institute is 
developing these statistical methods and models to use data 
from rare-disease patient studies that will further refine this 
process.
    They are also involved in patient-driven registries through 
PCORnet and will begin working with NORD on our rare disease-
focused registry program. So we should have good input from 
multiple agencies.
    All of these efforts will help our patients, but a national 
plan and standards would help prevent duplicated effort and 
resources. This is what we truly need.
    The other thing we advocate is significant reform to the 
Institutional Review Board system. I have been working with 
this system for the last 30 years; so, I am pretty familiar 
with all of its manifestations.
    Currently, all clinical trials for new treatments, whether 
a drug, biologic or medical device, must receive approval from 
an IRB.
    Each institution and study site typically requires approval 
and protocol adjustment by its own IRB. With a large number of 
sites needed for rare-disease study, this is one of the 
greatest impediments and cost to clinical trials.
    NORD recommends that Congress develop legislation that 
would de-risk the process and foster the creation of an IRB 
system that is portable across institutions.
    The de-risking of the IRB process and the encouragement 
requirement of reliance agreements between institutions 
receiving Federal funding would save cost and time while 
accelerating the clinical trials and clinical research process 
greatly. This will significantly increase the pool of study 
sites and allow greater patient participation.
    These are just two of our recommendations. My written 
testimony includes the rest.
    And I on behalf of NORD, I thank the committee for allowing 
us to testify today.
    Mr. Pitts. Chair thanks the gentleman.
    
    [The statement of Dr. Summar follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
    
    Mr. Pitts. Thanks to all the witnesses for your opening 
statements. And we will now begin questioning.
    I will recognize myself 5 minutes for that purpose.
    Ms. Furlong, we will start with you.
    Do you believe your guidance collaboration with industry is 
a scaleable model that can be used in other conditions, 
specifically, where there are unique factors that make Duchenne 
muscular dystrophy guidance a special case in the multi-
stakeholder effort that you led with encouragement from the 
FDA?
    Ms. Furlong. Thank you, Chairman Pitts, for the question.
    I certainly think that this methodology and process is 
exportable to other rare conditions. How we started the 
guidance or initiated the guidance was to develop a steering 
committee that was representative of the stakeholders, which 
included patients, academia, as well as industry.
    From there, the steering committee identified several 
areas, seven working groups, actually, of things that they felt 
were relevant, to include diagnosis, biomarkers, clinical trial 
design, natural history, and benefit-risk.
    And then we further developed a CAB, which is the Community 
Advisory Board, so that would be--incorporate the entire 
patient voice and any individual or patient group that wanted 
to contribute to the development of the guidance.
    The standardization for the guidance was that it would be a 
reference document and that it would include documented 
evidence that was published or accepted for publication by the 
end of July.
    So we felt--and we are writing up the methodology--that 
this methodology is exportable. It was certainly an 
investigation and a thorough, thoughtful, reasoned look at the 
community and the nuances of Duchenne.
    But I believe that most rare diseases could do the same. 
Their issues may be slightly different and their progress to 
date might be slightly different, but it is certainly 
exportable.
    Mr. Pitts. Thank you.
    Dr. Beall, communication with patients to make sure they 
can make informed decisions about clinical trial participation 
is critical.
    How does the cystic fibrosis community communicate with 
patients about the various options? And how do you think we can 
best translate your good practices into the Cures Initiative?
    Mr. Beall. Thank you very much.
    First of all, because 90 percent of all of our CF patients 
are seen in a network of care centers and that we also have a 
Clinical Trials Network, there is a very close relationship 
between our physicians and the patients that are involved.
    And that is critical for the recruitment of patients in the 
clinical trials. It is critically important for showing them 
the value and the risk of participating in clinical trials.
    And it is that close association between the physician and 
the patient and the recruitment process in a very closed 
network that is critical. That is why I think Clinical Trials 
Networks are critically important.
    So we also have established within our Clinical Trials 
Network a data safety monitoring board independent of the 
Cystic Fibrosis Foundation, but it is made up of experts.
    And that provides a degree of assurance to every single 
patient that there is somebody looking out for their continuing 
interest and for any risk that may be inherent in any single 
trial.
    So I think all of these things, plus we have worked very 
hard to try to create a culture of participation and a 
responsibility that each patient, when you have a small patient 
population, needs to participate in the process. So I think it 
is that reassurance that is so important.
    Mr. Pitts. Thank you.
    Mr. Pops, what stage of drug development could most use the 
assistance of patient insight about benefit expectations and 
risk tolerance?
    Mr. Pops. Thank you for the question.
    It is actually the most exciting part of the whole 
opportunity, that it is every stage, actually from 
identification of new drug candidates, all the way through to 
determination of the value of the medicine after the completion 
of the pivotal clinical trials.
    And I think that is the whole idea of this framework, is 
creating a structure where we can get that input on a 
continuous basis, and I think it could fundamentally transform 
the way we approach these development programs.
    Mr. Pitts. Thank you.
    Dr. Lichtenfeld, you have discussed examples of cancer 
drugs that have recently been successfully approved by FDA 
through an accelerated approval process.
    Are there best practices that we can learn from cancer and 
how FDA is expediting the approval process for particular 
drugs?
    Dr. Lichtenfeld. Thank you, Mr. Chairman.
    When we talk about best practices, I think the question 
really came up with Dr. Woodcock earlier today: What is the 
oncology community doing that is different than other 
communities?
    Let's understand it is a complex process in the sense that 
we have research that has been building literally for decades 
that has produced very exciting results that is actionable and 
companies are standing up to create drugs for the targets that 
we are finding for the new immunotherapies for genetic disease, 
what have you, genetic markers. So we are, in a sense, at an 
interesting and turning-point kind of place.
    But important, relevant to your question, the Office of 
Hematology Oncology Products has also stepped up to the plate. 
And as was mentioned earlier, the oncology community 
appreciates the efforts of the FDA staff to reach out to the 
patient community, to reach out to the pharmaceutical 
community, to reach out to those who do clinical trials, to be 
active participants, to be at the table.
    Lung-MAP was cited several times. The American Cancer 
Society was grateful to be able to have contributed to that 
effort, among many other organizations.
    But the FDA has become an active partner with the process. 
And so I don't know if that is a best practice or a best 
example. But it is that source of communication.
    But let's not forget it is also the opportunity because we 
are now in a place that we only dreamed of just a short while 
ago.
    Mr. Pitts. The chair thanks the gentleman.
    My time has expired.
    The chair recognizes the ranking member, Mr. Pallone, 5 
minutes for questions.
    Mr. Pallone. Thank you, Mr. Chairman.
    My questions are of Mr. Beall.
    The Cystic Fibrosis Foundation has done some great 
collaborative work that has resulted not only in successful 
marketing of Kalydeco, but also the recent positive test 
results of a complementary drug that may extend treatment to 
nearly half of all patients with CF. And, of course, I commend 
you for your efforts.
    But I wanted to ask you about a couple of points in your 
testimony. In your remarks, you spoke about the CF Foundation's 
strong relationship with the FDA and the importance of bringing 
good data to the table when consulting with the FDA, which I 
know is true. And I would like to hear more about that 
relationship.
    Obviously, we are hearing a lot today about the need for 
FDA to do more to seek and incorporate patient input into its 
review process.
    So the basic question, Mr. Beall, is: Can you tell us more 
about the CF Foundation's interaction with the FDA? And are 
there any lessons that can be learned by other disease groups?
    Mr. Beall. Well, I can give you a perfect example because, 
on Wednesday of this week, we had three officials, including 
Dr. Robert Temple, who is in the drug division at our offices, 
talking about the development of clinical trial protocols of 
drugs that might not enter into clinical trials until 3 to 5 
years from now.
    So that is a perfect example of this open discussion. 
Because we have a natural history of the disease. We know that 
the drugs that we have tested are treating the basic defect. We 
know the mechanism of action. We have a safety profile.
    And now we can start to talk about the future. And I think 
it is that kind of example. And that goes back many, many 
years.
    Soon after we discovered the CF gene, we talked about gene 
therapy and we had extensive dialogues with the FDA, not only 
with manufacturers, but with the FDA and the Foundation.
    So I could just say that we have always had a wonderful 
collaboration. We have data. We have natural history of the 
disease because of the patient registry.
    And, again, we come with data and we come with experience 
and we come with the networks that can make these things 
happen.
    So I just gave you an example. That was the example.
    Mr. Pallone. No. That is fine.
    We are hearing a lot about the various expedited drug 
review processes at FDA, and it is clearly a push by many to 
get the Agency to use these pathways more frequently and in 
more disease areas. And I share the goal of speeding the 
therapies to patient at the earliest possible time.
    But I think we need to be cognizant of the risks that could 
accompany that speed, and we especially need to be concerned 
about such risks if we are ultimately thinking about somehow 
requiring more frequent use of these expedited pathways through 
legislation. And I know you share that concern.
    Your testimony mentions the health risk that could result 
from approving therapies based on early data that needs more 
vigorous study, but you also describe the possibility that 
these kinds of approvals could endanger progress toward the 
development of other treatments.
    Can you just elaborate on both of those concerns, if you 
would.
    Mr. Beall. Well, certainly, one of the things when you are 
dealing with a small population--and now we are talking about 
personalized medicine where you may only have 25 patients with 
a certain genotype that may be approachable or therapeutic 
opportunities for that particular drug--if those patients were 
introduced to a drug that was less than effective, what happens 
when the next drug that could be effective--how do you do the 
clinical trial?
    So I think that is really very critical because we want to 
make sure that our first introduction is drugs that are 
efficacious, and then we move forward to the next level. 
Because then you really are depriving, if you don't have safe 
drugs, of developing good drugs and effective drugs that could 
move us above the therapeutic options that we have.
    So I think that that is the critical thing that we always 
face. There is always the risk. But now we are dealing with 
small populations, personalized medicine. Maybe there is only 
going to be 6, 10, 1,000 patients.
    So I think you have to be particularly critical on that 
issue with rare diseases.
    Mr. Pallone. OK. Yes. I just wanted to echo another point 
you made in your testimony about the importance of resources.
    And I couldn't agree more, that, as you say, FDA needs 
resources to ensure that they can rely on the best regulatory 
science available and they need adequate resources to enable 
them basically to meaningfully engage with the patient 
community.
    And we have this 21st Century Cures Initiative, which is 
progressing now. We have had some sort of larger meetings and 
now some hearings. And my colleagues always ask what can 
Congress do.
    And I think that the most effective thing we can do is 
provide adequate resources to make sure that FDA, as well as 
NIH, have the resources to fulfill the expectations we have for 
both agencies.
    And I hear not only from the agencies, but, also, from my 
constituents, that they don't have enough resources. So I just 
wanted to echo again what you said.
    Thank you, Mr. Chairman.
    Mr. Pitts. The chair thanks the gentleman.
    I now recognize the vice chairman of the subcommittee, Dr. 
Burgess, 5 minutes for questions.
    Mr. Burgess. Just before my time starts to run, could I 
make a unanimous consent request?
    Mr. Pitts. You may proceed.
    Mr. Burgess. I would like to move that the committee make 
people aware that, if someone wishes to contact or communicate 
with the Cures Initiative, it is [email protected].
    I know there are many people watching who think, ``I would 
like to interact with the committee staff.'' So that is the way 
to do it.
    Mr. Pitts. Thank you.
    Without objection, so ordered.
    Mr. Burgess. Very well. I knew they wouldn't deny me.
    Let me ask Ms. Furlong. You were kind enough to mention the 
work on the MD CARE Act, and thank you for that. As you know, 
we will likely be marking that up next week. So that is a big 
milestone.
    Can you talk about how the MD CARE Act needs updating and 
the type of updating that this committee has pursued?
    Ms. Furlong. Certainly. And thank you for the question, Dr. 
Burgess.
    The MD CARE Act was the solid foundation that set Duchenne 
and the muscular dystrophies--really galvanized their progress.
    So the MD CARE Act was enacted in 2001 and reauthorized in 
2008. And right now the amendments are really to look at what 
we have learned in the meantime.
    So the cardiac issues in Duchenne muscular dystrophy are 
real and they have to be tackled in order to answer the 
question. As you look at these potential therapies that were 
hopeful to be approved in the next months and years, they 
extend function. Will they protect or have a negative effect on 
the heart?
    So it is the gaps that we need to really look at with the 
amendments, in addition to the fact that, when this legislation 
was enacted in 2001, young boys with Duchenne didn't live to be 
adults.
    So now we have an adult population and we need to really 
address those adults in terms of their medical care and, also, 
to incentivize and understand how to treat them, how to 
encourage them to have long and independent lives as they 
become adults and reach for their dreams.
    So I think that the MD CARE Act is now looking with the 
muscular dystrophy committee from the NIH and other agencies. 
Their research plan has to be updated and these amendments to 
be incorporated so that we are really achieving the full effect 
that the MD CARE Act was initiated for.
    Mr. Burgess. Thank you.
    And of course, Mr. Beall will also acknowledge that the 
population of patients is changing because of some of the 
successes that have happened over the past several years.
    And in both of those illnesses, both cystic fibrosis and 
muscular dystrophy, it is important that we keep pace with the 
way the patient population is changing.
    We want people to live longer and fuller lives with their 
conditions and, at the same time, we don't want the legislation 
then to stymie that. So it is, in my opinion, an important step 
forward.
    Dr. Beall, we talked--or you talked about the development 
of mutation-specific therapies and the next evolution in 
precision medicine and you could see the cystic fibrosis 
example impacting the way we address other serious illnesses.
    Is there something more you would like to add to that?
    Mr. Beall. Well, again, we are clearly in the age of 
personalized medicine. Fortunately, with the completion of the 
human genome, we understand the genetics of so many more 
diseases and genetic diseases that it is a very critical time 
for us.
    Mr. Pitts. Microphone.
    Mr. Beall. Not on? OK.
    I just saw Dr. Collins downstairs, and he is excited 
because he was one of the discoverers of our CF gene.
    So we live in a very unique age, and I think more and more 
therapies are going to be directed towards specific mutations.
    And that is one of the reasons that we have to have these 
kinds of patient registries, so we can start to identify those 
mutations.
    When Vertex felt that they had a drug that might work on a 
certain mutation, the small drug that came out, G551D, we were 
willing--we were able to tell them in the United States we have 
1,100 of those patients within 5 minutes after they asked us 
because of a patient registry, because we have a documented 
history of the disease.
    So I think that is why it is very important to have 
personalized medicine, therapies and the options for that, but 
it is also--we have to be able to document the patients that 
can participate in the trials.
    Mr. Burgess. Yes. It is very powerful.
    And, of course, you referenced to the 1965 registry. In 
1965, you didn't know that we were going to know about the 
sequence of the human genome 30 years later.
    Mr. Beall. Well, but we have been able to document it. 
Today we have 26,000 patients whose data is provided to our 
patient registry every single year.
    Mr. Burgess. Let me ask you a question. I am going to run 
out of time pretty quickly. But--and this is either for Mr. 
Beall or Mr. Pops.
    The world is different now and you have people that are 
perhaps lucky enough to enter into a clinical trial and they 
are likely to perhaps have friends with the same condition.
    So in the old days, a randomized clinical trial, you 
wouldn't know which arm to which you were randomized, who was 
getting the target or study drug, who was getting either an 
older therapy or no therapy. But now people communicate. 
Facebook. Twitter. They are likely to be Facebook friends.
    How is that going to impact the ability to have a blind and 
randomized clinical trial? Are people likely to communicate 
with each other, I mean, look, ``I am getting a lot better on 
this stuff. How about you?'' ``Wait a minute. I haven't seen a 
darn thing''?
    Mr. Pops. I think it is a real question. It is a real issue 
because--and you can't pretend that it is not going to happen.
    This is already happening, particularly as you get large 
cohorts of patients in randomized studies in multiple 
countries. They are all communicating.
    So I think it is very important that we be really rigorous 
in maintaining the blind to the extent that we can.
    Mr. Burgess. To the extent that we can. But, also, we 
probably need to embrace the fact that the information is out 
there and being communicated and, to the extent that it can 
further enhance what we are doing----
    Mr. Pops. So let's take advantage of it.
    Mr. Burgess. Yes.
    Mr. Pops. Let's do more in the aftermarket. Let's approve 
drugs and collect this information and get a more nuanced view 
of the drugs' use in the real world and turn it to our 
advantage.
    Mr. Beall. And, in some cases, it is going to make it 
easier to do clinical trials when you can have large networks 
that exist out there, when they can report patient-reported 
outcomes and things like that.
    So I think sometimes it is looked at as a disadvantage, but 
we ought to turn it--as Mr. Pops just said, we ought to turn it 
to an advantage because I think it can expedite the ability to 
do clinical trials as we move forward with the technology.
    Mr. Burgess. Great. Thank you.
    Ms. Furlong. And it should expedite post-hoc analysis so 
that we can see the long-term effects. Because in a clinical 
trial of 12 months, for instance, plus or minus, you might not 
see the full effect of a drug that is multisystemic. So it will 
enable us to understand the full impact on the patients' lives.
    Mr. Burgess. Thank you, Mr. Chairman. I yield back.
    Mr. Pitts. The chair thanks the gentleman.
    Now recognize the gentlelady from Illinois, Ms. Schakowsky, 
5 minutes for questions.
    Ms. Schakowsky. Thank you very much.
    I had a question for Dr. Lichtenfeld--actually, for anyone 
on the panel that wants to comment on this.
    This is about quality-of-life outcomes. I mean, obviously, 
if this is a known life-threatening disease, you want to do 
everything you can to make sure that the therapies match the 
disease.
    But there are--you would say, when these quality-of-life 
outcomes are rigorously measured and supported by the FDA, they 
can and should be included in drugs' labeling and can by 
themselves be a basis for a drug's approval.
    I certainly know people who have suffered so much from side 
effects of drugs. And I just wonder, in the whole process of 
drug approvals, how much are these quality-of-life issues 
really looked at? As a basis for approval or just as a basis of 
whether or not they are used?
    Dr. Lichtenfeld. Thank you for your question.
    In fact, it is a work in progress. Let's understand that 
quality of life is a buzzword today, but it wasn't a buzzword 
very recently.
    So as we look at the issues, shall we say, of palliative 
care, of supportive care, quality of life, issues that the 
American Cancer Society and many others have been involved in, 
it is relatively new to the table.
    Having said that, there have been issues recently with one 
particular drug where, had the question really centered around 
was the--even though the drug may not have met the FDA 
standard--and this was about 2 years ago--even though it had 
not met the FDA standard, did it meet the quality-of-life 
standard? Did it improve the quality of life of the--it 
happened to be a breast cancer drug--for the women who took it?
    Because that would have been an important consideration. 
And, unfortunately, the quality of the data measuring quality 
of life was inadequate.
    So going forward, cancer patients have enough on their 
plates, as do everyone represented at this table, as do 
patients throughout this country. We need to be aware that 
quality of life is an important part of the treatment process, 
and we need to have tools in place.
    They are not uniform yet. They are not as good as we would 
like. But they have to be in place to measure quality of life, 
and that has to be considered. And patient-reported outcomes 
are very much a part of that process.
    Ms. Schakowsky. Yes. Go ahead, Doctor.
    Mr. Pops. I just wanted to make a comment as it relates to 
patients with chronic disease as well. We talked a lot about 
cancer and orphan, small diseases.
    We work in the field of chronic disease--schizophrenia, 
depression, addiction--where patients are taking medicines for 
long, long periods of time.
    And simple things that may seem prosaic to the researcher, 
like nausea----
    Ms. Schakowsky. Sure.
    Mr. Pops [continuing]. Fatigue, propensity to get addicted 
or dependent on the drug, these are really important inputs 
that we want to hear from patients about.
    Ms. Schakowsky. And is that part of the process?
    Mr. Pops. It is less part of the approval process today 
than I think it will be in the future. It is certainly part of 
the utilization process as patients make a determination, 
``Which medicine do I want to stay on for years and months?'' I 
think that is a critical part of it, but it is not really 
incorporated in the consideration of the approval.
    Ms. Schakowsky. Especially where all things might be equal 
in effectiveness, whether or not something causes nausea, 
fatigue, could be really important.
    Mr. Pops. That is right. Particularly if you are launching 
a new medicine into a large category where there might be an 
abundance of generic drugs that are safe and effective, but 
might not hit all of those parameters for certain subsets of 
patients for long periods of time.
    And we just want people to be sensitive to the fact that, 
from the patient perspective, there are differences between the 
medicines.
    Ms. Schakowsky. Right.
    And then, also, Dr. Lichtenfeld, I wanted to ask you about 
small-sized trials. And you mentioned one of the drawbacks.
    I had talked about the extent to which women aren't 
considered. And I would just be concerned--I understand the 
plus. I do. But if we rely too heavily on them, isn't there the 
real risk of excluding important populations?
    Dr. Lichtenfeld. Well, the answer is yes, there is a real 
risk of excluding important populations.
    In fact, when you talked about women and heart disease, I 
remember back in the early 1990s when the article came out 
talking about the absence of women in clinical trials for the 
treatment of hypertension and heart disease. So this is an 
issue I am aware of.
    But let's talk about the other side of the coin, and that 
is, when you are sitting--I have sat in the presentations at 
ASCO, at oncology meetings--and you see a presentation of 80 
patients and you see what we call waterfall plots--basically, 
the responses in survival that occur--and suddenly, 70 percent 
of those patients are having significant responses, In a 
disease where there was no treatment before, I don't think one 
asks the question--they ask the question in followup, but not 
at the moment.
    And what has happened and what has been exciting to me is I 
am now sitting in those presentations every June and I see--I 
wrote about it--it took a year for one of the drugs to go from 
clinical trial to approval because it was that effective in the 
disease where there was no other treatment available. That is 
pretty spectacular. That is new thinking. That is a new 
approach.
    Now, we have learned more as time has gone on. Yes. Doesn't 
mean we have stopped learning, as was mentioned before about 
cystic fibrosis. But when you suddenly see moments like that, 
no one would want to hold back. Develop the data, yes, but 
don't hold back the opportunity.
    In fact, even a phase 1 trial that was presented at this 
ASCO meeting in June, the company, actually--well, not the 
company, but ASCO in the press release indicated the company 
was willing after a phase 1 trial to put it into compassionate 
use. And that is pretty amazing, a major change in the way that 
traditionally we have seen cancer drugs move through the 
pipeline.
    Ms. Schakowsky. Thank you.
    I have overstayed my time. Thank you.
    Mr. Pitts. Sure. Thanks to the gentlelady.
    I now recognize the gentleman from Virginia, Mr. Griffith, 
5 minutes for questions.
    Mr. Griffith. Dr. Lichtenfeld, let's pick up there, because 
I think that that compassionate use is something that--we 
really need to be figuring out how we can make it more 
effective and how we can do it faster at the Federal level.
    You talked about in your testimony that patients needed to 
be involved both on saying what kind of nausea they had and 
what the pain levels were and so forth, and I agree with that.
    But I also think that, particularly when you have no 
treatment, that patients need to be involved in that, too. And 
as Ms. Furlong said earlier, when there isn't a treatment, you 
are much more willing to take those risks than you would be if 
there is some other treatment out there that might work, but 
this might be a little more comfortable.
    And I want to give both you and Ms. Furlong an opportunity 
just to address that further.
    Dr. Lichtenfeld. Well, thank you. And I appreciate the 
question, and I know you mentioned it earlier.
    It is a complex issue. It is not a new issue. As you may 
well be aware, it has been around for some time with the number 
of drugs that have gone through the pipeline, which seem to 
show some opportunities. Various state legislatures are 
involved.
    And I am sitting here today both as a representative of the 
Society, but also as an individual, and understand that there 
are discussions on both sides of that issue and they are 
complicated.
    Bottom line is that we need to understand what drugs work 
when they work. We need to understand that patients need to 
have access to promising drugs as soon as possible.
    Companies make those decisions as to how they are going to 
handle that process. The FDA, as a matter of fact, has approved 
almost all of the applications they received. And we need to 
have those discussions to come to a better resolution about how 
to address that issue.
    Mr. Griffith. And what I would say is that whatever we can 
do--I think I speak for a lot of the members of the committee--
I am probably a little more out there than some--but whatever 
we can do to help by changing the law to expedite that process, 
we will do.
    Dr. Lichtenfeld. We would be glad to have those discussions 
on behalf of the Society, sir.
    Mr. Griffith. Ms. Furlong, did you want to make another 
comment about risk assessment? Because, obviously, when your 
boys were sick, you probably would have taken anything that had 
any promise of hope.
    Ms. Furlong. I think I could tell you stories about looking 
in China to see some tea that you might be appalled about, but 
that was long ago.
    I think it really is up to the companies. FDA has always, 
to my knowledge, at least in the Duchenne and other fields, 
been willing to entertain and talk about compassionate use.
    I think for the rare disease community this really talks 
about and gets us back to trial design.
    In general, trials are designed to test a small subset of 
patients. In the Duchenne community, the 6-minute walk test is 
the standard primary outcome measure.
    So that means, as a child with Duchenne, you have to walk 6 
minutes and even further, as we learn more about the testing. 
It is a very narrow subset of people within a certain framework 
of that 6-minute walk test, which, as you can imagine, leaves a 
great number of people outside the trial.
    So I think trials have to be designed that are inclusive 
and welcoming of people that live with the spectrum of the 
illness, both very young as well as adults with very limited 
functional ability.
    That way, we can test those in those populations. We can 
have labels that are broad and then provide access to all. So I 
think that might be a better solution.
    Mr. Griffith. Thank you.
    I look forward to working with you all.
    And, with that, I yield the remainder of my time to Dr. 
Burgess.
    Mr. Burgess. I thank the gentleman.
    Dr. Lichtenfeld, I just wanted to follow up with you 
because your specialty has been involved in this type of 
activity probably longer than any other branch of clinical 
medicine, going back to 1955 when the developmental 
therapeutics program was put into place at the National Cancer 
Institute.
    So with that breadth of experience within your specialty, 
are there things that you want to share with others about what 
that experience has taught you?
    Dr. Lichtenfeld. Well, what we did back in 1965 or whenever 
was a lot different than what we are doing today. I don't want 
to take the time to really go into it. You may be aware of it.
    But here is the message. It didn't happen overnight. It 
took 40 years of research to get us to the tipping point where 
we understood the genome and had the opportunity to take 
advantage of that and move forward.
    Immunotherapy, the same story. It has taken us 40 years. 
That was a substantial amount--I don't want to underestimate 
the value of research investment to get us to the point where 
we are, where suddenly we look like we have so much to offer 
and to do.
    I also comment, with regard to my co-panelists, that they 
have populations and they have demonstrated that finding the 
patients where they are is critically important.
    We have a substantial amount of work to do to understand 
not only the clinical trial mechanism, but also the medical 
practice system, so we can make sure that patients and 
communities--I live in a small town in south Georgia--that my 
friends have opportunities to get these drugs in clinical 
trials and be part of that process. There is a lot of work to 
do.
    Mr. Burgess. Thank you, Mr. Chairman. I yield back.
    Mr. Pitts. The chair thanks the gentleman.
    Now recognize the gentleman from New York, Mr. Engel, 5 
minutes for questions.
    Mr. Engel. Thank you, Mr. Chairman and Mr. Pallone, for 
holding this hearing. I am pleased to have this opportunity to 
further consider how patient perspectives can best be 
incorporated into the therapeutic development process.
    As the author of the ALS Registry Act and the Paul D. 
Wellstone Muscular Dystrophy Community Assistance Research 
Education Amendments of 2008 and 2013, along with my colleague, 
Dr. Burgess, I have worked to be a voice with those with rare 
and orphan diseases.
    I am encouraged by the advances we have made into the 
causes and mechanisms of these diseases, as well as our 
progress toward treatments, but, obviously, we still have a 
long way to go.
    One of the most striking gains we have made is for 
individuals with Duchenne muscular dystrophy. As Ms. Furlong 
mentioned, our efforts have added an average of 10 years to the 
life expectancy of boys with Duchenne. And now, as life 
expectancy increases, we face new challenges in finding 
effective therapies.
    The patient community brings an important perspective and 
understanding to this process, and I am interested to see how 
we can best use that knowledge to assist medical researchers 
with therapy developments.
    So, Ms. Furlong, let me ask you this. I am particularly 
interested in the way the Duchenne patient community is engaged 
with the FDA to help inform the benefit-risk determinations 
made by agency reviewers, as well as the Duchenne community 
guidance document you referred to in your prepared testimony.
    Could you please comment on how you hope to see these 
efforts affect the therapeutic pipeline and the various 
stakeholders who are part of that pipeline.
    Ms. Furlong. Yes. Thank you, Mr. Engel, for the question.
    The benefit-risk really originated out of discussions with 
the FDA because, in our early discussions, it was known that we 
were telling anecdotal stories that the equation of benefit-
risk was different in, for instance, Duchenne muscular 
dystrophy than perhaps some more common disease.
    And in that the FDA suggested to us that they agreed, but 
they didn't have anything they could rely on, any quantified 
evidence-based document that could help them make those 
decisions.
    So we agreed to go out on benefit-risk and did the pilot 
with 120 parents. We learned that their priority is disease 
stabilization and they were willing to accept a great deal of 
risk. In fact, they are living with a great deal of risk, as 
they know that their child has a fatal illness.
    So the FDA has now asked us to expand that study to a 
greater number of patients than 120 patients and, also, to ask 
these questions of the young men with Duchenne. Our hope is 
that they will incorporate it into the review process and they 
will demonstrate to us how and when they use it and when they 
don't and what makes sense for them as they make their 
decisions.
    Mr. Engel. Thank you. And thank you for your advocacy and 
hard work. It is very much appreciated.
    Dr. Summar, can you talk about the role you think the 
patient perspectives should play in developing therapies for 
diseases like ALS and muscular dystrophy that have limited 
treatment options and for which quality of life is, obviously, 
an especially important factor to patients.
    How can the FDA best consider the views of patients and 
families when examining the benefit-risk calculus for these 
diseases?
    Dr. Summar. Thank you for that question, Mr. Engel.
    This really kind of expands across the entire field of rare 
diseases, but your question is particularly relevant for those 
two groups.
    Patients often tell us about things that they wish were 
better that we never thought of. One of the things I have run 
across time and time again is, when we go and ask our patients, 
``What is the worst part of this disease?''--a lot of times it 
is parents in the case of pediatric patients--they will list 
some things. And sometimes the things we thought were most 
important are number nine or ten on the list.
    So I think, when we look at what our therapeutic targets 
are, what our quality-of-life targets are for these diseases, 
patient and family input is a huge factor, and I think it is 
something we can incorporate a lot better than we have.
    I think during the early stages, particularly when we are 
designing our pivotal trials, clinical trials, looking at what 
end points are--I think that those are going to become more and 
more important.
    And the other thing, of course, is the small group sizes 
with these. Many times it is hard to pick one single outcome 
variable that you are going to be able to achieve.
    The smallest study I have been involved with was five 
patients for an approval process. Getting one exact target for 
that--fortunately, the effect of the drug was massive; so, we 
were able to do it. But if it had been milder, I might have 
needed more than one outcome variable.
    So I think families can help us determine what is important 
there. They can help us, also, as we talked about with some of 
what risk is tolerable in those situations. It is different. 
And there are 7,000 different rare diseases. Each one of these 
is unique in its own regard. But there are some commonalities 
like that.
    Mr. Engel. Well, thank you. And thank you for your 
comments, and also thank you for your interest.
    And I want to thank the panel for a very interesting 
discussion.
    Thank you, Mr. Chairman.
    Mr. Pitts. The chair thanks the gentleman.
    Now recognizes the gentleman from Florida, Mr. Bilirakis, 5 
minutes for questions.
    Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
    And I thank the panel for their testimony today.
    I know we have been talking about this and you have had an 
opportunity. I want to give you more of an opportunity to 
respond on this.
    On Wednesday, I asked one of the witnesses about his 
statement in including patients in the clinical trial process, 
but I want to make sure that you all have every opportunity to 
respond to this.
    If patients had a greater role in clinical trial design--
and I know you have touched upon this--if trials measured 
qualitative data from patients like, ``How do you feel?'', ``Is 
it less painful?'', what have you; ``How would things be 
different?'' and ``What would you like to see?''
    We will start with the----
    Mr. Beall. I would like to start.
    First of all, the patient-reported outcomes I think has 
been part of every clinical trial in cystic fibrosis for the 
last 10 or 15 years. Some of the tools are not the best at this 
point, but we are working to refine them.
    We have just spent as a Foundation a large effort to look 
at the patient-reported outcomes as a kind of specific 
validated tool for CF, and it is going to be submitted to the 
FDA and go through a validation process. In the past, we have 
used one that was generally for lung disease, but it may not be 
specific.
    So this is a science that is evolving. A decade ago or 15 
years ago, 20 years ago, PROs were not really incorporated.
    So it is a science that is evolving, and it has to be 
evolved not only with the FDA, it has to be evolved with the 
sponsors, too, because they have got to be willing to 
incorporate those into the clinical-trial process.
    So I am encouraged by the process, but I will tell you 
the--just in this last trial we had where their lung function 
went up and the exacerbations went down, we didn't have a 
statistically significant improvement in the patient-reported 
outcomes.
    Because when you are starting to treat the basic defect, 
you are treating the whole disease process and you are looking 
at extending lives.
    And the patients may not feel that from day to day, but 
over years, you may have a tremendous impact on those patients. 
So it is a tool that can be used, but it shouldn't be used 
exclusively.
    Mr. Bilirakis. Thank you very much.
    Ms. Furlong, do you have a response?
    Ms. Furlong. Sure.
    So I agree with Dr. Beall. And patient-reported outcomes 
are incredibly important, but I think this is where involving 
the patients in the design and conduct of clinical trials is 
really going to be important.
    Because, for instance, how do we measure energy and 
endurance? How do we know that turning over in bed is important 
to patients as opposed to an outcome measure such as the 6-
minute walk test?
    So I think things are important to patients that have a 
real effect on their lives. For instance, as you can imagine, 
if a boy can still text at the age of 18, that gives him 
independence. If a child can walk up a single step, they can 
enter buildings. If a child can roll over in bed, that makes 
the families' quality of life overall, in general, much, much 
better.
    So I think the use of patient-reported outcomes and 
including the patient voice in the discussion about what the 
clinical trial looks like and what the measurements are, both 
primary and secondary, is going to be incredibly important.
    Mr. Bilirakis. Thank you so much.
    Mr. Pops, do you have a comment or----
    Mr. Pops. I think these outcomes are so critical. In the 
world that we are developing drugs in, which is in psychiatry 
often, in schizophrenia, depression, addiction, the end point 
of the clinical trial--the hard end point is asking people 
essentially how they feel.
    And so how you feel is typically embodied in the set of 
validated scales, but those often don't capture some of the 
most important parts of how they actually feel over time.
    A perfect example might be an opioid dependence or an 
alcohol dependence, where a critical question the patients ask 
us when they take our medicine is, ``Is my craving going to go 
down? Am I going to crave this less? It may block the receptor 
and keep me from drinking, but is my craving going to change?''
    That was not a validated end point. That was something we 
couldn't incorporate in the label, but it is essential to the 
patient's perception of the disease.
    Mr. Bilirakis. Good point.
    Doctor?
    Dr. Lichtenfeld. About 4 weeks ago at ASCO, the oncology 
meeting, they showed a picture of a lady who was 96 years old 
who had received a phase 1 drug--that in itself is a 
fascinating point--whose cancer completely resolved.
    And on the bottom end of the before and after picture--on 
the after picture, you saw a trace of a little smile. And I 
noticed that smile and I tweeted it, actually. I took a picture 
and tweeted it and it got re-tweeted quite a bit. And then the 
lecturer said, ``Yes. That really is a smile'' in front of 
2,000 people.
    What I am trying to say by that example is that is what we 
have to be able to measure and aggregate in a scientific way to 
show that the treatments make a difference.
    One example of one lady in an unusual situation, but 
something that I think all of us agree--I would echo the 
comments that were already made--is so critical to 
understanding, particularly in the oncology world, what we do 
and how we do it and the goal that we have to have of improving 
quality of life.
    Mr. Bilirakis. Thank you.
    Dr. Summar?
    Dr. Summar. Yes. I will just use another example, too.
    We had a new medication we were looking at. Most of the 
patients with rare diseases are on the medicines they take for 
life. So it is every day, day in and day out. And these care 
plans are often complex and they really affect the whole 
family.
    So the new drug looked like it was promising from the 
standpoint of maybe a little bit better efficacy, a little bit 
better control, but it was five times a day instead of two or 
three times a day compared to the old one.
    And the families were like, ``Why would we add three more 
times a day of dosing for the small effect?'' And no one had 
really bothered to ask them that before we started.
    So I think there is all of these things that really getting 
the patient input early on is going to make a difference.
    Mr. Bilirakis. Thank you so much. Appreciate it.
    Mr. Chairman, can I ask one more question?
    Mr. Pitts. You may proceed.
    Mr. Bilirakis. OK. Thank you so much. Appreciate it.
    Dr. Beall, the CF Foundation's venture philanthropy model 
has produced incredible results. Congratulations. Your 
foundation found your breakthrough drug when it helped 
translate some of the early research through the valley of 
death, and now you have the Kalydeco.
    How are you able to establish this program? And how can 
other groups adopt this similar model?
    Mr. Beall. Well, it is a willingness to take risks. That is 
what you have to do in drug discovery. And we were frustrated 
by the fact that companies were not getting involved in the 
orphan diseases.
    So the whole concept here was to say, ``Take some of the 
risk out of biotech companies or pharmaceutical companies to 
get engaged in CF research.'' And, as I said, we spent $42 
million initially to start a high-throughput screening that led 
to Kalydeco.
    I think what is the most important and gratifying thing for 
the Cystic Fibrosis Foundation--and I know Ms. Furlong was in 
my office a number of years ago--and what we are seeing is so 
many other organizations are feeling the same impatience that 
our foundation felt 14 years ago in adopting this.
    One of the first times I talked about venture philanthropy 
at the bio meetings, we had 10 people in the audience. And now 
it is really becoming really inherent in what many voluntary 
health organizations are doing.
    In fact, FasterCures has been an organization that has been 
central to making some of that happen. There are law firms that 
specialize in it.
    So we love to share our ideas. We share our ideas all the 
time. And it has been very gratifying to our community that we 
happen to be fortunate enough to be able to start it because we 
had the resources. Bill and Melinda Gates gave us $20 million 
to start our program. We had other dollars to really make that 
initial investment.
    Mr. Bilirakis. Can you tell us how you successfully 
established the CF registry?
    Mr. Beall. As I say, it goes back a long time. But Dr. 
Zerhouni was here several years ago when he was the head of the 
NIH, and he says one thing about the CF community, it is a 
community with a culture of research.
    And every patient who goes to one of our care centers is 
asked, ``Do you want to participate in a patient registry?'' 
And I think it is 99.5 percent of the patients that say, ``Yes, 
I do'' and then signs the informed consent.
    So it is all part of the culture. It is part of the culture 
the organization creates. It is the physicians and it is the 
relationships and the recognition that it is an important part 
of having a disease because we can't cure this disease without 
their involvement.
    Mr. Bilirakis. Very good. Thank you very much. Appreciate 
it.
    I yield back, Mr. Chairman.
    Mr. Pitts. The chair thanks the gentleman.
    Dr. Summar, I didn't get to you in my round.
    On Wednesday, we heard an idea thrown out there that there 
are vast amounts of data available that are not being utilized. 
And we all know what an organ donor is. The idea was that we 
have data donors.
    Now, how would this play--and you mentioned the IRB system, 
the risk enterprise. What is your reaction to that?
    Dr. Summar. This is something we talk about when we are 
having coffee a lot.
    There are data sets all over the place. In fact, most of 
them end up usually lost when someone's computer gets recycled. 
We had a physician lose 15 years of data because his Excel 
spreadsheet didn't update.
    I think a way--find a way that balances, obviously, 
people's desire for confidentiality versus the irreplaceable 
and oftentimes irreproducible amounts of data that are out 
there. We really do need to find that balance.
    My reaction to that would be I would love to find a way 
forward with that. That one is going to--you can see a lot of 
sides to that question. But I definitely think it is worth 
looking at.
    And I think what we find is a lot of patients are like, 
``Yes. I will put it out there. I am fine with that.'' There 
will be a small core that won't. You can take a count for that. 
But I think most folks, if you ask them, saying, ``Would you 
feel OK if your data is out there so everybody can take a look 
at it?'' would be fine.
    You see people opening up their genomes, who had their 
genomes sequenced, saying, ``I will publicly post it along with 
my medical health history.'' A lot of folks want to help.
    Mr. Pitts. Thank you. Thank you.
    Mr. Burgess. I did that. We did that. I mean, that is a 
real thing that is happening right now. And, yes, privacy is 
something we all value, but it also is a voluntary 
relinquishing of a portion of that for the greater good.
    I think that is something we ought to not encourage--well, 
not encourage, but we certainly shouldn't stand in the way if 
that is an activity that----
    Dr. Summar. Right.
    Mr. Burgess. And unfortunately, I can't say that we don't 
always respect that, that we shouldn't stand in the way. But 
enough about that.
    Mr. Pitts. All right. The chair thanks the gentleman.
    That concludes the questions of the Members who are here. 
Another exciting, informative, very important hearing. Thank 
you so much for coming.
    Members will have followup questions, and we will send 
those to you. We ask that you please respond promptly. I remind 
Members they have 10 business days to submit questions for the 
record, and that means Members should submit their questions by 
the close of business on Friday, July 25th.
    I have a UC request, a statement for the record, from the 
National Health Council. Without objection, that will be 
inserted into the record.
    [The information appears at the conclusion of the hearing.]
    Mr. Pitts. Without objection, the subcommittee is 
adjourned.
    [Whereupon, at 12:19 p.m., the subcommittee was adjourned.]
    
    [Material submitted for inclusion in the record follows:]
    
    [GRAPHIC] [TIFF OMITTED] 
                                 [all]