[Senate Hearing 114-572]
[From the U.S. Government Publishing Office]
S. Hrg. 114-572
CONTINUING AMERICA'S LEADERSHIP IN MEDICAL INNOVATION FOR PATIENTS
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HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED FOURTEENTH CONGRESS
FIRST SESSION
ON
EXAMINING CONTINUING AMERICA'S LEADERSHIP IN MEDICAL INNOVATION FOR
PATIENTS
__________
MARCH 10, 2015
__________
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
LAMAR ALEXANDER, Tennessee, Chairman
MICHAEL B. ENZI, Wyoming BARBARA A. MIKULSKI, Maryland
RICHARD BURR, North Carolina PATTY MURRAY, Washington
JOHNNY ISAKSON, Georgia BERNARD SANDERS (I), Vermont
RAND PAUL, Kentucky ROBERT P. CASEY, JR., Pennsylvania
ORRIN G. HATCH, Utah KAY R. HAGAN, North Carolina
PAT ROBERTS, Kansas AL FRANKEN, Minnesota
LISA MURKOWSKI, Alaska MICHAEL F. BENNET, Colorado
MARK KIRK, Illinois SHELDON WHITEHOUSE, Rhode Island
TIM SCOTT, South Carolina TAMMY BALDWIN, Wisconsin
CHRISTOPHER S. MURPHY, Connecticut
ELIZABETH WARREN, Massachusetts
David P. Cleary, Staff Director
Lindsey Ward Seidman, Deputy Staff Director
Evan Schatz, Democrat Staff Director
John Righter, Democrat Deputy Staff Director
(ii)
C O N T E N T S
__________
STATEMENTS
TUESDAY, MARCH 10, 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
Burr, Hon. Richard, a U.S. Senator from the State of North
Carolina....................................................... 20
Mikulski, Hon. Barbara A., a U.S. Senator from the State of
Maryland....................................................... 22
Isakson, Hon. Johnny, a U.S. Senator from the State of Georgia... 24
Bennet, Hon. Michael F., a U.S. Senator from the State of
Colorado....................................................... 26
Cassidy, Hon. Bill, M.D., a U.S. Senator from the State of
Louisiana...................................................... 28
Whitehouse, Hon. Sheldon, a U.S. Senator from the State of Rhode
Island......................................................... 30
Collins, Hon. Susan M., a U.S. Senator from the State of Maine... 32
Warren, Hon. Elizabeth, a U.S. Senator from the State of
Massachusetts.................................................. 34
Baldwin, Hon. Tammy, a U.S. Senator from the State of Wisconsin.. 36
Casey, Hon. Robert P., Jr., a U.S. Senator from the State of
Pennsylvania................................................... 38
Franken, Hon. Al, a U.S. Senator from the State of Minnesota..... 40
Witnesses
Collins, Francis, M.D., Ph.D., Director, National Institutes of
Health, Bethesda, MD........................................... 5
Prepared statement........................................... 7
Hamburg, Margaret A., M.D., Commissioner, Food and Drug
Administration, Silver Spring, MD.............................. 10
Prepared statement........................................... 12
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
Response by Francis S. Collins, M.D., Ph.D. to questions of:
Senator Alexander........................................ 45
Senator Collins.......................................... 49
Senator Hatch............................................ 49
Senator Cassidy.......................................... 51
Senator Bennet........................................... 53
Senator Warren........................................... 54
(iii)
CONTINUING AMERICA'S LEADERSHIP IN MEDICAL INNOVATION FOR PATIENTS
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TUESDAY, MARCH 10, 2015
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The committee met, pursuant to notice, at 10:04 a.m., in
room SD-430, Dirksen Senate Office Building, Hon. Lamar
Alexander, chairman of the committee, presiding.
Present: Senators Alexander, Murray, Burr, Isakson,
Collins, Cassidy, Mikulski, Casey, Franken, Bennet, Whitehouse,
Baldwin, and Warren.
Opening Statement of Senator Alexander
The Chairman. The Senate Committee on Health, Education,
Labor, and Pensions will please come to order. Senator Murray
and I will each have an opening statement. We'll then introduce
our witnesses, and after the witnesses, Senators will have 5
minutes of questions. I have really been looking forward to
this day. This is a very important hearing.
Dr. Collins, I thank you for coming.
Dr. Hamburg, I thank you for coming, especially because
that caused a change in plans.
We don't have two people who know more about what we're
talking about than the two of you. This is an opportunity for
us to discuss that.
Let me see if I can put this in some sort of context. This
is a busy committee. In the last Congress, Senator Harkin used
to point out that we completed 25 pieces of legislation which
became law, and Senator Murray and I are working well together.
There are three major items that we intend to focus on in
the next 2 years, among all the others. No. 1 is fixing No
Child Left Behind, and we're working well together toward that
and hope to have a markup on that after the recess.
Second, we're working on simplifying and reauthorizing the
Federal Government's supervision of higher education in
America. We had a hearing on that recently, and it had an
impressive report. Senator Mikulski, Senator Burr, Senator
Bennet, and I had asked about simplifying regulations. That
will be second.
The third topic is to deal with this exciting new era of
medicine that we have and take a look at what we can do as a
Congress, working with the President, to reduce the cost and
the amount of time it takes to go from discovery of a medicine
or a treatment or a medical device and take it all the way
through to the medicine cabinet or the doctor's office.
We know important work has been done in the Congress on
that not so long ago. We have an opportunity this year to make
whatever contribution there is to make, and it's an area that
we ought to succeed in, because there's not really a political
partisanship about this issue.
In fact, the House of Representatives is moving on a
parallel track on something they call 21st Century Cures.
President Obama is extremely interested in precision medicine.
I attended his announcement of that interest at the White House
recently along with Dr. Collins and Dr. Hamburg. I've talked
with him about it and with Secretary Burwell.
Suffice it to say that I believe every single member of
this committee is interested in identifying what we can do to
make it easier to move those drugs, treatments, and devices
from discovery all the way through to the medicine cabinet.
We're not just talking about moving it through the FDA.
Sometimes it takes 2, 4, 6, 10, 12 years to get to the FDA's
front door. So we're not just talking about the FDA. We're
talking about the whole range of issues there.
Dr. Collins has described it this way. He wrote in 2013,
``Drugs exist for only about 250 of the more than
4,400 conditions with defined molecular causes. It
takes far too long and far too much money to get a new
drug into our medicine cabinets. This is an old problem
that cries out for new and creative solutions.''
Since Dr. Collins wrote that, the number of conditions with
defined molecular causes has increased to more than 5,400. The
number of new drugs approved has not kept pace with these
discoveries. Dr. Hamburg, who is here today, has said that we
are left relying on the 20th century approaches for the review,
approval, and oversight of the treatments and cures of the 21st
century.
President Obama, in his announcement of the new Precision
Medicine Initiative, said 21st century business will rely on
American science, technology, research, and development. The
President said,
``I want the country that eliminated polio and mapped
the human genome to lead a new era of medicine, one
that delivers the right treatment at the right time.''
In some patients with cystic fibrosis, this approach has
reversed a disease once thought unstoppable.
He introduced at that White House announcement a 27-year-
old young man whose cystic fibrosis has been cured because he
was 1 of 4 percent of the sufferers with that disease caused by
a mutated gene for which there is now a drug. The legislation
Senator Bennet and Senator Burr worked on may have helped to
contribute to that opportunity. This is a discussion that can
affect nearly every American and one which we're going to take
very seriously.
Senator Burr and I issued a white paper that we had been
working on for some time that focused on the issues that we
thought the committee ought to identify, and we've submitted
that to Senator Murray and to the rest of the members of the
committee for their consideration on: costing too much to bring
medical products through the discovery process and development
process taking too long, whether FDA's responsibilities include
unrelated activities to what the focus should be, the disparity
in scientific knowledge at the FDA and the fast pace of
biomedical innovation. Those are some of the issues that we
focused on.
What we hope to learn today from two distinguished leaders
of our government is exactly what we should be focusing on. We
don't want to waste our time, and we can't do everything. If
this train is moving through the station in the next 12 months,
and if our goal is to help get from discovery to the medicine
cabinet or the doctor's office, what are the two or three
things that we ought to spend our time on?
I believe we can do that, working together. We're excited
about it. It's a chance for your agencies and the rest of the
government to let us help you get the obstacles out of the way
that might be in the way of your getting your job done. Some of
them relate to money. Some don't. Some relate just to the pile-
up of administrative regulations.
At our hearing on higher education, Chancellor Zeppos from
Vanderbilt talked about the fact that he hired a Boston
consulting group to assess the cost of rules and regulations to
operate Vanderbilt University for 1 year, and the answer was
$150 million, $11,000 onto every student's tuition at the
university.
There's a whole range of things. I'm looking forward to
this. I thank you, Dr. Collins, and I thank you, Dr. Hamburg.
I'll now turn to Senator Murray, and we'll then turn to the
witnesses.
Opening Statement of Senator Murray
Senator Murray. Thank you very much, Chairman Alexander.
Dr. Collins, Dr. Hamburg, it's great to have you both here.
I have a lot of appreciation for the work that you do to
encourage innovation and improve health and well-being.
Dr. Hamburg, as you step down from your role at FDA, I
especially want to thank you for your many, many years of
service, and we're all very grateful for your leadership.
Thank you very much from all of us.
I am very pleased to be working with Chairman Alexander and
other members of the committee on ways that we can continue to
advance biomedical innovation for patients. I believe that we
are at a truly fascinating moment in medical innovation right
now. We increasingly have the ability to move away from a one-
size-fits-all model of treatment and instead treat patients
according to their unique characteristics.
We've seen enormous growth in life sciences as a source of
economic strength and job creation. My home State of Washington
is a great example. Life sciences are the fifth largest
employment sector in my State, and it's growing. These are good
jobs in an industry with global reach, and our country needs
more of them.
It is critical that we secure and build on the United
States' leadership in medical innovation. To do this, I believe
Congress has to look at how we ramp up investment in the kind
of research and development that helps drive this private
sector growth. That's something I will be very interested in
exploring as part of our bipartisan efforts in the coming weeks
and months.
Dr. Collins, I know that you are very concerned about the
impact of sequestration and what it has done to NIH, and I am,
as well. I hope that we can talk about that today as well. I'm
also eager to hear more about the many efforts at NIH to ensure
the United States remains the global leader in biomedical
research and discovery.
The FDA drug and device approval process is another topic
that I know will receive a lot of focus.
Dr. Hamburg, you recently announced that in 2014, the FDA
approved 51 new drugs, which is the most in almost 20 years.
You should be very proud of what that means for patients and
families across the country. I look forward to hearing from you
today about ways that we can build on that progress.
Another priority I will be focused on is the needs of women
and young children in the research, development, and approval
process. When we looked at the FDA approval process back in
2005, Senator Kennedy reminded us that when patients open up
their medicine cabinet, they deserve every assurance that the
medicines they take are safe and effective, and that is just as
true today. As our conversations about advancing medical
innovation move forward, I will be guided by his vision of
upholding that assurance.
In the weeks and months ahead, I hope we can reach an
agreement on policies that help get safe and effective
treatments to patients more quickly. That would be good for our
economy and could really make all the difference for so many
families we represent.
Thank you again to our witnesses for being here today.
Thank you, Chairman Alexander, for holding this hearing.
The Chairman. Thank you, Senator Murray.
We have a good attendance already of Senators. I would say
that we have formed a working group of the staff, a single
working group, on this subject for the purpose of identifying
how we will proceed. After this hearing, in the next few weeks,
the working group and Senator Murray and I will sit down and
talk about how we can have a bipartisan process and take into
account and focus our efforts in a way that gets a result. In
that, we'll be aware of what the House is doing, and we'll work
with Secretary Burwell and with the President, especially on
their Precision Medicine Initiative.
I would ask each witness to summarize, if you can, in about
10 minutes, your testimony so that Senators will have a chance
to have a conversation with you. I thank you both for coming.
Dr. Collins first--thank you--Director of the National
Institutes of Health, the largest supporter of biomedical
research in the world. He has been Director of NIH since 2009.
He is known for his leadership of the international human
genome project which led the first completely sequenced human
genome in 2003.
Next we'll hear from Dr. Hamburg. She is Commissioner of
the Food and Drug Administration. According to our staff, 25
cents of every consumer dollar that's spent in the United
States, you regulate when you regulate prescription drugs,
medical devices, food and tobacco products.
Dr. Hamburg has been in this role for 6 years.
I'm glad she's here, and I'm glad she's here because she is
retiring, and she has this wealth of knowledge accumulated over
the last 6 years. I especially asked her to come for that
purpose because I knew the committee would want to hear from
her.
Dr. Hamburg, thank you very much for your service to our
country. Even though you may be retired, we hope you'll
continue to advise us, especially during this next year as we
work through these issues. And I thank Senator Murray and
Senator Mikulski for keeping me straight on my comments.
Dr. Collins.
STATEMENT OF FRANCIS COLLINS, M.D., Ph.D., DIRECTOR, NATIONAL
INSTITUTES OF HEALTH, BETHESDA, MD
Dr. Collins. Good morning, Chairman Alexander, Ranking
Member Murray, members of this important committee. It is an
honor to appear before you today alongside my friend and
colleague, FDA Commissioner Peggy Hamburg. Our agencies have
much to gain by working together, and we have been doing so and
we're committed to that effort. In fact, Peggy and I spent a
productive 3 hours just yesterday afternoon, along with senior
leaders from both of our agencies who make up the NIH FDA
leadership council, discussing a wide range of projects we are
working on together.
I'd like, on behalf of the NIH, our employees, grantees,
and patient community, to thank members of this committee for
your continued support and for holding this bipartisan hearing
today. I appreciate the opportunity to discuss how we as a
nation can drive innovation through Federal investments in
scientific research.
Breakthroughs generated by NIH research--and I'm going to
show you a few visuals here, if you can see the screen--are
behind many of the gains our country has enjoyed in health and
longevity.
[Slides Shown.]
For example, over the past 60 years, deaths from
cardiovascular disease have fallen by more than 70 percent.
Meanwhile, cancer death rates have been dropping about 1
percent annually for the last 20 years. Likewise, HIV/AIDS
treatments have greatly extended lives, and prevention
strategies are enabling us to envision the first AIDS-free
generation.
Today, I want to share with you a few of the many promising
opportunities for biomedical research innovation. I can assure
you the potential of scientific research has never been
brighter than it is today. NIH remains strongly committed to
basic science, fundamental research that serves as the
foundation for discoveries that have long made America the
world leader in biomedicine and accounts for no less than 145
Nobel prizes that have been awarded to our scientists that we
support through NIH grants and through our intramural program.
One exciting example in basic science is the BRAIN
initiative. This bold, multiagency, multiyear effort is
enabling development of innovative technologies to provide a
clearer, more dynamic picture of how individual brain cells and
neural circuits interact in time and space. This initiative
will ultimately give us the tools for major advances in brain
diseases, from Alzheimer's and autism to schizophrenia and
traumatic brain injury.
NIH is also innovating in translational science, where
basic science findings are developed into clinical benefits.
Let me give you a few examples. Recent advances in technology
have led to the discovery of more than 1,000 risk factors for
disease. Drug development is a terribly difficult and failure-
prone business. A major reason for failures is that scientists
often just don't know how to choose the right pathways to
target for the next generation of drugs that they want to
develop.
With this in mind, we were excited just a year ago to
launch the Accelerating Medicines Partnership, or AMP. This is
an unprecedented, precompetitive, public-private partnership
using cutting edge scientific approaches to choose the most
promising targets for therapeutic intervention. Besides NIH,
AMP partners include, importantly, the FDA, 10
biopharmaceutical firms, and a number of nonprofits, including
patient advocacy groups.
Initially, AMP is focusing on three disease areas that are
ripe for discovery of the next generation of drug therapies:
Alzheimer's disease; Type 2 diabetes; and the autoimmune
disorders, rheumatoid arthritis and lupus. Through this
innovative and collaborative approach, we believe we can learn
how to treat and cure disease faster, and we can do it together
across this whole ecosystem.
NIH is also working to streamline the therapeutic
development pipeline through an effort at our newest center,
NCATS. More than 30 percent of promising medications fail in
human clinical trials because they are found to have
unacceptable toxicity despite promising pre-clinical studies.
Could we do better?
While the Tissue Chip for Drug Screening Initiative is
developing 3-D human tissue biochips that model the structure
and function of organs, such as the lung, liver, and heart,
these organoid chips--and you can see the heart chip there is
actually beating in real time because the cells that are on
that chip are cardiac muscle cells that are synchronized to
beat just as they would if they were in a heart. These give us
the opportunity to mimic complex functions of the human body
without putting humans at risk, enabling scientists to predict
more accurately how effective a therapeutic candidate would be
in clinical studies, eliminating toxic or ineffective drugs
earlier in the development process.
Scientific advances are also accelerating progress toward a
new era of precision medicine. Historically, doctors have been
forced to base their recommendations for treatment on the
expected response of the average patient. Recent advances,
including the plummeting cost of DNA sequencing, now make
possible a more precise approach to disease management and
prevention that takes into account individual differences in
genes, environment, and lifestyle.
With this in mind, NIH is thrilled to take a lead role in
the multiagency Precision Medicine Initiative that you all have
already mentioned in the opening statements and which we at NIH
are very excited about. In the near term, this initiative will
focus on cancer. To accelerate efforts, this project will
support research aimed at understanding why cancer has
developed drug resistance, using noninvasive methods to track
therapeutic responses to so-called liquid biopsies, and
exploring new treatments including combination therapies
targeted to the genetic profiles of a wide range of adult and
pediatric cancers.
As a longer-term and very bold goal of this initiative, NIH
will launch a national research cohort of 1 million or more
volunteers who will play an active role in how their genetic
and environmental information is used to prevent and manage a
broad array of diseases. A project of this magnitude will lay
the groundwork for new prevention strategies and novel
therapeutics. There's no better time than now to embark on this
enterprise to revolutionize medicine and move this precise
personal approach into everyday clinical practice.
In closing, to make this clear in terms of its impact on
human health, allow me to share a story that highlights the
early promise of precision medicine. When Maki Inada was
diagnosed with stage 3-B adenocarcinoma of the lung in 2008, it
was completely unexpected. She was 36 years old, never smoked a
day in her life, and yet her tumor was very large, as shown on
this film, 7 centimeters, with a very low likelihood of
survival beyond a year or two.
As Maki began the recommended standard chemotherapy, her
doctors, who were ahead of their time in precision medicine,
suspected she might have a particular mutation in a gene called
the epidermal growth factor receptor, or EGFR. Genetic testing
confirmed their hunch. Maki was prescribed Tarceva, a drug that
precisely blocks EGFR's signal.
After 3 months of treatment, Maki's large tumor shrunk
dramatically, as you can see. This was followed by surgery to
remove cancerous tissue plus retreatment with Tarceva. Today, 7
years after her diagnosis, her doctors can detect no signs of
cancer. What's more, Maki has now completed a triathlon, landed
her dream job as a biology professor at Ithaca College, and
welcomed a healthy baby girl.
Maki is the face of scientific innovation made possible by
sustained investments in biomedical research. With your
support, we can realize the vision of accelerating discovery
across the vast landscape of biomedicine, from basic science
inquiry to more precise personalized approaches to treatments
and cures.
Thank you, Mr. Chairman. My colleagues and I welcome your
questions.
[The prepared statement of Dr. Collins follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good morning, Chairman Alexander, Ranking Member Murray, and
distinguished members of the committee. I am Francis S. Collins, M.D.,
Ph.D., and I am the Director of the National Institutes of Health
(NIH).
It is an honor to appear before you today, alongside my dedicated
colleague, Dr. Hamburg, to discuss how we, as a Nation, can drive
innovation through Federal investments in scientific research. On
behalf of NIH, our employees, grantees, and patient community, I want
to thank members of this committee for your continued support and for
holding this hearing today.
As the Nation's premier biomedical research agency, NIH's mission
is to seek fundamental knowledge about the nature and behavior of
living systems, and to apply that knowledge to enhance human health,
lengthen life, and reduce illness and disability. All of us at NIH
believe passionately in this mission, and are dedicated to the pursuit
of innovative strategies to achieve it.
NIH has been advancing our understanding of health and disease for
more than a century. Scientific and technological breakthroughs
generated by NIH-supported research are behind many of the improvements
our country has enjoyed in public health. For example, our Nation has
gained about 1 year of longevity every 6 years since 1990.\1\ A child
born today can look forward to an average lifespan of about 78 years--
nearly three decades longer than a baby born in 1900. Deaths from
cardiovascular disease have been reduced by more than 70 percent in the
past 60 years. HIV/AIDS treatment and prevention may now enable us to
envision the first AIDS-free generation since the virus emerged more
than 30 years ago. Cancer death rates have been dropping about 1
percent annually for the past 15 years. These are extraordinary
strides--but we aim to go much further.
---------------------------------------------------------------------------
\1\ http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_02.pdf.
---------------------------------------------------------------------------
Today, I want to share with you a few of the many promising
opportunities for biomedical research innovation. I can assure you that
the future of scientific research has never been brighter.
Scientific advances are accelerating progress toward a new era of
personalized medicine. Historically, physicians have had to make
recommendations about disease prevention and treatment based on the
expected response of the average patient. This one-size-fits-all
approach works for some patients and some conditions, but not others.
Technology developments, along with plummeting costs of DNA sequencing,
now make it possible to develop an innovative approach to treatment
that accounts for individual differences in patients' genes,
environments, and lifestyles. To this end, through the President's
Precision Medicine Initiative announced in January, NIH and our
colleagues at FDA and the Office of the National Coordinator for Health
Information and Technology will work together on this bold new research
effort to revolutionize how we improve health and treat disease. A near
term goal of the President's Precision Medicine Initiative focuses on
cancer; cancer research has been leading the way in precision medicine
by defining the driver mutations in individual tumors and using this
information to design the ideal therapy for each patient. To accelerate
the pace of discovery, this initiative seeks to expand current cancer
genomics research to understand the development of resistance to
targeted therapy, to apply non-invasive methods to track patients'
responses to treatment, and to explore the efficacy of new drug
combinations targeted to specific tumor mutations.
As a longer term goal of this initiative, NIH also plans to launch
a national research cohort of one million or more volunteers, who will
volunteer to play an active role in how their genetic and environmental
information is used for the prevention of illness and management of a
wide array of chronic diseases. This venture will pioneer a new model
for doing science that emphasizes engaged participants, technologically
advanced collection of many different data types, responsible data
sharing, and privacy protection. A project of this magnitude will lay
the foundation for a myriad of new prevention strategies and novel
therapeutics. There's no better time than now to embark on this
ambitious new enterprise to revolutionize medicine and generate the
scientific evidence necessary to move this personal approach into
everyday clinical practice.
NIH also is supporting the basic science that is fundamental to
scientific advances in biomedicine. One way we are working to unravel
life's mysteries is with the President's Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative announced in
2013. NIH is partnering with colleagues at the National Science
Foundation, the Defense Advanced Research Projects Agency (DARPA), the
Intelligence Advanced Research Projects Activity (IARPA), and the Food
and Drug Administration (FDA), in this effort to revolutionize our
understanding of the most complicated biological structure in the known
universe, the human brain. This multiyear initiative will produce a
clearer, more dynamic picture of how individual cells and neural
circuits interact in both time and space. By measuring activity at the
scale of neural networks in living organisms, we can begin to decode
sensory experience and, potentially, even memory, emotion, thought, and
consciousness. Ultimately, the technologies developed within the BRAIN
Initiative may help reveal the underlying pathology in a vast array of
brain disorders and provide new therapeutic avenues to prevent, treat,
and cure neurological and psychiatric conditions such as Alzheimer's
disease, autism, schizophrenia, traumatic brain injury, and addiction.
NIH is also innovating in translational science--where basic
science findings are developed into clinical benefits. Let me give you
a few examples.
Recent advances in genomics, proteomics, imaging, and other
technologies have led to the discovery of more than a thousand risk
factors for disease--biological insights that ought to hold promise as
targets for drugs. Drug development is a terribly difficult and
failure-prone business. To the dismay of researchers, drug companies,
and patients, the vast majority of drugs entering the development
pipeline never emerge as patient-ready therapies. The most distressing
failures occur when a drug is found to be ineffective in the later
stages of development--in Phase II or Phase III clinical studies--after
years of work and millions of dollars have already been spent. A major
reason for such failures is that scientists often don't know how to
choose the right clinical pathway to target. If a drug is aimed at the
wrong target, it won't work against the disease it was intended to
treat.
With this in mind, we were thrilled to launch the Accelerating
Medicines Partnership (AMP) last year. This unprecedented public-
private partnership is using cutting-edge scientific approaches to sift
through a long list of potential therapeutic targets and biomarkers,
and choose those most promising for therapeutic intervention. Besides
NIH, AMP partners include FDA, 10 biopharmaceutical firms, and a number
of non-profits, including patient advocacy groups.
Accelerating Medicines Partnership (AMP)
------------------------------------------------------------------------
Non-Profit
Government Industry Organizations
------------------------------------------------------------------------
NIH............................. AbbVie............ Alzheimer's
Association
FDA............................. Biogen Idec....... American Diabetes
Bristol-Myers Association
Squibb. Arthritis
GlaxoSmithKline... Foundation
Johnson & Johnson. Foundation for the
Lilly............. NIH
Merck............. Geoffrey Beene
Pfizer............ Foundation
Sanofi............ Juvenile Diabetes
Takeda............ Research
Foundations
Lupus Foundation
of America
Lupus Research
Institute/
Alliance for
Lupus Research
PhRMA
Rheumatology
Research
Foundation
USAgainstAlzheimer
's
------------------------------------------------------------------------
This pre-competitive partnership is focusing initially on three
disease areas that are ripe for discovery: Alzheimer's disease, type 2
diabetes, and the autoimmune disorders, lupus and rheumatoid arthritis.
Costs are shared equally between NIH and the participating companies,
and all data is openly shared. Through this truly innovative and
collaborative approach, we believe we can learn how to treat and cure
disease faster.
NIH is also working to streamline the therapeutic development
pipeline through efforts at the National Center for Advancing
Translational Sciences (NCATS). One example is the Tissue Chip for Drug
Screening Initiative, a collaboration with DARPA and FDA, with a goal
of improving the process for predicting whether drugs will be safe in
humans.
More than 30 percent of promising medications fail in human
clinical trials because they are found to have unacceptable toxicity,
despite promising pre-clinical studies in animal models. The Tissue
Chip for Drug Screening Initiative is developing 3-D human tissue
biochips that model the structure and function of human organs, such as
the lung, liver and heart. These chips are then combined into an
integrated system that can mimic complex functions of the human body.
This technology should enable scientists to predict more accurately how
effective a therapeutic candidate would be in clinical studies,
eliminating toxic and/or ineffective drugs earlier in the development
process. Tissue chips will benefit basic and clinical researchers
throughout the entire pharmaceutical and biotechnology sector.
Another way NCATS is working to advance therapeutics development is
through the Discovering New Therapeutic Uses for Existing Molecules
program. This collaborative approach partners NIH researchers with
industry to provide opportunities to reposition and repurpose drugs for
new indications. By using agents that already have cleared several key
steps in the development process, scientists nationwide have a strong
starting point to contribute their unique expertise and accelerate the
pace of therapeutics development. This approach utilizes crowd-sourcing
to identify the most promising repurposing opportunities, avoiding
research duplication and reducing the time and money required to
determine if these well-developed agents can be used to treat other
medical conditions.
Today, I have provided you with a brief overview of NIH's past
successes and continuing commitment to basic, translational, and
clinical research. Our nation has never witnessed a time of greater
promise in biomedicine, and it is important for the United States to
continue to lead in this effort. With your support, we can anticipate a
future of accelerating discovery across NIH's broad research landscape,
from fundamental scientific inquiry to a new era of personalized
approaches to medical treatments.
This concludes my testimony, Mr. Chairman. I look forward to your
questions.
The Chairman. Thank you, Dr. Collins.
Dr. Hamburg.
STATEMENT OF MARGARET A. HAMBURG, M.D., COMMISSIONER, FOOD AND
DRUG ADMINISTRATION, SILVER SPRING, MD
Dr. Hamburg. Thank you, Mr. Chairman and members of the
committee. I'm very pleased to be here today to discuss our
shared goal of speeding innovative treatments to patients, and
FDA looks forward to working with you on this important effort.
As you have noted, this will be my last appearance before
the committee, as I am stepping down. I want to thank you for
your support over the years and our constructive engagement
with this committee to advance FDA's public health mission.
I came to the agency at a time of considerable uncertainty
and change in the biomedical product industry, a time when
dramatic advances in science and technology, some that my
colleague, Dr. Collins, just outlined, demanded new models and
approaches. In turn, we took a very serious look at our role in
advancing biomedical product innovation to ensure that we would
be a gateway, not a barrier, to the delivery of better, safer,
and more effective treatments and cures.
In fact, this has been a high priority for me throughout my
tenure, and I'm very pleased that, as Senator Murray noted,
last year we approved the most new drugs in almost 20 years and
more orphan drugs than ever before, and 41 percent of these new
approvals were first-in-class products, resulting in a
breathtaking array of truly innovative new therapies for
patients. Today, FDA approves drugs faster, on average, than
all other advanced nations, 40 days faster than Japan, 70 days
faster than Canada, and 174 days faster than Europe.
FDA has made substantial improvement in the efficiency of
medical device reviews as well. Moreover, we've accomplished
this while remaining the gold standard around the world for
safety and effectiveness. Yet despite these successes, too many
diseases still await treatments and cures. Serious public
health needs, such as treatments for Alzheimer's disease, are
not being met, and rising R&D expenditures are not matched by a
proportionate discovery of new treatments.
In this context, I want to address concerns raised by some
that FDA regulation is the principal obstacle to the
development of innovative treatments and suggestions that FDA's
authorities and procedures must be fundamentally restructured.
As a physician, I know that if you incorrectly diagnose a
patient's condition, the treatment that you'll prescribe is
unlikely to work. Unless we correctly diagnose why cures are
still lacking for many diseases, we're unlikely to find the
solutions that will actually deliver those cures. Let me give
you three examples of misconceptions.
First is the incorrect but commonly repeated assertion that
FDA's approval of new drugs lags behind other countries. The
reality is starkly different. Over 75 percent of the new drugs
approved by Japan, EU, Canada, Australia, Switzerland, and FDA
between 2009 to 2013 were approved first by the FDA, according
to a recent report by the British-based Centre for Innovation
in Regulatory Science. The result is that Americans are, in
fact, far more likely to get first access to new medicine.
Second, FDA is said to be rigid and inflexible in its
approach to requesting and using data for approval of a new
drug. In fact, FDA's clinical trial requirements have been
steadily increasing in flexibility. Forty-five percent of new
drugs are approved based on a surrogate end point. One-third
are approved on the basis of a single clinical trial.
Last year, we used expedited approval processes for more
drugs than ever before, about 66 percent. Thanks in part to the
new authority that you gave us in FDASIA, 74 drugs have
received the new breakthrough designation.
My final example is the concern that investment into
biotechnology has dropped precipitously in the United States
and that the FDA is to blame. In the words of the National
Venture Capital Association, biotechnology investment dollars
rose 29 percent in 2014 to $6 billion, placing it as the second
largest investment sector for the year in terms of dollars
invested. Jonathan Leff, a leading biotechnology investor
affiliated with NVCA, said that one of the two reasons for the
increased investment in biotechnology is the improved
regulatory climate in recent years at FDA.
I cite these examples to suggest not that the world of
biomedical research and product development is all fine, but to
urge that we start with the right diagnosis. We do not want
solutions based on inaccurate diagnoses. I caution against
solutions that seek to lower the safety and effectiveness
standards for approval of the medical products on which
Americans rely.
Remember that the great leaps forward in evidence-based
medicine over the last 50 years have come in part because of
the high standards for product approval that Congress put in
place after a series of disasters involving unsafe and
ineffective medical products. Those standards have also boosted
the confidence that Americans place in medical products and
that the world places in the American biomedical product
industry.
Together, we can build on the progress that has been made
in recent years to further advance biomedical science and
improve the lives of patients. There are some areas from the
FDA perspective that I believe we can all agree need to be
improved.
First, patients are uniquely positioned to inform medical
product development. Treatments can better meet their needs if
we can capture science-based, disease-specific patient input to
incorporate in the development and review process.
Second, more attention needs to be given to the development
of biomarkers and surrogate end points. These can help
scientists identify and target successful medical treatments
and shorten drug development times, as Dr. Collins was noting
in his remarks. FDA has accepted hundreds of biomarkers and
surrogates, such as blood pressure changes, blood sugar
reduction, and tumor shrinkage.
Yet biomarkers are still lacking for many diseases, such as
Alzheimer's. The biggest obstacle is that scientists do not
sufficiently understand the causes of Alzheimer's and other
diseases to identify drug targets or identify which patients
will benefit from certain drugs. To solve this problem, we must
support the establishment of strong public-private partnerships
bringing the best minds together to develop the science that we
need.
Third, real-world data provides a vital tool to monitor
medical products in use in the marketplace. FDA's Sentinel
initiative with more than 170 million lives is one of the
largest uses of big data in healthcare and proving vital for
monitoring safety and emerging safety concerns. The science of
using big data to establish product effectiveness is still in
its infancy. Real progress demands that we develop the
methodologies needed to harness the promise of real-world data.
And fourth, FDA and industry agree that the agency must be
able to attract and retain talented scientists to review
cutting edge products. We look forward to working with you to
improve our ability to hire and retain these experts.
Let me close by underscoring that speeding innovation while
maintaining standards for safety and efficacy serves patients
well, supports the needs of our healthcare system, and has
enabled the medical product industry in this country to thrive.
I thank you for your support for our efforts at FDA, the work
that you're going to be doing going forward to advance that
work, and the work of all of our colleagues in the biomedical
research community so that we can deliver on the promise of
science for patients.
Thank you.
[The prepared statement of Dr. Hamburg follows:]
Prepared Statement of Margaret A. Hamburg, M.D.
introduction
Mr. Chairman and members of the committee, I am Dr. Margaret
Hamburg, Commissioner of Food and Drugs at the Food and Drug
Administration (FDA or the Agency), which is part of the Department of
Health and Human Services (HHS). Thank you for the opportunity to be
here today to discuss discovery and development of innovative medical
products. My FDA colleagues and I appreciate the committee's interest
in advancing legislation to support our shared goal of speeding
delivery of innovative, safe, and effective treatments and cures to
patients who need them. We look forward to working with you on this
effort.
FDA has helped make America's biomedical industry the global leader
Over the past century, remarkable biomedical discoveries have led
to the development of medical products responsible for rescuing
millions of patients from devastating diseases that previously had led
to loss of life or severe reductions in quality of life. The evolution
of modern medicine is a story of tremendous hope, learning, and
achievement--and one that we all fervently wish to buildupon. I am
proud of the role that FDA has played in helping these discoveries
become safe and effective treatments for patients.
America has long been at the forefront of biomedical discovery.
Decades of taxpayer investments in biomedical research, including a
focused investment in cancer research, launched in the 1970s, produced
fundamental scientific advancements. Significant investments by U.S.
pharmaceutical and biotechnology companies, along with the work of NIH-
funded investigators across the country, have helped to translate these
insights into innovative medical products for patients. FDA oversight
of product approvals has built public trust in the safety and efficacy
of new drugs and devices and confidence in America's biomedical
industry. Major improvements in public health resulted and vital
industries flourished. As FDA, Congress, and stakeholders pursue
opportunities that provide the most promise for continued development,
it is critical that we maintain safety and efficacy of products on
which patients and physicians depend.
Public health crises led Congress to establish standards for safety and
effectiveness
It is important to recognize that innovative medical products will
only save lives if they work properly. As a result of strong standards
for medical product approval, our citizens now depend upon FDA to
ensure that the drugs and devices they rely on are safe and effective.
Concerns about the safety and effectiveness of medical products are
deeply rooted in our history. In the 19th Century, enterprising
traveling salesmen hawked questionable medical products. When
newspapers gained widespread circulation, sellers of medical products
became leading advertisers of cure-alls containing unlabeled
ingredients such as alcohol and narcotics. Eventually, Congress
responded by giving FDA authority to review new drugs for safety before
they could be marketed.
In 1961, reports started to surface connecting thalidomide, which
was widely prescribed in other countries to treat morning sickness
during pregnancy, to severe birth defects. Thousands of children in
Europe were born with severe birth defects. In response to the public
uproar, in 1962, Congress enacted the Kefauver-Harris Amendments to the
Federal Food, Drug, and Cosmetic Act (FD&C Act). Thanks to these new
amendments, manufacturers had to prove that a drug was not only safe,
but also effective. Approvals had to be based on sound science.
Companies had to monitor safety reports that emerged in the post-market
and adhere to good manufacturing practices that would lead to
consistently safe products. The amendments not only benefited patients,
they helped industry by raising scientific standards that ushered in
today's sophisticated, science-based life sciences industry.
As we seek to accelerate medical product development, it is
essential to take care to maintain those critical aspects of the FD&C
Act that ensure the safety and efficacy of these products. History has
shown that allowing inadequately tested drugs and devices on the market
can cause significant harm to patients, both because of unexpected
dangers and, in many cases, because patients may use ineffective
products when effective alternatives exist.
FDA has dramatically accelerated access to innovative medical products
This past calendar year, FDA approved 51 novel drugs and biologics,
the most in almost 20 years. Today, FDA's average drug review times are
consistently faster than other advanced regulatory agencies around the
world, providing Americans earlier access to new, innovative drugs than
patients in any other country.
In achieving these outcomes, FDA has maintained its commitment to
high standards to protect the public health, while also exercising
regulatory flexibility in order to help promote medical product
development. This flexibility, along with FDA's work to collaborate
with industry, has helped reduce product development and review times.
As a result, Americans are seeing more products being approved, and in
many cases, they have access earlier than patients anywhere else in the
world.
FDA routinely works closely with sponsors to facilitate flexible
approaches to drug development. One example is FDA's engagement with
sponsors to expedite drug development under the breakthrough therapy
program. We have also worked with sponsors on the use of surrogate
endpoints, non-traditional trial designs, and other available tools to
expedite the development of products to treat both common and rare
diseases. In fact, more than one-third (69) of the new drug
applications approved by the Center for Drug Evaluation and Research
(CDER) from 2008 through 2013 were approved on the basis of one human
study and supporting evidence. This included 167 novel drugs, some with
multiple indications (for a total of 184 new indications). Almost two-
thirds (112) have characteristics of a flexible development program
and/or engaged in one or more of FDA's expedited development programs
(fast track, breakthrough, accelerated approval, priority review),
without undermining or diminishing FDA's commitment to a strong safety
and effectiveness standard. These many innovative and flexible
approaches underscore FDA's commitment to making drugs that are shown
to be safe and effective available as rapidly as possible.
Early and frequent communication between sponsors and FDA is
significantly reducing overall drug development times. For instance, an
analysis of 184 new drug applications approved from 2008-13 concluded
that the median clinical development time for drugs that were the
subject of a Pre-IND or ``early'' meeting was 1.4 years faster than
drugs without such meetings. Similarly, drug development was reduced by
more than a year for companies that sought an End-of-Phase I meeting
with FDA, compared to companies that did not request such meetings; and
companies that had End-of-Phase II meetings with FDA had higher first-
cycle approval rates than those that did not. This analysis includes
drugs that did not qualify for an expedited development program.
For devices, FDA's Center for Devices and Radiological Health
(CDRH) is focusing on improving investigational device exemption (IDE)
submissions to allow earlier and more efficient clinical study
enrollment for devices. CDRH has reduced, by 34 percent, the number of
IDEs requiring more than two cycles to full approval. These
improvements resulted in reducing by over half the median time to full-
study approval. From 2011 to 2014, the median number of days to full
IDE approval has decreased from 442 to only 101, cutting the time it
takes to bring a new medical device to market by nearly a full year. In
addition, improvements to the de novo program have resulted in a 70
percent reduction in the average total time to decision for these
submissions.
As a result of these improvements, patients are able to receive
important treatments sooner. Today, 76 percent of the new drugs
approved by Japan, the European Union (EU) and FDA from 2009 to 2013
were approved first by FDA, according to a report released in May by
the British-based Centre for Innovation in Regulatory Science.\1\
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\1\ ``New Drug Approvals in ICH Countries, 2004-2013,'' Centre for
Innovation in Regulatory Science, R&D Briefing 54, 2014.
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In addition to earlier access to innovative products, patients are
also seeing substantial numbers of new treatment options on the market.
Of the 51 new molecular entities and new biological products approved
by FDA in 2014, 17 new approvals are ``first-in-class'' therapies,
which represent new approaches in the treatment of disease. The
greatest number of new drugs approved for ``orphan'' diseases, since
Congress enacted the Orphan Drug Act over 30 years ago, also was seen
in 2014. These approvals represent important advances for patients who
may have limited treatment options available. Among CDER's 2014
approvals are treatments for cancer, hepatitis C, and type-2 diabetes,
as well. CBER approved many important biological products in 2014,
including a groundbreaking vaccine for meningitis B and a vaccine to
prevent certain cancers and other diseases caused by a broader range of
Human Papillomaviruses.
There are even more opportunities to accelerate medical product
development
While tremendous progress has been made thus far, it is important
that FDA, Congress, and stakeholders continue working to promote
medical product development. In order to ensure that we are promoting
the development of products that work properly, it is important that
advances are grounded in science. Where there are gaps in scientific
understanding, stakeholders can work together to address these gaps so
that the public remains confident in the safety and efficacy of
products on the market and to ensure that investments in research and
development are more likely to have meaningful results.
I would like to share FDA's thoughts on some of the most promising
areas that we believe could truly reach our common goal of speeding
delivery of innovative, safe, and effective products to American
patients, focusing primarily on transformation of the early stages of
drug development and increased efficiency of drug testing and
manufacturing. Opportunities to achieve these priorities include:
promoting precision medicine; encouraging collaboration and data
sharing among scientists; incorporating patient perspectives and
experiences; bridging gaps in the science of biomarkers; streamlining
clinical trials; modernizing drug manufacturing; obtaining the best
experts to help accelerate cures; and reducing administrative burdens
and duplication.
Advancing precision medicine
Advances in a variety of fields, including genomics and systems
biology, are beginning to produce highly tailored medical treatments
based on unique patient characteristics. ``Targeted drug development''
is a growing area of drug discovery. It is the identification of
patients for inclusion/exclusion either in the pivotal studies
supporting approval or for the drug's use in the labeled indication
based on a genetic test, biomarker, or susceptibility test (e.g.,
bacterial resistance, tumor genetic mutation). These treatments are
specifically targeted to treat patients who are most likely to respond,
or more safely receive, the medication based on specific tests. In the
early 1990s, only 5 percent of FDA's new drug approvals were for
targeted therapies. Twenty years later, that number had risen to a
quarter of new approvals, and in 2013, approximately 45 percent of
FDA's approvals were for targeted therapies.
President Obama recently announced a Precision Medicine Initiative
to advance biomedical understanding by leveraging genomic advances,
health information technologies, and new methods of analyzing large
volumes of data. As part of that effort, FDA has been reviewing the
current regulatory landscape involving next generation sequencing (NGS)
as the technology moves rapidly from research to clinical practice.
With NGS technology, a single test potentially can be employed to
identify thousands--even millions--of genetic variants carried by a
single individual. To get the dialog started, FDA published a
preliminary discussion paper in late December that posed a series of
questions about how to best ensure that tests are not only accurate and
reliable, but are available for patients as soon as possible. Public
comment is essential, so FDA opened a public docket and held a public
meeting on NGS technology on February 20, 2015. As part of the
President's Precision Medicine initiative, FDA will develop a new
approach for evaluating NGS 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.
Utilizing real-world observational data
Real-world observational data provides a vital tool to monitor
medical product safety and identify and further evaluate concerns. With
appropriate privacy protections, leveraging large databases containing
patient EHRs, disease-specific registries, and claims data has resulted
in significant advances in our understanding of health and disease,
provided novel and sometimes surprising insights into potential
relationships between health-related factors and outcomes, and provided
important product safety data. FDA is currently querying large, diverse
health care data for product safety through its Sentinel Initiative and
exploring opportunities to expand the use of real-world observational
data to optimize the performance of medical products.
Although there is reason to believe that in the appropriate setting
these data may be helpful in providing information on the effectiveness
of marketed products, such as for new uses of approved products to
support label expansion, many experts in the field agree that more work
is needed to make these data operational for and directly applicable to
regulatory purposes. We should move quickly to further develop
methodologies needed to better understand and harness the promise of
real-world observational data for regulatory purposes.
Incorporating patient perspectives
Patients are uniquely positioned to inform medical product
development with firsthand experience gained from living with a
disease, including their use of available therapies to treat their
conditions. In Prescription Drug User Fee Act (PDUFA) V, FDA committed
to a more systematic and expansive approach to obtaining patient
perspectives through a Patient-Focused Drug Development Initiative. FDA
has, so far, held 11 public meetings on specific disease areas and
gleaned much valuable insight from patients. Important patient-focused
work is also already underway through the Medical Device Innovation
Consortium (MDIC). MDIC is developing a framework for incorporating
patient preferences into the device development and assessment process,
and compiling a catalog of methods for collecting patient-preference
information that can be used to develop, design, and market devices
that meet the needs of patients. One recent example, highlighting the
impact of patient perspectives, was the decision to approve a device to
treat obesity. The decision to approve the device was based in part on
the data from a study that showed a substantial portion of obese
patients would accept the risks associated with a surgically implanted
device, if they lost a sufficient number of pounds.
We believe that more can be learned and applied by engaging in a
transparent, multi-stakeholder approach, potentially through public-
private partnerships, that identifies sound and rigorous methods to
capture science-based, disease-specific patient input in an
analytically meaningful and useful form that can be incorporated
directly into drug and medical device development and review processes.
This should include capturing information on the natural history of
diseases, including identifying and measuring aspects that matter most
to patients. Developing guidance to enable patient groups to become
active participants in this process and to help industry incorporate
appropriate methods in drug development programs also will move the
field forward.
Bridging gaps in the science of biomarkers
FDA believes that accelerating the development of reliable
biomarkers is essential to advancing important new therapies. FDA
already accepts the use of hundreds of biomarkers for a variety of
purposes throughout drug development, such as proof-of-concept,
diagnosis of disease, enrichment of trials with patients most likely to
respond, and as surrogate endpoints that can support accelerated or
traditional drug approval. For example, 45 percent of drugs were
approved by FDA on the basis of a surrogate endpoint between 2010 and
2012. There remain, however, many diseases such as Alzheimer's disease
for which disease-specific biomarkers have not yet been developed, or
shown to be reliable for use in the regulatory review process. When we
do not understand the disease pathways, biomarkers appearing to be
linked to disease progression can fail because they are not, in fact,
in the causal pathway for the disease. A wide range of stakeholders is
necessary to achieve meaningful progress in developing additional
biomarkers that can be used by the scientific community. Important work
is already underway through the National Institutes of Health (NIH),
the Biomarkers Consortium in which FDA participates, and the Critical
Path Institute.
The principal barrier to biomarker development is the lack of
scientific understanding about the causes and biochemical pathways of
many diseases. Continued public and private investment in biomedical
research is key to filling this knowledge gap and to improving
understanding of how to show whether a biomarker is clinically
meaningful. Collaboration among NIH, FDA, academia, industry, and
patient groups can lead to development of standards of evidence for
using biomarkers for regulatory decisions.
Leveraging clinical trial networks
The time and expense associated with designing and conducting
clinical trials is one of the most significant limiting factors to drug
and device development. Widespread use of clinical trial networks and
master protocols could dramatically improve clinical trial efficiency--
and create a new drug and device development paradigm that benefits
both patients and industry. The recently initiated Lung Cancer Master
Protocol (Lung-MAP) is an excellent example. A master protocol creates
a single clinical trial infrastructure to test many drugs at the same
time. In the case of Lung-MAP, patients are assigned to one of five
different drugs being simultaneously tested, based on the results of
genomic profiling to screen for alterations in more than 200 cancer-
related genes. Additional drugs can be added, or dropped, as
appropriate, over time. FDA is highly supportive of the use of master
protocols, and we are working with key stakeholders to advance their
use.
Modernizing drug manufacturing
Advances in pharmaceutical manufacturing technology provide new
opportunities to lower costs, limit drug shortages, and reduce supply
chain vulnerabilities--and reinvigorate U.S. pharmaceutical
manufacturing. A promising example is the new technology that enables
forms of ``continuous manufacturing'' to produce a finished drug
product in a continuous stream, as opposed to traditional methods that
involve a series of sequential and discrete ``unit operations,'' such
as milling, mixing, and granulation. Unlike traditional manufacturing,
which can take close to a year from start to finish, continuous
manufacturing could take only a few days, increase equipment
utilization rates up to 95 percent, and dramatically reduce the risk of
production failure and negative environmental impacts. Continuous
manufacturing could also reduce the likelihood of drug shortages. FDA
has been working for over a decade to stimulate modernization of U.S.
drug manufacturing, but more work is needed, including supporting
academic research in this area and expanding opportunities for
collaboration, possibly through public-private partnerships or
consortia.
Hiring and retaining highly qualified experts
In order to achieve its mission in a complex, global, and rapidly
evolving scientific arena, FDA and industry agree: the Agency must be
able to attract, recruit, and retain talented leaders, physicians,
scientists, and other experts to effectively review cutting-edge
products and conduct post-market surveillance activities. Delays in
bringing selected candidates on board may prompt highly qualified
experts to pursue opportunities elsewhere.
Allowing use of central Institutional Review Boards (IRB)
The FD&C Act mandates review of a clinical trial on a device by a
``local'' IRB, or by FDA in rare circumstances, although there is no
comparable requirement for drug trials. This can require review of
multi-site studies by many different IRBs, and each IRB may require the
study sponsor to meet different, sometimes inconsistent requirements
for study approval, increasing the length and cost of trials. Studies
have shown that the use of a central IRB for multi-site drug studies
can significantly improve efficiency, without undermining trial
participants' protections. A modification of the FD&C Act to bring IRB
review of device studies in line with drug studies would accomplish the
goal of greater efficiency, without sacrificing oversight.
conclusion
I am incredibly proud of the progress that FDA has made during my
tenure to speed medical products to patients. I look forward to working
with Congress to accelerate product development more while continuing
to ensure that American families can rely on the safety and
effectiveness of products on the market.
The Chairman. Thank you, Dr. Hamburg.
We'll now begin a round of 5-minute questions. I'll start.
I only have two questions. I have a short one, which I hope
I'll get a short response from Dr. Collins, so each of you will
have a chance to answer the second question.
The first one is this. The National Academies have done a
couple of studies that show that 42 percent of an
investigator's time is spent on administrative tasks. The
taxpayer spends about $30 billion through NIH. Eighty percent
of that goes into research. In a conversation they had of
National Academies said that about 10 percent would be a
reasonable amount of time for an investigator, although it
would vary depending upon the investigation.
What are the opportunities for reducing that 42 percent
down more toward 10 or 12 or 15 percent to save money so that
we could have more multiyear investigations? Are there things
that we could do to change the law to make that easier for you
to do?
Dr. Collins. Thank you for the question, Senator. We, too,
are very concerned about the idea that investigators are
spending 42 percent of their time dealing with administrative
matters instead of directly engaged in research, and we're part
of the support of that survey, which showed that number has not
really changed from 2005 to 2012. We are undertaking a number
of things that we have the ability to do to try to limit the
amount of administrative oversight, but not all of that falls
within our purview. Some of it comes from other directions.
Some of it is from the universities themselves.
Things that we have done are to standardize the
biographical sketch, the CV, that individuals have to provide
when they apply for a grant. That actually turns out to be a
substantial assistance.
Something we're in the middle of, where perhaps some help
could be offered, is a revision of how to interpret the common
rule that oversees the research involving human subjects, which
has not gone through a revision in 20 years and which does not
currently take account of the risk involved in study and
applies a great deal of oversight to some studies that are
truly low risk as if they were, in fact, invasive surgical
procedures.
The Chairman. Dr. Collins, may I interrupt in this way?
Would you be willing to work with us to identify what those
things are, specifically, so that during this next several
months, we can--we need to make changes in the law that can
help with that, because I want to ask you and Dr. Hamburg this
question and----
Dr. Collins. Yes.
The Chairman [continuing]. We don't want to waste our time
in the next year, and we can't do everything. Could you say now
and then, if you want to submit it later in addition to your
statement--what are the one or two or three things that we
should focus on in order to make the greatest contribution to
the goal of moving medicines, devices, and treatments from
discovery to the medicine cabinet, as you put it, or to the
doctor's office--each of you?
Dr. Collins. Senator, I appreciate that question, and I
have a long list, and I'd very much look forward to talking
with you at a greater opportunity----
The Chairman. We'll do that.
Dr. Collins. If you want me to name two, one which sounds
pedestrian but is an incredibly vexing situation and terribly
wasteful of scientists' time is the current, very rigorous
oversight of attendance of scientists at scientific meetings.
This applies to both NIH and FDA.
We're currently spending about $16 million and using
hundreds of employees to go through a process which, as far as
I can say, has relatively little, if any, added value, all of
this triggered by some misadventures by other agencies who
convened conferences in places like Las Vegas, for which we are
all now paying a price. Scientists going to conferences is a
critical part of how we move things forward, how new ideas
emerge, and it is very much being inhibited by this very heavy-
handed oversight. We could much benefit from your help there.
The second one, I would say--NSF and the Department of
Energy and their scientific budgeting that happens every year--
they're allowed to carry funds over into a second year. We are
not. We come up to the end of September, oftentimes with money
that we need to spend or it goes away. If we had the
opportunity to carry that over, it wouldn't cost another dime.
We could be more flexible in how we spend the taxpayers' money.
The Chairman. Thank you, Dr. Collins.
Dr. Hamburg.
Dr. Hamburg. Thank you. I certainly agree with what Dr.
Collins said. Are you looking specifically for administrative
issues or broader?
The Chairman. I want to make sure we don't waste our time
and that we focus on getting a result. One or two things that--
whatever you think.
Dr. Hamburg. OK. Let me step to a slightly higher level in
terms of what I think are two critical and related needs in
terms of being able to advance FDA's activities and, in fact,
support biomedical research and product development.
One is that I do believe we need to invest more money in
regulatory science that develops the knowledge and the tools
and approaches and strategies that really enable us to assess
in an effective and efficient way the safety, efficacy,
quality, and performance of a product. It's been an under-
appreciated, under-developed, and under-invested-in area of our
overall biomedical product enterprise.
It's proving to be really essential as we are trying to
take that last set of steps from research and development into
a product that will really make a difference in people's lives.
We've laid out an important and exciting research agenda, and
we've done work with NIH in this domain.
The other area is to recognize that FDA and our scientists
have a huge amount to contribute to the overall process of
product development, as well as our important responsibility
for review, and, certainly, for us to be able to engage in a
consistent way earlier as research plans are being shaped so
that the right studies are done so that the return on
investment of moneys in research all along the way are really
driving toward a product that works.
The Chairman. Thank you very much.
Senator Murray.
Senator Murray. Thank you very much.
Dr. Hamburg, before I go to broader topics, I want to ask
you about the recent outbreaks of drug-resistant bacterial
infections that are associated with the use of the special
medical scopes known as duodenoscopes. One of the largest
outbreaks was in my home State of Washington. There were 32
patients infected, and although it's not clear what caused
their deaths, 11 have died.
FDA was supposed to have been regulating these scopes. Can
you explain how this could have happened and what actions FDA
has taken?
Dr. Hamburg. The duodenoscopes are very important medical
devices that serve a critical role in patient care and
diagnosing and treating a series of important problems, and
they are, in fact, used in more than 500,000 procedures a year
in this country, usually with great benefit to the patients.
The duodenoscope allows an approach that is less invasive than
open surgery and, overall, has less attendant risks to the
patient's health and safety.
Over time, we saw isolated cases of problems in terms of
infection in duodenoscopes and we would investigate those, and
they were always associated with some lapse in the disinfection
protocols. In late 2013, we learned for the first time of some
outbreaks unfortunately involving an antibiotic-resistant
strain of bacteria where, on investigation, it seemed as though
all of the procedures for disinfection had been followed.
After that, we began to work closely with our colleagues at
the CDC, with the healthcare provider community, and with the
companies making these to try to understand what are some
intrinsic design challenges in order to enable this scope to do
its job, where it has to kind of twist around and has what's
called an elevator mechanism.
We are actively engaged in trying to come up with better
strategies for disinfection and recommendations to increase the
margin of safety. We're going to be holding an advisory
committee meeting. We're working with stakeholders----
Senator Murray. Can you commit to a full FDA review to me
so we can understand----
Dr. Hamburg. Sure.
Senator Murray [continuing]. How this happened and protect
against it happening? Because I am deeply concerned about it.
Dr. Hamburg. As are we, and we are very actively engaged. A
lot of activities are going to be happening moving forward as
we continue to try to strengthen the safety of patients and
improve what are very important medical devices for care.
Senator Murray. I appreciate that.
On a broader issue, Dr. Collins, the United States has
always been a global leader in biomedical research and
innovation. Today, as you and I both know, sequestration really
threatens that leadership, and it's critical that we build on
the bipartisan budget deal that I reached with Congressman Ryan
last year that helped roll back those cuts from sequestration.
We are just about to enter another budget process.
Can you explain to all of us today how sequester impacted
research at NIH?
Dr. Collins. Thank you for the question. It certainly was a
serious blow to momentum. The $1.55 billion that were taken
away from our budget in the middle of the fiscal year resulted
in our inability to fund about 750 grants that otherwise would
have been funded that year, and those very good ideas basically
got left on the table.
As you know, we were able to make up some of that ground in
the subsequent years. Even in 2015, we did not recover the
entire $1.5 billion that was lost in 2013. The results of that,
in terms of what they've done to investigators, who are already
struggling with difficulty in getting their grants funded,
really has been quite significant.
The overall likelihood, if you send your best ideas to NIH,
of having that supported has dropped over the course of the
last 10 years since the budgets became flat, and inflation has
been eroding away at our ability to support research. It is
important to point out--and you've made this point--that this
is something which puts America at a limited competitiveness
status as well.
If you look to see what other countries are doing--I'll
show you a graph here--from 2011 to 2013 in terms of the change
in percentage of GDP invested in research, you can see that
countries like China and Brazil, South Korea, and so on are
substantially increasing their investment--they're reading from
our playbook from the 1980s and 1990s--whereas we stand alone
in this graph as actually losing ground. The consequences of
that is we're also losing opportunities for science, we're
losing jobs, and we're potentially at risk of losing young
investigators who are beginning to wonder whether there's a
future for them, and some of them are starting to give up.
Senator Murray. The threat of that sequestration going on
again in a few short months--what's that doing to you?
Dr. Collins. That hangs over us like a dark cloud, because
if sequestration is not dealt with, we stand to lose another
$19 billion that would have gone to medical research over the
coming years, and the consequences of that are really painful
to consider.
Senator Murray. Thank you.
The Chairman. Thank you, Senator Murray.
Senator Burr and then Senator Mikulski.
Statement of Senator Burr
Senator Burr. Dr. Collins, Dr. Hamburg, welcome.
Dr. Collins, in your testimony, you highlighted the
potential to better target medicines to specific patient needs.
What role does biomarker qualification play in advancing these
patient-focused therapies?
Dr. Collins. I appreciate the question. I mentioned that we
had a 3-hour meeting yesterday between NIH and FDA, and one of
our topics was biomarkers because of our shared interest in
trying to move this agenda forward. As Dr. Hamburg said in her
opening statement, there are lots of biomarkers that have been
used for a long time. Measuring your blood pressure is
basically a biomarker that we use to assess risks of
cardiovascular disease and stroke.
Of course, we would love to see biomarkers developed for
something like Alzheimer's disease, which she also mentioned. I
pointed out this Accelerated Medicines Partnership that we're
doing jointly with industry. It has that as one of its goals
for Alzheimer's.
We're making sure that all clinical trials that are trying
out new ideas about prevention of Alzheimer's disease use the
same set of biomarkers so that if something starts to work--
maybe it's a blood test, maybe it's a measure of protein in the
spinal fluid, maybe it's a scan of something like amyloid or
tau in the brain--we would know that, and we'd be able then to
begin to utilize that for therapeutics.
Senator Burr. You're both--NIH and FDA--participants in the
Biomarkers Consortium.
Dr. Collins. Yes.
Senator Burr. Since the consortium was established in 2006,
how many biomarkers has it qualified?
Dr. Collins. The Biomarkers Consortium, which is run by the
Foundation for NIH, has partnership from NIH, from industry,
from FDA, and from patient organizations. It is not itself
charged with doing biomarker qualification. It's charged with
identifying possible biomarkers that need more research and
making sure the research happens. The FDA has the role of
qualifying those biomarkers if they have reached that standard.
Senator Burr. They have full determination based upon what
the consortium comes up with as to whether they recognize a
biomarker.
Dr. Collins. They need to evaluate--and I'll certainly
depend on Dr. Hamburg to specifically state the process--
whether the science is strong enough for a particular biomarker
to be considered validated, qualified, so that it can be used,
and if rigorous studies have shown that it actually is a
predictor of what you want it to predict.
Senator Burr. Dr. Hamburg, let me turn to you, if I could.
FDA's Drug Development Tool Qualification Program notes the
importance of developing the animal models for use under the
animal rule. A few weeks ago, your colleague, Dr. Borio, was
before the committee as part of an oversight hearing.
As you know, human efficacy studies are not feasible in
some medical countermeasures. Therefore, FDA's animal rule is
particularly important for such products, which is why I
emphasized the importance of finalizing the animal rule
guidance with Dr. Borio before this committee.
As far as I can tell, there's been no further movement on
this issue since that hearing. I'd like to ask you when is the
animal rule guidance going to be finalized as required by law?
Dr. Hamburg. Let me first begin by thanking you for all the
extraordinary work you've done to advance public health
preparedness and the development and availability of important
medical countermeasures. The animal rule, as you note, is an
aspect of this that is key, because we do need to develop
medical countermeasures against certain threats where the
disease may not exist in nature, and we would certainly never
want to expose people to the disease to actually see if the new
drug or vaccine actually works.
We have taken the animal rule very seriously. It's one of
those areas of regulatory science that is challenging, because
we want to be able to know that by using animal data, which is
often imperfect, we can make a good enough assessment of safety
and effectiveness and appropriate use of a product against what
is generally going to be a terrible, life threatening disease.
We have been working on the animal rule for quite a while
and the best scientific strategies, engaging with the research
community and, obviously, companies as well. We did put forward
a draft guidance, and comment, ended on that back in August
2014. We received a lot of response, and we've had a lot of
meetings----
Senator Burr. Is this a priority?
Dr. Hamburg. It is a priority, absolutely.
Senator Burr. When are we going to have a final rule?
Dr. Hamburg. I think it will be soon. I can't say that
you'll have it before I step down at the end of the month. It
has been a priority of mine from very early in my tenure. As
you may know, I'd been working on many of these kinds of issues
before I joined the FDA.
It is a scientific challenge, and, in fact, the draft
guidance has shaped work that's being done in moving forward.
It hasn't stopped progress in terms of medical countermeasure
development. We will get it done, and I will go back from this
hearing and remind the team that there is a very important
Senator waiting for that, as are the American people.
Senator Burr. Then I would be remiss if I didn't mention at
the same time, biosimilar pathways and the fact that we have
yet to have that final guidance. I go to what Dr. Collins said
in response to Senator Murray's statement on what happens on
sequestration. You don't get the predictability. There's no
consistency. You can't fund the things that you think might
generate.
I would only say this, Dr. Hamburg. There are a lot of
companies and a lot of efforts out there that are waiting for
an animal rule to be finalized, that are waiting for a pathway
for biosimilars. We just approved the first biosimilar at FDA,
and we don't even have a pathway. We don't have a final
guidance for the other manufacturers out there.
You have a company that had one approved, but nobody else
knows how to get their biosimilars approved because there's no
guidance on how to approach it. My only suggestion is that this
is as important as how we fund research, and that having enough
biomarkers qualified, having final guidance for biosimilars,
having a final rule on the animal rule is all part of how we
have a robust response to disease and we change the outcomes of
patients in the future. I thank both of you.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Burr.
Senator Mikulski.
Statement of Senator Mikulski
Senator Mikulski. Thank you, Mr. Chairman, and thank you
for both convening this hearing in the spirit in which you did,
a bipartisan effort to really promote life science innovation
in this country, which leads to new ideas, new research, new
products that not only save lives but create jobs in our own
communities.
I'm going to also welcome Dr. Collins and Dr. Hamburg here.
I have the great joy of having both NIH and FDA located in my
State. We have two outstanding leaders here who really, every
day and every way, think about how they can advance the mission
of these agencies, and I would like to thank them for what they
do.
I'd like to thank them for hanging in there, because many
of the impediments that are created are impediments that we
create ourselves, not only to try to find new ideas, but maybe
we need to get back to some old fashioned ideas of working
together like the Chairman has said.
Dr. Hamburg, I know that you're leaving the FDA. I know
you're going to continue to serve in many capacities. They said
you're the longest serving, and I'm the longest serving, and
here we are, each turning a new page.
I'd also like to take this opportunity to thank the men and
women who work at both of these agencies, NIH and FDA. You have
to know that for my 28 years of service and what will soon be
30 years of service, to wake up every day to think about how I
can make the world a better place, and I have these two
fabulous agencies where my job is to help you be you, I cannot
tell you the pride and enthusiasm and joy that that has brought
me.
Let me get to what I think are the three criteria for
reform and then get to my questions. No. 1, let's respect the
mission of the agency, and let's respect the men and women who
work at the agency. Respect goes a long way to improving
morale. Morale goes a long way in increasing productivity. I
would hope the Congress of the United States would embrace the
idea of respecting the men and women who work in our Federal
agencies and not treat them as cheap throwaway lines on talk
shows.
The second is adequate resources so that you can do the job
and have the tools that you need. And third, let's approach
reform in a targeted way, as the Chairman has indicated. Let's
focus on specific problems and specific solutions.
I posit that to my members here to think about the three
Rs, respect, resources, and reform that's targeted, which then
goes to my question, Dr. Collins, and you, Dr. Hamburg.
Senator Murray raised the question of sequester. That then
goes to predictability. Could you share with the committee the
impact, because each one--like, Dr. Hamburg, in many of the
reports, they say there's been a big turnover at FDA. Whether
that's numerically justified, I'm not sure. So many accusations
aren't justified.
Could you share with us what that means in terms of the
predictability, sustainability, as well as the adequacy? We
know that you need more. I tried to lift the caps and so on.
What would predictability and certainty mean at FDA?
Dr. Hamburg. Certainly, predictability and certainty is
key. We hear it from the industries that we regulate in terms
of how we oversee them, and it's essential to us to be able to
do our job.
We need to be able to lay out programs that are not
occurring in 1-year timeframes, but over time. We need to be
able to recruit the best and the brightest scientists and other
professionals that we can that are highly competitive outside
of FDA. They need to know that they're going to be working in
an environment where they're going to get the resources that
they need and the support that they need in a continuing way.
We certainly need every dollar that we get. As was noted,
we have a very broad span of roles and responsibilities
overseeing products that matter greatly to every American every
single day, and we are stretched very thin. Uncertainty and
instability in our funding programs make it harder for us----
Senator Mikulski. It makes it hard to recruit and retain.
Dr. Hamburg. It makes it harder to recruit and retain and
to make wise choices.
Senator Mikulski. Therefore, get the experience that you
need. The other, then, with the predictability--what about you,
Dr. Collins?
Dr. Collins. I appreciate the question, and, Senator, your
strong support has been incredibly valuable, and we are all
grieving the fact that you're planning to move away in 2 years,
and we hope that this can be an opportunity for lots more
conversation and effort in the meanwhile. The idea of stability
is crucial for biomedical researchers, especially for those who
are early in their careers. They have visionary ideas. They're
fearless about taking on problems that maybe couldn't have been
approached before but the technology now makes it possible.
When they are uncertain about whether there's going to be
long-term support for that, it's very discouraging. Another
graph I'll show you is what mostly troubles investigators
today, which is what's happened to your likelihood of getting
supported by NIH over the course of the last 50 years, which
traditionally has run around 30 percent as your chance. It's
below 20 percent now. It's running about 16 or 17 percent.
That means five chances out of six, your idea is going to
get a no, and that means your science is left on the table
unattended. That is enormously discouraging. If we could turn
that corner--and the President's budget has--as you can see
that little uptick there--aimed to try to do that--we could
turn this whole circumstance around in the United States. We
could regain the kind of momentum and leadership that we've
had, unquestioned, over the past many decades. It is at risk if
we can't do that.
Senator Mikulski. When is adequacy--I know my time is up,
but I bring to my committee two things. During the sequester,
FDA couldn't use the user fees that the private sector was
paying in for them to hire. Here's the private sector giving
the money after arduous work to create a contemporary PDUFA.
That was one.
The very day before sequester, they announced that they had
lowered cancer rates in this country 12 percent. Instead of
pinning medals on people, we were getting ready to print pink
slips. I think that's not the right way to govern.
The Chairman. Thank you, Senator Mikulski.
Senator Isakson and then Senator Bennet.
Statement of Senator Isakson
Senator Isakson. Thank you, Mr. Chairman. This is my first
time publicly to be able to acknowledge the great contribution
of Senator Mikulski to public health in America and her service
to the American people, and I just want to thank her for all
she's done. It's been a pleasure to serve with you on this
committee.
Senator Mikulski. We're here together for 2 more years.
Senator Isakson. Dr. Hamburg, I don't want to be piling on,
but Senator Burr is right on target, and this is a long lead-up
to a question, and I apologize for that. It's a very important
question that needs to be answered.
You made a reference in your statement that some blame the
lack of investment in biotechnology on the FDA, and you refuted
that. It is quite true that investment follows certainty, and
certainty follows regulatory processes that work. I find it
troubling that the FDA has so much difficulty working through
the regulatory process.
In last year's user fee bill, Congress directed you to
update your regulation to fix the enforcement problems that
have affected manufacturers and suppliers of medical gas. That
was a year ago, yet we're still waiting on the report, and
we've heard that some say there's resistance in the agency to
doing so and issuing any new regulations.
Instead, the FDA seems to rely heavily and less formally on
approaches such as draft guidance, which Senator Burr
acknowledged, and untitled warning letters. These approaches do
not offer legal certainty, regulatory certainty to
stakeholders, and in the case of untitled letters, they fail to
ensure any policies that are enforceable evenhandedly among
stakeholders who are similarly situated.
Last May, Chairman Alexander, myself, and many members of
this committee sent you a letter posing specific questions
about the agency's use of draft guidance. We received the
answer 10 months later, last night, 12 hours before this
hearing. In that letter, you attached 172 outstanding draft
guidance issues, one of which goes back to 1988.
How is this effective regulation, and how is this effective
process?
Dr. Hamburg. We are taking a very active look at the
various guidances and what stage they're in. It's important to
understand that a guidance is just that. It's a guidance to
inform industry about our current thinking, and the process of
developing a draft guidance to a final guidance is all
extremely useful in that process. When the draft guidance goes
forward, it enables us to put forward how we are thinking about
the problem and to ask some questions and get information back
to further engage with all of the critical stakeholders.
It's an ongoing process. Guidances are not regulations with
the force of law, but it helps provide--especially when there
is a more dynamic issue at hand, it provides a mechanism to
begin an important conversation with a broader set of
stakeholders and continue it to the final guidance.
I agree with you that we should not have that many
guidances in draft. While the process of moving from a draft to
a final guidance has value as well, having the final guidance
is important and provides more certainty, as we were
discussing.
It won't be me coming back before you, but I hope that
soon, we will be able to demonstrate what has been done with
respect to some of those guidances that are in draft that may
no longer really need to be updated into final and those where
we can translate it into final. This is an area where, frankly,
we are not the only ones involved in shaping the guidance
process, and it does have to go through a series of other
reviews before it can be published as final. But I take your
point.
Senator Isakson. One other question that relates to that
point in a different way--I'm a victim of melanoma twice, and
the surgeon general has issued a report that melanoma is
costing America $8.1 billion a year in health, a major portion
of his most recent statements. I hear very little from the FDA
regarding that.
We worked hard on the Sunscreen Innovation Act, which
passed Congress last year, to try and expedite the time and
extent applications for ingredients to be approved for over the
counter sunscreen products. We are still waiting for that to
happen. Can you tell me why the FDA is so reluctant to follow
through on what Congress passed in the Sunscreen Innovation
Act?
Dr. Hamburg. We are committed to following through, and, of
course, preventing melanoma is a high priority, as well as
developing exciting new treatments for melanoma. But prevention
comes first. We're committed to what was laid out in the
Sunscreen Innovation Act in terms of responding to the
identified timelines and process.
We do need to work with industry to get the data that we
need to assess safety and effectiveness, and that is, of
course, because these products are used widely, applied often,
and, hopefully, with the right amount. They're used
chronically, and we need to understand about their absorption
of these chemicals and what that means for safety and efficacy
in the individuals using them, including, of course, many young
children who may be at greater risk in terms of chronic use.
We want to move forward. We want the American people to
have more options in terms of sunscreen products and the
protection that it can afford. We want to work with industry to
make sure that the ingredients in those sunscreens actually
work and that they're safe, especially for chronic use.
Senator Isakson. My time is up, but I'd like to urge you to
do everything you can to expedite the implementation of those
approvals. Thank you very much.
Dr. Hamburg. Thank you.
The Chairman. Thank you, Senator Isakson.
I'm calling on Senators in order of seniority if they were
here at the time of the gavel, that's what I'm doing.
Senator Bennet.
Statement of Senator Bennet
Senator Bennet. Thank you, Mr. Chairman. Thank you very
much for holding this hearing.
Thank you both for your leadership, and, Dr. Hamburg, I'm
sorry to see you go, and I know that the Chairman feels the
same as well.
A number of years ago, the Colorado bioscience community
came to me and said, ``We can't raise venture capital anymore
in the United States. It's all going to Europe. It's all going
to Asia.'' A lot of that had to do with the regulatory
uncertainty at the FDA.
I had the opportunity in 2012, as you know, to team up with
Senator Burr and Senator Hatch to write the breakthrough
therapy legislation that now has created a pathway at FDA under
your leadership that is responsible for the approval--a lot of
people thought there were only one or two drugs in that
pipeline by now. There have been 22 drugs approved as a result
of that legislation, and there are 55 more drugs in the
pipeline, as I understand it.
It has succeeded beyond our wildest dreams, It's fair to
say. I want to thank you for that as you begin to leave and ask
you to talk a little bit about the shift in the culture at the
FDA as a result of that designation and how we're going to keep
that going after you leave.
Dr. Hamburg. First, let me thank you for the work that you
did on breakthrough and so many other things and for inviting
me to talk to your biotech community in Colorado, and I've done
it in many other places as well, including, recently,
Massachusetts. Those kinds of listening sessions with the
medical device and pharmaceutical and biotech industries are
incredibly important, because we hear the concerns.
We heard loud and clear early in my tenure about the issues
of predictability and consistency, and we looked at our
programs and how we could strengthen them. The breakthrough
designation has been enormously successful, as you know, more
successful than we thought, and it did not come with additional
resources. It's an example of something that we want to be able
to continue and extend, but it does come at a cost.
The incredibly important lesson and the culture change that
has come with breakthrough and have been confirmed by the
success of breakthrough is the value of early engagement by the
FDA with the product sponsor to really help shape the product
development and research agenda, and then continuing contact.
That has really made a difference. We see it in breakthrough.
We see it in other areas as well as we look at some of our
recent approvals.
We can see a sort of informal analysis that when we engage
early, especially Pre-IND, we can really help the product
development process take critical time and cost off of their
product development, because we can really say, ``You don't
need to do that study, but do this study and use this
approach,'' because it will get to the answers that will really
make a difference in our approval process.
That's been enormously exciting. It does signal changes for
the future in how FDA organizes itself and how we work with the
broader research and industry community.
Senator Bennet. I hope that's right, and I've heard the
same thing from developers of these drugs. They're saying that
they feel that the FDA is engaging with them in a much more
productive way than they used to. My hope is that we're going
to hear that around medical devices and other kinds of things
going forward.
I want to ask you one other question. Over the last few
weeks, we've heard about infections and even deaths in
California and North Carolina hospitals from CRE, a bug that
CDC--I apologize for my voice today. I'm glad there are two
doctors here, but you're not of any use to me that far away.
Dr. Hamburg. But we don't always have the treatment you
need.
Senator Bennet. The CDC director has called it a nightmare
bacteria. Another very drug-resistant bacteria, Acinetobacter,
has been directly affecting our wounded troops returning home
from Iraq.
Senator Hatch and I, as you know, have been working on
legislation to require FDA to establish a new regulatory
pathway to encourage the development of antibiotics to treat
serious and life threatening infections. The legislation has
the support of antibiotic developers, public health groups and
provider groups. Your team has been enormously helpful in
working with us on the legislation.
Could you describe a little bit how this new pathway will
protect patient safety while ensuring that patients who have
unmet needs for antibiotics gain access to these important
drugs?
Dr. Hamburg. It's incredibly important as we face a world
where antimicrobial resistance is growing that we ensure that
we have new antibiotics in the pipeline, and especially new
antibiotics for infections that are resistant to the available
antibiotics. We see, increasingly, outbreaks in many different
settings, including the duodenoscope, where antimicrobial
resistance is causing a much greater and preventable burden of
disease and death because we simply can't treat those
infections.
The pathway that you're describing is an important one,
because if you look at an infectious organism in the disease,
it can be quite heterogeneous from much more minor infections
to the antibiotic-resistant ones we were just talking about. If
you look across that whole spectrum of patients who are
infected, you have a very different risk-benefit calculation
than if you focus on the more extreme, serious, life
threatening cases where there's antibiotic resistance.
If we can develop a product that's targeted to that part of
the spectrum, the risk-benefit calculations can come into a
clearer focus. We know we need drugs, and the risks can be
higher because the benefits are higher in that context. We need
to make sure that physicians using these drugs understand that
they're really being approved for a limited use, a special
population, and should be labeled as such, and there needs to
be education and awareness.
It will enable more products to be developed more rapidly
and to get to patients who need them. Then we can continue to
learn more about those products as they're in use and perhaps
extend the indications for use. It enables us to move much more
quickly off the dime to get important products to people and
creates new incentives for companies to get involved because
they can see a pathway that perhaps is shorter and more
streamlined.
The Chairman. Thank you, Senator Bennet.
I have Senators Cassidy, Whitehouse, Collins, and Warren as
the next four.
Senator Cassidy.
Statement of Senator Cassidy
Senator Cassidy. Dr. Hamburg, great job. In my 6 years
here, you've made really remarkable progress. Thank you for
that.
Dr. Hamburg. Thank you.
Senator Cassidy. You recently put out your FDA's
transparency initiative. I have tried to understand your
agency, but certainly don't understand it as you do. It does
seem like there's different divisions that do different quality
of work in terms of approving new applications. Intuitively,
there are some which have higher turnover than others. I
suspect those with lower turnover are the ones which have
better output.
I see that as a diagnostic. Frankly, that indicates in
those divisions with high turnover and lower output, there's
probably some issue there in management, leadership, you name
it, that is problematic. In your transparency initiative, will
there be more information regarding that so that we in
oversight can look at that on a granular level, trying to get a
sense of how your successor could perhaps improve those
processes?
Dr. Hamburg. Certainly, the transparency initiative was a
multifaceted undertaking intended to both expand understanding
of what the FDA is, what we do, how we do it, and why, but also
to hold us accountable in critical areas of activity and really
post for everyone to see the progress we were making on
critical issues.
You're right. The different parts of the FDA are
functioning with somewhat different performance with respect to
aspects of their work. It relates to both management and
assuring that we have consistent, high-quality management and
oversight. It has to do with having adequate resources to
support----
Senator Cassidy. Presumably, the resources somewhat flow
between the two, so one division--would it have far more
resources than the other?
Dr. Hamburg. Not always, because----
Senator Cassidy. If not always----
Dr. Hamburg. We were talking about the user fees before----
Senator Cassidy. I just have limited time, so let me kind
of go back to my point because I have a question for Dr.
Collins. If you could make that information more available,
That would help us----
Dr. Hamburg. OK.
Senator Cassidy [continuing]. As we look on a granular
level, because that is our responsibility to provide that
oversight.
Dr. Hamburg. Just one point there. The user fees are often
targeted to specific programs through a negotiation process.
The programs with user fees often have a bit more flexibility
and, hopefully, more predictability in terms of resources.
Senator Cassidy. I've got you.
Dr. Collins, I'm a doc, and, apparently, Senator Bennet
doesn't want a gastroenterologist taking care of his cough.
[Laughter.]
Senator Cassidy. That said, clearly, our goal is
translational research, correct?
Dr. Collins. Yes, one of the goals.
Senator Cassidy. Some of your grants go to MDs and some go
to PhDs. Do you track what percent of those grants going to
PhDs result in translational research and those which go to MDs
or MD PhDs result in translational research? Is there a
difference there?
Dr. Collins. We do track that. As you know, our workforce
is made up of a variety of individuals with different
backgrounds. PhDs are the majority, actually. MDs and MD PhDs
are also very significant contributors. In general, the MDs and
MD PhDs tend to be more focused on translation or clinical
efforts, but some of them are doing basic science.
Senator Cassidy. I get that.
Dr. Collins. Certainly, a lot of the PhDs are deeply
engaged in translation.
Senator Cassidy. The taxpayer wants translational research,
right? I come from academics, and some people are content with
writing a paper, but they're not necessarily looking forward to
translation.
When you track, how much weight is given to someone's
success in translation, and if someone is really successful in
translation--perhaps not as good as someone else, but really
successful in translation--how much would that weigh toward
their future of being awarded a grant?
If you have precise statistics, I would like to know what
percent of grants go to MD PhDs or MDs? What percent to PhDs?
Of those going to PhDs, how many result in translational
research, and of MDs, what percent? And if there is a
difference, as you suggest, it does seem as if perhaps we
should put weight more to the MD PhD, if their bias is toward
translation.
Dr. Collins. I can certainly provide that data for the
record.
We have, of course, encouraged translation at NIH by the
founding of this new center, the National Center for Advancing
Translational Sciences, which is providing resources for PhDs
and MDs to enable the kind of translational science they might
have trouble doing otherwise by themselves. We're very focused
on this.
Just a small caveat, though. I would say we need to be
careful not to discount the value of that fundamental basic
science, which has been the mainstay of NIH's success over the
years.
Senator Cassidy. I totally accept that, but I do know there
are some that do not take the entrepreneurial kind of next
step.
Dr. Collins. We can help with that.
Senator Cassidy. Last--and I'm going to say this because
I've said it before--in your testimony, you mentioned the great
success that we have had with HIV in terms of its eradication.
I'll point out that it still seems to be 10 percent of your
budget. Alzheimer's/dementia, is what, $800 million now, and
HIV is $3 billion, which is 10 percent of the NIH budget.
CBO just released--and this won't show up well--our
national debt, which they say by 2025 will be 77 percent, which
they say is dangerous to our future. Knowing that we're going
to go into a period of constrained resources because of our
last 6 years of escalating national debt, I would again push
that if HIV/AIDS, as you have mentioned, is substantially
addressed--still problems, but substantially--and Alzheimer's/
dementia is a balloon note, Medicare and Medicaid are just
going to go bankrupt dealing with this.
We should start shifting more aggressively resources from
that which has been addressed to that which we are confronting.
Just making that point once more.
I yield back.
The Chairman. Thank you, Senator Cassidy.
Senator Whitehouse.
Statement of Senator Whitehouse
Senator Whitehouse. Thank you, Chairman.
Thank you both for being here today. Rhode Island is a
small State, and we tend to have a lot of small and
entrepreneurial companies. I'm concerned that when there is an
FDA or other regulatory disadvantage that a company must bear
to bring a product online, that hits a lot harder on the small
company than it does on the big one.
I notice that in the Accelerating Medicines Partnership,
all the participants seem to be the big manufacturers.
Obviously, if you're a big manufacturer, a world in which only
big manufacturers can succeed is a good world because you don't
face disruptive technologies from little manufacturers. You're
probably not going to get a lot of objection from the big
manufacturers.
How do you push back against the incentive of big
manufacturers to squeeze out little ones and make sure that
little manufacturers get the attention that they need and are
included in these types of processes and are helped through
your process? Since I mentioned the Accelerating Medicines
Partnership, let me start with you, Dr. Collins, then I'll ask
Dr. Hamburg to jump in.
Dr. Collins. I appreciate the question, because we are very
much in support of the idea that all the partners in this
ecosystem need to flourish, the public and the private. AMP
actually aims to try to do that by making all the data
immediately accessible to everybody, including the small
biotech companies. They get to see it. This is a rather
unprecedented kind of partnership.
Recognize that the pharmas that are taking part--10
companies--are paying for half of the cost of the research.
This is $230 million over 5 years, half of it from NIH grants,
half of it from companies, all sitting around the same table to
design the process.
It should empower everybody, what we learn through this
process and making the data accessible. That would be the only
way NIH could really see this as something we could support.
The companies have gone along with it, which is really quite
impressive on their part.
In terms of other things, we have a very vigorous small
business program that supports a lot of startup biotech
companies, and I could cite you a number of remarkable success
stories that are now highly profitable companies that started
out on the basis of an NIH grant. We are increasing, actually,
our support of SBIR proposals and shortening the timetable for
review of those, because often weeks matter when you're a small
company just trying to get started and you need that initial
infusion of grant cash to do the experiments.
We're very invested in this space. Probably one of my
closest relationships in terms of working with industry is
through BIO, the Biotechnology Industry Organization, going to
their meetings every year, listening to their concerns, trying
to be sure that we are synergistic with the whole effort
they're trying to mount in terms of finding new cures, new
devices, new diagnostics.
Senator Whitehouse. Dr. Hamburg, my time is running down,
so let me ask you to comment on that. If you could also comment
on--where there's a controlled pharmaceutical, the DEA has a
process that begins at the end of the FDA process that delays
the ultimate approval. To my knowledge, DEA has never come to a
conclusion that is different than the FDA's conclusion, which
makes me wonder why we put that additional demand on the
process if the outcome is inevitable.
If you could talk about those two things--the DEA process
that follows yours and making sure that small providers have a
shot up against the big guns.
Dr. Hamburg. I'll try to be quick. On the small business
question, it's a very serious area of focus and concern for us,
because many of the medical product companies that we regulate
are small on the medical device side and in the biotech world.
As Dr. Collins noted, often, they are one product approval and/
or a few weeks away from going under. Yet, that's where a lot
of innovation occurs.
We have tried both to streamline our regulatory processes
and provide more outreach and assistance through the process
for small businesses to help with that process, to be more
responsive and provide that additional clarity. This is one of
the reasons why this investment in regulatory science is really
important, because there are common tools and approaches that
can be used by smaller companies that can't make the same
investments, whether it's in the biomarkers area or innovative
clinical trial design.
Senator Whitehouse. And the DEA process?
Dr. Hamburg. We are working on small business--high
priority. DEA, it's a complicated system. It's certainly not
one that we put in place. Would it be the way that we would
structure the process if we were starting from scratch? We
obviously make our decisions based on public health and medical
care, and our perspective doesn't always align with DEA.
We do try to work closely with them in critical aspects of
making important drugs available for people and in appropriate
oversight of the use of scheduled drugs. I would be
disingenuous if I didn't say that I have seen some of the
disconnects that you have seen, and it might be an appropriate
time to look at how best to align these different players in an
important area of work.
Senator Whitehouse. Thank you.
The Chairman. Thank you, Senator Whitehouse.
Senator Collins and Senator Warren.
Statement of Senator Collins
Senator Collins. Dr. Hamburg, first let me thank you for
your service. You and I have discussed many times the
technological breakthroughs that are making a real difference
for people who are living with diabetes. An example of that is
the continuous glucose monitor, which is helping patients
control their blood glucose levels, which is key to preventing
costly and sometimes deadly diabetes complications.
The NIH and FDA have been extremely supportive of these
innovations in diabetes care, and that is why I was so
surprised and troubled when CMS decided that it would not
reimburse or pay for insulin-dependent Medicare beneficiaries
to continue to have their continuous glucose monitors. We have
a situation now where an individual with Type 1 who is covered
with private insurance gets to be the age where they age into
Medicare, and they lose the coverage for the CGM.
This has led me to question whether CMS consults with the
FDA and NIH in making its coverage decisions. Do they consult
with you, and were your two agencies consulted in the case of
this denial of coverage?
Dr. Hamburg. I have to tell you I was not aware of this
situation, and I can see why it's concerning to you, and we're
going to have a lot more important breakthroughs in terms of
medical devices and, of course, new treatments for diabetes
that will make a difference. We work with CMS. We can work more
with CMS.
We've done some pilot projects with CMS to look at how we
can do some of our decisionmaking in parallel rather than in
series so that as data is being collected in the product
development space, data that will meet the needs of both
agencies can be gathered and examined. There, obviously, are
discussions with CMS on various specific products. As I said,
in our modern world, we need to do more of that.
I would also say that your point speaks to an issue that's
been a high priority for me, and that I leave FDA feeling like
we still haven't adequately addressed, which is part and parcel
what you're trying to do here, which is we have to look at the
whole ecosystem for biomedical product development and use and
recognize that each of the different components that often
operate in silos actually are very interdependent.
One of the things, for example, that I'm hearing now more
and more from investors in biomedical research is that it's not
the FDA regulatory process that worries them and that they see
as the barrier. It's reimbursement issues and getting that
right. We really need to take that ecosystem approach.
Senator Collins. Thank you.
Dr. Collins, I'm going to switch to a different issue just
in the interest of time. I hope you'll respond for the record
to my question.
Dr. Collins. I'll be happy to.
Senator Collins. You put up a fascinating chart in which
you showed the tremendous progress that we've made with
cardiovascular disease, with cancer deaths, and with HIV/AIDS.
What they all have in common is that Congress has made a
sustained investment over the years in NIH research, and it's
paid dividends in better treatments and in falling death rates.
I am, as you know, very concerned about the trajectory of
Alzheimer's disease, which is fast becoming our most costly
disease in this country. As a society, we spend $226 billion a
year caring for people with Alzheimer's. Out of that amount,
$153 billion comes from the Medicare and Medicaid programs. As
Dr. Cassidy says, the trajectory is frightening. It's going to
bankrupt our healthcare system, and it's also causing such
suffering for the victims and their families.
I know you mentioned the AMP and the BRAIN initiatives, and
I'm excited about those. But shouldn't we be doing even more to
do a concerted effort targeted at Alzheimer's, given what the
trajectory of this disease is?
Dr. Collins. I do appreciate the question, and I share the
concern. When you look at the cost of Alzheimer's disease and
the care of individuals afflicted, not to mention the suffering
their families go through, that individuals go through, we are
on a trajectory that anybody who looks at it has to be deeply
concerned about.
We are certainly ramping up Alzheimer's disease research at
a pretty unprecedented rate. I just looked at the numbers.
Between 2011 and the President's budget proposal for 2016, that
will be a 42 percent increase for Alzheimer's disease research,
greater than virtually any other area that NIH supports. Is it
enough? No. Frankly, we don't have enough that I could argue to
support all the ideas in lots of other areas as well.
The good news is that Alzheimer's disease research is in a
very exciting place, that we do have new ideas about
therapeutics. We have the ability to do drug screens on cells
growing in tissue culture that represent Alzheimer's compared
to normal in a way that we would not have dreamed we had that
ability as a model, and these are human cells. We can start to
really figure out how to address therapeutics in a systematic
and rational way. There's a lot of excitement in the field
about seeing that go forward.
We are doing everything we can to find those partnerships--
AMP is one of them--to be sure that we're building on the
capabilities of other agencies and other sources of funding.
The patient advocates are a wonderful group of supporters as
well.
Frankly, it is an example of the fact that we've lost about
23 percent of our purchasing power for research since 2003. We
really need to be able to get back on a stable trajectory. That
would benefit Alzheimer's. That would deal with this. That
would deal with a lot of other things that are looming out
there as our population ages.
Senator Collins. Thank you very much.
The Chairman. Thank you, Senator Collins.
Senator Warren.
Statement of Senator Warren
Senator Warren. Thank you, Mr. Chairman.
Thank you, Dr. Collins and Dr. Hamburg, for being here. I
also want to say, as others have, thank you, Dr. Hamburg, for
your many years of service. The Nation owes you a great debt.
Over the past 50 years, the American system of medical
innovation has transformed the health of literally billions of
people around the world. New treatments have given hope to
people diagnosed with leukemia, HIV, breast cancer, and other
diseases that were once a death sentence.
The basic mechanism for those remarkable achievements has
two parts, a foundation of taxpayer investment in basic
research followed by private industry investments that turn
that research into viable products. Of the 21 drugs with the
highest therapeutic impact approved between 1965 and 1992, two-
thirds stem directly from discoveries made through government
supported research.
A recent study in Health Affairs found that most of our
truly transformative modern drugs have their roots in public
funding. This is no accident. As we've talked about here, for
decades, Congress grew the budget of the National Institutes of
Health year by year. In the late 1990s, both parties worked
together to double the budget for NIH.
The support has dried up. Since 2003, the NIH budget hasn't
even kept up with the pace of inflation. As you note, Dr.
Collins, its purchasing power is down nearly 25 percent.
Dr. Collins, can you tell us how the collapse in
congressional NIH funding has hurt the American pipeline of
biomedical innovation?
Dr. Collins. Thank you for the question, because this is
the thing that worries me most and keeps me up at night. We are
not taking advantage of the remarkable abilities of American
science to innovate, to come up with new ideas that prevent and
treat disease. One can simply look at the way in which NIH has
to deal with the ideas that come to us and basically leave
about half of the ideas on the table that traditionally we
would have funded, and that tells you what we're doing here in
terms of slowing down the process of innovation all the way
from basic science through to clinical trials.
You might ask, ``Well, maybe the part that we're leaving on
the table is not quite as good as the stuff we're funding.''
We've actually looked at that, and because--when you look at
that top third of applications, this is the really great
science. We can't retrospectively go back and say that those
that scored in the 25th percentile weren't as good as those in
the 10th percentile. They're indistinguishable.
What does that say? That says we are leaving great stuff
that is not getting supported and traditionally would have
been. We are, of course, the foundation in many ways for this
wonderful success story of American science, which is public
and private working together. What we discover, as you point
out, has led to those breakthroughs that now people take for
granted. We can't keep taking it for granted if we don't
support it.
Senator Warren. Given how important this issue is, you'd
think our first priority here would be to figure out how to get
the NIH the resources it needs to replenish the pipeline of
great research that is the foundation for better treatments and
reliable cures. But, instead, Congress has focused on whether
to lower the FDA standards for approving drugs. I hear the
arguments, but this is a dangerous game.
The pain killer, Vioxx, made it through the FDA's rigorous
approval process but was later found to cause heart attacks. By
one estimate, it killed 38,000 Americans before being pulled
from the market.
Dr. Hamburg, what impact would lowering the FDA's safety
and effectiveness standards have on public health?
Dr. Hamburg. As I said in my remarks, lowering the
standards would be very, very dangerous, detrimental to the
health and safety of patients, bad for the healthcare system,
but also bad for our wonderful preeminence in terms of our
pharmaceutical, biotech, and medical device industries in terms
of their ability to actually deliver products for people who
need them.
We know that FDA's standards and our requirements around
safety and efficacy over the years have actually helped to
shape how biomedical research, clinical research, and
translational research get done--this notion of really
structuring our investments in research so that we ask the
right questions. We don't just publish papers, as Dr. Cassidy
was saying, but we actually make sure that we're leveraging the
opportunities in science and technology to get important
treatments, preventive strategies, and cures to patients.
Senator Warren. So you're saying, if I understand it, that
the high standards are important, not only for public safety,
but also for help shaping the research that's going to give us
the treatments that we need.
Dr. Hamburg. Absolutely.
Senator Warren. I want to say I am certain there are
changes we could make at the FDA to help speed up the approval
process and get rid of unnecessary bureaucracy. When science
supports change, I am eager to make change. Lowering FDA's
approval standards will not increase innovation.
We could abolish the FDA tomorrow, and we'd see tons of new
products on the market. The goal isn't new products to boost
profits for the industry. We don't want another Vioxx. The goal
is innovative, transformative products, products that are safe
and effective that will cure diseases, save money, save lives.
To achieve that goal, we need to start with the NIH.
Nearly everyone in Congress says they support funding that
agency. Talk is cheap, and Congress has decimated the NIH's
budget, singlehandedly choking off support for projects that
could lead to the next major breakthrough in Alzheimer's and
many other diseases.
We could dismantle the FDA, but that won't produce new
cures for the diseases that maim or kill us. If we're serious
about better health for children and seniors, then Congress has
to step up and make a real commitment of real dollars for
scientific research.
Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Warren.
Senator Baldwin.
Statement of Senator Baldwin
Senator Baldwin. Thank you, Mr. Chairman and Ranking
Member. I am encouraged by this bipartisan effort to examine
the entire discovery and development process for medical
treatments.
As someone who was raised by her grandparents--and my
grandfather was an NIH-funded scientist at the University of
Wisconsin Madison--you can understand that I have a long-term
passion for a strong, strong Federal investment in basic
research. I remain concerned that budget cuts mandated by the
Budget Control Act has put medical research at risk. In fact,
we've been talking about that this morning.
In fact, Dr. Collins, you have cautioned that we are
putting an entire generation of scientists at risk. The average
age of a researcher receiving her or his first grant is
increasing, and budget cuts are discouraging young scientists
from entering the field or forcing them to, in some cases,
leave the country in order to continue their research.
To help address this, last Congress I introduced the Next
Generation Research Act that would coordinate efforts within
NIH and streamline current programs to improve opportunities
for new investigators. It would also promote new policies to
help increase diversity and improve the success of
investigators who are applying for their second grants.
Dr. Collins, we've discussed this issue a number of times
before, and I'm encouraged that you share that interest and
passion here. Can you please discuss with the committee any
progress that has been made through NIH's existing programs,
such as the Early Stage Investigator Program and the Director's
New Innovator Award, to bolster this emerging research
workforce?
Dr. Collins. I really appreciate the question, because this
is such a fundamentally important issue if we're going to have
a future where American biomedical research continues to
flourish. We have, in fact, instituted a number of programs
that are aimed to try to encourage that next generation to see
a path for themselves as successful and visionary researchers.
One thing that we have done which has now been quite
helpful in that regard, is to make sure that if you're an early
stage investigator who hasn't come to NIH before with a
proposal, you compete against other investigators of that sort,
as opposed to being thrown into the main pool with very
experienced investigators who have been at this for a while.
That has done quite a bit to equalize the success rates amongst
the newbies versus those who have been in this business. That
is one thing.
Another thing we've done was increased the number of awards
which are sort of a bridge to independence from a post-doctoral
fellowship to an academic position, so-called K99R00 awards,
which we are finding to be a very successful way to make that
leap from a training position to an independent faculty
position in a research intensive university.
We're also making sure that we have our graduate students
and post-docs exposed to multiple different kinds of career
paths, because not all of them need to end up as research track
faculty in an intensive university. There are jobs in industry.
There's jobs in policy, in journalism, many other places where
PhD-level individuals are needed, and we want to be sure people
find the right match for themselves.
We have started new programs, an early independence award,
one that I'm quite excited about, which basically allows a very
talented PhD to skip the post-doc and go directly to an
independent position. I go to the presentations every year of
the new awardees there, and it's the most exciting day of the
year for me because of their vision and their ideas.
Similarly, we have this new innovator award, where you
can't apply if you have previously had an NIH grant, and your
idea has to be out of the box, groundbreaking, a little wacky
in order for you to even be allowed to apply for that proposal
mechanism. When we look at the output of that, it has been
truly impressive, the kind of outcome we've had.
All that's great, but, of course, it doesn't solve the main
problem we have, which is this loss in purchasing power for
research. We can try to balance things as best we can, protect
those young investigators. We can only go so far. We really
need to turn the corner.
Senator Baldwin. I appreciate that. Resources are obviously
key to this as well as the coordination of programs that we've
discussed in the bill that I've introduced and we'll certainly
be re-introducing.
I guess the flip side of that, Dr. Collins, is what would
the impact be of NIH's current programs for new researchers as
well as the impressive new initiatives if Congress should not
reverse sequestration?
Dr. Collins. We would continue to see this downward curve
which is very troubling, indeed. Surveys have indicated close
to 20 percent of researchers supported by NIH are now
contemplating moving to another country or to another kind of
career path because of the concern they have.
Last week I was in San Diego. I met with the MD, PhD
training students who were in the so-called medical scientist
training program. There was a room full of the most incredibly
gifted, talented, future physician scientists you could
imagine. In the past, when I met with groups like that 10 years
ago, it was all about the science and how excited they were.
This was a group whose brows were furrowed, who are really
deeply anxious about whether there's a path for them. Their
questions to me weren't so much about science, but as to
whether I could give them some sense of optimism about their
future. I tried, but it wasn't as easy as it should have been,
given the talent in that room.
Senator Baldwin. Thank you.
The Chairman. Thank you, Senator Baldwin.
Senator Casey.
Statement of Senator Casey
Senator Casey. Thank you, Mr. Chairman. I want to thank you
and the Ranking Member for having this hearing. These are
deadly serious issues, the ones that Dr. Collins just spoke to
about the impact of funding diminution. It's probably the worst
example of pennywise and pound-foolish that we can imagine.
Sometimes it comes down to one name, one person, one case.
The young girl in Pennsylvania, the 9-year-old, who,
thankfully, is healthy right now--Emily Whitehead, who had a
particular kind of leukemia. The only way her life was saved is
because of an experimental so-called T-cell therapy that was
pioneered by folks--researchers, I should say, NIH-funded
researchers at Children's Hospital in Philadelphia.
I have to ask when I come to these debates about funding
levels, which, frankly, are rather bizarre when you consider
the positive outcomes that we have through NIH--I have to ask
what if down the road, because we didn't make the investment,
because Congress failed, would the next Emily Whitehead be
saved? It's worth not just contemplating, but using those
examples as a springboard to action.
Dr. Collins, I want to go back to something you mentioned
before, and I know it's by way of reiteration, but it's
important to repeat ourselves around here so people get the
message a little better. Did you say that NIH has lost 23
percent of its purchasing power since 2003? Is that accurate?
Dr. Collins. That is, in fact, accurate. I can actually
show you a graph that would maybe make that more clear. If you
look there at the yellow line, that is the NIH budget adjusted
for the effects of inflation. You can see the doubling that
happened with that peak going up to 2003, and you can see the
steady deterioration since then, and that, in fact, adds up to
about a 22 or 23 percent loss in purchasing power over the last
12 years.
Senator Casey. The other part of this, which you
highlighted--and this is one I had not heard--is the percent of
those contemplating moving out of the United States because of
either the lack of funding, or I guess it would be uncertainty
regarding funding. What percent is that of researchers?
Dr. Collins. In this particular survey of NIH-funded
researchers, it was 18 percent who said they were significantly
contemplating that kind of drastic step.
I really appreciate you raising Emily Whitehead as an
example of what we need to have more of. I met Emily Whitehead
in the White House. Senator Alexander was there that morning as
well. Emily was there for the announcement by the President of
the Precision Medicine Initiative, as was her doctor, Carl
June.
This is the kind of amazing success story that we believe
is out there in greater numbers, but we have to be sure that
we're investing in all of the steps that it takes to get there.
I mean, what happened with Emily, you can trace back to 50
years of hard work understanding the immune system and
understanding cancer, ultimately getting to that point. It
didn't just arise out of nowhere.
Senator Casey. Doctor, I wanted to ask you about the
President's initiative, the Precision Medicine Initiative, in
the context of Emily and other children. Tell me about how that
initiative can--or any other undertaking or initiative that NIH
will be involved in that will focus more on the pediatric
research that leads to those breakthroughs.
Dr. Collins. The Precision Medicine Initiative aims to have
an early focus on cancer and a longer-term effort to try to
build this million strong cohort across the Nation to try to
take advantage of a coalescence of really exciting
technological opportunities. One is, of course, the genomic
revolution, the ability to be able to get information about DNA
at a remarkably low cost, considering where we have been.
Another is the advent of electronic health records, which
are now the norm in many healthcare delivery systems. Another
is the ability to use wearable sensors, that people are excited
about having access to, to detect various aspects of human
physiology, whether it's something that detects blood glucose
in a diabetic, which Senator Collins was asking about, or
something that is actually monitoring your environmental
exposures or your diet or your blood pressure. All of those
things are coming into their own.
To have a very large-scale cohort across the age
distribution, across gender, across geography, across
socioeconomic status, we could really begin to figure out what
are the risk factors for disease and what can we do about them
and how can we monitor and treat chronic disease more
effectively having that large-scale effort. This is a joint
effort between NIH, our partners at FDA, and the folks at ONC
that are involved with electronic health records meaningful
use. We're enormously excited about the way this could
transform our understanding of biomedicine.
Senator Casey. Thank you, Doctor.
Dr. Hamburg. Mr. Chairman, can I just add one brief
comment? I want to underscore that as you think about what can
be done to really harness the extraordinary advances in science
that are occurring today and the resources that NIH so
rightfully needs and desperately needs to ensure that that
important work, basic, clinical, and translational gets done,
that you not forget that in order to actually see those ideas
become real-world products, it has to be accompanied by
appropriate investments in FDA that give us the opportunities
to develop our area of science to ford that final bridge to a
real-world product and to help make sure that the investments
in the research at NIH are being done in the most efficient and
streamlined way as they are trying to actually move that
product through the development pipeline into the product.
One of the disconnects that worries me a lot--and I'm
sorry, but I have to say it since it's my last time before this
committee--is that everyone thinks that if you want to deliver
on the promise of science, more investment in NIH--that is
absolutely critical and foundational. You do not want an FDA
that isn't fully equipped to oversee the products that are
coming before them, that isn't well staffed to do efficient,
modern regulatory reviews, and you want to be able to bring the
knowledge and expertise of FDA and product development into
those earlier stages of research.
Dr. Collins. May I say I heartily agree with my colleague
and would like to endorse everything she just said.
Senator Casey. I agree as well. Thanks, Doctor.
Dr. Hamburg. Thank you for your indulgence.
Senator Casey. Doctor, thanks for your service.
Dr. Hamburg. Thank you.
The Chairman. Senator Franken.
Statement of Senator Franken
Senator Franken. Thank you, Mr. Chairman, for calling this
hearing, and thanks to you both for your service.
Dr. Hamburg, thank you. I worked closely with you on a
couple of things, I thank you for your service, and we are
sorry to see you go.
I also apologize for just getting here. I had a hearing in
Judiciary that was also very important.
I'm proud to represent Minnesota, as you know, Dr. Hamburg,
and our medical device industry, and we have spent some time
working together. When I first got in this job Dr. Shuren came
to Minnesota and had some discussions with the industry,
roundtables with him, and I noticed kind of a different culture
between the regulators and the device manufacturers, and I
wonder why that would be.
LifeScience Alley, along with the FDA, did something--it
was for the first time ever--a private-public consortium on
regulatory science. I wanted to ask you how you believe that's
going. The name of it escapes me. It's the Medical Device----
Dr. Hamburg. Medical Device Innovation Consortium.
Senator Franken [continuing]. Innovation Consortium.
Dr. Hamburg. MDIC.
Senator Franken. Yes, it says what it is. I like names like
that but can't remember them. The Medical Device Innovation
Consortium--from your perspective, how has that been working?
Dr. Hamburg. It is an example of the kind of thing we can
and should be doing more of, as you note, bringing together
private industry, academic researchers, not for profit
organizations, and government under one organization that is
committed to advancing the regulatory science needed to advance
medical device development. It has grown enormously since it
was started.
There was initially some skepticism perhaps, but it has
grown. It has identified critical areas of research whereby
advancing the research through this partnership will benefit
medical device development much more broadly, because it's
doing things like helping to design innovative clinical trial
approaches that will make the clinical trials less cumbersome
and make it easier for products to go into clinical trials to
demonstrate safety and efficacy.
It is also developing computer models and other simulations
where without the cost, the time, and the potential risk to
patients, you can really examine whether a device is going to
work and how the design should be tweaked, et cetera; looking
at how we can better integrate patient-reported outcomes and
their experience of using a device into the development and
review process. It's focusing on some of the most important
issues before us, doing it in a way that advances the science
and doing it in a way that actually creates knowledge that
becomes a common good for other product development in the
future.
Senator Franken. Thank you. We're proud that that private-
public partnership is working.
I want to talk a little bit about precision medicine and
what it's done. Sometimes when I think about precision
medicine, I think I was born a little too early. I think of
what things are going to be like 20, 30, 40, 50 years from now.
Let's talk about LDTs. The University of Minnesota has
developed a panel of more than 1,200 genetic variations that
can be tested to identify risks for specific genetic diseases.
The Mayo Clinic, which is in Rochester, MN, has also made
significant investments in developing and evaluating LDTs.
These folks are concerned that regulation that is not
thoughtful or careful enough could hamper the lifesaving
potential of LDTs and undermine the medical research designed
to identify and target root causes of disease. I applaud the
Chairman and the Ranking Member for working with the FDA and
industry efforts, the whole series of briefings on this
relatively new topic.
Dr. Collins, I'd like to know what role NIH will have in
advising the FDA with regard to regulation of LDTs, and to what
extent are your two agencies engaged with one another, which I
think Senator Collins talked about--no relation. As a
researcher yourself, what is your view on how the two agencies
should work together to promote safe, effective technologies in
a way that's ethical and safe for patients without interfering
with the innovative work?
Dr. Collins. Senator, I appreciate the question. This is an
area that NIH and FDA have been working together closely on
over the years and are particularly closely working on right
now to try to accomplish just what you said, to be sure that
the kind of laboratory developed tests, particularly in the
field of genetics, where things are growing so quickly, are
offered to patients in a way that benefits them and doesn't
slow down innovation, but also has appropriate oversight,
particularly in high-risk situations where false results can
actually lead to decisions that can be quite harmful.
FDA released back in the fall a guidance on risk-based
oversight of laboratory developed tests. We think that is a
very thoughtful document that has now sort of become the
foundation for multiple conversations and workshops, including
one just February 20th that was held on the NIH campus, to try
to get additional input about this.
What we can do, which is actually turning out to be quite a
nice partnership in a very specific way, is we have already a
database called ClinVar, which samples across the entire
medical literature what has been reported as far as this
particular DNA variation being connected with this particular
disease or disease risk. That database is being curated in a
way that people can find the information.
You can't necessarily look at that and know which of these
should you rely upon and which might be a result that one
person found but somebody else didn't. You need an expert panel
on top of that--a group that we call ClinGen, which is basic
clinical genomics oversight--of experts that looks at the data
base and makes decisions upon the evidence about whether a
particular DNA variation has been conclusively shown to be
associated with a medical risk, like a BRCA1 mutation that's
been seen in many people with breast and ovarian cancer, and at
various levels of certainty what they think about the whole set
of information that's there.
FDA is very interested in that particular NIH-funded effort
in order for them to be able to have expert advice about what
you can trust and what you can't. We're not the regulators. FDA
has that role. This is a great opportunity for our relative
roles to be nicely interdigitated, and it will be critical for
precision medicine.
As we see more and more of these opportunities playing out
with this cohort of a million or more people, we want to be
sure that as we feed them back information about themselves
that it's right and that they can trust it and it's been looked
at by experts and reviewed by the regulatory agency.
The Chairman. Dr. Hamburg, since this is your last hearing
in your current capacity, would you like to have the last word
on that question or any other question before we wind the
hearing up?
Dr. Hamburg. On that question, I would say that the world
of diagnostics is complicated. It's very, very important,
because at the end of the day, it is what guides the ability of
a healthcare provider or a patient consumer to make sure that
they are getting the best possible treatment for the condition
that they have.
Also, having accurate and reliable diagnostic tests is
crucial to our actually being able to do the fundamental
research that will reveal the opportunities in treatment,
prevention, and care, because if the test is inaccurate, all of
that research isn't going to mean much.
We think that at the core of all of this is our
responsibility to make sure that diagnostic tests work, whether
they're laboratory developed tests or much more advanced next
generation sequencing, which Dr. Collins was talking about at
the end there, which is really using genomic science and
technology to give us vastly expanded sets of information so
that one diagnostic tells you information about thousands,
millions of potential variants, not just one diagnostic, one
disease.
At the end of the day, our goal is not to create
unnecessary regulation, but to be able to assure the American
people, their healthcare providers, and the companies that make
these products that when a product goes into the marketplace,
it will do what it says it will do. In fact, that kind of
regulatory foundation is common sense.
It also is what enables innovation to be driven forward,
because when you have some tests that aren't held to the same
standard as other tests, then the incentive for those who are
coming from the traditional device industry, developing FDA-
regulated diag-
nostics--incentive for them to stay in that business when
someone else can just create a test and market it without any
of the same assessment and review is problematic.
It is kind of an interesting example of why things get very
complicated, but at the end of the day, FDA's role is to help
speed innovation to patients who need that innovation. We want
innovation that works, innovation that will make a difference
in promoting and protecting their health, and that will benefit
our healthcare system and the industries that are so much a
part of the U.S. economy.
Senator Franken. Thank you for doing that, and I apologize,
Mr. Chairman, for going so far over my time.
The Chairman. No, no. That's fine.
Senator Murray, do you have any concluding remarks?
Senator Murray. I would just say, Dr. Hamburg, well stated.
Thank you to both of you for excellent testimony. This was
a really good hearing.
Senator Alexander, I look forward to working with you on
this.
The Chairman. Thank you, Senator Murray.
Dr. Collins, just for the record, or if you know offhand,
you mentioned the success rate and how it has declined over 30
years. What about the absolute number of grants? Has that gone
down, too, or is that up?
Dr. Collins. The absolute number of grants that we fund
versus those that we receive--it's been bouncing around, but
it's under 10,000 now for new and competing grants.
The Chairman. Thirty years ago, it was what?
Dr. Collins. Thirty years ago--I'd have to get you the
number for the record.
The Chairman. I was trying to compare that with the success
rate.
Dr. Collins. Of course, the biomedical research community
has grown in that time table.
The Chairman. Right.
Dr. Collins. I can get you the specific numbers.
The Chairman. It would be interesting to see that. Thanks
to both of you.
Dr. Hamburg, thank you for being here.
Dr. Hamburg. Thank you.
The Chairman. It's very important that you were here, and
we thank you for your 6 years of service at FDA. I hope you'll
accept our invitation to stay in touch with us especially over
the next year as we work on these issues.
Dr. Collins, you're going to still be here.
Dr. Collins. I am.
The Chairman. We're going to stay in close touch with you.
This has been a good conversation, and the fact that the
two of you were here helps signal the importance of it, and the
attendance of the Senators. Of course, by 2017, we'll be in the
midst of the user fee discussion. The issues that we intend to
get into here are different from those.
What I would say to those in your agencies and to the
administration is this is a train that's on a track to get to
the station. It's going to get somewhere. Some of us are on the
Appropriations Committee, and we'll be working on the
sequestration, the funding levels. That's one thing that we can
do.
There's also the question, as I mentioned, of that 42
percent administrative cost. If there are some things that we
need to do, some laws we need to change, some other agencies,
and if we can get that from 42 to 32, that's $3 billion, one
time. So there's the question of re-allocation.
There are questions of other obstacles that you've run into
that you would say, ``If you could change that, that would make
our life better.'' This is in no way trying to diminish the
accomplishments of the FDA or the NIH over the last few years.
It's to say we're in this exciting era. The House, the
President, the Senate are all heading in the same direction.
We'd like to get there within a year or so, and we'd like to
have your help in making sure we do that well.
This is an unusual opportunity to get a result in a town
that doesn't that often see the President and the Republican
Congress on the same train headed in the same direction toward
an important station. By you being here, you helped to
emphasize that, and we look forward to continuing our
discussion.
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 today. The
committee will stand adjourned.
[Additional material follows.]
ADDITIONAL MATERIAL
Response by Francis S. Collins, M.D., Ph.D. to Questions of Senator
Alexander, Senator Collins, Senator Hatch, Senator Cassidy, Senator
Bennet, and Senator Warren
senator alexander
Question 1. We were able to move Ebola drugs into human, non-
randomized trials in 3 months. What can we learn from that process and
apply to other diseases that seem just as urgent and necessary as Ebola
for the patients and families with those diseases?
Answer 1. Sustained, long-term investments in basic, translational,
and clinical research enable NIH to build foundational knowledge for
understanding biological systems and to develop potential treatments
and cures for a broad range of diseases. The knowledge base and
research infrastructure supported by NIH facilitates the agency's
ability to respond to emerging health threats as well as scientific
opportunities. If a public health emergency arises, then NIH often can
leverage this knowledge base and research infrastructure, as well as
longstanding collaborations with Federal and industry partners, to
rapidly mobilize development of potential interventions.
For example, the rapid research response to the Ebola virus disease
outbreak in Western Africa is illustrative of the importance of long-
term research and infrastructure investments, effective partnerships
with industry, and strong collaborations with Department of Health and
Human Services agencies, especially the Food and Drug Administration
(FDA) and the Biomedical Advanced Research and Development Authority
(BARDA). Following the 2001 anthrax attacks, Congress significantly
increased the funds appropriated for biodefense research. With these
funds, the National Institute of Allergy and Infectious Diseases
(NIAID) expanded investment in this area, leading to the development of
medical countermeasures for bioterrorism agents as well as emerging and
re-emerging pathogens. Among these investments more than a decade ago
was support for NIH's Vaccine Research Center (VRC) for work on viral
hemorrhagic fevers, including Ebola. Scientists at the VRC, in
collaboration with industry partners, developed a vaccine against the
Ebola virus that was effective in animal models of the disease and is
under clinical evaluation for safety and immunogenicity in West Africa
currently.
When the Ebola virus disease outbreak occurred, interest among
NIAID's industry partners increased substantially, and NIAID was able
to respond quickly to move candidate Ebola diagnostics, therapeutics,
and vaccines that were already in development with NIH resources into
clinical trials. For example, in February 2015 NIAID and its partners
launched a randomized controlled clinical trial (RCT) to obtain safety
and efficacy data on the investigational therapeutic ZMapp as a
treatment for Ebola virus disease. ZMapp, a combination of monoclonal
antibodies directed against Ebola virus developed by Mapp
Biopharmaceutical, Inc., builds upon years of basic and preclinical
research supported by NIAID and other partners.
The ZMapp randomized controlled clinical trial was developed in
partnership with the FDA and Ebola-affected countries over a period of
several months to address the urgent need of current and future Ebola
patients while ensuring the trial was appropriately designed to
adequately demonstrate safety and efficacy. To date, the ZMapp RCT has
enrolled patients in the United States, Sierra Leone, Guinea, and
Liberia. The swift progression of ZMapp and other candidate Ebola
countermeasures to clinical trials was made possible because of
longstanding partnerships with FDA, Centers for Disease Control and
Prevention, the Office of the Assistant Secretary for Preparedness and
Response (ASPR), ASPR/BARDA, and Department of Defense colleagues, as
well as collaborations with industry partners and officials in the
affected countries.
In response to the Ebola outbreak, NIH also was able to capitalize
on its efforts in drug repurposing, which seek to identify existing
drugs that could be effective treatments for diseases other than the
ones they initially were developed to treat. Researchers from the
National Center for Advancing Translational Sciences (NCATS) and the
Icahn School of Medicine at Mount Sinai explored drug repurposing as a
means to rapidly identify potential existing drugs that may block Ebola
infection. The team developed a miniaturized test to screen for drugs
that block the ability of Ebola virus-like particles to enter and
infect cells. Miniaturizing the test enabled the team to utilize a
high-throughput screening format, whereby the test could be applied to
several hundred drugs at the same time. The team used the NCATS
Pharmaceutical Collection, a library of 2,816 approved and
investigational medicines, and identified 53 drugs with Ebola virus-
like particle entry blocking activity. Further testing must occur
before any of these drugs can be used as an Ebola treatment; however,
this process highlighted how drug repurposing and high throughput
screening can speed up the development of potential therapeutics to
address urgent health needs.
Long-term investments in biodefense research, drug repurposing, and
effective partnerships enabled NIH to respond quickly to the need for
Ebola vaccines and therapeutics. Similarly, investments in other
disease areas and across the biomedical research spectrum position NIH
to seize opportunities or respond to needs to develop interventions
that improve the health of individuals and the public.
Question 2. A former NIH director, Dr. Zerhouni commented that,
``The ability of any institution to adapt to its changing environment
will remain a key to its success.'' How do NIH and FDA need to evolve
to keep pace with where science is now? What does Congress have to do
to help you get there?
Answer 2. The pace of scientific discovery moves quickly, and NIH
works diligently to stay abreast of changes that could impact research
needs and opportunities. First, we listen to the scientific community
by sponsoring and attending workshops to understand the latest
research, assess any new directions that a field may be taking, and
consider whether and how NIH support could make a significant impact.
In addition, most NIH grants are investigator-initiated so NIH staff
are aware of the newest ideas proposed. NIH also analyzes its research
portfolios using a variety of approaches, including increasingly
sophisticated computational methods, to detect emerging research areas
that could flourish with an influx of resources. All of these
activities inform NIH's understanding of the biomedical research
landscape and influence NIH funding decisions to invest in high-
quality, cutting edge research. These funding decisions are based not
only on peer review of scientific merit, but also on scientific
opportunities, public health needs, and maintaining a balanced
portfolio of basic, translational, and clinical research.
Maintaining the agility to catalyze new scientific advances and
health discoveries would be improved with long-term stability in
overall NIH funding, which maximizes NIH's ability to plan for future
efforts. The President's fiscal year 2016 Budget includes $31.3 billion
for NIH, an increase of $1 billion over the fiscal year 2015 level. In
addition, the ability for NIH to be on the cutting edge of scientific
discovery is dependent upon its scientists and staff being part of the
conversation, both in terms of hearing the efforts on the ground and
providing a holistic view of the landscape that not all investigators
are aware of. Staff serve as cross-pollinators of ideas and concepts,
bridging fields and disciplines. However, current conference and travel
restrictions hinder the ability of NIH staff to attend scientific
meetings that enable them to participate in these discussions. We look
forward to working with the HELP committee on advancing innovation.
Question 3. Do you believe that a single government agency can keep
up with the rapid pace at which biotechnology is evolving?
Answer 3. Where appropriate to agency missions, a multi-agency
approach is hugely beneficial to biotechnology advances and
transformative to all biomedical and biotechnology research. The
coordinated efforts of NIH and the Department of Energy (DOE) on the
Human Genome Project (HGP) greatly contributed to the explosion of
biotechnology as an industry. From that effort, we learned that the
diverse perspectives of multi-agency efforts can speed up discovery by
utilizing the expertise unique to each agency's mission. For HGP, NIH
provided vast knowledge on genetics and molecular biology and DOE
provided insight into the effects of ionizing radiation on human
biology.
The NIH Tissue Chip for Drug Screening program is an example of a
current cross-agency collaboration utilizing and building upon advances
in biotechnology. This program is managed by NCATS and addresses the
current problem that promising medications often fail in human clinical
trials because they are determined to be toxic despite promising pre-
clinical studies in animal models. The research teams in the Tissue
Chip program are developing alternative models for testing drug
toxicity and effectiveness through the development of human-based
tissues and organs on microchips. NIH intentionally invited the Defense
Advanced Research Projects Agency and the Food and Drug Administration
to collaborate in this program in order to aggressively meet program
goals of tissue chip integration to develop a ``human on a chip'' that
could receive regulatory approval as an alternative drug testing model.
Question 4a. Just last week it was reported that drug companies
spend on average, almost 23 million hours each year complying with
recordkeeping for Investigational New Drug applications. FDA and NIH
have funded numerous efforts to improve the efficiency of clinical
trials, such as the Clinical Trial Transformation Initiative and the
Clinical and Translational Science Awards. I also received comments
from a Vanderbilt researcher that emphasized the importance of
increasing the efficiency with which clinical trials are conducted.
How can we better leverage these initiatives to get more drugs and
devices to patients?
Answer 4a. The NCATS Clinical and Translational Science Awards
(CTSA) program is actively addressing inefficiencies and roadblocks
common across clinical and translational research with the long-term
objective of having the CTSA sites serve as research hubs of a national
network of clinical and translational science. The resources provided
by these hubs are leveraged to 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. By developing solutions to common problems across
clinical trials and implementing them through the CTSA network, NIH can
demonstrate their utility toward more efficient clinical trials and
then disseminate those solutions more broadly to serve all clinical and
translational research.
Recently, NCATS published funding opportunity announcements for
Collaborative Innovation Awards, which are designed to stimulate team-
based research across the CTSA consortium. NCATS has also announced
plans to support the evolution of the CTSA program by soliciting
innovative approaches to increasing clinical trial efficiency and
effectiveness and by addressing the roadblocks common to clinical
studies recruitment of research study participants.
Question 4b. What is the biggest hurdle to more efficient clinical
trials? What are NIH and FDA doing to address this?
Answer 4b. One of the biggest hurdles to more efficient clinical
trials is the current lack of standardization in the various processes
required for trial initiation. NIH has ongoing efforts to address and
improve clinical trial development and efficiency. In terms of joint
efforts, under the auspices of the NIH-FDA Joint Leadership Council,
the agencies are collaborating in a number of areas to improve
efficiency and support to the clinical trial enterprise.
For example, NIH and FDA are collaborating on the development of a
protocol template to guide investigators in preparing clinical trial
protocols. The availability of a standard protocol template acceptable
to both agencies would improve the quality of the protocol document and
facilitate its preparation. It would also reduce the time needed for
review and enhance the consistency of the review process. A protocol
template could set a national standard for clinical trial protocol
documentation and improve transparency of expectations from FDA and NIH
on the quality of protocols, methods, data standards, and reporting.
NIH and FDA are also collaborating to promote the use of common
data elements (CDEs) in clinical trials. A CDE is a data element
defined uniformly across multiple sources or settings. Use of CDEs
improves data quality and opportunities for comparison and combination
of data from multiple studies and with electronic health records, and
facilitates FDA's review of clinical trials. In addition to encouraging
ongoing CDE initiatives, NIH and FDA are working to promote further
efforts to develop, disseminate, and encourage use of general core CDEs
across all clinical studies, disease-specific core CDEs modules, and
disease-specific supplemental CDEs.
Also, NIH and FDA are exploring ways to enhance communication
between FDA medical officers and NIH program officers who oversee
clinical trial portfolios that are regulated under an investigational
new drug application (IND) or investigational device exemption (IDE).
Such discussions would address trial design and statistical issues that
can enable the generation of sufficient evidence on the safety and
efficacy of the proposed approach.
Question 5. The United States has long been a leader in biomedical
innovation, but reports that our global edge is slipping are
concerning. For example, China's Beijing Genomics Institute went from
performing 1 percent of the Human Genome Project to analyzing 10 to 20
percent of all DNA sequenced around the world. While we hear a lot
about research funding as a contributing factor, the regulatory
environment here in the United States has been cited as a major
contributing factor. What can we do to maintain America's global
leadership in medical innovation?
Answer 5. As noted, the United States continues to be the largest
public funder of biomedical research worldwide; however, a number of
global indicators show that our competitive position in the life
sciences is weakening. Much of this loss in position is due to a loss
in purchasing power. NIH's fiscal year 2015 budget of $30.31 billion
represents a purchasing power cut of almost 20 percent compared to
fiscal year 2004. Relative to the major countries in North America,
Europe, and Asia, the United States now has the slowest annual growth
rate in medical research investment at 1.0 percent; China (16.9
percent), Australia (9.39 percent), Japan (6.89 percent), Canada (4.59
percent), Europe (4.19 percent), and other Asian countries (20.89
percent) are all increasing their annual investments in medical
research at a faster pace. Since 1992, the United States has fallen
from second to tenth in overall R&D intensity (R&D investment/GDP =
2.89 percent)--now ranking behind Israel, Sweden, Finland, Japan, South
Korea, Switzerland, Taiwan, Denmark, and Germany.\1\ The President's
fiscal year 2016 Budget level for NIH is $31.3 billion, an increase of
$1 billion over the fiscal year 2015 enacted level.
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\1\ ``Science and Engineering Indicators 2014'' National Science
Foundation, February 2014. http://www.nsf.gov/statistics/seind14/
index.cfm/chapter-4/c4h.htm#s2.
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NIH continually seeks to refine its policies and procedures in
order to speed the translation of research into health benefits. For
example, NIH is currently refining its clinical research policies to
promote and facilitate participant engagement in research and speed the
initiation of research through the use of a single Institutional Review
Board for multisite studies. At a time when increasing competition for
limited funding is resulting in investigators spending more time
writing grant applications and less time conducting science, NIH is
looking to speed the granting process and reduce administrative burden
on its investigators.
NIH is supporting a new ad hoc committee of the National Academy of
Sciences National Research Council that has recently convened to
examine and report on Federal Research Regulations and Reporting
Requirements: A New Framework for Research Universities in the 21st
Century. The committee is expected to identify regulations and reports
that constitute a burden, as well as improved approaches to reduce such
burdens. Its report is due in 2016. This step is in addition to ongoing
activities with the Federal Demonstration Partnership and the NIH
Scientific Management Review Board that also provide valuable input on
ways to reduce administrative burdens.
To help maintain America's leadership in medical innovation, NIH is
also exploring strategies to further encourage the development of
public-private partnerships to enhance innovation, leverage expertise
and resources, and develop solutions to challenging problems. In
addition, NIH is working to maximize the potential of data-sharing
within the scientific community to ensure that scientific findings are
accessible, transparent, and reproducible, which is key to the
identification of emerging trends and breakthroughs on the horizon.
Sharing data facilitates the accessibility of new research findings,
prevents duplicative research efforts, and expands the range of
research questions that can be addressed without generating new data.
Several high-quality repositories for both clinical and non-clinical
data either already exist or are under development.
Question 6. Challenges with the time and costs associated with the
research, development, and approval or clearance of drugs and medical
devices is not a new problem; it is an old problem that has been
recognized time and time again. There seems to be a confluence of
scientific knowledge, opportunity, and will to ensure that we are able
to fully realize the promises that discovery have presented, and we
must leverage this opportunity.
What do you see as the biggest challenges to getting safe
treatments and cures to patients faster?
What do we as Congress need to do?
Answer 6. The process of turning an observation in the laboratory,
clinic, and community into an intervention that can improve the health
of individuals and the public--has great potential but currently is
slow, expensive, and fraught with failure. By studying translation on a
system-wide level, we can nurture the field of translational science to
better understand the scientific and operational principles underlying
the process and improve them to accelerate the process of getting
treatments and cures to patients.
To address these challenges and realize the potential of scientific
discoveries to improve human health substantially, the NIH established
the National Center for Advancing Translational Sciences. NCATS is
``disease-agnostic''; it seeks system-wide insights into what is common
among diseases and the accompanying translational science process. This
approach takes advantage of the increasing appreciation that seemingly
disparate conditions can share underlying molecular causes, and has the
potential to accelerate the development of interventions to treat more
than one disease.
NCATS works with all of NIH, other Federal agencies, and many
external stakeholders to identify and address common scientific and
operational challenges that slow down or even block the translation of
discoveries into treatments, such as finding ways to:
Better predict the safety and effectiveness of potential
drugs as early as possible in the drug development pipeline;
Conduct multi-site clinical trials more efficiently,
including improving recruitment of trial participants; and
Train a well-qualified multi-disciplinary translational
science workforce.
It would be immensely helpful for the Congress to approve the
President's fiscal year 2016 budget level for NIH, which proposes a $1
billion increase over fiscal year 2015 for biomedical research,
specifically including a proposal to raise funding for the Cures
Acceleration Network within NCATS from $9.8 million to $25.8 million in
fiscal year 2016.
senator collins
Question 1. More than 60 percent of cancers in the United States
occur in people age 65 and older, and this percentage will only
increase as the baby boom generation ages. As the Chairman of the
Special Committee on Aging, I remain concerned that people over 65 have
historically been under-represented in cancer clinical trials.
Many older cancer patients do suffer from other serious diseases
and conditions accompanying the aging process, such as high blood
pressure, heart disease, and dementia. While I understand that there
may be concern given these comorbidities, would important lessons
likely be learned about how best to treat older cancer patients if more
were included in the clinical trials?
Answer 1. The relationship of cancer to age is not simple, and not
all cancer types show an increased incidence with advanced age. At the
same time, more than half of cancer cases are diagnosed in patients
over 65 and the number of new cancer cases is expected to rise from 1.7
million today to 2.5 million by 2040. Those increases will occur almost
entirely among people over 65.
Currently approximately two-thirds of patients in clinical trials
are 65 or younger. Despite some increases in the numbers of patients
aged 65 to 75 who now participate in trials, the number of patients
over age 75 who are enrolled in trials remains low. Patients over age
75 represent 10 percent or less of clinical trials enrollment. As
noted, these numbers reflect the prevalence of co-morbidities that may
disqualify such patients from enrollment, as well as other factors,
such as the difficulty of traveling to the sites of trials.
NCI is taking a number of steps to address these challenges,
particularly through the NCI Community Oncology Research Program
(NCORP) and National Clinical Trials Network (NCTN). NCORP Research
Base hubs have disease-specific committees that focus on older adults.
These committees have the responsibility for designing studies on
treatment, cancer control, symptom management, quality of life, and
cancer care delivery addressing the needs of older adult cancer
patients. The NCORP network of investigators, cancer care providers,
and academic institutions aims to bring cancer clinical trials and
cancer care delivery research to individuals in their own communities.
Research in the community setting allows access to a larger and more
diverse patient population in a variety of healthcare locations. This
can accelerate accrual to clinical trials, enable feasibility testing
of promising new interventions, and increase the generalizability of
study findings. NCORP also facilitates patient and provider access to
treatment and imaging trials from NCTN.
Historically, there has also been a tendency to use less aggressive
therapies in older patients with cancer. However, that approach has
been changing in response to several factors. First, many have noted
the importance of distinguishing between chronological age and
physiological age, especially in the oldest population groups, when
making treatment decisions. Older cancer patients who are otherwise in
good health are now likely to receive the same surgery, radiotherapy,
and/or drug therapy as relatively young patients. Moreover, it is
anticipated that fewer side-effects of cancer therapy will occur as
improved surgical methods are developed, radiotherapy is delivered with
greater precision and better division of doses, and drug therapy shifts
from traditional chemotherapy to the more targeted approaches of
``precision medicine.'' In addition, several new immunotherapies--from
the use of therapeutic antibodies to methods to strengthen the activity
of immune cells--may be quite well tolerated by patients at advanced
ages. To obtain the evidence regarding the use of these therapies in
elderly patients, it is important that such patients are included in
clinical trials. NCI continues to support the accrual of a diverse
patient population.
senator hatch
Question 1. As you know, the Obama administration announced its
Precision Medicine Initiative for the purpose of investing in a new
generation of lifesaving discoveries based on the recent advances in
genetic research--for many of which you are responsible by way of your
leadership of the Human Genome Project and the NIH. I understand that
one of the goals of the Initiative is to assemble a data base of one
million volunteers. The Utah Population Data base (UPDB) is a unique
resource that represents more than 7.3 million people connected to 23
million records, including vital statistics and medical records. The
UPDB is the world's largest repository of genealogies, and public
health and medical records, and it has been already a powerful resource
for advancing precision medicine. Using the UPDB, researchers at the
Utah Genome Project (UGP) have so far identified genes that contribute
to more than 30 diseases.
The extensive family histories within the UPDB are made possible by
a cultural emphasis within Utah on large families and carefully
assembled and extensive genealogies, the combination of which aids the
identification of inherited genetic mutations that cause specific
diseases. The data generated by the UGP can become an international
resource for genetic research. Given this brief overview of these
resources, I submit to you the following questions:
Cancers are a major focus of the UGP, and it is also looking at
UPDB families with exceptionally high incidences of leading chronic
diseases. Multigenerational families have already been identified in
which dozens of relatives are affected with the same disease, often at
an unusually early age. With regard to the Precision Medicine
Initiative, what are some of the specific areas that the NIH is
interested in studying in effort to prevent, diagnose, and treat?
Answer 1. The National Institutes of Health (NIH) appreciates your
interest in the President's Precision Medicine Initiative (PMI). The
PMI at the NIH has two main components: a near-term focus on cancers
and a longer-term aim to generate knowledge applicable to the whole
range of health and disease. Both components are now within our reach
because of advances in basic research, including molecular biology,
genomics, and bioinformatics.
The proposed national research cohort of one million or more
volunteers will provide a robust research resource for qualified
investigators to answer a wide range of questions related to the
prevention, diagnosis, and treatment of disease including cancers and
chronic conditions. The PMI will allow investigators to initiate
research on questions that the national research cohort is uniquely
poised to help answer. When the PMI is funded, the NIH Institutes and
Centers will issue requests for applications (RFAs) inviting extramural
investigators to propose ground-breaking precision medicine projects
within the ICs' mission areas. The RFAs will be published after the
Advisory Committee to the Director (ACD) has made its recommendations
to the NIH Director, and the Director has made his decisions regarding
implementation of the PMI at NIH in September 2015.
The PMI efforts hold tremendous promise to improve the ways we
anticipate, prevent, diagnose, and treat cancers. The cancer-focused
component of this initiative will be designed to address some of the
obstacles that have already been encountered in ``precision oncology:''
unexplained drug resistance, genomic heterogeneity of tumors,
insufficient means for monitoring responses and tumor recurrence, and
limited knowledge about the use of drug combinations.
Question 2. UGP researchers are particularly interested in the
practical application of genetic discoveries, including the discovery
of potentially pivotal pathways involved in chronic diseases. Because
the UPDB contains careful genealogy and phenotyping potential, the UGP
has the potential to find rare disease-causing variants that could
point to pivotal pathway targets--such as PCSK9 or sclerostin--for
which novel medicines could be developed. Are such practical
applications a goal of the Initiative? If so, what are some of the
specific areas that the NIH hopes to explore? Do you see the UPDB as
complementary to the mega-national cohort in potentially accelerating
key discoveries?
Answer 2. It is indeed a goal of the PMI to generate the scientific
evidence needed to move the concept of precision medicine into every
day clinical practice. As noted above, the PMI at the NIH has two main
components: a near-term focus on cancers and a longer-term aim to
generate knowledge applicable to the whole range of health and disease.
Furthermore, the initiative will tap into converging trends of
increased connectivity, through social media and mobile devices, and
Americans' growing desire to be active partners in medical research.
The PMI will also need to evaluate the most promising approaches to
bring precision medicine strategies to a broad array of diseases in
much larger numbers of people over longer periods. Toward this end, we
envisage assembling over time a longitudinal cohort of 1 million or
more Americans volunteered to participate in research, which may
include existing health care system cohort, research cohorts, and de
novo recruitment. On March 30, 2015, the NIH assembled a PMI Working
Group of the ACD which delivered a report to the full ACD in September
that articulates a vision for building such a cohort. The resulting ACD
recommendations will significantly inform what kind of resources are
appropriate to include in the cohort in the near and longer term. The
NIH anticipates a varied array of research activities in this new
research platform that will propel our understanding of diseases--their
origins and mechanisms, and opportunities for prevention and
treatment--laying a firm, broad foundation for precision medicine.
Question 3. On February 11-12, 2015, the NIH held a workshop called
``Precision Medicine Initiative: Building a Large U.S. Research
Cohort.'' Although it is the largest genetic research data base, the
UPDB was not invited to participate. Do you see the leaders of the UPDB
and UGP as a valuable resource that should be included in the NIH's
efforts to implement the Precision Medicine Initiative?
Answer 3. To help inform its report, the PMI ACD Working Group
described above gathered inputs from a wide variety of stakeholders
through a series of public workshops over several months on topics
around precision medicine. One of these workshops, held on May 28-29 at
Vanderbilt University, Nashville, TN, focused on recommending the
optimal strategy for designing and assembling the national research
cohort. Stakeholders associated with a wide variety of national
resources were part of this dialog. Notably, Dr. Willard H. Dere,
executive director of the Program for Personalized Health at the
University of Utah, was among our panelists on our key May 28 session
on leveraging existing research cohorts. In addition, a Request for
Information was issued on April 20 inviting stakeholders to help guide
the NIH by providing information on characteristics, purpose, or other
overall aspects in the development and implementation of a large U.S.
precision medicine cohort, and NIH received the input from over 150
researchers and organizations.\2\
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\2\ The RFI may be accessed at http://grants.nih.gov/grants/guide/
notice-files/NOT-OD-15-096.html.
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senator cassidy
Question 1. During a recent visit to NIH, Bill Gates was asked how
he sets funding priorities at his foundation. He answered ``Dollars for
DALYS''. The disability-adjusted life year (DALY) is a measure of
overall disease burden, expressed as the number of years lost due to
ill-health, disability or early death. Does NIH use a disease burden
measurement, such as DALYs, to set funding priorities? If not, what do
you use?
Answer 1. NIH carefully considers several disease burden measures
as indicators of public health need, which is one of several key
factors in priority-setting. Recent studies have shown a significant
positive correlation between various measures of disease burden and NIH
funding levels.\3\ \4\ \5\ However, other complex factors are important
to consider when assessing public health need and the best way for NIH
to fulfill its mission.
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\3\ Gillum LA, et al (2011). NIH disease funding levels and burden
of disease. PLOS One 6(2): e16837.
\4\ Sampat BN, et al (2013). New evidence on the allocation of NIH
funds across disease. The Milbank Quarterly 91(1): 163-85.
\5\ Moses H, et al (2015). The anatomy of medical research: US and
international comparisons. JAMA.
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In the interests of beginning a conversation about the alignment
between NIH funding levels and public health needs, NIH conducted an
exploratory analysis.\6\ Though there are many potential measurements
of disease burden, this analysis used both DALYs and deaths from WHO's
Global Burden of Disease 2010 study, and used both U.S. and global
measurements. The plots show how NIH's funding aligns with these four
measurements of disease burden, though some measurements may be more
appropriate than others for certain conditions. While this analysis has
some caveats, which can be found on the site alongside the plots, NIH
believes that it offers an initial picture of how NIH funding is
informed by public health needs.
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\6\ The results of the analysis are posted at http://
report.nih.gov/info_disease_burden.aspx.
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In addition to public health need, NIH leadership also takes into
account scientific merit, scientific opportunity, and portfolio balance
when deciding how to allocate resources. In short:
Public Health Needs: NIH responds to public health needs,
ranging from emerging infectious disease crises to the growing burden
of chronic disease management, as well as rare disease research.
Scientific Merit: NIH only funds research which has
undergone a two-stage peer review process and which has been judged
highly meritorious.
Scientific Opportunities: NIH constantly assesses its
research portfolio in light of the latest scientific developments.
Significant research advances often occur when new findings, sometimes
completely unexpected, open up new experimental possibilities and
pathways.
Portfolio Balance: NIH strives to ensure the diversity of
NIH's research portfolio. Considerations of balance must include the
ratio of basic research to applied, clinical, and translational, as
well as cellular to behavioral, and animal to human.
Question 2. In 2012, the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) completed an evaluation of
its Centers programs to determine if their methods for funding would
optimally support integrated, synergistic groups of investigators,
based on evolving research needs and forward-looking opportunities.
Although it was a laudable effort, it appears that the evaluation
relied heavily on qualitative measures, such as listening sessions, and
not quantitative measures (such as the Department of Defense's use of
Patents, Products, and Publications) that would be far more objective
and useful. Does NIH use a standard quantitative process to review its
funding decisions? Does NIH collect quantitative data on its funding
decisions? And, is a comparable evaluation done on other NIH Institutes
and Centers?
Answer 2. NIH conducts evaluations of its research programs using a
variety of methods designed to measure the extent to which programs are
operating efficiently and achieving their intended outcomes. There is
value in utilizing both qualitative and quantitative approaches in
these evaluations. For example, qualitative methods such as convening
expert scientific panels, patient-centered focus groups, or conducting
structured interviews provide data on the outcomes of a research
program in regards to patient experience, scientific progress or public
health impact. Quantitative measures may also provide data on outputs
and outcomes that indicate scientific progress or public health impact,
and can include metrics related to publications, patents,
commercialization activities, and clinically relevant outcomes such as
new clinical guidelines. NIH's RePORTER is a publicly available
electronic tool that allows users to search a repository of NIH-funded
research projects for quantitative output measures such as patents,
publications, and published clinical guidelines associated with each
award.
NIH evaluations often utilize a mixed methods approach and are
conducted over several time points because of the long time period over
which outcomes are produced. Qualitative methods such as those
involving expert opinions can provide data throughout the process, but
information should be collected as close as in time to the events in
question to ensure recollections are accurate. On the other hand,
quantifiable products culminating from research may accumulate over a
period of several years, during and after the research project is
completed. For example, publications are among the most immediate
quantitative research outputs, and yet research data must be cleaned,
analyzed, and results reported in manuscripts submitted to scientific
journals. Most journals have a publication lag-time of more than 1 year
from manuscript receipt to publication. Once articles are published,
their full bibliometric impact on the field cannot be assessed for at
least 3 years. Other quantifiable outputs such as patents will take
longer, and clinical outcomes may emerge in an even longer time period
as research results inform clinical care guidelines, which in turn are
implemented into widespread practice.
NIH is actively working to strengthen its evaluation practices.
Improvements are being made to NIH's grants administrative data bases
to better track research outputs and outcomes in automated,
standardized ways. Evaluations of best practices are developed and
shared among staff in the Institutes and Centers through a variety of
means such as regular meetings of the NIH Planning and Evaluation
Officers Committee and interest groups in evaluation and portfolio
analysis, including the Evaluation Special Interest Group and the
Portfolio Analysis Interest Group. In addition, the Institutes and
Centers often collaborate on evaluations of cross-cutting programs and
trans-NIH evaluations are conducted by several programmatic offices
within the Office of the Director.
Question 3. Can NIH provide an analysis of those who serve on NIH
review panels by academic background: those with a degree in Medicine,
those who hold science degrees, and those with both?
Answer 3. Among reviewers who served in fiscal year 2013-14, 73
percent had a Ph.D., 16 percent had an M.D., and 11 percent had both a
Ph.D. and M.D. The distributions of degrees among reviewers mirror
those of our applicant and grantee population, i.e., 55-58 percent of
investigators on R01-equivalent awards from each of these three groups
have served as reviewers in fiscal year 2013 and/or fiscal year 2014.
The composition of NIH peer reviewers closely resembles the composition
of the grantee community in terms of race, ethnicity, and geographic
location. NIH strives to include a diverse group of well-qualified
reviewers in the peer-review process, providing for the best evaluation
and assessment of applications.
senator bennet
Question 1. We look forward to reviewing the work you have
discussed in the President's Precision Medicine Initiative.
As you know, six of the top research institutions have joined
together to form the Oncology Research Information Exchange Network,
known as ORIEN. The University of Colorado is one of the participating
universities.
ORIEN partners have access to one of the world's largest cancer
tissue repositories and data from more than 100,000 patients who have
consented to the donation of their tissue for research.
Can you talk about ORIEN's work and if the NIH plans to coordinate
with ORIEN to achieve the President's Precision Medicine goals?
Answer 1. The Oncology Research Information Exchange Network
(ORIEN) is entirely distinct from the NCI fiscal year 2016 Precision
Medicine Initiative. In response to a request from ORIEN, NCI officials
met with representatives of ORIEN in February 2015. Based on that
meeting, NCI concluded that the exclusivity and commercial focus of the
ORIEN structure contradict longstanding NIH and NCI data sharing
principles.
Under the Precision Medicine Initiative, NCI will assemble and
analyze additional genomic data sets to increase our understanding of
cancer genomes and their relationship to gene variants that a patient
may have inherited. Based on the genomic information we uncover, NCI
will test new therapies against childhood cancers and several common
adult cancers. NCI will also develop better animal and cell-based
models of cancer, study mechanisms of drug resistance, and identify new
therapies and therapeutic combinations to overcome drug resistance. NCI
will build on what it and its research partners have already learned in
ways that will accelerate the pace of discovery and deliver benefits to
patients through clinical practice.
NCI's goals are to develop mechanisms for aggregating, storing, and
analyzing NCI/NIH-supported data sets, genomic and clinical, in a
manner that makes the information useable to all qualified researchers
in a responsible manner.
Question 2. As we debate constant funding cuts in Congress, or the
lack of investment in important priorities like health care and
education, bioscience reform and funding continues to be one area where
we have strong, bipartisan interest.
You've spoken in the past with me about how other countries
approach funding in the life science area.
Can you take a few minutes to discuss with the committee how we
should think about investment in life science innovation--not just as a
domestic priority--but as a global economic priority to keep us
competitive with other nations?
Answer 2. The United States continues to be the largest public
funder of biomedical research worldwide; however, a number of global
indicators show that our competitive position in the life sciences is
weakening. Investment in biomedical research not only improves public
health but also builds new knowledge and technology, leads to
innovation in the form of new goods, services, or processes,
contributes to national competitiveness, improves living standards, and
furthers social welfare. The economic benefits of improved health can
be staggering. Research-related gains in average life expectancy for
the period from 1970 to 2000 have an economic value estimated at $95
trillion, about $3.2 trillion per year. For cancer alone, every 1
percent decrease in death rate has been estimated to be worth between
$440 billion and $500 billion per year, or approximately 4 percent of
the U.S. gross domestic product.\7\
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\7\ Kevin M Murphy and Robert H Topel, ``The Value of Health and
Longevity'' U. Chicago and NBER, 2006. http://www.ucema.edu.ar/u/je49/
capital_humano/Murphy_Topel_JPE.pdf.
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While the economic benefits of investing in biomedical research are
evident, NIH's fiscal year 2015 budget of $30.31 billion represents a
purchasing power cut of almost 20 percent compared to fiscal year 2004.
Relative to the major countries in North America, Europe, and Asia, the
United States now has the slowest annual growth rate in medical
research investment from public and industry sources at 1.0 percent.
China (16.9 percent), Australia (9.3 percent), Japan (6.8 percent),
Canada (4.5 percent), Europe (4.1 percent), and other Asian countries
(20.8 percent) are all increasing their annual investments in medical
research at a faster pace. Since 1992, the United States. has fallen
from second to tenth in overall R&D intensity (R&D investment/GDP = 2.8
percent)--now ranking behind Israel, Sweden, Finland, Japan, South
Korea, Switzerland, Taiwan, Denmark, and Germany.\8\ Despite Europe's
current economic woes, the European Commission has urged its member
nations to increase their investment in research substantially,
recommending budgets of 80 billion Euros ($95 billion) in 2014-20, a 40
percent increase over the previous 7-year period.\9\
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\8\ ``Science and Engineering Indicators 2014'' National Science
Foundation, February 2014. http://www.nsf.gov/statistics/seind14/
index.cfm/chapter-4/c4h.htm#s2.
\9\ http://ec.europa.eu/programmes/horizon2020/en/what-horizon-
2020.
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These trends have resulted in the restructuring of the share of
total global investment. As a percentage of global R&D funding, the
United States declined by approximately 13 percent from 2004 to 2012,
while Asian economies increased by approximately the same share. U.S.
Government funding for medical research, specifically, has decreased to
a 50-percent share of the world's total public research investment,
down from 57 percent in 2004.\10\ There also have been major shifts in
the composition of the global scientific workforce. From 1996 to 2011,
China's science and technology workforce increased 6 percent annually
to reach 1.31 million workers, now making it the largest national
science and technology workforce in the world.\11\
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\10\ Moses et al., ``The Anatomy of Medical Research: US and
International Comparisons'' Journal of the American Medical
Association, 2015. http://jama.jamanetwork.com/article.aspx?
articleid=2089358.
\11\ Ibid.
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Policies related to life sciences R&D affect our Nation's ability
to thrive in an increasingly competitive and knowledge-driven global
economy. A growing number of indicators--from global R&D Investment to
trends in higher education and workforce training--show that expanded
investment and policies designed to enhance the life science industry
have enabled several countries to become strongly competitive with the
United States.
senator warren
Question. Our health care system currently rewards private industry
only for drugs that can be sold either at high cost or in very high
volume. That doesn't work for antibiotics, where dosages are
historically inexpensive and where new antibiotics should be used
sparingly to preserve their effectiveness. Last year, HHS commissioned
a report to assess the impact of different economic incentives for
antibiotic development.
Based on that report and your experience, can you tell the likely
impact of proposals to extend patent life for antibiotics, base
approval on fewer patients, or give small increases in reimbursements
for new products, on the number of new and innovative antibiotics
entering the pipeline?
Policy options to stimulate antibiotic development have been
considered outside of Congress, such as prize competitions, and
decoupling payments from sales volume. What policy options do you think
would be the most likely to increase the number of new and innovative
antibiotics entering the pipeline?
Answer. The HHS report you referenced, entitled Analytical
Framework for Examining the Value of Antibacterial Products, was
commissioned by the Office of the Assistant Secretary for Planning and
Evaluation (ASPE) and conducted by the Eastern Research Group. We defer
to ASPE on report outcomes and impacts.
[Whereupon, at 12:04 p.m., the hearing was adjourned.]