(1) 

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. 
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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 
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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. 
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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:] 
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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:] 
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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:] 
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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:] 
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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, multiagency 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:] 
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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:] 
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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:] 
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With this in mind, we at NIH are thrilled to take a lead role in 

the multi-agency Precision Medicine Initiative. 

[The graphic follows:] 
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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:] 
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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:] 
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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:] 
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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:] 
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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:] 
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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 
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1Structures 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. 

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. 

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 
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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 cuttingedge 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 
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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 earlystage 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 
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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 reemerging 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. 
22 

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 
23 

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 
24 

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. 
25 

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. 
26 

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 
27 

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, 
28 

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—— 
29 

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 
30 

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. 
31 

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 in-
32 

terested 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 inter-
33 

esting 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 
34 

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. 
35 

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. 
36 

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. 
37 

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 
38 

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 evi-
39 

dence 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. 
40 

1 Http://grants.nih.gov/training/nrsa.htm. 

2 Http://acd.od.nih.gov/bwf.htm. 

3 Http://grants.nih.gov/grants/guide/notice-files/NOT-OD-13-097.html. 

4 Http://grants.nih.gov/grants/rppr/rpprlinstructionlguide.pdf. 

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. 

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. 

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 
41 

5 Http://www.ncbi.nlm.nih.gov/. 

6 Http://sites.nationalacademies.org/pga/fdp/index.htm. 

7 Http://orcid.org/. 

8 Http://www.ncbi.nlm.nih.gov/sciencv/. 

project grants and provide a means of tracking their career outcomes, particularly 

if they continue to receive NIH research support. 

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. 

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

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 

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. 
42 

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 twothirds 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 
43 

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 
44 

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. 
45 

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 in-
46 

volved 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 
47 

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? 
48 

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 
49 

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 Ge-
50 

netics. 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. 
51 

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. 
52 

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. 
53 

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. 
54 

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 topdown 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. 
55 

1 Http://braininitiative.nih.gov/2025/BRAIN2025.pdf. 

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 
56 

2 Http://neuroscienceblueprint.nih.gov/. 

3 Http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml. 

4 Http://www.ncbi.nlm.nih.gov/pubmed/20624964. 

5 Http://www.humanconnectomeproject.org/. 

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. 

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. 

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. 

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. 

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 neuro-
57 

6 Http://www.braininitiative.nih.gov/. 

7 Http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml. 

8 Http://www.braininitiative.nih.gov/. 

9 Calculated from http://www.ncbi.nlm.nih.gov/pubmed/18480098. 

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-seriousmental-illness.shtml. 11 Http://www.nimh.nih.gov/health/topics/suicide-prevention/suicide-prevention-studies/armystudy-to-assess-risk-and-resilience-in-servicemembers-army-starrs-a-partnership-between-nimhand-the-us-army.shtml. 

science 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. 

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 crosscutting 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. 

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. 

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. 

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 
58 

12 Http://www.nimh.nih.gov/news/science-news/2014/suicide-in-the-military-army-nih-fundedstudy-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. 

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. 

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

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. 
59 

17Kaufman 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). 19Trinidad et al. Research Practice and Participant Preferences: the Growing Gulf. Science. 

331(6015): 287–288. (2011). 20For 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. 21Gymrek et al. Identifying Personal Genomes by Surname Inference. Science. 339(6117): 

321–324. (2013). 

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 deidentified. 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

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. 

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. 
60 

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. 
61 

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. 
62 

22 At http://www.nia.nih.gov/research/recommendations-nih-ad-research-summit-2015. 

—Increasing the transparency of NIH-funded clinical trials by expecting all NIHfunded 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’sRelated 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. 

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? 
63 

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 onemillion 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 
64 

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) cosponsored 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 af-
65 

23 Http://grants.nih.gov/grants/guide/pa-files/PAR-13-213.html. 

fected 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 onehalf 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. 

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 informa-
66 

tion. 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 highrisk 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 
67 

24 Http://www.cancer.gov/types/childhood-cancers/ccss. 25 Http://www.cancer.gov/researchandfunding/areas/childhood. 26 Http://www.cancer.gov/researchandfunding/areas/clinical-trials/match. 

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. 

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

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

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 vi-
68 

sion 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 speci-
69 

men repositories, and implementing a storage plan and a process for providing investigators with access to these materials for secondary analysis. 

Initiative IC Project 

Estimated 

Budget 

(in millions) 

Initiative 1: Develop tools that 

would enhance studies of environmental influences of pediatric 

diseases 

NIBIB Pediatric Research using Integrated Sensor 

Monitoring Systems (PRISMS) [RFA–EB–15–002, 

RFA–EB–15–003, RFA–EB–15–004] 

$28 

NIEHS Children’s Health Exposure Analysis Resource 

(CHEAR) [RFA–ES–15–009, RFA–ES–15–010, 

RFA–ES–15–011] 

$48 

NIAMS Validation of Pediatric Patient Reported 

Outcomes in Chronic Diseases (PEPR) 

Consortium [RFA–AR–15–014] 

$12 

Initiative 2: Study the influence of 

environment on in utero development with the goal of identifying 

the ‘‘seeds’’ of future diseases 

and conditions 

NCATS/NIEHS Tox21 Developmental Toxicity Program $8 

NICHD Developing Paradigm-Shifting Innovations for in 

vivo Human Placental Assessment in Response 

to Environmental Influences [RFA–HD–15–034] 

$39 

Initiative 3: Expand examination of 

environmental influences on later 

child development by leveraging 

extant programs 

NIEHS Collaborative Activities to promote High 

Dimensional Molecular Analyses in NIEHSsupported Children’s Environmental Health 

Studies [PA–15–123] 

$5 

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 indi-
70 

cate 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 immuniza-
71 

tion 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 
72 

27These values are post-rescission and post-sequester and obtained from the NIGMS Office 

of Budget. 

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, invest- ing 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. 

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 
73 

28 Https://list.nih.gov/cgi-bin/wa.exe?SUBED1=CANCER-ADVOCATES&A=1&sf25982419=1. 29 Https://list.nih.gov/cgi-bin/wa.exe?SUBED1=CANCER-ADVOCATES&A=1&sf25982419=1. 30 Http://www.cancer.gov/. 31 Http://www.cancer.gov/researchandfunding/areas/childhood. 

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 NCIadvocacy@nih.gov 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. 

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

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 can-
74 

32 Http://www.cancer.gov/publications/pdq/information-summaries/pediatric-treatment. 33 Http://www.cancer.gov/clinicaltrials/search . 

cer 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

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 im-
75 

pact 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 
76 

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 
77 

34 Http://paindatabase.nih.gov/search/quicksearch?fieldlthemes[0]=56&f[0]=fieldlresearchltype%3A110. 35Toblin RL, et al. Chronic Pain and Opioid Use in U.S. Soldiers After Combat Deployment. 

JAMA Intern Med. 2014;174(8):1400–1401. 36Substance Use Disorders in the U.S. Armed Forces. Institute of Medicine Report, September 

2012. 

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

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. 

In 2014, NIDA supported 18 grants focused on Military, Veterans, and their Fam- ilies 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 
78 

37 Center for Substance Abuse Treatment. Methadone-Associated Mortality: Report of a National Assessment. (2003). at <http://atforum.com/documents/CSAT-MAMlFinallrept.pdf>. 38 United States Government Accountability Office. METHADONE-ASSOCIATED OVERDOSE DEATHS: Factors Contributing to Increased Deaths and Efforts to Prevent Them. (2009). 

at <http://www.gao.gov/assets/290/287899.pdf>. 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). 

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 
79 

41Modesto-Lowe, V., Brooks, D. & Petry, N. Methadone Deaths: Risk Factors in Pain and Addicted Populations. J. Gen. Intern. Med. 25, 305—309 (2010). 42O’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). 43Kuehn, B. M. Methadone Overdose Deaths Rise With Increased Prescribing for Pain. JAMA 

308, 749 (2012). 44Webster, 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). 45Mattick, 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). 46Mattick, 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. 47Tetrault JM, Fiellin DA. Current and potential pharmacological treatment options for maintenance therapy in opioid-dependent individuals. Drugs. 2012 Jan 22;72(2):217–28. 

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

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. 

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. 

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

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 
80 

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 preclinical 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.]