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




  IMPLEMENTING THE 21ST CENTURY CURES ACT: AN UPDATE FROM FDA AND NIH

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON HEALTH

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                     ONE HUNDRED FIFTEENTH CONGRESS

                             FIRST SESSION

                               __________

                           NOVEMBER 30, 2017

                               __________

                           Serial No. 115-82






[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]










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                        energycommerce.house.gov
                                   ______
		 
                     U.S. GOVERNMENT PUBLISHING OFFICE 
		 
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                    COMMITTEE ON ENERGY AND COMMERCE

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

                         Subcommittee on Health


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




























  
                             C O N T E N T S

                              ----------                              
                                                                   Page
Hon. Michael C. Burgess, a Representative in Congress from the 
  State of Texas, opening statement..............................     1
    Prepared statement...........................................     3
Hon. Gene Green, a Representative in Congress from the State of 
  Texas, opening statement.......................................     4
Hon. Greg Walden, a Representative in Congress from the State of 
  Oregon, opening statement......................................     6
    Prepared statement...........................................     7
Hon. Fred Upton, a Representative in Congress from the State of 
  Michigan, prepared statement...................................     8
Hon. Frank Pallone, Jr., a Representative in Congress from the 
  State of New Jersey, opening statement.........................     9

                               Witnesses

Scott Gottlieb, M.D., Commissioner, Food and Drug Administration.    11
    Prepared statement...........................................    14
    Answers to submitted questions...............................    90
Francis Collins, M.D., Director, National Institutes of Health...    28
    Prepared statement...........................................    31
    Answers to submitted questions...............................   104

                           Submitted Material

Statement of the Healthcare Leadership Council, submitted by Mr. 
  Burgess........................................................    87 
 
  IMPLEMENTING THE 21ST CENTURY CURES ACT: AN UPDATE FROM FDA AND NIH

                              ----------                              


                      THURSDAY, NOVEMBER 30, 2017

                  House of Representatives,
                            Subcommittee on Health,
                          Committee on Energy and Commerce,
                                                    Washington, DC.
    The subcommittee met, pursuant to call, at 10:03 a.m., in 
room 2123, Rayburn House Office Building, Hon. Michael Burgess, 
M.D. (chairman of the subcommittee) presiding.
    Present: Representatives Burgess, Guthrie, Upton, Shimkus, 
Blackburn, Lance, Griffith, Bilirakis, Long, Bucshon, Brooks, 
Mullin, Hudson, Collins, Carter, Walden (ex officio), Green, 
Engel, Schakowsky, Matsui, Castor, Sarbanes, Lujan, Schrader, 
Cardenas, Eshoo, DeGette, and Pallone (ex officio).
    Staff Present: Ray Baum, Staff Director; Karen Christian, 
General Counsel; Kelly Collins, Staff Assistant; Zachary 
Dareshori, Legislative Clerk, Health; Paul Edattel, Chief 
Counsel, Health; Adam Fromm, Director of Outreach and 
Coalitions; Caleb Graff, Professional Staff Member, Health; Jay 
Gulshen, Legislative Associate, Health; Ed Kim, Policy 
Coordinator, Health; Bijan Koohmaraie, Counsel, Digital 
Commerce and Consumer Protection; Katie McKeogh, Press 
Assistant; Alex Miller, Video Production Aide and Press 
Assistant; Mark Ratner, Policy Coordinator; Kristen Shatynski, 
Professional Staff Member, Health; Jennifer Sherman, Press 
Secretary; Danielle Steele, Counsel, Health; Hamlin Wade, 
Special Advisor, External Affairs; Greg Zerzan, Counsel, 
Digital Commerce and Consumer Protection; Jeff Carroll, 
Minority Staff Director; Waverly Gordon, Minority Health 
Counsel; Tiffany Guarascio, Minority Deputy Staff Director and 
Chief Health Advisor; Jessica Martinez, Minority Outreach and 
Member Services Coordinator; Samantha Satchell, Minority Policy 
Analyst; Kimberlee Trzeciak, Minority Senior Health Policy 
Advisor; and C.J. Young, Minority Press Secretary.

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

    Mr. Burgess. The subcommittee will now come to order.
    The chair will recognize himself for 5 minutes for the 
purpose of an opening statement.
    The 21st Century Cures Act was a monumental achievement. 
Cures was the product of a bipartisan, multiyear effort by the 
Energy and Commerce Committee that brought our laws into a 
modern era of medicine. It has been nearly 1 year since Cures 
was signed into law. I remember remarking at that press 
conference a year ago to imagine a world in which government 
was not an obstacle but an ally in helping us deliver drugs and 
devices to patients and cures to patients. Today's hearing 
marks the Health subcommittee's first look into the 
implementation of what many in the healthcare community called 
a transformational bill that would positively impact not only 
the researchers and the scientists who are developing the 
latest breakthrough therapies, but physicians seeking treatment 
for their patients, giving hope to them, their loved ones, and 
other advocates.
    This morning we will hear from two leaders responsible for 
implementing the drug development and biomedical research 
provisions included in Cures. I want to welcome Dr. Francis 
Collins, the Director of National Institutes of Health, and Dr. 
Scott Gottlieb, Commissioner of the Food and Drug 
Administration, both back to this subcommittee. All of us know 
the demands your schedules put on both of you, and we 
appreciate you coming before us today.
    At the time of the Energy and Commerce Committee's launch 
of the 21st Century Cures initiative, the statement was made 
repeatedly that there were 500 cures and treatments to address 
10,000 known diseases. More progress was needed to alleviate 
the agony of an incurable disease.
    While the United States had maintained its global 
leadership in biomedical innovation, there existed a potential 
bridge in the growing divide between the revolutionary advances 
in science and technology and a less-than-adequate system for 
discovering, developing, and delivering new therapies.
    Members of the committee, both this committee and the 
Senate HELP Committee, held numerous public hearings, forums, 
roundtables in Washington, D.C., and around the country 
bringing together leading scientists and medical experts, 
patient and disease group advocates, and researchers across 
multiple sectors. The primary objective of these events was to 
uncover opportunities to strengthen and streamline the process 
by which cures are discovered and made available to patients. 
Cures accelerated the cycle of discovery, development, and 
delivery of new treatments and ensured that the United States 
remained at the helm of biomedical innovation.
    At the National Institutes of Health, the 21st Century 
Cures Act authorized resources to support biomedical research 
and reduce administrative burdens and provided almost $5 
billion in new funding to support the agency's four innovation 
projects. The Precision Medicine Initiative was authorized for 
$1.4 billion for the National Institutes of Health to build to 
a national biomedical dataset in order to accelerate health 
research and medical breakthroughs. The bill also authorized 
$1.5 billion for the Brain Research through Advancing 
Innovative Neurotechnologies Initiative to better understand 
the brain's physiology and to coordinate efforts across 
multiple Federal and private groups to expedite research for 
diseases like Alzheimer's.
    Cures also authorized $1.8 billion for cancer prevention, 
cancer diagnosis, cancer treatment and care through the Beau 
Biden Cancer Moonshot. Finally, the Regenerative Medicine 
Innovation Project was authorized at $30 million to support 
clinical research in the field of regenerative medicine in 
coordination with the Food and Drug Administration.
    The 21st Century Cures Act helped the Food and Drug 
Administration modernize the regulation of medical products 
throughout its lifecycle. It established the ``FDA Innovation 
Account'' and authorized $500 million in funding to implement 
Title III of the law, which included a broad range of 
deliverables from the Food and Drug Administration. These 
include creating a mechanism for the collection and 
incorporation of patient perspectives in regulatory 
decisionmaking, updating the way medical products are reviewed 
and approved, and advancing new drug therapies through a review 
pathway for biomarkers and other drug development tools to help 
shorten the development time while maintaining the same 
rigorous standard for safety and effectiveness. It also 
required the Food and Drug Administration to establish 
standards and definitions necessary to develop regenerative 
medicines.
    Before I close, I recognize the 21st Century Cures Act also 
touched upon other critical healthcare priorities, such as 
mental health and health information technology. Both of these 
areas should have their own separate hearings because of their 
importance to the medical community, and those are on the list 
for the very near future.
    I again want to welcome our witnesses and thank you for 
being here. I look forward to your testimony.
    My time has expired, and I will yield to the gentleman from 
Texas, Mr. Green, the ranking member of the subcommittee, 5 
minutes for an opening statement, please.
    [The prepared statement of Mr. Burgess follows:]

             Prepared statement of Hon. Michael C. Burgess

    The Subcommittee will come to order.
    The Chair will recognize himself for an opening statement.
    The 21st Century Cures Act (Cures) was a monumental 
achievement. Cures was the product of a bipartisan, multi-year 
effort by the Energy and Commerce Committee that brought our 
laws into a modern era of medicine. It has been nearly one year 
since Cures was signed into law. Today's hearing marks the 
Health Subcommittee's first look into the implementation of 
what many in the healthcare community called a transformational 
bill that would positively impact not only the researchers and 
scientists who are developing the latest breakthrough 
therapies, but physicians seeking treatments for their 
patients--giving hope to them, their loved ones, and other 
advocates.
    This morning we will hear from two leaders responsible for 
implementing the drug development and biomedical research 
provisions included in Cures. I want to welcome Dr. Francis 
Collins, Director of the National Institutes of Health, and Dr. 
Scott Gottlieb, Commissioner of the Food and Drug 
Administration, back to this subcommittee. All of us know the 
demands of your schedules and appreciate both of you coming 
before us today.
    At the time of the Energy and Commerce Committee's launch 
of the 21st Century Cures Initiative, there were only 500 cures 
or treatments to address the 10,000 known diseases. Certainly, 
more progress was needed to alleviate the agony of an incurable 
disease.
    While the U.S. had maintained its global leadership in 
biomedical innovation, there existed a potential to bridge the 
growing divide between the revolutionary advances in science 
and technology over the last decade and a less-than-adequate 
system for discovering, developing, and delivering new 
therapies. Members of the committee and the Senate HELP 
Committee held numerous public hearings, forums, and 
roundtables in Washington, D.C. and across the nation, bringing 
together leading scientists and medical experts, patient and 
disease group advocates, and researchers across multiple 
sectors. The primary objective of these events was to uncover 
opportunities to strengthen and streamline the process by which 
cures are discovered and made available to patients. Cures 
accelerated the cycle of discovery, development, and delivery 
of new treatments and ensured our nation remained at the helm 
of biomedical innovation.
    At the NIH, the 21st Century Cures Act authorized resources 
to support biomedical research and reduce administrative 
burdens and provided almost $5 billion dollars in new funding 
to support the agency's four innovation projects. The Precision 
Medicine Initiative was authorized over $1.4 billion for NIH to 
build a national biomedical data set in order to accelerate 
health research and medical breakthroughs. Cures also 
authorized $1.5 billion dollars for the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative to 
better understand the brain's physiology and coordinate efforts 
across multiple federal and private groups to expedite research 
for diseases like Alzheimer's. Cures also authorized $1.8 
billion dollars for cancer prevention, diagnosis, treatment and 
care through the Beau Biden Cancer Moonshot. Finally, the 
Regenerative Medicine Innovation Project was authorized $30 
million dollars to support clinical research in the field of 
regenerative medicine in coordination with the Food and Drug 
Administration (FDA).
    The 21st Century Cures Act helped the FDA modernize the 
regulation of medical products throughout its lifecycle. It 
established an ``FDA Innovation Account'' and authorized $500 
million dollars in funding to implement Title III of the law, 
which included a broad range of deliverables from the FDA. 
These include creating a mechanism for the collection and 
incorporation of patient perspective in regulatory decision-
making; updating the way medical products are reviewed and 
approved; advancing new drug therapies through a review pathway 
for biomarkers and other drug development tools to help shorten 
drug development time while maintaining the same rigorous 
standard for safety and effectiveness; and requiring the FDA to 
establish standards and definitions necessary to develop 
regenerative medicines.
    Before I close, I recognize that the 21st Century Cures Act 
also touched upon other critical healthcare priorities, such as 
mental health and health IT. Both of these areas should have 
their own, separate hearings because of their importance to the 
medical community and I look forward to holding them in the 
near future.
    I again want to welcome our witnesses and thank you for 
being here. I look forward to your testimony.
    I would like to yield the balance of my time to Ms. 
Blackburn of Tennessee, for a statement.

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

    Mr. Green. Thank you, Mr. Chairman.
    And thank you, Dr. Gottlieb and Dr. Collins, for being here 
this morning.
    And I want to thank former Chairman Upton and Congresswoman 
DeGette for being the original cosponsors of the 21st Century 
Cures.
    Next month will mark the 1-year anniversary of the 21st 
Century Cures Act being signed into law by President Obama in 
his last public signing ceremony. It was a great achievement, 
particularly at a time of hyperpartisanship and gridlock.
    The work started long before 2016. In 2014, we set out on a 
mission to do something positive to boost medical research and 
innovation and accelerate the discovery, development, and 
delivery of new cures and treatments.
    After countless hours devoted to roundtables, white papers, 
hearings, and drafts, Cures enjoyed bipartisan support and 
endorsements from over 700 organizations representing the full 
spectrum of stakeholders. It dedicated $6.3 billion in new 
investments to support priorities like the Beau Biden Cancer 
Moonshot, the BRAIN Initiative, and the Precision Medicine 
Initiative within the National Institutes of Health to combat 
prescription drug abuse.
    It also provides money to the FDA to advance the agency's 
mission and implement the policies in the underlying bill. This 
influx of investment is being put towards solving today's 
complex science problems, getting new treatments from the lab 
table to the bedside, and improving public health. 
Specifically, the NIH was provided $4.8 billion in new funding 
to advance cutting-edge research initiatives.
    The FDA was provided $500 million over 10 years to improve 
the agency's medical product review process and expedite 
patient access to drugs and devices without compromising the 
safety and effectiveness standards.
    In addition to this much needed funding, there were so many 
provisions in this package worthy of support, from facilitating 
development of new antibiotics, the fight against superbugs, to 
advancing the use of modern clinical trial designs, to 
fostering the next generation of medical researchers.
    While some of the provisions are technical in nature, the 
real world impact they could have is not abstract. Patients and 
families deserve to have their elected officials respond to 
their needs, and this bill was an earnest attempt to do just 
that.
    Like all negotiations and compromises, we didn't get 
everything we want, there is always more than can be done. But 
today is an opportunity to hear from the heads of FDA and NIH 
on implementation of things like patient-focused drug 
development, medical device innovation, improving science 
expertise and hiring capacity.
    It is only been a year since passage. These things take 
time. But I know folks out in the respective agencies have been 
hard at work to get new initiatives off the ground and build on 
past efforts to advance medical research and development of new 
science.
    While not the focus of today's hearing, Cures also included 
$1 billion to combat the prescription drug abuse and overdose 
epidemic. The funding was significant but pales in comparison 
to what is needed to combat this crisis. There are more 
Americans dying from this epidemic than were at the height of 
the AIDS epidemic.
    I hope this committee and Congress can fulfill its 
responsibilities to the American people and provide real and 
desperately needed funding to fight this epidemic that has 
raged in communities head-on. The 21st Century Cures 
demonstrates what we can accomplish when we work across the 
aisle, and I hope we can do so again.
    I look forward to hearing from our witnesses about the 
ongoing implementation of 21st Century Cures.
    And, Mr. Chairman, I want to yield the remainder of my time 
to Congresswoman DeGette.
    Ms. DeGette. Thank you very much, Mr. Green, for yielding, 
and thank you for all of your work that you did on Cures. I am 
going to be sorry not to have you as my seat partner and my 
partner in issues like this in the next Congress. You have done 
a wonderful job.
    And, Mr. Chairman, I want to thank you, too, for all the 
work you did on Cures.
    Fred Upton of course is my partner and he was our chairman 
at the time. And we really wanted to do something bold and big 
when we started conceiving of 21st Century Cures, and I think 
we achieved that. And so I am looking forward to hearing from 
our two witnesses today.
    Dr. Gottlieb, your agency was a key partner, and I know you 
have carried on that effort. And of course Dr. Collins was 
there from the beginning with us, helping us craft this bill.
    At one point I remember Dr. Collins said to me, very early 
on, he said, ``You know, we just need to let our young 
researchers go to conferences.'' And I said, ``If that is all 
we do, we will have failed.''
    And we did that and we did so much more. And so we are 
eager to hear how this bill has had impact in just 1 year, but 
we are even more eager to hear where we can take it next.
    So thanks for all you do. Thanks to all of this committee 
for working together on this bill. And I yield back.
    Mr. Burgess. The chair thanks the gentlelady. The 
gentlelady yields back.
    The chair recognizes the chairman of the full committee, 
the gentleman from Oregon, Mr. Walden, 5 minutes for an opening 
statement, please.

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

    Mr. Walden. Thank you, Mr. Chairman. Thanks for having this 
oversight hearing, if you will, of an incredibly important 
lifesaving law that was passed in the last Congress in a 
bipartisan way. I think it was some of the finest work this 
committee has ever done.
    And I know, Dr. Collins and Dr. Gottlieb, you haven't had 
anything else on your plate in the last year. But I say that 
facetiously, because you have had a lot, both of you have, and 
yet you seem to be doing a marvelous job implementing this vast 
bill and helping move forward to save lives and to improve the 
lives of families, friends, people we will never know.
    And the consequences of this legislation are not confined 
to this hearing room, they are not confined to the District of 
Columbia, or even the United States. The research and the 
progress that will be made in these sectors will affect 
everyone in the world. This is world changing. My colleagues on 
both sides of the aisle have done marvelous work getting this 
done.
    Now, my view has always been that once you pass a law, that 
is just the starting place. I know how difficult it was for 
Diana DeGette and Fred and Mike and Gene and everybody else to 
do this. But that was the starting point.
    Today we look and say: What is it going forward? How is 
this working? Are these tools effective? Are there changes that 
need to be made? We know you are making great progress and we 
appreciate the terrific work you are doing.
    I also want to recognize a very special guest here with us 
today, we have many in the room, but I want to draw special 
attention to somebody who has been part of this journey from 
the beginning, and that is young Mr. Max.
    Max, we are delighted to have you here. You are an 
extraordinary young man. And we are so very glad that you are 
here to share in this special birthday appearance of the 21st 
Century Cures legislation. And it is because of people like you 
that inspire us to do the best that this committee has to 
offer, the best work, the best legislation, because we know 
human lives are at stake.
    With that, I am going to put----
    [Applause.]
    Mr. Walden. With that, I am going to submit my eloquently 
written opening statement into the record and defer the balance 
of my time to the former chairman of the committee, the 
chairman on Energy now, Fred Upton. And I know there are other 
members on our side who would like to share in what time 
remains.
    So with that, I yield to the champion of 21st Century Cures 
and the improvement of people's lives around the world, my 
friend from Michigan, Mr. Upton.
    [The prepared statement of Mr. Walden follows:]

                 Prepared statment of Hon. Greg Walden

    Today the Subcommittee will review the implementation of 
critical components of the 21st Century Cures Act, a 
transformational law intended to modernize the nation's 
biomedical innovation infrastructure. Cures was signed into law 
in December of 2016, following a multi-year effort led by this 
committee to uncover opportunities to strengthen and streamline 
the process by which innovative medical products are discovered 
and made available to patients. I'd like to take this 
opportunity to commend our former Chairman, Fred Upton, as well 
as Representative Diana DeGette, for their unwavering 
dedication to getting this initiative across the finish line. 
I'd also like to recognize a very special guest who has been a 
part of this journey since the very beginning-Max, you are an 
extraordinary young man and we are so glad you could be here.
    In our increasingly connected world where scientific 
innovation is outpacing government regulation, we have the 
potential to revolutionize medicine, and do more to reduce 
human suffering in the process. Over the course of two 
Congresses, members of this committee consulted with leading 
scientists and medical experts, patient and disease group 
advocates, and researchers and innovators across multiple 
sectors to find ways to accelerate a path to cures in America. 
We identified things the government could do to encourage 
innovation; and we also identified areas where government 
regulations and red tape were getting in the way of the 
revolutionary discoveries happening in labs across America. 
These initiatives culminated in the passage of the 21st Century 
Cures Act. By increasing research collaboration, improving 
personalized medicine, investing in the next generation of 
young investigators, removing regulatory uncertainty, providing 
new drug development incentives, and modernizing clinical 
trials, Cures sought to maintain and enhance America's global 
status as the leader in biomedical innovation, and above all, 
save lives.
    I am proud of this committee's work to identify 
opportunities to improve our health care system, and to advance 
legislative solutions in a thoughtful, responsible, and 
bipartisan manner. The 21st Century Cures Act ushered in the 
changes necessary to bring our laws into a modern era of 
medicine. Today we will hear from the officials at the helm of 
implementing the research and development provisions authorized 
in the new law-NIH Director Francis Collins, and FDA 
Commissioner Scott Gottlieb. I look forward to hearing more 
about how these solutions are being implemented to keep our 
Nation at the forefront of innovation, and most importantly to 
deliver hope to millions of patients living with untreatable 
diseases.

    Mr. Upton. Well, thank you.
    When we began the process of crafting 21st Century Cures 4 
years ago, we began with one goal in mind, and that was helping 
patients and their families. And Diana DeGette, my great 
partner on the other side of the aisle, and I were inspired to 
act after hearing from folks in the research community, as well 
as patients and their families about the need for modernization 
and more resources at both the NIH and the FDA, to move 
quickly, bring lifesaving treatments to market.
    And all of us had inspirations in our district. For me, it 
was two sisters, the Kennedy sisters, Brooke and Brielle, who 
have a rare genetic disease called spinal muscular atrophy, or 
SMA. Cures provided the NIH and the FDA with billions, tens of 
billions of dollars in much needed resources so that our 
Nation's best and brightest could work on finding cures for 
diseases that impact virtually every single family, whether it 
be cancer, diabetes, Lupus, or, yes, rare diseases like SMA.
    And this hearing is a great thing for lots of reasons. Most 
notably, it is a reminder of how Republicans and Democrats came 
together to get a monumental piece of legislation signed into 
law despite our divided times. Diana worked with me on this as 
we worked for years and listened and worked to craft the 
language that would ultimately become law.
    The hearing is also a reminder that we have a lot of work 
still to do. The Kennedy girls, our buddy Max in the front row, 
along with millions of patients and families across the country 
are counting on us.
    And for that reason, I am immensely glad to welcome both 
Dr. Collins and Dr. Gottlieb on how the law is being 
implemented and what we in Congress can do to help that process 
a long and improve it.
    I yield now to the gentlelady from Tennessee, Mrs. 
Blackburn.
    [The prepared statement of Mr. Upton follows:]

                 Prepared statement of Hon. Fred Upton

    When we began the process of crafting 21st Century Cures 
four years ago, we began with one goal in mind: Helping 
patients and their families. Diana DeGette, my partner on the 
other side of the aisle, and I were inspired to act after 
hearing from folks in the research community as well as 
patients and their families about the need for modernization 
and more resources at the NIH and FDA to more quickly bring 
lifesaving treatments to market.
    Two of these inspirations were the Kennedy sisters--Brooke 
and Brielle--from Mattawan, Michigan. Brooke and Brielle have a 
rare genetic disease called Spinal Muscular Atrophy--or SMA.
    Cures provides the NIH and the FDA with billions of dollars 
in much-needed resources so that our nation's best and 
brightest can work on finding cures for diseases that impact 
every single family.
    Whether it be cancer, diabetes, lupus, or yes, rare 
diseases, like SMA.
    This hearing is a great thing for many reasons. Most 
notably, it's a reminder of how Republicans and Democrats came 
together to get a monumental piece of legislation signed into 
law despite our divided times. Diana worked with me on this 
endeavor hand-in-glove for years--yes years--as we listened and 
worked to craft the language that would ultimately become law.
    The hearing is also a reminder that we have much work left 
to do. The Kennedy girls, along with millions of patients and 
families across the country are counting on us. For that 
reason, I am immensely glad to welcome and thank Dr. Collins 
and Dr. Gottlieb for testifying before us today. I look forward 
to hearing from you both on how the law is being implemented 
and what we in Congress can do to help that process along.

    Mrs. Blackburn. Thank you so much.
    And we do welcome our witnesses, and we take this as an 
opportunity to thank you each for the help and the guidance 
that you have provided in what were then your roles and what 
are now your roles as we implement 21st Century Cures.
    It is so appropriate that we do this hearing because, as 
you have heard, there was so much more that went into this than 
just saying let's have people go to conferences or let's try. 
This was a way to change and reform the review and approval 
process so that it more adequately meets the innovation that is 
taking place in healthcare delivery systems.
    So we welcome you.
    We welcome Max and his bipartisan friends who have joined 
him this morning. What a great reminder, Max, that they have a 
reserved seat right there on the front row in sharing the 
success of this day.
    Mr. Chairman, I thank you for the hearing, and I yield 
back.
    Mr. Walden. And I yield back the balance of my time.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    The chair recognizes the gentleman from New Jersey, Mr. 
Pallone, the ranking member of the full committee, 5 minutes, 
please.

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

    Mr. Pallone. Thank you, Mr. Chairman.
    I want to welcome Dr. Collins and Dr. Gottlieb here today 
to discuss the implementation of the 21st Century Cures Act. 
While the law addressed several different issues facing our 
healthcare system, such as the opioid epidemic and mental 
health, today we will be focusing on the ongoing work at NIH 
and FDA to implement the provisions of the law aimed at 
improving the discovery and development of new treatments and 
cures.
    The Cures Act provided new funding to advance cutting-edge 
research at NIH. I am particularly proud that the law included 
funding for the Beau Biden Cancer Moonshot Initiative. This 
initiative aims to accelerate cancer research in America and 
improve our ability to prevent and detect cancers early on, and 
the hope is that one day we might find cures for the many 
different cancers, such as pancreatic cancer, that afflict 
patients today. I am interested in hearing how NIH is working 
to achieve this goal.
    I am also pleased that the Cures Act invested new funds in 
the BRAIN Initiative and the Precision Medicine Initiative, 
which includes the All of Us Research Program. The BRAIN 
Initiative funds important research on brain disorders, such as 
Alzheimer's, epilepsy, and traumatic brain injury. And the All 
of Us Research Program funds a historic effort to gather data 
from at least a million people that will help lead to the 
development of personalized therapies rather than one-size-
fits-all treatments.
    At FDA, the Cures Act aims to bolster the medical product 
review process in order to get treatment to patients faster 
while also maintaining FDA's gold standard for safety and 
effectiveness. For example, the law granted FDA added authority 
to develop and utilize new tools to facilitate drug 
development, provide greater flexibility in the clinical trial 
process, and support the development of continuous 
manufacturing.
    It also invested in increased patient engagement by 
encouraging the use of patient experience data in the review 
process. And the law also provided FDA with $500 million in new 
funding to ensure the agency has the necessary resources to 
recruit the best and brightest scientists and effectively 
implement the law.
    And so I look forward to hearing more about the progress 
the agency has made to date on all of these issues.
    And lastly, the Cures Act marked an important step towards 
the development of new treatments and cures. And I am pleased 
that the committee was able to work together on a bipartisan 
basis last Congress to pass this monumental law. And I of 
course particularly want to thank the chief sponsors, Fred 
Upton and Diana DeGette.
    It is critical that we hold hearings to ensure the law is 
working as it should and achieving its goals. And I look 
forward to hearing from our witnesses today and to further 
discussions on implementation of other provisions of the law.
    So I would like to yield the remainder of my time to 
Representative Lujan.
    Mr. Lujan. I thank the chairman and ranking member for 
organizing this hearing today and I thank the witnesses for 
their attendance.
    Last Congress we worked together to pass the Comprehensive 
Addiction and Recovery Act and the 21st Century Cures Act. It 
is fair to say it was a compromise, not everyone got everything 
they wanted.
    During the debate I pushed and have continued to advocate 
for more funding and resources to address the deadliest drug 
crisis in American history. We came together and we advanced 
legislation to provide $1 billion over 2 years to strengthen 
the response to this crisis.
    Still, 21st Century Cures Act's 2-year funding window 
creates planning problems for State and local governments. The 
uncertainty in funding to hire staff or plan beyond 2 years 
makes it difficult for people on the ground to do the work we 
are trying to empower them to do.
    We must do more. That is why I introduced legislation to 
extend Cures funding to combat the opioid epidemic for an 
additional 5 years. Honestly, a 5-year extension of this 
funding is the minimum we should be doing.
    I am grateful to the members of this committee who have 
cosponsored this bill, and I ask other members to add their 
voices to this effort. Let's work together to find common 
ground and move this.
    Because this drug crisis is tearing apart the fabric of 
communities across the country, we must work together to ensure 
that this important funding does not expire. Too many people 
are suffering without access to meaningful support systems.
    We must also step up our prevention efforts. One long-term 
avenue for prevention is the development of safe and effective, 
nonaddictive opioids. We also need to move forward research and 
treatments that stop the craving of opioids and alcohol.
    Dr. Gottlieb, I communicated with your office on this 
matter, and I understand the FDA is working with the NIH on a 
series of meetings to facilitate development of nonaddictive 
pain treatments. As you are aware, I sent you a letter on this 
issue. You responded by answering a few of the questions, but 
not all of the questions. I will be sending the letter again 
with expectations of more thorough answers and responses to all 
of the questions, and I will also be submitting them into the 
record.
    Mr. Chairman, thank you for again holding this hearing. And 
I yield back to Mr. Pallone.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    This actually concludes member opening statements, and the 
chair would remind members, pursuant to committee rules, all 
members' opening statements will be made part of the record.
    And again I want to thank and welcome our witnesses for 
being here today and taking their time to testify before the 
subcommittee. Each witness will have the opportunity to give an 
opening statement, and we will follow that with questions from 
the members.
    This morning we are going to hear from Dr. Scott Gottlieb, 
the Commissioner of the Food and Drug Administration, and Dr. 
Francis Collins, the Director of the National Institutes of 
Health.
    Dr. Gottlieb, we appreciate you being here today. Dr. 
Gottlieb, you are recognized for 5 minutes, please.

STATEMENTS OF THE HONORABLE SCOTT GOTTLIEB, M.D., COMMISSIONER, 
    FOOD AND DRUG ADMINISTRATION; AND THE HONORABLE FRANCIS 
     COLLINS, M.D., DIRECTOR, NATIONAL INSTITUTES OF HEALTH

                  STATEMENT OF SCOTT GOTTLIEB

    Dr. Gottlieb. Thank you, Chairman Burgess, Ranking Member 
Green, members of the subcommittee. Thank you for the 
opportunity to testify today on the anniversary of the 21st 
Century Cures Act and to update you on FDA's progress in 
implementing the provisions of this landmark legislation.
    The Cures Act gave FDA a broad new set of authorities and 
resources to adapt our policies and our organizational 
structure to make sure that our efforts are as modern and 
transformative as the medical products that we are seeing.
    Congress wanted us to have a strong workforce and policies 
that will enable the America people to capitalize on the 
breakthrough science that is transforming medicine.
    I am proud that my colleagues at FDA have worked hard to 
meet the commitments under the statute. And I want to commit to 
you that timely implementation of this legislation is one of my 
highest priorities. The Cures Act is a defining element of my 
own policy planning at FDA.
    When I arrived at FDA 7 months ago, I remarked that I 
couldn't imagine a better time to be leading the agency, owing 
to two important new opportunities. The first were 
opportunities offered by new science and technology. Gene and 
cellular therapies, more targeted drugs, regenerative medicine, 
digital health tools, and new biomaterials offer the potential 
for dramatically better and even curative therapies for many 
disorders.
    The second were opportunities provided by Congress. The 
reauthorization of the user fees and, more notably, the Cures 
Act offer FDA a new platform to fashion these scientific 
advances into practical treatments for patients. If I came 
before Congress 5 years ago and said that within the next 5 
years we might have a cure for sickle cell disease or 
hemophilia or common early stage cancers, such predictions 
would have been unrealistic.
    Such discussions are no longer imprudent. In fact, we 
should expect these opportunities. While these scientific 
advances won't be risk-free, these and equally profound 
clinical opportunities are before us.
    The Cures Act inspired a new approach to our work. It was a 
direction from Congress that you wanted us to think differently 
when it came to the potential for breakthroughs that could 
transform human health.
    We pledge to remain steadfast to our gold standard for 
safety and efficacy, but at the same time you asked us to look 
for ways that we can make our approach to the development of 
breakthrough products more scientifically modern and efficient 
to meet the urgent needs of patients.
    We have taken the spirit of Cures and set out to extend 
this directive across our own policymaking and planning. To 
build on what you asked to do, we will soon release a document 
that will take full measure of how we are expanding on the 
provisions of Cures to make sure we are continuing to expand on 
what Congress set out to achieve.
    I want to share with you today one such effort. With the 
advent of more targeted medicines, we are sometimes able to 
observe earlier in some cases outsized benefits. This is 
especially true when it comes to the field of oncology. These 
situations are compelling us to explore new ways to facilitate 
and expedite the development and review of these products.
    For example, we are currently examining approaches to 
better expediting review and approval of these products by 
leveraging FDA's existing expedited programs. Accelerated 
approval has typically been granted in circumstances where 
earlier stage or smaller datasets show benefit for a serious 
unmet medical need. But that showing of benefit is typically 
based on the drug's effect on a surrogate endpoint. In these 
cases that endpoint, like tumor shrinkage, is judged to be 
reasonably likely to predict clinical benefit.
    What do you do when we have a targeted drug introduced into 
a properly selected group of patients which has an outsized 
benefit on overall survival in a rare or deadly cancer, but 
where that benefit is seen in a small trial where we would 
still need more evidence to fully understand how to best use 
the drug in clinical practice?
    We might want to approve such a product earlier and require 
a post-market confirmatory study to validate the finding, 
similar to an accelerated approval approach.
    Even though the observed benefit in this case is on a 
clinical endpoint, an early look at survival, and not on a 
surrogate measure of benefit, we believe using an accelerated 
approval approach could often be valuable.
    Congress clarified our authority under FDASIA to grant 
accelerated approval based on intermediate clinical endpoints. 
We want to better define what is meant by intermediate 
endpoints to ensure that product developers with promising 
drugs take full advantage of this provision and can consider it 
in a broader range of such settings.
    As the mechanism of diseases like cancer become more 
clearly defined and drugs targeting these conditions more 
carefully tailored to the underlying biology of the disease, we 
are going to see more such cases, situations where a new drug 
offers an outsized survival benefit in a selected population of 
patients in a smaller earlier stage clinical trial.
    One reason we want to consider accelerated approval in 
these setting is that it would include authority to require 
confirmatory evidence to support the continued marketing of the 
drug and an expedited withdrawal mechanism if that evidence 
fails to confirm the benefit. We intend to further explore the 
application of these principles in additional policy work we 
are undertaking.
    To fully leverage these opportunities and in keeping with 
the spirit of Cures we are working on a similar proposal. For 
cancer drugs already approved for one indication, approval for 
a supplemental application, where the approval concerns a 
second indication, can sometimes appropriately rely on a more 
targeted dataset like a single arm study. We intend to issue 
guidance further clarifying the circumstances in which this is 
appropriate.
    In closing, this may be suitable, for example, when there 
is a clear and outsized treatment effect and the second 
indication concerns the same disease as the first one but for 
on new setting, for example, a targeted drug approved for a 
third line use that shows benefit in a second line indication.
    Cures refashioned and modernized FDA's footprint, enabling 
new technologies to reach patients more efficiently, giving the 
agency new authorities and resources to invest in our 
workforce, and it shapes our spirit of our mission. We will 
continue to build on its framework.
    I look forward to discussing our plans to fulfill and 
expand on these opportunities, and I look forward to answering 
your questions.
    [The prepared statement of Dr. Gottlieb follows:] 
    
    
    
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    Mr. Burgess. The chair thanks the gentleman.
    The chair now recognizes the Director of the National 
Institutes of Health, Dr. Collins, 5 minutes for an opening 
statement, please.

                  STATEMENT OF FRANCIS COLLINS

    Dr. Collins. Good morning, Chairman Burgess, Ranking Member 
Green, other distinguished committee members. It is an honor to 
be here today with my colleague, Dr. Scott Gottlieb, the FDA 
Commissioner.
    We were cheering a year ago today, November 30, when the 
Cures Act passed the House of Representatives 392 to 26. And as 
you well know, this act aimed to catalyze a very important goal 
shared by all Americans: to speed the pace at which scientific 
discoveries are translated into lifesaving treatments and 
cures. And I am here to talk to you today about how that dream 
is coming true.
    We at NIH greatly appreciate your leadership in passing 
this bipartisan act 1 year ago that enhances our authorities 
and our resources in ways that will help us to achieve this 
goal. Many thoughtful provisions are included in the act, such 
as reducing administrative burdens so our scientists can devote 
more of their time to research, expanding our ability to award 
prizes for exceptionally creative ideas, and strengthening 
measures to protect patient privacy when individuals are 
involved in research.
    In my written statement I have submitted a comprehensive 
report on how NIH has worked quickly to implement the 
provisions of the Act. We are motivated by a sense of urgency 
to help patients in need of breakthroughs. In my oral statement 
just now, I would like to focus on the Cures Innovation Fund.
    Among the vital areas of NIH-supported research being 
accelerated by this fund are the BRAIN Initiative, the Cancer 
Moonshot, the Regenerative Medicine Innovation Project, and the 
Precision Medicine Initiative. I am also delighted to have Max 
here representing the most important audience for anything we 
are talking about today, which are those patients who are 
waiting for answers to conditions that need those answers. And 
I would also like to recognize my friend Doug Oliver, at the 
end of the front row, who has been a very effective 
spokesperson for the importance of investing in regenerative 
medicine.
    Let's begin with the BRAIN Initiative. This pioneering 
effort is aimed at revolutionizing our understanding of the 
most complex structure in the known universe, the human brain. 
In fiscal year 2017, we leveraged our Cures innovation funding 
with our annual appropriation to launch no less than 110 
exciting new brain research projects.
    Some of these will develop detailed maps of neural 
circuits, others will create a census of cell types in the 
brain, and still others will create powerful new tools to 
monitor and modulate brain activities. This will advance 
efforts to develop new ways of detecting, treating, and even 
preventing many serious brain disorders, such as Alzheimer's 
disease, Parkinson's, schizophrenia, autism, drug addiction, 
epilepsy, and traumatic brain injury.
    With the help of the Cures Innovation Fund, a second 
research area, the Cancer Moonshot, is aggressively pursuing a 
very ambitious goal: to accelerate advances in cancer 
prevention, diagnosis, treatment and care, in collaboration 
with our good colleagues at FDA.
    To achieve that goal we must take a variety of innovative 
steps. These include enhancing the research infrastructure by 
creating a clinical trials network, with an unwavering 
commitment today to sharing, to move cancer treatment programs 
forward rapidly.
    In another innovative move, NIH recently joined with the 
FDA and 12 pharmaceutical companies to launch the Partnership 
for Accelerating Cancer Therapies, or PACT. This public-private 
partnership will initially develop biomarkers to speed the 
development of cancer immunotherapies, an exciting new approach 
to treatment that enlists a patient's own immune system.
    Recently, we have seen some amazing responses from 
immunotherapy, but we need to bring that kind of success to far 
more people with more types of cancer and do it quickly. The 
Cures Innovation Fund, with the support of this Congress, is 
helping to make that happen.
    The Cures Act also provides support for regenerative 
medicine research. This emerging area of science includes the 
use of cells and other technologies, such as engineered 
biomaterials and gene editing, to repair or replace damaged 
cells, tissues, or even whole organs.
    A result of the Cures Act, NIH has launched the 
Regenerative Medicine Innovation Project. This project recently 
made eight clinical research awards covering a broad spectrum 
of science and technology, and going well beyond the funding 
specifically provided by the Cures Act, because we found it to 
be so compelling.
    Some are focused on common diseases, including diabetes and 
vision disorders, while others are aimed at rarer conditions, 
such as sickle cell disease, which Scott has already mentioned 
is a very exciting time of potentially moving forward to cure 
in as little as 5 years, and a condition like idiopathic 
pulmonary fibrosis, and many others.
    Also, in partnership with the FDA, we are going to be 
hosting a workshop next week which is going to explore the 
state of regenerative medicine research involving adult stem 
cells. This conference will inform our future research 
directions by helping us to identify areas of greatest 
scientific and therapeutic promise.
    Finally, I want to tell you how thrilled I am that you 
supported the Precision Medicine Initiative, PMI, by including 
an authorization and funding in the Cures Act.
    The centerpiece of PMI is the All of Us Research Program, 
which will enroll 1 million or more Americans from every walk 
of life. These volunteers will contribute their health data in 
many ways, over many years, to create a research resource that 
will catalyze a new era of precision medicine.
    This is a truly ambitious goal, and we know that NIH cannot 
succeed on its own. So all across the nation, NIH is teaming up 
with the Veterans Administration, health provider 
organizations, community health centers, and other groups--
recently libraries all across the country--to figure out the 
best ways to recruit participants, especially those that are 
traditionally underrepresented in biomedical research.
    NIH has also partnered with five companies to create a 
participant technology center, and our partners are testing how 
wearable devices, like the ones I am wearing today, and many of 
you are probably wearing something like this, how can we use 
these to provide easy ways for all of us volunteers to 
contribute data on physical activity, sleep, heart rates, 
environmental exposures, and so on.
    Getting all these partners on board would have been nearly 
impossible had not the Cures Act included something called 
Other Transactions Authority for PMI, making it possible for 
NIH to move forward with unprecedented speed and flexibility to 
carry out beta testing of all the many components, and now a 
planned launch in the spring of 2018.
    As someone who grew up in a theater family, I know the 
value of a dress rehearsal before the curtain goes up. That is 
what a beta test is. But when it does go up, you and everyone 
else who supported the 21st Century Cures Act will deserve 
applause, not just for all of us, but for each of the many, 
many ways in which Cures supports the work of the National 
Institutes of Health, or as some have called us, the National 
Institutes of Hope.
    Speaking of hope, let me conclude with a favorite 
exhortation from the poet Peter Levi: Hope in every sphere of 
life is a privilege that attaches to action. No action, no 
hope.
    So thank you for your action in enacting Cures. Thank you. 
I will be happy to answer your questions.
    [The prepared statement of Dr. Collins follows:]
  
  
  
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    Mr. Burgess. The chair thanks both of our witnesses for 
their testimony, and we will move into the member question 
portion of the hearing.
    I actually want to recognize the chairman of the full 
committee, Mr. Walden from Oregon, for 5 minutes.
    Mr. Walden. I thank the chairman.
    And again thank you both, not only for your good work, but 
also your terrific testimony here today.
    And I also want to thank Dr. Gottlieb for his excellent 
efforts to make sure that our warfighters have access to 
cutting-edge medical devices and medicines that are both 
effective and safe for them. We appreciate the work you did 
with us and our friends at the Armed Services Committee and 
Pentagon to get that done.
    Dr. Gottlieb, the FDA Oncology Center of Excellence was 
created in Cures as a model of how collaboration in science 
among and within government agencies should be done in the 
future. This is a new model, and I know we were hoping here in 
Congress that this would succeed. And in your testimony you 
reference the role of OCE in the review and approval of two 
cell-based gene therapies that are indicated for treatment of 
cancer patients.
    Can you speak a little bit more about how groundbreaking 
these two treatments are and the role OCE played in their 
approval?
    Dr. Gottlieb. Thank you, Mr. Chairman.
    I just want to make one brief comment about the legislation 
that this committee helped craft and crafted with respect to 
the warfighter. I think it is going to give us a profound 
opportunity to expedite the approval of products destined for 
the battlefield setting and to help protect and promote the 
health of warfighters in the battlefield setting.
    We look forward to early implementation of that and robust 
implementation of that. We will try to make an effort early on 
to put out specifications on how we plan to make full use of 
that. I think it is going to provide a profound opportunity for 
our warfighters, and I thank the committee.
    With respect to the Oncology Center for Excellence, the 
products that you refer to were gene therapy products that we 
think are going to represent sort of a transformative 
opportunity as a class of products for the treatment of 
patients with a range of conditions, including cancer. These 
were CAR-T products where cells are genetically altered to 
attack cancer and personalize to the patient's individual 
cancer.
    With respect to the Oncology Center for Excellence, it was 
instrumental in the review of these products. We believe that 
the orientation for the future across the entire agency is to 
try to consolidate the clinical portion of the review among the 
agency's various medical product centers.
    We divide medical products into different centers, but the 
clinical aspects of the review remain the same, even if the 
product features are different. And so trying to consolidate 
that clinical portion of review provides a lot of efficiency, 
rigor, and also helps quicken the process. And so standing up 
this new oncology center we think is critical to the future of 
these classes of products.
    Mr. Walden. Thank you, sir.
    Dr. Collins, over the last several years NIH has been 
acting to address a biomedical research workforce that is 
tilted toward, frankly, late-career investigators. The 
population of grant recipients is highly concentrated, with 10 
percent of NIH-funded investigators receiving over 40 percent 
of NIH funding.
    Analyses conducted by your agency and others have shown 
that a more diverse population of NIH grant recipients would be 
beneficial to biomedical research. Cures required the NIH to 
develop strategies to promote and facilitate the next wave of 
young researchers, and in your testimony you talk about the 
Next Generation Researchers Initiative.
    Can you further elaborate on the multipronged approach you 
plan to take to increase the number of NIH-funded early stage 
and mid-career investigators.
    Dr. Collins. Thank you for the question. This is an area of 
great and high priority for us, and we appreciated very much 
the way in which the Cures bill called this out and gave us 
additional encouragement to think boldly about how we can be 
sure this next generation of researchers are getting their 
start as independent investigators with all of the energy and 
creativity that they bring to it.
    And we could look at our own demographics and see that we 
were increasingly seeing an aging of our workforce. And while 
we have many investigators who are highly productive as senior 
investigators, we were worried that the next generation was 
having a tough time coming on board.
    So over the course of this past year since the Cures Act 
passed, and guided by many conversations before that, we have 
come up with an approach which is going to provide additional 
resources for those who come to us for the first time with a 
grant that has not previously been funded by NIH, but this is 
their start, and to provide additional opportunities for those 
individuals, if they fall in the top 25 percent of applicants, 
to be able to receive funding.
    We made this decision fairly late in fiscal year 2017, but 
we were determined to go ahead and implement it. We are still 
in the process of identifying all of those investigators who 
were reviewed in fiscal year 2017 that otherwise would have 
missed the cut, but whom we now believe we can reach down to 
and find funds for.
    And we are also very concerned about those who are at risk 
of losing all of their funding. They got started into the 
pathway, they came back for their competing renewal, just 
missed the cut, and without that they may have to close their 
labs and do something else. We are also seeking then to 
identify those individuals and give them an additional boost.
    Now, that money has to come from somewhere, and that means 
that we may not be able to be quite as generous in other areas 
of research, including some labs that are extremely well-
funded, and as you can imagine, not everybody has been excited 
about that part.
    But we do believe it is the right thing to do. This is the 
future. If our mission is to try to find every place that we 
can to use the dollars that the Congress provides us to get the 
maximum benefit, those young investigators just getting started 
are a critical part of that.
    Mr. Walden. Thank you.
    Thank you both for the good work you are doing and for 
being here today before the committee.
    With that, Mr. Chairman, I yield back.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    The chair recognizes the gentleman from Texas, Mr. Green, 5 
minutes for questions, please.
    Mr. Green. Thank you, Mr. Chairman.
    Over the last decade there has been a growing recognition 
in the U.S. and abroad that antibiotic resistance poses a 
serious and growing threat to our health. Antibiotics are the 
underpinning of modern medicine. Without them important medical 
advances such as chemotherapy and surgeries become very risky 
because of the possibility of infection.
    Addressing this threat requires a multipronged approach, 
including reducing the inappropriate use of antibiotics in 
human healthcare and agricultural settings and developing new 
antibiotics and other therapies. We know that there are a 
number of challenges in discovering and developing new 
antibiotics.
    Dr. Collins, my first question. There are basic scientific 
barriers which impede new antibiotic discovery and development. 
Can you tell us what the NIH is currently doing and will be 
doing to address these barriers?
    Dr. Collins. We have a very important role to play. So 
thank you for the question.
    Yes, there have been challenges in terms of keeping this 
pipeline of discovery and development going for antibiotics, in 
part because some sort of looked at this as a bit of a market 
failure because of the expectation that new antibiotics would 
have potentially a very limited market for a while. You would 
want to save them for those circumstances where you really 
needed them.
    So NIH has an even larger role to play in this space in 
terms of the discovery part and in moving the new discoveries 
along the pipeline closer to commercialization, to de-risk 
those projects, so that antibiotics will be seen by the 
commercial sector as something that they are ready to pick up 
and go. And we at NIH, particularly through the National 
Institute of Allergy and Infectious Diseases, led by Tony 
Fauci, have a very significant amount of funding invested in 
this space.
    There have been some exciting developments. One is 
basically using new technologies to discover naturally 
occurring antibiotics that are created by soil organisms that 
we didn't previously know were there because we can't culture 
them in the lab, but new technologies have made that possible. 
There is a whole new generation of ideas coming from there.
    But this is not a solved problem. I am glad you are raising 
it. It is going to take the full effort of the public and the 
private sector, supported by this Congress, to be sure that we 
are inspiring the maximum energy in this space, because we have 
a ticking clock here for a significant number of individuals 
who are being found with infections for which none of our 
antibiotics currently would be able to work.
    Mr. Green. Well, we will not be able to succeed in the goal 
of developing antibiotics without a strong bench of scientists. 
What is NIH doing to ensure that these young scientists are 
pursuing careers in the antibiotic discovery and development?
    Dr. Collins. Well, this ties into the answer I gave a 
moment ago to Chairman Walden about the things that we are 
doing to try to encourage our first-time investigators to come 
on board and to be able to get successfully funded. And in fact 
many of those investigators are in this area of infectious 
disease. So as we are lifting all the boats for that category 
of investigators, we are also helping in this space.
    But the National Institute of Allergy and Infectious 
Diseases also, because this is a high priority, issues special 
funding announcements, specifically recruiting investigators to 
work in this space, recognizing that there are people out there 
who might just work on something else, but knowing that there 
is a funding opportunity, would raise their hands and say, 
let's work on this. And we have to do all those things 
together.
    Mr. Green. Dr. Gottlieb, this committee has taken the 
threat of antibiotic resistance very seriously. In 2012, 
Congress passed the Generating Antibiotics Now Act, the GAIN 
Act, which our former colleague, Phil Gingrey, who is here 
today. It came out of this committee and gave exclusivity to 
new antibiotics to treat serious and life-threatening 
infections.
    Just last year in Cures we passed the ADAPT, which created 
a new regulatory pathway for antibiotics that treat serious and 
life-threatening infections and meet an unmet need. I thank 
Congressman Shimkus for picking up that, cosponsoring. Can you 
give us a status update on implementation of ADAPT?
    Dr. Gottlieb. It continues to move forward.
    I will comment on a couple things, if I may, Congressman. 
To answer, to pick up an earlier comment you made, we are going 
to continue to take steps to try to reduce antibiotic use in 
veterinary animals. We have taken steps, as you know, to put 
them under veterinary supervision. And we are going to look at 
continued steps we can take to address some of the prevention 
claims in those labels and build on the good work that was 
begun by my predecessor, Dr. Hamburg.
    Another important provision--you mentioned the GAIN Act--
another important provision is obviously the LPAD designation 
that was created by the Cures Act. We are going to put out 
guidance on that this summer. We have had a limited number, but 
a robust number given the early days of pre-IND meetings with 
sponsors that are looking to take advance of that provision as 
a way to accelerate the approval of products targeted to 
resistant organisms.
    So I want to thank the committee for the collective good 
work that you have done through all of this legislation. This 
has been immensely important to the agency in giving us a new 
set of tools to address these issues.
    Mr. Green. Thank you. And I don't have any more time left. 
But, again, thank you for that effort.
    And thank both of you for being here today and the work you 
are doing. And, obviously, as a committee we want to continue 
to partner with you.
    Mr. Guthrie [presiding]. Thank you. The gentleman's time 
has expired. And I will recognize myself for 5 minutes for 
questions.
    Thanks, Dr. Collins, Dr. Gottlieb, for being here.
    When I am home a lot of times doing townhalls or whatever, 
a lot of times most of the things I talk about is what is 
happening from this subcommittee in the healthcare world and 
the research. It is just fascinating stuff that is going on. As 
Dr. Gottlieb said, we are talking about being able to hopefully 
be on the cusp of curing diseases we never thought about.
    I remember about this time last year the roundtable where 
Roger Daltrey was here. He was talking about teenage cancer. We 
also had a young man who was talking about cystic fibrosis. And 
I have a friend who lost his son in his mid-twenties to cystic 
fibrosis.
    So I was sitting there thinking about, wow, he is young, my 
daughter's age, and where we were a few years ago he probably 
had just a few years left to live. And depending on a lot of 
circumstances, but they talked about he may live a full life 
expectancy. And that is really what is happening with the 
research at NIH, what is happening in the private sector.
    And so I think for me what made 21st Century Cures 
exciting--and all of us have these experiences--I had a 
constituent whose son has Duchenne--or a constituent that has 
it--his father that has Duchenne Muscular Dystrophy, who would 
come to our office and say, ``There is this promising trial. My 
son is not in the trial. But it doesn't improve you, but it 
prevents you from regressing.'' So he was racing against time 
for his son not to get into a wheelchair, because his goal was 
for his son not to be in a wheelchair.
    Another one, a constituent called crying whose son was on 
the trial for the artificial pancreas. And then the trial was 
over. Of course, it was in a lab setting, so they couldn't take 
it home. And she said, ``My son has never felt this good since 
he was diagnosed, and now I have got to give this up. They have 
it back now because it has been approved.''
    And I felt that because I had a child with little childhood 
issues, and parents immediately become experts in the 
information around that childhood disease, it just drives your 
life, I can tell you that.
    And so we hear from a lot of people, and what we want to be 
able to say with confidence is that the money we are 
appropriating has been spent correctly, which I feel confident 
with your leadership at NIH.
    And, Dr. Gottlieb, we want to make sure that the FDA is 
doing everything to get these.
    Because if you are a parent and you are not in the clinical 
trial, but you are hearing that, ``Well, this is for a small 
basis, but we are not sure I can extrapolate along the whole 
population,'' You want it for your child if you can have it, 
but understand the safety and the efficiency that you guys 
have.
    And so what we wanted to do, my view of what 21st Century 
Cures is all about, how do we give you the tools in your 
research and in your approval process to make sure that people 
in those situations are confident that it is coming as fast as 
possible, if we have to accelerate the approval process in 
those things moving forward.
    And so I am excited for this overview, because I think this 
is an example--we have Mr. Upton and Ms. DeGette, who were the 
cosponsors, 392 to 20-something I think was the count--that it 
is something that drives all of us here in Washington, because 
we all these experiences personally or with our constituents.
    And the one area that I focused on, and it was the 
continuous manufacturing, that is kind of my background. So, 
Dr. Gottlieb, I appreciate you being here. And I understand the 
development of continuous manufacturing systems could be some 
of the most significant developments in the pharmaceutical 
industry in the next decade. And I am happy to hear that FDA is 
taking steps to facilitate progress in this arena so that our 
country can recognize the benefits of this faster, in a more 
reliable way to manufacture pharmaceuticals.
    Can you speak to the next steps in this arena? And will you 
be providing additional grants? And how do you envision this 
technology improving in the field?
    Dr. Gottlieb. Thank you for the question, Congressman.
    As you know, this committee provided us a good head start 
in trying to facilitate the continued development of this very 
important technology, as you rightly noted, providing grants 
for the development of tools that will help this technology 
continue to advance.
    We have allocated one such grant of I believe a million 
dollars. We have about $4 million left to allocate, we are 
going to do that, to look at other programs, mostly in academic 
institutions, that can help facilitate the development of the 
regulatory tools that we will use to better evaluate and allow 
this technology to advance.
    This is very important, you mentioned, to allowing more 
efficient, maybe lower cost development or manufacturing. It 
also is very important to trying to address drug shortages. 
Because of the nature of continuous manufacturing you don't 
have as much risk of discontinuities in the manufacturing 
process as you would through traditional manufacturing.
    And the final point I would make is that by using 
continuous manufacturing you require a much smaller, less 
expensive footprint. So I think that the rapid deployment or 
the further deployment of this technology is going to lend 
itself to potentially repatriating some of the manufacturing 
that we have seen go offshore coming back to the United States.
    And a final thought is that I think this technology is 
going to be very important to some of the newer, more complex 
products that we see in development, like gene therapy. So we 
think of continuous manufacturing with respect to small 
molecules. It is also being adopted with respect to biologics 
as well.
    Mr. Guthrie. Well, thank you. As I said, as my friend's son 
with Duchenne, they are racing against time, so speed is 
important. But the regulatory side is important, too, as I 
understand that, as well.
    My time has expired. I would like to recognize the ranking 
member of the full committee, Mr. Pallone, for 5 minutes for 
questions.
    Mr. Pallone. Thank you, Mr. Chairman. You already actually 
asked one of my questions, so I have to cut that out.
    But let me start out with Dr. Collins, and then I will go 
back to Dr. Gottlieb about continuous manufacturing, if I 
could.
    Dr. Collins, during the 21st Century Cures debate we had a 
lot of discussion about the future of the biomedical research 
workforce and its importance to the U.S. remaining the world 
leader in biomedical innovation. While I am glad that we are 
able to work together to advance policies that support the 
development of the next generation of researchers, I am 
concerned about reports on how the House tax bill could thwart 
such efforts.
    As you know, a fundamental element in pursuing careers in 
biomedical research is obtaining a graduate degree. 
Unfortunately, the House tax bill could put such education out 
of reach for students. According to my own Rutgers University 
president, Dr. Robert Barchi, the provision of the House tax 
bill that would tax as income tuition that schools waive for 
graduate students working as teaching or research assistants, 
would impose--and this is a quote from the Rutgers president--
would impose an especially heavy burden on our graduate 
students, many in STEM fields. Other college leaders have said 
that the change will make graduate education unaffordable, lead 
to fewer graduate students at time when the U.S. needs more 
studentsearning advanced degrees in the STEM fields to remain 
competitive.
    So I just wanted to ask you, are you worried that making 
tuition waivers taxable income for graduate students would harm 
our efforts to create the next generation of scientists? And 
how might such a result harm our ability to advance the 
discovery and development of new treatments in Cures, which of 
course was the galvanizing force behind 21st Century Cures, if 
you would?
    Dr. Collins. Congressman, thank you for the question, and 
it ties in with what I was saying a few minutes ago responding 
to Chairman Walden about the Next Generation Researchers 
Initiative, which we are putting a lot of time and effort into 
trying to be sure becomes a high priority.
    Certainly graduate students as the path toward those 
independent investigators of the future are absolutely 
critical, and we want to have all the best and brightest who 
are interested in pursuing those careers to have the 
opportunity to do so. And anything that represents a major 
impediment in that regard is something we should take with 
great seriousness.
    I am not an expert in tax reform or in the particular 
provisions of any of the bills that are under consideration, 
but certainly I think we can all agree that given that science 
has driven our economy in this country--by most estimates more 
than 50 percent of our gross since World War II has been on the 
basis of science and technology--this is a very important area 
for continued investment. And anything that would diminish the 
interest and the talent of the next generation in joining that 
workforce is something we should be very cautious and careful 
about.
    Mr. Pallone. I appreciate that. Thank you.
    So let me go back to Dr. Gottlieb. I know that Mr. Guthrie 
talked about the continuous manufacturing issue. And you 
mentioned, I think, Dr. Gottlieb, that you awarded the first 
continuous manufacturing grant in this fiscal year, I guess to 
the University of Connecticut, to build a manufacturing 
platform for complex dosage forms.
    What I wanted to ask though is, will you discuss further 
how many additional grant awards the agency intends to offer 
and what criteria the agency is considering when awarding these 
grants for the continuous manufacturing?
    Dr. Gottlieb. Thank you for the question.
    I mentioned we had $5 million to allocate. We allocated a 
million dollars of it and we are going to continue to allocate 
the other $4 million. I am not quite certain how many different 
grants we will give, but there will certainly be a number of 
grants awarded. And there are a number of academic institutions 
doing good work in this area, including one in my hometown of 
Rutgers University, that has a program looking at this.
    The criteria we look at are programs that are developing 
regulatory tools that can serve as the basis for how we are 
going to evaluate this technology when sponsors bring in 
applications where they are employing continuous manufacturing. 
So because it is so novel, it requires us to think differently 
about how we apply our own regulatory oversight to the 
manufacturing process, and that is going to also require us to 
develop new methodologies, new SOPs, but also new tools to 
evaluate the safety and reliability of the manufacturing 
process.
    And so we are looking for institutions that are helping to 
develop those tools. As I mentioned, there are a number of 
them, including one in my hometown, but UConn also had a good 
program in doing this.
    Mr. Pallone. Thank you so much.
    Thank you, Mr. Chairman.
    Mr. Burgess [presiding]. The chair thanks the gentleman. 
The gentleman yields back.
    The chair recognizes the gentleman from Michigan, Mr. 
Upton, the primary sponsor of the Cures bill, 5 minutes for 
your questions, please.
    Mr. Upton. Well, thank you, Mr. Chairman.
    I know that Diana DeGette and I appreciate all the kind 
words here today, but I just want to remind everyone that it 
was everyone on this committee as we passed it 51 to nothing. 
We had wonderful staff who worked plenty of weekends for lots 
of the year. We had a leadership on both sides of the aisle. We 
had an administration. And we had the appropriators. So 
together we did this, and it was a great victory for sure.
    And I know a number of us were at the Ken Burns dinner 
earlier this week, and I am very proud to say that he is 
working on a documentary on the NIH that he will be unveiling I 
believe next year through PBS. And I talked with Dr. Collins 
earlier in the week. I know that they have done some extensive 
filming already.
    I think that it is important for the American public to 
see, in a nonbiased way, the great work that the NIH has done 
and is going to do. And, obviously, this legislation is going 
to find the cures that so many families desperately want.
    I would like to start off just by asking Dr. Collins to 
explore a little bit more of the All of Us Project. To me, this 
is exciting. I know a little bit about it. I know that the 
unveiling is scheduled for next spring. I have some concerns 
about the privacy element of it in terms of what the 
individuals themselves will experience or some of the 
protections that might be there.
    How can we help? And tell us a little bit more about it and 
what it is going to be able to do.
    Dr. Collins. Glad to. And I appreciate your strong support, 
and that of this entire committee, for the concept that we are 
trying to pursue here, which is the largest-ever contemplated 
longitudinal cohort study in the United States of individuals 
across a wide diversity of ages, ethnicity, socioeconomic 
status, race, and so on.
    And this is going to be a platform for discovery for almost 
everything you want to know about what allows people to stay 
healthy, and what happens when illness strikes, and how can we 
best take care of it.
    I appreciate your mention of the Ken Burns film, by the 
way. And I hope members of this committee had a chance to see, 
earlier this year, the ``First in Human'' series that was 6 
hours on Discovery Channel about what it is like to be involved 
in a clinical trial at the NIH Clinical Center and what goes 
through all those experiences in terms of trying to find 
answers for untreatable diseases. It was inspiring and 
emotionally powerful.
    The All of Us Program is really a dream for many of us that 
we have had maybe for a couple of decades but has only become 
recently practical. We are counting on this million strong 
group of Americans to be our full partners. As I mentioned in 
the opening statement, we are doing a beta test right now. We 
have enrolled about 9,500 individuals just to see how the 
pieces of this are going to work.
    Mr. Upton. And how long does that beta test take? I mean, 
for the individual when they come in. Is it a blood sample? 
What is it that they do?
    Dr. Collins. It is blood sample. It is a series of fairly 
simple physical measurements. It is answering a whole series of 
questions in a questionnaire at your own convenience. And it 
is, of course, a detailed consent process so that people know 
what, in fact, they are getting into.
    You asked about privacy. And everybody is worried about 
that. And we are as well. And this is a program that has to 
maintain the highest standards of privacy and security in order 
to be credible. And we are working with partners that are top 
of the market here in terms of doing that. One of our major 
partners is, in fact, Verily and Google.
    And all of the patient identifiers are stripped off before 
any of the data is actually moved into a location where 
researchers have access to it, and everything is encrypted end 
to end. We have already been doing a series of penetration 
tests and hack-a-thons to see whether there are weak spots in 
this enterprise. And so far it is looking really good. But we 
are not going to do the full launch until we are absolutely 
convinced that all of those parameters have been taken care of.
    Mr. Upton. So when that volunteer participates in the 
program, how often will you come back to that individual? And 
what information will they continue to transmit over the rest 
of their lifetime?
    Dr. Collins. That is critical, because we do want people to 
feel like this is something they are proud to be part of it, it 
is giving them information back. Retention is going to be 
critical over decades. So they will be getting information back 
about themselves in terms of blood test results, ultimately 
their DNA analysis, which is going to get started sometime next 
year, as well as giving them information about how they fit in 
with the rest of this million-strong people. So we will be in 
touch with them at least every couple of months, seeking 
constantly to hear from them, what they like, what they don't 
like. They are really at the table here in designing this with 
us.
    Mr. Upton. So a lot of us are very familiar with the 
private group 23andMe.
    Dr. Collins. Oh, yes.
    Mr. Upton. Where people actually send their saliva. Is this 
going to be somewhat similar to that? Is it going to be more 
extensive?
    Dr. Collins. So 23andMe is a commercial operation which 
many of us, including myself, have taken advantage of. It does 
give people genetic information back. We have learned a lot 
from them in terms of how they do their educational materials 
to explain things that can be a little complicated in a 
sensible fashion that people can absorb.
    But we are going to give more than that. We are also 
interested in environmental exposure.
    Mr. Upton. I know my time is rapidly expiring. But I know 
that your predecessor we worked with at the FDA on 23andMe to 
make sure that this could actually be launched in a successful 
way. So I presume that you will be working very closely with 
the FDA on this to make sure that it meets all the proper 
requirements.
    Dr. Collins. So FDA has worked, I think, very effectively 
in this space, if I can speak for my colleague here, in terms 
of figuring out how to do the right balance between protecting 
consumers against fly-by-night genetic tests that are giving 
you inaccurate information versus those where people are really 
interested. And I think they have got the balance just right.
    Dr. Gottlieb. And also trying to develop a framework. We 
have taken a firm base approach to the regulation of these 
kinds of consumer genetic testing technologies and announced 
that about 2 weeks ago, where we are going to allow the test 
platforms themselves to iterate and regulate the firm itself to 
make sure it has good SOPs in place and then allow them allow 
them to go to market with iterations to their test the same way 
we approach digital health.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    The chair recognizes the gentlelady from Illinois, Ms. 
Schakowsky, 5 minutes for questions, please.
    Ms. Schakowsky. Thank you so much. I really appreciate, Dr. 
Collins and Dr. Gottlieb, for your being here today.
    One of the most critical components of the 21st Century 
Cures Act was providing the NIH with the $4.8 billion in new 
funding. And these dollars are certainly critical in advancing 
research and many meaningful initiatives, like precision 
medicine and the Cancer Moonshot, as you mentioned, Dr. 
Collins.
    But we must have a serious conversation about drug prices 
and we need to do more to address this growing problem. If we 
are spending billions to incentivize the development of new 
drugs, I think we also have to ensure that patients can afford 
those drugs.
    The development of new drugs and devices is meaningless 
unless the discoveries are affordable to patients. It is almost 
cruel to find a cure and then have it priced so high that a 
patient can't afford it.
    I hear from my constituents that the cost of the drugs that 
they pay for, that they need, is far too high, and that they 
are frustrated that they are paying twice for their 
prescription drugs, once in taxpayer dollars, funding for drug 
discoveries, and then again at the pharmacy.
    So, Dr. Collins, here is my question. I know that 
scientists dedicated their lives, your life, to make 
discoveries that make the world a better and healthier place. 
As NIH is funding research that will lead to the development of 
therapies, do you think that patients should be able to afford 
the drugs that result from your NIH-funded research and that 
hard work?
    Dr. Collins. So this is, obviously, a topic that is on many 
people's minds. The designate for HHS Secretary yesterday said, 
yes, we do have a problem with drug pricing. Everybody agrees 
that this is a serious issue.
    NIH has some roles to play but not to the degree that 
perhaps the public wishes or you might wish that we do. What we 
can do is to try to be sure that we are doing the front end of 
drug discovery, which is to identify the right targets and then 
to develop a pathway towards turning those into therapeutics as 
efficiently and accurately as possible so that the failure rate 
for drug development is not so incredibly high as it currently 
is.
    One of the reasons that drugs are so expensive is because 
the industry has to compensate for all those failures, which 
are over 95 percent depending on how you count. If we had a 
success rate of, let's say, 50 percent instead of 5 percent, 
you can imagine how the equation would look a lot different.
    Our goal--and the National Center for Advancing 
Translational Sciences, NCATS, is a big part of that--is to try 
to do better in terms of identifying ways to be more efficient, 
ways that we could do toxicology more cheaply, and other things 
such as that.
    But when it comes to actually having a role in determining 
the cost, the price of a drug once it has left NIH's hands, it 
has been commercialized--which it needs to be, we don't make 
pills--we don't really have any levers to pull in that 
situation. We depend on other places to do so.
    Ms. Schakowsky. Well, let me ask you this. First of all, 
you mentioned a kind of calculation, how many failures there 
are. We do not know that. We have asked for transparency of how 
much is actually spent to develop. We would like to see that 
data.
    But has the NIH ever exercised what I think is its right 
under these licenses to ensure that publicly funded drugs are 
reasonably priced?
    Dr. Collins. I believe you are referring to the march-in 
rights, which are a component of the Bayh-Dole Act. We have 
looked at that and have been asked on a couple of occasions to 
see whether that would apply in a case where a drug price seems 
to be unduly high and NIH has played some role in its early 
development.
    But if you look at the language of the bill, it really 
intends to cover a circumstance where a drug is simply not 
available to the public under any circumstances, and then NIH 
is entitled to step in. This is a little different when it is 
available but at high cost. Our legal experts don't feel that 
the law actually puts us in a position to step in.
    Ms. Schakowsky. I thank you for that. I do understand that 
it is outside NIH's purview to always ensure that the drugs are 
reasonably priced. But, really, I think we need to be partners 
in figuring out this piece, because I believe that some of the 
calculations and some of the prices really do say that many 
people are not going to be able to access the cures that are 
available that are shortening their lives. So I appreciate 
that. Thank you.
    Dr. Collins. Glad to work with you in any way we can.
    Ms. Schakowsky. I yield back.
    Mr. Burgess. The chair thanks the gentlelady. The 
gentlelady yields back.
    The chair recognizes the gentleman from Illinois, Mr. 
Shimkus, 5 minutes for questions, please.
    Mr. Shimkus. Thank you, Mr. Chairman.
    Again, welcome. We are glad to have you here. Kind of an 
exciting day, and it is fun to talk about this. And what I am 
enjoying about the hearing is hearing my colleagues on both 
sides address issues that we have both been working on, either 
separate at some time, then jointly.
    So Gene Green and I have picked up Phil Gingrey's work and 
worked on the ADAPT Act. So my first question kind of deals 
with--to Commissioner Gottlieb. We know the success we are 
having. The question is, are there additional policies that we 
might be able to do to even help in the guise of economic 
incentives that would help move on this antibiotic resistance 
attack and being able to get drugs quicker to the market if 
needed?
    Dr. Gottlieb. Congressman, I would be happy to work with 
you on thinking through what additional steps we can take. We 
do have a platform now and a tail wind of some really 
extraordinary legislation that has just been passed in recent 
years. As you know, the GAIN Act did provide additional 
incentives through exclusivity for the development of 
antibiotics that were targeted to unmet medical needs. It is 
the kind of situations you are talking about.
    And we are still in the early days of implementing LPAD and 
the ADAPT Act. We are going to put out guidance, as I 
mentioned, this summer sketching out the framework for how we 
intend to implement that.
    And we have had multiple pre-IND meetings with sponsors. We 
think that this is going to grow into a robust tool for trying 
to get earlier, more expedited approval of drugs targeted to 
these special situations.
    I think there are some things we can do to think about how 
we reimburse these kinds of products in the marketplace. So to 
the extent that we are asking sponsors to develop antibiotics 
that are going to be used on an emergency basis, or a very 
limited basis, a reimbursement model where you pay per use 
might not be the most efficient way to provide an appropriate 
incentive.
    So we might want to think of things like site licenses. 
These are things that have been considered in the past, where 
hospitals might pay a licensing fee for access to a drug of 
that nature. That might provide more of an incentive. That is 
obviously outside of my scope.
    Mr. Shimkus. Well, let me jump in here, because one hurdle 
we haven't overcome, we were told earlier in the process that I 
have been involved with, was the issue of tradable vouchers, 
which I didn't get across the finish line.
    So my colleagues understand that there is a need, and that 
may not be the venue. So I would hope we would keep thinking if 
there is something else that we can do that might get us to the 
table where we can send another signal about this. And you 
don't have to talk about it now. Just this is the place to 
raise that issue.
    Let me go on the same line of questioning on antibiotic 
resistance and talk about just where we are on therapid 
diagnostic test to be able to identify quicker so that we can 
intervene earlier. Any comments on that?
    Dr. Gottlieb. Well, this technology is becoming more and 
more available at the point of care. We used to rely on blood 
cultures that would take days to grow out organisms and we 
would just give sort of broad spectrum antibiotics until we 
figured out what patients were infected with and we could 
tailor therapy.
    Now you have the ability to sequence organisms or you gain 
the ability to sequence them at the point of care. We are doing 
things with respect to next-generation sequencing, in 
collaboration with NIH, that I think is going to be very 
important to making these opportunities available.
    Dr. Collins. If I may, we are running a prize competition 
right now. And, again, 21st Century Cures had a specific call-
out to us to do prizes using the EUREKA part of the bill.
    For AMR, we are basically asking competitors to come up 
with a means within 4 hours of being able to determine what is 
the infection and does it have multiple drug resistance in the 
case of a urinary tract infection or pneumonia or sepsis. That 
would be a dramatic game-changer if we had that information in 
that period of time. There are a lot of competitors out there. 
There is 20 million bucks out there for the one who wins this, 
10 from NIH, 10 from BARDA. And I think that could be a pretty 
exciting moment if we can get the technology to that point.
    Mr. Shimkus. Well, yes. Thank you very much. And I am going 
to end on this, which is still a positive note.
    So I am also very excited about the All of Us campaign. The 
University of Illinois is involved with it, and that is kind of 
part of my area. And so it is exciting.
    And same issues. We had a telecommunications subcommittee 
hearing yesterday on big data, algorithms, all this stuff. Then 
I segued into my visit with Washington University, which is 
close to my home. I am in the St. Louis metropolitan area. So I 
know that university well, and I know the associated hospital 
that they work in conjunction with.
    They have been so excited about the passage of the 21st 
Century Cures Act because in their research--and I toured them 
just last week during the break and did Alzheimer's, new 
technologies that really drill down to the cellular structure, 
antibiotics, which is one of the worlds on which I focus 
individually.
    And they just reiterated the importance of consistency. 
Sometimes we have been inconsistent in the funding streams, and 
the 21st Century Cures has established a consistent streaming 
and commitment to what we are doing in the health-related 
field. So I want to thank you, and thank you on behalf of the 
University of Illinois and Washington University.
    Dr. Collins. If I may, in one sentence, just say thank you 
all for what you did in the Innovation Fund for 21st Century 
Cures, providing consistent support over a course of 10 years 
for these projects, which clearly are going to need that kind 
of sustained funding in order to be successful. And it is often 
difficult to see a path for sustained funding in the year-by-
year appropriations. So thank you.
    Mr. Shimkus. I am done. I yield back.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    The chair recognizes the gentlelady from California, Ms. 
Matsui, 5 minutes for questions, please.
    Ms. Matsui. Thank you, Mr. Chairman, for holding this 
hearing today and for Dr. Gottlieb and Dr. Collins to be here 
today as we talk about the implementation of the 21st Century 
Cures Act.
    As we worked together on this bill, patients were always at 
the center of our conversations. And as we move forward, 
patients are still at the center as we implement this bill.
    I am particularly concerned with research and drug 
development that affects patients with rare diseases, because 
for a small population of patients it is often very hard to get 
drugs and treatments through the approval process. I just can't 
tell you how many individuals have come to me with their 
concerns, in wheelchairs, and with their stories.
    Because finding cures for rare diseases is not only 
important to the patients with rare diseases and their 
families, but to all of us, because you never know where a cure 
is going to come from, and often research and drug development 
on one disease may create results for another. So we need to 
leverage all the tools that we have.
    I would like to hear about some updates, some provisions 
that I worked on in Cures that were aimed at encouraging 
innovation for patients with rare diseases. Sections 3012 and 
3016 of the law were designed to encourage the development of 
targeted drugs for rare diseases, including allowing 
manufacturers to leverage data from previously approved 
applications for new indications.
    We see that all of the time with rare diseases as many 
patients use drugs off label as their only options, drugs that 
were approved as safe and effective but not for their specific 
condition.
    Dr. Gottlieb, can you provide an update on implementation 
of these provisions?
    Dr. Gottlieb. If I may, Congresswoman, I just want to build 
on what you said. And I appreciate your comments and your 
commitment to these efforts.
    To the extent there are challenges associated with the 
development of drugs for rare diseases, sometimes it is 
difficult to enroll these trials as well. We have taken steps 
to try to facilitate that.
    I think also what we are seeing are situations where, 
because the biological basis is so well established for some of 
these drugs and we can select which patients will likely derive 
a clinical benefit, we are seeing clinical benefit very early 
in the development process.
    And that was the point of trying to see how we can apply 
the accelerated approval mechanism to achieve what you 
outlined, the ability to expedite these products to the market 
when we do observe an extraordinary clinical response in an 
early stage trial, knowing we are going to be able to get the 
confirmatory evidence.
    Building on those two provisions that you mentioned, we are 
going to be releasing very soon a guidance that I first 
announced probably 3 or 4 months ago that we were developing, 
which is a targeted therapies guidance. It is going to outline 
very specifically how sponsors can get approval for products 
that are targeted to biological markers rather than certain 
disease tissue states, if you will. So tissue-agnostic drugs.
    And the best example would be a cancer that might appear in 
multiple organ systems but be driven by the same biological 
marker. If you can demonstrate that a drug targets the 
underlying biological mechanism, you can get approval now 
across all those different indications.
    We are also, to the point you made, making robust use, in 
my opinion, especially in the oncology setting, of the 
provision that allows us to give supplemental indications more 
easily based on existing data in the public domain or 
references to literature rather than having to, in many cases, 
replicate the new clinical trials in those indications where we 
have a very strong biological rationale to know that the drug 
works there.
    That was the other point of my opening testimony today, the 
ability to extend approvals in other settings that are 
proportionate to where the original approval was given. So you 
approve a drug in a second-line oncology situation, and then 
making it easier to then extend it into a frontline indication 
when the evidence starts to accrue.
    Ms. Matsui. Well, thank you very much for that update.
    Dr. Collins, how can NIH's Precision Medicine Initiative 
benefit rare disease patients?
    Dr. Collins. Precision medicine, as a concept, is trying to 
get away from one-size-fits-all to identifying the individual 
characteristics that are going to lead to better prevention and 
treatment.
    While the Precision Medicine Initiative flagship, called 
All of Us, is not particularly well designed to deal with rare 
diseases, because even with a million people there may be 
relatively few with a truly rare disease, the whole rare 
disease field is very attached to the precision medicine idea.
    You can see what has happened with cystic fibrosis, which 
was mentioned earlier, where we now have therapeutics that are 
specific for the particular kind of misspelling that that 
individual has in the cystic fibrosis gene. That is a good 
example. And we want to see much more of that, because there 
are at least 7,000 of these rare diseases for which we know the 
genetic mutation but we don't yet have a treatment.
    We at NIH are working hard with our colleagues at FDA on 
something called the Therapeutics for Rare and Neglected 
Diseases Program, TREND, which is part of the National Center 
for Advancing Translational Sciences, because there are some of 
these disorders that are so rare that industry is not 
interested, at least initially, in investing in them, although 
there is more interest now than there used to be in industry.
    And I think we are making real headway. And something that 
the 21st Century Cures bill did was to give TREND the ability 
to run phase three trials on those disorders which we did not 
have at NCATS before, and we are grateful for that.
    Ms. Matsui. OK. Well, thank you very much. And I yield 
back.
    Mr. Burgess. The chair thanks the gentlelady. The 
gentlelady yields back.
    The chair recognizes the gentleman from New Jersey, Mr. 
Lance, 5 minutes for questions, please.
    Mr. Lance. Thank you, Mr. Chairman.
    And good morning to you both.
    Dr. Gottlieb from Middlesex County. Is that right.
    Dr. Gottlieb. That is right.
    Mr. Lance. Very good.
    Dr. Gottlieb, throughout the 21st Century Cures dialogue we 
heard about a number of innovative treatments that companies 
were pursuing that would target specific genetic mutations in 
patients with rare diseases. I am the Republican chair of the 
Rare Disease Caucus here in the House.
    This is, of course, quite encouraging. But we have also 
heard that there can be multiple genetic subtypes of each rare 
disease and that can further complicate drug development in 
clinical testing in already challenging circumstances.
    To ensure that as many patients can benefit from these new 
technologies as possible and as quickly as possible, as you 
know, section 3012 authorizes the FDA to rely on data that 
accompany previously submitted drugs that use the same or 
similar technology.
    Could you elaborate a little further--and I know you have 
been discussing this--about the ways in which the FDA has 
utilized its authority to date and what we should be doing 
more, perhaps, here at the congressional level?
    Dr. Gottlieb. Thank you, Congressman. And the provision, I 
think, that you have built into 21st Century Cures that you are 
referencing, I think, really anticipated the future and what we 
are seeing.
    The truth of the matter is, it is still early days in terms 
of the drugs that we are seeing that are targeting in many 
cases what are inherited disorders where you have a genetic 
change that drives a disorder but you have multiple subtypes 
that all produce the same clinical circumstance. And the 
question becomes, if you study one genetic subtype, when and 
how do you extend the approval into the genetic other subtypes 
without requiring the sponsor to enroll in a clinical trial in 
each one, especially when each one might be only a handfulof 
patients?
    We are currently having discussions with sponsors around 
this very principle. I think what Congress built into the law 
is giving us the latitude that we need to be thoughtful about 
how we can think about this and extend approvals across the 
range of subtypes that drive a common phenotype. And I think 
you will see us exercising that authority in some upcoming 
approvals. And we also plan to address this, to some extent, in 
the targeted therapies guidance that we will be releasing soon.
    Mr. Lance. Thank you, Doctor.
    And how does FDA's familiarity with an underlying 
technology affect subsequent product applications and the 
supporting data the agency expects to be included?
    Dr. Gottlieb. Well, I think our ability to understand how 
the product works and how it intervenes in the molecular basis 
for a disease is what drives our ability to make these 
extensions that you are talking about and give us confidence 
that a drug that works in one setting is going to have the same 
clinical performance in another setting where there might be a 
slight genetic variation but it leads to the same phenotype. So 
what you reference is instrumental in our ability to make these 
determinations.
    Mr. Lance. Thank you.
    I was pleased that language was included in the bill 
authorizing grant funding for the study and expansion of 
continuous manufacturing. New Jersey has been a leader in this 
area, including our state university, Rutgers, and others as 
well, bringing together research institutions and industry to 
advance technology.
    What steps are being taken by the FDA to carry out the 
language included in the act regarding what I have just 
discussed?
    Dr. Gottlieb. This has been a very high priority for the 
agency trying to facilitate the development of a platform for 
continuous manufacturing. We are going to continue to give 
grants to institutions that are helping to develop the tools 
that are going to enable us to continue to move this forward.
    We think continuous manufacturing represents the future. It 
is going to provide a much, much more robust way to manufacture 
products, especially some of the newer products that we are 
seeing. We think that it provides certain safeguards from 
potential drug shortages.
    And I think it also might help us repatriate manufacturing 
back here to the United States. The ability to manufacture off 
a small footprint that is driven by high technology lends 
itself to domesticating that process as opposed to outsourcing 
it to other countries as we have seen with traditional 
manufacturing. So I am hopeful that this is also going to help 
us build up a robust domestic industry.
    Mr. Lance. Thank you. I certainly encourage repatriation. 
And congratulations on your appointment and your confirmation. 
And, Dr. Collins, it is always a pleasure to be with you, and I 
look forward to being with you again at NIH, particularly on 
Rare Disease Day.
    And, Mr. Chairman, I yield back 8 seconds.
    Mr. Burgess. The chair thanks the gentleman.
    The chair recognizes the gentlelady from Florida, Ms. 
Castor, 5 minutes for questions.
    Ms. Castor. Thank you, Mr. Chairman.
    Dr. Collins, the 21st Century Cures Act funded NIH to 
provide support for biomedical research through the NIH 
Innovation Fund. This focused on four vital research priorities 
to address some of the greatest challenges in disease 
prevention and treatment.
    Back home in Tampa, we are home to the only NCI-designated 
cancer center in Florida, the Moffitt Cancer Center. And just 
in my short time in Congress I have been floored at the 
progress that we have made in treatments and cures for cancer. 
And yet, there is so much more to be done. And I think the Beau 
Biden Cancer Moonshot that is part of 21st Century Cures is an 
exciting research initiative because it will accelerate cancer 
research and improve screenings and treatments for cancer.
    Can you discuss some of the research that the Beau Biden 
Cancer Moonshot Initiative is funding and how it may contribute 
to addressing the burden of cancer across the country?
    Dr. Collins. Yes, I would be happy to.
    We convened a blue ribbon panel of some 28 individuals who 
are the most visionary folks we could identify to figure out 
what would be the best way to take additional resources coming 
forward from 21st Century Cures and do things that we otherwise 
wouldn't have been able to do. And they came up with a series 
of 10 different areas that were ripe for further investment.
    And I don't have time to go through all of them. I will 
just mention one because it is so much on everybody's mind 
right now as a source of great excitement, and that is the area 
of cancer immunotherapy.
    This, which for 40 years has been labored by a very small 
group of people, particularly Dr. Steven Rosenberg at the NCI, 
has arrived in the last few years as the most exciting 
development in cancer treatment in a very long time. We have 
had surgery, we have had chemotherapy, we have had radiation, 
and that was sort of it.
    And now we have a fourth modality, and a modality which, 
when it works, is capable of taking somebody with widely 
metastatic disease from melanoma, or somebody with advanced 
leukemia or lymphoma, and not just providing a response, 
providing what appears to be a cure. And when you see that, it 
is enough to make you believe that we should put every bit of 
energy in this to figure out how to get it to work for all 
cancers.
    And that is what the Moonshot is making it possible for us 
to do. Working with industry and this partnership that we just 
announced a month ago, we are trying to figure out why doesn't 
it work when it doesn't and what could we learn from that. Why 
doesn't it work for pancreatic cancer? Why doesn't it work for 
most cases of prostate cancer or breast cancer? It seems to 
work for a certain subset, but the immune system ought to be 
able to recognize those cancers too. What can we do to find 
that answer, working closely with our colleagues at FDA in 
this?
    And you have probably heard that just in the last few 
months the first so-called CAR-T cell approaches to leukemia 
and lymphoma are being approved, which is an example of this.
    So, again, thank you to the whole Congress for recognizing 
that this was one of those areas that was ready for a big 
boost. And the $300 million----
    Ms. Castor. Well, I share your excitement for 
immunotherapy. I have heard it directly from my researchers at 
home and from families now, that they have additional hope in 
their life.
    How about Alzheimer's disease? Give us the same sketch for 
hope and promise now under the 21st Century Cures Innovation 
Fund in Alzheimer's.
    Dr. Collins. So 21st Century Cures funded the BRAIN 
Initiative, which is an incredibly ambitious effort to 
understand how those 86 billion neurons between your ears do 
what they do, and each one of them with maybe a thousand 
connections. And that is going to provide us with this 
foundation of information about neuroscience that we just have 
not had.
    There is a huge effort, of course, more directed at 
Alzheimer's disease, and Congress has been increasing our 
funding through the regular process.
    Ms. Castor. Right. There hasn't been enough in the past.
    Dr. Collins. And it has been going up wonderfully well. And 
we are now in a position, I think, to take both the basic 
science coming from the BRAIN Initiative and the clinical 
applications that are possible through the regular 
appropriation and really turbo charge this effort to come up 
with answers.
    And we need those answers, as all of us know who look at 
those 5 million people who are already affected and look at 
what is going to happen in the next few decades with the aging 
of our population if we don't come up with a solution.
    I am guardedly optimistic, although this is a really hard 
problem, that we are on the path that is going to figure out 
what to do to prevent this disease in those who are at high 
risk before it even strikes.
    Ms. Castor. How can the public monitor progress here? You 
might go online and do a Google search, but that won't get to 
the heart of the matter of what is happening over the coming 
years because of these investments.
    Dr. Collins. So we try our best through NIH to make public 
information available, but we don't think it is appropriate for 
us to be out there marketing what we do. So we are educators, 
but we are not necessarily doing the best job of communicating 
to people who are interested. We count on the media or we count 
on interested advocates to get the word out, particularly the 
Alzheimer's Association and other advocates like that.
    And I do think the consciousness of the public has been 
raised about this. But in terms of tracking what is happening 
month by month, we need better opportunities to do that. I 
agree with you.
    Ms. Castor. Thank you very much. I yield back.
    Mr. Burgess. The chair thanks the gentlelady. The 
gentlelady yields back.
    The chair recognizes the gentleman from Florida, Mr. 
Bilirakis, 5 minutes for questions, please.
    Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
    Thank you for your testimony.
    Dr. Collins, as one of the co-chairs of the Congressional 
Parkinson's Caucus, I was proud that we included a neurological 
condition surveillance system as part of Cures. It is estimated 
that one in six people suffer from neurological disorders. This 
neurological surveillance system would gather information about 
patients, including incidences, prevalence, and also 
demographics and outcome measures.
    I know that the CDC would run the surveillance program, but 
NIH has the experts that would use the data. How will having 
this information available to NIH assist biomedical research at 
the agency and in the research community at large?
    Dr. Collins. Thank you for the question.
    That feature of 21st Century Cures, which as you point out 
is assigned to CDC to develop this neuroscience assessment of 
prevalence and incidence of neurological conditions, it is 
certainly something that if the data were available we would 
find it quite useful. I think at the present time, because of 
the funding issues, CDC has not been able to act upon that.
    We are certainly deeply invested in Parkinson's disease 
research, including working with industry on something called 
the Accelerating Medicines Partnership. It is possible that the 
All of Us program that is going to enroll a million Americans 
over the course of the next 3 or 4 years will provide some 
useful information here because some of those folks are going 
to have Parkinson's, quite a few, in fact, when you consider 
how frequent the illness is and the fact we are talking about a 
million people.
    But it won't quite substitute for what you asked CDC to do. 
I think this is a circumstance where the ability to get the 
information is not trivial. It takes a lot of resources, a lot 
of time. And here is where CDC, as I understand it, is having a 
hard time figuring out how to actually do what Cures Act asked 
them to do.
    Mr. Bilirakis. Thank you.
    Dr. Gottlieb, during my Cures roundtables in my district I 
heard from a woman who had a child with Duchenne Muscular 
Dystrophy. She talked about two hurdles: the challenge of 
acceptable biomarkers and the need to incorporate patient-
reported data. In Cures, we had a provision dealing with 
patient-reported data, as you know.
    You mentioned in your testimony there is a new section on 
patient experience data. Can you update us on when that came 
online, how FDA will incorporate that data in the review 
process, and what does FDA hope this type of feedback will lead 
to?
    Dr. Gottlieb. We are starting to do that right now, 
Congressman. Cures did give us the ability to expand on these 
opportunities to try to build in better measures of the patient 
experience as a measure of how we look at efficacy for purposes 
of approval.
    I think the opportunities that we are going to have that I 
am most excited about are better opportunities to look at 
things like physical performance. So you talked about Duchenne 
Muscular Dystrophy. One of the objective endpoints that we use 
in measuring outcomes in that clinical setting is traditionally 
a walk test that is meant to approximate physical function and 
look at whether or not new therapies are improving physical 
function or slowing the rate of decline in that clinical 
setting.
    But what if we had a tool that allowed a patient to wear a 
device, maybe it is a watch, that measures their physical 
performance in routine daily living? That might be very 
preferable to trying to do it in an artificial setting of a 
clinical trial where you are doing it in a sort of random 
fashion when a patient comes into a doctor's office for an 
evaluation or checkup. If you are able to look ata patient in 
their daily life, that might provide a much more objective 
measure of how a drug might be impacting their life.
    And so these are the kinds of opportunities that I think we 
have with new technology. They are the kinds of opportunities 
that I think that this legislation is giving us the legal basis 
to make better use of. And this is what I am looking to the 
future for.
    Mr. Bilirakis. Very good. Thank you.
    Again, Dr. Gottlieb, the other issue that was brought up in 
my roundtable was the challenge of acceptable biomarkers. This 
has been an issue that I have brought up in prior hearings.
    Can you update us on changes FDA has made? And how can we 
encourage the greater use of biomarkers, particularly for rare 
disease patients where traditional clinical trials may be too 
hard for them to--they are limited in population, as you know. 
So if you could answer that, I would appreciate it.
    Dr. Gottlieb. Thank you, Congressman.
    Here, again, Cure has provided us with new opportunities. 
The legislation did provide us an opportunity for the 
incorporation of drug development tools into our regulatory 
process. We have a biomarker qualification program now. We have 
eight biomarkers that are under consideration, all by various 
consortia.
    We also have another program that allows us to develop 
other kinds of measures that can measure efficacy or 
performance of patients in clinical settings. And we are going 
to qualify the first, for major depressive disorder, very soon, 
a new survey tool that looks at outcomes for patients who are 
suffering from MDD in the clinical setting. Again, this was a 
qualification process that was created by Cures as well.
    So these are moving forward. We are seeing a lot of 
interest in these kinds of opportunities, and we think this is 
going to provide a very important framework for the future.
    Mr. Bilirakis. Excellent. Thank you very much.
    I yield back, Mr. Chairman.
    Mr. Burgess. The chair thanks the gentleman. The gentleman 
yields back.
    The chair recognizes the gentlelady from Colorado, 5 
minutes for questions, please.
    Ms. DeGette. Thank you, very much, Mr. Chairman.
    One of the proudest achievements we had in 21st Century 
Cures, I thought, was the establishment of the Oncology Center 
of Excellence at the FDA.
    Dr. Gottlieb, as you mentioned in your testimony, this 
first-of-a-kind center enhances coordination between the FDA's 
drug device and biologic centers to leverage the agency's 
expertise on cancer. I am hoping that the OCE model will be a 
success that we can use for other diseases. Can you tell us 
what this center is already doing to advance the work in cancer 
treatment?
    Dr. Gottlieb. So we have already been able to use the 
center to do consolidated clinical assessments on a range of 
products. I think the most profound sort of manifestation of 
the opportunity that such a center affords us is what we saw 
with respect to the approval of two gene therapy products 
targeted to some rarer cancers that I think do provide a 
meaningful opportunity, and perhaps a profound opportunity, for 
patients to get more advanced and potentially more curative 
therapy in settings where there wasn't very good available 
therapy prior to the approval of these products.
    I think the essential point is that the center allows us to 
consolidate the clinical review and take a more 
multidisciplinary approach to how we look at the evaluation of 
efficacy and safety around these products. And we do think that 
this kind of center approach represents the future of how we 
want to approach other therapeutic spaces.
    Ms. DeGette. For other diseases?
    Dr. Gottlieb. Immunology, a center for neuroscience. These 
are things we are contemplating. Now, it is very important that 
we get it right in the setting of oncology since this is our 
test case and our first model for this.
    Ms. DeGette. And can you do more if you get full funding 
for this center?
    Dr. Gottlieb. Well, we appreciate what Congress tried to do 
in appropriating funds to the center through NIH. As Dr. 
Collins will attest, there have been some challenges associated 
with transferring those funds to FDA, some legal challenges.
    And so we look forward to continuing to have discussions 
about how we could fund this. It hasn't been funded to date in 
part because of the challenges associated with how the money 
was allocated, to nobody's fault. So we do want to work on 
that.
    Ms. DeGette. It is a frustration for us too. So if there is 
something we can do to help, let us know.
    I just have a couple of more quick questions. I want to ask 
about the IRB provisions. You guys know that for about 10 years 
I worked on a Protection for Patients in Research Act that 
would streamline the IRB process, and I was really happy to get 
some of that signed into law as part of Cures.
    I know that many of the IRB provisions in Cures have not 
been implemented yet, but I am hoping maybe you can talk to us 
about how the Cures provisions that streamline the IRB process 
will help reduce administrative barriers for scientific 
research.
    And we will start with you, Dr. Collins.
    Dr. Collins. Quickly, I think it has been very helpful to 
have those features in the Cures Act. One thing that we are now 
insisting upon is that multisite trials, which used to have 
multiple different IRBs, each of which might have some opinions 
about the wording of the consent form, we no longer think that 
that is the right way to do things. And having a single IRB for 
multisite trials has now become the norm. And, basically, if 
that is not to be the case, we need to understand why.
    And your support for that has been really helpful because 
we generally lost many months in the process of trying to----
    Ms. DeGette. We lost many months, and we lost many millions 
of dollars every time we did a research study.
    Dr. Collins. Indeed. So this makes a lot of sense, and we 
appreciate the opportunities to do that.
    Ms. DeGette. And sort of a related issue, and that is the 
clinical trials. The Cures provisions establish processes at 
the FDA to qualify biomarkers, incorporate patient experience 
and real-world evidence into trials. The committee recently 
built on the Cures provision in the FDA Reauthorization Act. 
What more can we do to improve the way and modernize the way we 
are doing clinical trials?
    We can start with you, Dr. Gottlieb, on that one.
    Dr. Gottlieb. I think that there is a lot we can do. And 
here again, Cures gives us a platform for doing it. And this is 
one place where I think that we are trying to take the spirit 
of what Congress did in Cures and wanted us to do and extend 
it.
    And so we are looking at opportunities to build in more 
modern approaches to how we design clinical trials, more 
adaptive designs, seamless clinical trials, other ways to make 
clinical trials easier to enroll and allow us to get measures 
of clinical benefit earlier. There is a lot we can do, I think, 
to think differently about how we move away from a very old 
paradigm for design of clinical trials and modernize these 
approaches.
    Ms. DeGette. So I will just ask both of you for all of 
these issues I am talking about. If you need additional 
legislative authority, please let us know so that we can work 
together in a bipartisan way to expand this. Because I think 
this is really going to help us get cures much more quickly to 
approval.
    And thank you, Mr. Chairman. I yield back.
    Mr. Burgess. The chair thanks the gentlelady. The 
gentlelady yields back.
    I am going to recognize myself 5 minutes for questions. I 
delayed at the beginning.
    Let me just pick up on that point that Ms. DeGette just 
made. This is, of course, our first oversight hearing on the 
Cures bill and it is the 1-year anniversary of the House 
passage of the legislation, but really the lines of 
communication should be constantly open.
    And I would just echo what she said. If there are statutory 
changes that need to be made to give you the flexibility to 
deliver the products we want you to deliver, we would like to 
hear from that. Let's not wait another year to have those 
discussions, is all I would say.
    Both of you--and I have got several questions that I will 
probably submit for the record because I am going to run out of 
time--but each of you mentioned a specific disease that I would 
like just a little bit more information.
    Dr. Collins, you mentioned sepsis.
    And, Dr. Gottlieb, you mentioned sickle cell.
    On the issue of sepsis, you said a 4-hour diagnostic. My 
generation of physicians, you had to draw blood cultures so 
many hours apart. Two weeks later, if they grew something, 
great, then you isolated the bacteria. You put it on Kirby-
Bauer sensitivity media. Seventy-two hours later, you would 
have the antibiotic to use if the patient was still with you. 
And you talk about a 4-hour timeframe. That is pretty 
incredible.
    Dr. Collins. It is. And it is still not a reality, but I 
can tell you the competitors for this prize are coming along 
pretty quickly. We already narrowed it down to a manageable 
group that is making notable progress.
    Yes, I am in the same generation of physicians you are, Dr. 
Burgess, and the idea of waiting all that time. Because, of 
course, what did we do then? We basically had to give every 
imaginable possibility, cover it, with the appropriate 
antibiotics, which meant everybody got broad spectrum 
antibiotics, probably got steroids, probably got all kinds of 
other support without really knowing what we were doing. We 
were flying blind.
    We want to take the blinders off and get the technology 
that is now capable of doing this. And much of it is based on 
genomics, the ability to find the DNA of that organism and have 
it tell you what that organism is capable of. There is no 
reason we can't do that.
    And yet, you are right, it took a long time to get to the 
point of actually talking about this as a reality. Even a few 
years ago most cases of sepsis were being managed pretty much 
like you and I did when we were residents.
    Mr. Burgess. Empirically, never use one drug if three will 
do. Yes, I remember those days.
    Dr. Gottlieb, you mentioned sickle cell. And it wasn't 
really part of the Cures bill, but at one of our 
reauthorization hearings in this room probably a year and a 
half ago the statement was made it had been 40 years since the 
FDA had approved a new sickle cell drug.
    And you talk that there is one now that is on the horizon 
or has it been approved? Could you elaborate on that?
    Dr. Gottlieb. This is a reference, Congressman, to gene 
therapy. We are seeing products in development using tools of 
gene therapy targeting a range of blood disorders, including 
sickle cell disease.
    Gene therapy lends itself--I think some of the early 
applications of it that we are going to see are going to be 
what we call ex vivo applications where you take cells out of 
the body, you manipulate them with genes, and you reinsert them 
in the body.
    And one of the opportunities is around the ability to do 
that to blood cells. And we know that if you can get patients 
with sickle cell disease to express more fetal hemoglobin, you 
can treat the underlying disease. You don't cure it, but you 
effectively dramatically reduce the phenotype.
    And so there are approaches like that, trying to use gene 
therapy to change the nature of blood cells in these patients 
where you take them out, you change them to express fetal 
hemoglobin, and then you put them back in.
    I will just close by saying these aren't going to be risk 
free. So it is going to be important that we carefully select 
the patients who are going to benefit the most from these kinds 
of approaches. But we are going to see these opportunities, I 
believe in the near future, if not in sickle cell disease, in 
other blood disorders.
    Mr. Burgess. And, again, my point, for illustration, was 
the very long time horizon between the FDA's approval of the 
last sickle cell medication. And it is encouraging there is 
something on the horizon on gene therapy.
    And I heard a discussion from a couple of researchers 
yesterday about some retinal diseases that they were targeting. 
And, again, this just seems like something that is tailor made 
for surrogate endpoints to be able to use either the perception 
of light, the restoration of vision, able to read a certain 
size print.
    And it was a one-time therapy, which then gets into the 
whole issue, how do you price something that is only given one 
time? If it gives you back your sight, it is probably worth a 
lot as far as value to the patient.
    I am sorry, Dr. Collins, you wanted to say something?
    Dr. Collins. I was just going to say with regard to sickle 
cell, there is a protocol now in the clinical center at NIH 
that has treated more than a dozen patients using a gene 
therapy vector, and it gets better and better as they keep 
refining it. And there are individuals now in that protocol who 
have essentially normal hemoglobin values and who say they have 
never felt better, they are free of those horrible crises that 
were part of their life.
    We are really making progress in this space. But it has got 
a ways to go to be sure that the risk--because you have to do 
something to make space for the corrected cells in the bone 
marrow. So you have to do a limited ablation. That is not a 
trivial thing to do, and we need to be sure we are getting that 
part right.
    Mr. Burgess. Well, I appreciate the update. That is 
encouraging.
    And I would just say, several years ago, I guess it has 
been over a decade ago, I had the opportunity to talk to Dr. 
DeBakey. We gave him a gold medal honoring him here in the 
House of Representatives.
    And one of our discussions, he and I went down to the VA 
the next day, and he told me when he graduated from medical 
school--and I guess it was sometime in the 1930s--he said: ``I 
knew I wanted to go into research, I knew I wanted to be a 
researcher, but there was nowhere in America to go, and I had 
to go to Germany in order to learn how to be a researcher, to 
get the credential to be a researcher.''
    Now scientists come from all over the world to the National 
Institutes of Health to get the credential to be a researcher. 
I hope Ken Burns reflects that in his opus.
    Thank you. I will yield back my time.
    And who am I recognizing next?
    I recognize Mr. Cardenas from California, 5 minutes for 
questions, please.
    Mr. Cardenas. Thank you very much, Mr. Chairman, and also 
Ranking Member Green. Thank you so much for having this really 
important hearing.
    Implementing 21st Century Cures, so far it appears we are 
doing a pretty good job of making progress. And so I want to 
thank you for that. And also if you could please share with 
your team our thanks for doing all that good work with the law 
that we passed here. Also, I want to thank you two gentlemen, 
doctors, for your service.
    My first question is--we will start with FDA--are there any 
vacancies in your department?
    Dr. Gottlieb. There are, Congressman. We are undertaking a 
process to try to reform our hiring system. I think, as you 
know, we have had challenges onboarding people in a timely 
fashion, and that has led to a backlog of vacancies that we are 
very focused on addressing.
    Mr. Cardenas. Do vacancies in any way contribute to a 
slowing down of the incredibly important work and progress of 
saving lives?
    Dr. Gottlieb. Yes. The truth of the matter is, you can 
always do more with more. It is hard for me to argue that if we 
are down hundreds of slots in our drug center, for example--and 
I think that is what you refer to--that that doesn't have an 
impact on the overall operation.
    We recently launched a hiring pilot around the user fee 
slots, and we are going to announce very soon the results of 
the new hiring process that we are going to be implementing on 
a pilot basis that dramatically shortens the time that it will 
take us, we believe, to onboard a new hire. If that pilot is 
successful, we plan to try to roll it out on a wider basis 
across the agency.
    Mr. Cardenas. Thank you.
    And same question to NIH. Are there any vacancies in your 
department?
    Dr. Collins. So we are fortunate in that more than 80 
percent of the dollars that go to NIH go out in grants to 
institutions all over the country, in all 50 states. And so the 
work that we support largely doesn't get done within our own 
four walls. We do have an intramural program which is about 11 
percent.
    Mr. Cardenas. Do you have vacancies?
    Dr. Collins. We do in that area because we are always 
turning over. And there was a hiring freeze at the beginning of 
the administration, which we are happy to say we have now come 
to a place where we are able, for the most critical hires, to 
be able to bring people on board.
    Mr. Cardenas. So there is a semi-freeze still? Critical 
hires, you make the point, you get to hire them, but others are 
still in abeyance?
    Dr. Collins. We are very focused right now on ways that we 
might be able to improve our administrative efficiencies. So 
Dr. Tabak, who is my principal deputy, and I are looking at all 
the hires very carefully and personally to be sure that we are 
making the right----
    Mr. Cardenas. And as well you should. I am not questioning 
your practices. My real question to you on that front is, what 
can Congress do to help you be more efficient of filling those 
vacancies, if there is anything that we can help in that, 
effecting a better, streamlined process?
    Dr. Gottlieb. Cures is going to help with the resources 
that you provided to us to be able to go out and target hires 
with certain technical expertise where we have a hard time 
competing on a salary basis with people with extraordinary 
expertise. And so that is helpful to us.
    I think that our challenge--we don't have a hiring freeze 
in place right now, we are able to move on hires--our bigger 
challenge has been the length of time it takes to onboard 
someone and the fact that if you are recruiting a medical 
reviewer who is a physician in an academic institution looking 
to make a career move and it takes us 12 months to bring them 
on, they might take another job in that interim.
    And so we need to find processes that allow us to compress 
that timeframe. We think we have done it. I have pulled over 
from Cedar one of their very senior executives, an 
extraordinary woman who is a very senior manager, worked at NIH 
for a while, to head up this hiring pilot. And we are very 
focused on trying to make this work with respect to the PDUFA 
slots. And then, if we can validate our new hiring template 
that we will be rolling out soon to provide transparency around 
it, we will implement it on a wider basis.
    Mr. Cardenas. Thank you.
    In the interest of time, I want to get to my last question. 
And if you could please think of Max asking you this question 
and try to keep your answer short. I only have 30 seconds left.
    If Max were to ask you, ``Should we continue to help people 
become scientists and doctors and get an education?'' should we 
continue to help them do that?
    Dr. Collins. Not only should, we have to. That is the 
future.
    Mr. Cardenas. OK. So if Congress actually took away some of 
the little things that help them get their education, would 
that be a good thing or a bad thing?
    Dr. Collins. That would not achieve the goal that we all 
would have to agree is critical for our future.
    Mr. Cardenas. Remember, you are talking to Max. Is that a 
good thing or a bad thing?
    Dr. Collins. It is a bad thing, Max.
    Mr. Cardenas. Thank you. Thank you very much.
    I yield back the balance of my time.
    Mr. Guthrie [presiding]. The gentleman yields back.
    And the gentleman from Indiana, Mr. Bucshon, is recognized 
for a 5 minutes for questions.
    Mr. Bucshon. Thank you, Mr. Chairman.
    Commissioner Gottlieb, as physicians we share a common 
desire to ensure patients see tangible benefits from 
advancements in science and medicine. The 21st Century Cures 
Act law laid a critical foundation to advance personalized 
medicine, especially as it relates to therapeutics.
    One area which was not really addressed by Cures was 
improving the regulatory paradigm for clinical diagnostic 
tests, which are often the entryway into personalized medicine. 
Both FDA-approved in vitro diagnostics and laboratory-developed 
tests have experienced incredible growth in terms of the number 
of tests offered in the market and the levels of their 
complexity. So physicians and patients rely on these tests more 
and more to make critical, life-altering decisions.
    Unfortunately, the diagnostics regulatory framework remains 
outdated, inconsistent, and insufficient, leading to potential 
patient safety concerns and barriers to innovation, in my view. 
Congress needs to do more, and I applaud your recent statements 
that it is time for legislation in this area.
    My colleague and I, Diana DeGette, released a discussion 
draft of the Diagnostics Accuracy and Innovation Act, DAIA, as 
you probably know, which aims to modernize the regulatory 
framework for diagnostic tests. Notably, the DAIA would create 
a new pathway to regulate clinical diagnostic tests outside of 
the medical device framework while ensuring consistent 
regulation regardless of the test developer.
    We believe the DAIA takes the best of what the FDA, CMS, 
and the states have to offer and creates a new, modernized 
regulatory paradigm building on the expertise and capacity of 
these critical entities.
    I am pleased that the agency, the FDA, is working now on 
technical assistance on the draft legislation, and I look 
forward to working with you and the agency to make the 
diagnostics reform a reality of this Congress.
    So the question I have is, what is your sense of what 
improvements need to occur in this important area and how it 
relates potentially to the personalized medicine space and how 
Congress can be helpful?
    Dr. Gottlieb. Thank you for the question, Congressman.
    As you know, we for a very long period of time exercised 
enforcement discretion with respect to this entire space. But I 
think as we see these technologies become more sophisticated 
and become more important to the clinical practice of medicine, 
and as we see some variability in the quality of the products 
that patients are using, on which they are making very 
important medical decisions, we do think there is a role for 
FDA to play in certain aspects of these products and across 
certain products.
    But we also believe that the traditional medical device 
approval process is a poor fit for the regulation of LDTs, 
laboratory-developed tests. And we think that there is an 
opportunity, in our view, to fashion a regulatory framework 
through legislation that can provide a more appropriate fit to 
the kind of technology we are talking about here.
    And so we are very eager to work with Congress on this. I 
think the opportunity couldn't be more ripe to do that. I think 
that the clinical opportunities for patients couldn't be more 
seductive and the need to do that.
    So we will provide whatever support and technical 
assistance we can to Congress, including the white paper that 
we put out, which laid out some of our thinking on this.
    Mr. Bucshon. Thank you very much. I appreciate that.
    Ms. DeGette. Will the gentleman yield?
    Mr. Bucshon. Yes. I will yield to Diana DeGette.
    Ms. DeGette. Thank you.
    So, Dr. Gottlieb, we really want to get going on this early 
in the new year. So the quicker we can get that technical 
assistance, the better.
    Thanks.
    Mr. Bucshon. Thank you.
    This is just kind of a doctor thing. I was a doctor before. 
So, Dr. Collins, I am interested in, the NIH many years ago, as 
you know, interleukin treatment, which is an immunotherapy type 
treatment, maybe 25 years ago even, especially as it relates to 
malignant melanoma I think----
    Dr. Collins. Exactly.
    Mr. Bucshon [continuing]. The NIH pioneered a lot of that 
work. Now it is 20 years, 25 years later, or whenever the date 
is, but I remember this from my residency in medical school.
    I mean, we are in an exciting time, but it has been quite a 
long time since immunotherapy has really been something we have 
been trying to develop, right? What do you think has slowed us 
down? I know we have gotten to a good place now, but what do 
you see as the barrier to actually getting us across the finish 
line to making this better?
    Dr. Collins. Well, Dr. Bucshon, it is a good example of how 
you have to build over many years from basic science efforts, 
from a lot of failed hypotheses, ultimately building the 
strength to understand how the immune system can be brought to 
bear on cancer. And now, understanding things like checkpoint 
inhibitors and how you can take immune cells out of the body 
and take them to school and teach them what they should go and 
look for in that person's cancer, we know how to do that now.
    I think now the big barrier is to figure out how do we take 
the successes with melanoma, with leukemia, with lymphoma, with 
some cases of lung cancer and kidney cancer, and get this to 
work for everything.
    It should. Every cancer is making abnormal proteins, which 
the immune system should be able to see. But cancers are very 
clever in hiding that. And if we could activate in every 
situation--pancreatic cancer, brain cancer, prostate cancer, 
breast cancer, ovarian cancer, all the places where we still 
don't do very well--and get the immune system to work there, 
then we could really declare victory.
    We have got a long way to go, but, boy, it is so different 
than where we were a few years ago where we weren't sure this 
was ever really going to work. And now it clearly is. We just 
need to expand that effort. And the Moonshot is making that 
possible.
    Mr. Bucshon. I am glad you highlighted the importance of 
funding basic science research and how that really over decades 
sometimes leads to things that you don't necessarily think it 
might lead to, but it gets you to a place where we are today, 
especially as it relates to immunotherapy.
    Dr. Collins. That is a great point. Thank you.
    Mr. Bucshon. Thank you. I yield back.
    Mr. Guthrie. The gentleman yields back.
    The gentleman from California, Ms. Eshoo, is recognized for 
5 minutes for questions.
    Ms. Eshoo. Thank you, Mr. Chairman.
    It is wonderful to see both of you here.
    And, Dr. Collins, I always like to say to my constituents 
that NIH stands for our National Institutes of Hope.
    And I think that you have both spoken to that today with 
not only your opening statements, but in your answers to 
questions to members. So thank you for your special leadership 
for people in our country.
    Dr. Gottlieb, in the 21st Century legislation Congresswoman 
Susan Brooks and myself had a bill that was included, 
Strengthening Public Health Emergency Response Act, and it 
established a priority review voucher, a PRV, to encourage the 
development of medical countermeasures, countermeasure drugs 
and vaccines at FDA.
    And I know that the FDA plans to issue guidance to address 
this. I would like to get maybe a quick update from you on the 
timeline of that guidance.
    Dr. Gottlieb. I appreciate the question, Congresswoman. I 
can get back to you specifically. I believe that that guidance 
is going to be out before the spring. I can give you a more 
specific timeframe on that.
    Ms. Eshoo. OK. That would be wonderful.
    And under the current legislation, the PRV sunsets in 2023. 
But if a product were being developed today, many of them need 
more time. So 5 years would bring us to the middle of a 
development cycle. Are you concerned about the uncertainty that 
that would yield?
    Dr. Gottlieb. As you know, Congresswoman, the 21st Century 
Cures Act also provided for GAO to undertake a more 
comprehensive look at the PRVs more generally, and I think we 
are looking forward to that evaluation to have a better sense 
how these are impacting development and how they are providing 
an incentive for sponsors to try to develop therapies against 
some of these unmet needs that Congress is looking to target 
additional incentives towards.
    So we are hopeful that that will help validate some of what 
the early experience has been, but I think we are really 
looking towards that report to answer some of these questions.
    Ms. Eshoo. Good. Thank you very much.
    Under the original legislation, the 21st Century Cures Act, 
H.R. 6, that the House passed, and we are celebrating its first 
anniversary today, the funding was mandatory. And then the 
final legislation authorized the increases to FDA and NIH, but 
didn't appropriate funding, making it subject to the annual 
appropriations process.
    So for all that the legislation calls for, which is 
obviously very important, how are both of your agencies doing 
with the appropriations process?
    Really, up front, because when the SPRO was put into this 
thing I just rolled my eyes, because we wouldn't have a drop of 
oil left in that strategic reserve if everything that claims to 
be funded by it were actually funded. And I understand that 
that is only part of it.
    But how are we doing?
    Dr. Collins. So my understanding is--and, again, this was 
pretty complicated financial negotiation--that the way in which 
this now applies is that the funds provided by 21st Century 
Cures do get allocated. All it requires is for the 
appropriators to basically----
    Ms. Eshoo. I know how it works. I am just asking, is it 
working for you? Are you getting enough money to do what you 
need to do in the timeframe that you have set forward and the 
challenges of the legislation? I know what the process is.
    Dr. Collins. OK. I got it. I am sorry.
    Ms. Eshoo. You don't need to repeat that. I already said 
it.
    Dr. Collins. We are in fact able to utilize the funds that 
came forward in fiscal year 2017. We look forward----
    Ms. Eshoo. Of course you can use them, that is not the 
point. Are you getting what you need in terms of funding for 
the first year of a 10-year period?
    Dr. Collins. Yes, we are.
    Ms. Eshoo. How about you, Dr. Gottlieb?
    Dr. Gottlieb. We have been allocated the funds that we 
expected to date.
    Ms. Eshoo. Good.
    Dr. Collins. I will tell you, I ran into Chairman Cole in 
the hallway coming here. He wanted all of you to know that he 
loves the fact that you provided funds to NIH, but he wishes 
that somehow----
    Ms. Eshoo. Well, we don't provide funds.
    Dr. Collins. Well, in a way. But he wishes that somehow 
people who gave him his allocation would pay attention to what 
he needs also. I had to pass that along from Chairman Cole.
    Ms. Eshoo. Well, he can talk to Members. He doesn't have to 
give you the message.
    I just want to add one more thing, and that is that I think 
not enough spotlight has been placed on this going to our 
future scientists and researchers, that this tax bill that is 
moving through the Congress in terms of graduate and 
postgraduate education is a killer. It is an absolute killer. 
So that should be part of the record.
    Thank you, gentlemen, very much.
    Mr. Carter. [presiding.] The gentlelady yields back.
    The gentlelady from Indiana, Mrs. Brooks, is recognized for 
5 minutes for questions.
    Mrs. Brooks. Thank you, Mr. Chair.
    And before my colleague from Colorado has to go to another 
hearing probably, I just wanted to thank her and former 
Chairman Upton for working with both sides of the aisle to get 
the most important piece of legislation. I have been here 5 
years. I think it is the most impactful and important piece of 
legislation that I have been involved in. I am very proud of 
it.
    I also was very proud to have worked with Congresswoman 
Eshoo on the piece of legislation that got included in this.
    I want to ask you, Dr. Gottlieb, to follow up just a little 
bit more, since we did get included the medical 
countermeasures, which for the record, just to make sure, these 
are specific material threats identified by the intelligence 
community as posing a material threat sufficient to affect 
national security or that has been de termined to seriously 
threaten national health security.
    And there is no commercial market for this. This is why we 
had this limited priority review voucher. And it is seen as our 
private sector partners' very real incentive to continue to 
develop critical vaccines, whether it is things like Ebola or 
Anthrax or other types of threats.
    Now, since we have gotten this passed, has the FDA seen an 
increase or a renewed interest from the private sector partners 
in engaging with the FDA in the medical countermeasure space?
    Dr. Gottlieb. I would have to get back to you with the 
specifics, Congresswoman. I know we have had some engagement 
with sponsors. I would have to get back do you to let you know 
how far along that engagement is. We have had pre-IND and some 
discussions with sponsors, I am aware of that.
    Mrs. Brooks. We would welcome you getting back with us 
because that is what the point of it was, was trying to make 
sure that the private sector had the incentives in which to 
engage, and we need to know what is working and what is not 
working.
    You also in your written testimony talked about the FDA's 
emergency use authorization, the 2017 guidance extending 
authorities to be applicable to animal drugs. Can you share any 
updates or any hurdles the FDA has faced or potential 
challenges in implementing this emergency use authority?
    Dr. Gottlieb. The EUA authority now out now applies to 
animal drugs, as you have said. I would have to get back to 
you, again, in terms of where we are talking to sponsors. I am 
not aware of the interactions that we have had to date. But we 
see this as a big opportunity to potentially give EUA to drugs 
targeted to animals where if you had a pandemic, for example, 
where the infection was transmissible to the animal and they 
can become a vector, you want to be able to treat the animal as 
well in the kind of a setting.
    Mrs. Brooks. Thank you for explaining that so well because 
that is so very important. We focus on people, but because 
animals can transmit so many diseases, I think that is 
critically important.
    Dr. Collins, in my time remaining, can you talk with us a 
little bit more with respect to the Precision Medicine 
Initiative, the focus on the All of Us Research Program. And I 
understand when I was in another hearing you might have spoken 
about it already a bit. But obviously this large group of 
volunteers from around the country that are going to be 
providing genetic data, biological samples, and so forth, a new 
growing field.
    What are some of the challenges you are seeing or what are 
your hopes for this All of Us Research Program? Can you talk 
about it a bit further?
    Dr. Collins. My hopes are that with a million participants 
this is going to be the most significant study ever undertaken 
to identify what the factors are that allow people to stay 
healthy, because many of these participants will be healthy, 
and if illness happens, what is the best way to manage it?
    So we will have such an enormous database. It will be 
accessible, with all the personal identifiers removed, to 
researchers who have qualified ideas to try the learn from it.
    It will also be a platform where many clinical trials can 
also get started because these participants will have been 
preconsented for contact to see if they would be interested in 
taking part in a clinical trial, say, for diabetes or 
Alzheimer's risks. So that should greatly speed up the ability 
of doing all kinds of research that now is slow and expensive.
    But I think most of all, to be part of this, these millions 
folks are going to teach us things about health in America that 
we just didn't know and how we can move from the one-size-fits-
all approach, which is kind what we are stuck with most of 
medicine, into something that is much more individualized, the 
precision medicine idea.
    It will take a while for this to build up its strength in 
terms of what it is going to teach us about medicine. But over 
the course of the coming years, I don't think very many things 
will happen in terms of understanding health without somebody 
pointing out what all of us told us because of the size and 
scale of that effort.
    Mrs. Brooks. You have contracted or you are entering into 
partnerships, if I am not mistaken, with hospitals, various 
community health centers, I assume----
    Dr. Collins. Yes.
    Mrs. Brooks. --the VA, to be a part of this.
    Dr. Collins. All of those.
    Mrs. Brooks. Will the other researchers that might not be 
affiliated with those institutions have access as well?
    Dr. Collins. Absolutely. Anybody who is qualified to be 
able to put forward a hypothesis that is scientifically 
reasonable will have access. We are not trying to limit this at 
all. The joy that I hope will come out of this is these 
discoveries which will come from people who maybe didn't even 
know they were interested in this but had a great idea.
    Mrs. Brooks. And how will people be recruited to be 
participants?
    Dr. Collins. So those who are currently covered by health 
provider organizations that have signed on to be our partners 
will be approached. But anybody in the United States will be 
able to join.
    When we launch this next spring, you will see a lot about 
this. We hope all the Members of Congress will decide to join. 
It will simply mean getting on the Internet, reading some 
material, deciding about a consent, giving a blood sample, and 
doing a very simple physical exam.
    Mrs. Brooks. Thank you very much. Thanks for your work.
    I yield back.
    Mr. Carter. The gentlelady yields back.
    The gentleman from New York, Mr. Engel, is recognized for 5 
minutes for questions.
    Mr. Engel. Thank you very much.
    And let me say, I have long been a committed advocate for 
those suffering from rare diseases in their families. I was the 
author of the ALS Registry Act and the two most recent Muscular 
Dystrophy CARE Act reauthorizations.
    And the work has shown me how great the need is for new 
therapies and just how much hope and comfort medical 
breakthroughs can bring to patients and their families. And 
that is why I was pleased to support the passage and contribute 
to the 21st Century Cures Act.
    So thank you to both doctors for being here today and for 
helping us carry this important work forward.
    Let me ask both of you this question. I feel that there 
should be formalized, straightforward ways to gauge the safety 
and efficacy of medical treatments, and that is why I worked to 
ensure that language on biomarkers was included in the 21st 
Century Cures. These tools are valuable. They tell us the state 
of a person's health. It can help make these kinds of 
evaluations better.
    I was happy to work with Congresswoman McMorris Rodgers to 
include provisions on biomarker development qualification. I 
know that the FDA regularly employs biomarkers during the drug 
approval process, but there has not been a formal procedure in 
place for biomarker development and use.
    My understanding is that a lack of taxonomy and evidentiary 
standards has made it difficult to develop workable biomarkers 
that can be replicated during the drug approval process.
    So I am wondering if each of you would talk a bit more 
about how NIH and FDA will work with each other, industry, 
academia, and other stakeholders, to develop better biomarkers 
and improve the way they are used for clinical trials and drug 
approvals.
    Dr. Collins. I will start. Congressman, I appreciate the 
question because that is something of intense interest for both 
of our agencies.
    For several years we have run something called the 
Biomarkers Consortium, which is a joint NIH/FDA/industry effort 
to try to identify opportunities where biomarkers that seem to 
be potentially valuable in terms of predicting response to 
therapy can be validated, and there has been a lot of activity 
in that space.
    More recently, take an example of cancer, this new 
Partnership for Accelerating Cancer Therapies, PACT, has as its 
main goal identifying biomarkers for cancer immunotherapy that 
could be folded into the way in which we make selections about 
which clinical applications are going to work.
    We worked with the FDA a year or so ago also to develop a 
biomarkers glossary so that we could all really agree about 
what the terminology means. You mentioned that taxonomy can 
sometimes be a little tangled up. So we have an agreed-upon way 
of using the language and the terminology.
    But I will turn it over to my colleague, because obviously 
this is critical for figuring out how best we can come to 
approve therapies.
    Dr. Gottlieb. I will just add briefly, Congressman, I think 
this is another place where Cures and the provisions that you 
worked on, you talked about, have given us important new tools 
to create a framework that is going to lead to more development 
of these kinds of biomarkers.
    To give you some sense of what we have already achieved, we 
have entered into or received 11 letters of intent around the 
qualification of biomarkers through the provisions that you 
crafted for the development of drug development tools and have 
engaged with 10 external sponsors already around the 
development of these biomarkers.
    And we have even more engagement with especially the 
development of clinical outcomes assessment tools also, which 
are another element that have become critically important to 
try to foster more efficient drug development.
    So that might not sound like a big number. In our 
estimation it is a profound number given the fact that these 
are still early days in the development of these new frameworks 
and we are seeing this level of interest.
    Mr. Engel. Thank you. Thank you both.
    Dr. Gottlieb, I want to focus on biomarkers. So let me ask 
you this question. With respect to the section of 21st Century 
Cures on qualification of drug development tools like 
biomarkers, the proposed FDA workplan for 21st Century Cures 
Act Innovation Account activities says: ``Once fully 
implemented, this section has the potential to transform drug 
development and review.''
    Could you expand on that, please? And how do you think that 
drug development tools like biomarkers will affect patients on 
the real world level? And how soon will we see these effects?
    Dr. Gottlieb. Well, one of the challenges in the past was 
that when we had validated tools that were used to help make 
drug development itself more efficient, in many cases those 
tools were validated in the context of a single clinical trial, 
and that clinical trial was the intellectual property of a 
single sponsor. They didn't become tools that were in the 
public domain that could be easily used by other sponsors who 
could then piggyback on these kinds of opportunities to use 
biomarkers as a way to facilitate more efficient development.
    I think what Congress foresaw in the development of this 
new framework was the ability to have consortia and other 
entities, academic institutions, others, develop biomarkers 
that can become part of the public domain and become tools that 
many sponsors could use in an efficient fashion to help make 
their development programs more efficient.
    So we are very helpful that this new framework, which it is 
an entirely new paradigm and way of thinking about the 
development of biomarkers as drug development tools, is going 
to lead to a lot of new opportunities.
    Mr. Engel. Well, I want to thank both of you for excellent 
testimony and also for excellent work. Thank you so much.
    Thank you, Mr. Chairman.
    Mr. Carter. The gentleman yields back. Now the chair will 
recognize himself for 5 minutes for questions.
    Let me begin by thanking both of you for being here and 
both of you for the important work that you do.
    Dr. Gottlieb, I will start with you. I wanted to ask you 
about the executive order that was signed by President Trump 
the beginning this year that had to do with the one-in, two-out 
rule of regulations that were being imposed by the agencies, a 
rule, by the way, that I very much support and am very happy 
that he put into place.
    But I was just wondering, has this really impacted you in 
any way in trying to implement care or cures?
    Dr. Gottlieb. Not in a negative fashion, Congressman. We 
have periodically over the course of the history of the agency 
taken opportunities to do periodic looks at our regulations to 
make sure that they are not outdated, that they are still 
having their intended purpose. And I think that the executive 
order provides us another good basis to do that, and that is an 
important exercise.
    We have certainly been able to find places where there are 
regulations that are outdated or maybe no longer relevant that 
we think perhaps we could repeal in its entirety. I mentioned a 
couple of times we have a regulation defining standards of 
identity for the baking of cherry pies. We have one such 
regulation on the books.
    But keep in mind that the executive order applies to 
regulations that are imposing new regulatory burdens. Many of 
our regulations are deregulatory. In many cases we are 
promulgating regulations that are actually saving money and 
making the process itself more efficient.
    So we have been able to operate very efficiently under that 
framework, and we think it is a constructive framework.
    Mr. Carter. Great.
    Dr. Gottlieb, you and I have spoken many times. As you 
know, currently I am the only pharmacist serving in Congress. 
And of importance to me and all of my colleagues, of course, is 
the opioid epidemic in our country.
    One of the things that I have pushed as a pharmacist has 
been the fact that in my mind there is a gap, if you will, I 
refer to it as a gap, between what physicians can prescribe for 
pain, that being Tylenol, Acetaminophen, Tramadol, if you will, 
and then you go to the opioids. And I refer to that as the big 
gap there.
    Now, once you get past perhaps Lyrica and Neurontin, you 
really don't have any other choice but to go to the opioids. 
And as part of Cures and as part of CARA, you have been given 
the authority in the FDA of streamlining, of fast-tracking some 
of these nonaddictive treatments.
    First of all, have you gotten from the pharmaceutical 
manufacturers any applications for these type of drugs? And 
have you done anything to implement this?
    Dr. Gottlieb. We are seeing the development of what you 
would refer to as nonaddictive opioids, drugs that maybe hit 
the same receptor but through a different pathway and might not 
have the same addictive qualities. I mean, it still needs to be 
demonstrated through rigorous science whether in fact that is 
going to hold true.
    But we are seeing the development of these kinds of 
products. As you know, some of them are in early stages of 
development. Such products would qualify potentially for all 
the opportunities for expedited review, including breakthrough 
therapy status, and that would be something that would be 
confidential, however, unless the sponsor chose to disclose it.
    I would also pull into the discussion the development of 
medical devices, because we talk about systemic therapy for the 
treatment of pain in many situations where the pain itself is 
very localized. And there is a way to, through a more 
sophisticated device, deliver anesthesia locally. You can 
potentially prevent the application of systemic therapy.
    And so we are seeing those opportunities as well, and we 
are going to be taking steps in the near future to try to 
incentivize those kinds of opportunities.
    Mr. Carter. And you of course understand how imminent this 
problem is and how we need help. So I suspect this will be on 
the top of your to-do list.
    Dr. Gottlieb. It is on the top of my to-do list.
    Mr. Carter. Dr. Collins, I suspect NIH is very much 
involved in this in collaboration as well. I know that your 
Partnership for Accelerating Cancer Therapies is something that 
you have been working on to address really the cancer problem, 
but my hope is that this is something that you will duplicate, 
if you will, to deal with the opioid problem as well.
    Dr. Collins. And we are in fact deeply engaged in that, 
Congressman. We will in fact on December 12th and 13th hold a 
meeting of 33 pharmaceutical company representatives, NIH and 
FDA, building on studies that we have carried out over the last 
few months to really put in place a framework for a public-
private partnership that has never been tried before, to do 
exactly what you are talking about, to develop these 
nonaddictive but highly potent pain medicines, which we 
desperately need.
    I will just point out this morning in the New England 
Journal there are two publications on the development of 
monoclonal antibodies against something called CGRP that are 
showing great benefit for migraine for people who have been 
resistant. It is a good example of a nonaddictive kind of pain 
medicine working on a very different pathway than opioids.
    We have a lot of basic science we can build on now to do 
that, but we need the full partnership of industry as well, and 
I think everybody is ready to do that.
    Mr. Carter. There is no question in my mind about it. As I 
have said, over my years of practice in pharmacy I have seen 
nothing short of miracles come out from the research and 
development from the pharmaceutical manufacturers. They need to 
step up now and they really need to help us with this problem. 
This is a national epidemic, and I am very confident that if 
they set their minds to it, they can do just that.
    Dr. Collins. They are ready to do just that. It has been 
really quite exciting working with companies over the course of 
the last 6 or 7 months to see just how ready they are to roll 
up their sleeves and put their time and resources into this 
problem.
    Mr. Carter. Absolutely. And I appreciate you, both of you, 
and your cooperation in assisting them and fast-tracking this 
as much as we can.
    OK. The chair now recognizes the gentleman from Missouri, 
Mr. Long, for 5 minutes for questions.
    Mr. Long. Is that because I am the only one left?
    Mr. Carter. Yes, sir.
    Mr. Long. Thank you, Mr. Chairman.
    I want to reiterate what my friend Congresswoman Brooks 
next to me said earlier. And that is, when people ask me, 
``What is your biggest accomplishment in Congress? What are you 
the most proud of?'' Just 21st Century Cures, period, case 
closed.
    And that was done in a huge bipartisan fashion. As Chairman 
Upton mentioned earlier, 51 to nothing out of this committee, 
which you never see. And there were a lot of people that had a 
big part in that, such as Diana DeGette and Chairman Upton.
    And I would be remiss without mentioning my buddy, Super 
Max, right here on the front row, who was a big reason that we 
got that through, and he attended a lot of hearings.
    And thank you, Super Max.
    But we do a lot of things in a partisan fashion here in 
Washington, unfortunately, I think, most of the time. But one 
thing that we did do in a bipartisan fashion was 21st Century 
Cures.
    And also, there were a lot of folks that when they looked 
out at a hearing here in the 115th Congress and were looking at 
the Director of the National Institutes of Health, a lot of us 
got together from both sides of the aisle and said we would 
like to see you sitting there again. And so that came to 
fruition also.
    So it is an honor to have both of you gentlemen here today. 
It truly, truly is.
    Dr. Gottlieb, I am going to ask you a couple of questions 
here. 21st Century Cures included a provision to facilitate 
better dissemination of healthcare economic information, and in 
January the FDA published draft guidelines on this issue.
    Could you discuss any feedback FDA has received from 
stakeholders? And what do you think is working well? And are 
there any ways you think that communication could be improved?
    Dr. Gottlieb. Thank you for the question, Congressman.
    I think this is a very important provision of Cures. I 
think to the extent that we can facilitate a more seamless 
exchange of information between product manufacturers and 
payers, we can incentivize the development of different kinds 
of contracting arrangements that maybe could allow products to 
be priced more closely to value.
    I think this is an important element of trying to make sure 
we have a competitive market for how products get priced in the 
market. So I think that this is important to clarify what FDA's 
role is and isn't in regulating this information.
    You are right, we received a lot of questions with respect 
to the draft guidances that were put out almost a year ago. We 
are going to be finalizing those guidances in the very near 
future. I said before the end of this year earlier, we might 
slip slightly into the new year in terms of when we get out 
those final guidances.
    But our aim will be to go beyond what we did in the draft 
guidances to try to create a framework that provides for the 
free exchange of this kind of information and articulates, as 
Congress intended, that FDA doesn't intend to play a role in 
regulating the exchange of useful information in this context, 
even if it might have some authority to do that.
    Mr. Long. You note in your testimony that the use of real 
world evidence could help streamline clinical development and 
could help inform the safe and effective use of medical 
products. Could you speak to the FDA's efforts to incorporate 
real world evidence into regulatory decisionmaking?
    Dr. Gottlieb. We are already seeing those efforts come to 
fruition, in part owing to the authorities and the nudge that 
we got from Congress that you wanted us to make more widespread 
use of this evidence, especially as the tools for collecting 
this evidence and drawing conclusions on the basis of it got 
more sophisticated.
    We recently approved a supplemental indication on a heart 
valve based entirely on real world evidence gathered from a 
patient registry. And we have also granted supplemental 
indications to some drugs in part on the basis of real world 
evidence that was derived from real world data.
    So this is becoming a part of the regulatory process. I 
think where it is going to have even more prominent application 
is in the post-market setting where we are opening up a 
framework for sponsors to be able to satisfy their post-market 
requirements on the basis of real world data or real world 
evidence collected from real world data.
    Mr. Long. OK. Thank you.
    And I noted earlier that--of course things pop into my mind 
that don't pop into other people's mind--but when you were 
talking about gene therapy, just as you said that, Gene Green 
walked in.
    So I think it is a different gene therapy, unless you want 
to tell us something, Gene.
    I yield back.
    Mr. Carter. The gentleman yields.
    The chair recognizes the gentlelady from Indiana, Mrs. 
Brooks.
    Mrs. Brooks. Thank you for allowing me to speak out of 
order, Mr. Chairman.
    My good friend and colleague from Missouri, Mr. Long, 
besides acknowledging that it was awesome to have Max and his 
mom here, and I want to thank him, but I also want to 
acknowledge that a Hoosier family has also been here, Laura 
McLinn and her son Jordan, who is back in the office. He 
suffers from Duchenne Muscular Dystrophy, and they have also 
been active in Indiana in advocating for Cures. And I just 
wanted the folks who are testifying and who are devoting their 
lives to know that this matters to so many families. And I just 
wanted to acknowledge them for being as here as well.
    Thank you. I yield back.
    Mr. Carter. The gentlelady yields back.
    Seeing there are no further members wishing to ask 
questions, I would like to thank all of our witnesses again for 
being here today.
    I would like to submit a statement from the Healthcare 
Leadership Council for the record.
    [The information appears at the conclusion of the hearing.]
    Mr. Carter. And pursuant to committee rules, I remind 
members that they have 10 business days to submit additional 
questions for the record. And I ask that witnesses submit their 
response within 10 business days upon receipt of the questions.
    Without objection, this subcommittee is adjourned.
    [Whereupon, at 12:31 p.m., the subcommittee was adjourned.]
    [Material submitted for inclusion in the record follows:]
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