[Senate Hearing 114-476]
[From the U.S. Government Publishing Office]




 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2016

                              ----------                              


                        THURSDAY, APRIL 30, 2015

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:02 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
    Present: Senators Blunt, Cochran, Moran, Alexander, Kirk, 
Cassidy, Capito, Lankford, Murray, Durbin, Mikulski, Schatz, 
and Baldwin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        DOUGLAS R. LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER 
            INSTITUTE
        GARY H. GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND 
            BLOOD INSTITUTE
        JON R. LORSCH, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF GENERAL 
            MEDICAL SCIENCES
        TOM R. INSEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL 
            HEALTH

                 OPENING STATEMENT OF SENATOR ROY BLUNT

    Senator Blunt. The Appropriations Subcommittee on Labor, 
Health and Human Services, and Education, and Related Agencies 
will come to order.
    Certainly, we are pleased this morning to see Dr. Francis 
Collins and the Institute Directors from the National Institute 
of Health (NIH) with us. Glad to have you here to talk about 
the budget. We look forward to your testimony and the 
opportunity to talk with each person on the panel about these 
issues as they come up.
    Throughout history, the practice of medicine has been 
largely reactive. Even today, we have to wait until the onset 
of most diseases before we are able to treat them or begin the 
process of curing them.
    Science does not fully understand the genetic and 
environmental factors that cause major diseases such as cancer, 
diabetes, Alzheimer's disease, and because of that, treatments 
are often imprecise, often unpredictable, and unfortunately, 
often not effective.
    This budget proposes a revolutionary concept of precision 
medicine, an initiative that would really address each 
individual in a precise and often different way, instead of one 
size fits all approach.
    The Precision Medicine Initiative will allow physicians to 
individualize the treatments on patients based on their unique 
genetic make-up. By having access to each individual's genetic 
make-up now, a physician has the potential, we hope, to decide 
not to use or to use specific and targeted drugs.
    As the chairman of the subcommittee, I certainly will 
support this project. I hope we can prioritize and I intend to 
prioritize funding for NIH as one of the things the committee 
does even in a year where our funding challenges are greater 
than they sometimes are.
    We always have funding challenges, at home, at work, and in 
the government, have those funding challenges, but part of that 
challenge is to decide how to prioritize how we spend our 
money, and certainly I am anticipating that this committee will 
be as supportive as we possibly can of not only the Precision 
Medicine Initiative but also of the ongoing work of NIH and the 
promise it holds for the future.
    I look forward to working with you, Dr. Collins, with the 
ranking member, and the members of this committee, as we pursue 
the ideas you are going to bring to the table today, and the 
potential of what can be done of NIH largely and specifically 
at each of the Institutes that are well represented here today.
    We are lucky to have the chairman of the full committee 
with us, and the ranking member of the full committee will be 
here as well. It is a great opportunity for me to get to work 
with Senator Murray, and Senator Murray, if you have an opening 
statement, we will have that before we go to Dr. Collins.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. All right. Thank you very much, Chairman 
Blunt. Dr. Collins, thank you to you and your team for being 
here. It is good to see all of you again, and I look forward to 
this really important discussion today.
    All of us here, today, can agree there is a lot more we 
need to do to keep families and communities healthy and 
continue investing in priorities that strengthen our economy 
from the middle out.
    Of course, the work of the National Institutes of Health 
(NIH) is vitally important to this effort. The NIH supports 
basic research that makes medical advances possible. It gives 
hope to those who are living with chronic and life threatening 
disease and helps drive economic growth and competitiveness.
    We have all been touched in one way or another by the 
research NIH has supported, from its pioneering use of gene 
therapy to treat cancer, to development of antiviral therapies 
to treat HIV, or efforts to reduce the incidence of diabetes 
and pre-term births.
    Biomedical research is an important investment to ensure 
our government works for all of our families. The investments 
we make in NIH as well as in education and other programs in 
this bill that is supported indirectly will help ensure that 
America's workforce in the years ahead will be able to create 
and take on the jobs of the 21st Century.
    That is why like Chairman Blunt referenced, I am deeply 
troubled by the steady erosion of NIH's purchasing power over 
the last decade.
    I am equally concerned about the similar erosion that has 
occurred in many other categories of the budget that are 
essential to promoting a strong and growing middle class, 
whether it is funding for rebuilding our roads and bridges or 
for PELL grants or child care block grants.
    Making sure that we are investing responsibly in our 
national priorities like research, infrastructure and education 
remains one of my highest priorities.
    Of course, last month the Senate debated and passed a 
budget resolution, and unfortunately that budget proposal and 
the one that was passed by the House, falls short of the 
funding levels that we do need to ensure stable and increasing 
support for NIH and other priorities.
    I am very proud, as you will remember, back in 2013, 
Democrats and Republicans were able to reach a budget agreement 
to roll back sequestration for fiscal years 2014 and 2015. 
Rather than going back to the days of uncertainty and 
shortsighted counterproductive cuts, we have to build on that 
bipartisan agreement and replace those automatic spending cuts 
for 2016 and beyond.
    The President's budget would do just that, by fully 
replacing sequestration of defense and non-defense 
discretionary spending. That approach makes it possible to 
provide a $1 billion increase in funding to support NIH efforts 
in increasing our understanding of the human brain and 
addressing the growing threat of antibiotic resistant bacteria, 
or advancing work on developing an universal flu vaccine, or 
finding treatments and cures for diseases that cause suffering 
and cut lives short.
    Their budget also supports a bold new initiative to exploit 
the recent advances in genomics, molecular biology, and data 
management, to support the shift from one size fits all 
medicine to one tailored to specific individuals.
    Precision medicine holds great promise for future advancing 
the treatment of cancer and ultimately the full spectrum of 
disease.
    I am very proud that my home State of Washington is home to 
several institutions that have really been pioneers in the 
field, and that includes Fred Hutchinson Cancer Research 
Center, the University of Washington, which are using precision 
medicine technology today to tackle breast cancer, eye disease, 
and Alzheimer's disease.
    Dr. Collins, the clinical researchers I met with back home 
believe these new approaches are going to transform the field 
of medicine, and I know that is something you agree with.
    While there is much opportunity, however, funding 
constraints have made it harder than ever for new researchers 
to land their first grant. The private sector funds very little 
basic biomedical research, leaving researchers dependent on a 
stretched pool of funding of NIH funding.
    I am very pleased to see, Dr. Collins, that your budget is 
sensitive to the problem, and focuses on leveraging NIH's 
resources to identify and support innovative and exceptional 
junior scientists. This is just one of the challenges the NIH 
faces in what many feel is a remarkable time for medical 
research.
    I really am hopeful that Democrats and Republicans can come 
together again this time and build on the bipartisan foundation 
that was set in last Congress so that we can make the 
investments we need to seize on these opportunities that are so 
important for our families and our economy.
    Thank you very much, Mr. Chair.
    Senator Blunt. Thanks, Senator Murray. Dr. Collins, we are 
eager to hear from you.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Good morning, Chairman Blunt, Ranking Member 
Murray, Chairman Cochran, members of the subcommittee. It is an 
honor to appear before this panel given its long history of 
supporting the National Institutes of Health (NIH's) mission to 
seek fundamental knowledge and apply it in ways that enhance 
human health, lengthen life, and reduce illness and disability.
    [The graphic follows:]
    
    

    As a Federal research agency, we are acutely aware that to 
achieve our mission we must serve as effective and efficient 
stewards of the resources provided by the American people.
    [The graphic follows:]
    
    

    One way we are doing this is by focusing on prioritization 
of NIH resources. This involves developing advanced methods of 
portfolio analysis, identifying compelling scientific 
opportunities, fostering creative trans-NIH collaborations, and 
enhancing the use of the Common Fund.

                      PUBLIC-PRIVATE PARTNERSHIPS

    We are also forging novel interagency partnerships, like 
the NIH-DARPA-FDA project to build human biochips for testing 
drug toxicity like the one I am holding, as well as innovative 
public/private efforts, like the Accelerating Medicines 
Partnership, that is seeking to identify new drug targets for 
Alzheimer's disease, Type II diabetes, and autoimmune 
disorders.
    [The graphic follows:]
    
    

    To help set priorities, we are developing an overarching 
NIH strategic plan to be linked with individual Institute and 
Center plans, and this will set the stage for the future of 
biomedical research.
    [The graphic follows:]
    
    

    We are also working to optimize the peer review process to 
enhance the diversity, the fairness, the rigor, and the 
reproducibility of NIH supported science, and finally, we 
remain firmly committed to strengthening and sustaining the 
biomedical workforce by incentivizing early stage young 
investigators and revitalizing physician scientists training.
    [The graphic follows:]
    
    

    With these goals in mind, we are confident, we will be able 
to support the best science while advancing our core mission 
and inspiring public trust. We take this stewardship 
responsibility with great seriousness.
    Let me assure you the future of biomedical research has 
never been brighter, thanks in large part to NIH's strong 
support of basic science, the foundation for discoveries that 
have long made America the world leader in biomedicine.
    One exciting example is the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) initiative. This 
bold, multi-agency effort is enabling development of innovative 
technologies such as what you see here on the screen, to 
produce a dynamic picture of how individual brain cells and 
neural circuits interact in time and space. This initiative 
will give us the tools for major advances in brain diseases, 
from Alzheimer's and autism to schizophrenia, epilepsy, and 
traumatic brain injury.
    [The graphic follows:]
    
    

    Scientific advances are also accelerating progress towards 
a new era of precision medicine. Historically, doctors have 
been forced to base most of their treatment recommendations on 
the expected response of the average patient.
    [The graphic follows:]
    
    

    Recent advances, including the plummeting costs of DNA 
sequencing, now make it possible for us to apply a more precise 
approach that takes into account individual differences in 
genes, environment, and lifestyle.
    [The graphic follows:]
    
    

    With this in mind, we at NIH are thrilled to take a lead 
role in the multi-agency Precision Medicine Initiative.
    [The graphic follows:]
    
    

    In the near term, this initiative will focus on cancer. 
Such research will include efforts to understand why cancers 
develop drug resistance, explore non-invasive ways of tracking 
therapeutic response, and test new treatments aimed at the 
genetic profiles of a wide range of cancers.
    [The graphic follows:]
    
    

    As a longer term goal, NIH will launch an unprecedented 
national research cohort of one million or more volunteers who 
will play an active role in how their genetic and environmental 
information is used to develop new strategies for disease 
management and prevention. There is no better time than now to 
embark on this enterprise and move this precise personal 
approach into virtually all areas of health and disease.
    [The graphic follows:]
    
    

    In closing my opening remarks, let me share a story that 
highlights the promise of precision medicine and puts a human 
face on it. Seven years ago at the age of 12, Elana Simon 
received a devastating diagnosis, a rare and often fatal type 
of pediatric liver cancer called fibro lamellar hepatocellular 
carcinoma, quite a mouthful.
    This disease was poorly understood and there were no 
effective drug treatments. Elana was fortunate to have been 
diagnosed early enough that with surgery to remove most of her 
liver, she successfully beat cancer.
    [The graphic follows:]
    
    

    The story does not end there. Four years after her surgery, 
Elana began interning in her father's lab at Rockefeller 
University, reaching out through social media, this determined 
young woman found 15 other individuals with this same cancer, 
and their tumors, including hers, could then be subjected to 
complete DNA sequencing.
    [The graphic follows:]
    
    

    The results were nothing short of remarkable. Elana 
identified a genetic mutation that appeared to be driving the 
cancer in all of the cases, every single one, providing a 
target for a designer drug that is now under active 
development. Since then, Elana has published her findings in 
the journal of Science, participated in the White House Science 
Fair, entered Harvard, and introduced the President at the 
White House launch of the Precision Medicine Initiative.
    [The graphic follows:]
    
    

    This is the kind of scientific success we want to see 
replicated over and over. With your help, the time is now to 
accelerate the pace of such breakthroughs.
    [The graphic follows:]
    
    

    Dr. Collins. Thank you, Mr. Chairman. My colleagues, who I 
would like to briefly introduce, and I welcome your questions.
    To my left, Dr. Anthony Fauci, the Director of the National 
Institute of Allergy and Infectious Diseases; Dr. Gary H. 
Gibbons, Director of the National Heart, Lung, and Blood 
Institute; Dr. Thomas Insel, Director of the National Institute 
of Mental Health; Dr. Douglas Lowy, who has recently been 
appointed as the Acting Director of the National Cancer 
Institute, and Dr. Jon R. Lorsch, Director of the National 
Institute of General Medical Sciences.
    Thank you.
    [The statement follows:]
         Prepared Statement of Francis S. Collins, M.D., Ph.D.
    Good morning, Chairman Blunt, Ranking Member Murray, and 
distinguished Members of the Subcommittee. 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 to present the 
Administration's fiscal year 2016 budget request for the NIH, and 
provide an overview of our central role in enhancing the Nation's 
health through scientific discovery.
    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. I can report to you 
today that NIH leadership, employees, and grantees continue to believe 
passionately in that mission.
    As a Federal research agency, we are also acutely aware that in 
order to achieve our mission we must serve as effective and efficient 
stewards of the resources we have been given by the American public. 
One way in which we are accomplishing this is by focusing intensively 
on prioritization of NIH resources. This involves developing and 
applying advanced methods of portfolio analysis, identifying the most 
compelling scientific opportunities within each Institute and Center, 
fostering creative trans-NIH collaborations, and enhancing use of the 
Common Fund. We are also implementing novel external partnerships like 
the NIH-DARPA-FDA project on a human biochip for testing drug toxicity, 
and the Accelerating Medicines Partnership with ten pharmaceutical 
companies to develop the next generation of drug targets for 
Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and lupus. 
To support this focus on priority setting, we are developing an 
overarching NIH strategic plan, and will be linking this with 
individual Institute/Center (IC) strategic plans that reflect the rapid 
current progress in bioscience. We are also working to optimize the 
peer review process to enhance diversity, fairness, and the rigor and 
reproducibility of NIH-supported science. And finally, we remain 100 
percent committed to strengthening and sustaining our most important 
resource, the scientists who do this critical work, by incentivizing 
early stage young investigators, revitalizing physician-scientist 
training, and increasing the diversity of our research workforce. With 
these goals in mind, we are confident we will be able to support the 
best and brightest ideas, while maintaining our core mission and 
inspiring public trust in the world's premier biomedical research 
agency.
    NIH has been advancing the understanding of health and disease for 
more than a century, and many of our contributions stem from our 
Nation's commitment to investing in basic science research. Basic 
science lays the foundation for advances in disease diagnosis, 
treatment, and prevention by providing the building blocks for clinical 
applications. Basic science is generally not supported in the private 
sector, and NIH's focus on understanding fundamental biological 
processes fosters innovation and ultimately leads to effective ways to 
treat complex medical conditions. Our successful investment in basic 
science is reflected by the awarding of no less than 145 Nobel prizes 
to NIH-supported scientists; the vast majority of these individuals 
were recognized for basic science advances.
    A compelling current example of how basic science is 
revolutionizing the future of biomedical research is in a potential 
treatment for the deadly Ebola virus. The experimental Ebola treatment, 
ZMapp, received a lot of attention last summer when it was shown to 
provide protection in a non-human primate model, but was in very short 
supply and had never been rigorously tested in humans. ZMapp is a 
cocktail of three monoclonal antibodies directed against the coat 
protein of the virus. But it's important to know where those antibodies 
actually bind to the protein, and how that would interfere with Ebola's 
ability to infect cells. NIH-supported researchers at The Scripps 
Research Institute in California set out to answer these questions. 
Using a high-resolution imaging technique called single-particle 
electron microscopy, the researchers recently mapped in exquisite 
three-dimensional detail the binding of the ZMapp antibodies on the 
surface of the Ebola virus.\1\ The images revealed that two of the 
three antibodies work by neutralizing the virus, by preventing it from 
attaching to and fusing into the host cell, while the third antibody 
acts as a beacon, alerting the host immune system that the virus has 
invaded and must be destroyed. Not only has this elegant experiment in 
basic structural biology provided the scientific rationale for ZMapp as 
an effective Ebola treatment--something we are actively testing in 
clinical trials--it also provides key information for the development 
of additional therapies for this rapidly mutating virus. Moreover, it 
illustrates the power of this three-dimensional imaging technique to 
identify targets for future drugs and vaccines.
---------------------------------------------------------------------------
    \1\ Structures of protective antibodies reveal sites of 
vulnerability on Ebola virus. Murin CD, Fusco ML, Bornholdt ZA, Qiu X, 
Olinger GG, Zeitlin L, Kobinger GP, Ward AB, Saphire EO. Proceedings of 
the National Academies of Sciences. 2014 November 17.
---------------------------------------------------------------------------
    Another way we are trying to unravel life's mysteries through basic 
science is with the Brain Research through Advancing Innovative 
Neurotechnologies (BRAIN) Initiative--and we are grateful to this 
subcommittee for its fiscal year 2014 and fiscal year 2015 support, and 
hope to ramp this up further in fiscal year 2016. This bold, multi-
agency effort to revolutionize our understanding of the human brain 
will enable the development and use of innovative technologies to 
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, and 
thought. Ultimately, the technologies developed under the BRAIN 
Initiative may help reveal the underlying pathology in a vast array of 
brain disorders and provide new therapeutic avenues to treat, cure, and 
prevent neurological and psychiatric conditions such as Alzheimer's 
disease, autism, schizophrenia, epilepsy, traumatic brain injury, and 
addiction.
    Scientific advances are also accelerating progress toward a new era 
of personalized medicine. Historically, physicians have had to make 
most 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. With this in mind, we are excited to take 
a lead role in the multi-agency Precision Medicine Initiative (PMI). A 
near term goal of the PMI focuses on cancer; cancer research has been 
leading the way in precision medicine for many years, 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 
demonstrating clinical benefits, 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 will also launch a 
national research cohort of one million or more volunteers who will 
play an active role in how their genetic, environmental, and medical 
information is used for the prevention of illness and management of a 
wide array of chronic diseases. The goal will be to expand the benefits 
of precision medicine into myriad aspects of health and health care. 
Voluntary participants will share clinical data from electronic health 
records, results of imaging and laboratory tests, lifestyle data and 
environmental exposure recordings tracked through real time mobile 
health devices, and genomic information. Participants will be at the 
center of the project design, and they will have access to their own 
health data, as well as research using their data, to help inform their 
own health decisions. Through this dynamic community, researchers will 
be able to advance the information derived from this cohort into new 
knowledge, approaches, and treatments. 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 individualized approach into 
everyday clinical practice.
    Another way we are turning discovery into health is in our efforts 
to combat the problem of Antimicrobial Resistance (AMR). Because most 
bacteria, viruses, and other microbes multiply rapidly in a short 
period of time, they can evolve and develop resistance to antimicrobial 
drugs. Public health surveillance has documented an alarming increase 
in AMR, especially those strains that cause hospital-acquired 
infections. Each year in the United States, more than two million 
people acquire serious infections from bacteria that are resistant to 
antibiotics designed to treat those infections, and approximately 
23,000 of these people die. Recognizing the growing public health 
threat of AMR, NIH is engaged in the Administration's National Plan to 
Combat Antibiotic Resistant-Bacteria--a multi-agency venture, in 
collaboration with the U.S. Food and Drug Administration, the U.S. 
Department of Agriculture, and the Centers for Disease Control and 
Prevention, designed to reverse these disturbing trends. To this end, 
we will expand efforts to develop new antibiotics, like the teixobactin 
recently identified by an NIH grantee that shows great promise against 
the difficult-to-treat infections, methicillin-resistant Staphylococcus 
aureus (MRSA) and resistant tuberculosis. We will work to develop a 
rapid diagnostic test for resistant organisms that will be of critical 
clinical and public health utility. With this goal in mind, the 
National Institute of Allergy and Infectious Diseases recently awarded 
funding for nine research projects supporting enhanced diagnostics to 
rapidly detect antimicrobial-resistant bacteria. We will also build a 
national genome sequence database on all reported resistant human 
infections. And we will create a rapid response clinical trial network 
that is ready to test new antibiotics on individuals infected with 
highly resistant strains of bacteria.
    Preventing disease has always been a top priority for NIH, and 
influenza is one area of prevention in which we are poised for 
significant progress. Currently, to provide protection against the 
rapidly evolving influenza virus, a new vaccine must be produced each 
year. Despite our best efforts, some guesswork is involved, and the 
vaccine isn't always ideal--as we know all too well after this 
particularly difficult flu season. In an average year, the flu claims 
up to 49,000 American lives and costs the U.S. economy about $87 
billion. But it does not have to be that way. NIH-funded researchers 
continue to move forward on a universal flu vaccine--designed to 
produce broad protection against virtually all strains of the flu for 
extended periods of time and, thus, potentially reduce the need for 
annual flu shots and the risk of a global pandemic. I am happy to 
report that universal flu vaccine candidates have now moved into early 
stage clinical trials.
    So far, I've described for you several examples of NIH's commitment 
to basic, translational, and clinical research. But, none of this would 
be possible without a diverse and talented biomedical workforce. 
Recruiting and retaining the brightest minds regardless of race, 
ethnicity, gender, disability, and socioeconomic status is critically 
important not only to NIH, but to the entire American scientific 
enterprise. That is why we are taking new and aggressive steps to 
attract the most talented individuals from all groups. The BUilding 
Infrastructure Leading to Diversity (BUILD) Initiative is a bold 
experiment, consisting of a set of training awards designed to attract 
a diverse array of students into the training pipeline and encourage 
their futures as NIH-supported researchers. In addition to BUILD, we 
also established the National Research Mentoring Network (NRMN). The 
network establishes a nationwide, interconnected set of skilled mentors 
linked to mentees from a variety of scientific and social backgrounds. 
These efforts should strongly support our goal to enhance the diversity 
and maximize the talent of the biomedical workforce.
    While all of these exciting research efforts and scientific 
opportunities are leading to a much deeper understanding of health and 
human disease, much more work needs to be done. The NIH has lost 
approximately 22 percent of its purchasing power for research since 
2003, and the likelihood that a grant applicant will achieve funding 
after peer review has fallen to the lowest in decades, now less than 20 
percent. Other countries are expanding their support for medical 
research. To put NIH back on an increasingly stable trajectory, the 
President's fiscal year 2016 budget request for the NIH is $31.311 
billion, $1 billion or 3.3 percent above the enacted fiscal year 2015 
level. This budget request reflects the President's and the Secretary's 
commitment to improving the health of the Nation and to maintaining our 
Nation's leadership in the life sciences. The request highlights 
investments in innovative research that will advance fundamental 
knowledge, and speed the development of new therapies, diagnostics, and 
preventive measures to improve public health, including $200 million 
for the Precision Medicine Initiative and an additional $100 million to 
combat AMR.
    The fiscal year 2016 budget request will enhance NIH's ability to 
support cutting-edge research and training of the scientific workforce. 
Within this budget, we will increase Research Project Grants (RPGs), 
NIH's funding mechanism for investigator-initiated research. NIH 
expects to support 10,303 new and competing RPGs in fiscal year 2016, 
an increase of 1,227 above the fiscal year 2015 estimate. The budget 
request allocates resources to areas of the most extraordinary promise 
for biomedical research, while maintaining the flexibility to pursue 
unplanned scientific opportunities and address unforeseen public health 
needs.
    I have provided you with examples of how investments in biomedical 
research through NIH are advancing human health, spurring innovations 
in science and technology, stimulating economic growth, and laying the 
groundwork for the future of the United States biomedical research 
enterprise. We have never witnessed a time of greater promise for 
advances in medicine than right now. With your support, the future of 
medicine can be very bright.
    This concludes my testimony, and I look forward to answering your 
questions.
                                 ______
                                 
              Prepared Statement of Anthony S. Fauci, M.D.
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2016 budget request for the 
National Institute of Allergy and Infectious Diseases (NIAID) of the 
National Institutes of Health (NIH). The fiscal year 2016 budget 
request for NIAID is $4,614,779,000 which is $255,938,000 more than the 
fiscal year 2015 enacted amount of $4,358,841,000.
    For decades, NIAID has made important contributions to the 
development of diagnostics, therapeutics, and vaccines for infectious 
and immune-mediated diseases.
                      infectious diseases research
    HIV/AIDS.--NIAID's long-term investment in HIV/AIDS research has 
revolutionized HIV prevention and treatment, including the development 
and refinement of antiretroviral therapies to treat and prevent HIV 
infection. NIAID also is pursuing several promising approaches in HIV 
vaccine development. For example, NIAID is building on the findings 
from RV144, the first HIV vaccine trial to show modest efficacy. New 
Phase I/II trials will use improved adjuvant and booster shot 
strategies in an attempt to increase the protective effect observed in 
RV144. NIAID Vaccine Research Center (VRC) scientists and grantees also 
are advancing HIV vaccine design by studying how certain antibodies 
neutralize HIV and how vaccines could induce the most powerful of these 
antibodies. In addition, NIAID is supporting research on alternatives 
to long-term antiretroviral treatment for HIV, such as passive transfer 
of anti-HIV antibodies as well as gene therapy approaches that may make 
an HIV-infected person's cells resistant to HIV infection.
    Ebola.--NIAID was well-positioned to respond rapidly to the Ebola 
outbreak in West with government and industry partners, developed and 
conducted early-stage clinical testing of an experimental Ebola vaccine 
called cAd3-EBOZ. This candidate and another product, VSV-ZEBOV, 
supported in part by NIAID, entered large-scale clinical trials in 
Liberia in February. These trials are led by a Liberia-U.S. clinical 
research partnership and will examine safety and efficacy of the 
vaccines. In late February, the research partnership also launched a 
trial in Liberia and the United States to test the investigational drug 
ZMapp, a combination of three monoclonal antibodies against Ebola. In 
addition, NIAID conducts Ebola clinical research at the Special 
Clinical Studies Unit in the NIH Clinical Center. The Unit is 
designated to provide state-of-the-art care in a research setting to 
U.S. citizens who become infected with infectious diseases requiring 
high containment such as Ebola.
    Influenza.--During the current influenza season, we have observed a 
mismatch between circulating influenza strains and this season's 
influenza vaccine. The mismatch and resulting low vaccine effectiveness 
have highlighted the importance of NIAID efforts to develop a universal 
influenza vaccine that could generate long-lasting protection against 
multiple influenza strains without the need to frequently reformulate 
the vaccine. NIAID, in collaboration with the Biomedical Advanced 
Research and Development Authority (BARDA) and the Centers for Disease 
Control and Prevention, is planning a Phase I clinical trial to 
investigate the human immune response to universal influenza vaccine 
candidates. In addition, VRC scientists at NIAID are developing a 
ferritin nanoparticle influenza vaccine that may improve the potency 
and durability of seasonal influenza vaccination.
    Malaria.--NIAID continues to make research progress against 
malaria. An early-stage trial at the NIH Clinical Center showed that an 
NIAID-supported vaccine candidate composed of weakened malaria 
sporozoites was safe and protected against malaria. NIAID has begun 
trials in Africa to test this candidate against naturally occurring 
malaria infections. In addition, NIAID scientists have identified 
genetic mutations that make malaria parasites resistant to artemisinin, 
a key drug for treating the disease.
    Other Infectious Diseases of Domestic and Global Health 
Importance.--NIAID-supported researchers are combating emerging and re-
emerging infectious diseases worldwide. Recent advances include 
clinical studies of candidate vaccines for the mosquito-borne viruses 
dengue and chikungunya, progress in understanding the emergence of 
Middle East Respiratory Syndrome (MERS) coronavirus, and new genetic 
clues to illness caused by enterovirus D68. NIAID also is working to 
address hepatitis C virus (HCV). Novel HCV antiviral drugs have greatly 
improved therapeutic options. NIAID scientists have pioneered shorter 
courses of treatment with these novel drugs, finding in some cohorts 
that triple-drug regimens can cure 90 to 100 percent of HCV patients in 
just 6 weeks.
    In addition, NIAID is playing an important role in the White 
House's initiative on Combating Antibiotic-Resistant Bacteria. Key 
NIAID efforts in antibacterial resistance (AR) research include 
sequencing bacterial genomes for a national database; co-sponsoring a 
monetary prize with BARDA to encourage development of rapid 
diagnostics; and supporting an AR-targeted clinical research network. 
NIAID also is supporting the discovery of new antimicrobial treatments. 
The novel drug teixobactin, identified from soil bacteria by NIAID 
grantees, is effective against several antibiotic-resistant bacteria in 
laboratory testing, and similar approaches could yield additional drug 
candidates.
          research on immunology and immune-mediated disorders
    NIAID continues to make important advances in the treatment and 
prevention of immune-mediated disorders. NIAID's Immune Tolerance 
Network recently showed that early introduction of peanut into the 
diets of infants at high risk for peanut allergy was safe and led to an 
81-percent reduction in subsequent peanut allergy. NIAID is convening 
clinicians, professional groups, and other stakeholders to revise 
current clinical practice guidelines to implement this groundbreaking 
finding.
    Multiple sclerosis (MS) is a chronic autoimmune disease and one of 
the most common neurological disorders of young adults. NIAID-funded 
researchers found that autologous stem cell transplants after high-dose 
immunosuppression halted progression of the most common form of MS in 
nearly 80 percent of participants.
                               conclusion
    NIAID research on infectious and immune-mediated diseases has 
spurred the development of vaccines, therapeutics, and diagnostics to 
improve the health of millions globally and has enhanced our ability to 
respond rapidly to emerging and re-emerging infectious diseases such as 
Ebola virus disease and influenza.

                           PRECISION MEDICINE

    Senator Blunt. Thank you, Dr. Collins. We will start with 5 
minutes rounds, and we will have as many rounds as we can while 
we have this great opportunity to talk to you and about what 
the NIH is doing.
    Precision medicine is, obviously, a long way into the 
future and it might very well define most medicine at some 
future point. What would you see as the 5 and 10 year short 
term markers to look at to see whether we are getting where we 
all would like to get as we move toward this Precision Medicine 
Initiative?
    Dr. Collins. I very much appreciate the question. This is 
something we are all quite excited about, and actually we just 
concluded yesterday a 2 day public workshop trying to map out 
exactly that kind of issue, what kind of uses could a cohort of 
a million individuals be put to if that were present 5 years 
from now.
    As an example, we really do not at the present time have 
the ability to take full advantage of what we have learned 
about individual differences in drug response and see how those 
work in the real world.
    The FDA has on the label now more than 100 drugs 
information that say knowing the genetic information about the 
patients would be useful in this situation in order to choose 
the right dose and make sure it is the right drug for that 
patient. In practice, that is not happening. The logistics are 
not there.
    Imagine you have a million people whose complete genomes 
have already been determined with their full participation and 
permission, and are available with a click of a mouse so that 
when a decision is being made about writing a prescription, it 
is possible for the healthcare provider to immediately know 
whether the dose needs to be adjusted or whether that is just 
the wrong drug for that person.
    We could then really rigorously test what is gained by that 
additional information in terms of outcomes, and a large scale 
study of this sort, which is currently not possible, would make 
that happen. That would be an example.
    I want to turn to my colleague, Dr. Lowy, because the other 
part of the precision medicine effort is this early focus on 
cancer, which I think will reap rewards maybe even sooner than 
the process of getting this million cohort underway.
    Dr. Lowy. Thank you, Dr. Collins. Thank you, Senator Blunt, 
for your comment and your strong support for NIH.
    We really are at an inflection point where it comes to 
cancer treatment. As a result of the genomic revolution, we now 
understand in much more detail than ever before that cancer 
instead of being one disease, even breast cancer, for example, 
is many different diseases, and the opportunity for targeted 
treatments that we hope will be better, smarter, and have fewer 
side effects, really is at hand.
    We already have several clear examples of targeted FDA 
approved drugs that are able to do just that. With the new 
Precision Medicine Initiative, we are able, at a much larger 
scale, to be able to conduct clinical trials that involve both 
adults and children, that instead of being focused principally 
on the organ site where the cancer develops, instead is focused 
on the abnormalities in the cancer, and the targeted drugs to 
treat those specific abnormalities.
    I have gone into this in more detail in my written 
comments, but I just wanted to highlight for you some of the 
key elements.
    Senator Blunt. Dr. Collins, the million person cohort, how 
would you intend to assemble that and put that information 
together to start with?
    Dr. Collins. That is very much a topic of intense 
conversation right now. We have put together a working group of 
experts who met this week and who will meet again each month 
between now and August. In fact, the next meeting, which is 
actually going to be in Senator Alexander's State, in Nashville 
at Vanderbilt, will look at this very question, what is the 
ideal kind of cohort that you want to achieve as far as 
demographics.
    We believe that we can accomplish some of this by taking 
advantage of cohorts that have already been put together by 
various healthcare delivery systems or perhaps by the Veterans 
Administration, and therefore, be able to do this more cheaply 
than if you had to start from scratch.
    Undoubtedly, there will be gaps in terms of the 
representation. We want to be sure, for instance, that this has 
power to be able to tell us things about health disparities. We 
will need to figure out how to fill those gaps.
    By August, this working group will make strong 
recommendations, and we will then be ready starting in fiscal 
year 2016, which of course, is not far away, to initiate the 
process of putting this cohort together.
    Senator Blunt. Thank you. Senator Murray.

    REPRESENTATION OF U.S. POPULATION IN MILLION PERSON COHORT STUDY

    Senator Murray. Let me just follow on that, the million 
person research cohort is very intriguing, but has to be done 
right. How do you ensure it successfully represents all 
elements of the U.S. population, women, minorities?
    Dr. Collins. We very much want to have that kind of ability 
to sample across the population, obviously, women and men, 
obviously multiple different racial and ethnic groups, across 
socioeconomic status, across age.
    With a million, of course, you have the opportunity even in 
some of those subsets to have a lot of people involved. That is 
the point of this, having that kind of power.
    Exactly how we do this is what we have charged this group 
to wrestle with. I think we might want to over sample certain 
minority groups in order to be sure that we have enough 
representation to be able to have powerful observations made 
possible about health disparities.
    Certainly, we will want to be sure that we have involved 
women in at least 50 percent of the population that gets 
studied.
    One more thing I should say. We think of the participants 
in this particular study not just as subjects or patients. They 
are participants. They are our partners. They are going to be 
at the table as we design this study, and are already at the 
table.
    I think that is going to be critical for defining the 
nature of what we are about here. We are asking people to be 
volunteers. We are asking them to share information. They will 
get back lots of information as well. We want them to feel like 
this is an important national program and being part of it is 
something to be proud of.
    Senator Murray. How long will this take?
    Dr. Collins. To assemble the cohort, to put the million 
together, is not going to be an overnight effort. We would 
guess this is going to take at least 3 or 4 years to get the 
entire cohort put together. We would hope, of course, to be 
able to begin to learn things from it even before we have 
reached that very large number.

                           DEMENTIA RESEARCH

    Senator Murray. I want to ask you a specific question. Your 
budget noted that recently two studies have come out, one here 
in the United States and one here in Germany, suggesting that 
the rates of dementia are falling. That is really intriguing 
and sort of unexpected, and if accurate, it is very 
encouraging.
    What is NIH doing to confirm whether those trends are real 
or not?
    Dr. Collins. Senator, we observed those papers as well with 
great interest. It was surprising. I think there is a reason to 
be a little skeptical about whether one can be completely 
confident in the conclusion, which if true, would be quite 
important.
    Much of this data is based upon death certificates. As we 
all know, death certificates often do not accurately record the 
cause of deaths in individuals with dementia. It may say 
pneumonia, or it might say heart failure, when in fact, the 
primary problem was Alzheimer's disease.
    The National Institute on Aging actually does have two 
different studies underway to try to see whether in a rigorous 
epidemiological analysis whether there is evidence to in fact 
point to that decrease in incidence, or whether some of this is 
a diagnosis issue.
    It is possible because there is a vascular contribution to 
Alzheimer's disease, and perhaps we are doing better now in 
managing things in that category of cardiovascular disease, 
that might have resulted in a diminution in incidence or at 
least a delay in the onset.
    We need to really know the answer to that. I appreciate you 
raising it. It is a very hot topic in discussion right now.

              STATUS OF NEW AND EARLY STAGE INVESTIGATORS

    Senator Murray. Yes, I think it is intriguing, especially 
if it is true and it works and it is related to vascular, and 
we learn something, I think that would be outstanding. I will 
be following that, too.
    I wanted to ask you, since 2009, NIH has been monitoring 
the disparities between application success rates for 
experienced investigators versus earlier stage investigators. I 
mentioned this in my opening remarks.
    As you know, the latter experiences significantly lower 
success rates compared to our experienced investigators. While 
securing an initial research project grant has always been 
challenging, we know that, I am very concerned that it is much 
more so for those scientists and physicians who have just 
completed their training and may end up driving promising 
talent from the field.
    Can you tell us what you are doing to level the playing 
field in terms of experienced and less experienced 
investigators?
    Dr. Collins. Senator, I appreciate the question very much 
because this is something I think troubles all of us. I am 
going to ask Dr. Lorsch, who is Director of the National 
Institute of General Medical Sciences, where a lot of our 
training support is, to answer the question.
    Dr. Lorsch. We are very concerned about this, Senator, as 
well. We are looking at a number of different ways to address 
it. In addition to targeting the first application of new 
investigators, I think a critical stage is also their renewal, 
because if you get them into the system and then they are not 
able to renew their application, that is a significant 
vulnerability for them. We are going to be looking at that 
stage as well.
    We have also started a new funding mechanism pilot which is 
a single grant per investigator. We think it is going to be 
considerably more efficient in terms of getting taxpayers more 
for their money, and also more flexible and stable for 
investigators. We will be in the near future, rolling out a new 
investigator version of this pilot program.
    Senator Murray. Okay. I think this is so important. We want 
to inspire people to come in. If they think there is no chance 
or we are losing a lot of our knowledge, as we have an aging 
cohort, I think that is troubling.
    Dr. Collins. If I may say, I think there is no magic that 
will really solve this as long as the budget continues to 
decrease. That is affecting everything, and we are doing 
everything we can to protect those early stage investigators, 
but there are only so many things you can do.
    Senator Murray. Thank you. Thank you, Mr. Chairman.
    Senator Blunt. Chairman Cochran.

                              IDEA PROGRAM

    Senator Cochran. Mr. Chairman, thank you. Dr. Collins, I 
see you and think back about our trip to Mississippi where you 
reviewed the results with local researchers of an IDeA Program. 
That indicated to you, I think, at that time there were 
opportunities for accomplishing breakthroughs in medical 
research among economically challenged citizens.
    I wondered whether the NIH grant success program and 
process has resulted in funding that has led to breakthroughs 
in research for cardiovascular diseases, which seemed to target 
African Americans in greater numbers of percentage of the 
population than others.
    What is your latest information you can provide the 
committee about the need for continued funding for that 
program?
    Dr. Collins. Thank you, Senator. The IDeA Program is one we 
are very proud of and which gives an opportunity for funds to 
be made available through several different kinds of programs, 
the IDeA Network of Biomedical Research Excellence (INBRE) and 
the Centers of Biomedical Research Excellence (COBRE), to 
States that do not have as strong a tradition in terms of 
research intensive universities but who still have remarkable 
talent within their State borders.
    I am going to ask Dr. Lorsch, who oversees the IDeA Program 
now, because it is in his Institute to say a bit about how that 
program is going. We are actually quite excited about it.
    Dr. Lorsch. Thank you very much. The IDeA Program is one of 
my favorite things to talk about. I appreciate the opportunity. 
As you know, the IDeA Program aims to ensure that cutting edge 
biomedical research is being conducted in all 50 States in the 
Nation.
    I think the easiest way to see the importance of this 
program is to think about what biomedical research would look 
like in this country if it were not being conducted across the 
Nation, if it were say only in 25 States.
    If you think about every dimension of research, whether it 
is the kind of research questions being asked, the approaches 
used to address those research questions, or very importantly, 
our ability to attract young talent into the system, something 
Senator Murray addressed as well, those things would all be 
diminished dramatically if cutting edge research were not going 
on throughout the Nation.
    That is why we are very committed to this program and we 
think it is really an essential part of our portfolio.

        STATUS OF ADDITIONAL FUNDING AND CARDIOVASCULAR DISEASE

    Senator Cochran. Thank you. To follow up on the actual 
request, is it your intention to make a formal request for 
additional funding of what is the status of the 
Administration's position?
    Dr. Collins. The IDeA Program in the President's budget 
proposal for fiscal year 2016 is the same as for 2015. The 
reason for that is there was an exceptional increase for the 
IDeA Program going from 2013 to 2014 and we are now just trying 
to normalize those kinds of trajectories for all parts of it. 
You should not take that in any way as a diminution of 
enthusiasm for the IDeA Program.
    Senator, you also asked about cardiovascular disease and 
what that effect has been on minorities, and I cannot help but 
say the place that I often go to look for that information is 
also something that you and I visited in Mississippi, and that 
is the Jackson Heart Study.
    If it is all right, I might ask Dr. Gibbons to say a word 
about the status of that particular study.
    Senator Cochran. Thank you.
    Dr. Gibbons. Thank you, Dr. Collins and Senator. As you are 
aware, we have made tremendous progress in bending the curve 
and reducing coronary disease in this country by over 70 
percent over the last 50 years. There are still pockets of 
communities and segments of our population who have not enjoyed 
the fruits of those advances, including African Americans, 
typically African Americans in the southeast.
    The Jackson Heart Study has really emerged as a national 
treasure in providing us with an opportunity to further 
understand what are the drivers of these disproportionate 
burdens of disease in African Americans.
    Indeed, one example I would give you quickly is we 
recognize there is a great prevalence of end stage kidney 
failure amongst African Americans, five fold more than the rest 
of the population, often driven by high blood pressure, which 
is very prevalent.
    Thanks to the Jackson Heart Study and advances we are 
making in genomics, we are now discovering and funding research 
for discovery of the genetic basis of this predisposition, 
identifying genes such as the APOL1 gene, indeed, sickle cell 
trait, something that was previously thought to be relatively 
benign, as important contributors to these health disparities.
    Moreover, these pathways give us insights into how we 
actually might prevent this disease and actually bend the 
curve, a key driver again of end stage renal disease and 
expenditures for health care in this country.
    Again, you should be quite proud of this national resource 
in Jackson, Mississippi.
    Senator Cochran. Thank you very much, Mr. Chairman.
    Senator Blunt. Thank you. Senator Mikulski.

 HOW WILL AN ADDITIONAL BILLION DOLLARS IMPACT NATIONAL INSTITUTES OF 
                            HEALTH RESEARCH

    Senator Mikulski. Thank you, Mr. Chairman. Dr. Collins and 
all of you, we are so glad to see you once again. We have 
talked among ourselves under the leadership of Senator Blunt. 
We would like for the subcommittee to be able to visit NIH so 
they could talk in more depth and more firsthand to see the 
great work that is being done by the people who work there.
    Of course, you know if you are the Senator from Maryland 
about NIH, Hopkins and University of Maryland. We are glad to 
see you, long-standing friends like Dr. Fauci, to new friends.
    Let me get right to my appropriations question. The 
President has put in his request a $1 billion increase. I want 
to know what that means, and is that enough. I understand NIH 
has lost 20 percent of its purchasing power since the doubling 
ended in 2003 due to inflation.
    I am concerned that yes, although you have more than the 
management capability to set priorities, you are going to have 
to end up picking winners and losers. Winners and losers in the 
United States of America. You cannot dial up an NIH just 
because there is a headline or a world crisis.
    With Dr. Fauci and your leadership during the Ebola crisis, 
and we have turned so long from AIDS, other issues, and so on, 
you cannot dial up a National Institute of Allergies. We want a 
cure for Alzheimer's and we want it yesterday. We all hear 
that, all around this table.
    With the resources that you have, I am concerned. I am 
concerned that while we go for precision medicine, which I 
support, I worry about zip code medicine, the disparity in 
Baltimore this morning between the neighborhood in which I 
live, called Roland Park, and a neighborhood called Harlem 
Park, where they filmed ``The Wire'' about two miles from where 
our disturbances are occurring, it is a 22-year life expectancy 
difference even controlling for violence. I will live to 88 to 
92. That dear lady and that church lady is going to make it to 
maybe 68 to 72.
    I could go on about it. As you know, we have a lot of 
issues here. Dr. Thornton, our Superintendent of Education, 
talked to me about the 85,000 kids that went home fine on 
Monday, 300 created disturbances, unacceptable. We talked about 
how damaged our children are. I said what do you need in the 
school system. He said mental health, mental health, mental 
health. Either my kids are addicted or their caregiver is 
addicted.
    What is $1 billion going to get you to help America with 
all we have to do? I do not want to pick winners and losers 
between the 26 Institutes. What is it that you truly need to do 
the job you need to do to serve America while we are trying to 
do ours?
    Dr. Collins. Senator, thank you, very sobering indeed, the 
stories you just shared about what is happening in Baltimore, 
and I think all our hearts are deeply troubled and wish for the 
best for that fine city.
    We have seen over the course of the last 12 years a 
significant diminution in NIH's ability to do research across 
the board. Our most important resource, the people doing the 
work, are clearly pretty stressed at the moment.
    If you try to plot out what the reasons for that are, and I 
will show you a graph up there, the yellow line is basically 
what our purchasing power is for biomedical research going back 
to 1993, and you can see there was that doubling between 1998 
and 2003, but since that time, we have steadily lost ground. 
The sequester added an additional severe blow to our ability to 
get our work done, taking as it did $1.5 billion away in the 
middle of a fiscal year end from which we have not fully 
recovered.
    The $1 billion in the President's budget would go a long 
way toward putting us back on a stable upward trajectory, and 
we have waited a long time to be able to achieve that. It would 
allow us to give 1,200 additional grants in fiscal year 2016 
compared to the previous year. That would be welcome, indeed.
    It would allow us to do things like the Precision Medicine 
Initiative, which as I said earlier, we would very much want to 
have focus on looking at health disparities with the ability to 
not only get answers as to causes but to come up with 
implementation plans for intervention.
    Senator Mikulski. The $1 billion would help, but what would 
lifting the caps do?
    Dr. Collins. Certainly, if you look at that diagram, you 
can see that we are down more than $10 billion over where we 
would have expected to be if we had stayed on that dotted green 
line, which was the trajectory for NIH going back to about 
1970. It is going to take quite a bit to make up that ground.
    The other thing I might show you is the consequence of that 
for people who are trying to get their research funded by NIH, 
that is the success rate, that is what an investigator who has 
sent their grant into us is facing. You can see going back a 
couple of decades, that has traditionally been in the range of 
25 to 35 percent. More recently, with the flat budgets, 
influenced by inflation, we are down in the zone of 16 to 17 
percent, which is very unhealthy, and has caused, I think, a 
great deal of demoralization.
    Senator Mikulski. I do not understand percentages. What is 
the number?
    Dr. Collins. The number of grants? One out of six would be 
funded at this time.
    Senator Mikulski. How many do you turn away?
    Dr. Collins. That would be five out of six.
    Senator Mikulski. Is it 200? Is it 2,000? What does that 
mean?
    Dr. Collins. I see where you are going. The number of 
grants that we fund in each year at the present time is about 
9,000, so that means we are turning away about 55,000. You know 
what, I do not think I can tell the difference between a grant 
that just made the cut and got funded and one that missed it, 
because in that zone, they are all terrific, so we are leaving 
a lot of great science, maybe half of it, on the table, which 
we would not have done in past years.
    Senator Mikulski. That is a stunning number.
    Dr. Collins. Yes.
    Senator Mikulski. My time is up. I think we have made our 
point. You need at least a 5 percent increase to stay in place 
and to begin to catch up.
    Senator Blunt. Thank you, Senator Mikulski. Senator Moran.
    Senator Moran. Mr. Chairman, I would yield to the next 
Republican or Democrat.
    Senator Blunt. Senator Alexander.
    Senator Alexander. Thanks, Senator Moran. Mr. Chairman----
    Senator Moran. The problem is I cannot find my glasses.
    Senator Alexander. Before he finds his glasses, Dr. 
Collins----
    Dr. Collins. I think we have just seen a parable about the 
importance of precision medicine. One size fits all does not 
always do it.

                  FUTURE OF ELECTRONIC MEDICAL RECORDS

    Senator Alexander. I was trying to think of how to do that, 
and I want my 30 seconds back.
    When we get to one minute, I want to switch to a red tape 
topic, but to begin with, let me start with where the other 
discussions are. I went to the precision medicine announcement 
that the President made to demonstrate support for it. You were 
there. Senator Murray and I are incorporating the President's 
proposal into one of the top priorities of the HELP Committee, 
which is our innovation effort that we are working on with you.
    How important would a properly functioning electronic 
medical record system be to your effort to develop a cohort of 
one million individuals so that you could sequence their 
genomes?
    Dr. Collins. Senator, it would be enormously important. We 
are counting on being able to utilize the advent of electronic 
health records to make this possible, recognizing that at the 
present time, there is a lot of work yet to be done in terms of 
having those become truly interoperable between----
    Senator Alexander. But the faster we get that going, the 
easier it will be to do what you are doing. You mentioned 
clicking the mouse, if you are a doctor and you are prescribing 
a medicine, you want to find whatever the genetic information 
is. If the electronic medical record system is not operating 
well, it makes that more difficult; is that right?
    Dr. Collins. Exactly. Many doctors are a bit frustrated 
about this. I will say----
    Senator Alexander. They are really frustrated about it.
    Dr. Collins. Really frustrated, yes. Your institution, 
Vanderbilt, has been, I think, in the lead here in looking at 
ways to try to make this system more optimized, which is one of 
the reasons we are bringing our next precision medicine 
workshop to that institution.

                         FUTURE COLLABORATIONS

    Senator Alexander. We are going to work on that. The 
Administration and Senator Murray and I are setting up a 
working group to identify the five or six steps that we can 
take to improve the electronic medical record system, so we 
will be working with you on that.
    The day you and I visited last week, on the same day, Dr. 
Venter came by, whom I had never met, which I thought was 
interesting, because if I have it right, the two of you led 
parallel efforts to sequence the genome, one public, one 
private. He said to me that his institute in California also 
plans to identify one million individuals and sequence their 
genomes.
    Based upon the experience that you had earlier when you 
were working in parallel, side by side, is there anything 
comparable about what he is doing and what he is planning and 
what you are planning? Is there anything to learn from the 
early experience about collaboration? That is a lot of 
sequencing.
    Dr. Collins. Yes.
    Senator Alexander. Are they just completely separate? Do we 
know yet?
    Dr. Collins. I think there are wonderful ways to make this 
a collaboration. I ran into him in the hallway after he had 
just been visiting with you, and of course, I have been in 
touch with him repeatedly over the years, and recently made a 
plan to come and visit his Human Longevity Institute there in 
California.
    Exactly what his plan is in terms of who the million people 
are that he will be sequencing has not fully emerged. 
Everything is a bit of a work in progress.
    I promise you there is so much to be gained by working 
collaboratively. One thing that we will be very clear about 
with the public project, once again, is we want this to be a 
project where scientists, researchers with great ideas will be 
able to get access to the data as quickly as possible because 
this will be incredibly valuable as a resource, and that will 
be an important part of the work.
    Senator Alexander. It is an interesting development and 
huge, one million individual cohorts. Has that been done 
before?
    Dr. Collins. No, not in this country and not anywhere. The 
British have a cohort of half a million, but of course, we have 
to be bigger. We also have a very different kind of population. 
The British cohort, which we will also link up with and learn 
everything we can from, because there is a great opportunity 
here for international collaboration, but it is a different 
population.

                REGULATORY AND ADMINISTRATIVE OBSTACLES

    Senator Alexander. We are fortunate to have this robust 
private sector that also is ambitious. I will be interested to 
learn over time whether there is any collaboration between the 
two.
    Let me switch to red tape. You and I talked about this in 
the office. What I want to invite you to do is to submit to the 
committee that Senator Murray and I co-chair and I would 
imagine Senator Blunt and Senator Murray would be interested, 
too, in your list of regulatory obstacles or administrative 
obstacles that make it harder for you to succeed.
    You mentioned you would like to have the money we 
appropriate for 1 year carried over to the next year.
    Dr. Collins. Right.
    Senator Alexander. Like other agencies do. You mentioned 
the amount of paperwork you have to do for scientists to go to 
conferences. You actually mentioned five or six or eight or ten 
other things. Some of them have to do with what the Office of 
Management and Budget requires, I assume, but some of it has to 
do with things that we do.
    I would like to invite you to give those specific 
recommendations to us to see if we can fix them. This 
innovation project we have going means we are going to have a 
law passed, and in that law, we can include some of these 
things. I would also like to include in that whatever we can do 
about the National Academy of Sciences' finding that 42 percent 
of the amount of time an investigator spends on a grant is on 
administrative work.
    You get $24 billion for research that you give to 
universities. If we can reduce by 5 to 10 percent the amount 
that is spent on administrative work, my back of the envelope 
math suggests that is about $1 billion. Senator Mikulski was 
asking about $1 billion. There is $1 billion, which could be 
used for more grants.
    I simply invite you to work with us on that, and while we 
are trying to appropriate more money, we might be able to save 
some money, and that would double the amount of money that 
would be available to you.
    Dr. Collins. Senator, I will be glad to submit that list, 
and I appreciate what you and Senator Murray are doing with 
this innovation project. This could help us a lot getting some 
of these obstacles out of the way.
    Senator Alexander. Mr. Chairman, I said double the amount 
of money available. The savings might double the amount of the 
new appropriation.
    Senator Blunt. Thanks, Senator Alexander. You got your 30 
seconds back and a little bit more, and everybody is doing a 
pretty good job trying to hold to their time, and we will have 
time for a second round if anybody can stay for that, and we 
would like that information when you put it together, Dr. 
Collins, for this committee as well.
    [The information follows:]

  --Enhance privacy protections for research participants by 
        strengthening the protection of individual-level genomic data.
  --Remove the restriction prohibiting NCATS from supporting clinical 
        trials research beyond Phase IIb.
  --Raise the Loan Repayment Cap for researchers to make the caps 
        comparable to other loan repayment programs.
  --Reduce reporting requirements and eliminate unnecessary reports.
  --Authorize the Director of NIH to require sharing of data from NIH-
        funded research.
  --Allow NIH to retain payments received for mice and other research 
        substances.

                    COORDINATION OF MEDICAL RESEARCH

    Senator Blunt. Senator Durbin.
    Senator Durbin. Chairman Blunt, thank you very much. Let me 
just say at the outset rather than address the panel, address 
my colleagues. Gathered in this room at this moment are the key 
players in the United States Senate when it comes to this whole 
issue of medical research.

                 HEALTH, EDUCATION, LABOR AND PENSIONS

    Senator Alexander is chairman of the HELP Committee or 
whatever the nomenclature is these days, with his ranking 
member, Senator Murray. Senator Blunt as chairman of this 
Appropriations Committee, again with Senator Murray. My overall 
chairman of the committee, Thad Cochran, and chairman of the 
Defense Appropriations Subcommittee, which I am honored to 
serve on as ranking.
    We have an opportunity here. We know American people are 
skeptical if not cynical about who we are and what we do, but 
my guess is if you had to pick one hearing room on Capitol Hill 
this morning, that virtually every visitor and every family 
would be interested in hearing what is going on, it would be 
this room at this moment.
    There is not one of us that is not vulnerable to some 
medical diagnosis for ourselves or someone we love that could 
be life changing and we pray when we look into the eye of that 
doctor and say is there anything you can do, and he will say 
you are in luck, we just have a new drug, a new surgery, a new 
approach.
    Can I suggest to my colleagues here on both sides of the 
aisle, would it not be significant in our lives and in the 
history of America if we decided to be the driving force to 
make certain we make a statement once and for all about 
biomedical research in the future of this company rather than 
let it be tossed about by the whims of budgets year in and year 
out?
    Senator Cochran, I look at our Defense Appropriations 
Subcommittee, and I chaired it before you, and I said I am 
going to focus on medical research in the Department of 
Defense.
    The first year, we increased medical research by 28 
percent, and the second, 11 percent. I contacted Dr. Collins 
and said are we able to coordinate this so that the flagship 
NIH can work with the Department of Defense, the CDC, the 
Department of Veterans Affairs, even the Department of Energy, 
to make certain we are moving in that direction.
    Before I ask you a question, I just hope that as we think 
about, for example, an infusion of OCO funds, strictly limited 
to the Defense Department, that we kind of stand our ground 
here and say it will not be strictly limited, there are some 
things that need help and this is one of them, and we want to 
put in our bid, and make our stand to make sure that medical 
research, biomedical research, starts moving forward again.
    Dr. Collins suggested to me a couple of years ago 5 percent 
real growth for 10 years. I wish we could do more and calling 
for more. I urge everybody here because gathered in this room 
at this moment are the people who make the decision in the 
United States Senate, and I have talked to each one of you, and 
I know you are all committed to it, so I hope we can reach that 
point.
    Incidentally, congratulations having been chosen to be a 
member of the Irish American Hall of Fame in Chicago, Illinois 
on Saturday night. Congratulations.
    Are we coordinating this research that is going on across 
the Federal Government in medical research?
    Dr. Collins. Thank you, Senator. Yes, I think I can say 
with considerable detail and confidence that we are. You 
mentioned the interactions with the Department of Defense, and 
you and I spoke about that, and we actually went back and 
looked very carefully at our portfolio and theirs to identify 
whether there were areas that were duplicative, and we did not 
find duplication.
    We found synergy. We found great examples of places where a 
particular problem was getting funded by both agencies but in a 
way that covered different parts of the problem.
    We also are working more closely, I would say, than 
probably at any time in history between agencies like FDA, CDC, 
CMS, where we just recently last week had a meeting of senior 
leadership, and with DARPA, where we are working in a whole 
variety of interesting ways to develop a combination of 
engineering and life science approaches.
    I am carrying with me today three different organs on a 
chip. This is a blood brain barrier, by the way. This is a 
kidney. This is a lung. They are all basically taking advantage 
of stem cell. That is a collaboration with DARPA of trying to 
put basically a lot of human biology on a chip to enable us to 
be able to test new drugs, for instance, to see whether they 
are toxic or not.

                         DIVERSITY IN RESEARCH

    Senator Durbin. I probably do not have enough time for you 
to give an adequate answer to this, but yesterday I was visited 
by a pretty well known lady named Barbara Streisand, who is 
pushing for this area of research to make sure that women are 
included in heart research trials. She believes adequate 
attention has not been paid in this area, and some share that 
belief.
    I hope that we are thinking about the appropriate diversity 
in the testing to be able to come up with results that help all 
of us across the country.
    Dr. Collins. Senator, I totally agree with you. I have also 
met with Ms. Streisand, and I think she is a very effective 
advocate for the importance of paying attention to the needs 
for women's health.
    One thing that we have recently done is to insist that 
people who are funded by the NIH who are looking at animal 
models of disease have to study both males and females. 
Traditionally, many of them have studied only one sex, and that 
is clearly leaving out a lot of really important insights.
    Senator Blunt. Thank you, Senator. Senator Moran.

      NATIONAL INSTITUTES OF HEALTH'S STEWARDSHIP OF FEDERAL FUNDS

    Senator Moran. Mr. Chairman, thank you. Dr. Collins, I 
could see you earlier but I could not see what was in front of 
me. Nice to be able to see both. Thank you very much. Thank you 
for being here with your colleagues.
    Dr. Collins, you were in my office late last week, I guess 
it was. We had a conversation. I want to ask you to follow up 
on the conversation, if someone can humbly give you an 
admonition, I tried to give you one.
    You talked about in your testimony the stewardship 
initiative at NIH. In my view, they are related. I want you to 
tell us again, tell us in more detail about what you are 
indicating in your testimony about stewardship at NIH, but I 
want to reiterate what I indicated in my office.
    Many groups, people, individuals, folks afflicted by every 
disease, ask Members of Congress to help NIH to find a cure and 
a solution for their health and their lives.
    We have taken the opportunity to defer to NIH to make the 
decisions about prioritization of medical research. The theory, 
I think, before I arrived in the Senate and became involved in 
this issue, has been scientists should make the decisions about 
where the most promising opportunities are in finding the cure 
or treatment.
    What I want to know from you is that you are fulfilling 
that responsibility, that NIH in the absence of Congress' 
direction about where to focus the dollars, that NIH is making 
the best decisions possible to find the cures that are the most 
readily available and most demanding by our citizens and the 
population of the world.
    In other words, if you do not do that prioritization, then 
I think it is going to become incumbent upon Congress to make 
decisions that are better made by you.
    Dr. Collins. Senator, I appreciate your raising this issue. 
It is a very important one, and even as we hope and pray for a 
lifting of sequester caps that would allow NIH to get back on a 
stable trajectory as well as many other important activities of 
the Government, we take very seriously the importance of 
enhancing our current focus on stewardship, to be sure that we 
are paying absolutely close attention to how every dollar is 
spent.
    Over the course of the past many months, sort of looking at 
areas of that sort, we have in fact quite a vigorous plan here 
in terms of how to put forward those stewardship initiatives.
    One is to develop an overarching NIH strategic plan 
covering our entire 27 Institutes and Centers, each of which 
has had its own strategic plan, but we have not had those 
synthesized into an overarching document that can guide our 
priority decisions. We will have that and will submit it by 
next December.
    We also can use new methods that are actually much more 
sophisticated than what we have had in the past to do a 
portfolio analysis and see exactly where are our dollars 
currently going, are there gaps, are there areas where we piled 
up things in a greater proliferation in some spots and not 
enough in others.
    We are going to look closely at our portfolio of HIV/AIDS 
research and see whether in fact now that it is 2015 we 
desperately need to find an answer to this disease and to end 
this epidemic. We need to focus particularly heavily on 
vaccines, on new forms of therapeutics, on potentially the 
cure, on comorbidities.
    We have an active grant by grant review going on right now 
of our HIV/AIDS portfolio to see how that matches with the 
priorities that should be most appropriate at the present time.
    We are going to make sure that we have best practices for 
how funding decisions are made within the Institutes because 
peer review is part of that but not all of that. We have to 
make decisions based upon scientific priorities that our 
councils and our directors are responsible for, and we want to 
be sure that we are making the most of those opportunities.
    We will continue to look for partnerships so that as much 
as possible we can find other dollars besides the NIH dollars 
to pursue important scientific projects with other agencies or 
with the private sector.
    We will certainly focus intensely on early stage 
investigators, which have already been raised as a major issue, 
and one we are very concerned about. How could we enhance the 
opportunity to give those early stage investigators the 
confidence there is a career path for them and they can take 
risks and do innovative research without fear of losing 
support.
    As was mentioned by Senator Alexander, we are going to look 
closely at administrative burdens, many of which we do not 
control, but for the ones we do have some say over, we are 
going to try to do everything we can to reduce those and give 
scientists more time to do science instead of paperwork.
    That is a partial list of what is actually quite a vigorous 
array of activities. I want to assure you, very much, from my 
own personal commitment that we are taking this with great 
seriousness. We do not expect people to say oh, well, you are 
just NIH, so you deserve dollars. We have to show that we are 
using our appropriated funds wisely and that every dollar is 
being put to good use. There will be much more to say about 
that in the coming months.
    Senator Moran. I think as you heard from Senator Durbin and 
really every member that has spoken, we are interested in 
finding additional resources for you.
    We understand this issue cannot be resolved only by your 
efficiencies, but as we find those additional dollars, the 
assurance that I am looking for is that you then have the 
capability to make the decisions where those dollars can best 
be spent for the best outcome for the health and well being of 
our country. I thank you for your answer.
    Dr. Collins. Thank you, Senator.
    Senator Blunt. Thank you, Senator Moran. Senator Schatz.

                               TELEHEALTH

    Senator Schatz. Thank you, Mr. Chairman. Thank you, Dr. 
Collins. I have become increasingly interested in telehealth, 
and I think there are a number of Federal agencies that are 
doing great work in this space. DOD and the VA come to mind. I 
think CMS has some work to do. Some of that has to do with 
their statutory challenges, and some of that I think they could 
push their authorities a little bit more.
    I know NIH is doing a number of research projects. I wonder 
if you would not mind taking a minute or two and letting us 
know what you are up to and what you have found.
    Dr. Collins. I appreciate the question. Yes, many of the 
Institutes have investments in this space. I have to tell you, 
more recently, what has really emerged as an even more hot area 
and a very promising one is the idea of mHealth, using cell 
phone technologies to make this even more transportable where 
people are walking around with their own potential telehealth 
gadgets in their pockets. That is going to be a very 
significant part of what we want to test in the Precision 
Medicine Initiative. I can think of a telemedicine application 
the National Eye Institute is using to try to assess with 
babies in the newborn ICU which of those are developing a 
retinopathy of prematurity by basically taking photographs and 
then sending that to an expert across the country to say this 
baby needs treatment, that one does not.
    Dr. Gibbons, I think, has a telemedicine application for 
asthma, as I recall. Do you want to say a word about that?
    Dr. Gibbons. Yes. Certainly, one of the areas of concern 
with asthma, the leading chronic condition affecting children, 
relates to being able to transcend those geographic barriers, 
particularly in rural communities where this is a particular 
problem. A lot of times, it is getting a sense of the child's 
symptoms and course of disease.
    That is where there is really an opportunity as Dr. Collins 
alluded to to use leverage technologies that enables that 
information to get to the experts quickly to be able to manage 
the patients care.
    With technologies that actually exist, on a Smartphone now, 
are able to assess the breathing capacity of the child.
    We have a program, that we are funding that leverages 
resources that are local, such as schools, where this 
information can be ascertained, the child's symptoms and 
disease course development, and treatment again transmitted in 
that local environment, leveraging those local resources.
    We are looking at using these new mobile technologies in 
different ways to enhance care for both children and adults.
    Senator Schatz. Thank you. Let me just make a small point 
about telemedicine, telehealth. This has been something people 
have been working on for decades, and as a result, people think 
of VTC or telemedicine center-based delivery of care.
    I think it is entirely possible that for at least some 
treatments, the mobile phone just sort of outpaced all of it. I 
want to make sure that when we do national health policy and we 
do our appropriations, and we encourage you to do telehealth, 
that we are not conceiving of a sort of 1995 center for 
telemedicine, but we are enabling people to get the healthcare 
they need through their phone, HIPAA compliant and all the rest 
of it.
    It is important to say because I do think that we have a 
statutory infrastructure and some inertia that is based on what 
was possible 10 or 15 years ago.
    Dr. Collins. Senator, I am glad you point this out. I think 
our NIH portfolio has shifted dramatically in the direction of 
mHealth, mobile health, using cell phone technology, which is 
bursting with potential for whatever, either maintaining health 
or for perhaps monitor chronic illness.
    Many of us now are walking around with wearable sensors. I 
have my Fitbit. I do not know how many other people in the room 
have something that is currently monitoring their physiology. 
That is such a great opportunity for medicine and we are all 
over that.

                        COST BENEFITS OF MHEALTH

    Senator Schatz. One other question with respect to 
telehealth. I think we are going to come up against the 
question of scoring, with respect to Medicare reimbursing for 
telehealth services. There is sort of an ongoing discussion 
about whether or not it will increase total costs to the 
system.
    My strong belief is it will decrease total costs to the 
system. That does not mean that CBO scores it accordingly. I am 
just wondering whether you are doing any research that gives us 
any insight as to what would happen to total costs within a 
healthcare system utilizing mHealth.
    Dr. Collins. We are certainly interested in rigorous 
studies to assess whether mHealth applications are improving 
outcomes. There are so many potential applications that are out 
there that people are excited about, but many of them have not 
really been put to a test. In order to decide whether you are 
achieving any cost savings, first you have to figure out did 
this application actually improve the long term outcome, did 
you reduce illness, did you manage it more effectively. That is 
very much in our sweet spot in terms of what we are trying to 
support.
    Senator Schatz. Thank you.
    Senator Blunt. Senator Capito. Thank you, Senator Schatz.

         APPROACHES TO STUDYING ALZHEIMER'S AND OTHER DISEASES

    Senator Capito. Thank you. I want to thank the panel. This 
is very interesting to everybody. I am just going to make a 
quick comment about the IDeA program that Dr. Lorsch, I 
believe, you are in charge of. Two of our institutions in West 
Virginia, WVU and Marshall, are the recipients of grants there, 
so I would like to invite you to join me in West Virginia to 
show me what is going on and what the possibilities are there.
    Dr. Lorsch. I would be absolutely delighted to come.
    Senator Capito. Good deal. That is a good deal. My real 
passion here in the area is Alzheimer's. Both of my parents 
just recently passed away. Both of them had increasing 
dementia.
    I am going to go back and look at the death certificates 
and see what was actually listed as the cause of death. Having 
lived through it, when you said it may be decreasing, my eyes 
almost popped out of my head. From what I saw just on the 
ground, I cannot imagine that is the case. It could be just 
poor data.
    I know you are getting ready to revise the research 
milestones for the National plan. Could you talk a little bit 
about that, what NIH is doing in that area?
    Dr. Collins. Alzheimer's disease is an area of intense 
focus and has, of course, enormous consequences. We need to 
find answers. Five million Americans currently affected. The 
cost personally to those individuals, to their families, is 
enormous. The economic cost we know is approaching $200 billion 
a year just in the United States.
    We need to find ways to prevent or delay this disease. 
There are efforts across many different parts of NIH to do so, 
led by the National Institute on Aging. This extends from very 
basic science studies, trying to understand what is actually 
happening in the brain that leads to the deposits of these 
proteins, amyloid and tau.
    An interesting recent development has been, what has been 
called ``Alzheimer's in a Dish,'' namely the ability to take 
stem cells, adding an appropriate cocktail to convince them to 
become neurons, put them into a Petri dish, but not as flat 
cells but in a three dimensional space where they act more like 
they would in a normal circumstance.
    You can then actually tell the difference between those 
cells if they came from somebody with the dominantly form of 
Alzheimer's as opposed to a normal person.
    That is an enormously powerful development, because it 
gives us a chance to look at human cells to see what is really 
going on in a way that does not put people at risk, and allows, 
for instance screening drugs to see which of those might be 
most promising.
    That is the basic part of it. On the clinical side, I 
think, just a month ago, a report by Biogen of what appeared to 
be a possible positive result, first time, after dozens of 
failed trials, from a monoclonal antibody directed against 
amyloid. It has gotten a lot of people interested in whether we 
might be on to something.
    A very small trial, only about 300 patients. You always 
have to be careful here, because it is so easy for those things 
not to end up being replicated. The initial excitement is 
certainly something that with cautiousness, people are feeling 
a bit more optimistic about.
    Another thing we are doing is to partner with industry in 
an unprecedented way.
    Senator Capito. Is that the Accelerating Medicines 
Partnership?
    Dr. Collins. Yes, it is, AMP, which involves 10 
pharmaceutical companies working with the NIH on Alzheimer's, 
Type II diabetes, rheumatoid arthritis, and Lupus. I, 
personally, co-chair the executive committee of that group. We 
have only been at it a year and we are ahead of the schedule on 
what we thought would be possible. This area of research is 
showing considerable promise, all the way from the basic to the 
clinical.
    I think we are on a roll here in terms of tackling what has 
been, for most of the years we have studied it, a really 
frustrating disease. We are starting to get a much better 
handle on what is going on in the Alzheimer's brain.
    It is clear that one thing we need to do if, we are trying 
clinical trials, is to start early before too much damage has 
been already done to the brain. I assure you this is an intense 
area of focus.
    Senator Capito. I would encourage that and will be a great 
supporter of that. I just anecdotally read an article, I 
believe it was in the Sunday paper, about a clinical trial or a 
small area, I believe it was in South America, that identified 
they had a pocket of early onset Alzheimer's in the 40s age 
bracket. Very interesting to me because it mentioned some of 
the same things you mentioned.
    Dr. Collins. Yes, that is an NIH sponsored trial in 
Colombia for families that have this dominantly inherited form 
of Alzheimer's.
    Senator Capito. We could learn a lot from that.
    Dr. Collins. Yes. They are involved in a very significant 
way in these clinical trials.
    Senator Capito. The interesting thing to me, too, having 
lived through it with two parents simultaneously, is it is not 
the same for every person, which really, I think, makes it more 
difficult in terms of researching and figuring out how to 
attack it.
    There are a lot of families, across probably every family 
sitting up here today and in the audience that has been touched 
by this.
    Thank you for your work.
    Dr. Collins. Thank you, Senator.
    Senator Blunt. Thank you, Senator Capito. Senator Baldwin.

                            PAIN MANAGEMENT

    Senator Baldwin. Thank you, Mr. Chairman. Thank you and 
welcome. I want to start asking some questions about chronic 
pain, opioid treatment, and alternatives.
    Let me just give a little bit of context. Obviously, we 
know that chronic pain is a condition that affects over 100 
million Americans. For some individuals, prescription opioids 
are an important part of the treatment plan, but it is also 
clear if you are following any of the trends in the Nation that 
we are in the midst of a national crisis as a result of 
significant over prescription of opioids and misuse.
    Dr. Collins, you recently stated in a blog post, I think, 
that when it comes to chronic pain, opioids are not always the 
answer, and speaking to the lack of evidence--let me see, what 
did you say. There is an absence of unbiased scientific review 
to examine evidence of the safety of long term prescription 
opioid use and the impact of such use on patients.
    I would like to first ask two questions related to that. 
First, please tell us about the collaboration you are doing 
with the VA on an inquiry into alternative pain management 
strategies, not just for physical pain, but also PTSD.
    In what time you have remaining, if you do, what potential 
does the research on the effectiveness--what does the latest 
science tell us about the broad use of opioids to treat chronic 
pain and what is the NIH doing to advance our scientific 
understanding of pain management?
    Dr. Collins. Thank you, Senator. This is indeed an enormous 
concern, and an enormous public health problem, 17,000 people 
lost their lives last year to opioid overdose, most of those 
unintentional. The number of prescriptions that are written for 
opioids is dizzying. It adds up to basically one prescription 
per American per year. That does not sound like that is what we 
need to do in order to deal with the problems of chronic pain.
    It is, in fact, the case that studies that have been done 
on the use of opioids and chronic pain generally have not been 
carried out for more than 4 to 6 weeks, and yet often times 
chronic pain goes on longer than that.
    There is a lack of data, but the data we do have certainly 
would cause anybody to conclude that opioids are probably not a 
good choice for chronic pain, unless it is associated with 
severe tissue injury, as in the case of say cancer.
    We have a lot that we need to come up with in terms of 
alternatives. That is what these 13 projects we are doing 
jointly with the VA--and ``we'', in this case are, the National 
Center for Complimentary and Integrated Health and the National 
Institute for Drug Abuse (NIDA). We are working together on 
this.
    I think they are trying to assess for various types of 
pain, particularly, if it is, what you might call ``central 
pain,'' coming from conditions associated, for instance, with 
PTSD, where the use of a drug like an opioid, which is better 
suited for peripheral pain, just does not seem to work, and in 
fact, carries a lot of risk.
    Alternatives such as antidepressants, cognitive behavioral 
therapy, interventions that involve something that might seem 
new age but actually seems to have some value to a lot of 
people, yoga. All of those are being looked at as alternatives 
to putting people down a very difficult path of opioids which 
may lead to addiction and all the problems associated with 
that.
    Meanwhile, NIDA is deeply engaged in looking for other 
alternatives for pain management that are not addictive, coming 
up with opioids that cannot be abused because they cannot be 
injected. All of these initiatives are high priorities.
    I traveled to Atlanta this year, as I did last year, along 
with Dr. Volkow, who is the head of NIDA, to a summit that Hal 
Rogers chaired, of Appropriations in the House, that runs every 
year. There were 1,000 people there from all over the country 
working together to try to tackle what everybody now sees as a 
major and growing health problem in the U.S. We will do 
everything we can to help with that.

             IMPROVED OPPORTUNITIES FOR THE NEXT GENERATION

    Senator Baldwin. I have just a couple of seconds remaining, 
so I will hopefully have you follow up in writing. One of the 
highlights that you focused on in your testimony was our shared 
priorities to improve opportunities for the next generation of 
innovators and researchers across our Nation.
    I know you have initiated and we have talked much about the 
initiation of a number of policies to promote new researchers.
    We have identified a significant gap in the data on the 
existing research workforce. We have a lack of a comprehensive 
way to track the success of the careers of researchers.
    I have been working closely with you on my Next Generation 
Researchers Act, which would ensure that NIH accelerates 
current and new policies to address this, and foster new 
researchers.
    Let me just say I would like to hear more about why we do 
not have a good system in place already to track this 
information on our biomedical workforce, and what additional 
steps NIH is taking to address this gap.
    Senator Blunt. I think we will take that for the record or 
when we get to a second round, if Senator Baldwin wants that to 
be her question, that would be great.
    Senator Baldwin. For the record.
    Dr. Collins. Okay.
    [The information follows:]

    Successful biomedical research relies on the talent and dedication 
of the scientific workforce. A sustained supply of highly trained 
people of the best quality is needed to bring new insights to our 
understanding of biology and to advance the translation of these 
insights into improved health for all. To this end, NIH supports 
training of graduate students and postdoctoral researchers, both with 
dedicated training grants and fellowships, and by supporting ``hands-
on'' research experiences on research grants. Although the number of 
fellowships and traineeships through the Ruth L. Kirschstein National 
Research Service Award (NRSA) program has remained relatively constant 
over time, the number of students supported on research grants has 
grown substantially.\1\ Until relatively recently, NIH has routinely 
monitored the career outcomes of trainees and fellows receiving NRSA 
support, but has not had systems in place to do the same for students 
supported by research grants.
---------------------------------------------------------------------------
    \1\ Http://grants.nih.gov/training/nrsa.htm.
---------------------------------------------------------------------------
    In June 2012, the Biomedical Workforce Task Force, an Advisory 
Committee to the NIH Director (ACD) issued the Working Group Report on 
the Biomedical Research Workforce.\2\ The Working Group made 
recommendations to ACD about the funding and training of graduate 
students and postdoctoral researchers in order to attract and retain 
the best and most diverse scientists, engineers and physicians from 
around the world. This report highlighted the lack of data on the 
career progression of individuals who participated in NIH-supported 
research grants as graduate students and postdoctoral researchers. This 
led ACD to recommend the establishment of ways to identify and track 
all NIH-supported students and postdocs using approaches similar to 
those that have long been in place for the NRSA awards.
---------------------------------------------------------------------------
    \2\ Http://acd.od.nih.gov/bwf.htm.
---------------------------------------------------------------------------
    As a consequence of this recommendation and directives included in 
the National Institutes of Health Reform Act of 2006 (Public Law 109-
482), the collection of information on undergraduate and graduate 
students was announced on August 2, 2013 and fully implemented with the 
issuance of the Research Performance Progress Report (RPPR) on October 
17, 2014.\3, 4\ Information gathered through RPPR (an annual report of 
progress completed by each NIH grantee) will enable NIH to calculate 
more accurately the number of students supported by research project 
grants and provide a means of tracking their career outcomes, 
particularly if they continue to receive NIH research support.
---------------------------------------------------------------------------
    \3\ Http://grants.nih.gov/grants/guide/notice-files/NOT-OD-13-
097.html.
    \4\ Http://grants.nih.gov/grants/rppr/rppr_instruction_guide.pdf.
---------------------------------------------------------------------------
    The Science Experts Network Curriculum Vitae (SciENcv), which is an 
electronic system built by the National Center of Biotechnology 
Information (NCBI) in collaboration with the Federal Demonstration 
Partnership (FDP), is also expected to help track NIH grantees 
throughout their careers.\5, 6\ This tool enables researchers to easily 
assemble biographical information and simplify the work flow associated 
with Federal funding. SciENcv gathers and compiles information on 
expertise, employment, education and professional accomplishments.
---------------------------------------------------------------------------
    \5\ Http://www.ncbi.nlm.nih.gov/.
    \6\ Http://sites.nationalacademies.org/pga/fdp/index.htm.
---------------------------------------------------------------------------
    The system is publicly available as of fiscal year 2015. In its 
current version, SciENcv helps researchers assemble an NIH biosketch by 
leveraging existing information from NIH eRA Commons (the online 
interface NIH applicants use to submit grants) and PubMed. It is also 
piloting the creation of a National Science Foundation biosketches. In 
addition, SciENcv allows users to link the content of their profiles to 
a persistent, unique identifier offered by Open Researcher and 
Contributor ID (ORCiD), as well as incorporate data stored in their 
ORCiD profiles into their SciENcv profiles.\7\
---------------------------------------------------------------------------
    \7\ Http://orcid.org/.
---------------------------------------------------------------------------
    During fiscal year 2015, the current version of SciENcv will be 
enhanced in multiple ways.\8\ It will be updated to allow users to 
describe the impact of their past discoveries, to ingest data from 
additional external systems, and it will permit data to be transferred 
to other systems. In
---------------------------------------------------------------------------
    \8\ Http://www.ncbi.nlm.nih.gov/sciencv/.
---------------------------------------------------------------------------
    Fiscal year 2015 and beyond, other Federal agencies will be added 
to the document generating capabilities of the system, moving the 
Nation toward an information collection system that will provide 
greater insight into the impact of Federal research funding and improve 
the ability to track the outcomes of NIH trainees and the scientific 
research workforce.

    Senator Blunt. Okay. Senator Cassidy.

                      BALANCING FUNDING PRIORITIES

    Senator Cassidy. Gentlemen, I am a doctor. I know so much 
of what you all have done. Dr. Fauci, in 1985, when I was a 
resident at L.A. County Hospital, the diagnosis of AIDS was 100 
percent death sentence. Now, if you take your medicine, you are 
more likely to die of Alzheimer's than of AIDS, it seems.
    For you all, thank you all from a guy that has just seen 
firsthand what you have done.
    I want to build upon that which Senator Moran was saying. 
You said, Dr. Collins, that the report will be available next 
December, do you mean 2015 or 2016 in terms of rebalancing how 
you are spending priorities?
    Dr. Collins. That will be December of this year, 2015.
    Senator Cassidy. There is an article from 2011 suggesting 
that that principal variable in determining funding was 
disability life years adjusted, DALYs, and that accounted for 
33 or 39 percent of the variance, I think, and there really was 
no other correlation.
    What other factors will you be using to determine whether 
or not you should rebalance funding or how you should 
rebalance?
    Dr. Collins. Generally, we look at the public health 
burden, and DALY is a very well established way to do that. We 
also look at scientific opportunity. It is not going to be 
successful to throw money at a problem if nobody has an idea 
about what to do about it.
    We look at what our peer review process is telling us about 
the excellence of the science.
    Senator Cassidy. To a certain extent, and I do not mean to 
interrupt, I have 4 minutes and then this guy is going to ride 
herd, so to a certain extent, there is a certain sort of the 
past is prologue on that approach.
    I will just tell you my concerns. I have done some back of 
the envelope figuring, we have been looking at this for a 
while. You mentioned the work that is being done for a vaccine 
for HIV/AIDS. The best I can figure, we are spending about $400 
million for that. We are spending less than $600 million in 
total for Alzheimer's.
    For just the vaccine aspect of HIV/AIDS, we are spending 
two-thirds as much as we are for Alzheimer's. On a per death, 
and again, this is back of envelope so you may tell me it is 
wrong, we are spending almost $190,000 per HIV death, and we 
are spending $6,700 per Alzheimer's death. Ten percent of our 
budget on HIV/AIDS, 1.9 percent on Alzheimer's.
    I can go down the list. By the way, I am a hepatologist, so 
there are kind of similar numbers where we are spending as an 
economy for Alzheimer's--you mentioned $200 billion a year, for 
liver disease, $51 billion a year, and for HIV/AIDS, all 
categories, $16 billion a year. There seems to be just a total 
out of whack in terms of the burden on society, death, DALYs, 
cost of Medicare/Medicaid, et cetera, on where we are spending 
right now.
    Can you correct that at all in a relatively short period of 
time?
    Dr. Collins. I think our goal is to end the AIDS epidemic, 
and we are not there yet, as you know, 50,000 new cases every 
year.
    Senator Cassidy. I accept that, but on the other hand, if 
you look at the incidence of disease, there is far more 
incidence right now of Alzheimer's than there is of HIV, and 
the means of preventing HIV is well known. Obviously, vaccine 
would be the Holy Grail.
    Are we going to wait--I guess my question is we have this 
balloon note on Alzheimer's, 200 billion climbing, are we going 
to wait until we figure out a vaccine for HIV/AIDS before we 
begin shifting to the new battle? Do you see what I am saying?
    Dr. Collins. I think I do. Again, I want to assure you that 
we are looking with more scrutiny than ever at that HIV/AIDS 
portfolio. I should ask Dr. Fauci to weigh in here since he is 
the expert for us.
    Dr. Fauci. I certainly understand the point you are making, 
but I think one of the other variables that was not mentioned 
when you talk about DALYs and scientific opportunities is the 
ability or not to completely eliminate a disease.
    I think when you are dealing with an infectious disease 
that causes an epidemic or pandemic, that is a different story 
from other diseases such as chronic illnesses which are equally 
as serious, as devastating, and have impact on society, but do 
not have the potential to actually be completely eliminated the 
way we eliminated polio and other infectious diseases in this 
country.
    Although I fully understand and appreciate the point you 
are making, I am looking forward to a time when I am sitting in 
front of this committee and we have ended the AIDS pandemic and 
there will not be any argument about what you want to do with 
the money because you will not need the money.
    Senator Cassidy. I accept that. That is a good point. Does 
that mean we increasingly consume--I think in 2011, the budget 
for HIV/AIDS was about $2.5 billion, $2.4 billion, and now it 
is almost $3 billion.
    We have to set priorities. We are spending $300 billion a 
year on Alzheimer's/dementia. It would be great if we could 
stomp it out, but spending $19,000 per death for HIV/AIDS and 
$6,700 per death for Alzheimer's seems like a prioritization 
which does not reflect we are spending 200 to $300 billion a 
year. Do you see what I am saying?
    Dr. Fauci. I understand your point. Also, just to get this 
point on the table, if you do the kinds of calculations of how 
much money you would save per HIV infection prevented--even a 
vaccine that is not the best vaccine in the world, that is 50 
percent effective, we would save about $6 billion a year by 
preventing HIV infections with that vaccine.
    Those are the things that we are aiming at. The other point 
I want to make is that when Dr. Collins was talking about 
examining the portfolio, one of the first important steps is to 
look at the portfolio itself, and then determine within that 
portfolio, are we spending money on the highest priorities 
within that portfolio, we would suggest this prioritization 
within the portfolio as the first shift, and then take a look 
after that and determine whether there is a need for any 
further redistribution.
    We are looking at that and taking it very seriously.
    Senator Cassidy. I am way over. Thank you for the 
indulgence.
    Senator Blunt. Thank you. Senator Lankford.

                   STATUS OF ALZHEIMER BYPASS BUDGET

    Senator Lankford. Thank you. Can I do one wrap up question 
on Alzheimer's? I appreciate the conversation that is ongoing 
on this, and obviously this is one of the multiple diseases 
that have a tremendous expense, diabetes, cancer, Alzheimer's, 
consuming a great deal of both financial cost and pain across 
the entire country.
    Last year, Congress passed the Alzheimer's Accountability 
Act, which required a report, and to be able to get that budget 
estimate together, what it would take. When do you expect that 
to be complete?
    Dr. Collins. Senator, I appreciate the question. Yes, this 
was an Act which got folded into the Omnibus bill, which 
basically asked NIH to put forward what is called a ``bypass 
budget'' for Alzheimer's research, as we do now for cancer.
    The instructions were such that we are to have the first 
version of the bypass by some time this summer in order for it 
to apply to fiscal year 2017. We are on track to do that. I 
should say we will in the next 24 hours issue a new set of 
recommendations about Alzheimer's research based upon the 
summit we held in February and the synthesis of those 
recommendations. That will be coming out tomorrow.
    Senator Lankford. Terrific. Thank you. I look forward to 
going through that report. I am like many people on this dais, 
I watched my grandmother, and we have all walked through this. 
My mom currently has Parkinson's. We walk through this life 
together.
    Dr. Collins. Senator, if I may, because we had this 
conversation about Alzheimer's and AIDS, I would say we have 
actually increased Alzheimer's spending since 2011 by 40 
percent, more than any other disease in NIH's portfolio, 
specifically because of the scientific opportunities and the 
enormous public health need.

                              TELEMEDICINE

    Senator Lankford. Thank you. When Senator Schatz was 
talking about telemedicine, I want to reinforce some of things 
done there. Obviously, we have work to do with CMS on the 
billing process of that as well.
    Let me do one caveat. This is not to belittle them at all, 
so I am not going to just pick on somebody that is not here. 
The Census Bureau in 2010 spent $3 billion developing a hand-
held device to be able to do the Census on, and at the end of 
it, had to pun it. We literally lost $3 billion on a hand-held 
device to take the Census, that eventually they went back to 
pen and paper.
    As much as we can use current technologies, and allow the 
public sector to take the lead on that, and make requests of 
it, please continue to do that. I know NIH has done that a 
tremendous amount. When we go into some of these other 
technologies, do not reinvent the wheel.
    Dr. Collins. I am totally with you. In fact, for this 
Precision Medicine Initiative, there is enormous interest from 
private sector developers of these various mHealth apps. We 
have no need, I think, to develop any of our own because they 
are chomping at the bit to have theirs tried out in this kind 
of large scale study.

       COST DRIVERS BETWEEN BASIC RESEARCH AND CLINICAL RESEARCH

    Senator Lankford. Great. Thank you. Please press on with 
that. Let me ask a general question, a philosophical question. 
We have seen an increase in costs in drug and device 
development over the past several years. It seems to continue 
to accelerate without a cap on it.
    Can you help me understand what is driving the increased 
costs between basic research and clinical research all the way 
from the time of concept to the time of actually getting in the 
marketplace? What are the key factors that you see that is 
increasing the cost more than anything else? I know it is not 
only one thing, but if you could give me a couple ideas here of 
what we should watch for, what is driving the cost change.
    Dr. Collins. A lot of it is high failure rates. That is in 
fact, very troubling when you consider how rarely an idea about 
a new drug makes it all the way through to FDA approval. It is 
less than 1 percent of the time.
    All that cost, of the failures, has to be added into the 
overall enterprise. One of the things we are doing at NIH to 
try to help with this is the formation of the National Center 
for Advancing Translational Sciences, which aims to identify 
some of the places where failure happens, where bottlenecks 
occur, and develop new technologies in concert with the private 
sector to see what can be done about that.
    I mentioned the idea of human cells on a chip as a way of 
testing drug toxicity, instead of using animals. This approach 
is looking like it might work, and that would be a big step 
forward as one of the places where things get bottled up and do 
not work well.
    Another is the whole idea of precision medicine, where 
instead of trying to develop a blockbuster drug and finding it 
does not work when you apply it to thousands of people, you 
actually identify the subset of individuals for whom that drug 
is particularly well suited, you run a much smaller trial, and 
you have a much better chance of success. Cost of the trial 
goes down and chance of success and ultimate FDA approval goes 
up.
    Those are all things that are in the works. I share with 
you the concern, we have to turn that curve around, and we are 
attentive.
    Senator Lankford. You have identified these bottlenecks. Is 
there any one spot that you see the costs increasing more than 
any other area, as it goes from concept to actually 
distribution?
    Dr. Collins. I guess the clinical trial, of course, is the 
most expensive part, when you look at where the dollars really 
start to build up. If you have to do a clinical trial of 
thousands of people and follow them over a period of time, that 
is going to be very expensive. We have to come up with ways to 
do smaller trials, to have biomarkers that allow you to know if 
the drug is working without waiting 4 or 5 years to see what 
has happened. Those efforts are really a high priority.
    Senator Lankford. Okay. Thank you.
    Senator Blunt. Senator Kirk.

                UNIFIED FEDERAL ELECTRONIC HEALTH SYSTEM

    Senator Kirk. Dr. Collins, I wanted to ask your opinion 
about some work I have been doing to drive this Senate 
Appropriations Committee to have one unified Federal electronic 
health record between DOD and VA.
    My hope is to make sure that using the 25 million patients 
that the VA has and the two million patients the DOD has, we 
have one unified record. My hope is we have this open code and 
open source to repeat the success that Motorola had with the 
Android system, where they had 70,000 apps from industry that 
was written to open code of Android.
    Could you give me a comment on that? I will be coming to 
you with a consortium across Illinois, with the five hospitals, 
and I will say including Barnes-Jewish, which is particularly 
good at working with NIH.
    Dr. Collins. My hat is off to you for what you are doing 
with DOD and VA to try to make this into a seamless electronic 
health record. I know everyone in the Service are anxious to 
see that happen. It has been difficult, I think, sometimes with 
those transitions.
    This all fits together actually with a broader effort to 
try to see if electronic health records that are being 
collected on all of us can be made more interoperable so that 
you can walk around from one State to the next and have your 
health records accessible when you need them.
    With our Precision Medicine Initiative, there is a great 
need for the electronic health record to be usable in the best 
way. We are working with the Office of the National Coordinator 
for Health IT on that very issue, meaningful use.
    The White House has a new Chief Data Scientist, D.J. Patil, 
who is working with us on prevision medicine, I believe he is 
also involved in the DOD/VA efforts to get electronic health 
records to talk to each other.
    You would think this would be easier than it is, it is 
actually quite a challenge because of the way in which health 
records are not standardized, where the information in them is 
often text based, therefore, difficult to do easy melding.
    Senator Kirk. I will interrupt you that I have put forward 
Kirk's pretty good plan, that all imagery be a JPEG and all 
documents be an MS Word. My vision thing is because the VA 
represents about 10 times the patients DOD has, that we go with 
a VA standard, if DOD tries to cut its own rug.
    Dr. Collins. I really appreciate your idea of a pretty good 
plan. Right now, I think the perfect could actually be the 
enemy of the good, and what we need right now is something that 
is good enough as opposed to what we have.
    This whole idea of the blue button, where individuals can 
get their own electronic health record, would be enormously 
beneficial if it was actually seamlessly reduced to practice.
    Senator Kirk. Thank you. Thank you, Mr. Chairman.

              NATIONAL INSTITUTES OF HEALTH STRATEGIC PLAN

    Senator Blunt. Thank you, Senator. I want to comment on two 
or three points, and then we will go to Senator Murray. On the 
stewardship discussion, the strategic plan, I am very 
supportive of that. I think that is a major announcement on 
your part. As I understood the announcement, the 27 Centers you 
currently have have their plans.
    This will be the first time you strategically evaluate and 
try to prioritize where you want to go as you look at all the 
27 Centers to really come up with an overall strategic research 
plan. Do I understand that correctly?
    Dr. Collins. That is absolutely right, Senator.
    Senator Blunt. You hope to have that available by the end 
of this year?
    Dr. Collins. By December; yes, sir.
    Senator Blunt. It will be very helpful. I want to encourage 
you to do that. I am supportive of it. The questions are better 
asked by you, frankly, to start with. You have those 27 plans 
to look at, you have the forum to hash that out and have the 
internal arguments you need to have about why this is maybe a 
bigger priority than that.
    Clearly, I see this as responsive to the discussions that 
you and I have had and that you have had with many other 
members of this committee about prioritizing research.
    On the Alzheimer's discussion, I think in the bill last 
year, the objective was for you to have a plan that would reach 
a goal by 2025, and that goal was what? To have a cure for 
Alzheimer's?
    Dr. Collins. Or a delay in the onset, a major advance in 
terms of preventing or delaying the onset.
    Senator Blunt. We should expect that report by when? I 
think you have already said, Francis.
    Dr. Collins. In terms of what we were asked for 
specifically in the new piece of the Omnibus is not only a plan 
but a bypass budget of what it would take to get there. The 
plan itself gets refreshed every year, and there will be a new 
version of the research plan tomorrow.
    We are also going to attach to that to an estimate of what 
it would take to accomplish the task because we have been asked 
to do so by the Omnibus language.
    Senator Blunt. We will be seeing something tomorrow?
    Dr. Collins. Tomorrow you will see the outcome of the 
summit on research that was held in February bringing people 
from the U.S. and outside the U.S. to really nail down what are 
the highest priorities right now for research in this space.
    I believe this will be the second time we have had such a 
summit, and this is a major refresh of what the research agenda 
is.
    Senator Blunt. I think the precision medicine discussion, 
the BRAIN discussion, and the strategic plan discussion, 
probably make enough news for today, or I would press you a 
little bit on why you cannot tell us today what you are going 
to tell people tomorrow. I look forward to that tomorrow.
    Dr. Insel, as you know, I have been very interested in how 
we prioritize mental health or bring it to the same level of 
parity to all other health issues.
    The statistic that I believe is generally used now and NIH 
is always the source, is one out of four adult Americans have a 
behavioral health problem, diagnosable behavioral health 
problem, that is almost always treatable if diagnosed. Is that 
number still a good number? Do you have a better number we 
should be using?
    Dr. Insel. I think in this case, we tend to focus more on 
those who have the most disabling or what we now call serious 
mental illnesses. I think the total number runs to about 9.6 
million adults about 4.1 percent of all U.S. adults.
    What is critical to remember in contrast to what we talked 
about for Alzheimer's disease, these are chronic diseases, of 
young people, so 75 percent of that number have onset before 
age 25. That makes this a particularly challenging public 
health issue.
    Senator Blunt. We all heard Senator Mikulski's story 
earlier today about how when talking to people at schools, what 
is the single biggest thing we could do to help, and obviously 
this is right in the area you are working on.
    What about the other number, if one out of nine is 
debilitating or serious, what would be the bigger contextual 
number of behavioral health that is diagnosable and treatable?
    Dr. Insel. Across the board, about one in four is the 
number that we think about across the life span in terms of 
people being affected.
    Senator Blunt. In the Armed Services Committee I was on 
last year, I think that is Armed Services as opposed to Defense 
Appropriations, I may have asked this in one of those two, I 
asked the Surgeon Generals of the military if they thought that 
the one in four statistic applied to people in the military. 
The answer I got was that we do not have any reason to believe 
it is not about the same, that the military recruits from the 
general population about the same.
    What has been happening in the military as it relates to 
how we deal with behavioral health problems?
    Dr. Insel. As you know, Senator, the suicide rate in the 
military, particularly in active duty, has gone up 
significantly, doubled, actually surpassing the civilian rate 
for people in the same age bracket.
    It is beginning to come down slightly, in the last 3 years, 
but we have gotten new numbers just in the last couple of days, 
so it is still up there. It is still high.
    DOD and especially the Department of the Army have been 
very, very focused on how to bend the curve there. We have been 
working with them through the Army STARRS Project with over 
100,000 soldiers over the past 5 years, and that project has 
given us a much better sense of how to focus their efforts on 
those who are at highest risk.
    Senator Blunt. Thank you. Senator Murray.

                            DRUG REPURPOSING

    Senator Murray. Thank you. Dr. Collins, I wanted to ask you 
while you were here, I noticed a very exciting announcement by 
NIH that one of your researchers or some of your researchers 
were able to use FDA approved drugs to activate stem cells in 
the brain to actually repair damage caused by multiple 
sclerosis.
    That is really exciting. As we all know, up until now, we 
have not been able to repair damage after it has occurred.
    I want to ask you while you are here what are the next 
steps on that?
    Dr. Collins. That was an exciting finding. Basically, the 
National Center for Advancing Translational Sciences, NCATS, 
has this ability to take any kind of an assay that you have 
developed and screen it against all the FDA approved drugs very 
quickly.
    Because if you could find a circumstance where you have a 
disease like multiple sclerosis where there is a drug that is 
already out there, that has been used for other things, that 
has activity here, you can quickly jump across many different 
hurdles to get to a clinical outcome, which we all desperately 
need to see happening for multiple sclerosis.
    The investigators supported by the National Institute of 
Neurological Disorders and Stroke did that screen using the 
kinds of cells that make Myelin, which is the stuff that 
basically provides the insulation for nerves, and were able to 
show in a Petri dish there were two drugs in that FDA 
collection that seemed to show benefit in terms of stimulating 
those cells to make the Myelin, which is what you want them to 
do.
    Then they tried that in the mouse model, and both of them 
appeared to have activity in the best animal model we have. 
That means the next step would be to think about how to move 
this into a human clinical trial.
    One of the drugs is an antifungal, of all things. The other 
is a steroid. Neither of those had ever been thought of in this 
circumstance. We are excited about that, too.
    I might also say there is another exciting finding in 
multiple sclerosis research. Only in the last month, Dr. 
Fauci's Institute supported an effort. Maybe you can quickly 
say something about that. That was a human trial that looked 
pretty promising.
    Dr. Fauci. Thank you, Dr. Collins. The study that Dr. 
Collins is referring to was we funded, by our Institute, the 
National Institute of Allergy and Infectious Diseases, because 
it was an immunologically based study, was from our immune 
tolerance network, which really was very exciting.
    We took 25 individuals who had relapsing-remitting multiple 
sclerosis and performed autologous stem cell transplantation 
preceded by very aggressive immunosuppression in the same way 
you would give a stem cell transplant for someone with cancer.
    As it turned out to our great surprise and gratification, 
the numbers were extraordinary, 80 percent of the 25 people in 
the trial went into a remission in the sense they did not 
experience that multiple relapse. The patients have been 
followed now for 3 years, and the results are really quite 
impressive.
    Although we always have a caveat that the number of 
patients is relatively small, 25, but 80 percent of 25 patients 
with such positive outcomes is really encouraging.
    We are continuing to very aggressively pursue the approach 
used in this story.

                            UPDATE ON EBOLA

    Senator Murray. I am very excited about that. Thank you. 
Looking forward to more on that.
    Finally, I would just note, we have been here almost two 
hours, Mr. Chairman, and how times change. Six months ago, this 
entire discussion would have been on Ebola. No one has asked 
you about that today. That is either good news, like we do not 
have to worry any more, or it is a sign of the times that our 
attention span is way too short.
    Can you just update us really quickly on the status of 
clinical trials to test candidates on vaccines and 
therapeutics?
    Dr. Collins. Dr. Fauci.
    Dr. Fauci. Thank you very much for the question. It is good 
news, good news in the sense that from a public health 
standpoint, that the numbers of cases in West Africa have 
diminished dramatically. There has not been a case in Liberia 
in almost 40 days, which means the country of Liberia very 
likely will be declared Ebola free very soon. In Sierra Leone, 
case numbers are currently down. The number of cases in Guinea 
is still smoldering, and as we always say, you cannot claim 
victory until the last case is gone, and we are not there yet.
    From a research standpoint, there are a couple of trials 
that are going on now that we are very pleased about. One is a 
therapeutic trial in which we have taken ZMapp the most 
promising of the multiple experimental therapeutics against 
Ebola and launched a randomized, controlled trial involving 
centers in West Africa and here in the United States.
    We had one of our own patients that we had recently 
released, healthy, following Ebola, on that trial, as well as 
in the West African countries. We now have 12 people on that 
trial. There were 10 of them in Sierra Leone, one in Liberia, 
and one in the United States.
    In addition, we launched in February the randomized 
controlled trial of the NIH Ebola vaccine developed at the 
Vaccine Research Center together with an Ebola vaccine 
developed in collaboration with the Canadians as well as an 
American company, NewLink Genetics. We now have completed the 
early Phase II trial of about 50 to 100 individuals.
    The good news is that the vaccine appears to be safe. The 
results of the safety studies that we did in Bethesda at the 
NIH and at Silver Spring have proven consistent with what we 
see in West Africa. There have been 10 adverse signals that 
would be reasons to stop the study, but importantly, the 
vaccines are inducing the kind of protective immune response 
that you would predict, because it matches the monkey response.
    That is no guarantee that the vaccines will report against 
Ebola, but that is a very strong indicator it is likely to 
work.
    The thing that is complicating the vaccine trial, Senator, 
is that as we are launching the trial, the good news is the 
infections are going down. It might be difficult to prove that 
the vaccine does actually work, but every indication that we 
have of the kinds immune responses that it is inducing suggests 
strongly to us that it will work.
    Senator Murray. Thank you. Thank you very much for the 
update. Thank you, all of you, for working on that.
    Senator Blunt. Senator Cochran has no further questions. 
Senator Cassidy.

                        UPDATE ON MENTAL ILLNESS

    Senator Cassidy. Dr. Insel, I tell everybody that--I mean 
major mental illness is so drastically under addressed in our 
society. In that same article I referenced earlier in 2011, it 
said of those things that were over funded, mentioning AIDS and 
a couple of other conditions, that which was under funded was 
depression, as one example.
    First, if the criteria by which going forward will 
determine funding levels includes the possibility for clinical 
advance, and I am asking, I do not know, major mental illness, 
is that something on which increased research dollars will be 
more likely? Is there a potential for that major advance that 
would help a child with schizophrenia? You see where I am going 
with this.
    Dr. Insel. Of course. I appreciate the question, Senator, 
and there is no doubt greater investment will give us better 
returns, and this is an investment, not a cost at our end.
    I think to go back to your earlier question, I just think 
we need to frame this a little more broadly because one of the 
issues that we deal with particularly in thinking about 
schizophrenia or depression or bipolar illness, is we do not 
know enough about the basics.
    When we talk about the dollars for DALYs (Disability 
Adjusted Life Years) or we look at the disease burden, it is 
based on what we are spending on a particular disease. You 
should understand that perhaps half of our budget goes into the 
fundamentals.
    Senator Cassidy. I am so totally in agreement with you. In 
fact, one of my frustrations, it almost seems that if we are 
going to fund things which have been successful, we almost 
apriority are saying we are going to fund things we previously 
funded, as opposed to maybe we need to fund some things we 
never have before, because otherwise we will never to the point 
where we are successful.
    Dr. Insel. That gives me an opportunity to highlight the 
BRAIN initiative, which we heard a little bit about earlier.
    Senator Cassidy. Totally. It looks like even that is under 
funded. It seems like there should be $3 billion going for the 
BRAIN initiative.
    In your documentation you sent to us, you mentioned $300 
billion society spends on mental illness. Does that include 
Alzheimer's or is that independent?
    Dr. Insel. That is independent of Alzheimer's.
    Senator Cassidy. We have $300 billion on----
    Dr. Insel. Schizophrenia, bipolar disorder, depression and 
other mental disorders.
    Senator Cassidy. That is just flabbergasting. By the way, 
in my previous work, I did a lot of work in prisons. I learned 
that jails and prisons are the number one setting to treat 
mental illness. If you include--I do not know if you include 
the cost of incarceration, but if you do, that number would be 
drastically higher.
    Dr. Insel. Absolutely. We had tried to put that into the 
calculation, but could not get a full accounting.
    Senator Cassidy. The $300 billion does not include--of your 
budget, how much is going into that basic research to find the 
basis for the major mental illness?
    Dr. Insel. Roughly, 50 percent.
    Senator Cassidy. What is your total budget, $1.5 billion?
    Dr. Insel. 1.45.
    Senator Cassidy. Now, 12 percent of your dollars are going 
to HIV, and I hate to make a kind of continuing litany about 
this--by the way, my State has a very high per capita incidence 
of HIV, and my patient population had a disproportionate number 
of HIV. I am absolutely aware of the nature of the issue of 
HIV.
    It does seem that if we have too few dollars going to the 
BRAIN initiative, and you have roughly $800 million going to 
something, basic research for something that is costing us at 
least $300 billion, probably far more, it seems like we should 
be throwing everything we have at understanding that basic sort 
of science regarding that.
    The 12 percent, where does that come from? I guess in 
priority, when I go back and look and we are spending $19,000 
per death in HIV, I have a sense we are probably spending 
$2,000 per death in major mental illness, ball park.
    Dr. Insel. Let me give you some help there. With 41,000 
suicides each year in this country, that is the most recent 
number we have, 90 percent of them are due to mental illness. 
The mortality here is extraordinary. It is higher than most 
forms of cancer, higher than traffic fatalities, double, almost 
triple the rate of homicide deaths.
    Senator Cassidy. You mentioned 75 percent of those begin 
somewhere between the age of 15 or 25, or something like that?
    Dr. Insel. That is right.
    Senator Cassidy. I happen to know that the death rate, even 
if it is not suicide, among those with major mental illness, 
their average longevity is in the mid-50s as opposed to they 
die from trauma, getting beat up, et cetera.
    Dr. Insel. Those are the ones who do not die from suicide.
    Senator Cassidy. Now, I will just make a point. Dr. 
Collins, you have a tough job. As a guy with an Irish last 
name, hey, congratulations as well for being in the Irish Hall 
of Fame.
    When I hear about this, and again, I am guessing we 
probably spend $500 per death, if you want to talk about dying 
before the age at which somebody should ordinarily die, I would 
just hope that rebalancing would invest the dollars in the 
basic science then we can say we have so much success, we need 
to continue to fund that success as well.
    I do not mean to slight any other condition, except to say 
as a policy maker, every one of us knows somebody with a major 
mental illness, and the fact that the funding for that seems to 
be so woefully less and documented objectively relative to 
other diseases, puts the onus upon us to somehow address that.
    Thank you all for your work. We all stand in the shadow of 
it and we thank you for it. I yield back.

                            CLINICAL TRIALS

    Senator Blunt. Thank you. A couple of things. Dr. Gibbons, 
the budget request talks about a new program to less 
expensively identify, recruit, and enroll patients in clinical 
trials. How does that impact your work? How would that work and 
how does that impact your work in heart, blood, and lung 
research?
    Dr. Gibbons. Thank you, Senator, for that question. As you 
pointed out and Dr. Collins responded earlier, as public 
servants, it is our intention to be accountable stewards of the 
taxpayers' money.
    We are always vigilant for opportunities to be more 
efficient and more effective and economical at what we do in 
making these investments.
    As Dr. Collins alluded to, one of the more expensive 
aspects of biomedical research relates to clinical trials, and 
certainly we are always looking for different ways to ask and 
answer these important questions to transform and advance 
medicine.
    One type of study that we are looking at most recently, as 
you alluded to, are what we are calling ``simple pragmatic 
trials.'' Many trials cannot fit that category and must be done 
in the traditional way.
    However, we are taking advantage of transformation in 
biomedicine in which so much more information about a patient 
is in a digital format, and where with health systems, we can 
track and identify patients who might be eligible for a trial. 
They are embedded within a system where we can recruit them. 
Data is collected that identifies their clinical 
characteristics, in which the trial then can be launched in the 
context of where they ordinarily get care.
    Indeed, the follow up, the end points, can also be captured 
perhaps in their electronic medical record, again, within these 
health systems.
    This is a transformation that has really only happened in 
the last 5 to 10 years, and we now want to leverage that 
embedded clinical infrastructure to do research in the same way 
we do patient care.
    That has enabled us to do those trials. One current study 
relates to chronic kidney disease, where there is a high 
incidence of coronary deaths and morbidity that relates to 
that.
    As mentioned, PhRMA may spend $100 million to do a clinical 
end point study for cardiovascular disease, but by taking the 
strategy of embedding this within a health system, we can track 
patients with chronic kidney disease, often making many touch 
points within the health system, do a randomized trial to look 
at the effect of, for example, Vitamin D, which is thought/
hypothesized to influence cardiovascular outcomes, and do a 
study on a pretty large scale, 5,000 individuals.
    That can be done for one-tenth of the amount that 
traditional sort of trial can be done. That is how we are 
trying to be more efficient and effective and economical doing 
clinical research.

                                MHEALTH

    Senator Blunt. Another thing I wanted to mention was on the 
mHealth and mobile health, cell phone technology, while I do 
not think you are in the approval process business very much, 
if at all, you clearly are in the discussion business. You are 
going to be in these discussions about how do we want to let 
this develop, and in what way should it develop.
    You mentioned Fitbit that many of us carry. It is helpful. 
If it goes wrong, it is not actually life threatening. I think 
there are lots of other things that could be helpful and not 
life threatening that will quickly improve people's capacity to 
both report in new ways and monitor their own health 
situations.
    I would encourage that discussion as much as possible, 
while we want to look at things that truly can be life 
threatening, but otherwise, let this develop on its own. There 
is a market out there. This will develop, by the way, 
somewhere.
    The only question is, I think, whether we put enough 
obstacles that it does not develop in the United States, and we 
are trying to figure out how to get it from some other country. 
For example, a blood pressure monitoring device that is easier 
than the current way you monitor your blood pressure.
    Any comment you might have on that, Dr. Collins.
    Dr. Collins. I totally agree with you that this is an 
enormous opportunity, but we need not screw it up. There is 
always the possibility of doing that if we are not thoughtful.
    I think again NIH's role, where I think we can be really 
helpful, is to collect data, and figure out what is the 
evidence that these various kinds of wearable sensors can 
improve health, either by improving the likelihood of staying 
healthy or managing a chronic illness like hypertension or 
diabetes.
    You are right, it gets much more complicated if the monitor 
is doing something that could potentially be harmful. If you 
have an artificial pancreas on your wrist instead of something 
telling you how many steps you took, the difference becomes 
quite acute.
    We are aware of that. Obviously, the FDA has an incredibly 
important role here. We are working more closely with the FDA 
than ever in space like this. Of our four workshops on 
precision medicine, the fourth in late July will be at Intel in 
California.
    We are inviting a lot of the people who have the most 
inspiring ideas about mHealth to come and talk about what they 
need in order to have precision medicine be a platform for 
testing out what they are developing, to get answers as quickly 
as possible in the real world, in a well monitored situation, 
so you know what is working.
    Senator Blunt. Thank you. Senator Murray.
    Senator Murray. Thank you.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Blunt. Thank you, Dr. Collins, and thanks to your 
whole team that came today. The record will stay open for one 
week for additional questions.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
                Questions Submitted by Senator Roy Blunt
                     maximizing taxpayer investment
    Question. Dr. Lorsch, I read your recent paper with interest about 
how to maximize taxpayer investments in biomedical research. Can you 
discuss some of the principles we should consider?
    Answer. Thank you very much for your interest in how the National 
Institute of General Medical Sciences (NIGMS) is working to maximize 
the scientific returns on the taxpayers' investments in fundamental 
biomedical research. The first key principle is that a broad and 
diverse scientific research portfolio leads to strong returns. By 
increasing the diversity of our portfolio, we spread risk and increase 
the chances of important scientific discoveries being made. Second, 
fundamental research works best when it is initiated by individual 
investigators rather than directed in a top-down manner. Third, funding 
a larger number of investigators at moderate levels rather than fewer 
investigators at high levels provides the best scientific payoffs. 
Finally, shifting our funding to support research programs and 
individual investigators rather than specific projects enhances 
investigators' ability to pursue creative and ambitious scientific 
research directions.
    Question. Dr. Lorsch, you are proposing a new grant, the Maximizing 
Investigators' Research Award, that would revamp the National Institute 
of General Medical Sciences grants funding. This grant would be longer 
than current R01 awards, the budget could be modulated based on 
continuing reviews to avoid abrupt termination of research groups, and 
would allow researchers to focus more on their scientific research 
rather than on writing grant requests. Could you talk about this 
proposal and how you see it possibly transforming how research grants 
are allocated?
    Answer. Thank you for your interest in how NIGMS is working to 
transform research grant allocation. The overall goal of the Maximizing 
Investigators' Research Award (MIRA) is to improve the efficiency of 
our funding mechanisms to increase the scientific return on the 
taxpayers' investment in fundamental biomedical research. More 
efficiently distributing funding among the Nation's highly talented and 
promising investigators should improve scientific productivity and 
diversity as well as the probability of making important scientific 
breakthroughs. By supporting an investigator's research through a 
single, unified grant rather than through a series of separate, 
individual research project grants, MIRA will reduce the time spent 
writing and reviewing grant applications, giving investigators more 
time to focus on conducting research and training the next generation 
of scientists. The MIRA mechanism will also give investigators more 
freedom to explore new avenues of inquiry that arise during the course 
of their work. Lastly, as correctly noted in your question, MIRA also 
provides improved funding stability for investigators by lengthening 
the period of the award relative to current NIGMS R01 grants and by 
allowing budgets to be modulated after each round of competitive peer 
review rather than simply deciding only to fund or not fund the 
proposal. This increased stability will enable researchers to take on 
more ambitious scientific goals, assume more risk, and approach 
problems more creatively than is currently possible.
                          alzheimer's disease
    Question. Dr. Collins, there is a government goal to have a cure 
for Alzheimer's disease by 2025. In your professional opinion, how much 
money does the NIH need in fiscal year 2016 to keep pace with this goal 
and is the budget request sufficient to do so?
    Answer. NIH acknowledges, with thanks, the significant budget 
increases provided in fiscal years 2014 and 2015 for new research on 
aging, including Alzheimer's disease (AD). The addition of these new 
funds to our base appropriation has enabled us to plan carefully for 
their use, consistent with funding the best peer-reviewed science and 
the priorities established at the Alzheimer's Disease Research Summits 
convened by NIH in 2012 and 2015, as well as the Summit on Alzheimer's-
Related Dementias and a major meeting on AD among individuals with Down 
Syndrome--a population at extremely high risk of developing the 
disease--in 2013. With the resources requested for NIH in the fiscal 
year 2016 President's Budget, we estimate that could further expand 
Alzheimer's research activities by another $51 million to a total of 
$638 million.
    The recommendations and milestones that have emerged from these 
planning activities, along with other emerging opportunities in AD and 
related dementias, will be carefully considered as NIH develops an 
annual bypass budget estimate for the President and Congress, as 
mandated in section 230 of the Consolidated and Further Continuing 
Appropriations Act, 2015. Each annual bypass budget will be estimated 
based on the NIH components of the most recent update to the National 
Plan to Address Alzheimer's Disease and will outline funding 
opportunities commensurate with these plans and priorities. We 
anticipate that the first AD bypass budget, for fiscal year 2017, will 
be released in the summer of 2015.
                            brain initiative
    Question. Dr. Collins, the Subcommittee began funding the BRAIN 
Initiative in fiscal year 2014. This is an exciting research initiative 
that could revolutionize the field of neuroscience and advance 
therapies for numerous diseases, including Alzheimer's. Could you 
elaborate on the goals, objectives, budget and timeline for the BRAIN 
Initiative? In particular, could you tell the Subcommittee what funding 
commitment we are undertaking and provide details on the 10 year budget 
picture?
    Answer. Brain disorders, such as Alzheimer's disease, autism 
spectrum disorder, epilepsy, schizophrenia, depression, addiction, and 
traumatic brain injury, are among the most disabling and costly chronic 
diseases. Unfortunately, not enough is known about brain circuit 
function to meet the tremendous challenges posed by these disorders. 
The Brain Research through Advancing Innovative NeurotechnologiesSE 
(BRAIN) InitiativeSE aims to revolutionize our understanding of the 
human brain by accelerating the development and application of 
innovative technologies that will allow scientists to explore how the 
brain records, processes, uses, stores, and retrieves vast quantities 
of information, and shed light on the complex links between brain 
function and behavior. Researchers seeking new ways to treat, cure, and 
even prevent brain disorders have long desired this picture of the 
brain in action.
    With widespread input from the scientific community, the BRAIN 
Working Group of the Advisory Committee to the NIH Director developed 
BRAIN 2025, a roadmap to reach the goal of developing and applying 
innovative technologies to gain a deeper understanding of brain 
circuits.\1\ BRAIN 2025 highlights seven high-priority research areas 
that collectively aim to map the circuits of the brain, measure the 
fluctuating patterns of electrical and chemical activity flowing within 
those circuits, and understand how their interplay creates our unique 
cognitive and behavioral capabilities. In BRAIN 2025, the BRAIN Working 
Group recommended that the BRAIN Initiative ``ramp up to $400 million 
per year over the next 5 years (fiscal years 2016-2020), and continue 
at roughly $500 million per year for the last 5 years (fiscal years 
2021-2025).'' NIH has begun to ramp up the Initiative, but out-year 
funding levels will be subject to the annual budget process. In fiscal 
year 2014, NIH invested a total of $46 million in the BRAIN Initiative 
by using a combination of new and redirected funding. The request for 
BRAIN in the fiscal year 2015 President's Budget was $100 million. 
Based on the fiscal year 2015 enacted appropriation, the current 
budgeted level is $65 million (although NIH projects that its total 
fiscal year 2015 BRAIN investment will be higher). Besides the BRAIN 
Initiative funds, from individual Institutes or Centers, the NIH 
Blueprint for Neuroscience, a consortium of the neuroscience 
Institutes, Centers, and Offices at NIH, contributes the bulk of the 
additional funds.\2\ The fiscal year 2016 President's Budget proposes 
an additional $70 million for the BRAIN Initiative at NIH, for a total 
of $135 million.
---------------------------------------------------------------------------
    \1\ Http://braininitiative.nih.gov/2025/BRAIN2025.pdf.
    \2\ Http://neuroscienceblueprint.nih.gov/.
---------------------------------------------------------------------------
    Question. Dr. Collins, you requested an increase of $135 million 
increase in fiscal year 2016 for the BRAIN Initiative. However, this 
number is not in line with the professional judgement budget that 
requests $190 million. I am concerned that your budget request asks for 
several new initiatives such as Precision Medicine and Antibiotic 
Resistance, yet you are unable to adequately fund the big initiatives 
you currently have. How should the Subcommittee address this dilemma?
    Answer. The President's Budget carefully balances the funding needs 
of new initiatives, existing initiatives, and other base activities. 
The BRAIN Initiative request of $135 million is an increase of over 100 
percent compared to the fiscal year 2015 level of $65 million, and will 
allow a major expansion of activities to achieve the Initiative's 
ambitious goals as laid out in BRAIN 2025. NIH appreciates the 
Subcommittee's support for this Initiative, and hopes the Subcommittee 
will give equal consideration to the other highly promising initiatives 
in the President's Budget.
                             mental health
    Question. Dr. Insel, you are shifting the National Institute of 
Mental Health (NIMH) towards projects focusing on using brain imagery 
to detect mental illness. How will your new strategic research plan 
enable health professionals to identify people who are at risk of a 
mental illness and begin treatment early in the disease process?
    Answer. Against a backdrop of rapid scientific advances and 
dramatic changes in the landscape of mental healthcare, National 
Institute on Mental Health (NIMH) has issued a new Strategic Plan for 
Research.\3\ The four Objectives of the Plan describe the continuum of 
mental health research, ranging from understanding basic mechanisms of 
disease, to defining the trajectories of mental illnesses, to 
developing innovative treatment and prevention strategies, to ensuring 
public health impact.
---------------------------------------------------------------------------
    \3\ Http://www.nimh.nih.gov/about/strategic-planning-reports/
index.shtml.
---------------------------------------------------------------------------
    The best time to address a mental illness is before the appearance 
of symptoms that disrupt daily life. Healthcare providers seeking 
preemptive interventions will need biomarkers that can give them the 
ability to predict the onset of illness for individuals, not just 
populations, at risk. To realize this, research must identify 
biomarkers--including brain images--and behavioral indicators with high 
predictive value, as early in the course of illness development as 
possible. Therefore, the Strategic Plan for Research includes Strategy 
2.2: ``Identify clinically useful biomarkers and behavioral indicators 
that predict change across the trajectory of illness.'' To implement 
this strategy, NIMH will support research to identify early biological 
and environmental risks, protective factors, and underlying mechanisms 
to serve as novel intervention targets and develop biomarkers and 
assessment tools to predict illness onset, course, and intervention 
response across diverse populations.
    For example, a group of NIMH-funded researchers recently developed 
a magnetic resonance imaging (MRI) approach to track brain development 
in healthy infants. These researchers found marked regional differences 
in cortical development in infants' brains. High-growth regions were 
located in the association cortex, an area of the cerebral cortex that 
is involved in higher-order processes such as cognition, and low-growth 
regions were located in the sensorimotor, auditory, and visual 
cortices. This study provides a comprehensive picture of how much 
asymmetric growth occurs very early in life.\4\ Such differences in 
growth rates across the brain may inform our understanding of mental 
illnesses, as researchers previously observed abnormal developmental 
patterns in several neurodevelopmental illnesses, such as 
schizophrenia, autism spectrum disorder, and Williams' syndrome. 
Insights from such patterns may help us learn when and where to 
intervene to get developmental trajectories back on course.
---------------------------------------------------------------------------
    \4\ Http://www.ncbi.nlm.nih.gov/pubmed/20624964.
---------------------------------------------------------------------------
    Another example is the Human Connectome Project, which has given us 
unprecedented multimodal maps of the healthy human brain, providing a 
reference atlas of macro-level brain connections that can be used to 
study development, diseases, and species differences.\5\ With this 
technology, in the near future we expect maps of neurodevelopment in 
health and illness. The deeper understanding of the brain's structure 
and function made possible by these new tools and techniques will lay 
the groundwork for better therapeutic and preventive interventions.
---------------------------------------------------------------------------
    \5\ Http://www.humanconnectomeproject.org/.
---------------------------------------------------------------------------
    Strategy 2.2 exemplifies just one way in which the priorities of 
the new NIMH Strategic Plan for Research align with changes in the 
broader landscape of neuroscience research. In particular, this 
emphasis dovetails with the BRAIN Initiative, which is supporting the 
creation of new tools for decoding the language of the brain.\6\ The 
development of tools and technologies that will deepen our 
understanding of the brain's structure and function will also give us 
new approaches to map aberrant brain activity associated with mental 
illnesses. The deeper understanding of the brain's structure and 
function made possible by these new tools and techniques will lay the 
groundwork for better therapeutic and preventive interventions.
---------------------------------------------------------------------------
    \6\ Http://www.braininitiative.nih.gov/.
---------------------------------------------------------------------------
    Question. Dr. Insel, how will the BRAIN project support the 
objectives outlined in the strategic plan? Will understanding the 
fundamental science of the brain enable you to intervene before a 
person has their first psychotic break?
    Answer. In March 2015, NIMH released the new NIMH Strategic Plan 
for Research.\7\ The four Objectives of the Plan describe the continuum 
of mental health research, ranging from understanding basic mechanisms 
of disease, to defining the trajectories of mental illnesses, to 
developing innovative treatment and prevention strategies, to ensuring 
public health impact. NIMH has highlighted several cross-cutting themes 
in the Strategic Plan which investigators are strongly encouraged to 
consider in proposed studies, including the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative.\8\ The new 
Plan drives the Institute in several new directions--and one of the 
most audacious is a focus on preventing psychosis.
---------------------------------------------------------------------------
    \7\ Http://www.nimh.nih.gov/about/strategic-planning-reports/
index.shtml.
    \8\ Http://www.braininitiative.nih.gov/.
---------------------------------------------------------------------------
    Approximately 100,000 adolescents and young adults have a first 
episode of psychosis (FEP) each year in the United States.\9\ The 
majority of people with serious mental illnesses, including those with 
psychosis, experience significant delays in seeking care--nearly 2 
years, on average. Through a series of major initiatives, NIMH is 
striving to improve early identification of individuals at high risk 
for FEP, to reduce the period of untreated psychosis to less than 12 
weeks, and to maximize recovery among persons in the earliest stages of 
psychotic illness.
---------------------------------------------------------------------------
    \9\ Calculated from http://www.ncbi.nlm.nih.gov/pubmed/18480098.
---------------------------------------------------------------------------
    Last year, NIMH launched a series of studies, the Early Psychosis 
Prediction and Prevention (EP3) initiative, to define preventive 
interventions to reduce psychosis. The next step will be creating a 
network of centers for the prodrome and first episode care, called the 
Early Psychosis Intervention Network (EPINET), to reduce the number of 
first psychotic episodes from 100,000 to below 50,000 each year.\10\ By 
2016, NIMH plans to launch EPINET to align science and clinical 
practice with a goal of preventing psychosis in high-risk individuals 
and ensuring recovery for those who have had a first episode of 
psychosis.
---------------------------------------------------------------------------
    \10\ Http://www.nimh.nih.gov/funding/grant-writing-and-application-
process/concept-clearances/2015/early-psychosis-intervention-network-
epinet-a-learning-healthcare-system-for-early-serious-mental-
illness.shtml.
---------------------------------------------------------------------------
    Most of what we currently know about human brain circuitry comes 
from studying healthy individuals. To understand changes in neural 
structure and function related to mental illnesses, including 
psychosis, we need tools and technologies that enable new approaches to 
map aberrant brain activity associated with mental illnesses. The BRAIN 
Initiative is designed to accelerate the development of just such tools 
and technologies, showing how individual cells and complex neural 
circuits interact in both time and space. An improved understanding of 
the brain's structure and function made possible by these new tools and 
techniques will lay the groundwork for better therapeutic and 
preventive interventions, reducing the duration of untreated psychosis 
in individuals experiencing FEP, and improving clinical and functional 
outcomes among persons in the earliest stages of serious mental 
illnesses.
    Question. The National Institute on Mental Health (NIMH) recently 
finished the largest study of mental health risks ever conducted among 
military personnel. Dr. Insel, can you discuss what this study has 
resulted in, particularly in terms of treatment and resources available 
to active duty servicemembers and veterans?
    Answer. The Army Study to Assess Risk and Resilience in Service 
members (Army STARRS) is the largest study ever undertaken of military 
mental health.\11\ Army STARRS covers the entire active duty Army since 
2004, via Army and Department of Defense administrative data, combined 
with rich new data collected by the study via confidential surveys and 
other methods from approximately 110,000 soldiers from across the armed 
forces. Although historically the suicide rate in the U.S. Army has 
been below the rate for demographically similar civilians, the suicide 
rate in the Army began climbing in the early 2000s, approximately 
doubling between 2004 and 2008, tripling between 2004 and 2012, and 
exceeding the civilian rate after 2008; meanwhile, the suicide rate 
among demographically similar civilians stayed approximately constant. 
Concerns about this increase led to a partnership between the Army and 
NIMH to identify risk and protective factors for suicide and associated 
outcomes in Army soldiers, to inform the Army's prevention and 
treatment programs.
---------------------------------------------------------------------------
    \11\ Http://www.nimh.nih.gov/health/topics/suicide-prevention/
suicide-prevention-studies/army-study-to-assess-risk-and-resilience-in-
servicemembers-army-starrs-a-partnership-between-nimh-and-the-us-
army.shtml.
---------------------------------------------------------------------------
    Army STARRS will complete its initial phase in June 2015. The study 
has assessed a range of hypotheses regarding suicide risk, rejecting 
some and confirming others. For instance, the study found that many of 
the original theories about the drivers for the increase in suicide--
e.g., increasing history of multiple deployments, wider use of 
accession waivers, and the shift from group quarters to single-soldier 
housing--were not borne out empirically; such findings enable Army 
leaders to focus on more promising areas for prevention. In parallel, 
the study has developed algorithms for identifying relatively small 
groups of soldiers within the wider Army population who, based on 
statistical analyses of their characteristics and experiences, have 
significantly elevated suicide risk and account for a disproportionate 
fraction of all Army suicides (i.e., 5 percent of soldiers who account 
for around 40 percent of all suicides, and 1 percent of soldiers who 
account for approximately a quarter of suicides). Such methods 
complement the Army's ongoing prevention and intervention efforts by 
enabling the Army to focus particularly on soldiers with the highest 
predicted risk.
    Army STARRS released its first findings related to suicide attempts 
and deaths in a series of three JAMA Psychiatry articles in March 
2014.\12\ Findings include: the rise in suicide deaths from 2004 to 
2009 occurred not only in currently and previously deployed soldiers, 
but also among soldiers never deployed; nearly half of soldiers who 
reported suicide attempts indicated their first attempt was prior to 
enlistment; and, soldiers reported higher rates of certain mental 
disorders than civilians, including attention deficit hyperactivity 
disorder, intermittent explosive disorder (recurrent episodes of 
extreme anger or violence), and substance use disorder.\13, 14, 15\ 
This and subsequent research by Army STARRS points to empirically 
identified risk and protective factors for suicide and related 
outcomes--including fatal and non-fatal accidents--which, in addition 
to enabling the Army to focus its prevention and treatment programs, 
also informs the development of novel efforts to reduce suicide and 
suicidal thoughts and actions among service members at higher risk.\16\
---------------------------------------------------------------------------
    \12\ Http://www.nimh.nih.gov/news/science-news/2014/suicide-in-the-
military-army-nih-funded-study-points-to-risk-and-protective-
factors.shtml.
    \13\ Http://archpsyc.jamanetwork.com/
article.aspx?articleid=1835337.
    \14\ Http://archpsyc.jamanetwork.com/
article.aspx?articleid=1835338.
    \15\ Http://archpsyc.jamanetwork.com/
article.aspx?articleid=1835339.
    \16\ Http://www.ncbi.nlm.nih.gov/pubmed/25441238.
---------------------------------------------------------------------------
                                 ______
                                 
               Questions Submitted by Senator Jerry Moran
                              common rule
    Question. Current Federal regulations known as the ``Common Rule'' 
permit the use of de-identified or anonymous human biospecimens for 
research without obtaining the donor's informed consent. De-identified 
or anonymous samples lack traditional identifiers that might permit the 
specimen to be traced back to an individual. Anonymous or de-identified 
samples are coded with a unique identifier in place of name, hospital 
chart number, social security number, or other obvious and publicly 
available means of identification. The key to the code is held 
separately from the samples and researchers using de-identified samples 
do not have access to the key so the researcher cannot re-identify an 
individual.
    The U.S. Department of Health and Human Services is considering 
changes to the Common Rule that would no longer permit the research use 
of unidentified samples without informed consent of the individual, 
with the rationale that modern genetic technology makes it possible to 
identify the donor of any sample. The broad array of human biospecimens 
includes fluids and cell or tissue collections. There is widespread 
concern in the pathology community that a requirement to obtain 
informed consent for the research use of unidentified human 
biospecimens would have a detrimental, if not devastating impact on 
research. Often times these exploratory, retrospective and correlative 
studies are performed on minimal budgets and the implementation of the 
proposed changes could threaten pathology as an academic pursuit 
capable of contributing to biomedical research in a meaningful way.
    Given this background, what is the evidence in terms of actual, 
documented cases where researchers have abused their access to 
biospecimens in an attempt to specifically identify research subjects 
and is this proposed change by HHS an appropriate response considering 
the scope of the problem?
    Answer. The Advance Notice of Proposed Rulemaking (ANPRM) for the 
Common Rule, published in 2011, proposed a change in the current Rule 
to require that informed consent be obtained for the use of 
biospecimens collected for clinical purposes (such as research with 
excess pathological specimens) even if they were de-identified. The 
proposal was to make the change prospective so that biospecimens 
collected before the effective date of the new rule would not be 
subject to the requirement. Importantly, ANPRM also proposed to allow 
the consent to be broad, in other words, through a brief, standardized 
form that described the research purpose in broad, non-specific terms. 
ANPRM also proposed that the Institutional Review Boards review would 
not be required for the use of the biospecimens if consent was obtained 
using an approved template. When individuals are enrolled in research 
and their biospecimens are collected, de-identified, and shared for 
future research, the investigators who recruit them are already 
obtaining consent for their enrollment, and thus the ANPRM proposal 
would only modify (and, in fact, streamline) the existing consent 
requirement for biospecimens obtained in research.
    ANPRM proposed to require consent be obtained for the research use 
of de-identified biospecimens for two reasons. First, and most 
important, is that asking research participants or patients to consent 
to the use of their biospecimens in research is more respectful of 
their interests than using their de-identified biospecimens without 
their consent. A growing body of literature suggests that research 
participants and patients want to be asked to give their consent to 
research.\17, 18, 19\
---------------------------------------------------------------------------
    \17\ Kaufman et al. Public Opinion about the Importance of Privacy 
in Biobank Research. American Journal of Human Genetics. 85(5): 643-
654. (2009).
    \18\ Vermeulen et al. A Trial of Consent Procedures for Future 
Research with Clinically Derived Biological Samples. British Journal of 
Cancer. 101(9): 1505-1512. (2009).
    \19\ Trinidad et al. Research Practice and Participant Preferences: 
the Growing Gulf. Science. 331(6015): 287-288. (2011).
---------------------------------------------------------------------------
    Second, the proposed change also recognizes that the current 
premise allowing the use of de-identified biospecimens without consent, 
in other words, that no harm can come to individuals because the 
biospecimens are de-identified, may no longer be valid. Rapid advances 
in bioinformatics and data analytics are enabling the re-identification 
of individuals by combining data generated from their biospecimens with 
data from a third party. Increasingly refined techniques for the re-
identification of individuals from data generated from biospecimens 
continue to be published in the scientific literature.\20\ In one case, 
researchers were able to demonstrate a technique that re-identified 
individuals by using data from biospecimens and several other publicly 
accessible sources, although they did not reveal the identities.\21\ 
Individuals whose biospecimens are used in research are now being 
exposed to a risk that did not exist when human subject protections 
were developed in the mid-1970s, and it is, therefore, no longer 
appropriate to use their biospecimens without consent.
---------------------------------------------------------------------------
    \20\ For example of a recent finding, see Philibert P et al. 
Methylation array data can simultaneously identify individuals and 
convey protected health information: an unrecognized ethical concern. 
Clinical Epigenetics 2014, 6:28 doi:10.1186/1868-7083-6-28.
    \21\ Gymrek et al. Identifying Personal Genomes by Surname 
Inference. Science. 339(6117): 321-324. (2013).
---------------------------------------------------------------------------
    These changes are important for another reason as well. Requiring 
consent will help move the biomedical research enterprise to a more 
participatory model where patients are more engaged and involved in 
advancing research.
    Question. Wouldn't a better approach be to insure that civil and/or 
criminal penalties are in place to appropriately punish those 
potentially rare investigators that abuse their access currently 
granted to them by local Institutional Review Boards?
    Answer. Increasing penalties for unauthorized re-identification of 
biospecimens may also be a good idea. However, from an ethical 
standpoint, it cannot take the place of seeking consent. In addition, 
any new prohibition against re-identification should not include 
legitimate research intended to reveal vulnerabilities in de-
identification and anonymization techniques, such as the publication by 
Gymrek et al.
                         translational research
    Question. The time required to discover, develop, and obtain FDA 
approval for a new drug is about 14 years with an associated cost of $2 
billion or more. The failure rate of this process exceeds 95 percent.
    Considering these steep challenges, I am very interested in the New 
Therapeutic Uses initiative within the National Center for Advancing 
Translational Sciences (NCATS). This initiative facilitates 
partnerships between pharmaceutical companies and academic researchers 
to explore new uses for investigational drugs for treating a variety of 
diseases. This program is a unique opportunity to accelerate promising 
new treatments to patients, patients that cannot wait 14 years for a 
new drug to become available to them. Through your leadership, several 
companies have provided access to shelved drug compounds to test ideas 
for new therapeutic uses, and you have facilitated collaborations 
between these firms and academic investigators. Within 3 months of 
receiving funding, academic researchers have advanced such drug 
compounds to patients suffering from Alzheimer's disease and 
schizophrenia.
    What can we do to not only continue to support this drug 
repurposing initiative, but to also establish a systematic 
translational research process to identify new uses for FDA-approved 
drugs?
    Answer. A single drug or specific combination may be effective in 
treating several distinct disorders. ``Repurposing'' refers to studying 
drugs that are already approved to treat one disease or condition to 
see if they are safe and effective for treating other diseases. For 
every drug that is approved by the Food and Drug Administration (FDA), 
many others are abandoned after initial clinical testing but before FDA 
approval due to lack of effectiveness or for business reasons. The 
National Center for Advancing Translational Sciences (NCATS) focuses on 
drug repurposing because of the potential for rapid therapeutic 
advances and lower costs.
    To enable such ``repurposing'' on a broad scale, researchers can 
tap the NCATS Pharmaceutical Collection, a comprehensive database and 
compound screening library of drugs and investigational medicines 
approved for clinical use by regulatory authorities in the United 
States, Europe, Canada, and Japan. The Collection is available in two 
forms: as a free electronic resource that lists the drugs and their 
regulatory status, and as a compound library used in collaborative 
high-throughput screening assays at the NCATS Chemical Genomics Center.
    Screening of these drugs already has led to clinical trials. One 
group of scientists wanted to understand whether drugs used to treat 
other conditions might also be used to better treat hepatitis C. In a 
drug repurposing screen, the team identified a compound called 
chlorcyclizine that inhibited the ability of the hepatitis C virus to 
infect cells. Chlorcyclizine is an over the counter antihistamine to 
treat seasonal allergies. In early 2014, FDA-approved chlorcyclizine 
for clinical trials to test whether it can be used to treat hepatitis 
C.
    Launched in 2012, Discovering New Therapeutic Uses for Existing 
Molecules (New Therapeutic Uses) is a collaborative initiative designed 
to facilitate partnerships between pharmaceutical companies and the 
biomedical research community to advance therapeutics development. This 
innovative program matches pharmaceutical companies that have 
investigational drugs or biologics with academic investigators who have 
new ideas for disease indications in which the drugs could be tested. 
Through New Therapeutic Uses, NCATS is re-engineering how the public 
and private sectors collaborate and is creating new and rapid ways to 
test novel treatments for diseases with unmet medical needs. Through 
the program, NCATS provides researchers with access to a selection of 
pharmaceutical industry agents that have cleared many key steps in the 
drug development process, including safety testing in humans, with the 
ultimate goal of identifying promising new treatments for patients. 
Repurposing these agents for a new use offers the potential for rapid 
completion of development and ultimate regulatory approval. NCATS 
crowdsourced these agents through New Therapeutic Uses, providing 
scientists nationwide with a strong starting point from which to engage 
in therapeutics development.
    New Therapeutic Uses is designed to streamline the legal and 
administrative process for research collaboration across organizations 
through template partnership agreements, which are available on the 
NCATS website. During the program's pilot phase, these agreements 
reduced the time required to establish collaborations between industry 
and academia to about 3 months, far less than the more typical 9 months 
to 1 year. In June 2013, as part of the pilot phase, NIH awarded $12.7 
million to nine academic research groups for projects to explore new 
treatments for patients in eight disease areas. Within 3 months, one-
third of the project investigators were testing compounds in humans for 
new uses, including potential treatments for schizophrenia (two agents) 
and Alzheimer's disease. NCATS is celebrating one of the first 
promising results of this program: Center-supported scientists at Yale 
University School of Medicine have found that an experimental compound 
originally developed as a cancer therapy potentially could be used to 
treat Alzheimer's disease. The compound successfully reversed brain 
problems in mouse models of the condition, and now the researchers are 
testing it in a Phase 2a clinical trial.
    Question. What can we do to support drug rescue and repurposing 
efforts to identify promising new treatments for children and 
adolescents in addition to adults?
    Answer. A significant amount of NCATS' repurposing efforts are 
focused on rare diseases, and since more than 50 percent of rare 
diseases are pediatric, these efforts may be particularly effective in 
identifying promising new treatments for children and adolescents.
    In May 2014, NCATS announced new funding opportunities to build on 
the pilot phase of the New Therapeutics Uses program. NCATS is 
collaborating with AstraZeneca; Janssen Research & Development, LLC; 
Pfizer; and Sanofi to make 26 agents available, including, for the 
first time for this program, some that are suitable for exploring 
pediatric indications.
                            clinical trials
    Question. The University of Kansas Medical Center is one of only 21 
medical centers in the country that has an Alzheimer's Disease Center, 
a National Cancer Institute-designated Cancer Center, and a NIH 
Clinical and Translational Science Award (CTSA) program. Eight of the 
17 NCI cancer drug therapies advancing to clinical trials have been 
formulated at the University of Kansas, and three of these drugs have 
been successfully developed and approved by the FDA. Additionally, KU 
Cancer Center has partnered with industry, academia, government, and 
disease philanthropy organizations to advance ten promising new cancer 
treatments to patients over the past five and a half years.
    Considering these successes, how do we expand the number of cancer 
(and other) clinical trials offered in Kansas and other rural States?
    Answer. The National Cancer Institute (NCI) and NIH share your 
commitment to ensuring patients living in rural areas have access to 
clinical trials. As a result of the recent restructuring of NCI's 
National Clinical Trials Network (NCTN), including the launch of the 
NCI Community Oncology Research Program (NCORP) in August 2014, more 
people in Kansas and other rural States have the opportunity to 
participate in cancer clinical trials. NCORP supports many different 
types of cancer research in the community setting, with access to large 
and diverse patient populations. The overall goal of NCORP is to bring 
cancer clinical trials (cancer control, prevention, screening, 
treatment, and imaging), as well as cancer care delivery research 
(CCDR), to individuals in their own communities to generate a broadly 
applicable evidence base that contributes to improved patient outcomes 
and a reduction in cancer disparities.
    NCI supports 53 NCORP sites across the country (7 research bases, 
34 community sites, 12 minority community sites), including two sites 
in Kansas--the Wichita NCORP and the Kansas City NCORP. These 53 
community sites and research bases extend their reach even further 
through a network of 837 component sites--local cancer centers, 
hospitals, and clinics that are affiliated with the NCORP network and 
make NCI-supported clinical trials available in a community setting. 
For example, in Kansas, the Wichita and Kansas City NCORPs include 24 
component sites, from Liberal and Dodge City in the west, Wellington 
and Winfield in the south, Salina and Lawrence to the north, Parsons 
and Fort Scott to the east, and points in between. Currently, NCI 
supports 109 active clinical trials in Kansas.
    To address the need to provide clinical trial access to rural 
populations in other States, NCTN also supports 30 ``Lead Academic 
Participating Sites'' (LAPS) at academic medical centers. While most 
centers are located in urban areas, those located within rural States 
do provide another point of access to NCI-supported clinical trials for 
cancer patients in these rural communities. For example, LAPS sites 
include the; the University of Oklahoma Health Sciences Center in 
Oklahoma City, Oklahoma; the University of Alabama at Birmingham; and 
the Norris Cotton Cancer Center in Lebanon, New Hampshire.
    Question. One of NIH's important roles is supporting clinical 
trials. I understand you've taken some steps recently to increase the 
impact of NIH funded trials. Can you describe the changes you're making 
and the impact you're expecting?
    Answer. Twenty-four NIH Institutes and Centers (ICs) fund clinical 
trials. Over the last 3 years, NIH has been engaged in a trans-NIH 
effort to enhance the stewardship of clinical trials funded by NIH. 
Activities that are designed to increase the impact of NIH-funded 
clinical trials include:
  --Facilitating access to clinical trials of Food and Drug 
        Administration (FDA)-regulated products by instituting clearer 
        and more specific requirements for clinical trial registration 
        and results submission as established by Title VIII and through 
        enhancements to ClinicalTrials.gov.
  --Increasing the transparency of NIH-funded clinical trials by 
        expecting all NIH-funded clinical trials to register and submit 
        summary results to ClinicalTrials.gov.
  --Enhancing the efficiency of clinical trial research and reducing 
        unnecessary burdens by promoting the use of single 
        Institutional Review Boards (IRBs) in multi-site in NIH-funded 
        human subject's research.
  --Collaborating with FDA to develop a clinical trial protocol 
        template. Such a template would facilitate the preparation and 
        improving the quality of clinical trial protocols, reduce the 
        time needed for review and enhance the consistency of the 
        review process.
  --Promoting early and improved communication between NIH and FDA on 
        clinical trial design.
  --Exploring strategies to increase enrollment and retention of 
        participants in NIH-funded clinical trials.
  --Improving the skills of clinical trial investigators by 
        implementing a requirement for good clinical practice training 
        for NIH-funded investigators and NIH staff with 
        responsibilities for conducting, overseeing, and/or managing 
        clinical trials.
  --Enhancing stewardship through improved clinical trial award 
        monitoring systems and identifying best practices for data and 
        safety monitoring of clinical trials.
    These efforts are progressing well. Because they are multi-faceted 
and approach various aspects of the clinical trial enterprise, we 
anticipate that their impact will be significant.
                          alzheimer's disease
    Question. Dr. Collins, over the last 2 years Congress has provided 
the National Institute on Aging with approximately $125 million in 
increased funding to support good science that addresses Alzheimer's 
disease and other dementias. As you know, there is a National 
Alzheimer's Plan that specifically lays out a series of scientific 
milestones that researchers think need to be met in order to make a 
meaningful impact on the trajectory of Alzheimer's by 2025. If Congress 
were to provide additional Alzheimer's research funding as requested in 
the budget, does NIA have a plan in place to make sure that those 
resources will be specifically targeted to meet the milestones the 
scientific community has established?
    Answer. The National Institute on Aging (NIA) acknowledges, with 
thanks, the significant funding increases provided in fiscal year 2014 
and fiscal year 2015 for new research on aging, including Alzheimer's 
disease (AD). These new funds enabled us to plan carefully for their 
use, consistent with funding the best peer-reviewed science and the 
priorities established at the Alzheimer's Disease Research Summits 
convened by NIH in 2012 and 2015, as well as the Summit on Alzheimer's-
Related Dementias and a major meeting on AD among individuals with Down 
Syndrome--a population at extremely high risk of developing the 
disease--in 2013.
    In particular, the 2015 Summit built on the foundation laid by the 
2012 NIH AD Research Summit, the U.S. National Alzheimer's Project Act 
(NAPA)/National Plan to Address Alzheimer's disease, and the 2013 G8 
Global Dementia Summit. Participants reviewed progress made since the 
2012 Summit and evaluated issues of critical importance for 
identification and implementation of successful therapeutic 
interventions for AD.
    At the Summit's conclusion, a select group of experts, including 
NIA/NIH staff, representatives from other funding agencies supporting 
Alzheimer's research, academic and industry scientists who chaired the 
Summit sessions on behalf of all the presenters, and members of the 
National Alzheimer's Project Act (NAPA) council, formulated a set of 
research recommendations. These recommendations, in turn, will inform 
our research priorities and serve as the basis for updating and 
refining the NAPA research milestones. The recommendations were 
recently made available.\22\ In addition, the fiscal year 2017 NIH 
Bypass Budget on AD, which will be released this summer, will outline 
funding opportunities commensurate with these plans and priorities.
---------------------------------------------------------------------------
    \22\ At http://www.nia.nih.gov/research/recommendations-nih-ad-
research-summit-2015.
---------------------------------------------------------------------------
                           initiative funding
    Question. If Congress were to appropriate $32 billion for NIH in 
fiscal year 2016--a number I understand the biomedical research 
community has coalesced around in recent years--what key initiatives 
would NIH fund that you are not currently funding?
    Answer. The key initiative in the fiscal year 2016 President's 
Budget that NIH is not currently funding is the $200 million Precision 
Medicine Initiative. This proposal includes $70 million for expanding 
current cancer genomics research to initiate new studies of how a 
tumor's DNA can be used to predict and treat tumor cells that develop 
resistance to a therapy, apply new noninvasive methods to track 
response to therapy, and explore the efficacy of new combinations of 
cancer drugs targeted to specific tumor mutations. It also includes 
$130 million to develop a one-million or more volunteer participant 
research cohort. These funds will support several related activities: 
1) Enrolling and consenting; 2) Building a biorepository; 3) Core 
phenotyping; 4) Genome analysis; 5) informatics; and 6) staffing. NIH 
also seeks to increase the number of new and competing Research Project 
Grants, which has been relatively flat over the years despite 
increasing research opportunities and many more grant applications. The 
result has been a much lower success rate for applicants than in the 
past, which makes it necessary for investigators to submit even more 
applications and discourages trainees from pursuing a biomedical 
research career. Additional funding, as requested in the fiscal year 
2016 President's Budget, would begin to address this situation.
                         rare disease research
    Question. We have seen major progress on some of the most common 
diseases affecting Americans, much of which is due to the 
groundbreaking work supported by NIH. However, over 30 million 
Americans suffer from rare diseases, 95 percent of which have no cures 
or treatments. Could you shed some light on what the NIH is doing to 
accelerate rare disease research and innovation?
    Answer. Given the unique challenges associated with rare diseases, 
a team approach towards research is particularly important. The 
National Center for Advancing Translational Sciences (NCATS) supports 
collaborative models for advancing discovery and therapeutics 
development for rare diseases, creating partnerships among government, 
industry, academia, and patient advocacy groups. New discoveries about 
the molecular basis of rare diseases offer unprecedented opportunities 
to improve the diagnosis and treatment of these conditions. NCATS is 
capitalizing on these opportunities through its rare diseases research 
programs, particularly its Rare Diseases Clinical Research Network 
(RDCRN) and the Therapeutics for Rare and Neglected Diseases (TRND) 
program.
    RDCRN is designed to advance medical research on rare diseases by 
facilitating collaboration, study enrollment, and data sharing. Through 
the network of participating multi-site consortia, physician scientists 
and their multidisciplinary teams at hundreds of clinical sites around 
the world work together with representatives of nearly 100 patient 
advocacy groups to study more than 200 rare diseases. RDCRN facilitates 
clinical research in rare diseases through support for: 1) 
collaborative activities, including longitudinal studies of individuals 
with rare diseases, clinical studies, and clinical trials; 2) training 
of clinical investigators in rare diseases research; 3) pilot and 
demonstration projects; 4) uniform data collection protocols; 5) cost-
sharing infrastructure; and 6) access to information about rare 
diseases for basic and clinical researchers, academic and practicing 
physicians, patients, and the public. The RDCRN website is a resource 
for healthcare providers, researchers, patients and caregivers, and the 
general public. Each consortium of RDCRN studies a minimum of three 
related rare diseases. It also includes a novel web-based contact 
registry for patients who are considering participating in RDCRN 
clinical studies. Since its launch, RDCRN has enrolled 30,603 
participants in multisite clinical research studies, and trained 208 
young investigators in rare diseases clinical research. Ninety-one 
studies are currently underway. In October 2014, NIH announced nearly 
$29 million in awards to expand RDCRN to support 22 consortia and a 
Data Management and Coordinating Center.
    The TRND program's goal is to speed the development of treatments 
for rare and neglected diseases. The program operates via collaborative 
research partnerships with public and private entities, which leverage 
the unique strengths and capabilities of each party to develop new 
technologies and models that improve the efficiency of therapeutic 
development. TRND scientists provide drug development expertise and 
resources, working with research partners to develop potential 
therapeutics through first-in-human clinical testing. This also 
includes guiding the design of clinical trials and submitting IND 
applications to the Food and Drug Administration. These efforts 
effectively ``de-risk'' therapeutic candidates and make them more 
attractive for adoption by outside business partners. At the end of 
2014, TRND had a portfolio of 14 active projects targeting drug 
development for some of the most devastating diseases affecting either 
small populations in the United States or large populations in the 
developing world. To-date, six projects targeting chronic lymphocytic 
leukemia, Niemann-Pick disease type C1, sickle cell disease, GNE 
myopathy, Duchenne muscular dystrophy, and retinitis pigmentosa yielded 
successful IND applications to FDA and have entered human clinical 
trials. In 2014, two projects were successfully de-risked and adopted 
by larger pharmaceutical industry partners to continue development: 
Baxter International adopted the sickle cell disease treatment from our 
collaborator, AesRx, while Shire Pharmaceuticals adopted a compound 
targeting autosomal dominant retinitis pigmentosa from our collaborator 
BIKAM Pharmaceuticals. These outright adoptions are in addition to 
several collaborators successfully leveraging TRND de-risking support 
to obtain additional external funding from venture capital and 
philanthropic organizations to support continued development of their 
new therapeutic candidates.
                  alzheimer's/down syndrome connection
    Question. At a hearing last year, you provided a thoughtful 
response to a question I asked about what NIH is doing to explore the 
link between Down syndrome and Alzheimer's disease. You indicated that, 
in the next year or two, there will be new initiatives focused on the 
very special population of individuals with Down syndrome to see what 
NIH could learn from them. One of those was a recently announced grant 
to study Alzheimer's biomarkers in people with Down syndrome. I applaud 
NIH for moving forward with that study, and encourage you to complete 
it. Could you provide us with an update on the status of other 
initiatives related to the Alzheimer's-Down syndrome connection?
    Answer. In individuals with Down syndrome (DS), the triplication of 
the amyloid precursor protein (APP) gene on chromosome 21 results in 50 
percent greater levels of both APP and amyloid beta, a pathological 
hallmark of Alzheimer's disease (AD). For this reason, adults with DS 
are at extremely high risk for developing AD. Most individuals with DS 
develop AD's characteristic amyloid plaques and tau tangles in the 
brain by their 30s and 40s, and a high percentage (estimates of up to 
80 percent) develop clinical dementia as they age into their 70s. 
Because individuals with DS are at high risk of developing AD dementia, 
identification of interventions to prevent and treat the disease in 
this population is a priority. In addition, the study of disease 
modifying interventions among DS-affected individuals may provide 
important insights about the efficacy and timing of such interventions 
targeting AD in the general population.
    In April 2013, the National Institute on Aging (NIA) and the Eunice 
Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD) co-sponsored a conference to help set a research 
agenda aimed at speeding the development of possible therapies to treat 
AD in individuals with DS. Representatives from academia, industry, 
Federal agencies, and private foundations explored topics such as the 
AD pathway, animal models, biomarkers, and cognitive assessments. As a 
result of discussions at this conference, the AD and DS research 
communities have engaged in more active collaborations. In addition, 
NIA and NICHD have partnered on an initiative, ``Biomarkers of 
Alzheimer's Disease in Down Syndrome'' to encourage multidisciplinary 
integrative studies aimed at identifying the longitudinal progression 
of AD in adults with DS using clinical, cognitive, imaging, genetic, 
and/or biochemical biomarkers. Projects will be awarded later in fiscal 
year 2015.
    NIH-supported researchers are working on other fronts to better 
understand the intersection of DS and AD. For example:
  --A recently funded clinical trial is testing the first immunotherapy 
        for the treatment of Alzheimer's disease in DS. This Phase I 
        trial will evaluate the safety and tolerability of an active 
        vaccine in adults with DS aged 35-55. Effects on cognitive 
        function and AD biomarkers will also be explored.
  --One ongoing study is documenting amyloid deposition in asymptomatic 
        adults with DS and following these individuals to understand 
        the course of amyloid deposition and its effect on functioning 
        over time.
  --An NICHD-supported study is identifying changes in brain 
        inflammation, cerebrovascular dysfunction, and white matter 
        integrity losses that signal changes in cognition, behavior, 
        and functioning reflecting AD in adults with DS.
  --NICHD-supported investigators are developing a predictive model by 
        which the changes in imaging and biomarker measures will allow 
        a composite assessment of the likelihood of cognitive decline 
        and AD in adults with DS.
  --Researchers in an NICHD-funded study found that adults with DS had 
        a significantly higher likelihood of dementia if their parents 
        had earlier reported higher levels of depression, suggesting 
        that addressing parents' mental health may have long-term 
        benefits for their adult children with DS.
  --Using mice bred to have symptoms of both DS and AD, scientists 
        found evidence of male/female differences in several regions of 
        the brain known to be affected in AD because of abnormal 
        transmission of chemical signals from one brain cell (neuron) 
        to another. Ultimately, understanding sex differences in the 
        brains of individuals with DS may have important implications 
        for developing new drug treatments.
                             down syndrome
    Question. According to the NIH Strategic Plan for Down Syndrome, at 
least one-half of all individuals with the condition also have one or 
more co-occurring medical and psychiatric conditions. These include 
Alzheimer's disease, childhood leukemia, congenital heart disease, 
autism spectrum disorders, sleep apnea and epilepsy, to name a few. It 
seems like there is much that can be learned by studying people with 
Down syndrome, and not just about the condition itself. What is NIH 
doing in this area?
    Answer. Co-occurring conditions are common among those individuals 
with intellectual and developmental disabilities. For example, NIH-
funded scientists recently studied the genes in 452 infants with Down 
syndrome (DS) to better understand a specific type of heart defect 
common in infants with DS, called atrioventricular septal defects 
(AVSDs). The researchers found that the 210 infants in this group with 
AVSDs were more likely to have rare, large genetic information missing. 
This missing information is critical to embryonic development, 
suggesting that the missing genes can also negatively affect the 
development of other organ systems and may influence the type of care 
these children receive.
    In June 2014, the National Institute of Mental Health (NIMH) and 
the Eunice Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD) co-sponsored a workshop on ``Mental Health in 
Intellectual and Developmental Disabilities: Research Challenges and 
Opportunities,'' which identified many of the issues that face those 
with intellectual disabilities such as DS who also have a diagnosis of 
a mental health or behavioral disorder. More research is needed into 
the identification of such comorbid conditions in those with 
intellectual disabilities, as well as the development of effective 
treatment strategies to help improve their quality of life.
    Together with NIMH, NICHD continues to encourage studies that 
develop and validate outcome measures for use in clinical trials for 
individuals with intellectual and developmental disabilities (IDDs), 
including Down syndrome, which often includes co-occurring conditions. 
These two institutes recently published a funding opportunity in order 
to encourage applications to develop this significant area of research, 
especially important in efforts to develop pharmacological treatments 
for individual with IDDs.\23\ In addition, NICHD sponsored a scientific 
workshop in April 2015 focused on the development of outcome measures 
for cognitive, behavioral, and physical measures for clinical trials 
for people with Down syndrome.
---------------------------------------------------------------------------
    \23\ Http://grants.nih.gov/grants/guide/pa-files/PAR-13-213.html.
---------------------------------------------------------------------------
    To continue to address the health needs of people with DS, NIH is 
supporting a wide range of research-related activities to assist the DS 
research community in making progress on their work. In late 2014, led 
by NICHD, NIH released Down Syndrome Directions: The NIH Research Plan 
on Down Syndrome, which provides an updated strategy, with specific 
research goals and objectives, for the field of Down syndrome research. 
The Plan was developed by the NIH Down Syndrome Working Group with 
input from researchers, healthcare providers, self-advocates, and 
families through two opportunities for public comment. The plan 
includes a new section on DS and aging, a call for more research on co-
occurring health conditions associated with DS, and highlights of 
research accomplishments since the plan was first issued in 2007.
    In 2013, NICHD, in coordination with the NIH Down Syndrome Working 
Group and the Down Syndrome Consortium, launched DS-Connect, a Web-
based health registry to facilitate contacts and information sharing 
among individuals with DS and their families, researchers and 
healthcare providers. People with DS or their family members are able 
to enter contact information and health history in an online, secure, 
confidential database. Included in the questionnaires that registrants 
are asked to complete are several sets of queries on comorbid 
conditions, such as leukemia, congenital heart defects, and autism and 
other developmental disorders; the responses to these questions are 
anonymized so that researchers may get a better idea of the frequency 
of these comorbid conditions, and design their research studies 
accordingly. Researchers who are interested in recruiting participants 
for their research studies can contact the DS-Connect Registry 
Coordinator, who scans the database for individuals who might meet the 
criteria. The Coordinator then contacts those families and provides the 
family with the researcher's contact information. Ultimately, the 
registry will link to biorepositories of tissue samples and other 
resources, making it easier for participants to take part in clinical 
studies for new medications and other treatments for DS.
                            pediatric cancer
    Question. Pediatric cancer death rates have declined by nearly 70 
percent over the past four decades. However, cancer remains the leading 
cause of death from disease among children. Despite our progress, 
advancements in treatments for childhood cancers are needed. Could you 
provide an update on current NIH priorities for childhood cancer 
research and your most promising initiatives.
    Answer. The National Cancer Institute (NCI) recognizes the 
importance of research that specifically addresses pediatric cancers 
and has an extensive portfolio of research focusing on cancers in 
children and adolescents. NCI supports a broad range of biomedical 
research that extends from basic science, which enhances our 
understanding of the fundamental mechanisms of cancer, to clinical 
research, as well as research focused specifically on childhood cancer 
survivorship. Supporting research across this spectrum to benefit 
children with cancer continues to be a priority for NCI and NIH. 
Promising opportunities and initiatives are underway in a number of 
areas, including cancer genomics research, pre-clinical testing, 
precision medicine clinical trials, immunotherapy approaches to treat 
pediatric cancers, and survivorship research.
    For example, to take advantage of new information about pediatric 
cancer, especially in genomics, NCI convened a workshop in February 
2015 to discuss the opportunities for future improvement in detection, 
diagnosis, prevention, and treatment that build on recent genetic 
discoveries. The workshop participants included leading pediatric 
genomics research from across the United States, international genomics 
experts, and representatives from the pediatric cancer advocacy 
community. This field is informed by NCI's Therapeutically Applicable 
Research to Generate Effective Treatments (TARGET) program, which uses 
genomic approaches to catalog the full range of molecular changes in 
several childhood cancers to increase our understanding of their 
pathogenesis, improve their diagnosis and classification, and identify 
new candidate molecular targets for better treatments. The related NCI 
Cancer Genome Characterization Initiative includes genomic studies of 
various pediatric cancers that often do not respond well to treatment. 
Results from this and other genomics research and collaboration will 
continue to inform future NCI-supported clinical trials for children, 
such as the Pediatric MATCH initiative, described below. In addition to 
these efforts, NCI has prioritized the development of new treatments 
for pediatric cancer in the NCI Experimental Therapeutics (NExT) 
Program. This program focuses on advancing breakthrough discoveries in 
basic and clinical research into new therapies, and several new 
inhibitors with potential for pediatric cancer are being studied for 
this purpose.
    NCI continues to support research to develop treatments 
specifically for children because children are not just small adults--
for example, NCI support was critical to the development and recent FDA 
approval of the drug dinutuximab to treat high-risk neuroblastoma. At 
the same time, NCI is actively pursuing drugs that have been effective 
in treating adult cancers and show promise for certain childhood 
cancers. To that end, the Pediatric Preclinical Testing Program (PPTP), 
which identifies new candidate agents for treating childhood cancers, 
has collaborated with more than 50 companies to undertake the 
preclinical evaluation of more than 80 therapeutic agents. To date, 
several PPTP-tested agents have moved into clinical testing.
    NCI continues to support a strong portfolio of clinical trials for 
children and adolescents through NCI support of the Children's Oncology 
Group, the Pediatric Brain Tumor Consortium, and the Pediatric Oncology 
Branch at the NIH Clinical Center. These trials include promising 
immunotherapy approaches, such as T cell therapy to treat certain 
leukemias, lymphomas, and solid tumors; immune system molecules coupled 
with powerful toxins to selectively kill cancer cells in children with 
certain leukemias and lymphomas; and the trials that led to the 
approval of dinutuximab, mentioned above, which is also an 
immunotherapy treatment. In addition to ongoing clinical trials 
evaluating molecularly targeted agents that are being led by the 
research groups listed above, NCI is also developing a new precision 
medicine clinical trial for children, Pediatric MATCH (Molecular 
Analysis for Therapy Choice), which will be led by the Children's 
Oncology Group as part of the proposed Precision Medicine Initiative. 
Pediatric MATCH will provide opportunities to test molecularly targeted 
therapies in children with advanced cancers and few other treatment 
options. This precision medicine trial is modeled on the adult MATCH 
trial set to launch in the coming months. The study will use DNA 
sequencing to identify children whose tumors are predicted to respond 
to an approved or investigational therapy based on a genetic 
abnormality uncovered during the sequencing. NCI will work with 
pharmaceutical companies to make drugs available for pediatric patients 
in a similar manner as it is doing for the adult MATCH trial. Pediatric 
MATCH provides a tremendous opportunity to test molecularly targeted 
therapies in children with advanced cancers who have few other 
treatment options. The genomic data captured in the trials will also 
provide an invaluable resource for studying the genetic basis of 
treatment failure for pediatric cancers.
    Equally important is NCI's support of survivorship research 
focusing on pediatric and adolescent cancer survivors, including the 
late-effects of cancer treatment and the coordination of long-term 
follow-up care. Therefore, NCI continues to support the Childhood 
Cancer Survivor Study (CCSS), which is studying the long-term effects 
of cancer and cancer therapy on approximately 35,000 survivors of 
childhood cancer who were diagnosed between 1970 and 1999.\24\ NCI has 
supported CCSS since its launch in 1994, and recently approved another 
5-year funding cycle for the study.
---------------------------------------------------------------------------
    \24\ Http://www.cancer.gov/types/childhood-cancers/ccss.
---------------------------------------------------------------------------
    This response represents a summary of some of the most promising 
research opportunities and efforts underway. NCI also encourages you to 
visit the ``Childhood Cancers Research'' page on its website for 
additional information about current research, including more 
comprehensive descriptions of some of the programs mentioned above, and 
links to specific NCI-supported clinical trials that might be of 
interest.\25\
---------------------------------------------------------------------------
    \25\ Http://www.cancer.gov/researchandfunding/areas/childhood.
---------------------------------------------------------------------------
    Additionally, the NIH Common Fund's Gabriella Miller Kids First 
research program, launching in fiscal year 2015, will develop a data 
resource of well-curated clinical and genetic sequence data that will 
allow scientists to identify genetic pathways that underlie specific 
pediatric conditions but that may also be shared between apparently 
disparate conditions. By integrating data from many conditions, we 
expect entirely new ways of understanding childhood development and 
disease to emerge, stimulating research toward more effective 
preventions and therapies for diverse conditions. In fiscal year 2015, 
the program will integrate data from pediatric cohorts addressing the 
following conditions: structural birth defects, childhood cancers with 
a suspected genetic component, or childhood sarcomas that have failed 
to respond to therapy (as a jump start for the Precision Medicine 
Initiative that NIH expects to launch in fiscal year 2016).
                           precision medicine
    Question. In Kansas, Children's Mercy Hospital is on the cutting 
edge of precision medicine for children with a leading clinical 
pharmacology group and the only genomic medicine center in the United 
States housed in a free-standing children's medical center.
    In the President's Precision Medicine Initiative, what percentage 
of the research cohort will be pediatric patients, is there a plan to 
include pediatric pharmacogenomics/precision medicine expertise on the 
Advisory Committee, and is there a plan to allocate funds specifically 
for precision medicine in children?
    Answer. NIH recognizes the importance of research on children to 
understanding the root causes of many diseases. NIH is therefore highly 
engaged in considerations of the opportunities and challenges presented 
by the potential inclusion of pediatric populations in the Precision 
Medicine Initiative (PMI).
    One immediate goal of PMI will be to significantly expand efforts 
in cancer genomics to successfully treat more cancers, and pediatric 
populations will be included in this effort. For example, starting in 
2016, the National Cancer Institute (NCI) will begin accrual to a 
clinical trial in the pediatric cancer population that will focus on 
identifying and using specific genetic abnormalities that occur in 
childhood malignancies, which differ substantially from those in 
adults, to choose the targeted drug therapies for participants. More 
information about this trial can be found at NCI's website.\26\
---------------------------------------------------------------------------
    \26\ Http://www.cancer.gov/researchandfunding/areas/clinical-
trials/match.
---------------------------------------------------------------------------
    Question. Or, will pediatric programs have to compete with adult 
programs for funding using a review process that might be adult focused 
and might not adequately address pediatric specific issues?
    Answer. A long-term goal of PMI is to launch a national cohort 
study of a million or more American research participants in order to 
build a comprehensive scientific knowledge base to put precision 
medicine into practice. To achieve this goal, NIH formed a PMI Working 
Group of the Advisory Committee to the Director (ACD) charged with 
delivering a report to the ACD in September that articulates the vision 
for building the research participant cohort. This report will be 
guided by our ACD PMI Working Group members, which includes 
pediatrician Dr. Pearl O'Rouke. In addition, NIH is actively seeking 
inputs from the pediatric research community through their 
participation in four PMI workshops being held between April-July 2015. 
Each workshop focuses on a different aspect of cohort development, 
including: scientific opportunities presented by the cohort, as well as 
digital health data considerations, participant engagement and health 
disparities considerations, and mobile health technology opportunities 
in the cohort. These workshops will be held publicly and present 
additional opportunities for stakeholder input on how different 
populations, including pediatric populations, may contribute to and 
benefit from the PMI research participant cohort. All of these inputs 
will inform the report made by the ACD PMI Working Group to the NIH 
Director.
                                 ______
                                 
                Questions Submitted by Senator Jack Reed
                    national children's study (ncs)
    Question. For fiscal year 2015 and beyond, how will NIH ensure that 
the funds previously allocated to the National Children's Study 
continue to support pediatric research and that funds are not diverted 
to other populations or used to supplant other investments across the 
NIH that are currently devoted to pediatric health? Can you provide an 
update on the plan for fiscal year 2015 funds
    Answer. Following the closure of the National Children's Study 
(NCS) in late 2014, NIH developed a plan to redistribute the fiscal 
year 2015 funds, which incorporates important aspects of the original 
goals of NCS, as well as those areas of significance highlighted by the 
Institute of Medicine and Advisory Committee to the NIH Director 
working group reports. This plan focuses on developing tools to enhance 
studies of environmental influences of pediatric diseases, studying the 
influence of environment on in utero development, and leveraging 
existing programs to expand examination of environmental influences on 
later child development.
    More specifically, one program in the plan supports the development 
of integrated health monitoring systems to facilitate the evaluation of 
environmental exposure factors, physiological parameters, and behavior 
in natural environments. An additional program aims to identify 
specific technology gaps and develop new technologies or adapt existing 
technologies to explore the effects of environmental factors on 
placental structure and function across pregnancy. The development of 
these technologies could have broader implications, and drive and 
inform research in other fields.
    The focus of another program is on developing reliable, validated 
clinical tools for patient reported outcomes on children to improve the 
assessment of outcomes in clinical trials or other research settings 
and personalize ongoing care of chronic diseases in children, and 
examine the impact of environmental stressors on children's health. An 
additional effort being supported, the Tox21 Developmental Toxicity 
Program, will assess the relationship between environmental chemical 
exposures and associated toxic effects on human development and 
developmental biology pathways. Results will help identify chemicals of 
concern for further study, and drive development of predictive models 
of chemical effects on human development. These data and tools likely 
will have a tangible and immediate impact on both our understanding of 
developmental effects of environmental chemical exposures, and on 
chemical risk assessment relevant to child health. The Children's 
Health Exposure Analysis Resource (CHEAR) program aims to develop a 
network of laboratory hubs, supporting comprehensive analytical 
services to extend or complement the objectives of children's health 
studies to measure environmental exposures. All of these programs will 
advance and inform future research in this critical area to expand our 
knowledge of human development, health, and disease.
    NIH has begun accepting applications for the funding opportunity 
announcements (see table below), and awards will be made following 
Advisory Council meetings of participating NIH Institutes in September 
2015.
    In addition to supporting new and existing programs, a small 
portion of the fiscal year 2015 funds will be allocated toward 
maintaining the existing data and specimen repositories, and 
implementing a storage plan and a process for providing investigators 
with access to these materials for secondary analysis.

----------------------------------------------------------------------------------------------------------------
                                                                                                      Estimated
           Initiative                    IC                              Project                      Budget (in
                                                                                                      millions)
----------------------------------------------------------------------------------------------------------------
Initiative 1: Develop tools                  NIBIB      Pediatric Research using Integrated Sensor           $28
 that would enhance studies of                         Monitoring Systems (PRISMS) [RFA-EB-15-002,
 environmental influences of                                         RFA-EB-15-003, RFA-EB-15-004]
 pediatric diseases
                                --------------------------------------------------------------------------------
                                             NIEHS    Children's Health Exposure Analysis Resource           $48
                                                     (CHEAR) [RFA-ES-15-009, RFA-ES-15-010, RFA-ES-
                                                                                           15-011]
                                --------------------------------------------------------------------------------
                                             NIAMS        Validation of Pediatric Patient Reported           $12
                                                     Outcomes in Chronic Diseases (PEPR) Consortium
                                                                                   [RFA-AR-15-014]
                                --------------------------------------------------------------------------------
Initiative 2: Study the                NCATS/NIEHS            Tox21 Developmental Toxicity Program            $8
 influence of environment on in
 utero development with the
 goal of identifying the
 ``seeds'' of future diseases
 and conditions
                                --------------------------------------------------------------------------------
                                             NICHD    Developing Paradigm-Shifting Innovations for           $39
                                                     in vivo Human Placental Assessment in Response
                                                       to Environmental Influences [RFA-HD-15-034]
                                --------------------------------------------------------------------------------
Initiative 3: Expand                         NIEHS        Collaborative Activities to promote High            $5
 examination of environmental                             Dimensional Molecular Analyses in NIEHS-
 influences on later child                               supported Children's Environmental Health
 development by leveraging                                                     Studies [PA-15-123]
 extant programs
                                --------------------------------------------------------------------------------
    Total......................  ..................  ..............................................         $140
----------------------------------------------------------------------------------------------------------------

              pediatric inclusion in nih clinical studies
    Question. Data is required from investigators on the enrollment of 
women and minorities in clinical studies, but NIH does not 
systematically track enrollment data to determine if children are being 
enrolled appropriately. What are the barriers to applying the same 
standard to pediatric populations that is in place for women and 
minorities with regard to data collection
    Answer. NIH and Congress share an interest in ensuring that 
adequate attention and resources are devoted to pediatric research. The 
child inclusion policy was developed and implemented in 1998 to ensure 
that children were included in research studies, unless there is an 
appropriate reason not to include children. Age is an important 
variable in clinical research. Although the child inclusion policy 
focuses on the young, older individuals (ages 65+) also are at risk for 
exclusion and should be considered in these discussions about the age 
of NIH research participants.
    There are several barriers in requiring investigators to report 
enrollment data with regard to the age of study participants. First is 
the amount of administrative burden that would be imposed on 
investigators to report on the number enrolled in each year of age. For 
example, some epidemiological studies include a wide age range 
stretching from age 16 to over age 60 and large sample sizes of over 
10,000. Asking investigators to report on the number enrolled in each 
year of age would be very burdensome. Unlike sex, race, and ethnicity, 
there are no standard agreed upon age-groups that could readily be used 
to simplify reporting age; and there are no standard age-range 
definitions for infant, toddler, early childhood, adulthood, middle-
age, elderly, etc.
    The burden is amplified further when considering how NIH would use 
this detailed data over and above what is already collected through the 
narrative text in the application and progress report and in 
ClinicalTrials.gov for clinical trials. Investigators provide age range 
and inclusion plans with their initial application and address progress 
in recruiting in the narrative of the yearly progress report. This is 
used, along with other reported information, to determine if 
satisfactory progress is being made and enrollment is on track with 
stated study goals. For clinical trials, at the time of trial 
registration in ClinicalTrials.gov, responsible parties must indicate 
the age range of those eligible for enrollment. Users can search for 
trials by three age categories: child (age 017), adult (18-65), and 
senior (66+). After trial completion, the summary results information 
that is required to be submitted includes a measure of the age (e.g., 
median, mean) of the study population overall and by arm of the trial. 
This information will be available for more trials if NIH moves ahead 
with its proposed policy to require registration and results reporting 
in ClinicalTrials.gov for all NIH-supported clinical trials.
    Finally, knowing the exact number of children enrolled will not 
reflect the strength of the NIH portfolio in terms of supporting 
pediatric research. For example, in a given year one could find that 
NIH is supporting 100 research grants that in aggregate have enrolled 4 
million children. The following year, this figure could climb to 7 
million for the same 100 research grants due to the increased 
enrollment in two or three large epidemiological studies. Although one 
would see an increase of 3 million, this increase does not reflect an 
expanded portfolio including children but rather a strengthening of the 
small number of studies where the increased enrollment was already 
expected and actually occurred.
    NIH requires clinical research applicants to discuss the age range 
of their participants and their plans for the inclusion (or exclusion) 
of children. These plans are evaluated by peer reviewers for 
appropriateness in the context of proposed science. Adequacy of 
enrollment is considered by program staff when evaluating the yearly 
progress of the research. For clinical trials, information on the ages 
being recruited and measures of the age of the study population and 
each arm of the trial are required in the summary results required for 
ClinicalTrials.gov. Given these existing requirements for 
investigators, it may be difficult to justify the additional burden of 
asking them to provide yearly enrollment numbers by age.
Future Plans
    NIH is interested in finding ways to better understand the 
portfolio and to look for gaps and opportunities for advancing research 
in relation to different ages. Discussions are underway in how to use 
the data already collected from peer review, text mining, and 
ClinicalTrials.gov to better understand the NIH clinical research 
portfolio in relation to age. This may require community engagement, 
such as a workshop, to determine whether consensus can be achieved 
about age-ranges that would be most useful to apply across a number of 
clinical research areas. This information could be used by NIH to 
better identify the number and types of clinical trials that fall into 
these age ranges and help to better identify potential gaps in the 
research portfolio without adding substantial administrative burden on 
the investigator community.
                 institutional development award (idea)
    Question. As you know, Rhode Island participates in the NIH IDeA 
program and COBREs have been very important in building a biomedical 
research infrastructure in the State. Many institutions were, 
consequently, very disappointed last year when the COBRE solicitation 
was withdrawn. What is the outlook for another round of COBREs and what 
can be done to expedite that?
    Answer. Thank you very much for your interest in the Institutional 
Development Award (IDeA) program. The National Institute of General 
Medical Sciences (NIGMS) both recognizes and shares your view of the 
importance of the program for building much-needed biomedical research 
capacity in Rhode Island and other States that historically have 
received low levels of NIH support. The current Funding Opportunity 
Announcement (FOA) for the Centers of Biomedical Research Excellence 
(COBRE), PAR-14-035, is active until January 2016. NIGMS will be 
accepting applications at the next published receipt date for the 
current announcement, which is on January 28, 2016. We fully expect 
that when the current FOA expires, the funding announcement will be re-
issued. Eligible institutions in Rhode Island may apply for the January 
28th receipt date and for any future receipt dates defined in the 
anticipated new FOAs.
                             sequestration
    Question. I have long supported efforts to increase funding for the 
National Institutes of Health and there are bipartisan efforts to do so 
in this Committee. As you know, NIH research not only helps create new 
cures, products, and industries that can improve countless lives, but 
will also ultimately lead to job creation and a more highly skilled 
workforce. I fully support an increase in funding for NIH, but I am 
concerned that under the fiscal year 2016 sequester-level budget caps, 
any increase for NIH will come at the expense of other important 
health, education, and research programs funded by this Committee. For 
example, the CDC Section 317 immunization program takes what we know 
about vaccines from decades of research and puts it into practice by 
providing vaccines to uninsured and under-insured individuals and 
developing state immunization infrastructure critical for responding to 
outbreaks. Could you elaborate on how your work is affected by the many 
other health and education programs funded by this Committee?
    Answer. As the largest research arm of the Department of Health and 
Human Services (HHS), NIH's collaborative efforts with other HHS 
agencies--as well as other agencies and programs under the jurisdiction 
of this Committee--are vital to transforming NIH's fundamental 
scientific discoveries and technical information into effective, 
knowledge-based approaches that advance the health and safety of the 
public, such as disease treatments, preventive interventions, 
protective health policies and regulations, and public health 
campaigns. In turn, the information provided by other agencies and 
programs funded by the Committee informs the policies and priorities of 
NIH-funded research.
    NIH's investments and the ensuing research results are making 
advances possible in the sciences of human health and disease and 
delivering innovations in diagnosis, treatment, and prevention; In 
order to fully realize the benefit of scientific knowledge, NIH must 
take a collaborative approach to translating these advances into 
practice. For example, NIH is collaborating with the Centers for 
Medicare & Medicaid Services (CMS) to make appropriate NIH research 
findings relevant to CMS's evidence needs. As the largest purchaser of 
healthcare in the United States, CMS touches upon the lives of one in 
three Americans and houses the Nation's only population-based 
healthcare database--a uniquely valuable resource for driving and 
tracking advances in health and disease research. NIH collaborates with 
CMS to enhance the scope and availability of CMS data for NIH-supported 
research, share research findings of interest about what works, and 
implement NIH evidence to enhance human health. Indeed, in fiscal year 
2014 alone NIH collaborated with CMS on over 90 collaborative 
activities, ranging from research initiatives to survey development, 
public education campaigns, and participation in advisory committees.
    In addition to interagency coordination, interdepartmental 
coordinating efforts also work to achieve common goals more 
effectively, such as the Federal Government's efforts to address 
Alzheimer's disease (AD), which affects more than 2 million Americans. 
NIH partners with the Centers for Disease Control and Prevention (CDC), 
Agency for Healthcare Research & Quality (AHRQ), CMS, the Food and Drug 
Administration (FDA), and the Health Resources and Services 
Administration (HRSA) in implementing the National Alzheimer's Project 
Act and responding to the evidence needs of our Federal partners as we 
address the rising numbers--and costs--associated with AD. Another 
example is the NIH's participation in HHS' efforts regarding autism 
spectrum disorders (ASD), which has seen a 123 percent increase in 
prevalence between 2002 and 2010. In addition to NIH-funded research on 
the underlying biology of ASD, the role of genetic and environmental 
factors in ASD etiology, and the benefits of interventions and 
services, NIH manages the Interagency Autism Coordinating Committee 
(IACC), which coordinates all efforts within HHS concerning autism by 
developing an annual Strategic Plan for Autism Spectrum Disorder 
Research and advising the HHS Secretary on issues related to autism. 
Membership of the Committee includes the directors of five NIH 
Institutes, seven other HHS agencies (the Administration for Children 
and Families, the Administration for Community Living, AHRQ, CMS, CDC, 
FDA, and HRSA), the Department of Education, and the Department of 
Defense (DOD), as well as a number of public stakeholders, to ensure 
that a variety of perspectives from within the autism community are 
considered in the Committee's strategic planning and coordination 
efforts. The exchange of information between agencies and the public 
facilitated by the IACC has catalyzed several endeavors to benefit 
those with autism and their families.
    HHS agencies also collaborate on a variety of large-scale efforts 
to broadly measure population health and disease to best understand how 
to target all the Department's efforts. NIH's participation in such 
activities informs its research priorities through in-depth 
understanding of public health needs. The National Health Interview 
Survey (NHIS), coordinated by the CDC's National Center for Health 
Statistics (NCHS) has collected data on the Nation's health since 1957 
through personal household interviews which provide data to track 
health status, healthcare access, and progress toward achieving 
national health objectives. In a similar collaborative effort, NIH also 
helps support and develop the CDC's National Health and Nutrition 
Examination Survey (NHANES), a large program of studies designed to 
assess the health and nutritional status of adults and children in the 
United States. NIH and CDC also partner on surveillance efforts related 
to children and young adults, as in the collaborative SEARCH for 
Diabetes in Youth study, a multi-center study aimed at understanding 
more about the types of diabetes, its complications, and how having 
diabetes affects the lives of children and young adults.
    HHS must be poised to address emergency health risks, and the 
Department relies upon interagency collaborations to aid this effort. 
Under the leadership of the HHS Office of the Assistant Secretary for 
Preparedness and Response (ASPR), NIH collaborates with CDC, FDA, and 
Departments of Defense, Veterans Affairs, Homeland Security, and 
Agriculture in the Public Health Emergency Medical Countermeasure 
Enterprise (PHEMCE), the coordinating body for Federal agencies in 
charge of employing medical countermeasures to protect the civilian 
population from potential adverse health impacts from chemical, 
biological, nuclear, or radiological threats.
    NIH is the largest source of funding for biomedical research in the 
world, investing approximately $30 billion annually in medical research 
that benefits the American people--and our Federal partner agencies--in 
many ways. Together with our larger `HHS Family' and other Federal 
partners, NIH influences a vast spectrum of activities that improve 
public health and human services outcomes throughout the life span of 
Americans. With more than 115 programs across HHS alone, the ultimate 
success of our Federal partners is enhanced by interagency 
collaborations that enable agencies to combine the knowledge base of 
their agency and the diverse expertise of staff to address their 
collective mission and enhance the public health impact of HHS's 
diverse programmatic activities.
                                 ______
                                 
             Questions Submitted by Senator Jeanne Shaheen
                 institutional development award (idea)
    Question. I am very pleased that my home State of New Hampshire 
actively participates in NIH's Institutional Development Awards (IDeA) 
program. From 2009 through 2014, the IDeA program provided almost $50 
million to the State of New Hampshire for biomedical research and 
development and for workforce development to train new generations of 
researchers. This has allowed New Hampshire's research universities to 
build more research infrastructure and train new scientists so that we 
can more successfully compete for NIH funds. We appreciate NIH's 
support of the IDeA program.
    In this year's budget request NIH asked for an overall increase of 
3 percent over the fiscal year 2015 funding level. However, NIH did not 
ask for an increase for the IDeA program, recommending $273 million, 
the same as last year. Can you explain why?
    Answer. We thank you for your continued support of the IDeA 
program. In addition, we appreciate your recognition of the role that 
IDeA institutions play in providing research infrastructure, building 
research capacity, and developing the biomedical workforce. The IDeA 
program continues to be a critical component in NIH's efforts to ensure 
diversity within our biomedical research portfolio. Between fiscal year 
2013 and fiscal year 2014, the overall National Institute for General 
Medical Sciences budget increased by 2.6 percent relative to its post-
sequestration level, whereas the budget for the IDeA program increased 
by 4.5 percent.\27\ The fiscal year 2016 President's Budget allows the 
overall budget of NIGMS to catch up with the larger increases IDeA 
received the previous year.
---------------------------------------------------------------------------
    \27\ These values are post-rescission and post-sequester and 
obtained from the NIGMS Office of Budget.
---------------------------------------------------------------------------
                            pediatric cancer
    Question. I have been engaged with the pediatric cancer community 
in New Hampshire, and I want to make sure that families of children 
living with pediatric cancer are engaged with the NIH and other 
appropriate resources to ensure that they are receiving the support and 
guidance they need. I also want to be sure that families that are 
interested in the work that NIH is doing around pediatric cancer have 
access to that information and any additional relevant opportunities 
like clinical trials. How can we work to ensure the most effective 
communication and collaboration with this community?
    Answer. The National Cancer Institute (NCI) appreciates your 
interest in ensuring that families and children affected by cancer have 
access to all of the relevant information available through NCI and 
NIH. NCI is committed to making this information easily accessible on 
its website, as well as through engagement with NCI's Office of 
Advocacy Relations (OAR), which provides information and builds 
relationships with the broader cancer advocacy community, as well as 
the childhood cancer advocacy community specifically. NCI invites 
interested advocates to sign up for the OAR listserv to stay informed 
about ongoing activities and research advances, and they can also 
contact OAR directly at [email protected] to be sure the office is 
aware of their specific interest in childhood cancer research.\28\ OAR 
has coordinated a number of public meetings and other outreach 
activities with the childhood cancer research community in recent years 
and would look forward to welcoming your constituents to participate in 
future efforts.
---------------------------------------------------------------------------
    \28\ Https://list.nih.gov/cgi-bin/wa.exe?SUBED1=CANCER-
ADVOCATES&A=1&sf25982419=1.
---------------------------------------------------------------------------
    For example, OAR facilitates a Federal advisory committee comprised 
exclusively of advocate leaders, NCI's Council of Research Advocates 
(NCRA). NCI considers the pediatric cancer advocate voice to be 
essential in these types of activities, and in September 2014, NCI 
named childhood cancer survivor and pediatric oncology researcher, Dr. 
Greg Aune, to the NCRA. Additionally, in February 2014, NCRA hosted a 
meeting to discuss the barriers to drug development in pediatric 
oncology. The board convened a diverse group of experts from across 
NCI, the FDA, and the larger research community (including childhood 
cancer advocates) to discuss the current state of pediatric cancer 
research and the potential role of the advocacy community in reducing 
barriers to developing new drugs specifically for children. The seminal 
meeting provided a forum for NCRA members, NCI, and the larger 
pediatric cancer advocacy community to engage in dialogue around 
potential solutions to help accelerate pediatric cancer research. This 
meeting, as are all NCRA meetings, was open to the public, and was also 
available via NIH public videocast for those who could not attend in 
person. The videocast remains available on the NIH website.\29\
---------------------------------------------------------------------------
    \29\ Https://list.nih.gov/cgi-bin/wa.exe?SUBED1=CANCER-
ADVOCATES&A=1&sf25982419=1.
---------------------------------------------------------------------------
    Pediatric cancer advocates regularly have calls and meetings with 
OAR and NCI Acting Director Dr. Doug Lowy's staff, including three in-
depth phone discussions and at least one in-person meeting this month. 
This high level of engagement has been consistent for the past few 
years. Other recent examples also include conversations convened by NCI 
with the childhood cancer advocacy community to discuss research 
initiatives of particular interest, such as NCI's clinical trials 
enterprise, which has gone through a significant transformation in 
recent years. OAR hosted a number of conference calls with advocates to 
discuss these changes and the new NCI National Clinical Trials Network 
(NCTN). The NCI-supported Children's Oncology Group, which develops and 
coordinates pediatric cancer clinical trials that are available at more 
than 200 member institutions, is a critical component of NCTN. 
Therefore OAR hosted a call specifically for the childhood cancer 
community to hear from NCI leadership about this transition and discuss 
questions. OAR also participates regularly in meetings organized by the 
childhood cancer community--for example OAR staff and NCI pediatric 
oncology leadership participated in the Coalition Against Childhood 
Cancer's second annual summit in June 2014, and OAR staff have joined a 
number of conference calls organized by the coalition.
    NCI also includes advocates in scientific discussions, and invited 
four community leaders to attend an NCI-sponsored 2-day February 2015 
workshop examining childhood cancer genomics. Former NCI Director Dr. 
Harold Varmus had announced this workshop at a meeting with childhood 
cancer advocates at the White House in September 2014, as part of a 
broader call to the scientific and advocacy communities to come 
together to discuss key challenges and opportunities in pediatric 
cancer research. The workshop participants included leading pediatric 
genomics research from across the United States, international genomics 
experts, and representatives from the pediatric cancer advocacy 
community. As a follow-on, just last month, OAR organized a conference 
call for the broader childhood cancer community to hear about the 
February 2015 workshop from NCI and pediatric cancer advocates.
    NCI also makes a number of important resources available to the 
public through its website.\30\ Resources and information specific to 
pediatric cancer research and treatment include a ``Childhood Cancers 
Research'' page, highlighting ongoing NCI initiatives specific to 
childhood cancers, as well as basic research that has led to advances 
for childhood cancers.\31\ NCI also provides the ``Physician Data Query 
(PDQ) Cancer Information Summaries'' as a resource to patients and 
health professionals. These are comprehensive, evidence-based summaries 
on topics that cover adult and pediatric cancer treatment, supportive 
and palliative care, screening, prevention, genetics, and complementary 
and alternative medicine. There is an extensive library of PDQs 
focusing on pediatric cancer treatment available on NCI's website. 
Patient versions are written in lay language and include links to the 
NCI Dictionary of Cancer Terms, and many patient summaries also include 
illustrations. All pediatric cancer treatment summaries are 
available.\32\ NCI also maintains a searchable database of NCI-
supported clinical trials. These include trials open at centers across 
the country via the Children's Oncology Group, as well as trials 
underway at the NIH Clinical Center through the NCI Pediatric Oncology 
Branch.\33\
---------------------------------------------------------------------------
    \30\ Http://www.cancer.gov/.
    \31\ Http://www.cancer.gov/researchandfunding/areas/childhood.
    \32\ Http://www.cancer.gov/publications/pdq/information-summaries/
pediatric-treatment.
    \33\ Http://www.cancer.gov/clinicaltrials/search .
---------------------------------------------------------------------------
    NCI's Office of Government and Congressional Relations has also 
worked with staff in your Manchester office to provide information in 
response to constituent inquiries focused on childhood cancer. We are 
happy to continue to serve as a resource to your staff and encourage 
them to reach out to us if constituents need information in addition to 
what is available via the sources outlined above.
    Additionally, the NIH Common Fund's Gabriella Miller Kids First 
program is engaging a wide range of pediatric research experts and 
stakeholders as it develops and refines plans to build a data resource 
of well-curated clinical and genetic sequence data that will allow 
scientists to identify genetic pathways that underlie specific 
pediatric conditions but that may also be shared between apparently 
disparate conditions. In fiscal year 2015, the program will integrate 
data from pediatric cohorts addressing the following conditions: 
structural birth defects, childhood cancers with a suspected genetic 
component, or childhood sarcomas that have failed to respond to therapy 
(as a jump start for the Precision Medicine Initiative that NIH expects 
to launch in fiscal year 2016). This program will continue to engage 
interested stakeholders as it evolves in future years, and will widely 
disseminate information learned through the program to benefit 
researchers, clinicians, and patients.
                                 ______
                                 
              Questions Submitted by Senator Brain Schatz
               research centers in minority institutions
    Question. I want to express my support for the National Institute 
on Minority Health and Health Disparities, or NIMHD, as well as the 
Research Centers in Minority Institutions, or RCMI program. The RCMI 
program develops and strengthens the research infrastructure of 
minority institutions, including our University of Hawaii John A. Burns 
School of Medicine.
    The RCMI program provides grants to institutions that award 
doctoral degrees in the health professions or health-related sciences, 
and which have a large enrollment of students from racial and ethnic 
minority groups that are underrepresented in biomedical sciences. It 
also brings more racial and ethnic minority scientists into mainstream 
research, and promotes minority health research.
    Given that there is now a new Director for the NIMHD, are there 
plans to increase funding for the NIMHD, the RCMI program, and for 
health disparities research?
    Answer. The National Institute on Minority Health and Health 
Disparities (NIMHD) has a unique and critical role at NIH as the 
primary Federal agency for leading, coordinating, and facilitating 
research to raise national awareness about the prevalence and impact of 
health disparities and disseminating effective individual, community, 
and population-level interventions to reduce and ultimately eliminate 
health disparities. The elimination of health disparities requires a 
multidisciplinary approach, with collaboration, coordination, and 
integration across NIH Institutes and Centers (ICs), other Federal 
agencies, and private-sector organizations. Other ICs support research 
on health disparities by individually supporting and co-funding 
important projects that address health disparities and by examining 
ways to fully understand and solve the underlying biological and non-
biological causes of disparities. The fiscal year 2016 Budget request 
for NIMHD is $281.5 million, an overall increase of $10.6 million over 
fiscal year 2015. With its funding, NIMHD will continue to identify new 
opportunities to advance its mission through collaborating with the 
other ICs, strengthening partnerships, and identifying new 
collaborations. Moreover, opportunities to compete for research centers 
via the Research Centers in Minority Institutions (RCMI) program will 
continue, increasing opportunities for less research intensive 
institutions who have not previously received RCMI funding to develop 
centers, and increase career development opportunities for 
investigators in collaboration with the NIH.
                    national children's study (ncs)
    Question. The National Children's Study was established as part of 
the Children's Health Act of 2000. It was intended to be a longitudinal 
study to evaluate the impact of environmental and biological factors 
related to children's health and development.
    While many advances have been made in children's health, numerous 
disparities in race, ethnicity, and socioeconomic status persist. We 
know that family and community factors play important roles in 
children's health. A longitudinal study looking at these and other 
environmental factors would be a powerful tool to better understand 
numerous factors contributing to children's health.
    I know that the National Children's Study was recently terminated. 
In your statement about its closing, you said that the models for the 
study were found to be ``unworkable,'' and so the study as it was 
designed was ``not feasible.'' The remaining $165 million of funds that 
were appropriated for the study in 2015 have, according to your staff, 
been disbursed to other valuable pediatric and environmental studies.
    Dr. Collins, how can we be sure that a longitudinal study focused 
on children and environmental exposures will be pursued in the 
aftermath of the closing of the National Children's Study?
    Answer. Following the closure of the National Children's Study 
(NCS) in late 2014, NIH developed a plan to redistribute the fiscal 
year 2015 funds. While a longitudinal study ultimately was not 
included, this plan focused on developing tools to enhance studies of 
environmental influences of pediatric diseases, studying the influence 
of environment on in utero development, and leveraging existing 
programs to expand examination of environmental influences on later 
child development. NIH has begun accepting applications for the funding 
opportunity announcements, and awards will be made following Advisory 
Council meetings of participating NIH Institutes in September 2015.
    NIH leadership met with key stakeholders in the field of pediatric 
research to discuss the fiscal year 2015 plan, which was received 
positively. However, during the course of these and other meetings, 
concerns were raised about the lack of inclusion of a longitudinal 
study to examine pediatric cohorts throughout development. Currently, 
NIH is developing its plans for fiscal year 2016, and the current 
options being considered include leveraging extant longitudinal cohorts 
to investigate the impact of environmental factors on prenatal and 
perinatal development--through development of a larger synthetic cohort 
or smaller, disease-specific cohorts--and expanding extant programs to 
include a focus on pediatric/pediatric environmental health. Examples 
of potential cohorts that may be leveraged include the Nulliparous 
Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), the Child 
Health and Development Study, and the Maternal-Fetal Medicine Units 
(MFMU) Network.
    Regardless which option is pursued, fiscal year 2016 plans would 
ensure recruitment plans are robust enough to address racial and ethnic 
minority health issues. Additionally, extensive input from the 
community will be solicited. Meetings with key pediatric and 
environmental health organizations will be held, as well as regional 
webinars to enable broader stakeholder outreach. Meetings with the 
research teams leading the extant cohorts also would occur to ensure 
complete understanding of what synergies could be achieved by engaging 
with them.
                  hepatitis b scientific review group
    Question. Hawaii is the State with the highest rate of liver cancer 
in the United States. Hepatitis B infection is the number one cause of 
liver cancer, and is also the number one cause for liver 
transplantation in Hawaii. The overall Hepatitis B prevalence rate in 
Hawaii is 1-3 percent, which is ten times higher than the overall 
prevalence rate in the rest of the U.S.
    Currently, it is estimated that over 40,000 people have Hepatitis B 
in Hawaii, but most are not aware of their disease. It is also 
estimated that Hepatitis B infects one in 20 immigrants in Hawaii, and 
is more common among Asian and Pacific Islander populations. To 
adequately address Hepatitis B, we need strong and dedicated research.
    Dr. Collins, I am told that the NIH has many disease-specific 
``Scientific Review Groups'' to initially review grant applications 
focused on specific diseases. Yet, despite the hundreds of applications 
for research related to bepatitis B, there is no bepatitis B-specific 
Scientific Review Group. Why is this? Wouldn't it make sense to help in 
the identification of meritorious applications for bepatitis B research 
to have review groups that are specialized in Hepatitis B
    Answer. In the Center for Scientific Review last year, about 61 
applications referred specifically to HBV in the two groups that most 
commonly review such research. These two are Digestive, Kidney and 
Urological Systems integrated review group, which focuses on those 
areas of the body, and the Infectious Diseases and Microbiology 
integrated review group, which focuses on infectious diseases such as 
Hepatitis B. There were a few applications in other areas, depending on 
the specific science that they address. We expect each review group to 
handle more than 200 applications per year, so the number of 
applications devoted to hepatitis B is about a third of the load we 
would expect for a single study section, too small a number for a 
dedicated a scientific review group. What we do to ensure the best 
investments across many diseases is to focus on either the organ most 
affected or on how to attack the infectious mechanism of the specific 
disease. So hepatitis B virus (HBV) applications are reviewed in 
committees that examine either liver disease or similar viruses. Our 
experience is that is the best way to produce progress. As you point 
out, there are related diseases and conditions that affect many people 
concurrently. Such groups of diseases and conditions often benefit from 
being considered as a whole, because the underlying mechanisms, either 
of the disease or of the body, or both, have common aspects that allow 
us to make progress in more than one area. What we learn about liver 
cancer, for example, may well lead to new insights about hepatitis B, 
or vice versa. These new and interrelated insights provide some of the 
most fertile ground for breakthroughs.
    Liver cancer and Hepatitis B are diseases that strike entirely too 
many people throughout the United States, especially in Hawaii. Several 
of the NIH Institutes study these significant diseases. The National 
Institute for Allergy and Infectious Diseases (NIAID), for example, 
provides support for a number of approaches to HBV antiviral drugs, 
including novel classes of antiviral drugs that work by different 
mechanisms than currently licensed HBV polymerase inhibitors. NIAID 
also continues to support research projects focused on novel HBV 
therapeutics through the Partnerships for Development of New 
Therapeutic Classes for Select Viral and Bacterial Pathogens 
initiative. These partnership awards will help advance the development 
of new classes of therapeutic drugs to treat HBV.
                                 ______
                                 
              Questions Submitted by Senator Tammy Baldwin
                          long-term opioid use
    Question. I am concerned about the lack of research on and 
understanding of the health consequences of long-term opioid use to 
treat chronic pain as well as inadequate research on the best 
approaches to treat various types of pain.
    Can you please discuss the research that the NIH, including the 
National Institute on Drug Abuse (NIDA), is conducting in these areas 
and provide an update on the NIDA--``Prescription Opioid Use and Abuse 
in the Treatment of Pain'' research initiative?
    Answer. Although opioid medications have a legitimate role in the 
treatment of acute pain and some chronic pain conditions, it is clear 
that they often are overprescribed or are prescribed without adequate 
safeguards and monitoring and that their misuse can have devastating 
effects. This is partially the result of inadequate research on the 
best approaches to treat various types of pain, but it also is because 
clinicians may find prescribing opioids to be the easiest and least 
expensive course for addressing pain.
    To better understand these issues, NIDA launched in 2005 a research 
initiative on ``Prescription Opioid Use and Abuse in the Treatment of 
Pain.'' This initiative encourages a multidisciplinary approach using 
both human and animal studies to examine factors that predispose or 
protect against opioid abuse and addiction. Under this initiative, NIDA 
funded 41 grants covering clinical neurobiology, genetics, molecular 
biology, prevention, treatment, and services research. This initiative 
resulted in 116 publications that are informing the treatment of 
chronic pain as well as the development of screening and diagnostic 
tools that physicians can use to assess the potential for prescription 
drug misuse in their patients.
    In addition, NIDA has initiated multiple strategic partnerships to 
advance development of medications for pain, leveraging NIDA funds with 
the strengths and resources of outside organizations, including 
academic institutions, pharmaceutical and biotechnology companies, 
private and public foundations, and small businesses. This includes 
research to identify new pain medicines with reduced abuse, tolerance, 
and dependence risk, as well as devising alternative delivery systems 
and formulations for existing drugs that minimize diversion and non-
medical use (e.g., by preventing tampering) and reduce the risk of 
overdose deaths. For example, a partnership with Signature Therapeutics 
is working to develop an abuse deterrent formulation of oxycodone that 
uses prodrug technology--attaching an extension to the opioid molecule 
that renders it inactive if injected, snorted, or smoked; instead it 
must pass through the digestive system to begin the process of 
releasing the opioid. Early phase trials have supported safety, dose 
proportionality, and a clinically beneficial extended release profile.
    NIH spends over $400 million annually to support chronic pain 
research ranging from basic treatments and clinical studies to 
determine optimal pain management approaches. This research includes:
  --Clinical studies that address the efficacy of bio-behavioral 
        approaches that target modifiable risk factors for pain (e.g., 
        stress, depression, sleep disorders, etc.) including education, 
        cognitive therapy, and mindfulness.
  --The effects of drugs on novel molecular targets, for example 
        Calcitonin Gene Related Protein, involved in nervous system 
        changes associated with chronic pain.
  --Research on the development of new opioid compounds that exhibit 
        novel properties as a result of their combined activity on two 
        different opioid receptors (i.e., mu and delta).
  --New technologies including spinal cord stimulation and 
        transcutaneous magnetic stimulation of the brain.
  --Studies to evaluate the integration of complementary therapies such 
        as massage, acupuncture, yoga, with pharmacological approaches 
        to pain management are ongoing.
  --Clinical studies evaluating the benefit of delivering integrated, 
        multidisciplinary modalities for management of chronic pain.
    Education is another critical component of any effort to curb the 
abuse of prescription medications and must target every segment of 
society, including healthcare providers (doctors, nurses, dentists, 
pharmacists). The NIH Pain Consortium supports 12 Centers of Excellence 
for Pain Education (CoEPEs) that act as hubs for the development, 
evaluation, and distribution of pain management curriculum resources 
for medical, dental, nursing and pharmacy schools. NIDA also has 
developed, in partnership with the Office of National Drug Control 
Policy, two online continuing medical education courses on safe 
prescribing for pain and managing patients who abuse prescription 
opioids. To date, these courses have been completed by over 100,000 
clinicians combined.
    NIH maintains a publically available and searchable data base of 
federally funded pain research.\34\
---------------------------------------------------------------------------
    \34\ Http://paindatabase.nih.gov/search/quick-
search?field_themes[0]=56&f[0]=field_research_type%3A110.
---------------------------------------------------------------------------
      nih's collaboration with the department of veterans affairs
    Question. In addition to NIH's collaboration with the Department of 
Veterans Affairs to explore non-drug related treatments for pain 
management, what other work is NIH conducting on opioid use, substance 
abuse treatment, and pain management for military personal, veterans 
and their families?
    Answer. Substance use disorders (SUDs) are a significant health 
concern for military personnel, veterans, and their families. Post-
traumatic stress disorder (PTSD) and SUDs frequently co-occur, and 
research has shown that veterans who have PTSD also have a higher risk 
for alcohol and drug dependence. In addition, a study published in 2014 
found an alarming high prevalence of chronic pain (44.0 percent) and 
opioid use (15.1 percent) in the U.S. military after combat 
deployment.\35\ These rates, much higher than estimated rates in the 
general public (26 percent and 4 percent, respectively) likely 
contribute to the dramatic increase in prescription drug abuse among 
military personnel--from 2 percent in 2002 to 11 percent in 2008, 
according to a 2012 IOM report.\36\ The National Institute on Drug 
Abuse (NIDA) continues to support a range of research efforts examining 
the intersection of substance use, psychological, neurological, and 
physical health comorbidities, including pain.
---------------------------------------------------------------------------
    \35\ Toblin RL, et al. Chronic Pain and Opioid Use in U.S. Soldiers 
After Combat Deployment. JAMA Intern Med. 2014;174(8):1400-1401.
    \36\ Substance Use Disorders in the U.S. Armed Forces. Institute of 
Medicine Report, September 2012.
---------------------------------------------------------------------------
    In 2014, NIDA supported 18 grants focused on Military, Veterans, 
and their Families totaling $5,049,419; 19 grants focused on PTSD 
totaling $4,984,849; 4 grants focused on Suicide and Suicide prevention 
totaling $2,043,637; and 2 grants focused on traumatic brain injury 
totaling $521,658.
    In 2013, NIDA along with the National Institute on Alcohol Abuse 
and Alcoholism (NIAAA), National Center for Complementary and 
Integrative Health (NCCIH), and the Department of Defense (DOD) issued 
a funding opportunity announcement on ``Prevention and Health Promotion 
Interventions to Prevent Alcohol and Other Drug Abuse and Associated 
Physical and Psychological Health Problems in U.S. Military Personnel, 
Veterans and their Families'' providing almost $21.75 million in 
research funding, with the NIH spending about $10.25 million total for 
seven grants (3 NIDA, 2 NIAAA, 2 NCCIH) and DOD spending over $11.5 
million total for five grants.
    NIDA also partnered with the NCCIH and the Department of Veterans 
Affairs (VA) in a 2013 funding initiative focused on non-
pharmacological approaches to pain management in military personnel, 
veterans, and their families. Thirteen research projects totaling 
approximately $21.7 million over 5 years are exploring nondrug 
approaches to managing pain and related health conditions such as PTSD, 
drug abuse, and sleep issues. The effort seeks to enhance options for 
the management of pain and associated problems in U.S. military 
personnel, veterans, and their families. Thirteen grants were funded 
through this initiative (1 NIDA, 1 VA, and 11 NCCIH, including co-
funding of 1 by the VA).
    Some additional examples of ongoing NIH research focused on 
military, veterans, and their families related to opioid use and 
substance use disorder treatment include:
Opioid use
  --Feasibility and efficacy of requiring mandatory use of prescription 
        drug monitoring programs
  --Identification of malleable risk and protective factors for 
        intervention targets for military/veteran populations
  --Novel prevention training programs to increase help-seeking 
        behaviors Substance use disorder treatment
  --Studies to develop integrated treatment programs for SUDs and co-
        occurring disorders including PTSD among U.S. military service 
        members and veterans.
  --Development of novel treatment strategies, including both 
        behavioral treatments and medication development, for SUD with 
        co-occurring conditions such as PTSD and TBI
  --Development and implementation of family based interventions
  --Understanding what interventions work for whom and under what 
        conditions
  --Adapting existing evidence-based prevention interventions for 
        military/veteran populations, their families, and communities.
    This work is coordinated through the National Research Action Plan 
(NRAP), a collaborative effort across DOD, VA, and the Department of 
Health and Human Services to improve the coordination of agency 
research into behavioral health conditions and reduce the number of 
affected men and women through better prevention, diagnosis, and 
treatment.
          safety of methadone for the treatment of opioid use
    Question. Recent reports and experts have warned that methadone can 
often increase the risk of overdose and is one of the most addictive 
opiates. In fact, the American Academy of Pain Medicine recommends that 
all insurers remove methadone from preferred drug lists, and CDC warns 
that methadone should not be considered a drug of first choice for 
chronic pain.
    What is the current state of science on the safety of methadone for 
the treatment of opioid use disorders and its potential for abuse?
    Answer. The use of methadone for pain has increased dramatically in 
the United States since 1999. The rate of overdose deaths involving 
methadone in the United States in 2006 was more than five times the 
rate in 1999. It is important to note that increases in methadone 
overdose deaths during this time were related to the increase in 
methadone prescriptions for chronic pain, and not to its use in opioid 
use disorder treatment programs; this is likely due to both increased 
tolerance in patients with opioid use disorders and more intensive 
oversight of patients in these programs.\37, 38, 39\ Methadone is 
metabolized slowly at variable rates in different patients and its 
analgesic effects may wear off before it is cleared from the body, 
leading some patients to take more too soon.\40\ Unlike methadone 
treatment for opioid use disorders, pain patients may receive multiple 
methadone doses per day that sum to a higher total dose, which 
increases risk of overdose.\41\
---------------------------------------------------------------------------
    \37\ Center for Substance Abuse Treatment. Methadone-Associated 
Mortality: Report of a National Assessment. (2003). at .
    \38\ United States Government Accountability Office. METHADONE-
ASSOCIATED OVERDOSE DEATHS: Factors Contributing to Increased Deaths 
and Efforts to Prevent Them. (2009). at .
    \39\ Chou, R. et al. Methadone Safety: A Clinical Practice 
Guideline From the American Pain Society and College on Problems of 
Drug Dependence, in Collaboration With the Heart Rhythm Society. J. 
Pain 15, 321--337 (2014).
    \40\ Chou, R. et al. Clinical Guidelines for the Use of Chronic 
Opioid Therapy in Chronic Noncancer Pain. J. Pain 10, 113--130.e22 
(2009).
    \41\ Modesto-Lowe, V., Brooks, D. & Petry, N. Methadone Deaths: 
Risk Factors in Pain and Addicted Populations. J. Gen. Intern. Med. 25, 
305--309 (2010).
---------------------------------------------------------------------------
    In 2006, the Food and Drug Administration (FDA) issued an alert and 
updated packaging information to reflect the risks of death, narcotic 
overdose, and cardiac arrhythmias associated with methadone in pain 
treatment.\42\ Since that time, rates of methadone-related overdoses 
have begun to decline; in comparison, deaths due to prescription 
opioids generally have only begun to level off in 2012-2013. At the 
peak in 2005, overdoses due to methadone accounted for more than 40 
percent of all prescription opioid overdose deaths. In 2013, this rate 
dropped to just over 20 percent.
---------------------------------------------------------------------------
    \42\ O'Donnell, J. & Vogenberg, F. R. Applying legal risk 
management to the clinical use of methadone. P T Peer-Rev. J. Formul. 
Manag. 36, 813--822 (2011).
---------------------------------------------------------------------------
    A frequently-cited reason for use of methadone for pain is its low 
cost, a factor that has caused it to remain a preferred, first-line 
chronic pain treatment for many insurance providers.\43, 44\ In 2012, 
the Center for Disease Control and Prevention (CDC) published a report 
concluding that ``methadone remains a drug that contributes 
disproportionately to the excessive number of opioid pain reliever 
overdoses and associated medical and societal costs.'' CDC further 
cautioned that methadone should not be considered a drug of first 
choice by prescribers or insurers for chronic non-cancer pain.
---------------------------------------------------------------------------
    \43\ Kuehn, B. M. Methadone Overdose Deaths Rise With Increased 
Prescribing for Pain. JAMA 308, 749 (2012).
    \44\ Webster, L. R. et al. An Analysis of the Root Causes for 
Opioid-Related Overdose Deaths in the United States: Analysis of Opioid 
Overdose Deaths. Pain Med. 12, S26--S35 (2011).
---------------------------------------------------------------------------
    However, methadone is a safe and effective treatment for opioid use 
disorders. Findings from two comprehensive Cochrane reviews comparing 
methadone maintenance treatment to placebo found that methadone 
treatment significantly improves treatment outcomes.\45, 46\ Patients 
on methadone were over four times more likely to stay in treatment and 
had significantly fewer positive drug tests for other opioids compared 
to control. Opioid Use Disorder patients who receive methadone 
treatment have decreased mortality compared to those who do not receive 
medication as well as reductions in other negative outcomes including 
criminal activity and HIV risk.\47\
---------------------------------------------------------------------------
    \45\ Mattick, R.P., Breen, C., Kimber, J., and Davoli, M. (2009). 
Methadone maintenance therapy versus no opioid replacement therapy for 
opioid dependence. In Cochrane Database of Systematic Reviews, The 
Cochrane Collaboration, ed. (Chichester, UK: John Wiley & Sons, Ltd).
    \46\ Mattick, R.P., Breen, C., Kimber, J., and Davoli, M. (2014). 
Buprenorphine maintenance versus placebo or methadone maintenance for 
opioid dependence. Cochrane Database Syst. Rev. 2, CD002207.
    \47\ Tetrault JM, Fiellin DA. Current and potential pharmacological 
treatment options for maintenance therapy in opioid-dependent 
individuals. Drugs. 2012 Jan 22;72(2):217-28.
---------------------------------------------------------------------------
                           co-occurring pain
    Question.Senator Baldwin: Many women who experience one type of 
pain condition such as Temporomandibular Disorder (TMJ) often suffer 
from co-occurring conditions, like chronic fatigue syndrome, 
endometriosis, or fibromyalgia. Unfortunately, women's reports of pain 
are often taken less seriously by healthcare professionals, leading to 
misdiagnoses and delayed treatment. I am encouraged by NIH's efforts, 
including the Trans-NIH Working Group on Chronic Overlapping Pain 
Conditions, to better understand co-occurring pain issues, and believe 
it is important that these efforts include a focus on improving 
treatment for women.
    What progress has been made and what more needs to be done to 
advance our understanding of overlapping conditions that 
disproportionately affect women--like TMJ--and to reduce gender 
disparities in diagnostics and treatment for pain?
    Answer. Women are more likely to experience chronic pain 
conditions, including those that overlap such as systemic exertion 
intolerance disease, headache, vulvodynia, low back pain, and 
temporomandibular disorders (TMD), which are a group of conditions that 
cause pain and dysfunction in the jaw joint and the associated muscles 
and supporting tissues.
    The Interagency Pain Research Coordinating Committee (IPRCC), a 
Federal advisory committee that is addressing ongoing research needs 
for chronic overlapping pain conditions across the government, was 
established in 2012 in response to language in the Affordable Care Act. 
Its efforts to develop a comprehensive Federal pain research strategy 
will provide an effective platform to enhance all pain research, 
including basic, translational, and clinical research on chronic 
overlapping pain conditions. Since the establishment of the IPRCC, the 
Trans-NIH Working Group on Chronic Overlapping Pain Conditions is no 
longer active in order to avoid duplicative efforts. The NIH Office of 
Pain Policy with the NIH Pain Consortium is also leading efforts, in 
consultation with outside experts, to develop research tools that will 
advance the clinical research agenda on overlapping pain conditions.
    The National Institute of Dental and Craniofacial Research (NIDCR) 
supports precision medicine research to identify and understand genetic 
and molecular differences, including variations based on sex and 
gender, which can affect the initiation, progression, and treatment of 
orofacial pain. NIDCR-funded studies are integrating information about 
the differences between men and women in their genetic makeup and 
temporomandibular joint (TMJ) mechanics that could help identify those 
at risk for developing TMD and predict the likelihood of progression to 
chronic disease. The Orofacial Pain: Prospective Evaluation and Risk 
Assessment (OPPERA) clinical study has found almost no difference in 
the rate at which men and women develop TMD for the first time (acute). 
However, females are far more likely to progress to chronic TMD than 
males. Ongoing efforts are investigating the role of hormones, genetics 
and other factors in this difference. Researchers are studying how the 
neurons that transmit the pain sensation to the brain are affected by 
estrogen and also how psychological stress, a known risk factor for 
developing TMD, may further increase the likelihood that chronic TMD 
will result. The relationship between stress, pain, and hormones is 
also being investigated in the context of overlapping pain conditions 
using an animal model of TMD and irritable bowel syndrome.
    Question. What research has been done to help develop safe and 
effective techniques for joint repair and regeneration for patients 
with TMJ, and has the NIH analyzed the problems associated with current 
joint replacements?
    Answer. NIDCR funds a diverse research portfolio related to the 
development, structure, function, repair, regeneration and replacement 
of the TMJ. Novel biomaterial scaffolds are being generated using laser 
techniques to improve the migration and attachment of cells to the 
structure, along with approaches to comprehensively characterize TMJ 
stem cells to identify the ideal cells for repair and regeneration of 
the joint. These advances in basic research are now being translated 
into pre-clinical studies using animal models. NIDCR funding of small 
business grants has supported the development of novel nanotechnology 
diamond coatings to minimize the deterioration of a TMJ implant and the 
damage to surrounding tissue that results from the wear debris.

                          SUBCOMMITTEE RECESS

    Senator Blunt. The subcommittee is in recess until 10:00 
a.m. on Thursday, May 7. Thank you all.
    [Whereupon, at 11:53 a.m., Thursday, April 30, the 
subcommittee was recessed, to reconvene at 10 a.m., Thursday, 
May 7.]