```

[Senate Hearing 114-572]
[From the U.S. Government Publishing Office]

                                                        S. Hrg. 114-572
 
   CONTINUING AMERICA'S LEADERSHIP IN MEDICAL INNOVATION FOR PATIENTS

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

                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS

                          UNITED STATES SENATE

                    ONE HUNDRED FOURTEENTH CONGRESS

                             FIRST SESSION

                                   ON

  EXAMINING CONTINUING AMERICA'S LEADERSHIP IN MEDICAL INNOVATION FOR 
                                PATIENTS

                               __________

                             MARCH 10, 2015

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and Pensions
 
 
 
 
 
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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

                              ----------                              

                        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\
---------------------------------------------------------------------------
    \1\ ``New Drug Approvals in ICH Countries, 2004-2013,'' Centre for 
Innovation in Regulatory Science, R&D Briefing 54, 2014.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \6\ The results of the analysis are posted at http://
report.nih.gov/info_disease_burden.aspx.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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.]

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```