[Senate Hearing 114-591]
[From the U.S. Government Publishing Office]
S. Hrg. 114-591
CONTINUING AMERICA'S LEADERSHIP: THE FUTURE OF MEDICAL INNOVATION FOR
PATIENTS
=======================================================================
HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED FOURTEENTH CONGRESS
FIRST SESSION
ON
EXAMINING THE FUTURE OF MEDICAL INNOVATION FOR PATIENTS
__________
APRIL 28, 2015
__________
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
LAMAR ALEXANDER, Tennessee, Chairman
MICHAEL B. ENZI, Wyoming PATTY MURRAY, Washington
RICHARD BURR, North Carolina BARBARA A. MIKULSKI, Maryland
JOHNNY ISAKSON, Georgia BERNARD SANDERS (I), Vermont
RAND PAUL, Kentucky ROBERT P. CASEY, JR., Pennsylvania
SUSAN M. COLLINS, Maine AL FRANKEN, Minnesota
LISA MURKOWSKI, Alaska MICHAEL F. BENNET, Colorado
MARK KIRK, Illinois SHELDON WHITEHOUSE, Rhode Island
TIM SCOTT, South Carolina TAMMY BALDWIN, Wisconsin
ORRIN G. HATCH, Utah CHRISTOPHER S. MURPHY, Connecticut
PAT ROBERTS, Kansas ELIZABETH WARREN, Massachusetts
BILL CASSIDY, M.D., Louisiana
David P. Cleary, Republican Staff Director
Evan Schatz, Minority Staff Director
John Righter, Minority Deputy Staff Director
(ii)
C O N T E N T S
__________
STATEMENTS
TUESDAY, APRIL 28, 2015
Page
Committee Members
Alexander, Hon. Lamar, Chairman, Committee on Health, Education,
Labor, and Pensions, opening statement......................... 1
Murray, Hon. Patty, a U.S. Senator from the State of Washington,
opening statement.............................................. 3
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas....... 47
Scott, Hon. Tim, a U.S. Senator from the State of South Carolina. 51
Warren, Hon. Elizabeth, a U.S. Senator from the State of
Massachusetts.................................................. 52
Cassidy, Hon. Bill, a U.S. Senator from the State of Louisiana... 54
Bennet, Hon. Michael F., a U.S. Senator from the State of
Colorado....................................................... 56
Isakson, Hon. Johnny, a U.S. Senator from the State of Georgia... 58
Casey, Hon. Robert P., Jr., a U.S. Senator from the State of
Pennsylvania................................................... 60
Witnesses
Austin, Christopher P., M.D., Director, National Center for
Advancing Translational Sciences, National Institutes of
Health, Bethesda, MD........................................... 5
Prepared statement........................................... 7
Pettigrew, Roderic I., Ph.D., M.D., Director, National Institute
of Biomedical Imaging and Bioengineering, National Institutes
of Health, Bethesda, MD........................................ 9
Prepared statement........................................... 11
Woodcock, Janet, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration, Silver Spring, MD...... 13
Prepared statement........................................... 14
Shuren, Jeffrey E., M.D., J.D., Director, Center for Devices and
Radiological Health, Food and Drug Administration, Silver
Spring, MD..................................................... 25
Prepared statement........................................... 27
(iii)
CONTINUING AMERICA'S LEADERSHIP: THE FUTURE OF MEDICAL INNOVATION FOR
PATIENTS
----------
TUESDAY, APRIL 28, 2015
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The committee met, pursuant to notice, at 10:03 a.m., in
room SD-430, Dirksen Senate Office Building, Hon. Lamar
Alexander, chairman of the committee, presiding.
Present: Senators Alexander, Burr, Isakson, Collins, Scott,
Roberts, Cassidy, Murray, Casey, Bennet, and Warren.
Opening Statement of Senator Alexander
The Chairman. The Senate Committee on Health, Education,
Labor, and Pensions will please come to order. This morning,
we're holding a hearing on Continuing America's Leadership: The
Future of Medical Innovation for Patients.
Senator Murray and I will each have an opening statement.
Then we'll introduce our panel of distinguished witnesses.
After our witnesses' testimony, Senators will each have 5
minutes of questions.
This is our third hearing in the committee on examining how
we can get safe drugs, medical devices, and treatments from the
discovery process through the regulatory process into medicine
cabinets and into doctors' offices for patients who need them.
Today, we have experts from the National Institutes of Health
and the Food and Drug Administration who can speak to specific
challenges to that process, what NIH and FDA are working on to
address these challenges, and barriers that remain in their
way.
Each of our witnesses today knows a great deal about
innovation. Their daily work puts them up close with cutting
edge technologies that are changing the face of modern
medicine, from researching spinal stimulation to help paralyzed
people regain control of their limbs to approving the next
breakthrough medication that could cure cystic fibrosis.
In many cases, our witnesses have overseen advancements in
their fields that have embraced innovation and moved the
American medical field forward for patients.
Dr. Austin, for example, founded and directed the NIH
Chemical Genomics Center while he was at the National Human
Genome Research Institute to advance the translation of
discoveries of the Human Genome Research Project into insights
on diseases and conditions and ultimately treatments.
Dr. Pettigrew established the Quantum Grants at the
National Institute of Biomedical Imaging and Bioengineering to
achieve medical moon shots by supporting high-risk, high-reward
projects to address major healthcare problems, such as
microchips to capture circulating tumor cells for early
detection and to monitor treatment.
Dr. Shuren has overseen a major advancement in heart valve
replacement therapy and the first approval of a next-generation
gene sequencing platform. There is not much in drug innovation
that Dr. Woodcock has not overseen or been involved in over the
last 10 years, including the first personalized medicines.
What I hope to hear today is what FDA and NIH currently are
doing and how Congress can help create the environment so the
NIH and FDA keep pace with today's cutting edge scientific
advancements.
Senator Burr and I released a white paper in January that
looked at the process of getting drugs and devices from
discovery to medicine cabinet, and much of what the report
covered is relevant here today. Today, medical products take
more time and money to discover, develop, and reach the
American patients than ever before.
We have heard that the FDA has difficulty regulating the
most cutting edge medical products. This disparity between the
pace of scientific discovery and FDA's scientific knowledge is
threatening America's position as a global leader in medical
innovation. We read in the paper and hear stories about drugs
and devices available to patients outside the United States
first, such as the heart valve mentioned earlier or a drug for
multiple sclerosis.
Private investment is shifting away from early stage drugs
and devices in part due to increasing regulatory burden and
uncertainty. Countries across the globe are seeking to
capitalize on America's shrinking competitive advantage in the
biomedical space.
In response to that report, we've gotten a glimpse of some
of the exciting new technologies on the way. We want to make
sure the FDA is ready for the developments coming, such as
bioelectric medicine, where nanotechnology sends electric
signals to restore nerve function; regenerative adult stem cell
therapies derived and put back into the same patient; and
therapies based on the whole genome sequence intended to
prevent any clinical symptoms from ever occurring.
FDA has quite the task before them to keep up with these
and many other technologies and to be able to judge the
benefits. At our first hearing, we heard from Dr. Collins, the
head of the NIH, and Dr. Hamburg, the former FDA Commissioner.
Dr. Collins highlighted the need for reforms on the travel of
NIH scientists and the need for the ability to roll funds over
from 1 year to the next.
Dr. Hamburg said that more needs to be done on regulatory
science, and that FDA needs to be involved earlier in medical
product development to ensure the most efficient process.
We know that opportunities exist today: the ability to use
real world data to improve health, both to shorten the time to
get to market, and then also to make sure that medical products
are safe once on the market; the ability to know about a
disease, including the genetic and molecular impact, and target
those markers before symptoms are ever present.
Our task is to help ensure that the exciting new
technologies being developed and discoveries being made are
reaching patients and that the NIH is equipped to support the
early stage research required to make these advancements and
that the FDA is equipped to handle them.
I look forward to hearing from the panel how Congress can
ensure that our biomedical research and review systems are
ready for these opportunities and have the expertise and tools
to address the challenges.
Senator Murray.
Opening Statement of Senator Murray
Senator Murray. Well, thank you very much, Chairman
Alexander. And thank you to everyone here today, especially our
witnesses, for joining us.
I'm very proud to represent a State that is a leader in
biomedical innovation. I see maintaining our country's central
role in the life sciences as a top priority, and I believe we
need to be doing everything we can to make sure the next life-
saving, world-changing cures and treatments are developed right
here in the United States. The conversation we're having this
morning about the future of medical innovation for patients and
families is a really important part of this effort.
I had the chance to visit the Fred Hutchinson Cancer
Research Center in my home State of Washington recently. As I
always am when I visit my State's world-class research
facilities, I was struck both by how far we've come in terms of
medical and technological advancement and also by how much more
there is to discover.
Over the last half century, our medical system has taken
huge leaps forward. We've moved from a system in which many
patients had no idea whether medical products would help them,
hurt them, or do nothing at all, to one in which FDA-approved
treatments are the global gold standard for safety and
effectiveness, a standard that patients and families have come
to trust when making decisions about their health.
Clinical research has, of course, been a key contributor to
this progress. I'm pleased that recently there has been
increased focus on the need for clinical trials to include
women, children, and other patients from all backgrounds. This
is critical, because we need to understand how products work
for every patient and family. I will continue to make this a
priority as we look for ways to advance medical innovation.
Today, medical experts are continuing to push the limits of
science and technology. We now increasingly have the capability
to treat patients based on their own unique characteristics and
medical histories.
In my home State alone, scientists supported by the NIH are
exploring ways to stop cancerous cells from metastasizing,
which is the No. 1 cause of cancer deaths, and develop 3D
analysis of internal biological surfaces so devices like joint
replacements can be better integrated into the human body.
These are just a couple of the many incredible examples of
scientific work being done today. Our task in Congress and in
our bipartisan effort to support medical innovation for
patients is to support this work and ensure that our country
continues to uphold the highest standards of medical safety and
effectiveness.
The two questions I am especially interested in exploring
today are: What more can Congress do to help get patients the
best, safest treatments more quickly? In general, what role can
Congress play in realizing this goal by helping to move the
ball forward on the most difficult scientific challenges?
Over the last few years, Congress has put in place tools
like FDA's breakthrough designation and accelerated drug
approval, which have helped patients and families get treatment
more quickly for serious and unmet medical needs.
One example is FDA's accelerated approval of a new drug to
treat breast cancer in women. NIH estimates that in 2014, more
than 230,000 women were diagnosed with breast cancer in the
United States, and 40,000 died from that disease.
Until this February, there hadn't been a new drug approved
for a particularly common form of breast cancer in over 15
years. FDA granted breakthrough therapy designation to help
speed development of a new drug, based on preliminary evidence
that the drug may offer a substantial improvement over
available therapies. Then, based on a single Phase 2 study of
165 women, FDA used its accelerated approval authority to
approve the drug. Now this treatment is available to patients
while the sponsor completes a Phase 3 study.
This focus on regulatory flexibility, where appropriate, is
helping patients and families get the care they need when they
need it, and I'm hopeful we can continue to make progress on
this.
Another area where I hope we can be helpful is finding ways
to advance the development of new medical products for
patients. We've heard from Dr. Hamburg that FDA has the fastest
drug approval times in the world. But the private sector
development of new medical products can take years before those
products ever reach the FDA's door.
I am hopeful that as our discussions continue, we can find
ways to support efforts to tackle difficult scientific
challenges in the development process, and, in addition,
explore innovative ways to determine which products are really
going to make a real difference for patients and families, and
weed out products that are not earlier on in the process.
This would reduce spending on dead ends and bring down
development costs. And, much more importantly, it would help
direct private sector resources to the research and development
that will get the best results for patients and families.
I look forward to hearing from Dr. Woodcock and Dr. Shuren
about how FDA's existing tools are working and what other steps
might be helpful. I am eager to hear from Dr. Austin and Dr.
Pettigrew about how our work in Congress can help break through
difficult science in the development process.
I want to thank again all of our witnesses for coming and
sharing your expertise with us. I'm confident that with your
insight, our bipartisan effort to advance innovation for
patients will be better equipped to help tackle the medical
challenges our country faces and help families and communities
stay healthy.
Thank you very much, Mr. Chairman.
The Chairman. Thank you, Senator Murray, and as I think the
witnesses know, this innovation project is a priority of
Senator Murray and me and this committee. We're working closely
with the President and with the administration and with the
House of Representatives, and we expect to have a result
sometime during this Congress. So your participation is
welcomed.
We would appreciate it if you could summarize your remarks
in about 5 minutes. That way, we can have more conversation.
I'm delighted to welcome you. Thank you for being here. You've
got big jobs running important centers.
First, we'll hear from Dr. Austin. He is Director of the
National Center for Advancing Translational Sciences, which was
established in 2011. It's the newest of the 27 NIH institutes
and centers. It is designed to transform translational science
so new treatments and cures for disease can be delivered to
patients faster.
The second witness is Dr. Roderic Pettigrew. He is Director
of the National Institute of Biomedical Imaging and
Bioengineering at NIH. Its mission is to improve health by
leading the development and accelerating the application of
biomedical technologies.
Dr. Janet Woodcock is next. She is Director of the Center
for Drug Evaluation and Research at the Food and Drug
Administration, which performs the essential public health task
of ensuring that safe and effective drugs are available to
improve the health of people in the United States. She's been
there for nearly 30 years and has led many of the FDA drug
initiatives.
Finally, Dr. Jeff Shuren has been the Director of the
Center for Devices and Radiological Health at the FDA for over
5 years. That center is responsible for assuring the safety,
effectiveness, and quality of medical devices; assuring the
safety of radiation-emitting products; and fostering device
innovations. Among his earlier work experience was a year
detailed to Senator Kennedy's HELP Committee staff. So we
welcome him back.
Why don't we begin with Dr. Austin.
STATEMENT OF CHRISTOPHER P. AUSTIN, M.D., DIRECTOR, NATIONAL
CENTER FOR ADVANCING TRANSLATIONAL SCIENCES, NATIONAL
INSTITUTES OF HEALTH, BETHESDA, MD
Dr. Austin. Well, good morning, Chairman Alexander, Ranking
Member Murray, and distinguished members of the committee. It's
an honor to appear before you today to discuss these topics,
because, as Senator Alexander just pointed out, NCATS was
formed in 2011 to address the systemic issues that we're
talking about today. These are issues that we deal with, and
they're very important to us and we work on them every day.
It's really an honor to be here, not only to represent
NCATS, but alongside my NIH colleague, Dr. Pettigrew, and our
colleagues from FDA, Dr. Woodcock and Dr. Shuren, to discuss
how we stimulate innovation through Federal investments in
scientific research. On behalf of NCATS and the NIH, I want to
thank the committee for your continued support.
I appreciate the opportunity to talk with you about some of
the innovative and exciting efforts we have ongoing at NCATS to
improve the process of translating fundamental understanding to
interventions that will improve the health of patients. Today,
I'll describe just three examples of the ways that we're doing
this.
First, predicting toxicity or adverse events is one of the
major reasons that drugs fail in development. This is a generic
problem that bedevils every translational project, no matter
what the disease is.
We're tackling this in multiple ways, one of which is
through the Tissue Chip for Drug Screening program. This is a
program that you may have heard about. Dr. Collins likes to
talk about it. It's a collaborative effort with DARPA and with
the FDA in which bioengineered human-based organs on microchips
are being developed with the intent to test drug safety and
effectiveness more rapidly and effectively than current
methods.
The chip that I have with me today represents a kidney, and
it was actually developed at the University of Washington
together with a company in Seattle called Nortis. NCATS is
building on its initial phase in which there were 10 different
organs, the kidney among them, developed.
We're now funding projects to link these organs together
with the eventual goal within the next 4 or 5 years of having
10 organs on a chip, a human on a chip, if you will, and
possibly even chips from individuals so that one could make a
chip from each one of us in this room, for instance. Once
completed, these integrated systems will be used as models for
disease, as well as, we hope, to predict whether a drug or a
vaccine or a biologic would be effective in humans and/or toxic
in humans.
Another roadblock that I'm sure you've heard a lot about is
that many drugs make it part of the way down the development
spectrum, but then they don't progress to actual treatments.
For either scientific reasons or business reasons, they're
deprioritized.
To address this problem, we started a program about 3 years
ago called Discovering New Therapeutic Uses for Existing
Molecules. It's an innovative approach to match ideas that
academic researchers have on how compounds could be used to
treat currently untreatable diseases. The program matches those
academic researchers with pharmaceutical industry compounds
that have already undergone significant research and
development and are available for testing on those other
diseases.
NCATS is celebrating one of the first promising results
from this program. It's a potential treatment for Alzheimer's
disease. NCATS-supported researchers through this program at
Yale collaborated with AstraZeneca researchers to find that an
experimental compound which was originally developed by
AstraZeneca as a cancer treatment could be used to treat
Alzheimer's disease. The compound successfully restored brain
function in mouse models of the disease, and now the Yale
researchers are testing it in humans with Alzheimer's to test
its effectiveness.
The third example is to address the problem of multisite
clinical trials, which are the last step needed to bring most
drugs to market. The current clinical trial system in the
United States is extremely inefficient. The NCATS Clinical and
Translational Science Award program is addressing this problem.
The CTSA sites across the country serve as research hubs to
support a national network for clinical translational studies.
One example of how this program is improving the efficiency
of clinical trials occurred in the aftermath of the 2013 Boston
Marathon bombing, where doctors from several local hospitals in
Boston quickly formed a team to design a high-quality,
multisite study to examine ear injuries as a result of the
blast. The CTSA hub at Harvard had an agreement in place that
enabled multiple institutions to rely on a single committee to
review, approve, and monitor the study. A study involving seven
sites was able to get going within days instead of the typical
months that this would require.
This innovative ability to streamline review of multisite
clinical studies enables NIH-funded research to generate
results more quickly without compromising the protection of
human participants. The CTSA program is also now working on
improving participant recruitment to clinical trials and to
leverage electronic health records to speed clinical research.
NCATS' mission is to catalyze the generation of innovative
methods and technologies that will advance the development and
implementation of diagnostics and therapeutics across a wide
range of diseases and conditions. NCATS looks forward to
building on these recent successes, such as the ones I've just
illustrated.
It's important for you to know that to accomplish this
mission, because we view translation as a team sport, we
collaborate on every one of our projects with other partners in
government, academia, industry, patient organizations. This
allows us to leverage our expertise and resources with those of
our partners, thus using taxpayer dollars most effectively to
bring more treatments to more patients more quickly.
Finally, a month ago, I had the privilege of hosting
Senator Mikulski for a tour of our research laboratories
located in Rockville, MD, which allowed me to show her some of
the innovative technologies that I've just mentioned. I'd like
to extend an invitation to the rest of the committee to visit
and see firsthand the exciting things that NCATS is doing.
This concludes my testimony, Mr. Chairman, and I look
forward to your questions.
[The prepared statement of Dr. Austin follows:]
Prepared Statement of Christopher P. Austin, M.D.
Good morning, Chairman Alexander, Ranking Member Murray, and
distinguished members of the committee. I am Christopher P. Austin,
M.D., and I am the Director of the National Center for Advancing
Translational Sciences (NCATS), one of the Institutes and Centers of
the National Institutes of Health (NIH).
It is an honor to appear before you today, alongside my NIH
colleague Dr. Pettigrew and our colleagues from Food and Drug
Administration (FDA), Dr. Woodcock and Dr. Shuren, to discuss how we
stimulate innovation through Federal investments in scientific
research. On behalf of the NCATS and the NIH, I want to thank the
committee for your continued support and for the opportunity to talk
about some of the innovative and exciting efforts that NCATS is
undertaking to improve the process for transforming research
discoveries into cures so that we can bring more treatments to more
patients more quickly.
Recent and rapid discoveries of mechanisms of disease, sequencing
of the human genome, and advances in technology have led to greater
scientific opportunities that have the potential to substantially
improve human health. NCATS is working on innovative ways to improve
the process for transforming these discoveries into cures so that we
can bring more treatments to more patients more quickly.
NCATS defines translation as the process of turning observations in
the laboratory and clinic into interventions that improve the health of
individuals and the public--from diagnostics and therapeutics to
medical procedures and behavioral changes. Translational science is the
field of investigation focused on understanding the scientific and
operational principles underlying each step of the translational
process. NCATS studies translation on a system-wide level. NCATS'
translational science efforts focus on the entire spectrum of
translational research--basic research, pre-clinical research, clinical
research, medical practice, and public health. At all stages of the
spectrum, NCATS develops new approaches, demonstrates their usefulness,
and disseminates the findings. Patient involvement is a critical
feature of all stages in translation.
innovation in methods and tools
The translational science approach generates new technologies and
data that overcome common roadblocks to translational success, thus
making the process more efficient and effective for all. One
technological innovation is a bioengineered system that represents
human organs, more commonly known as a tissue chip. Through the NCATS
Tissue Chip for Drug Screening program, a collaborative effort with the
Defense Advanced Research Projects Agency and FDA, researchers are
creating human tissue chips that consist of miniature 3D models of
living organs and tissues on transparent microchips. The chips contain
living cells and are designed to replicate the complex biological
functions of specific human organs. The tissue chips are being
developed to test drug safety and effectiveness more accurately and
cost-effectively than current methods. NCATS is building on its initial
success in developing chips that contain single tissue or organ models
by funding projects to integrate several of the organ-specific chips
into a full system that represents a ``human on a chip.'' Once
completed, these integrated systems will be used to predict whether a
drug, vaccine or biologic agent would be toxic to, or effective in,
humans.
NCATS shares its unique research approaches and resources so that
they can be broadly applied to translational science efforts at other
public and private sector organizations. In a recent collaboration with
the National Institute of Neurological Disorders and Stroke, NCATS
scientists incorporated an innovative approach to find a compound that
could enhance the activity of the parkin protein, which is implicated
in Parkinson's disease. Parkin is suspected of playing an important
role in the removal of faulty mitochondria (a cell's ``powerhouse'') in
brain cells, but for patients with Parkinson's disease, this
maintenance mechanism is disrupted. NCATS researchers designed a test
(called an assay) to measure the activity of the gene for parkin. With
this assay, the research team is now conducting high-throughput screens
using the NCATS' chemical libraries to identify compounds that increase
parkin activity. While specifically designed to address this problem,
the screening and assay methods designed by NCATS researchers can be
used by other scientists to solve many other translational research
problems.
NCATS also applies innovative methods through its Discovering New
Therapeutic Uses for Existing Molecules (``New Therapeutic Uses'')
program. Launched in 2012, this initiative uses an innovative strategy
that matches the ideas of academic researchers to pharmaceutical
industry compounds that have already undergone significant research and
development, and are available for testing on other diseases. To
accelerate the ``match-making'' process, NCATS developed template
agreements to streamline the legal and administrative process of
research collaboration among multiple parties. NCATS is celebrating one
of the first promising results from this program, a potential treatment
for Alzheimer's disease. Alzheimer's disease is the most common form of
dementia, a group of disorders that cause progressive loss of memory
and other mental processes. About 5 million Americans have Alzheimer's
disease, and current drug therapies can only ease symptoms of the
disease without stopping its progression. New treatments--so-called
disease-modifying therapies--are needed to halt Alzheimer's by
targeting its underlying mechanisms. Blocking that path to therapeutic
success is the costly, complex process of drug development. Through the
New Therapeutic Uses program, NCATS-supported scientists at Yale
University School of Medicine collaborated with AstraZeneca to find
that an experimental compound originally developed by AstraZeneca as a
cancer therapy potentially could be used to treat Alzheimer's disease.
The compound successfully reversed brain problems in mouse models of
the condition, and now the researchers are testing it in humans to
assess its effectiveness. We know that there is more that we can be
doing to address this disease, and multiple institutes at NIH are
aggressively pursuing other research on possible clinical therapies and
a better understanding of the changes in the brain that lead to
Alzheimer's disease, including through partnerships with the private
sector. To that end, the President's fiscal year 2016 Budget includes
$638 million for Alzheimer's disease research.
collaboration and patient engagement
NCATS also applies innovative approaches to translation by
fostering collaboration and patient engagement. NCATS' Rare Disease
Clinical Research Network is a highly collaborative network of 22
clinical research consortia and a data management center. The network
is composed of approximately 2,600 researchers, including NIH
scientific program staff, academic investigators, and members of 98
patient-advocacy groups. Scientists from multiple disciplines at
hundreds of clinical sites around the world work together with patient
advocacy groups to study more than 200 rare diseases. Since its launch,
nearly 29,000 patients have been enrolled in network clinical studies.
Ninety-one studies are currently under way.
The NCATS Therapeutics for Rare and Neglected Diseases program
establishes robust collaborations among NIH, academic scientists,
nonprofit organizations, and pharmaceutical and biotechnology companies
to support faster translation of drug discovery and development. When
successful, these projects are acquired by biopharmaceutical companies
for further development toward approved treatments for patients.
a national network for clinical and translational research
The NCATS Clinical and Translational Science Awards (CTSA) program
focuses its efforts on addressing the inefficiencies and roadblocks in
clinical and translational research, from scientific discovery to
improved patient care. The 62 CTSA sites serve as research hubs to
support a national network for clinical and translational studies. The
hubs support collaborations in education and training initiatives,
share best practices and methods, promote team science, and conduct
multi-site clinical studies through a shared infrastructure. A good
example of such collaboration happened in the wake of the April 2013
Boston Marathon bombing. Doctors from several local hospitals quickly
formed a team to design a high-quality multi-site study to examine
blast-related ear injuries. Harvard's CTSA hub had an Institutional
Review Board reliance agreement in place that enabled these
institutions to rely on a single committee to review, approve, and
monitor the study. Therefore, this seven-site study was launched within
weeks rather than the more typical months. This innovative ability to
streamline the review of multi-site clinical research studies enables
NIH-funded research to generate results more quickly without
compromising the protection of human participants. NCATS has announced
plans to support the evolution of the CTSA program by soliciting
innovative approaches to increasing clinical trial efficiency and
effectiveness, addressing the roadblocks common to clinical studies
recruitment of research study participants, and supporting
collaborative innovative research in both translational science and its
methods.
conclusion
NCATS' mission is to catalyze the generation of innovative methods
and technologies that will enhance the development, testing and
implementation of diagnostics and therapeutics across a wide range of
human diseases and conditions. NCATS looks forward to building on its
recent successes to bring more treatments to more patients more
quickly.
This concludes my testimony, Mr. Chairman. I look forward to your
questions.
The Chairman. Thanks, Dr. Austin.
Dr. Pettigrew.
STATEMENT OF RODERIC I. PETTIGREW, Ph.D., M.D., DIRECTOR,
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING,
NATIONAL INSTITUTES OF HEALTH, BETHESDA, MD
Dr. Pettigrew. Good morning, Chairman Alexander, Ranking
Member Murray, and distinguished members of the committee. It
is an honor to appear before you today along with my
distinguished colleagues on this panel, Doctors Austin,
Woodcock, and Shuren, to discuss some of the tremendously
exciting innovations made possible by Federal investments in
biomedical research with a focus on medical impact.
I want to thank the members of this committee for your
continued support, for holding this hearing today, and for the
opportunity to share our work with you. The National Institute
of Biomedical Imaging and Bioengineering, commonly known as
NIBIB, conducts research that sits at the intersection of the
physical sciences, the life sciences, and engineering.
Together, these disciplines are creating new biomedical
technologies to improve health.
We serve as a catalyst for emerging technologies and a
stimulator of innovation across the NIH in academia and
industry. I think it is worth noting that our working
definition of innovation is simply invention put to use. In
laboratories that we fund across the country, innovative
research is working on developing breakthrough technologies.
I'd like to show and tell you about a few of these in a
brief video. These examples provide a broad view of NIBIB-
supported technologies at various stages of development from
proof of concept to commercialization.
[Video Shown.]
This video entitled ``Eight Awesome Technologies Your Tax
Dollars are Paying to Create'' provides this overview. The
first one is a tissue engineered human liver. It looks like a
contact lens. It can be implanted in a mouse. It grows in a
mouse and turns the mouse's metabolism into a human-like
function. It then allows one to evaluate candidate drugs for
toxicity and biological features.
This is a hand-held MR assistant which is capable of
detecting a variety of targets from bacteria to viruses to
components of cancer cells. This is quite an innovation that
provides a completely portable, hand-held, take it anywhere you
can go, fully functional ultrasound system that replaces the
conventional system that you saw there. It would cost about \1/
20\th of a conventional system, and I have one here in my left
hand that I'm holding up. This was a partnership with General
Electric.
This addresses the devastating problem of paralysis due to
spinal cord injuries. Implantation of the electrical stimulator
at the lumbar spine in an epidural type of stimulation allows
the patients that were treated who were completely immobilized
for several years to regain voluntary motion as you saw in the
video.
This addresses the problem with the availability of organs
to transplant in patients, extending the time of presentation
from 1 day to 4 days in order to identify a greater population
of patients that might benefit from such transplantable organs.
This addresses a problem with vaccination and makes it a
simple process that is painless with a vaccine that can be
delivered in the mail. It uses this biodegradable patch that
you see here that's the size of a thumb. I actually have one of
those here. You place it on the skin, press it, and you're
vaccinated. It is biodegradable and dissolves in about 5
minutes so you don't have the hazardous waste to be concerned
about, and it's a stable temperature so you can send it in the
mail.
This is an optical needle microscope that is battery
powered. You place it on the surface. It provides sufficient
magnification that you can identify healthy cells, distinguish
those from cancerous or pre-cancerous cells, as being shown
here, and therefore provides a point of care test for
identifying cervical cancer and oral cancer, as was done in
this clinic in Botswana.
This final example addresses a problem of visualization of
tumors at the cellular level. This innovation developed by a
Nobel laureate has a molecule that seeks out cancer cells and
fluoresces after it enters the cells. You can see the tumor
there that was florescent. Similarly, for nerves, those are
demonstrated as well so that the surgeon can be better able to
distinguish nerves from cancer cells and potential entwining of
the two.
Those are examples that illustrate the type of innovative
technologies that we are developing. In summary, our institute,
NIBIB, drives innovation. We innovate technologies that expand
medical knowledge. We innovate diagnostics and therapies for
this and future generations. We integrate engineering with the
physical and life sciences to catalyze practical solutions to
complex biomedical problems.
Our goal is to accelerate the creation of usable
technologies to improve human health across the Nation and
worldwide. I thank you for the opportunity to appear before you
today, and I look forward to your questions.
[The prepared statement of Dr. Pettigrew follows:]
Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D.
Mr. Chairman and members of the committee: I am pleased to present
this testimony to you for the hearing on Biomedical Innovation. I am
Roderic I. Pettigrew, Ph.D., M.D., Director, National Institute of
Biomedical Imaging and Bioengineering (NIBIB). We are 1 of 27
Institutes and Centers at the National Institutes of Health. NIBIB is a
relatively new IC. It was created in December 2000 and we awarded our
first grants in 2002. NIBIB supports more than 800 grants and the work
of more than 5,000 researchers, and an Intramural Research Program at
NIH. At NIBIB we focus on creating biomedical technologies to improve
health.
Our mission is to lead the development and accelerate the
application of biomedical technologies to improve health. We are
advancing medical care through better understanding, prevention,
detection, and treatment of disease. We conduct and support emerging
technology research and development that lead to innovative biomedical
solutions. Integrating engineering and physical sciences with life
sciences by building partnerships with industry, academia, and other
Federal agencies is a high priority for the institute. In this
testimony I share a few examples from the many exciting NIBIB-funded
research efforts, which are leading to practical innovations that
advance public health.
reversing paralysis through spinal stimulation technologies
Spinal cord injury can be devastating and affect almost anyone,
from victims of auto accidents, to athletes, to soldiers on the
battlefield. An estimated 276,000 people were living with a spinal cord
injury in 2014. Each year approximately 12,500 new cases occur.\1\
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\1\ Spinal Cord Injury Facts and Figures at a Glance. February
2015. The National SCI Statistical Center, The University of Alabama at
Birmingham.
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Once thought of as an injury with no hope of recovery, a novel
therapy that involves electrical stimulation of the spinal cord has
restored function to an unprecedented degree in 7 patients treated to
date. This is a first-of-its-kind experimental study funded by NIBIB.
Following treatment, severely paralyzed patients recovered everyday
bodily functions, including bowel, bladder and sexual function. The
return of these important basic functions has dramatically improved the
quality of life of all who were treated. These patients also regained
the ability to voluntarily stand and achieve limited limb movement,
providing hope that further recovery may be possible with improvements
to this treatment approach. Although this research is still in its
infancy and not yet at the clinical trial stage, it has given real hope
to people living with paralysis around the world. They have seen the
positive impact in the small group of study participants and are eager
to have such technologic advances transform their lives as well.
next generation cell engineering
Our immune systems are highly proficient at attacking and
destroying anything viewed as foreign when it enters the body. Yet
cancer cells are largely ignored by the immune system because they are
derived from our own cells and retain some of the same characteristics.
A relatively new approach tested through a grant funded by NIBIB, uses
cell engineering to reprogram the immune system to identify cancer
cells and destroy them. In a recent advance, researchers have developed
a vaccine made of nanoscale biomaterials that is injected under the
skin. Once injected, the nanomaterials form a 3D scaffold, creating a
relatively large surface area for the immune system to assemble
``killer'' cells specifically programmed to attack tumors. The power of
this approach was demonstrated in a mouse model, in which the 3D
vaccine generated a potent immune response to lymphoma cells and
inhibited tumor growth. While this study tested the feasibility of a
single cancer vaccine, the same scaffold could also hold different
antigens or drugs to treat a range of cancers or infectious diseases.
This research promises a new class of therapeutic agents which harness
and enhance the power of our natural defense mechanisms against
disease.
advancing precision medicine: early detection of cancer cells at the
point-of-care
Many therapies today work well for some people, but not for others.
Matching a treatment to the unique features of an individual's disease
is the goal of the President's Precision Medicine Initiative. NIBIB is
supporting research in technology development to realize the vision of
customized treatment. For example, researchers have developed a
miniature palm-sized device to isolate rare circulating tumor cells
from a small routine blood sample. Tested in a proof-of-concept study,
this novel device was able to isolate breast cancer cells from the
blood of 36 women. Physicians were then able to grow the tumor cells
from six of the blood samples in the laboratory to characterize their
genetic and molecular features and test sensitivities to drugs. A
subset of these human cells were able to also grow tumors in mice where
the effectiveness of the selected drugs in inhibiting tumor growth was
demonstrated. In this initial study, treatments were not given to
patients; however this approach successfully demonstrated the potential
to identify a range of genetic changes, or mutations, in an
individual's cancer cells to enable personalized therapy.
mobile technology to advance healthcare
Depending on a variety of factors, such as environmental exposure
and lifestyle, individuals with the same genetic makeup can have very
different health outcomes. The use of mobile technology has the
potential to greatly assist researchers in gaining a better
understanding of the environmental and behavioral factors that cause
disease with the goal of preventing or intervening in the process.
Today, smartphones are natural points of engagement for the large
percentage of U.S. adults who own them. Interfacing smartphones with a
variety of biosensors may allow the linkage of an individual's
electronic medical records and genomic data with information captured
by the smartphone on environmental exposure and behavior if it were
done with appropriate security and privacy protections. From measuring
secondary smoke exposure to counting steps, or testing vision,
smartphones can record, track, and transmit a significant amount of
health information. Smartphones can also be used as a tool for
healthier living. They can be programmed to send automatic reminders to
take a medication or an alert when a dose is missed. The overarching
potential application relevant to the Precision Medicine Initiative is
to link and enrich the genomics and electronic health record data with
a broad range of medical exposure and lifestyle information. This set
of ``big data'' can then be evaluated or ``mined'' to identify new ways
to improve human health.
brain initiative
Approximately 100 billion neurons and 100 trillion connections make
up the human brain and there is an enormous amount to explore and
discover in this, the most complex of all human organs. As an institute
that is very active in the BRAIN Initiative, which has been a priority
for the President, as outlined in his fiscal year 2016 Budget proposal
for an additional $70 million, NIBIB supports research that leads to
the next generation of neuroscience discovery tools and technologies.
These technologies are being developed to advance our understanding of
the function of neural circuits and systems in health and disease. In
one example, researchers are developing a completely new noninvasive
method for portable 3D human brain visualization called Magnetic
Particle Imaging. Based on intrinsic bioelectric properties and the use
of injectable magnetic nanoparticles, this project could provide higher
imaging clarity and a completely new way to characterize and understand
changes in brain circuit function in mental and neurological disease.
conclusion
NIBIB drives technological innovation to expand biomedical
knowledge and create improved diagnostics and therapeutics for this and
future generations. By integrating engineering with the physical and
life sciences, NIBIB develops practical solutions to complex biomedical
problems. These advances are improving human health across our Nation
and worldwide.
The Chairman. Thank you, Dr. Pettigrew.
Dr. Woodcock.
STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION, SILVER
SPRING, MD
Dr. Woodcock. Thank you, Mr. Chairman. I'm really pleased
to be here to discuss the State of medical product development,
an activity that is so critical to human health, including, in
our case, at CDER, combating emerging infections like Ebola,
finding treatments for rare diseases, enabling healthy aging,
and preventing the development of disease at all.
CDER, the Center for Drug Evaluation and Research that I
lead, has a big impact on drug development, both domestic and
worldwide. I'm pleased to report, as reflected in my written
testimony, that a large number of innovative new medicines are
being approved and are in the pipeline. In fact, U.S. patients
do, in the vast majority of cases, have first access to these
treatments.
To ensure continued safety monitoring of these drugs after
approval, we've developed the cutting edge Sentinel network
that can analyze information from 178 million Americans'
medical records without compromising their privacy and watch
over these new medicines after they're approved.
Congress has had a big role in these successes, from
activating the PDUFA program that provides adequate resources
for FDA to monitoring development of drugs and provide advice
to developers as well as review the applications in a timely
manner. Congress also directed establishment of Sentinel for
safety and in FDASIA started the breakthrough designation
program that has been highly successful in getting the most
innovative drugs to patients quickly.
There are still problems, as already has been mentioned.
Drug development costs too much and takes too long. This is
mainly caused by the high failure rate. Even for the drugs that
make it to human testing, 8 out of 10 of those fail in human
testing. It's not due to the FDA requirements, but because they
don't work or because they're too toxic or they're no better
than existing drugs. The problem is really with failure rate.
FDA published the Critical Path Report that I actually
authored in 2004 to bring attention to these problems and start
working on solutions. There are many steps that have been
taken. There are many steps that can be taken. For example,
Chris Austin described what NCATS is doing, which is a focused
effort on trying to improve the situation. But we do need to
continue to improve the efficiency of drug development if we're
going to continue to get drugs to patients rapidly and
affordably.
Now, in particular, I thank Senators Hatch and Bennet for
their leadership introducing the PATH Act to establish a
limited population antibacterial drug program which could be
helpful in addressing unmet needs in a very fragile area of
antimicrobial drug development. I look forward to working with
the committee as this provision advances. I also look forward
to working on other aspects of the overall challenges of drug
development.
Now, one caveat, as you consider options, is, as we say in
medicine, first do no harm. When CDER receives a large number
of unfunded mandates, our attention can be diverted and review
performance suffers. This happened after the FDA Amendment Act
in 2007, and I have a chart that we will provide you that shows
the dip in FDA performance following enactment of that statute.
As we consider actions to enable innovation, we need to
make sure that we don't break what is working but that we
improve on the current system.
Thank you, and I look forward to your questions.
[The prepared statement of Dr. Woodcock follows:]
Prepared Statement of Janet Woodcock, M.D.
Mr. Chairman and members of the committee, I am Dr. Janet Woodcock,
Director of the Food and Drug Administration's (FDA) Center for Drug
Evaluation and Research (CDER). I am privileged to have the
responsibility to oversee much of FDA's efforts to review the safety
and efficacy of new pharmaceuticals. Thank you for having me here today
to give you my views on current efforts and areas for improvement.
When I came to FDA in the 1980s, the process by which FDA approved
new drugs for marketing to patients was under considerable criticism--
for being slow, for lagging behind other countries, and for lacking
transparency to, and collaboration with, the developers of new drugs.
Today, thanks to the efforts of those across the Agency, our
Nation's drug review process reveals a very different picture--we are
delivering new, lifesaving therapies to patients faster than any other
developed country and more expeditiously than ever before. In 2014,
almost two-thirds of the novel (``new molecular entity'') drugs
approved by CDER (26 of 41, 63 percent) were approved in the United
States before receiving approval in any other country. In addition, we
have significantly strengthened the drug safety surveillance system in
the United States, modernized drug review processes, and introduced new
genomic and related sciences into the drug evaluation process.
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factors speeding drug review and development
No single action or programmatic change has brought us to where we
are today; rather, it has been a steady program of improvements, new
investments through PDUFA, new authorities and other factors. These
improvements were based upon both externally and internally identified
gaps, so that now we have more predictable review times, additional FDA
resources to adequately address the workload from applications, and
additional interaction between FDA staff and drug manufacturers to
ensure promising drugs reach patients quickly.
prescription drug user fee program
The approval by this committee of the Prescription Drug User Fee
Act of 1992 (PDUFA) has been one of the most important components of
our improvements in review times. As its name suggests, PDUFA provided
funds in the form of user fees for FDA to hire sufficient staff to
undertake the growing workload of applications to market new drugs in
the United States. But it had much broader implications. It established
the principle that timely review was important, not just to
manufacturers, but also to patients, and that FDA should commit to
conducting those reviews in a predictable manner.
I became Director of CDER not long after PDUFA's enactment and was
determined from the start to ensure that the program was run in a
business-like fashion, with use of modern project management
techniques, establishment of specific goals, and accountability on the
part of review staff and managers to adhere to those goals. The result
has been a concerted effort across the Center with steady lowering of
review times, greater predictability for industry, and most
importantly, faster patient access to new therapies.
So, I thank the committee for the user fee program. It has helped
revolutionize our Nation's drug review process speeding access to new
drugs and without compromising the Agency's high standards for product
safety, efficacy, and quality. In 2014, CDER met its PDUFA goal dates
for 98 percent of the novel drugs we approved (40 of 41).
In addition to PDUFA, there have been a number of other important
initiatives that have contributed to our progress in achieving these
goals, including expedited FDA review programs, greater collaboration
with industry, and the use of surrogate endpoints to advance drug
development.
expedited fda review programs
FDA's expedited review programs were established in recognition of
the need to find ways for therapies intended for serious conditions in
patients with unmet medical needs to get into the hands of patients and
health professionals more quickly.
Accelerated Approval
Around the time of PDUFA's passage, FDA created an ``Accelerated
Approval'' program to permit certain drugs intended to treat serious
and life-threatening medical conditions to be approved on the basis of
a ``surrogate endpoint''--that is, using a biomarker or measure that is
``reasonably likely'' to predict clinical benefit instead of directly
measuring benefits to patients. As a condition of accelerated approval,
sponsors must conduct or complete required post-approval studies to
confirm that the drug actually helps people. Surrogate endpoints serve
as stand-ins for clinical endpoints that measure the real benefits of
drugs: whether a patient actually feels better or can function better,
or lives longer. Surrogate endpoints generally allow clinical studies
to be conducted in smaller populations of individuals over shorter
periods of time, reducing both the time and cost of drug development.
More information about how surrogate endpoints and other biomarkers are
being used to advance drug development is included below.
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CDER has approved over 90 new drug and biologics applications more
rapidly because of the Accelerated Approval program. In 2014, CDER
approved 8 of the 41 novel drugs approved (20 percent) under FDA's
Accelerated Approval program.
Priority Review
Drugs with the potential to deliver a significant improvement in
safety or effectiveness over existing therapy for serious or life-
threatening illnesses may also be designated for ``priority review.''
Priority review drugs receive a shortened, 6-month FDA review goal. For
example, from the beginning of 2008 through the end of 2014, 93 novel
drugs and biologics approved by CDER received the shortened, 6-month
review dictated by priority-review designation. In 2014, 25 of the 41
novel drugs approved by CDER were designated Priority Review.
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Fast Track
Another expedited program that helps reduce the time to market for
drugs being developed for serious and life-threatening illnesses is
known as ``fast track.'' Fast-Track designation generally may be used
for drugs intended to treat a serious condition where nonclinical or
clinical data demonstrate the drug's potential to address an unmet
medical need.
When a drug receives Fast-Track designation, FDA works closely with
its sponsor to facilitate submission of the drug development plan, the
design of clinical trials, and to identify any other data necessary to
support FDA approval of the drug. Moreover, once the sponsor begins to
develop the data to support approval, it can submit that data for
``rolling review.'' Rolling review allows a sponsor to submit portions
of a marketing application in advance of the entire application, rather
than submitting all portions of the marketing application at once,
which is the usual process.
Seventy-six novel drugs and biologics were approved by CDER from
2008 to 2014 with Fast-Track designation. Seventeen of the 41 novel
drugs (41 percent) approved by CDER in 2014 were designated as Fast
Track.
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Breakthrough Therapy Designation
In 2012, Congress provided the ``Breakthrough Therapy'' designation
as another new tool for expediting important new advances in therapy
for serious and life-threatening illnesses.
Breakthrough therapy designation may be granted for a drug that is
intended to treat a serious condition, where preliminary clinical
evidence (i.e., in people) indicates that the drug may demonstrate
substantial improvement on one or more clinically significant endpoints
over available therapies. Such breakthrough therapies, like drugs that
receive Fast-Track designation, receive intensive guidance from FDA, to
help sponsors better tailor their drug development program and, thus,
maximize the prospects for a rapid and successful path to approval. In
addition, breakthrough therapy drugs receive an organizational
commitment from FDA's senior managers and experienced review staff to
collaborate in advancing the review of these potentially high-impact
drugs.
As of April 16, 2015, CDER and the Center for Biologics Evaluation
and Research (CBER) have designated more than 84 new therapies as
breakthrough therapies, and 24 have received marketing approval.
Moreover, initial experience with the breakthrough process has yielded
more rapid FDA review times in many cases and shortened overall
development times for these therapies. Continued success of the
breakthrough therapy drug program is expected as a result of FDA's
intensive collaboration with new drug sponsors. CDER designated 9 of
the 41 novel drugs (22 percent) approved by the Center in 2014 as
breakthrough therapies.
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greater collaboration with industry
The movement toward greater collaboration between industry and FDA,
embodied in such initiatives as the Breakthrough Therapy program, is
reflected throughout our efforts and is one of the more significant
changes that has occurred during my time at FDA. In recent years,
meetings between FDA and industry have become routine and have proven
to be invaluable in improving communication about planned clinical
trials, development milestones, and data requirements.
The impact of improved FDA/industry communication is becoming
increasingly evident. Recently, FDA took a look at the development
times of new drugs that were approved with the benefit of pre-
Investigational New Drug (IND) meetings and compared them to the
development times for drugs that were approved without such meetings.
The results were quite remarkable. For instance, for all new drugs
approved between 2010 and 2012, the average clinical development time
was more than 3 years faster when a pre-IND meeting was held, than it
was for drugs approved without a pre-IND meeting. A 2014 article in The
Lancet, ``Biomedical research: increasing value, reducing waste''
(January 11, 2014), noted that 85 percent, or $200 billion, of annual
global spending on research is wasted on badly designed studies, and I
believe that greater industry-FDA collaboration can significantly
reduce such wasted effort.
Another result of improved collaboration between industry and FDA
is a substantial reduction in the number of application review
``cycles.'' The phenomenon of ``multiple review cycles'' occurs when a
sponsor submits a marketing application for approval and FDA does not
approve the drug during the first-review cycle. The most efficient
outcome for both the Agency and industry is for an application to
receive approval on the first-review cycle, if the drug is ultimately
approvable. Not receiving FDA approval on the first cycle means that
the sponsor must go back and take steps to collect additional data or
address a deficiency in their marketing application and then resubmit
their application, which FDA must then review again. But achieving
first-cycle approval requires a well-prepared application with no major
deficiencies.
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As a result of better collaboration between industry and FDA, which
has helped companies identify the data and analyses needed for approval
before the application is submitted, first-cycle approvals, which until
recently occurred for fewer than half of all novel drug submissions,
are now exceeding 70 percent. For example, CDER approved 78 percent of
the 41 novel drugs it approved in 2014 on the first cycle. This
translates into reduced costs for industry and earlier patient access
to new therapies, as illustrated by the charts. The early and frequent
communications that characterize some of the expedited development
programs were not possible before user fees were established, so, once
again, I commend this committee for the authorization--and
reauthorization--of the user fee program.
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using surrogate endpoints to advance drug development
As noted above, FDA routinely permits the use of surrogate
endpoints as the basis for Accelerated Approvals, when the surrogate is
reasonably likely to predict clinical benefit in a serious or life-
threatening disease that lacks good therapies. However, when scientific
study has progressed sufficiently to establish the correlation between
the surrogate endpoint and clinical benefit, the surrogate endpoint
then may be relied upon as the basis for traditional approval, thereby
negating the need for the confirmatory studies requirement, to which
drug sponsors are subject, under Accelerated Approval. For example,
reducing elevated blood pressure levels is a well-known surrogate
endpoint to reflect reduction in cardiovascular outcomes such as
stroke. Over many years, FDA has allowed the traditional approval
pathway to be used in approving a wide range of blood pressure
medicines, thereby dramatically expanding options for fighting stroke
and other related cardiovascular conditions.
During the last 5 years (2010-14), out of a total of 197 novel
drugs and original biologics approved across FDA, 84 (43 percent)
relied upon a surrogate endpoint for approval. A table listing the
surrogate endpoints relied upon for these 84 approval determinations
(covering both traditional approvals and accelerated approvals) is
attached as an appendix.
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a growing record of action on new therapies
Each of the improvements noted above has contributed to speed both
the development and the review of new therapies to prevent and fight
disease. This past year provides an example of how those improvements
are working; FDA approved 51 novel drugs and original biologics, 41 by
CDER, 10 by CBER. Additionally, 21 of these 51 novel drugs were for
orphan diseases.
The lag in approval times compared to approvals in other countries
that existed many years ago has been reversed. Today, FDA approves
drugs faster on average than all other developed nations: 40 days
faster than Japan; 70 days faster than Canada; and 174 days faster than
the European Union (EU). As the British-based Centre for Innovation in
Regulatory Science recently reported, over 75 percent of the new drugs
approved by Japan, EU, Canada, Australia, Switzerland, and FDA, from
2004 to 2013, were approved first by FDA. Yet, another independent
analysis concludes that FDA continues to lead the EU and other advanced
regulatory authorities in the introduction of novel drugs, as shown by
the following graph.
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The most important effect of this progress is that American
patients with untreatable or poorly treated diseases are receiving the
newest therapies rapidly and well before their counterparts in other
nations. In addition, the major enhancements that FDA has made in the
drug safety surveillance system means that American patients can also
be confident that these newly approved drugs continue to have intense
scrutiny after they are marketed in the United States to detect any
unexpected side effects and allow for quick and appropriate FDA action.
the path forward
Despite the progress that has been made, and as this committee has
noted, there are hurdles to overcome, if we are to ensure continued
U.S. leadership in the biomedical sciences. While Congress and FDA have
worked successfully together to greatly reduce FDA review times, many
of the serious challenges for drug development occur before FDA review
even begins. If the explosion in basic scientific knowledge is going to
efficiently translate into the treatments and cures patients need, we
must work together to overcome critical infrastructure and scientific
hurdles that prevent the advances we all desire. In January 2015, the
Administration unveiled the Precision Medicine Initiative, a vital new
research effort to catalyze improvements in targeting treatment to the
right patient at the right time. Launched with a $215 million
investment in the President's 2016 Budget, the Precision Medicine
Initiative promises to arm clinicians with new tools, knowledge, and
therapies that will work best for each patient. Below, I have described
a few specific areas which advance the development of new therapies for
patients.
Reducing Clinical Trial Costs
First, the cost of clinical trials continues to grow and is the
greatest source of cost increases in medical product development.
Today, developers of a new medicine spend many millions of dollars
planning a clinical trial, developing an elaborate trial
infrastructure, finding and enlisting investigators, conducting the
trials, and managing the trial data. Each time a new drug is tested,
the process is repeated, at great expense, only to dismantle the
infrastructure when the study is completed.
We believe that there are ways to greatly improve clinical trial
efficiency, such as widespread use of clinical trial networks and
master protocols, and we would like to work with you to examine those
possibilities.
Enhancing the Science of Biomarkers and Other Tools
Second, the science of identifying and evaluating the utility of
biomarkers and other scientific tools must be greatly enhanced. These
tools can be used to predict and evaluate the effects of candidate
drugs, both before clinical testing, and in people. Biomarkers are
technically defined as physical, biochemical, or genetic
characteristics that are objectively measured and evaluated as
indicators of health, disease, or in assessing the response to a
therapeutic intervention. In other words, biomarkers are the results of
tests done on the body, such as blood sugars or a chest x-ray.
Biomarkers have many uses in drug development, such as identifying
appropriate patients to enroll in a clinical trial, performing safety
monitoring, and selecting therapy for treating specific patients.
Hundreds of biomarkers are used today in drug development. However,
biomarkers based on new scientific understanding have been slow to come
into clinical use, largely because the evidence supporting their
validity has been lacking. The lack of new, well-understood biomarkers
also impacts drug development, these new tests could speed evaluation
of drug performance, including drug safety, and prediction of
effectiveness. Similar to the problems with clinical trials, the
scientific infrastructure for evaluating the validity of new biomarkers
has not kept pace with the need for this activity.
Typically, drug sponsors interact with FDA about new biomarkers
during clinical drug development, when an IND has been filed for a new
molecule. These discussions are confidential, and while new biomarkers
may be used in a specific drug development program, they are not
necessarily subject to broad scientific scrutiny. To address this
situation, CDER recently established a Biomarkers Qualification
Program. In this program, biomarkers that have demonstrated performance
for a certain use are designated by FDA as qualified biomarkers, and
can be used during the regulatory process by any developer for that
specific context of use. These qualified biomarkers are only a subset
of the biomarkers FDA has used in the review process.
FDA recognizes that there is still confusion about how new
biomarkers can be qualified through this process. Some believe that
many biomarkers are ``stalled'' in the qualification process. The
actual case is that most of the programs in the biomarker qualification
process are still in the evidence-gathering stage--which may take
considerable time due to the need for more development work within the
scientific community.
However, it is important to note that biomarkers do not need to go
through this formal qualification process, and most do not. As
mentioned previously, FDA has the ability to work directly with drug
sponsors who wish to utilize various new biomarkers within their drug
development program. For example, sponsors can propose a surrogate
endpoint--one type of biomarker--to be used in clinical trials based
upon the scientific communities' existing knowledge about the
particular surrogate endpoint. A sponsor can request FDA's agreement on
this surrogate endpoint through the ``Special Protocol Assessment''
process that is embodied in the PDUFA program. These product-specific
surrogate endpoints are one example of biomarkers that do not need to
pass through our formal qualification process in order to be used to
support drug development and review. Biomarkers are also important in
the growing field of so-called ``personalized'' or ``precision''
medicine, in which drugs are targeted at a genetically determined or
other disease characteristic that only occurs in a subset of people
with the disease. Targeted drug development is one of the most
promising areas for future drug therapy. Patients are chosen for
treatment based on specific test results (such as a genetic test or
other biomarker), indicating that the patient's disease (tumor,
hepatitis C, cystic fibrosis) is likely to respond to the drug.
In the early 1990s, targeted therapies represented only 5 percent
of FDA's new drug approvals. In recent years, roughly one-quarter of
the drug approvals has been supported by targeted drug development
programs, and that rate appears to be growing over time. Important,
new, recently approved, targeted cancer treatments include: Mekinst
(trametinib) and Tafinlar (dabrafenib) for forms of melanoma; Imbruvica
for forms of lymphoma and leukemia; and Zykadia (ceritnib) for a form
of lung cancer. The development of such targeted therapies is clearly
expanding rapidly. Similarly, targeted treatments for other diseases
have been approved, including treatments for cystic fibrosis and
ground-breaking treatments for hepatitis C that are potentially
curative for the majority of treated patients. As targeted therapies
become ubiquitous, advances in standardizing and increasing our
understanding of the biomarkers that enable use of these therapies will
be necessary.
Harnessing Evidence from Clinical Experience
Another source of information about drug effects is evidence from
clinical experience (called ``real world evidence'' or ``big data,'' by
some). I have aggressively developed FDA's Sentinel Initiative, a
national electronic system that is transforming FDA's ability to track
the safety of drugs and biologics once they reach the market. Sentinel
enables FDA to actively query diverse health care data sources--such as
electronic health record systems, administrative and insurance claims
data bases, and registries--to evaluate possible medical product safety
issues quickly and securely. The Sentinel Initiative is one of the
largest uses of this type of information in health care and is proving
vital for monitoring safety and analyzing safety signals. But the
science of using evidence from clinical experience to establish product
effectiveness, e.g., to evaluate new uses of drugs, is still in its
infancy. So we must first develop the methodologies needed to harness
its promise.
Strengthening Patient Engagement
The final example focuses on making patient experience more central
to drug development. FDA recognizes that patients living with a chronic
disease are experts in the effects of that disease and its current
treatments. As you know, the FDA Safety and Innovation Act (FDASIA)
instructed the Agency to begin a process for incorporating more patient
experience into drug development, and we have had numerous public
meetings to gain important insights from patients. But we recognize
that information needs to be collected in a structured and
representative way to be most useful in drug development. I hope that
we can work with you to further the movement toward patient-focused
drug development in your upcoming legislation.
conclusion
There are other areas in which we hope to work with you as well,
including modernizing drug manufacturing, encouraging the development
of new antibiotics, and improving the processes for FDA review of drug/
device combination products. I believe all of the challenges I have
described above are ones on which FDA, the drug industry, and patient
groups have common interests. We look forward to working with Congress
to address these challenges in ways that will serve patients and
pharmaceutical innovation well.
Thank you again for inviting me to share my views today.
______
Attachment
novel drugs--approved using surrogate endpoints*
(January 1, 2010-December 31, 2014)
Before the U.S. Food and Drug Administration (FDA) approves a drug
or biologic, the product must show substantial evidence of
effectiveness in clinical trials and that the benefits outweigh the
risks. Clinical trials measure benefit using clinical endpoints,
surrogate endpoints, or other types of measurements. Clinical endpoints
measure how a patient feels or functions better, or lives longer.
Surrogate endpoints are biomarkers, such as a laboratory test,
radiographic image (e.g., x-rays, MRIs), and physical sign (e.g., blood
pressure), that substitute for clinical endpoints in certain
circumstances.
---------------------------------------------------------------------------
* In the last 5 years, FDA approved 197 novel drugs and biologics;
84 relied upon surrogate endpoints.
---------------------------------------------------------------------------
A surrogate endpoint may serve as the basis for traditional
approval when it is known, through scientific study, to predict
clinical benefit. A surrogate endpoint may serve as a basis for
Accelerated Approval when it is reasonably likely to predict a drug's
intended clinical benefit. Drugs approved under Accelerated Approval
are subject to the requirement of post-approval confirmatory trials.
From 2010-14, FDA approved 197 novel drugs, known as new molecular
entities (NMEs), and New Biologic Approvals that include both New Drug
Applications (NDAs) and Biologic License Applications (BLAs). The
following table shows the 84 NME drugs and original biologics approved
during that time period that relied upon a surrogate endpoint for an
approval determination (i.e., traditional approval or Accelerated
Approval). Many of these drugs have orphan designation, which means
that they are intended to treat rare or uncommon diseases.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
The Chairman. Thanks, Dr. Woodcock.
Dr. Shuren.
STATEMENT OF JEFFREY E. SHUREN, M.D., J.D., DIRECTOR, CENTER
FOR DEVICES AND RADIOLOGICAL HEALTH, FOOD AND DRUG
ADMINISTRATION, SILVER SPRING, MD
Dr. Shuren. Mr. Chairman and members of the committee,
thank you for the opportunity to testify today.
Medical technology is transforming the way America
practices medicine and making a difference in patients' lives.
Expediting patient access to new medical devices is critical
but only if that technology is safe and effective. We know that
unnecessary regulatory burden can drive innovators to seek more
favorable environments, which can impact timely patient access
to potentially lifesaving therapeutics.
We also know that lax oversight can lead to patient harm.
Medical devices that have not been shown to be safe and
effective can hurt American patients and can drive up
healthcare costs.
In 2010, FDA's medical device program faced severe
problems. Some consumer, patient, payer, and practitioner
groups thought we weren't doing enough to assure patient
safety, while industry felt that we had raised the safety and
effectiveness bar too high and that we were taking far too long
to review new device submissions. In fact, from 2000 to 2010,
measures of device review performance showed steadily worsening
performance year after year.
Recognizing the need to address these concerns and
strengthen the device program, CDRH began to make systematic
changes to our policies, processes, and management oversight.
Since then, the performance of the device program has been
steadily improving.
For example, since 2010, we've reduced the average total
review time of 510(k)'s for moderate-risk devices by 10 percent
and cut the number of pending submissions by about 30 percent.
For PMAs for high-risk devices, we've cut the average total
review time by 26 percent and are on track to reduce it by one-
third, and we've cut the number of pending submissions by 43
percent.
For De Novos, a pathway for innovative lower risk devices,
we've cut nearly 2 years off the review process and seen almost
a doubling of De Novo requests. At CDRH, we have focused our
strategic priorities on reducing the time and cost of bringing
devices to market so that companies will bring their devices to
the United States first while still meeting the U.S. safety and
effectiveness standard.
One of our priorities is to strengthen the clinical trial
enterprise. We've already reduced the median time to full
approval of a clinical trial by almost 1 year and are poised to
meet our goal of reducing the median time from 442 days to 30
days, and our first cycle approval times for clinical trials
has increased ninefold.
We've recently launched a pathway for breakthrough devices
called the Expedited Access Pathway program. This program
provides manufacturers the opportunity to ship the collection
of some data where we otherwise require premarket to the post-
market setting. Post-market data includes information gathered
as a part of routine clinical practice, such as through device
registries and electronic health records. In fact, we are
already relying on registry data to approve expanded device
indications.
If our proposal for a national surveillance system for
medical devices is fully implemented, we can further reduce
premarket data requirements through greater reliance on post-
market data collection and, just as important, improve patient
safety. Last year, we created a multi-stakeholder planning
board which included patients, practitioners, payers, and
industry. The board recently released their recommendations for
implementing the system.
CDRH also believes that patients should have a say in our
review decisions. We've begun our initiative to utilize patient
preference data in our review of a device's benefits and risks.
Just recently, CDRH used such data in the approval of the first
device to treat obesity since 2007.
Flexibility already built into the existing statutory
framework for medical devices allows us to adapt to emerging
technologies. For example, over the past few years, we decided
to no longer oversee many lower risk software medical devices
we previously regulated. We recognize that our oversight is
best suited for higher risk functions, and by removing our
oversight in the low-risk digital area, we are able to help
stimulate the development of health-related mobile apps.
In response to the emergence of next-generation sequencing
platforms, we have leveraged data from curated data bases
rather than require new clinical studies to help bring
innovative tests to market. We recently proposed a new
regulatory model for next-generation sequencing tests that
would routinely rely on evidence generated by the clinical
community rather than on company-sponsored clinical studies.
Today, the medical device program is in a better place to
protect and promote public health than when I testified before
you in 2011. But we know we still have more to accomplish.
It is my hope that whatever this committee decides to do--
and we appreciate the opportunity to work with you--it does not
impede the strong progress we have made nor lose sight of the
tremendous effort and dedication of the medical device program
staff and managers.
Mr. Chairman, I commend the committee's efforts and I'm
pleased to answer questions the committee has.
[The prepared statement of Dr. Shuren follows:]
Prepared Statement of Jeffrey Shuren, M.D., J.D.
Chairman Alexander, Ranking Member Murray, and members of the
committee, I am Jeffrey Shuren, Director, Center for Devices and
Radiological Health (CDRH) at the Food and Drug Administration (FDA). I
am pleased to be here today to discuss FDA's work to promote patient
access to innovative medical devices while ensuring appropriate patient
protections.
introduction
Advances in medical technology are transforming established medical
practice and bringing completely new models of treatment, prevention,
and diagnosis to patients right now. New devices include not only
improvements over existing technology--devices that make less-invasive
treatments possible and provide new options to patients whose condition
would have been considered untreatable in the past--but also
technologies that will be keystones in emerging fields, such as
precision medicine. Genetic testing offers the promise of targeting the
right treatment to the right patients, reducing ineffective treatment
decisions, and speeding the delivery of therapies that work. Health
information technology can empower people with chronic diseases to
manage their own health and well-being by putting medical ``apps''
right into the hands of patients. FDA has responded to the promises--
and challenges--posed by these devices with flexible, risk-based
approaches to its oversight role and with strong performance in
bringing new, safe and effective products to market.
At the same time, FDA needs to ensure it is delivering on its
oversight role. This role requires that FDA facilitate patient access
to new medical technology while providing the oversight to minimize
unnecessary risks and ensure devices provide clinical benefit. At one
end of the spectrum, unnecessary regulatory burden could drive
innovators to seek more favorable environments, potentially depriving
American patients of timely access to needed therapeutic and diagnostic
devices. At the other end of the spectrum, lax oversight could lead to
patient harm from devices that have not been tested and shown to be
safe and effective, and affect the marketplace by reducing confidence
in the health care system that devices will do what they are intended
to do without harming the patients they are intended to benefit. A
flexible, risk-based approach to oversight of medical technology is
critical to striking the right balance.
FDA's existing framework establishes flexibility that has allowed
FDA to develop innovative approaches to medical device oversight,
approaches that reduce unnecessary burden without compromising
assurances that devices marketed to American patients are safe and
effective. Improvements to FDA's device program have already resulted
in decreased review times and timely patient access to important new
devices. And while other changes are too new to evaluate, early signs
are positive and point to additional improvements in timely access for
U.S. patients to safe and effective devices.
______
Glossary of Key Terms
510(k)--An application to FDA for market clearance of Class II
devices and a small number of Class I devices. The manufacturer must
demonstrate that the device is ``substantially equivalent'' to a
legally marketed device. FDA currently reviews 510(k)s for fewer than
10 Class III devices that were legally marketed before 1976. FDA is in
the process of reclassifying or finalizing calls for PMAs for these
devices.
De Novo--A premarket request for FDA to classify a novel device
into Class I or Class II.
IDE--Investigational Device Exemption: An application to conduct
studies on human subjects.
MDUFA--Medical Device User Fee Act: An agreement between FDA and
industry that FDA will take certain actions and attain performance
goals in exchange for industry user fees.
PMA--Premarket Approval Application: The application to FDA for
Class III devices. The manufacturer must demonstrate a reasonable
assurance of safety and effectiveness to gain approval of a PMA.
______
the u.s. regulatory environment for devices: 2010-15
Performance of FDA's Device Program
In the early part of this decade, many policymakers and FDA
stakeholders called for reform of FDA's device program, arguing that
FDA regulation was driving companies to relocate overseas or market
their devices abroad before introducing them in the United States. To
support their arguments, critics pointed to contemporary surveys of
device manufacturers and FDA's own data showing a decline in the
performance of its premarket program from 2000 to 2010. Although FDA
raised questions about the methodology used in some of these
studies,\1\ the underlying premise that industry's perception of FDA
oversight can affect decisions about introducing new technology in the
U.S. marketplace is important. This premise, as well as FDA's own
awareness of the Agency's worsening performance numbers, moved FDA to
implement a number of new policies and programmatic changes over the
past 5 years to improve its performance and to adapt its oversight to
the global marketplace, and to new technologies. Added funding and
increased capacity, as the result of the 2012 reauthorization of MDUFA
also helped reverse the direction of the Agency's medical device
premarket program.\2\
---------------------------------------------------------------------------
\1\ These arguments often rely on studies published early in this
decade to support these assertions--the methodology of which FDA has
questioned. See Letter from Jeanne Ireland, Assistant Commissioner for
Legislation, FDA, to Ranking Member Henry A. Waxman (July 11, 2011)
http://democrats.energycommerce.house.gov/sites/default/files/
documents/Waxman-FDA-Concerns-Regarding-Makower-Study-of-Medical-
Device-Regulation-2011-7-18.pdf.
\2\ FDA estimates that it has added at least 190 of the planned 240
staff authorized by MDUFA III, since the end of fiscal year 2011. These
additional staff members have contributed to FDA achieving the new
performance goals under MDUFA III.
---------------------------------------------------------------------------
Today, the performance of FDA's device program has significantly
improved. FDA is on track to meet all of its MDUFA performance goals
related to device review, and premarket performance measures of FDA's
device program show marked improvement since the start of the current
decade on several measures related to how quickly devices come to
market in the United States.
FDA is making progress in bringing down total review times for
510(k) submissions, de novo requests, IDEs, and the higher risk PMA
applications. While data is not complete for the years 2013 and 2014
because some applications remain open, existing data show improvements
on several important measures:\3\
---------------------------------------------------------------------------
\3\ Appendix A provides additional data showing the current
performance of FDA's device program, including data over several years
that show the course of improvement over the past 5 years.
---------------------------------------------------------------------------
Time to decision on device submissions has decreased:
510(k)s: The vast percentage of device premarket
submissions received by FDA in any given year are 510(k)s. In
fiscal year (FY) 2010, it took 116 days for a total time to
decision on a 510(k). By fiscal year 2014, total time had
dropped by 10 percent to about 105 days (these figures compare
review times when 75.8 percent of submissions are closed).
PMAs: Original PMAs generally account for only about
1 percent of all device applications received by FDA. Average
total time to decision in fiscal year 2014 has decreased to 236
days from 320 days at its peak in fiscal year 2009, or an
improvement of 26 percent (these figures compare review times
when 41 percent of applications are closed). Once all fiscal
year 2014 applications are closed, we project performance will
meet or exceed fiscal year 2012 levels, which would be at least
a 32 percent improvement since 2009.
IDEs: Median total time to full IDE approval decision
has decreased from 442 days in fiscal year 2011 to 101 days in
fiscal year 2014, reducing the time it takes to bring a new
medical device to market by nearly a full year. The number of
IDE studies requiring more than two cycles to full approval has
been reduced by 34 percent.
De novo: The average total time to final decision for
de novo requests (510(k) plus de novo review) submitted after a
device was found to be not substantially equivalent through the
510(k) process has been reduced from 992 days in fiscal year
2010 to 300 days in fiscal year 2014.
Another measure of the performance of the medical device
program is that FDA is working with industry to ensure that submissions
are complete and ready for review. As a result, the percentage of
submissions that are cleared and approved has increased since 2010:
The percentage of 510(k)s cleared increased from 73
percent to 84 percent.
The percentage of PMAs approved increased from 59
percent to 86 percent.
The number of pending submissions at the end of a year has
significantly decreased since 2010:
The number of 510(k) submissions has been reduced by
30 percent.
The number of PMA submissions pending has been
reduced by 43 percent.
Our experience also suggests that there is marked improvement in
the medical device industry's perception of FDA. In 2014, CDRH made
providing excellent customer service a strategic priority and launched
an effort to improve customer service that included staff training,
surveys to assess interactions with customers and measure customer
satisfaction, and, based on feedback from customers, actions to improve
the quality of CDRH actions and services. CDRH's 2014 results show 83
percent satisfaction. While customers include everyone who interacts
with FDA's medical device program, CDRH's results generally appear to
track our experience.
framework for device oversight
The basic framework under which FDA oversees devices was put in
place almost 40 years ago, when Congress enacted the Medical Device
Amendments of 1976 (MDA). The MDA established a flexible framework for
FDA's oversight of medical devices and required that FDA tailor its
oversight of devices to the degree of risk presented. Although the
framework established under the MDA recognizes that medical devices
inherently carry risk, the MDA did not mandate that FDA eliminate risk.
Rather, FDA applies only the level of oversight necessary to establish
a reasonable assurance of safety and effectiveness for devices. Under
this framework, only about half of all devices are subject to any
premarket review by FDA, and, of the devices that are subject to
premarket review, FDA reviews clinical data for fewer than 20 percent
because there are other, less-burdensome means to determine that there
is a reasonable assurance that a device is safe and effective.\4\
---------------------------------------------------------------------------
\4\ The 20 percent includes in vitro diagnostics (IVD) devices,
which typically contain test results based on human-derived samples.
When IVDs are excluded, the number of submissions with clinical data
drops to fewer than 10 percent.
FDA oversight of devices is tailored to three risk-based
---------------------------------------------------------------------------
classifications:
Class I, or low-risk devices: FDA does not review any
premarket information for Class I devices, with the exception of a
small subset of Class I ``reserved'' devices. Class I makes up about 50
percent of all medical devices. An example of a Class I device is an
elastic bandage.
Class II, or moderate-risk devices: FDA generally reviews
510(k) submissions for these devices, which requires a demonstration of
substantial equivalence to a legally marketed device. About 80 percent
of all 510(k)s contain only non-clinical data. Examples of Class II
devices include glucose test strips and infusion pumps.
Class III, or high-risk devices: FDA generally reviews
PMAs containing clinical and non-clinical data to determine whether
there is a reasonable assurance of safety and effectiveness for these
devices. FDA generally reviews about 40 PMAs a year. Examples of PMA
devices include heart valve replacements and diagnostic tests used to
select ovarian cancer patients for a drug regimen.
FDA's evidentiary standard for premarket review of devices is valid
scientific evidence, a standard established by Congress in 1976 that
still sets the benchmark for evidence to support premarket submissions.
This benchmark ensures that the evidence is of sufficient quality that
it can be relied on to determine whether or not a device should be
approved or cleared. Although valid scientific evidence includes
randomized-controlled clinical trials, the overwhelming majority of
devices come to market based on non-clinical data, small clinical
studies, or both. The valid scientific evidence standard encompasses
many other forms of evidence, such as bench testing, journal articles,
observational data, and foreign studies.
In vitro diagnostic (IVD) devices have been regulated by FDA under
its risk-based device framework since the inception of the device
program. Diagnostic tests can be used in the context of acute
outbreaks, such as the recent Ebola outbreak, and in the diagnosis and
treatment, including management, of chronic diseases like cancer and
diabetes. Success in combating these diseases depends on diagnostic
tests that can accurately detect them and be used to select and manage
treatments. A case in point is the widespread use of glucose meters and
diabetes test strips. These devices can empower people with diabetes to
manage their diseases independently, but only when the devices are
accurate. In recent years, test reports of falsely high and low blood
sugar levels have led to multiple recalls of these products over
concerns that false readings could lead to incorrect treatment
decisions; in particular, insulin administered in response to falsely
high measures of blood sugar could lead to acute hypoglycemia, coma,
and even death, if left untreated. The American Diabetes Association
issued a statement of strong support of FDA oversight of these tests,
stating:
The American Diabetes Association strongly endorses [FDA]
oversight of test strip manufacturers[]. The Association
applauds the FDA's requirements that all test strips meet
existing FDA standards for medical devices, since those
standards are designed specifically to require the greatest
accuracy in readings when an error would place a patient's
health and life in danger.\5\
---------------------------------------------------------------------------
\5\ http://professional.diabetes.org/News_Display.aspx?CID=93129.
For IVD devices, a reasonable assurance of safety and effectiveness
means that a test has analytical and clinical validity. ``Analytical
validity'' assesses how well the test detects or measures certain
markers in human specimens. ``Clinical validity'' assesses whether the
marker has clinical significance, such as correlation with disease or
the ability to predict a therapeutic response to a drug. As FDA's
recent announcement--that it intends to exempt carrier screening tests
from premarket review--shows, the level of data FDA requires to show
analytical and clinical validity for IVD devices depends largely on
risks from the device.
The central features of FDA's device program--a risk-based
framework that tailors oversight to device risk; a flexible review
standard that requires a reasonable assurance of safety and
effectiveness; and an adaptive but scientifically grounded evidentiary
standard of valid scientific evidence--have served the public well.
While there have been multiple amendments to FDA's original authority,
providing new premarket pathways and enhancing FDA's post-market
oversight, the framework put in place by the MDA continues to provide
the tools to assure safety and effectiveness of therapeutic and
diagnostic devices while allowing FDA to adapt its oversight to the
demands of rapidly evolving medical technology.
adapting fda's oversight role to current challenges: 2010-15
The new policies and programmatic changes FDA has implemented in
the past 5 years respond to the needs of American patients to have
timely access to high-quality, and safe and effective devices, and to
challenges created by rapidly evolving fields of medical innovation.
These initiatives have had far-ranging objectives, from providing FDA
review staff with new tools to assess the benefits as well as the risks
of a device to American patients to promoting regulatory certainty and
empowering patients to manage their well-being. Among these initiatives
are process improvements and policy changes to its oversight of
clinical investigations of devices.
Streamlining Clinical Trials
In 2014, FDA established a Clinical Trials Program to coordinate
its oversight of clinical studies of devices; provide interventions if
a review of an application to conduct a clinical investigation of a
device (Investigational Device Exemption or IDE) takes more than one
cycle; offer more opportunities for interactions with sponsors; expand
training for review staff; and establish new or modified policies in
this area. For example, recognizing that devices that are studied in
the United States in the early stages of clinical assessment are more
likely to reach U.S. patients sooner in pivotal trials and as marketed
devices, FDA implemented a pilot program in 2011 to encourage early
feasibility studies, or early stage clinical studies, of devices in the
United States. In 2013, FDA issued final guidance on early feasibility
studies;\6\ under this program, FDA may accept a higher degree of
uncertainty during the device development process to facilitate
important early clinical evaluation of promising technologies. As a
result, we are beginning to see an increase in companies submitting
IDEs for early feasibility studies in the United States and more
approvals of such IDEs. In the past 2 years, we have reduced the median
time to approval for early feasibility studies by 70 percent, from 226
days in fiscal year 2013 to 66 days in fiscal year 2015.
---------------------------------------------------------------------------
\6\ Investigational Device Exemptions (IDEs) for Early Feasibility
Medical Device Clinical Studies, Including Certain First in Human (FIH)
Studies: Guidance for Industry and FDA Staff (October 1, 2013),
available at http://www.fda.gov/downloads/medicaldevices/
deviceregulationand
%20guidance/guidancedocuments/ucm279103.pdf.
---------------------------------------------------------------------------
Devices that are studied in the United States in the early stages
of development are more likely to reach U.S. patients sooner in pivotal
studies and as marketed devices. In the past 15 fiscal years, for those
original PMAs whose approval was based on FDA-approved pivotal clinical
studies, 94 percent (283 out of 300) of these approvals were based on a
single pivotal clinical study. More recently, in the past 5 years, the
number has increased to 98 percent (82 out of 84). Of the 82 FDA-
approved original PMAs whose approval was supported by a single pivotal
clinical study, 32 (39 percent) included studies enrolling subjects
outside of the United States. For IVD devices, where clinical studies
are typically conducted in at least three sites, sponsors generally
choose to have one of those sites inside of the United States to
address differences between the United States and other countries in
how medicine is practiced, patient populations, and disease
progression.
FDA is facilitating and encouraging the use of innovative clinical
trial designs and statistical methods such as adaptive clinical trials
and Bayesian statistics. By incorporating existing clinical information
about devices into statistical analyses, adaptive clinical trials such
as the Bayesian approach can support a marketing application for a
device based on shorter and smaller clinical trials. In 2010, FDA
published a guidance document on how Bayesian methods can be used to
design and analyze data from medical device clinical trials.\7\ FDA's
efforts to promote the appropriate use of adaptive trial designs to
support premarket device applications date to the late 1990s\8\ and in
recent years, many devices have come to market based on adaptive trial
designs. For the period from 2007 to May 2013, FDA received 250
submissions that were adaptive, most of which were pre-submissions and
IDEs. About 30 percent of these used Bayesian methodologies. In
addition, there were 17 PMAs and PMA Supplements that used adaptive
clinical trials from 2007 to May 2013, eight of which used Bayesian
methodologies.
---------------------------------------------------------------------------
\7\ Guidance for the Use of Bayesian Statistics in Medical Device
Clinical Trials (February 5, 2010), available at http://www.fda.gov/
medicaldevices/deviceregulationandguidance/guidance
documents/ucm071072.htm.
\8\ Gregory Campbell (2011) Bayesian Statistics in Medical Devices:
Innovation Sparked by the FDA, Journal of Biopharmaceutical Statistics,
21:5, 871-87, DOI: 10.1080/10543406.2011
.589638. This article refers to 16 approved PMAs that relied on
Bayesian analysis and one cleared 510(k); there have been several
additional device approvals since 2011, but an exact number is not
available.
---------------------------------------------------------------------------
These programmatic improvements and policy changes have already
yielded results in significantly reduced time to approval of IDEs and
increasing approval rates. While the full effect of these programmatic
improvements on U.S. health care will not be known for several years,
streamlined processes for initiating device studies in the United
States and reductions in the time to approval for U.S. clinical studies
are promising developments in the effort to ensure U.S. patients have
timely access to medical devices of public health importance.
Flexible decisionmaking
In recent years, FDA has also implemented a series of new premarket
policies that build on the risk-based framework established by the MDA.
While these policies are relatively new, and the programmatic effects
cannot yet be measured, many of the policies have affected important
review decisions, impacting public health by speeding access to new
safe and effective devices.
Benefit-Risk: FDA's standard for premarket review of high-risk
devices has always required the Agency to weigh the benefits of a
device against its risks. For the past 3 years, however, FDA has used a
more flexible, patient-centric, and transparent benefit-risk framework
to evaluate devices. Under this framework, developed with public
feedback, reviewers weigh a number of factors to arrive at a decision
of whether the benefits of a device outweigh its risks, including: the
type, magnitude, and duration of a risk or benefit, the probability
that a patient will experience the risk, patient tolerance for risk,
availability of alternative treatments, and the value the patient
places on treatment. Under this approach, devices that present a small
but real likelihood of preventing serious disability or death could,
with appropriate risk mitigation such as labeling, reach the market
despite greater uncertainty about its risks. Also, in appropriate
cases, FDA may defer some data otherwise collected premarket to the
post-market setting to promote timely access to the benefits of devices
of public health importance, provided there is still a reasonable
assurance of safety and effectiveness. FDA currently applies this
benefit-risk framework to all reviews of high-risk and novel lower-risk
devices.\9\
---------------------------------------------------------------------------
\9\ Factors to Consider When Making Benefit-Risk Determinations in
Medical Device Premarket Approval and De Novo Classifications (March
28, 2012), available at http://www.fda.gov/downloads/medicaldevices/
deviceregulationandguidance/guidancedocuments/ucm296379.pdf.
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Patient Preferences Initiative: Increasingly, patients seek to be
involved in decisionmaking about their own health. Recognizing the
importance of considering patients' views in deciding how the probable
risks and benefits of medical technology should be weighed, in 2013 FDA
launched the Patient Preferences Initiative. The initiative seeks to
incorporate valid scientific evidence of patient preferences on the
benefit-risk tradeoffs of medical devices into premarket review and
other decisionmaking by FDA's device program. For example, a team of
FDA scientists published an article with leading behavioral economists,
illustrating how patient preferences can inform medical device approval
decisions.\10\ The authors successfully tested a new method for
capturing patient sentiment and translated it into a decisionmaking
tool for incorporating patient preferences into clinical trial design
for obesity treatments. They were able to estimate the tradeoffs in
risks that obese patients are willing to accept in exchange for a
certain amount of weight loss, and the minimum number of pounds they
would have to lose to tolerate the risks of a weight-loss device. FDA
used the results of this study to inform the product approval decision.
---------------------------------------------------------------------------
\10\ Marin P. Ho, et al., Incorporating Patient-Preference Evidence
into Regulatory Decision-Making, Surgical Endoscopy DOI 10.1007/s00464-
014-4044-2 (2015).
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Use of Patient Preferences to Approve a New Weight- Loss Device
In 2015, FDA approved a new weight-loss device--the Maestro
Rechargeable System, a new therapeutic option for certain obese
patients. The decision to approve the device was based in part on the
patient preference data, which showed that a substantial portion of
obese patients would accept the risks associated with a surgically
implanted device if they lost a sufficient number of pounds. Maestro is
the first FDA-approved obesity device since 2007.
Expedited Access Program: In 2014, FDA proposed a program for
expedited patient access to devices that are of potential significant
public health benefit because they are intended to treat or diagnose
patients with life-threatening or irreversibly debilitating conditions
whose medical needs are unmet by current technology--what some have
called ``breakthrough devices.'' Under this program, FDA would provide
earlier and more interactive engagement with sponsors of such devices,
including the involvement of senior management and a collaboratively
developed plan for collecting the scientific and clinical data to
support approval--features that, taken together, should provide
patients with earlier access to safe and effective medical devices. The
program would target devices with potentially high impact on patient
health because, for example, they fulfill an unmet need by offering an
important advantage over existing devices. To promote earlier patient
access, some data collection for devices marketed under this pathway
might be moved from pre- to post-market, provided there is still a
reasonable assurance of safety and effectiveness concerning the device.
FDA issued final guidance\11\ in April 2015. The Expedited Access
Pathway program went into effect on April 15, 2015.
---------------------------------------------------------------------------
\11\ http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/Guidance
Documents/UCM393978.pdf.
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regulatory science: new uses of evidentiary and analytical tools
FDA has also invested in several new regulatory science programs
over the past several years to reduce the time and cost but not the
quality of data development for devices. These programs promote the
development and use of tools, analytical methods, and data sources in
premarket applications to bring safe and effective devices to market
faster and at less cost.
Medical Device Development Tools (MDDTs)
An MDDT is a scientifically validated tool--a clinical outcome
assessment (e.g., patient-reported or clinician-reported rating
scales), a test used to detect or measure a biomarker, or a non-
clinical assessment method or model (e.g., an in vitro, animal, or
computational model) that aids device development and regulatory
evaluation. In August, 2014, FDA announced a pilot program under which
anyone can submit scientific information to FDA to ``qualify'' an MDDT.
Once qualified, MDDTs can be used to support premarket applications. In
practice, this can enable sponsors to support a PMA, de novo request,
or a 510(k) using smaller and shorter clinical trials. The MDDT program
builds on FDA's successes, developing computational models like the
Virtual Family (VF), a set of highly detailed, anatomically correct,
computational whole-body models, designed to mimic humans of both sexes
at various stages of growth.
Regulatory Science--The Virtual Family (VF)
FDA collaborated with researchers and industry to create the VF, a
set of four highly detailed, anatomically correct whole-body models of
an adult male, an adult female, and two children. Currently, the VF
models are used for electromagnetic, thermal, acoustic, and
computational fluid dynamics (CFD) simulations--simulations that can
supplement or replace data from clinical investigations of devices. At
the end of 2014, the VF was used in more than 120 medical device
submissions to FDA and was cited more than 180 times in peer-reviewed
literature. Recently the Virtual Population 3.0 became available. The
VF are available free of charge to researchers for use in device
development.
Medical Device Innovation Consortium (MDIC)
In 2012, FDA and LifeScience Alley (a biomedical trade association)
co-founded a new nonprofit partnership--the Medical Device Innovation
Consortium--the first public-private partnership (PPP) whose mission is
to advance medical device regulatory science. MDIC is a collaboration
among Federal agencies, industry, nonprofit organizations, and patient
advocacy organizations, and provides a venue for leveraging of
resources, people, and intellectual capital to find solutions to common
challenges in the precompetitive space. MDIC supports the development
of non-clinical device development tools that can reduce the need for
or size of clinical studies to support market approval as well as steps
to reduce the time and cost of clinical trials. MDIC has several active
project focus areas, including the following:
Patient-centered Benefit-Risk: This project focuses on
developing scientifically robust ways to measure patient perspectives
on the benefits and risks of medical devices, and a framework for
incorporating patient perspectives into device development and
regulatory decisionmaking.
Clinical Trials Innovation and Reform: MDIC is working
with FDA, NIH, industry, academia, and patient groups to explore ways
to improve the efficiency and cost-effectiveness of medical device
clinical trials while maintaining data quality. The goal is to
streamline the clinical trial process and restore the United States to
the country of first choice to conduct clinical research for medical
technology innovation. The project aims to innovate and reform the U.S.
clinical trial process by defining and tackling top barriers to
efficient design and conduct of medical device clinical trials.
Computer Modeling & Simulation: The goal of this project
is to reduce the time and cost of bringing devices to market while
improving patient safety by advancing the science around computer
modeling and simulation for medical devices. These models, when of
sufficient quality to be considered ``regulatory grade,'' can be used
to assess device performance, thus reducing or obviating the need for
other more expensive or burdensome types of scientific evidence (such
as human clinical studies).
MDIC's collaborations focus on advancing regulatory science to
propel device development through the regulatory process and to market,
resulting in smarter regulation and earlier patient access to safe,
effective, and high-quality devices.
real-world data
In September 2012, FDA published a report, ``Strengthening Our
National System for Medical Device Postmarket Surveillance,'' which
proposed a National Medical Device Surveillance System (MDS) for
improving and addressing the limitations of our current system for
monitoring medical device safety and effectiveness. This report
recommended establishing a national infrastructure for gathering and
analyzing real-world data, or data collected as part of routine
clinical practice and patient experience. The purpose of such a
national system is to identify potential safety signals in near real-
time; better understand the benefit-risk profiles of medical devices on
the market; and facilitate the clearance and approval of new devices,
or new uses of existing devices.
In the past year, FDA has achieved tremendous progress laying the
groundwork for the MDS. FDA has begun implementing the unique device
identification (UDI) rule for the highest risk devices, including
development of a Global UDI Data base (GUDID) as the repository for
information that unambiguously identifies devices through their
distribution and use. By promoting incorporation of UDIs into
electronic health information (such as electronic health records, or
EHRs, and device registries), a vast quantity of untapped real-world
data from clinical experience with devices housed in EHRs and other
electronic information sources may become available for use in
understanding the benefit-risk profiles of medical devices. In
addition, FDA continues to build registry capabilities both
domestically (such as the National Breast Implant Registry) and
internationally (such as the International Consortium of Vascular
Registries). FDA established a Medical Device Registry Task Force
consisting of key registry stakeholders as part of the Medical Device
Epidemiology Network (MDEpiNet) Program, a collaborative program that
FDA co-founded to develop new and more efficient methods to study
medical devices and to enhance FDA's ability to more fully understand
the safety and effectiveness of medical devices after they are
marketed. FDA commissioned the Engelberg Center for Health Care Reform
at the Brookings Institution to convene and oversee deliberations of
the Medical Device Postmarket Surveillance System Planning Board. In
February 2015, the Planning Board issued a report, ``Strengthening
Patient Care: Building an Effective National Medical Device
Surveillance System,'' outlining recommended steps toward the
development, oversight, and effective use of medical devices, while
supporting improvements in patient safety and health outcomes.
FDA's work in developing registries has relieved post-market burden
by allowing device sponsors to submit data from registries instead of
conducting their own new post-market studies. FDA is also pursuing
strategies to use data from the most robust registries in the premarket
context, and has already relied on registry data to expand access to
transcatheter aortic valve replacement devices.
Use of Real-World Evidence to Expand Use of Minimally Invasive
Heart Valve Replacement
Before 2014, transcatheter aortic valve replacement, a minimally
invasive alternative to open heart surgery, was indicated only for
patients with aortic stenosis for whom open heart surgery was too
risky, who were yet healthy enough to undergo certain placement
procedures. At the same time, clinical experience indicated this device
could offer good outcomes to inoperable patients with no other options.
In 2014, FDA expanded approval for the Edwards Sapien Transcatheter
Aortic Valve Replacement to patients deemed inoperable without
requiring controlled clinical trials of the new use. FDA approved the
expanded indication based on registry data from clinical use of the
device.
Adapting to New Technology
FDA's device program aims to be adaptive in responding to new
technologies. Recent policies have focused FDA oversight of health IT
on medical devices that present greater risks, with the goal of
permitting access to a range of products while ensuring the safety and
effectiveness of medical devices--a subset of mobile medical apps that
present a greater risk to patients if they do not work as intended--
such as those that provide or assist health care practitioners with
treatment and diagnosis. FDA's device program is leading the
development of clear, streamlined pathways for technologies that are
pivotal to the success of precision medicine, such as companion
diagnostics and Next-Generation Sequencing devices. The approach to
oversight in these areas demonstrates the adaptability of the existing
regulatory framework.
Mobile Medical Applications and Other Health IT: As the
number and functionality of mobile applications, or apps, exploded in
recent years, in 2013, FDA announced a policy under which FDA intended
to focus its regulatory oversight on those mobile medical apps that
pose the greatest risk to consumers and exercise enforcement discretion
for the majority of mobile apps as they pose minimal risk to consumers.
FDA followed this policy with a preliminary health IT report produced
in collaboration with the Office of the National Coordinator and the
Federal Communications Commission, as required by the Food and Drug
Administration Safety and Innovation Act (FDASIA) of 2012;\12\ this
report outlines a series of recommendations and actions for the public
and private sectors to take in this dynamic area of health IT to avoid
duplicative regulation, while promoting innovation and protecting
patient safety. The agencies accepted public comment on this report to
inform its development. Recently, FDA has issued guidance under which
FDA clarified that it intends to exercise enforcement discretion for
medical device data systems,\13\ a form of health IT that, while low
risk, is widely used in the delivery of health care. With these
actions, FDA helped to make clear the narrow arena of health IT where
the Agency intends to continue its oversight--namely, the space
occupied by the riskiest forms of medical software--while clearly
stating its intention to not focus its oversight over a broad range of
other medical device software products.
---------------------------------------------------------------------------
\12\ See FDASIA Health IT Report (April 2014), available at http://
www.fda.gov/downloads/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/UCM391
521.pdf.
\13\ Medical Device Data Systems, Medical Image Storage Devices,
and Medical Image Communications Devices: Guidance for Industry and FDA
Staff (February 9, 2015), available at http://www.fda.gov/downloads/
medicaldevices/deviceregulationandguidance/guidancedocuments/ucm
401996.pdf.
---------------------------------------------------------------------------
FDA recently proposed a similar policy for all low-risk devices
used to promote health and well-being and to help individuals with
chronic disease maintain wellness. The policy extends to products used
to promote physical fitness, maintenance of a healthy weight,
relaxation, and similar states of well-being, so long as the product
does not present inherent risks to users. As with FDA's recent policies
concerning health IT, FDA proposed this policy to provide greater
certainty to product developers and users that FDA intends to focus its
oversight in these emerging areas of product development on medical
devices that present more than low risk.
Companion Diagnostics: Companion diagnostic tests play an
important role in promptly determining which therapies are safe and
effective for a particular patient and are a key component of precision
medicine. FDA has approved 20 companion diagnostic tests, all of them
within the PDUFA performance goals for the corresponding drug or
biological product, ensuring the timely marketing authorization of
both. In 2014, FDA issued guidance\14\ describing a clear marketing
pathway for developers of companion diagnostic tests and pharmaceutical
manufacturers, receiving strong support from both pharmaceutical and
conventional test manufacturers for providing regulatory clarity in
this rapidly advancing area of medicine. Companion diagnostics approved
by FDA in recent years include the BRACAnalysis CDxTM test,
a laboratory-developed test that aids in determining which ovarian
cancer patients are more likely to respond to the drug
LynparzaTM (olaparib), based on certain BRCA variants; the
THxIDTM BRAF Kit, which detects certain mutations in
melanoma tissue samples to aid in selecting patients for drug therapy
with Tafinlar (dabrafenib) or MekinistTM (trametinib); and
the therascreen KRAS RGQ PCR Kit, a test that screens out colorectal
cancer patients with genetic mutations known to predict a
nontherapeutic response to the biological products Erbitux (cetuximab)
and Vectibix (panitumumab).
---------------------------------------------------------------------------
\14\ In Vitro Companion Diagnostic Devices: Guidance for Industry
and Food and Drug Administration Staff (August 6, 2014), available at
http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf.
---------------------------------------------------------------------------
Next-generation Sequencing: Many newly developed genomic
diagnostic tests rely on next-generation sequencing (NGS), an advanced
technology, which is becoming a keystone of precision medicine. NGS
tests can rapidly generate an unprecedented amount of genetic data for
each patient. Most IVD devices are used to detect a single or a defined
number of markers to diagnose a limited set of conditions; in contrast,
a single NGS test can identify thousands or millions of genetic
variants that can be used to diagnose or predict the likelihood of an
individual developing a variety of diseases. FDA has provided marketing
authorization for an NGS test for cystic fibrosis using innovative
approaches to establishing the test's effectiveness. As part of the
President's Precision Medicine Initiative FDA will develop a new
approach for evaluating Next Generation Sequencing technologies to
facilitate the generation of knowledge about which genetic changes are
important to patient care and foster innovation in genetic sequencing
technology, while ensuring that the tests are accurate and reliable.
Next-generation Sequencing: Cystic Fibrosis (CF)
FDA authorized marketing for the Illumin MiSeqDx Cystic Fibrosis
System in vitro diagnostic test, which detects 139 genetic mutations
that are relevant to whether an individual will develop CF or transmit
the CF genetic mutation to his or her children. FDA worked with the
test developer to apply novel approaches to establishing clinical
validity by using publicly available, quality-weighted human reference
genomes (databases) that were created through collaboration between FDA
and the National Institutes of Standards and Technology (NIST), and
analytical validity by using data showing the test could accurately
detect a representative sample of variants,
FDA recently published a white paper outlining a possible approach
to review of this technology that would greatly reduce burden by
leveraging data in existing high-quality curated genetic data bases as
an alternative to conducting new clinical trials and by reviewing
analytical performance for only a subset of variants. FDA has received
positive feedback from thought leaders in this area for identifying
ways to adapt its review practices to this important new
technology.\15\
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\15\ Lander, Eric S., Cutting the Gordian Helix--Regulating Genomic
Testing in the Era of Precision Medicine, NEJM2015, DOI: 10.1056 p.
150.
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conclusion
This is a time of remarkable advances in medical device technology,
advances that can extend lives, and minimize suffering for American
patients. New technologies hold out promise for empowering patients in
their own health care decisionmaking and for delivering precision
treatments that are truly targeted to individuals. At the same time,
the promise of advances in medical technology will only be realized if
the patients and providers who use them are confident that they are
safe and can do what they are intended to do.
FDA's device program has evolved alongside changes in medical
technology and in the global marketplace. FDA has implemented several
new policies and programmatic improvements to ensure American patients
have timely access to devices without compromising standards of safety
and effectiveness. Devices are coming to market more quickly, and more
devices that go through FDA's premarket program are being approved and
cleared for marketing. In addition, FDA has made its review of
investigational devices more efficient and expeditious, streamlining
the pathway to conducting clinical investigations in the United States.
The improvements in FDA's device program have occurred under a
long-standing framework that tailors FDA oversight to a device's risks
and benefits. This framework provides flexibility to adapt to new
technology and to consider a variety of different forms of evidence. At
the same time, the framework establishes a standard for devices
marketed to American patients: there must be a reasonable assurance of
safety and effectiveness for devices, demonstrated by valid scientific
evidence. We believe this framework serves the public well, allowing
FDA to meet the demands of rapid innovation and a changing global
marketplace, while promoting public confidence in high-quality, safe,
and effective devices.
Thank you for the opportunity to testify today about the steps FDA
is taking to foster innovation. I am happy to answer questions you may
have.
______
Appendix A. Medical Device Premarket Program Performance
mdufa iii
Performance Goals: Preliminary data for MDUFA performance goals
through September 30, 2014, indicate that FDA is on track to meet all
of its performance goals while maintaining a high workload. In fiscal
year 2014, FDA received over 6,000 submissions for PMAs, PMA
supplements, 510(k)s, de novos, and HDEs.
The 4th quarter MDUFA III Performance Report presents preliminary
performance for the fiscal year 2013 and fiscal year 2014 MDUFA III
submissions. Further details can be found in the MDUFA III Quarterly
Performance Reports available on FDA's MDUFA III website. (Table 1)
---------------------------------------------------------------------------
\16\ Current Performance presents the percentage of actions that
FDA completed within the review-time goal as of September 30, 2014.
\17\ Review Progress presents the number of submissions that had
actions taken in fiscal year 2014, plus submissions pending but overdue
as of September 30, 2014, whether or not they met the MDUFA goal date,
out of all MDUFA cohort submissions.
Table 1.-- Fiscal year 2014 MDUFA III performance for selected submission types, as of September 30, 2014.
----------------------------------------------------------------------------------------------------------------
Performance Current
Goal [In Performance\16\ Review Progress\17\ [Percent
percent] [In percent] complete]
----------------------------------------------------------------------------------------------------------------
PMA, Panel-Track PMA Supplements, and
Premarket Reports:
Substantive Interaction..................... 75 95 37 of 45 (82 percent)
Decision with no Advisory Committee input... 80 100 7 of 43 (16 percent)
Decision with Advisory Committee input...... 70 0 of 2
180-Day PMA Supplements:
Substantive Interaction..................... 75 94 127 of 178 (71 percent)
Decision.................................... 90 100 78 of 178 (44 percent)
Real-Time PMA Supplements:
Decision.................................... 90 99 272 of 333 (82 percent)
510(k) Premarket Notifications:
Substantive Interaction..................... 75 97 2,739 of 3,166 (87 percent)
Decision.................................... 93 99 1,811 of 3,133 (58 percent)
CLIA Waivers:
Substantive Interaction..................... 95 100 14 of 14 (100 percent)
Decision for dual submissions ((510(k) and 90 0 of 1 (0 percent)
CLIA waiver).
Decision with no Advisory Committee input... 95 100 8 of 14 (57 percent)
Decision with Advisory Committee input...... 95 0 of 0
----------------------------------------------------------------------------------------------------------------
premarket notification (510(k)) program
Average Time to Decision for 510(k)s: Total time to decision
includes the time spent by FDA reviewing the application as well as the
time spent by the submitter responding to questions from FDA. 510(k)
average total time to decision has decreased since its peak in fiscal
year 2010. (Chart 1) fiscal year 2013 and fiscal year 2014 cohorts are
not yet fully closed; as of December 31, 2014, the fiscal year 2013
510(k) cohort was 99.2 percent closed and 2014 cohort was 75.8 percent
closed. Comparison of receipts cohorts at the same closure\18\ levels
show a 16 percent decrease in total review time (Chart 2) between
fiscal year 2010 and fiscal year 2013 and a 10 percent decrease in
total review time between fiscal year 2010 and fiscal year 2014. (Chart
3) The fiscal year 2013 cohort had the same average total time to
decision as fiscal year 2014 at the 75.8 percent level of closure.
---------------------------------------------------------------------------
\18\ Use of closure level provides a means for fair ``apples to
apples'' comparisons, as performance is compared using the same
percentage of work completed in a given year.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Organizationally, CDRH medical device premarket review offices are
divided into review divisions, which are comprised of review branches.
FDA is also closing the gap between the premarket review branches with
the fastest and slowest review times. In 2003, the lowest performing
branch reached 34 percent of its 510(k) MDUFA decisions within 90 FDA
Days. In fiscal year 2013 and 2014, most branches were reaching
decisions within 90 FDA days 90 percent of the time or better.
Substantially Equivalent (SE) Determinations and Pending
Submissions: Improvements to the 510(k) program have increased the
number of submissions determined to be substantially equivalent (SE)
since 2011 (decision cohort). The number of submissions determined to
be SE in fiscal year 2014 is 10 percent greater than in fiscal year
2010. The impact of CDRH improvements is further observed in the number
of pending 510(k) submissions, which has been reduced by 30 percent
from its highest level in fiscal year 2010.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
510(k) Refuse to Accept (RTA) Program: Under the RTA Program FDA
conducts an early review against specific acceptance criteria to assess
whether the submission meets a minimum threshold of acceptability and
should be accepted for substantive review. The assessment of the
completeness of the 510(k) occurs during the early acceptance review,
while the assessment of the quality of the submitted information occurs
during the substantive review. Since the initiation of the Refuse to
Accept (RTA) program on January 1, 2013, the RTA rate has been
decreasing from 58 percent during the second quarter of fiscal year
2013 to 39 percent during the last quarter of fiscal year 2014. (Chart
6)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Training and increased FDA and Industry experience regarding the
RTA process have contributed to the decreased rate while improving the
quality of 510(k) submissions. FDA is undertaking a process improvement
exercise to further reduce the RTA rate and improve consistency of this
program. Overall acceptance rate, when RTA 1st and 2d cycles are
combined, was 84 percent in fiscal year 2013 and 90 percent in fiscal
year 2014.
premarket approval application (pma) program
Average Time to Decision for PMAs: Average time to decision has
decreased since its highest point in fiscal year 2009. (Chart 7) As of
December 31, 2014, the fiscal year 2012 original PMA cohort was 98
percent closed, the fiscal year 2013 cohort was 72 percent closed and
the fiscal year 2014 cohort was 41 percent closed. Comparison of
receipt cohorts at the same closure levels show a 32 percent decrease
in total review times (Chart 8) between fiscal year 2009 and fiscal
year 2012 when the cohort is 98 percent closed, 3 percent decrease in
total review times between fiscal year 2009 and fiscal year 2013 (Chart
9) when the cohort is 72 percent closed, and a 26 percent decrease in
total review times between fiscal year 2009 and fiscal year 2014 (Chart
10) when the cohort is 41 percent closed. Examination of the
applications included in these cohorts, detected a correlation between
average total time to decision and panel meetings (see further
explanation below).
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
FDA is also closing the gap between the divisions with the fastest
and slowest review times. Performance has decreased significantly, from
a difference in total average days to final decision between the
highest and lowest performing divisions of 633 days in fiscal year 2008
to 197 days in fiscal year 2014.
Effect of an Advisory Panel Meeting on Average Total time to
Decision: As part of the review process, FDA may present a PMA to an
expert advisory panel for its recommendations. Medical device advisory
committees provide independent, professional expertise and technical
assistance on the development, safety and effectiveness, and regulation
of medical devices. PMAs that undergo an advisory panel review have
different performance goals than PMAs that do not go to an advisory
panel because holding an advisory panel meeting adds more time to a
review. Examination of the fiscal year 2013 cohort shows the highest
percentage of PMAs undergoing an advisory panel review since 2007,
which led to what appears to be an increase in review times. But when
``apples-to-apples'' comparisons are made, total review times continue
to show a decrease.
PMAs that undergo an advisory panel review typically take longer to
reach a final decision, as accounted for in MDUFA III performance
goals. Because the average total time includes both PMAs that go and do
not go to an advisory panel meeting, the spike in review time for
fiscal year 2013 reflects the significantly higher percentage of
applications with an advisory panel meeting (33 percent). (Chart 11)
However, when comparing reviews times of PMAs with a panel meeting
(Chart 12) across different years and PMAs without panel meetings
across different years, we continued to see improved performance in
fiscal year 2013 for both categories of PMAs. In addition, the percent
of PMAs that will undergo advisory panel review in fiscal year 2014 is
considerably less than fiscal year 2013. A decrease in the percent of
PMAs which will go to an advisory panel meeting in fiscal year 2014
along with other program improvements lead us to expect lower average
total review times in fiscal year 2014.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Approved and Pending PMAs: Improvements to the PMA program have
resulted in an increase in the number of applications approved since
2011 (decision cohort). The number of applications approved in fiscal
year 2014 was 27 percent greater than fiscal year 2010. (Chart 13)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Note that the fiscal year 2015 cohort only includes 3 months of
data. The impact of CDRH improvements is further observed in the number
of pending original PMAs, which has been reduced by 43 percent from its
highest level in fiscal year 2010. (Chart 14)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
de novo program
Average Time to De Novo Granting: Improvements to the de novo
program have resulted in a 70 percent reduction in the average total
time to decision for these submissions. Average total time to final de
novo decision for devices with post-NSE de novo requests (includes FDA
and Industry days for 510(k) NSE review and post-NSE de novo review)
has been reduced from 992 days in fiscal year 2010 to 300 days in
fiscal year 2014. Average total time to decision for direct de novo
requests are even lower than for de novo requests using the post-NSE
review pathway. (Chart 15) While time to decision has significantly
decreased since fiscal year 2010, the number of de novo requests
received has almost doubled (25 de novo requests in fiscal year 2010
versus 46 and 41 in fiscal year 2013 and 2014, respectively).
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
investigational device exemption (ide) program
IDEs Approved within Two Cycles: Improvements to the IDE Program
(e.g., establishing a formal Clinical Trials Program, process
improvements, policy changes, extensive training for CDRH review staff
and the device industry, and new guidance documents) have greatly
shortened the time for an IDE to reach approval, so that a clinical
trial can begin. The number of IDE studies that get fully approved
within two cycles has increased significantly. The percentage of fully
approved IDE studies within one cycle has increased ninefold compared
to fiscal year 2011 and the percentage fully approved within two cycles
has increased fourfold compared to fiscal year 2011. (Chart 16) In
fiscal year 2014, 63 percent of IDEs submitted were approved within 2
cycles.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Median Days to IDE Full Approval: The median number days to full
IDE approval has decreased from 442 in fiscal year 2011 to only 101 in
fiscal year 2014, reducing the time it takes to bring a new medical
device to market by nearly a full year. (Chart 17)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Clinical Studies: Devices that are studied in the United States in
the early stages of development are more likely to reach U.S. patients
sooner in pivotal studies and as marketed devices. In the past 5 fiscal
years, 82 FDA approved original PMAs were supported by a single pivotal
IDE study. Of those, 32 (39 percent) included studies enrolling
subjects outside the United States. For in vitro diagnostic devices
(IVD), where clinical studies are typically conducted in at least three
sites, sponsors generally choose to have one of those sites inside the
United States to address differences between the United States and
other countries in how medicine is practiced, patient populations, and
disease progression.
FDA is facilitating and encouraging the use of innovative clinical
trial designs and statistical methods such as adaptive clinical trials
and Bayesian statistics. For the period from 2007 to May 2013, FDA
received 250 submissions that were adaptive, most of which were pre-
submissions and IDEs. About 30 percent of these used Bayesian
methodologies. In addition, there were 17 PMAs and PMA Supplements that
used adaptive clinical trials from 2007 to May 2013, eight of which
used Bayesian methodologies.
customer satisfaction
Industry Customer Service Rating for Premarket Program: Excellent
customer service means understanding and addressing, as appropriate,
stakeholders' and colleagues' needs through active listening, problem
solving, seeking out the ideas of others, explaining the rationale for
our decisions and requests for information, learning from our mistakes,
and doing our best. Providing excellent customer service improves our
interactions supports better regulatory outcomes, thereby improving
patient health.
By providing excellent customer service, we do not alter our
regulatory obligations. Customer service does not mean letting unsafe
or ineffective devices on the market--rather it involves identifying
and meeting our customers' needs, as appropriate, while achieving our
mission and vision.
The experience of receiving excellent customer service can
encourage device makers to choose the United States first when bringing
their products to market; in turn, U.S. health care providers gain
access to the technologies that they need to administer quality health
care to patients. In June 2014 CDRH began measuring customer
satisfaction and established a goal of 70 percent satisfaction by the
end of 2014. The Center's performance was 83 percent (95 percent
confidence level and 2 percent margin of error). The performance of the
premarket program was 86 percent satisfaction (95 percent confidence
level and 3 percent margin of error). Among its industry stakeholders--
industry, industry consultants, and industry trade associations--was
even higher, 89 percent (95 percent confidence level and 4 percent
margin of error). (Chart 18)
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
The Chairman. Thank you very much.
Senator Roberts has an important engagement in a few
minutes. I'm going to call on him at this time.
Statement of Senator Roberts
Senator Roberts. Mr. Chairman, I thank you, and I apologize
to my colleagues. I have several questions I'd like to submit
for the record.
I just want to say that I share Senator Murray's concern
with regard to the fact that with the FDA, as the agency has
grown with large new requirements to publish regulations for
food, tobacco, other things, we have seen additional delays in
getting guidances and regulations necessary for medical product
innovation and the public health finalized and approved. I know
they'll have good answers as to how they are prioritizing their
work with these new authorities.
I also want to note that in Kansas, we've seen the medical
research and development field expand greatly in recent years,
anchored by a research hospital and medical school at the
University of Kansas, the home of the ever-fighting and
optimistic Jayhawks. The recent National Cancer Institute
designation for KU has created nearly $1 billion in economic
activity and over 1,800 jobs locally. I am very confident we
will continue to lead in this area.
I thank the chairman for his indulgence and the patience of
my colleagues. Thank you.
The Chairman. Thank you, Senator Roberts, for your succinct
statement.
We'll now move to 5 minutes of questions for committee
members, and I'll begin.
Dr. Woodcock, you said something very important about the
mandates from 2007. We know in this committee that--I mean, we
are a feast of well-intentioned good ideas here, and they come
from all directions, from the right and the left. We see that
in higher education, where a number of us have invited the
higher education community to talk to us about simplifying
regulations, and they came back with 59 specific
recommendations.
Our purpose here is to enable you, not to slow you down. We
want to align Federal policies--and that means our laws and our
regulations--with an opportunity for more, not less, safe
innovation.
I would invite each of you to form your own internal red
team for red tape, and if you see things that are in the law or
in regulation or even that the Office of Management and Budget
makes you do that you think are nonproductive, let us know,
because this train is going to get to the station. We're
working with the House and the President, and this is an
opportunity to clear the clutter out of the way and to take
advantage of a rapidly changing landscape.
Now, Dr. Austin, we've heard a lot about the valley of
death. I had some Vanderbilt researchers explaining that to me
the other day. More money obviously would help. You talked
about it some. What else can we do to shorten the period from
discovery to medicine cabinet and this middle ground where so
many--8 out of 10--medicines fail for business reasons or for
medical reasons? Is there anything else we should do?
Dr. Austin. Thank you for the question. First, it is
important to say that there--as it will not surprise you to
learn--are many, many more of those valley of death crossing
projects that we have proposed to us than we can possibly fund.
The number is currently 96 percent that we cannot fund.
It's important to realize that--to see change that's
happened since I was in training 30 years ago, there were tens
of opportunities to intervene in a rapid way for patients with
untreatable diseases. Now that's in the thousands. The
opportunities have really exploded.
The Chairman. If 8 out of 10 don't succeed, if that's
anywhere close to right, are there any other steps you can take
to reduce that number with whatever dollars you have?
Dr. Austin. Yes, and to give you some examples, one beyond
the direct support is that these projects traditionally have
been done in a rather disparate fashion. This requires a team
to do this. It requires people of different expertises, often 8
or 10 different expertises, and different sectors, so academia,
biotech, pharma, VC, patient groups, regulators, and,
traditionally, they've tended to work in silos.
It is one of the reasons why everything NCATS does is done
as a collaboration. What we find is what our mothers told us,
that many hands make light work, and if you put together a
team----
The Chairman. Collaboration is one answer. Anything else?
Dr. Austin. I can't let this go by without mentioning the--
--
The Chairman. If you can do it in 25 seconds, I would
appreciate it so I can go to another question.
Dr. Austin. The administrative limitations that Dr. Collins
has talked about, the travel, the hiring issues. Those are big
issues for us because of the----
The Chairman. I have encouraged Dr. Collins literally--I
had a good visit with him last week--to form a red team for red
tape and give us a list. We know that some of those things are
your fault, and some of them are our fault.
Dr. Austin. Yes.
The Chairman. Some of them is the Office of Management and
Budget. We can put the spotlight on all of them, and we'll try
to change the ones that we can that get in the way of your good
work.
Dr. Woodcock and Dr. Shuren, I have just a few seconds
left. We hear that in Europe, it's easier for regulators to
take advantage of outside expertise. As the world changes and
so much is going on in the area in which you work, surely you
can't have enough smart people inside the system to make all
the decisions you need to know. Are there things we can do to
make it easier for you to appropriately involve experts from
outside your agencies to help you deal with these issues?
Dr. Shuren. Well, in trying to address that, we set up what
we call a network of experts. We are leveraging the networks
already existing in healthcare professional and scientific
organizations. I'd say our biggest holdup is some questions
rely on confidential information that's in the possession of
the company and it's theirs to own. And because we can't share
that information, we can't leverage those experts as well as we
could. That is a limitation.
The Chairman. Thank you very much.
Senator Murray.
Senator Murray. I want to start by mentioning two letters
that I sent to the FDA about the serious outbreak in my State
linked to the use of special medical scopes. I acknowledge that
after my first letter, FDA took several actions to help protect
patients.
Dr. Shuren, I know your center's staff is working to
provide me with information about the agency's full review of
this situation, a review Commissioner Hamburg committed to me
in March. I want to underscore again today how important that
review is so that we can work to prevent outbreaks like that
from happening ever again.
Dr. Shuren. We take it very seriously, too, and we'll be
getting back to you shortly. We're also continuing to look for
ways to provide more information out to the public as we
continue to work with the companies, with the healthcare
professionals, with hospitals, with the CDC and others. Next
up, just to flag for everyone, there will be an advisory
committee meeting on May 14 and 15 to discuss many of these
important scientific issues.
Senator Murray. Very good. Thank you very much for that.
Dr. Woodcock, we've heard testimony about the extraordinary
time and expense it takes to develop a new lifesaving drug,
from having an idea to FDA approving a product for patients.
We've heard many ideas about why this is the case and how to
improve things, like better drug development tools like
biomarkers.
How do you think we can cut down on the cost and time it
takes to develop new lifesaving products?
Dr. Woodcock. The limitations, as I said in my oral
testimony, are really related primarily to the science. We have
been working for quite some time on improving the
infrastructure that is used to move these products along and to
evaluate them. I do think what NCATS is doing is extremely
important, because they're doing a focused scientific effort.
It's developing new biomarkers, in which we're engaged with
many consortia on; developing clinical trial networks so that
each clinical trial isn't set up separately at great expense
and time and then taken down, and 8 out of 10 times, nothing
comes of it because the drug fails. Also streamlining
electronically how we collect data from clinical trials and
elsewhere, and we're making tremendous advances on that and the
standards.
Now, what NCATS is doing and other people are working on is
the predictive toxicology, because I believe what Senator
Alexander was referring to in a great sense--this valley of
death--relates to the academic community who have wonderful
ideas, but they don't have the funding to advance their ideas
beyond the laboratory stage and into people, because you have
to do the safety testing. You can't just put laboratory
chemicals into people. You have to evaluate them.
We need a more streamlined way, a common way, perhaps, that
these could be evaluated and get into early clinical testing
and how to get the expense down on that, or to fund it in some
way, or provide more funding. As Dr. Austin said, there is very
little funding that can be provided by NCATS to help all these
scientists around the country take their ideas beyond the
laboratory stage.
I think there are quite a number of things that can be
done, but I wouldn't underestimate the difficulty of doing each
one of them. They are scientific problems, and they need
collective solutions.
Senator Murray. Thank you.
Dr. Shuren, in order for FDA to operate with speed and
efficiency needed to review new products and protect public
health, FDA must be staffed by some of the top scientists in
the United States. Commissioner Hamburg talked to us about the
challenges the agency faces in hiring and retaining qualified
personnel to support your mission. Can you tell us whether
you've encountered similar challenges?
Dr. Shuren. All the time. I have great staff, but we have a
very hard time recruiting and particularly retaining people.
It's because, for one, I can't pay a competitive salary to
industry. I can't attract people or--I train people. We are the
training ground for industry. I train them. They become more
marketable, and they leave and they get salaries of two or more
times what they're getting paid today.
The other is if you come from industry, a lot of times your
retirement is in stock just for that company. I can't wall them
off. They have to divest that stock, and as a result, I've had
great people say, ``I'd come, but I can't because this is my
family's future.''
We have a high workload. This is something we deal with
through user fees. But, if you combine the high workload with
the less pay, then it is hard to get people, and that's why I
always have a high staff turnover. As a result, it hurts
companies. In the middle of a review, your lead reviewer or
your medical officer leaves, and I don't have a deep bench in
my center. It's a small center.
Senator Murray. Industry steals your employees but they
need you.
Dr. Shuren. That's exactly right, and we've got to change
that, because it best serves not just industry, but it
ultimately serves patients, and that's what this is all about.
Senator Murray. Dr. Woodcock, I assume you see the same
thing?
Dr. Woodcock. Absolutely. I mean, our scientists need to go
toe to toe with the best industry scientists, and yet when my
people leave, for either academia or industry, they typically
may double their salaries from what they're getting at CDER.
Senator Murray. Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Murray.
Senator Scott.
Statement of Senator Scott
Senator Scott. Thank you, Mr. Chairman.
Thank you to the panel for participating in this hearing,
and, certainly, your task is a daunting task without any
question. We look forward to being as helpful as we can.
Over the last year, I had an opportunity to meet an
incredibly young health advocate from Summerville, SC, a guy
named Zion Thomas, who is often referred to by his nickname,
The Mayor. He is an 11-year-old kid who has more energy and
more charisma than most of us sitting around the table, except
for his doctor and Elizabeth over there, of course. No offense,
of course, to Senator Alexander.
[Laughter.]
The challenge when you start calling names is that you find
yourself in trouble and digging a deep hole with a shovel that
you won't put down. Anyway, I will tell you that Zion continues
to be one of the strongest advocates for health issues because
he, from the age of 6 months, has been in and out of the
hospital because of the impact of sickle cell on his life and
on his family's, and all its challenges.
I'm happy to report that South Carolina has done a pretty
good job, and, specifically, the Medical University of South
Carolina, which has opened a sickle cell treatment clinic that
has been a breath of fresh air for Zion and his entire family.
Despite the fact that sickle cell disease impacts close to
100,000 people in the United States, there is still no cure,
and only one drug has been approved by the FDA to treat the
symptoms of the disease.
The problem I see is that I know that companies are working
very hard to find that cure for kids like Zion but,
unfortunately, they continue to hit road blocks along the way.
Part of the road blocks has been the approval process,
according to some of the companies, with the FDA.
The main frustration I hear--and not simply from those
companies trying to develop cures for sickle cell, but just
companies going through the approval process--is that the
agency can't quite articulate to the drug companies exactly
what they are looking for from the clinical trials process in
order to advance the drugs toward final approval.
Dr. Woodcock, what is the FDA doing now to ensure that
companies understand through communication between the FDA and
those companies what is necessary and what the results should
be along the way in multiple trials?
Dr. Woodcock. We have negotiated under the PDUFA program
something called a special protocol assessment. We have 90
days, I think it is, or maybe less, to get back to the company.
If they have a list of questions they've submitted to us--Do
you agree with this trial? Will this trial be sufficient to
support approval? Do you agree with these endpoints? Do you
agree with these inclusion criteria, et cetera, et cetera?--we
get back to them in writing, whether we agree or not. And if we
don't agree, we negotiate with them until we get an agreement.
We've done over 1,000 of these special protocol
assessments. This is a very valuable tool under the user fee
program for the companies to get predictability about what the
FDA would like them to do in order to get onto the market.
I think as a result of that and our program of meeting with
companies during the development process, we have a very high
what's called first cycle approval rate. In other words, when
the companies submit an application to us, almost 80 percent of
the time, we're able to approve it. If it's going to be
approved, we're able to approve it, during that cycle, because
they know what they're supposed to send us, and they're able to
fulfill our requirements.
I agree with you, especially for the smaller companies,
that they still feel uncertain and they want that clarity. That
process is available to all.
Senator Scott. Thank you.
The Chairman. Thank you, Senator Scott.
We have Senator Warren, Senator Cassidy, and Senator
Bennet.
Senator Warren.
Statement of Senator Warren
Senator Warren. Thank you, Mr. Chairman.
This committee is beginning to develop legislation to
accelerate the development of new cures and treatments. To do
that effectively, we must start with where medical innovation
comes from. Real innovation comes from NIH. A recent analysis
by Harvard researchers found that most of our truly
transformative drugs are based on insights gained through
federally funded research.
Another analysis found that two-thirds of the 21 highest
impact drugs approved between 1965 and 1992 stem directly from
public sector research. The private sector commercializes these
discoveries, but they would never happen in the first place
without strong government support.
Now, the industry knows this. The Biotechnology Industry
Organization testified that, ``There is no private sector
alternative for much of the basic research that NIH supports.''
John Castellani, President and CEO of PhRMA, has said that,
``Government-supported basic research is one key to
how we collectively progress in discovering novel
compounds for addressing patients' unmet medical
needs.''
Dr. Austin, do you agree that many of the drugs on the
market today are based on scientific insights gained through
NIH or other publicly funded research?
Dr. Austin. Absolutely. It's a fact.
Senator Warren. It's a fact. Good. We'll go with that.
Dr. Pettigrew, in addition to providing the basic science
used to develop new drugs, can you describe other ways that we
benefit from NIH-funded research?
Dr. Pettigrew. Thank you for the question, Senator. I think
the issue here really is impact, as you pointed out. This is a
process that is a continuum. It starts with basic science. The
objective of basic science is to understand the laws of nature,
and with that understanding, we are more informed about how
things work and what goes wrong. That leads to fashioning
solutions to these problems, and then those solutions have to
be translated.
The other things that we do at the NIH is to integrate that
knowledge with our ability to invoke the practical solutions
and design them through engineering and the physical sciences
along with the life sciences to fashion such solutions to the
kinds of problems you identified.
Senator Warren. Dr. Austin, would you like to add anything
to that?
Dr. Austin. A couple of things. The first is that--and I
can speak from both sides of this, because I'm a basic
researcher by training, but I'm also a clinician, and I also
spent many years in the pharmaceutical industry. I've seen all
sides of it.
Fundamental science is the seed corn on which all
interventions are based. It is necessary, but almost never
sufficient. This is a very long process of going from--what
fundamental science does is fundamentally to figure out how
something works normally, and when it breaks, why does it
break.
Then the issue is how to fix it, and how to fix it actually
requires a quite different skill set in any field, from
figuring out why it's broken, and translation is really to fix
it, and that's a completely different field. Sometimes there's
a feeling that the intervention to improve what's broken
happens kind of naturally, and it's well worked out about how
to do this, and we know how to do it.
The fact is, as Dr. Woodcock was saying, our understanding
of this process is extremely poor. The science underlying the
translational process is extremely poor, and our operational
structures to do it are extremely poor. So I would say, yes,
basic science is the seed corn of everything, but it requires
enormous energy to get through the next 10 or 15 years to
actually have an intervention which improves human health.
That's what we're working on.
Senator Warren. Dr. Woodcock, I see you nodding yes. Would
you like to add an amen to that?
Dr. Woodcock. Well, I think Dr. Austin put it extremely
well. It's very under-appreciated, and I'm sure you all have
researchers coming to you--because I do all the time--saying,
``I discovered this. It should be treating people tomorrow.''
All right? Actually, then, when you think it takes 15 years to
get from a discovery to actually treatment, people really don't
understand what goes in between there.
There's an enormous amount of work and effort, and,
frankly, at that stage, at the ``I have a discovery'' stage,
it's 10,000 compounds getting down to one that actually gets
approved. And that isn't because of FDA requirements. That's
because of the scientific process.
Senator Warren. Let's just stay focused on that about the
scientific process, then, if we're talking about innovation. We
have to be blunt. Medical research funding in this country is
in crisis. Since 2003, the NIH budget has not even kept pace
with inflation. Its purchasing power is down about 25 percent.
To increase medical innovation, the NIH needs more resources.
We've got to keep this pipeline going.
Last week in the New York Times, Newt Gingrich said that
when it comes to breakthroughs that could cure--not just treat,
but cure--the most expensive diseases, government is unique. It
alone can bring the necessary resources to bear, and it is
ultimately on the hook for the cost of illness. It is
irresponsible and short-sighted, not prudent, to let financing
for basic research dwindle.
I agree. If we want medical innovation in this country, we
need to double down on support for NIH. If we want to improve
the quality of life for Americans and reduce Federal healthcare
spending, we need to double down on NIH spending.
This committee has a chance to make a real difference, Mr.
Chairman, but that chance begins with support for the NIH.
Thank you.
The Chairman. Thank you, Senator Warren.
Senator Cassidy
Statement of Senator Cassidy
Senator Cassidy. Dr. Woodcock, I asked Dr. Hamburg just
before she left, but I wasn't really quite sure I could
comprehend the answer. The Manhattan Institute did an FDA
report card finding wide variance in performance among the
agency's drug review divisions. For example, median drug
approval in the fastest division, oncology, was two to three
times faster than neurology, cardiovascular, and renal.
Neurology took nearly 600 days to approve a new drug.
Cardiovascular took 400. Oncology and antiviral took slightly
less than 200. These high performers, oncology and antiviral,
actually have a higher workload than the other divisions.
Now, I've learned in life that leadership often plays a
role. Given the problems that you and Dr. Shuren--presumably,
those are common in both. What metrics do we have on these
divisions? How do we explain the difference? How do we minimize
it?
Dr. Woodcock. Well, I think that report was highly
misleading. First of all, CDER met all PDUFA goals. They have
six timelines for getting back to companies with a full review,
and all those divisions met their timelines. I can tell you,
though, if the Nation had declared a war on neurodegenerative
disease at the same time they declared a war on cancer, we
wouldn't be having this conversation.
Senator Cassidy. Now, let me ask--and I agree with you. We
need a war on neurodegenerative disease. Believe me. I'm with
you. That said, it does suggest that the workload at the
antiviral and the oncologic divisions is actually higher, and
yet they have approval times that are one-third of those of the
others.
Dr. Woodcock. Yes, and they----
Senator Cassidy. Then we have had a war on cardiovascular
disease, and that's one of the divisions that does poorly.
Dr. Woodcock. Well, does poorly. All right. When
cardiovascular disease--we have a large number of treatments
available for myocardial infarction. I won't go into this in
great detail, but, we have a large number of available
therapies. These are comparative trials that are done. They
often involve 25,000 patients or more.
To review that level--and they often have very small
incremental benefits, like 0.1 percent improvement in mortality
or stroke or something like that. That's quite a different
issue than, like, what Senator Murray was talking about--breast
cancer, where that drug doubled the time that it took for the
tumor to start growing again.
These are apple and orange comparisons, I believe. And I
will tell you that I was at the center a decade and a half ago
when the oncology division was routinely criticized over and
over and over again for not approving cancer drugs fast enough.
Now, because of advances in genetics, we actually understand
the molecular basis----
Senator Cassidy. May I interrupt just for a second?
Dr. Woodcock. Yes.
Senator Cassidy. Again, I have limited time. I don't mean
to be rude. One marker that kind of sorts things out sometimes
is your turnover in each division. Obviously, if there's more
turnover--and you alluded earlier, you and Dr. Shuren--turnover
can play a factor. Are the turnovers in the divisions constant?
Are they all similar?
Dr. Woodcock. Well, I would say in the neurology division,
due to the problems that Dr. Shuren was alluding to in hiring
and competitiveness of our salaries, we are really down on
neurologists. We're having a desperate time getting enough
neurologists, because the good news is that research in
neurodegenerative diseases is actually picking up. We've had
some turnover in that division with retirements of people who
have been there a long time, and we cannot really recruit
neurologists. This is a huge issue for us.
Senator Cassidy. I got you--and not to cut you off.
Dr. Austin, I walked in from another hearing as you were
speaking about these consortiums and some of the problems
thereof. I'm really interested about the intellectual property
rights as we go forward. I have an article from 2012,
``Recalibrating Intellectual Property Rights to Enhance
Translational Research Collaborations.'' It makes sense to me
that if you have a consortium, and you come up with an
invention, someone has to figure out who owns the IP.
Dr. Austin. Yes.
Senator Cassidy. That in itself--you've got to use somebody
else's IP, which--I've learned a new term--if it's a platform,
they can choke off the research if the licensing fee is too
high. I'm actually seeing people in the audience nod their
heads. What thoughts do you have? Do we need to do something
legislatively about this IP? Because I do get a sense that this
is a choke point going forward.
Dr. Austin. The good news is--I can tell you from our
perspective--we have never had a project fail because of IP.
Senator Cassidy. I was told that industry is going to be
different than government. Government tends to make it work
better. Industry is going to be the sticky wicket.
Dr. Austin. About half of our projects are with companies,
and we have--probably the reason that we have made this work is
that we view this area that you're describing as an area of
innovation. Science is not the only area that needs innovation.
Novel public-private partnership models is also a model of--a
way that we innovate.
If we have time, I could tell you about some of the
examples that we've developed and that are----
Senator Cassidy. I'm out of time, so let me ask you this
quickly. Do we need to do something legislatively, or is this
something that you all are going to be able to figure out?
Because otherwise, there's going to be bipartisan agreement in
addressing an IP issue that's going to thwart cost-effective
relations----
Dr. Austin. This is something that I'd have to consult with
my NIH colleagues and get back to you with.
Senator Cassidy. Please. If all of you would do that--I
mean, you know better than we. We are willing to help you. I
don't understand IP, but the Chairman is a lawyer, and he tells
me he can handle it.
I yield back. Thank you.
The Chairman. That's a very helpful question, and we would
appreciate a response on that.
Senator Bennet
Statement of Senator Bennet
Senator Bennet. Thank you, Mr. Chairman, and thank you for
holding this important hearing. I thank all the panelists.
Dr. Woodcock, I was hoping you could touch briefly on what
we've learned through the new breakthrough therapy process
that's been set up at the FDA. I want to thank you for working
with us on that bill. When Peggy Hamburg was here, she
testified that 23 of the 55 drugs approved during her time as
Commissioner of the FDA came through the breakthrough therapy
process. So something must be working.
As you know, Senators Burr, Hatch, and I also recently
introduced a parallel bill on the device side, and I wonder
whether you, Dr. Shuren, could also comment on the potential
for that. What are the pitfalls? What are the limitations, but
also the successes?
Dr. Woodcock.
Dr. Woodcock. Well, this program has been much more active
than we expected. We expected, based on historical trends, that
we would see one or two breakthrough drugs a year. We've
designated, since the program was enacted, 84 drugs. Not all of
them are going to make it, and I think that's the major
pitfall. We don't want to raise the hopes of desperate
patients, and then only to have that drug fail.
People have to be clear that when we designate a
breakthrough, it doesn't mean it's going to work at the end of
the day. However, we have approved 24 of these, and the track
record is very good, that, usually, that early clinical
indication is right.
The interesting thing about breakthrough--and I think the
most important thing--is it has shortened the development time.
That's really a first time. These other things have focused on
FDA review. For a priority drug, FDA review is 6 months or
less. There's not much to come and go on there.
We have the 15 years of drug development time, and the
breakthrough designation--by FDA working very closely with the
companies, we've had companies come up and testify and so forth
that up to 2 years has been cutoff of that development time. I
think it's a successful program.
It is, again, stressing, where staff, to Senator Cassidy's
point--many of them are antivirals and oncology drugs because
the science is advanced due to HIV and the war on cancer. We
understand those diseases better and we're able to actually
develop better therapies. However, the good news is we've had
designations in psychiatry and we've had designations in
serious dermatologic conditions and rare diseases of children
and so forth, and we can only hope that those bear fruit as
well.
Senator Bennet. What explains--you said you thought maybe
we would have one or two designated, and now we've got 80
designated and 24 approved. What explains that delta between
what we thought was going to happen and what actually has
happened?
Dr. Woodcock. I believe there's been an inflection point in
drug development. You know, everyone was very upset about drug
development. It was slowing down in the early 2000s and mid-
2000s.
Really, what happened is the companies started investing in
innovation, and it's the advances in science--what Senator
Warren was talking about--that are paying off in certain
fields. We know enough that we can--Chris was talking about the
fixes to the problems. We know better what to target and how to
do that.
For antivirals, for cancer drugs, we can actually get drugs
that are highly effective. Most of the older drugs maybe only
work--6 percent improvement or something like that. These
breakthroughs we're seeing--we're seeing curative therapies in
some cases.
Senator Bennet. Dr. Shuren, could you talk a little bit
about the potential in the medical device side and what some of
the things we should be thinking about are as we explore this?
Dr. Shuren. The potential here is tremendous, and we're
very excited to have a breakthrough device program at the
center. We started piloting this approach back in 2001 as the
Innovation Pathway. In fact, one of the products that came
through had funding support from NIH, and I think that's a nice
example where, for government, we might be able to marry up
this investment in important technology and then move it
through the regulatory process in a much more streamlined
fashion, with collaboration between NIH and FDA.
While we just launched that program the other week
formally, based on our experiences, I want to first of all say
thank you to you and Senator Burr and Senator Hatch for the
opportunity to work with you in providing some suggestions in
legislation to help sort of codify and maybe move that program
forward more expeditiously.
Senator Bennet. Mr. Chairman, I'm out of time or about out
of time. I just want to make one observation. When I first got
here 6 years ago, I used to say that it was nobody's day job in
Washington to figure out how we are going to keep a thriving
bioscience industry here in the United States.
I think it would only be fair to say we have made a
tremendous amount of progress in the last number of years in
part because of the leadership at the FDA. I'm grateful for it.
I think we have a long way to go, but I think we are certainly
moving in the right direction.
The Chairman. Thank you, Senator Bennet.
Senator Isakson.
Statement of Senator Isakson
Senator Isakson. Thank you, Chairman Alexander.
Dr. Woodcock, I was at the Association of County
Commissioners convention in Georgia last Sunday. That may seem
to be irrelevant to this hearing. Ross King is the association
director for the county commissioners of Georgia. His daughter,
Jackie King, died last year. She died of melanoma. In her 2-
year fight against melanoma, she joined up with me to help
promote the Sunscreen Innovation Act which we passed here about
6 months to a year ago.
My question to you is this. The surgeon general has issued
a call to action on skin cancer. More Americans have skin
cancer than lung cancer, prostate cancer, breast cancer, and
the others combined. It costs us $8.1 billion a year.
One of the cancers that comes directly from the sun is
melanoma, which is the deadliest of all cancers. I have had
two, which, fortunately, I got in time. It's a very deadly
cancer. It's what Jackie King died of.
Why is it that now that we've passed the Sunscreen
Innovation Act, which directed the FDA to look at these
ingredients in over-the-counter drugs that are approved in
foreign countries, that are innovative and helpful in
sunscreen--why do you continue to delay in taking action? Some
of those have been pending for 12 years.
Dr. Woodcock. We have taken the actions directed by the
Sunscreen Innovation Act. The way the process is set up for the
monographs for how over-the-counter ingredients are regulated--
we have followed that process. That process calls for data
submission prior to the finalization of the monograph for
products. That is the scheme that is currently in effect.
Senator Isakson. If you carried that scheme to its
conclusion, when will we have some results?
Dr. Woodcock. Well, it would require the manufacturers to
submit the data that we have asked them to submit about the
safety of these additional sunscreens to the FDA, and then we--
the monograph process is a regulations process. We have to
propose and finalize regulations for each segment of any
monograph, and there are multiple categories.
There are 88 categories of over-the-counter drugs, I
believe, that we need--to go through this process. Some of them
are in final form. The sunscreen one is not.
Senator Isakson. The monograph is not in final form?
Dr. Woodcock. Right.
Senator Isakson. Is that because you don't have what you
need from the manufacturers of the ingredients?
Dr. Woodcock. In part, and in part it's because the
monograph process follows a sort of stately progression, and as
the science evolves, the process of proposing and finalizing
regulations always seems to lag behind the scientific changes
that occur. We're always trying to catch up. We started on the
monograph for sunscreens in the 1970s, and we're still working
on it.
Senator Isakson. Well, it's been a long time, and it's time
to bring some of it to a conclusion. I know you can't answer
this off the top of your head, but if you would, let me know or
let the committee know what the progress is on the sunscreen
ingredients, if there are any manufacturers who are delinquent
in getting you the information that you need. Please let us
know, because I would like to do everything we can to promote
them getting all the information in so you can do it in a
timely fashion--finish your monograph.
Dr. Woodcock. I totally agree, and we will be happy to get
back with you.
In fact, I introduced the regulation that allows these
other ingredients to be considered in the monograph process in
the late 1990s so that we could put more ingredients into this
process.
Senator Isakson. All right. I'm getting ready to show my
ignorance because my staff is always smarter than I am, and
I've just been handed a note, so I'm going to ask this
question. If it's a dumb question, my staff got me to ask it.
[Laughter.]
And since it's my staff, I know it's not a dumb question.
The bill changed the law and gave sunscreen a separate order
process. Is that correct?
Dr. Woodcock. That's correct for the time and extent, to my
understanding, but not for the final process.
Senator Isakson. Has that time and extent been expedited?
Dr. Woodcock. To the extent we were able to under the new
law, we've obeyed all the provisions.
Senator Isakson. Because that's really what led to the
whole Sunscreen Innovation Act, because one of those time and
extent applications was 12 years old and still did not have
action. I'm not trying to pick on you, but it's a big
important--anybody that's lost a child to melanoma or anybody
that's suffered from skin cancer knows how important it is.
Dr. Woodcock. You are not picking on me, and I share your
frustration about the monograph process. It is not very
functional in today's world.
Senator Isakson. Well, I'll pick on Dr. Shuren for 1
second.
Dr. Shuren, we sent you a letter about a year ago asking
about the draft guidance. Right before the May 10th hearing,
you submitted a partial list of the amount of draft guidance
that FDA had issued. This Friday, we got the rest of that list
to the committee, and I have it before me. It lists whether
you're going to withdraw draft guidance, finalize draft
guidance, or reissue draft guidance.
My question is just--and you don't really need to respond
to this except to respond in writing. Will you let us know when
you plan to take those actions on finalization, revision, or
withdrawal? There are 144 pending draft guidances for the
agency right now. We'd like to know what the timing of those is
going to be.
Dr. Shuren. I know we'll get back from the agency.
I can say for the device program, we're withdrawing 30 from
last week. The 43 remaining--the 40 we will finalize within the
next 18 months, and the majority of those are actually less
than 5 years.
The other thing I'll point out is we put in performance
goals in December of last year about finalizing draft
guidances, commitments that we will finalize 80 percent within
3 years, 100 percent by 5 years, or reissue or withdraw. That's
our starting point, and we hope to make greater progress from
there, too.
Senator Isakson. Thank you very much.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Isakson.
Senator Murray, do you have any closing comments or
questions?
Senator Murray. Well, Mr. Chairman, thank you for this
hearing. I thought it was really excellent. I do have a few
more questions. I will submit them for the record to get
responses.
I thought this was a great hearing. We've got a lot of work
in front of us, but I think, working in a bipartisan way, we
can move forward, and I appreciate your work on this.
The Chairman. Thanks, Senator Murray.
Dr. Woodcock, you said the monograph process--you seemed to
suggest the monograph process is outdated. Who requires it? Do
we require it, or do you require it?
Dr. Woodcock. The monograph process was a workaround around
the 62 amendments which required efficacy data for all drugs
that would be on the U.S. market. It wasn't known, but there
were up to 500,000 over-the-counter drugs which apparently came
from about 200 active ingredients.
The Chairman. Well, let me ask this. If you were the king
or the queen, would you change it?
Dr. Woodcock. Yes. I would have a more effective process to
finalize the monographs and also keep them up to date with
modern science, because at the time it was done, it was thought
we could just put a monograph out, and then we'd be done. We've
learned things like the toxicity of Tylenol, acetaminophen----
The Chairman. Would that require a change in the law?
Dr. Woodcock. It would require something.
The Chairman. Would you please give our staff technical
advice about what that change might look like?
Before I conclude, I see Senator Casey is here. He was here
earlier, so let me call on him now, and then we'll conclude the
hearing after that.
Statement of Senator Casey
Senator Casey. Mr. Chairman, thank you. I want to thank you
and the Ranking Member for the hearing. I know I've been in and
out, so I'll be within my time limit for sure.
Dr. Woodcock, I wanted to start with you with a question,
but I first wanted to ask you--I notice you went to Penn State?
Are you a Pennsylvania native?
Dr. Woodcock. I am.
Senator Casey. Where are you from?
Dr. Woodcock. Hollidaysburg, PA.
Senator Casey. Blair County.
Dr. Woodcock. Absolutely, yes.
Senator Casey. I just wanted to get that on the record.
Dr. Woodcock. Idyllic childhood.
Senator Casey. I wanted to ask you, in the context of rare
pediatric diseases--I understand that FDA recently awarded the
third and final priority review voucher as authorized under
FDASIA. I wanted to ask you, in particular, regarding this
question. What are the three products that were approved and
awarded that priority review voucher--or vouchers, I should
say, plural. I don't know if you have that.
Dr. Woodcock. I do have that here somewhere, because I
think that is important. There was one for a tropical disease.
There was--hold on. I'm sorry. We can get back to you on that.
Yes, we did--here they are. Vimizim for Morquio Type A
syndrome; another one called Unituxin for pediatric people with
high-risk neuroblastoma; and then recently Cholbam, cholic acid
for bile acid disorders and peroxisomal disorders.
Those are obviously very rare diseases where there was not
very much satisfactory treatment available. That's really good
news.
Senator Casey. I appreciate that, and maybe we'll followup
with some questions about companies that are interested in
seeking a priority review voucher. That would be helpful, and
we can submit these for the record.
I want to thank you for that. I just have a last question,
I guess, for Dr. Austin regarding the so-called tissue chip.
Let me just ask a preliminary question. Is the product safe
now for use in humans?
Dr. Austin. No. That's an important question. This is a
research project at this point. This project only started 3
years ago. It's made much more rapid headway than I
anticipated, at least. It is very much in the testing-
validation stage now. We are working very closely--and have
from the beginning--with colleagues from the FDA about this.
Perhaps within 3, 4, or 5 years, we'll be at the point
where this might be able to be used for some conditions of
qualification. But, there's a lot more work to go.
At this point, the most immediate applications--and we're
beginning to see this already--a number of these chips are
being used actually in research applications to be able to
understand human diseases and why they happen and how they
might be fixed in a way that works better and more quickly than
animal models. For regulatory applications, the requirements
are simply much more stringent. We're definitely working in
that direction and working hand-in-glove with the FDA, but we
have a ways to go.
Senator Casey. I'll leave the rest of the time. I want to
thank our witnesses for being here. I also want to, Mr.
Chairman, thank you and the Ranking Member, and I'll refer back
to something Senator Warren said and that a number of us have
been saying for a number of years. We have to get more
researchers to NIH for all the reasons that were cited, and,
frankly, we're years behind in doing that.
Thank you very much.
The Chairman. Thank you, Senator Casey, and thanks, Senator
Warren.
Let me thank the witnesses. You have distinguished careers.
You run immensely important centers and, in one case, an
institute. You know the ways of Washington. I mean, if we
wanted to talk about Obamacare or right-to-work laws, we could
have a big fight on this committee.
Senator Murray and I aren't interested in a big fight on
this subject. We're interested in getting a result, and we're
not here to make it harder for you to do your job. We're here
to enable you to do it better.
We would like to know from you, specifically, what we can
do to make it easier for you to align Federal policies with
innovation so that we can get discoveries and treatments all
the way through the process into the medicine cabinets so they
can help Americans. We know that part of that has to do with
funding, and we'll discuss that, and we'll deal with that in
the Appropriations Committee and to some extent here.
There are bound to be other specific things that, with your
experience, you sit there some days and say, ``Why do I have to
do this when I could do it better? '' For example, if the
monograph is outdated, and if there's a way to fix it, we'd
like to know how to fix it.
If it makes a difference at NIH, as Dr. Collins says it
does, to give you a chance to take the funding that we
appropriate for 1 year and roll it over to the next year, as we
do with some agencies, then please put that on your list. In
other words, we would like to invite you to give the bipartisan
working group that Senator Murray and I have formed specific
suggestions from your agencies about what we can do to enable
you to do your job.
We don't want to produce a bill that reduces your
productivity. We'd like to increase it. You know what you're
doing much better than we know what we're doing. We'll still be
appropriately critical. We'll have our questions. We're here to
enable you, and we invite that.
The time for receiving that is the next few months, because
right now, we're working on elementary and secondary education.
We're doing pretty well with that. We're going to move next, as
a major priority, to the Higher Education Act, and in the
meantime, we're getting ready for this. As I said earlier,
we're working on a parallel track with the House. We're working
with President Obama, who is very interested in the precision
medicine initiative, as all of you know.
This is an invitation that I hope you won't pass up. We
thank you for your service, and we look forward to your further
comments.
The hearing record will remain open for 10 days. Members
may submit additional information for the record within that
time if they would like.
Thank you for being here. The next HELP Committee health
hearing will be on May 5th. The committee will stand adjourned.
[Whereupon, at 11:27 a.m., the hearing was adjourned.]