[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]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
______
U.S. GOVERNMENT PUBLISHING OFFICE
28-733 WASHINGTON : 2019
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
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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.]
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