[Senate Hearing 115-277]
[From the U.S. Government Publishing Office]





 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2019

                              ----------                              


                         THURSDAY, MAY 17, 2018

                                       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, Alexander, Moran, Capito, Hyde-
Smith, Murray, Durbin, Reed, Shaheen, and Murphy.

                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
        RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        WALTER J. KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF 
            NEUROLOGICAL DISORDERS AND STROKE
        NORMAN E. SHARPLESS, M.D., DIRECTOR NATIONAL CANCER INSTITUTE
        NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE


                 opening statement of senator roy blunt


    Senator Blunt. The Appropriations Subcommittee on Labor, 
Health and Human Services, Education, and Related Agencies will 
come to order.
    We are glad to have our friends from NIH (National 
Institutes of Health) here today: Dr. Collins and the Institute 
Directors.
    Recent support, I think, of medical research from our 
subcommittee and the full committee and the Congress is clear. 
During the 3 years that Senator Murray and I have worked 
together on this committee, we have increased funding for the 
National Institutes of Health by 23 percent, $7 billion above 
where we were just 3 years ago. We have nearly tripled the 
Alzheimer's research amount, started the Precision Medicine 
Initiative, and targeted resources to such revolutionary 
projects as the BRAIN Initiative, the universal flu vaccine, 
and efforts to combat antibiotic resistance.
    A renewed investment in NIH has provided and can provide 
millions of Americans and their families with hope that they 
would not otherwise have. NIH-funded research has raised life 
expectancy, vastly improved the quality of life for all 
Americans. And in addition, I am hopeful that we can see ways 
to lower healthcare costs and to create economic growth by 
supporting the jobs, the research and the innovation that are 
such an important part of dealing with healthcare issues now.
    Both this administration and the last one have proposed 
cuts in NIH funding. There is rarely a straight line in 
success, but so far, we have been able to maintain an upward 
momentum in the opportunity that I think everybody on this 
subcommittee certainly sees at the moment we are in.
    In addition to that, things around the world like the West 
Africa challenge 3 years ago with the devastating outbreak of 
Ebola, the disease killed more than 11,000 people in Africa, 
became a major public health threat in the United States, and 
both NIH and CDC (Centers for Disease Control and Prevention) 
were an important part of responding to that. We see now 
another outbreak in the Democratic Republic of Congo. There was 
more news on that topic even this morning, and we need to be 
well prepared to continue to be able to do what we need to do 
to respond to those kinds of challenges.
    Earlier this month, the National Institutes of Health 
launched enrollment in the All of Us study, which will collect 
health information from 1 million Americans, an idea that Dr. 
Collins mentioned, I think, 2 years ago for the first time as 
an NIH goal. All of Us has the potential to unlock precision 
medicine for the majority of diseases that we suffer from 
today. This initiative has the potential to change our health 
system from one-size-fits-all to really understanding more 
about personalized medicine.
    We are also at a point where we see some drug repurposing 
happening. We are testing current drugs that we know are safe 
to see what other uses we might find in those drugs. There is a 
current clinical trial targeting the most common adult leukemia 
with a drug first approved to test arthritis more than 25 years 
ago. That particular work is being done at the University of 
Kansas. Certainly Senator Moran has been a real advocate for 
NIH research, and he and I hope to visit The University of 
Kansas Medical Center before too long and look at that project, 
along with others.
    The National Academy of Sciences published a report in 
February that shows that NIH funding contributed to every one 
of the 210 new drugs approved by the Food and Drug 
Administration from 2010 till 2016. That is quite a record, and 
we appreciate the fact that that work continues.
    We see increased grants among young researchers. Anything 
you have to say about that would be welcome. But this has been 
an effort that this committee has entered into together, and 
Senator Murray has been a great partner in NIH, as we hope to 
be appropriately involved in our oversight responsibilities as 
well.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Good morning. Thank you, Dr. Collins and the Institute Directors, 
for appearing before the Subcommittee today to discuss the National 
Institutes of Health's fiscal year 2019 budget request.
    My support for medical research is clear. During my time as 
Chairman of this Subcommittee, I am proud to have increased funding for 
the National Institutes of Health by 23 percent, or $7 billion, in the 
last 3 years. This investment nearly tripled funding for Alzheimer's 
research, started the Precision Medicine Initiative, and targeted 
resources to such revolutionary projects as the BRAIN Initiative, a 
universal flu vaccine, and efforts to combat antibiotic resistance.
    I stand by an investment in NIH because it has provided millions of 
Americans and their families with hope. NIH-funded research has raised 
life expectancy and vastly improved the quality of life for all 
Americans. In addition, it has lowered healthcare costs and spurred 
economic growth by supporting jobs in research and generating 
biomedical innovations.
    However, I understand that it is difficult to always quantify 
success in medical research. Both this Administration and the last one 
has proposed cuts to NIH. There is rarely a straight line to success. 
Not every grant funded will result in a breakthrough. However, this is 
not the time to abandon our commitment to medical research. The 
advances made in just the past 3 years is example enough to show why 
funding for the NIH is so important.
    Three years ago, West Africa faced one of the most devastating 
infectious disease outbreaks of the last 50 years--Ebola. This disease 
killed more than 11,000 people in Africa, and became a major public 
health threat in the United States. Now, the Democratic Republic of 
Congo faces another Ebola outbreak. In response, the World Health 
Organization will deploy an Ebola vaccine that appears to provide 
protection for 2 years. This has been made possible, in part, due to 
the support of the National Institutes of Health.
    Earlier this month, the NIH launched enrollment into the All of Us 
study which will collect health information from one million Americans. 
All of Us has the potential to unlock precision medicine for the 
majority of diseases we suffer from today. This initiative will change 
our health system from one-size-fits-all to personalized medicine.
    It is also important to point out discoveries in the revolutionary 
work of drug repurposing--testing current drugs we know are safe for 
other uses. There is a current clinical trial targeting the most common 
of adult leukemia with a drug first approved to treat arthritis more 
than 25 years ago.
    These are just a few examples of how investing in medical research 
can save lives and shows that this is not the time to back away from 
our support. As further evidence of the benefits of these investments, 
the National Academy of Sciences published a report in February that 
showed that NIH funding contributed to every one of the 210 new drugs 
approved by the Food and Drug Administration (FDA) from 2010-2016. Let 
me say that again. Every single drug approved by the FDA over a 6-year 
period had some NIH research associated with it.
    The increased funding over the past 3 years, has also allowed the 
best researchers in the country to have their research funded to 
discover the next breakthrough. I am proud to say that the number of 
grants have increased 2,200 during this period. We finally are in a 
pattern of long-term investment in medical research.
    I have worked closely with Senator Murray and other Members of the 
Subcommittee to prioritize our commitment to NIH. I know that we will 
continue to do so this year.
    Thank you for being here today.

    Senator Blunt. But let me turn to Senator Murray for her 
comments.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Well, thank you very much, Mr. Chairman.
    Dr. Collins, it is great to see you again too and all of 
your amazing team. Thank you all for being here today. And I 
just want to say it is a pleasure to see Ann Houser back there 
as well. She has done a lot to support our subcommittee's work 
for many years. She is a great credit to the agency, and I 
wanted to recognize her back there as well.
    President Trump's budget for fiscal year 2019 once again 
seeks deep cuts across the spectrum of health activities, 
including a reduction to the National Institutes of Health that 
would cut its funding down to roughly $100 million below the 
2017 enacted level. That request is out of step with the 
sentiments of Congress and the country.
    Less than 2 months ago, Congress passed and President Trump 
signed into law a bipartisan bill that increased funding for 
NIH by $3 billion, the second largest increase in the agency's 
history. Those funds will be used to accelerate efforts to 
discover cures to Alzheimer's, cancer, and other diseases, 
tackle the opioid addiction crisis, and develop a universal flu 
vaccine, and new antibiotics and more.
    President Trump's request would undermine these efforts 
slowing their progress.
    By comparison in just the past 3 years, Congress has 
provided NIH an overall increase of $7 billion boosting its 
budget by almost a quarter. After adjusting for inflation, the 
NIH budget still falls short of its peak in 2003 and grants 
remain highly competitive, especially for our early stage 
investigators, but the numbers are trending in the right 
direction. I am hopeful in the bill our subcommittee will 
shortly begin writing, we will be able to continue closing the 
gap. I know that Chairman Blunt feels the same way, and I want 
to thank him for his work on this.
    These funding increases reflect a sustained commitment to 
invest in medical research with the goal of achieving 
breakthroughs that benefit all of us, including those who have 
been historically under-represented in clinical research, and 
preserve our Nation's leadership in biomedical research. We are 
in a time of immense promise and challenge for the research 
community, the promise of unprecedented new tools, 
technologies, and computational power balanced by the challenge 
of making the most of the staggering and ever-growing amount of 
data that NIH produces, the BRAIN Initiative efforts to cure 
Alzheimer's disease, the Cancer Moonshot, and the All of Us 
initiative to advance precision medicine that are massive 
undertakings that pose extraordinary challenges, how to manage 
and make sense of it all, allow the research community to 
leverage it as much as possible, and find that proverbial 
needle in an immense haystack, while at the same time ensuring 
each patient's data remains secure.
    I believe that much of NIH and its grantees are up to this 
task. I see the potential every time I visit the Allen 
Institute for Brain Science in Seattle, but few organizations 
have their level of sophistication.
    2 years ago, the committee tasked NIH with developing a 
strategic plan for outlining how it would manage and make the 
most of the data it is producing. NIH released that plan 
earlier this month on schedule, but the real work lies ahead. I 
am concerned there still remains no senior member of the 
leadership responsible for that portfolio. I see that NIH 
recently posted an opening for a chief data strategist and 
understand you are actively reaching out to those in the 
private sector in the hope of attracting the right person to 
public service. It is essential we find them quickly, bring 
them on board, and make sure you properly support them to 
implement your strategic plan. I look forward to hearing more 
about NIH's plans in this area when we turn to the questions.
    I am pleased the administration's fiscal year 2019 budget 
abandoned its ill-conceived proposal to drastically cut grant 
support funding that it proposed last year, but troubled that 
it now seeks to arbitrarily slash researchers' salaries by 20 
percent. The budget claims this proposal would stretch grant 
dollars to fund more research, but like the previous proposal, 
it is blindly destructive and short on details, a gimmick not 
meant to be taken seriously.
    I see the budget follows Congress' lead by preserving the 
increase we provided to address opioid addiction and spur the 
development of non-addictive pain treatments. These are 
critical investments of great importance to the members of this 
subcommittee, and I think I can speak for all of us in saying 
we expect NIH to make the most of those resources entrusted to 
address this crisis. We and those we represent are really 
counting on you on this one.
    Finally, few agencies enjoy greater trust than the National 
Institutes of Health. So it was particularly troubling that 
questions have been raised about the impartiality of a study to 
assess the health benefits of moderate alcohol consumption. Dr. 
Collins, I know you have been focused on determining the facts 
with this and ensuring the integrity of NIH's research 
practices, and hopefully you will provide us with an update on 
that.
    Thank you very much, Mr. Chairman.
    Senator Blunt. Thank you, Senator Murray.
    I am glad again to welcome Dr. Francis Collins, the 
Director of the National Institutes of Health and the Institute 
Directors that are here with him today. I think the new 
Director of the National Cancer Institute, Dr. Ned Sharpless, 
is here for his first appearance before the committee, and we 
are glad you are part of this team and look forward to the 
chance to visit with all of you later.
    But, Dr. Collins, glad to have your testimony right now.

          SUMMARY STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D.

    Dr. Collins. Well, it is an honor to be here, Mr. Chairman.
    Also with me here at the table: Dr. Nora Volkow, at my 
left, your right, the Director of the National Institute on 
Drug Abuse. You mentioned Dr. Sharpless, our newbie, to my 
right. Walter Koroshetz, Director of the National Institute of 
Neurological Disorders and Stroke; next to him, Dr. Richard 
Hodes, Director of the National Institute on Aging; and over at 
the far end, somebody you know pretty well who is in his 439th 
hearing or something like that----
    [Laughter.]
    Dr. Collins [continuing]. Dr. Anthony Fauci, who is the 
Director of the National Institute of Allergy and Infectious 
Diseases.
    I just want to say to all of you, Chairman Blunt, Ranking 
Member Murray, and all the friends of NIH that are here today, 
thank you. You have gone above and beyond in your support of 
NIH research and the patients for whom it brings healing and 
hope. In behalf of all of them, I am immensely grateful for 
your consistent support, and the words you have just spoken 
give me a great sense of confidence that we are on a very good 
and strong path towards the future.
    [The graphic follows:]
 
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    Dr. Collins. I spend a lot of time with early stage 
researchers. I will show you a few pictures. Wherever I go, I 
set aside time to hear directly from them about their dreams, 
their ideas, and yes, their concerns. I know you too have met 
many of them, both in your home districts and sometimes in your 
much appreciated visits to NIH.

    [The graphics follow:]

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    Dr. Collins. As we move forward with implementing the 
fiscal year 2018 budget and you begin considering the fiscal 
year 2019 request, it is a good time to think about those early 
stage researchers to ask what are we doing to foster this next 
generation of discovery and what can we do to help our Nation 
remain the world leader in biomedical innovation.
    [The graphic follows:]

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    Dr. Collins. I believe the answers could be said to lie in 
certain key areas, and I would call them the five keys to 
success in science today. They are, first and foremost, a 
stable trajectory of support, followed by a vibrant workforce, 
computational power, new technologies and facilities, and 
perhaps most important of all, scientific inspiration.
    [The graphic follows:]

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    Dr. Collins. The good news is that, thanks to you, early 
stage researchers are now beginning to see a stable trajectory 
of support. Your work over the last 3 years is helping us begin 
to reverse a distressing decade-long decline in NIH's 
purchasing power for research, which is carried out in every 
State of the Nation. Strong, stable public support lies at the 
heart of NIH science, and of course, that is absolutely vital 
to our second key to success, a vibrant workforce. Clearly 
success cannot lie simply in boosting the number of grants 
made. It must also include increasing the number of creative 
minds that are receiving those grants.
    So I want to show you a new metric we are using to evaluate 
success. This shows the trend in the number of individual 
principal investigators supported by NIH over the past 15 
years. As you can see, that number is once again growing 
nicely. Note especially the surge that occurs around 2016, a 
surge that reflects when you began to change the trajectory of 
NIH support, and shows how that investment in NIH science is 
starting to pay off.
    [The graphic follows:]

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    Dr. Collins. The third key to success, already mentioned by 
Senator Murray, is computational power. Like so much else, 
biomedical research has been transformed by the recent 
explosion in computing power and all of the big data it is 
generating. For example, the BRAIN Initiative, which you have 
supported for the past 5 years, has created new imaging tools 
that are churning out troves of amazing data, and there is also 
data generated by structural biology and microbiome research 
and the All of Us research program supported by your precision 
medicine appropriation. Just 10 days ago in a major national 
launch event, all of us began the full scale of enrolling 1 
million Americans, building on their pilot phase that already 
enrolled over 25,000, aiming to determine how individual 
differences and lifestyle, environment, and biological makeup 
can influence health and at an unprecedented scale.
    [The graphic follows:]

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    Dr. Collins. To realize the full potential of these and 
other resources, we also must develop new technologies and 
facilities. Quite often it is the technology itself driving the 
need for equally innovative facilities. Take the case of the 
new cell-based treatments, immunotherapy and gene therapy. Many 
involve removing cells from the patient's body using technology 
to re-engineer those cells and returning them to the patient. 
The challenge is that many of our labs are not set up to handle 
these highly individualized processes, so it is crucial that we 
make upgrades to keep pace. The President's fiscal year 2019 
proposal includes a much needed increase in buildings and 
facilities to assist with that.
    [The graphic follows:]

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    Dr. Collins. But now on to my favorite of these topics, 
scientific inspiration. I can assure you that NIH-funded 
researchers come to work every day full of innovative ideas and 
the wherewithal to see those ideas through. I could talk about 
this all day, but mindful of the clock, let me just share one 
example.
    [The graphic follows:]

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    Dr. Collins. More than a decade ago, NIH launched a special 
project on spinal muscular atrophy, or SMA. This is a uniformly 
fatal inherited disease. As you see here, in its severe form, 
it leaves babies floppy, unable to hold their heads up, feed 
well, and eventually even to breathe. Death by 15 months is the 
tragic and almost universal result.
    10 years ago there was no treatment for SMA, but 
researchers had just discovered the DNA (deoxyribonucleic acid) 
mutations that cause it. So NIH supported more research, 
working closely with patient advocates and industry to move 
promising leads into therapeutic development. One of the most 
exciting comes from Jerry Mendell's team at Nationwide 
Children's Hospital in Columbus, Ohio, which recently tested 
gene therapy in 15 infants with severe SMA. They infused the 
viral vector designed to deliver the normal gene to the spinal 
cord and held their breath.
    And over the next few months, something truly dramatic, 
almost miraculous, happened. Like little Mateo Almeda, whom you 
see in this video, 100 percent of the infants who got the 
highest dose of the gene therapy were alive at 20 months and 
nearly all could talk and eat on their own, and some like 
Mateo, shown here at age 2 standing up on his tiptoes, were 
able to walk--and this is truly astounding--even play on the 
monkey bars with his dad. As a direct result of an NIH-inspired 
effort, we are seeing the emergence of lifesaving gene therapy 
for SMA.
    So in closing, I am proud to lead NIH at this time of 
unprecedented scientific opportunity and with such strong 
congressional support. The resources you have entrusted to us 
will be used to bring hope to untold numbers of patients and 
their families.
    [The graphic follows:]

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    Dr. Collins. In that spirit, I would like to finish with a 
favorite quote from the poet Peter Levi. ``Hope,'' he wrote, 
``in every sphere of life is a privilege that attaches to 
action. No action, no hope.'' At NIH our idea of action is to 
support the best investigators to apply the best science to 
find answers for those millions waiting for their hopes to be 
realized.
    Thank you, and I look forward to your questions.
    [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 have served as the Director of the National 
Institutes of Health (NIH) since 2009. It is an honor to appear before 
you today.
    Before I discuss NIH's diverse investments in biomedical research 
and some of the exciting scientific opportunities on the horizon, I 
want to thank this Subcommittee for your sustained commitment to NIH to 
ensure that our Nation remains the global leader in biomedical research 
and advances in human health.
    I want to personally express gratitude to this Subcommittee and its 
leadership for its support in crafting and passing the fiscal year 2018 
Consolidated Appropriations Bill. The fiscal year 2018 Omnibus provides 
an incredible increase of $3 billion for NIH, including funding for 
opioid- and pain-related research, Alzheimer's disease, antimicrobial 
resistance, and development of a universal influenza vaccine. NIH has 
immediately set to work to invest those additional resources into 
groundbreaking research.
    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. As some of you have 
witnessed first-hand on your visits to NIH, our leadership and 
employees carry out our mission with passion and commitment. This 
extends equally to the hundreds of thousands of individuals whose 
research and training we support, located in every State of this great 
country, and where 81 percent of our budget is distributed.
    The fiscal year 2019 Budget provides $34.8 billion for NIH to fund 
the highest priority scientific discoveries while also maintaining 
fiscal stewardship of Federal resources. This Budget will consolidate 
research functions across the Department, optimize available grant 
dollars to fund research, invest in NIH's buildings and facilities, and 
support NIH priority areas including combatting the opioid epidemic, 
advancing Precision Medicine, and investing in translational research.
    The fiscal year 2019 Budget consolidates HHS research programs into 
three new institutes within the NIH. The Budget provides $380 million 
for the activities of the Agency for Healthcare Research and Quality 
(AHRQ), consolidated into the National Institute for Research on Safety 
and Quality. The National Institute for Occupational Safety and Health 
(NIOSH), including the Energy Employees Occupational Illness Program 
(EEOCIPA), currently administered by the Centers for Disease Control 
and Prevention, and the National Institute on Disability, Independent 
Living, and Rehabilitation Research (NIDILRR), currently administered 
by the Administration for Community Living, are also proposed for 
consolidation into the NIH.
    America's continuing leadership in conducting biomedical research 
requires infrastructure and facilities that are safe, compliant with 
all laws and regulations, and conducive to cutting edge research and 
research support. NIH owns 281 facilities, including a research 
hospital, laboratories, and offices. NIH's Backlog of Maintenance and 
Repair exceeds $1.8 billion. NIH is currently working with the National 
Academies of Sciences, Engineering and Medicine to identify NIH 
facilities and infrastructure most in need of repair. We look forward 
to providing that report to the Committee as soon as it is final.
    The fiscal year 2019 Budget makes much needed investments in NIH's 
facilities. The Budget proposes $200 million to support multiple 
biomedical research infrastructure priorities. The fiscal year 2019 
Budget will allow NIH to continue to repair and upgrade deteriorated 
infrastructure. In a recent analysis requested by this Committee, the 
condition of NIH laboratories ranks near the lowest in the Federal 
Government due to the high likelihood of floods, power outages, and 
mechanical failures. Items on the backlog list include: install steam 
and chilled water distribution systems; conduct structural repairs to 
older buildings; upgrade plumbing systems; repair elevators; upgrade 
heating, ventilating, and air conditioning systems; replace 
deteriorated electrical systems, and more. In addition, due to the age 
and use of NIH facilities, NIH must invest funds in removing 
contaminants and hazardous waste before construction or capital repairs 
can begin in most of its buildings. The Budget will allow NIH to track 
what contaminants are being cleared from each of our buildings, which 
will ultimately help NIH do a better job of anticipating the cost and 
time required to begin new projects in existing buildings.
    Truly exciting, world class science is taking place. I would like 
to provide just a few examples of the depth and breadth of the amazing 
research the fiscal year 2019 Budget supports across the Institutes and 
Centers of NIH.
    Over the past 15 years, communities across our Nation have been 
devastated by increasing prescription and illicit opioid misuse, 
addiction, and overdose. This Committee made a historic investment of 
$500 million in our work in fiscal year 2018, and the fiscal year 2019 
Budget builds on that with an investment of $850 million to support a 
range of activities to advance research on pain and addiction. NIH has 
and will continue to support cutting-edge research on pain, opioid 
misuse, addiction, and overdose. Drug addiction is a complex 
neurological condition, driven by many biological, environmental, 
social, and developmental factors. Continued research will be key to 
understanding the crisis and informing future efforts. Pain is an 
equally complex condition affecting millions of Americans. NIH will: 
explore new formulations for overdose reversal medications capable of 
combatting powerful synthetic opioids; search for new options for 
treating addiction and maintaining sobriety; continue to research how 
best to treat babies born in withdrawal through our ACT NOW trial; 
develop biomarkers to objectively measure pain; build a clinical trial 
network for pain research; and attempt to find non-addictive and non-
pharmacological approaches to chronic pain. Thanks to your support, all 
hands are on deck at NIH for this public health crisis.
    Another exciting area of continued investment in fiscal year 2019, 
building on this Committee's long-standing support, is Precision 
Medicine. On May 6th, NIH officially launched the national roll-out of 
the All of Us Research Program. This program will partner with one 
million or more people across the United States to provide the most 
diverse biomedical data resource of its kind and gain unprecedented 
insights into the biological, environmental and behavioral influences 
of disease. The fiscal year 2019 Budget, including resources from the 
21st Century Cures Act, supports the ramp up of the program. After 
pilot testing system and forming partnerships with community 
organizations across the country, national enrollment is about to 
begin. All of Us will not focus on only one specific disease. Rather, 
it will be a national data resource to inform many research studies on 
a wide variety of health conditions. The data provided by one million 
participants will provide opportunities for researchers--including 
academics and citizen scientists--who want to understand how and why 
different people experience certain diseases and conditions while 
others do not, and why many people respond differently to treatments 
and prevention methods that will help accelerate medical breakthroughs.
    NIH is the largest funder of basic biomedical research in the 
United States, providing a critical research foundation for both the 
public and private sector. Building on that solid foundation of basic 
research, NIH also supports translational research that turns 
observations in the laboratory, clinic, and community into 
interventions that improve the health of individuals and the public, 
whether those interventions be diagnostics, therapeutics, medical 
procedures, or behavioral changes. For example, Congress created the 
Cures Acceleration Network (CAN) at the National Center for Advancing 
Translational Sciences (NCATS) to advance the development of high-need 
cures and to reduce significant barriers between research discovery and 
clinical trials. For example, CAN currently supports NCATS' Tissue Chip 
for Drug Screening program, which was designed to revolutionize the 
process for predicting drug safety. Researchers developing miniaturized 
platforms that could support miniature models of living organs--such as 
the lung, liver, and heart--that could be integrated into connected 
organ systems. New Tissue Chip initiatives were funded in fiscal year 
2017 and this support will continue into fiscal year 2019.
    CAN uses flexible research awards using the special authorization 
called other transaction authority to attract non-traditional 
government partners, and to expand, modify, and, if needed, discontinue 
activities to meet program needs. The fiscal year 2019 Budget will 
allow NCATS, through CAN, to continue to invest in high-risk, high 
reward initiatives designed to address significant scientific and 
technical challenges that hinder translational research.
    One of my personal priorities is developing the next generation of 
talented biomedical researchers. Last year, I shared with the Committee 
NIH's plans to build on our support for early-stage investigators 
through a new initiative known as the Next Generation Researchers 
Initiative. The fiscal year 2019 Budget includes a dedicated fund of 
$100 million in the Office of the Director to incentivize additional 
Institute and Center support for these researchers. NIH remains 
committed to the development, support, and retention of our next 
generation of investigators.
    We have never witnessed a time of greater promise for advances in 
medicine than right now. Your support has been critical, and will 
continue to be. Thank you again for inviting NIH to testify today. We 
look forward to answering your questions.

    Senator Blunt. Well, thank you, Dr. Collins.
    We will have 5-minute rounds of questions. There will be 
time for a second round if we are still in the hearing when we 
have the vote at 11:15. I think it is one vote. And so we will 
try to work around that and continue the hearing.

                      PUBLIC/PRIVATE PARTNERSHIPS

    One of the things that we put in the appropriations bill 
this year was an effort that, frankly, we were asked to put in 
where there would be some partnership money from pharmaceutical 
companies into opioid research, the idea being that like other 
partnerships, for example, the AMP partnerships between NIH and 
other biopharmaceutical companies, that we could deal with that 
quicker. You have decided and frankly, without consultation 
with the committee, not to do that. It might very well relate 
to the alcohol study that Senator Murray brought up. I would 
like you to respond to both of those topics, starting with why 
you decided not to do what you had asked us to put in the 
budget to allow you to do.
    Dr. Collins. Senator, I will be glad to explain that, and I 
know this is a topic that many people have been interested in 
and have been wrestling with a bit, as we have.
    We have been in deep conversations with industry partners 
for a year about ways in which we might develop a partnership 
to come up with better ways to treat addiction, to treat 
overdose, and to come up with non-addictive treatments for 
chronic pain, which are desperately needed. Working with 33 
such companies over the course of many months, we have 
identified a number of areas of opportunity which we could do 
effectively in a public-private partnership with them in ways 
that neither sector could do alone. And that includes such 
things as sharing data, sharing assets, repurposing compounds 
that might have been tried for something else or have been 
abandoned and could turn out to be valuable for pain, and 
running clinical trials together in that space.
    The good news is that partnership is very much alive and 
will, in fact, be going forward. I think we are pretty close to 
having the full plan laid out, and I would expect in the next 
few weeks to be able to say much more about exactly how we are 
going to conduct this.
    The controversy, Senator, was whether in fact, given the 
circumstances around the opioid crisis and the fact that there 
are lawsuits now filed against no less than five of these 
companies claiming that they may have played some role in the 
opioid crisis in the first place by marketing such drugs as 
OxyContin, whether it is in fact a good idea or potentially 
carries a reputational risk for NIH to receive funds from the 
company.
    And ultimately I convened an expert group of advisors from 
outside who had lots of experience in both sectors and who were 
very finely tuned to the questions of reputational risk and 
ethics. And to my surprise, they made a strong recommendation 
that we go forward with the partnership but not have actual 
cash contributions from the companies involved. Their concern 
was that that would create at least the impression, if not the 
reality that the project going forward would be in some way a 
conflict of interest, would be driven by something other than 
the best needs of the public.
    I had to accept that strong recommendation coming from 
those groups. The Foundation for NIH, by the way, which is our 
partner in all of these partnerships, also convened their board 
and came up with the same recommendation.
    And so with apologies for not having consulted, as I should 
have, with you and other members of this subcommittee, we felt 
we had to make the decision that we did.
    Again, the good news is the partnership will go forward 
very much as planned, but we are not asking the companies to 
contribute money, but we are asking them to contribute 
expertise and resources and data and assets and help with our 
clinical trials network.
    Yes, the alcohol issue was also in this particular 
discussion because we are in the midst of another place that I 
wish we were not where there is deep concerns about whether a 
study, which has really just gotten launched in the last 2 or 3 
months, which aims to look at whether there might be medical 
benefit of modest doses of alcohol in humans. And this 
particular study was set up in such a way that the funding is 
largely coming from the beverage industry, and there is 
evidence that NIH employees assisted in recruiting those funds 
for this study in a way that would violate our usual policies.
    We are in the midst of investigating that through the 
Office Management Assessment and through a working group that I 
have convened. There are sufficient concerns about that study 
that I would like to tell you that 1 week ago, we decided to 
suspend enrollment in that study of the moderate effects of 
alcohol on cardiovascular health while we continue the 
investigation and make a decision about whether the study is in 
fact still worth pursuing.
    So all of those are complicated issues and believe me, have 
caused considerable pain and stress upon the people involved. 
But again, for NIH, our reputation is so critical, and if we 
are putting ourselves in a circumstance where that could be 
called into question, I felt we had to look at that very 
seriously and come up with another strategy.
    Senator Blunt. Thank you.
    I could probably ask another question quickly and get way 
beyond my 5 minutes but I am not going to do that, and I hope 
nobody else will either. If you want to stay for a second round 
of questions, we are going to do that.
    Senator Murray.

                                BIG DATA

    Senator Murray. Thank you very much.
    And I wanted to go back to the big data because one of the 
greatest challenges facing science today is how to manage and 
effectively use this massive amount of data that researchers 
are now producing, and without the tools to efficiently manage 
and manipulate data, the value of it is significantly reduced. 
Likewise, we do not want scientists spending time recreating 
data that already exists from other research projects. And as 
you know, the committee directed NIH in the 2017 omnibus to 
develop a strategic plan to address these issues, which you 
released last week.
    Now that you have the plan, can you tell us what the 
timeline for implementation is?
    Dr. Collins. The plan is very ambitious, Senator. And I am 
glad you had a chance to look at it. It is the product of many 
deliberations with experts both within NIH and outside and also 
responding to a request for comments from more than 800 
individuals and organizations who put forward a plan.
    Basically it does lay out what we need to be doing in the 
area of infrastructure, in the area of the data ecosystem, in 
the area of software and tools, particularly in the area of the 
workforce. We realize our bench is not as deep as it should be 
for expertise in this space, and also just sustainability, how 
do we put together something that is not here today and then in 
trouble tomorrow. All of those are laid out in the strategic 
plan in a broad and bold way.
    The way in which we are going to implement this certainly 
includes a number of things that are already underway because 
we have really been working on this issue since 2012 when a 
working group of my advisory committee made the first set of 
recommendations. We are, for instance, moving some of our 
largest datasets into the cloud in a fashion that protects the 
security and privacy of the participants but makes that data 
accessible to researchers from all over the place. And that is 
a big step forward, and most of our big datasets will need to 
be handled in that way going forward.
    And as you mentioned in your opening comments, we are 
actively recruiting for a chief data strategist, someone who we 
would ideally hope to recruit from industry and maybe from 
Silicon Valley with deep experience in how to handle big 
datasets and machine learning and artificial intelligence.

                        BARRIERS IN DATA SHARING

    Senator Murray. Are there barriers that are worrying you 
like cases where researchers face challenges sharing their data 
or delay releasing the data until they have published their 
findings, things like that?
    Dr. Collins. We are certainly attuned to the risks there of 
people hording data. I am happy to say the 21st Century CURES 
bill gave me as the NIH Director some authorities about 
requiring data access and data release from our grantees, which 
I used to have to do some cajoling, but now I have the 
opportunity to have more clout and that has helped us in that 
regard.
    I think the general ethic of the scientific community has 
shifted, though, much more in the direction of it is your 
responsibility to make your data available as soon as someone 
else might be able to use it. We have encouraged that a lot.
    Senator Murray. Okay, good.

                  DATA SHARING IN ALZHEIMER'S DISEASE

    And Dr. Hodes, I wanted to ask you. Given the scale of 
investments that we are making in Alzheimer's disease, the data 
we are generating may be used to accelerate some major 
scientific breakthroughs. Has NIA (National Institute on Aging) 
looked at its existing data sharing policies to determine how 
they are working? Do we know what percentage of grant 
recipients are fulfilling their data sharing obligations on 
this project?
    Dr. Hodes. Thank you very much for the question.
    I would echo very much what Dr. Collins has just said about 
NIH's role in general.
    I think we have had a history in the Alzheimer's research 
community of a strong willingness to share, and I think that 
has increased over past years. I think we are at a stage when 
we are dealing in part with technical feasibilities of making 
data cross-interpretable, shareable, and compatible and are 
working very hard in collaborations across Federal agencies and 
with outside groups to make that sharing more effective. But I 
think we have the culture, as well as the armamentarium to 
enforce sharing, and I think we are on an excellent trajectory 
in that regard.
    Senator Murray. Thank you.

                        MODERATE DRINKING STUDY

    Dr. Collins, just one more question on the moderate 
drinking study. NIH is a huge enterprise, and if this was 
happening in one institute, it could be happening in others. 
Are you doing anything to make sure this has not compromised 
studies elsewhere in NIH?
    Dr. Collins. I am very concerned that this might be the tip 
of a larger iceberg, and that is part of the reason that I 
pulled together this very distinguished group of experts to 
look at it. We will look closely to see if there are other 
examples of this sort because that would be very much against 
the principles that we stand for, which is separation of 
funding sources from outside with decisions about science, and 
also of course, our peer review process ought to be absolutely 
above any reproach as far as conflicts.
    I would be glad to report back to you after we have done a 
bit more digging into this. But I think this is one of my roles 
as the NIH Director. When we find something that has gone awry, 
we do not just assume that it is a little thing that you could 
put a band aid on. We make sure that it is not reflective of 
some larger issues, and then we aim to fix those too.
    Senator Murray. Thank you very much.
    And thank you, Mr. Chairman.
    Senator Blunt. Senator Alexander.
    Senator Alexander. Thank you, Mr. Chairman.
    First, let me say to Chairman Blunt and to Senator Murray, 
Senator Durbin, all the members of the committee, how much I 
appreciate their leadership and the increase in funding for the 
National Institutes of Health. And I pledge my support to do 
that for the future.
    Second, it is good to see a piece of legislation that had 
such broad bipartisan support. Senator McConnell said it was 
the most important law of 2016. Actually it would be so useful 
in its implementation. A part of that is because of the talent 
of the team we see before us and others like Dr. Gottlieb who 
know what they are doing and are leaning forward and taking 
advantage of the new authority.
    Third, we have developed quite a consensus on science and 
research. As Senator Blunt said, a 23 percent increase in 
biomedical innovation. I would add to that that in the Energy 
and Water Appropriations Subcommittee, which Senator Feinstein 
and I chair, we increase funding for the Office of Science this 
year 16 percent. That was the third straight year of record 
funding for the Office of Science that supports the national 
laboratories. So when you get 3 straight years for the National 
Institutes of Health, 3 straight years of record funding for 
the Office of Science, and you add to that in the Obama 
administration and in the first 2 years of this administration 
we have funded supercomputing at impressive levels to keep us 
first in the world in that, I think the only people not on 
board with the President's America First comments are the 
Office of Management and Budget.
    So I am going to try to talk to the President and others at 
the White House and say why do you not include this in your 
America First agenda. I mean, why not buy medical innovation, 
why not national laboratories, why not supercomputing? We need 
to lead the world in that. Congress wants to do it, both 
Republicans and Democrats. We need to get the OMB (Office of 
Management and Budget) on board.

                     NON-ADDICTIVE PAIN STRATEGIES

    Now, let me use the rest of my time to ask you about one 
area, non-addictive pain strategies. We have 25 million 
Americans who hurt badly, chronic pain, 100 million who hurt 
some, and then non-addictive treatment for opioid abuse. 95 
percent of the treatment for opioids is more opioids. It is 
medicated assisted abuse. And sometimes they say you do not 
ever get off opioids.
    So my question is in 2 minutes and a half, what progress 
are you making? Senator Murray and I have included in the 
opioids bill the transactional authority that you asked for to 
give you even more flexibility in funding. What progress are 
you making on pain, new pain strategies, and why are 95 percent 
of the treatments for opioids more opioids? Why do we not have 
more treatments like Vivitrol or some other treatment that 
helps people get away from opioids?
    Dr. Collins. So I am fortunate to have at the table two 
experts who can handle both parts of that question. Maybe we 
will go first to Dr. Volkow to talk about the treatments for 
addiction and what we might be working on in that space. And 
then I will ask Dr. Koroshetz to respond about non-addictive 
treatments for pain. We are deep into that as well.
    Dr. Volkow. Thanks, Francis.
    This is one of our priorities, how do we develop 
alternative medications for the management of opioid addiction. 
We currently only have three of them, and two of them are what 
we call agonists, opioid agonists. And Vivitrol is an 
antagonist.
    Senator Alexander. And I am right that two are about 95 
percent of the treatment. Right?
    Dr. Volkow. Correct. That is correct. Those are the 
numbers.
    And part of the problem is not all of the patients respond 
to the Vivitrol intervention, and part of the problem is it is 
very difficult to induct someone that is addicted right away 
into Vivitrol. And that is when we lose the patients. So we are 
trying to expand the alternative medications that we can give 
to patients and focusing also on strategies that are not 
involved in the opioid system so that we can help those 
individuals be able to recover and be at one point able to stay 
without opioid medications.
    Dr. Koroshetz. So I think that you are absolutely right 
that one thing that could really help in the long term stemming 
the opioid problem is developing non-addictive pain medicines 
to replace opioids in the prescription box for patients.
    Senator Alexander. And we funded $500 million in research 
this past year--Senator Blunt and Murray did--and $500 million 
more proposed by the budget for this coming year.
    Dr. Koroshetz. That is right. And so we, working with our 
industry partners, as Francis mentioned, have a plan to really 
accelerate the development of new medications. From the basic 
science point of view, we have a number of different targets 
that look very promising to develop medicines that are not 
interacting with the opioid pathway.
    One that is in current testing now is what is called anti-
nerve growth factor therapy, which came from really very 
important basic science years ago on the intersection of that 
growth factor and the pain system. And companies are now 
developing antagonists to nerve growth factor which look 
promising in early results. So just one example, but we think 
there are many more.
    Senator Alexander. Thank you, Mr. Chairman.
    Senator Blunt. Senator Reed.
    Senator Reed. Thank you very much, Mr. Chairman.
    Thank you all. I particularly want to thank Dr. Sharpless 
for giving me an opportunity to look at the pediatric oncology 
program and meeting all the tremendous women doctors and Ph.D.s 
who lead that effort. So thank you.

                                STAR ACT

    With the support of another tremendous woman, Senator 
Capito, we were able to pass the STAR Act. And can you give us 
an idea of how you will use this? It will pass, we hope, the 
House very soon and become law.
    Dr. Sharpless. Sure. I should not directly comment on 
pending legislation, but--and first off, thank you for the 
visit. I think it really means a lot to the pediatric 
oncologists to have the Senate come up and express an interest 
in work that they are doing and I think is really, really 
wonderful. And thank you for your support and Senator Capito's 
support of pediatric cancer research.
    The STAR Act--the intent of it is very laudable to address 
issues, some issues in pediatric oncology and childhood cancer 
that are important. So one is the issue of survivorship. The 
good news about pediatric cancer is we are curing more and more 
kids, but the problem is--well, the two problems are we are not 
curing everyone. We still have kids die of cancer. And then a 
lot of the kids we cure are left with lifelong toxicity. So the 
results from therapy can be quite debilitating, infertility, 
disfiguring surgery, and cognitive dysfunction that last for 
decades.
    So survivorship has become a major issue. There are 
probably half a million pediatric cancer survivors now in the 
United States. And trying further research to understand the 
basic science of survivorship and why these toxicities occur 
and what we can do is a really important area of pediatric 
oncology research.
    Similarly, I think we had this issue of aggregated data in 
pediatric cancer. One of the shortages of that are samples, 
biospecimens that can be sequenced and analyzed and catalogued, 
and then presented to the research community in an aggregated 
format that is de-identified and secure but usable for 
research.
    And so I think those two addressing survivorship and 
biospecimens are really important and something NCI (National 
Cancer Institute) is behind.

                TRANS-NIH PEDIATRIC RESEARCH CONSORTIUM

    Senator Reed. Thank you very much.
    And Dr. Collins, thank you again for your hospitality on my 
visit.
    You have recently announced the creation of a trans-NIH 
pediatric research consortium. Can you give us an idea of what 
you want to accomplish with that, Doctor?
    Dr. Collins. I would be very happy to.
    We have the National Institute of Child Health and Human 
Development, which sounds like it is the place where pediatric 
research gets done and a lot does get there. But it is actually 
only about 18 percent of pediatric research across all of NIH. 
Most of the institutes--you have just heard a great example 
from the Cancer Institute--are also heavily invested in 
pediatric research.
    I have asked Diana Bianchi who is the new Director of the 
Child Health Institute to convene a trans-NIH group at a high 
level from all of the institutes that are players, which is 
essentially all of them, to see whether we could come up with a 
more coordinated strategic plan for defining where are the 
greatest priorities in pediatric research and how can we work 
together, whether it is cancer or whether it is autism, whether 
it is birth defects, whether it is development, whether it is 
behavioral issues. I believe with her leadership--and she is a 
very strong leader, indeed--that we have the chance to put 
forward a plan for pediatric research that will be quite 
exciting. That has just gotten going, and I would be glad to 
report back to you in the coming months about how this is 
leading us in new directions.

                      FOGARTY INTERNATIONAL CENTER

    Senator Reed. I would be remiss if I did not applaud the 
Fogarty Center, named after my beloved predecessor in the 
United States Congress, John Fogarty. But this is the 
international arm, if you will, of NIH, and we celebrated the 
50th anniversary. And it seems particularly important today, as 
we talk about Ebola emerging in countries like this, that we 
have this agency in very close rapport with CDC.
    Can you just comment upon the next wonderful 50 years of 
the Fogarty Center? And tell Peter Kilmarx I said hello.
    Dr. Collins. Senator, I appreciated very much your being 
there at that 50th anniversary celebration and speaking to the 
group.
    One of the things Fogarty has done that has been most 
powerful, even though it is the smallest of all of our 
institutes, is their training program for fellows.
    I am just going to quickly ask Tony Fauci to tell you a 
story or two about how those Fogarty fellows have played a 
significant role in global health challenges like Ebola and 
Zika.
    Dr. Fauci. Thank you, Dr. Collins.
    Yes, the Fogarty International Center really has been very 
important and very much interdigitated with what we do as the 
National Institute of Allergy and Infections Diseases (NIAID) 
in the area of infectious diseases. You may recall that when we 
had the Ebola outbreak in West Africa in 2014, 2015, and early 
2016, there were cases that, as you might expect, traveled not 
knowing they were infected with Ebola to other places such as 
Mali and Nigeria. And those cases did not result in outbreaks 
in those countries. Almost all the people taking care of those 
individuals infected with Ebola virus who traveled to Mali and 
Nigeria were trained as Fogarty fellows. So we had a pre-
existing network of people there who had been trained in 
science and public health with support from the NIH. That was a 
dramatic public health example of how the Fogarty Center was a 
true partner, not only with regard Fogarty activities on our 
NIH campus in Bethesda, MD but Fogarty activities in Bamako, 
Mali and Lagos, Nigeria. It was really quite striking.
    Senator Reed. With a speech like that, you could be elected 
to Congress from the 2nd district. Thank you.
    [Laughter.]
    Senator Blunt. Senator Capito.

                          OPIOIDS PARTNERSHIP

    Senator Capito. Thank you, Mr. Chairman and the ranking 
member, and thank you all of you.
    And Dr. Collins, it is great to see you again.
    My first question is on opioids and what you are doing. And 
we have talked numerous times about this. Obviously, I live in 
an area that is highly affected here.
    Two questions. You mentioned and you said that we had put a 
$500 million historic investment into this. But you have 
mentioned in your response to questions that you have private 
partners. Could you elaborate on how the private partnership 
works, and what kind of commitment dollar-wise that private 
partnership is committing to add to the $500 million that we 
are doing in the research?
    Dr. Collins. Happy to.
    We have worked intensively since your wonderful decision to 
make $500 million available in fiscal year 2018 and to have 
that in the base so that it will be there in 2019 and beyond. 
Working with all of the institutes across NIH, we have put 
forward an opportunity for new and bold ideas to come forward, 
and we are in a place now, I think, of having a remarkable 
portfolio that we are ready to launch.
    You also graciously gave us that first year of support as 
2-year money so that we could, in fact, carry over some of the 
fiscal year 2018 funds into 2019 since it is late enough in the 
year that starting brand new things is a little challenging. 
But we have figured out how we are going to spend a significant 
fraction of that $500 million right away.
    It does include a wide variety of applications, including 
some of the things that have already been discussed by Dr. 
Volkow and Dr. Koroshetz, but also such things as what to do 
about the neonatal abstinence syndrome, which is of such deep 
concern to all of us in terms of how best to manage, what 
happens to those babies, and what is their long-term future.
    The public-private partnership, which you mentioned, is 
actually a modest part of this broad portfolio but an important 
one. Again, as we talked about earlier, the decision was made 
by me based on strong recommendations that that partnership 
should involve assets that are contributed by industry that 
have value, data, compounds, scientific expertise, but not a 
cash contribution. It is a little challenging right now to 
attach a dollar value to what their in-kind contributions are 
going to add up to, but it will be substantial.
    Senator Capito. Good.
    Dr. Collins. So putting that all together, we think we are 
in a good place to move both the public-private partnership and 
the rest of this broad portfolio together quite rapidly.

                      NEONATAL ABSTINENCE SYNDROME

    Senator Capito. Good. Thank you.
    Dr. Volkow, on the neonatal abstinence syndrome, obviously 
we are the State most highly affected by that as well. And this 
is an area of deep concern to everybody. We have got 1,000 more 
kids in foster care. A lot of these babies probably will be the 
repeat mothers. They have repeat exposure. I mean, they have 
numerous exposures to numerous drugs not just particularly one. 
And I believe you visited our Lily's Place down in Huntington 
to see what kind of care they are getting there.
    The research that you are doing and the ACT NOW trials-- 
are those being conducted across the Nation, or how do you find 
the right place to conduct those kinds of--and where are you 
doing that?
    Dr. Volkow. Well, the ACT NOW is one of the programs that 
will be funded through the new money that has come for the 
opioid crisis and will allow us to actually maximize protocols 
that will enable us, for example, to determine what are the 
optimal interventions for the best outcomes on neonates. And 
that includes protocols that may not require the administration 
of medications to those neonates with abstinence.
    We have other research studies also ongoing. And I was at 
West Virginia last week and I was in Huntington. And I was 
horrified to hear that one out of five newborns had opioids on 
them. And one of the points that is highlighted is that we need 
to address the needs of the neonate, but we need to address the 
needs of the mother once the baby is born. So the outcome from 
that infant and child is not addressed. So we are working with 
research of new medications and new non-medication 
interventions to improve the outcomes of those neonates.
    And the other aspect that Francis mentioned is we are very 
interested in understanding how the brain of these newborns is 
going to have been influenced by getting exposed to opioids, as 
well as other drugs, during fetal development when the brain is 
very, very vulnerable.
    Senator Capito. Right. I am anxious to hear how we progress 
with that.
    I guess one of the points of asking my question is there a 
wealth of data all around the country with people who are hands 
on in these scenarios dealing with this right now that I think 
can feed not only good information but can help you conduct 
trials on a local level. It sounds like that is what you are 
already moving forward on.
    Dr. Volkow. Correct.

                      CLINICAL TRIALS--ALZHEIMER'S

    Senator Capito. I am really pleased to be on the STAR Act, 
the childhood cancer act. I am glad to hear about the 
survivorship. That is something of great importance to me. A 
lot of this I am very interested in, as Dr. Collins knows, but 
I do want to go over to Dr. Hodes because Alzheimer's on the 
other end of the spectrum is something that I have personally 
been touched with.
    And I would like to know, Doctor, one of the things I have 
heard is that it is hard to recruit patients for clinical 
trials for Alzheimer's. Is that the case? What are you finding 
there? I mean, I know it is hard by the time you start 
exhibiting the symptoms, you are already in it. How are you 
developing all those trials with different----
    Dr. Hodes. Senator, it is an excellent question. And it is 
a challenge to us for multiple reasons.
    As you have commented upon, for individuals who are already 
affected with symptoms, we carry out studies that are extremely 
important. But there is also a sense that in order to be most 
effective in preventing the appearance of symptoms that we need 
to intervene earlier before irreparable damage is done.
    This means that we need to recruit people who are not 
coming through a normal process where they see a clinician who 
suggests they participate in a clinical trial. These are people 
who are at high risk but show no symptoms. So we need to 
develop and are developing strategies for screening those at 
high risk and then the charge of finding people who are 
committed, dedicated to participate in studies to see if we can 
make a difference through early intervention.
    Studies such as All of Us present a unique opportunity for 
this with a million people, for example, who have signed on for 
their interest in participating in research. We can screen 
those who, by a variety of metrics, may be at high risk for 
developing symptoms years or decades later and take an 
opportunity to intervene with those now. So we are in the midst 
of a nationwide program which will be announced this summer to 
look at multiple modalities for recruiting patients into 
studies.
    Senator Capito. Good. Thank you. We want to support that. 
Thank you.
    Senator Blunt. Senator Shaheen.

                                FENTANYL

    Senator Shaheen. Thank you, Mr. Chairman.
    And thank you to you and Senator Murray and Senator 
Alexander for your commitment to research and funding for NIH.
    And to you, Dr. Collins, and everyone there, thank you so 
much for the work that you are doing. You give hope to so many 
people across this country.
    Dr. Volkow, thank you for coming to New Hampshire. I 
especially appreciate the work that is being done to address 
the opioid epidemic. Like my colleagues on this committee, we 
have been very hard hit in New Hampshire, as you know, from 
your visit to Catholic Medical Center and other places in the 
State.
    I was interested in your discussion about new drugs that 
are in development. As you are looking at what the potential 
is, are you separating out fentanyl as a particular opioid that 
has very deadly properties and therefore requires a different 
kind of response, or are you lumping that in with everything 
else?
    Dr. Volkow. We cannot lump it with everything else because 
what we are hearing from the field and being reported in the 
literature is that when people overdose with fentanyl, the 
doses that were used of Narcan are not sufficient actually to 
reverse the overdoses. The other concern is if you get exposed 
to fentanyl, because of its potency, your risk of addiction is 
much higher.
    So as of now, we, for example, have not ever done a trial 
of how do you treat someone that is addicted to fentanyl, and 
that is one of the projects that we would like to implement as 
soon as we get the approvals.
    But also with respect to the medications, we are actually 
funding researchers who are partnering with pharmaceuticals to 
develop a stronger antagonist. So this is the nasal Narcan, 
which we actually developed, but it is not sufficient for 
fentanyl. So we are developing with companies longer lasting, 
more potent or alternative medications that may not be based on 
the same mechanism as naloxone. Because the other challenge is 
not just fentanyl, but what we are observing is people are 
overdosing with multiple medications, alcohol, benzodiazepines, 
and fentanyl. So this is not sufficient.

         CO-OCCURRING MENTAL HEALTH ISSUES AND SUBSTANCE ABUSE

    Senator Shaheen. And we see so many people who have co-
occurring mental health issues along with their substance use 
disorder. So often they are using substances to address their 
mental health issues.
    So are you doing any research that looks at the two 
problems together that may give promise as we think about what 
the future holds?
    Dr. Volkow. We cannot do that because the comorbidity is 
many times much more frequent, the isolation. And if you 
address, for example, the depression of someone that is 
addicted to opioids, you are not going to succeed.
    Also a very important component followed by the overdose is 
we really do not know which ones are intentional, therefore 
suicide. So if you are reverting someone on an overdose that 
has suicidal behavior and you do not intervene, you are not 
going to succeed.
    So we are prioritizing. We are recognizing that the reality 
is comorbidity, comorbidity of addiction with mental illness, 
and comorbidity of addiction with pain. And those are more 
challenging than when they are in isolation.
    Senator Shaheen. So did you want to add anything to that?
    Dr. Collins. I think Dr. Volkow very accurately 
characterizes the situation.
    I think one of the things that we are most concerned about 
in terms of this crisis, just if I can show you this graph, is 
the way in which the epidemic, in terms of the overdose deaths, 
has shifted from being prescription opioids to now fentanyl 
just going straight off the chart as it gets into the heroin 
supply. And as more individuals who have fallen into addiction 
cannot find sufficient access to prescriptions, then they shift 
over.

                                 EBOLA

    Senator Shaheen. Absolutely. That is what we are seeing in 
New Hampshire where we have the highest rate of overdose deaths 
from fentanyl.
    Dr. Fauci, Senator Blunt mentioned the Ebola epidemic and 
the news report this morning that said the first case had been 
found in an urban area, a large city, in the Democratic 
Republic of Congo. And given DRC's other challenges, how 
worried are we that that epidemic is going to get out of 
control again?
    Dr. Fauci. Given our prior experience, we are on very high 
alert about this Ebola outbreak. There are some factors that 
mitigate against their having the same situation as we saw in 
West Africa, but there are also factors that actually might 
favor that. As you mentioned, the first cases that were 
reported in very early May, the first week in May, were in a 
place called Bikoro, which is on a remote area called Lake 
Tumba. The bad news is that it is very difficult to get help 
in. The good news is it is very difficult to get anybody out.
    But what you heard this morning in the report is that there 
are multiple different zones. Bikoro is one zone. Another zone 
is Mbandaka, which is an area that has a city of 1.1 million 
people. And even though there is only one case there, there is 
a total now of 44 cases. Even though only two have been 
confirmed, there are 20 that are probable and 20 that are 
suspicious. So there are probably many more cases.
    What we are doing now is shipping in with the WHO (World 
Health Organization) helping, obviously, the kinds of things 
that were the fruits of the work that we did with the support 
of this committee and others to develop countermeasures. And I 
will very briefly give you an example.
    You heard probably on the media that the WHO has authorized 
the shipping of the VSV vaccine that had its first phase one 
trial right at the Clinical Center at the NIH, and then we did 
it in Africa and that was the one that did the ring 
vaccination.
    We also have ZMapp, which is that triple combination of 
antibodies that we published in the New England Journal of 
Medicine from the intramural program at NIH that went over 
there in Liberia. That is also being shipped.
    And we have some experimental drugs, one we are partnering 
with Gilead, and some monoclonal antibodies that have been 
developed by the Vaccine Research Center.
    So although in direct answer to your question, we are on 
high alert. We are always concerned when there is Ebola. But we 
right now have a number of countermeasures that we are able to 
develop to go in and hopefully block that. So our hopes are--
our expectations are always cautious, but the hopes are that we 
will not have the kind of outbreak that we saw in West Africa.
    Senator Shaheen. Thank you,
    Thank you, Mr. Chairman.
    Senator Blunt. Senator Durbin.
    Senator Durbin. Thanks, Mr. Chairman.
    Let me say at the outset that in a world of frustration and 
partisanship, what is happening in this room this morning is a 
welcome exception. You will find more positive feelings, more 
achievement I hope, and more bipartisanship than in almost any 
other room on Capitol Hill. And I want to salute the chairman 
of the subcommittee, Senator Blunt, his ranking member, Senator 
Murray. I told her I was going to praise her before she left. 
And certainly Senator Alexander in his work and Senator 
Shaheen. This is a great assignment because with the help of 
the folks sitting at this table, we actually feel like we are 
taking steps forward.
    And to Senator Blunt for his leadership on this, we have 
established a standard I think and I hope it is one that we can 
live by of sustainable, reliable increases in medical research 
funding in the United States of America. Dr. Collins told me 
several years ago that is what we need, and we are doing our 
best to meet that need.

                                 CRISPR

    One of the areas that I have recently learned a little bit 
about was in ``Foreign Affairs'' magazine of all places, and I 
happened to be reading it. And this liberal arts lawyer came to 
try to understand something called CRISPR, which is included in 
your publication here of promising technologies.
    And ironically--I talked to Dr. Collins about this 
earlier--a family from Illinois came to see me last week, and 
the mother, the wife, has myotonic dystrophy, and it is a 
genetic disease which she has unwittingly passed on to her 
children, a son and daughter, whose circumstances are even more 
challenging than her own, and of course, their future is really 
unknown. I mentioned CRISPR to them, and they lit up. They said 
this is the one area where we feel like there is a chance.
    Please, Dr. Collins or one of your colleagues here, give us 
a moment about CRISPR and what we are doing.
    Dr. Collins. I am happy to because I agree that this is one 
of the most exciting things that has happened in a long time in 
terms of providing tools both for basic science and for 
therapeutic applications. It opens up entirely new vistas 
particularly for individuals with genetic disorders where we 
know there is a misspelling in the DNA. This provides an 
opportunity to go and fix that in a very precise fashion.
    So it is also a great story about basic science because 
this particular enzyme called Cas9 was discovered in a very 
obscure area of people trying to understand how bacteria can 
fight off their own viruses. Bacteria have their own viruses 
and somehow they manage to survive. And it is a very elegant 
system where the bacteria have an enzyme that basically 
recognizes a foreign DNA sequence and goes and snips it and 
inactivates it. But it is programmable.
    And so Jennifer Doudna and her colleagues and Feng Zhang 
and his colleagues and a few other people who are arguing about 
who gets the credit basically came up with a way to take that 
bacterial system and make it work in all kinds of cells, 
including human cells.
    It is very precise. You program it. It can find in a 3 
billion letter instruction book--that is our DNA genome-- the 
one that you want to alter and zero in on it and very precisely 
make a cut or make a substitution.
    Now, of course, in the basic science lab, this is 
fantastic. Every laboratory that is doing molecular biology is 
using CRISPR Cas9, including mine, including all the people at 
this table who have active laboratories. But therapeutically 
the promise here is what I think has us particularly excited.
    As I mentioned to you earlier, sickle cell disease may well 
be the first success of this because for sickle cell disease, 
the problem is in the bone marrow stem cells. You can take them 
out. You can purify them. You can utilize this enzyme system to 
fix the sickle mutation and then put them back. And that should 
be not just a treatment but a cure for people with this 
disease, 100,000 of them in the U.S. I think that is going to 
happen in the next 5 years. The first clinical trials are 
probably going to start this year.

                                 VAPING

    Senator Durbin. I hate to interrupt you because this is 
important. I have one other topic I want to mention. And I hope 
that this subcommittee can zero in on the CRISPR technology and 
what is happening there. I think there is so much promise.
    But I wanted to mention one other thing that is important 
to most of us. 27 percent of the high school students in the 
State of Illinois have something in common. 27 percent of them 
are now using e-cigarettes and vaping. It used to be 28 percent 
using tobacco cigarettes. Now they are into e-cigarettes and 
vaping. And the people who are peddling these products that 
they inhale with nicotine are putting them in candy flavors. 
Here is one. The brand is Lung Candy and the flavoring is Cake 
Batter. In this listing here--it is a long listing of flavors 
for children to see opportunities for vaping. We see exactly 
what is happening.
    Can I get a comment from any of you about what you consider 
to be the perils or danger of this type of addiction?
    Dr. Collins. Dr. Volkow.
    Dr. Volkow. Indeed, we are very concerned because one of 
the issues why 50 percent of teenagers say that they are 
starting to vape only with flavors, 30 percent of them are 
starting to vape with nicotine and are becoming addicted to 
nicotine.
    And in studies that have been already published, it has 
been shown that if you start to vape, you are much more likely 
to then go into nicotine vaping, and then if you got into 
nicotine vaping, then to go into smoking tobacco. So a major 
concern is that we will be losing a lot of the advances that we 
did on prevention of smoking among teenagers.
    Another aspect that people do not really recognize is that 
nicotine acts as a priming. So anything that you take when you 
have nicotine on board becomes much more reinforcing. And as a 
result of that, if you get exposed to drugs while you are 
having nicotine on board, you are much more likely to become 
addicted. So the concern is not only that these teenagers will 
become cigarette smokers, as the data has already shown--the 
risk goes up--but also by doing this, their brain becomes 
primed to the addictiveness of other substances.
    Senator Durbin. Thank you.
    Thanks, Mr. Chairman.

                                  ZIKA

    Senator Blunt. Thank you, Senator Durbin.
    Dr. Fauci, let me give you a couple minutes to talk about 
two things. First, Zika. I was at St. Louis University during 
the Zika crisis where they were working on Zika vaccine 
research and felt like they were coming to conclusions. So are 
we going to have something available next time? And second, 
flu, specifically universal flu, or whatever you want to talk 
about on your research on those two topics.
    Dr. Fauci. Thank you, Mr. Chairman.
    First, we will take Zika. As you know, as I reported to 
this committee on more than one occasion, we have progressed in 
our vaccine trial from the phase 1 trial that we originally did 
at the NIH to now deploying a phase 2b trial, 2b being 
relatively advanced to not only ask is it safe, but does it 
induce the kind of response that you would predict would be 
effective.
    And I am pleased to report to you that today we have 
ongoing a phase 2b trial in several countries in South America, 
in Mexico, in the Caribbean, Puerto Rico, in Texas, and in 
Florida to determine if the vaccine is safe and if it does 
induce that response. It is scheduled to have between 2,400 and 
5,000 people in the study. We are recruiting very rapidly. We 
anticipate--and I am pretty cautiously optimistic about that--
that we will have it fully accrued by the end of 2018. And then 
if in fact there is an outbreak, we could get an efficacy 
signal.
    And if there is not, then we are working very closely with 
the FDA (Food and Drug Administration) if we can get enough of 
what we call immunogenicity data--namely, it shows that it does 
induce the kind of response that you want--and bridge that to 
the animal data, which are very convincing that this is a 
vaccine that can induce a good response--we are working with 
the FDA to determine if in fact we can get an accelerated 
approval. You never anticipate what their decision will be, but 
they are being very cooperative.

                         UNIVERSAL FLU VACCINE

    Next, universal flu vaccine. Again, we are very grateful to 
the committee for supporting the addition of the $40 million in 
the 2018 omnibus for a universal influenza vaccine. So let me 
report where we are with that.
    We had a meeting in Rockville in June of 2017 in which we 
developed, in association with experts from all over the world 
and in the United States in influenza, what we call a strategic 
plan and a research agenda, which we published in the Journal 
of Infectious Diseases in February of this year.
    We are now implementing that plan both from a basic science 
standpoint but also with candidates that are at various stages 
of development, namely either preclinical in animal study or a 
phase 1 or phase 2.
    And I might just close by saying you may have read just a 
couple of days ago an NIAID-sponsored phase 2 trial with the 
universal flu vaccine candidate in association with the company 
BiondVax has been initiated. And we started a few months ago 
one of the trials from our vaccine Research Center.
    So things are on track. Obviously, as I mentioned to this 
committee, it is not going to be an overnight type of a thing, 
but we are well on the road at various iterations of going 
towards a universal flu vaccine.
    Senator Blunt. And do you see a point, if we got there--I 
am assuming what we are trying to get is for every year we 
would not have to try to calculate what that year's flu was 
like and, more often than not, be slightly off target.
    Dr. Fauci. You are absolutely correct, Mr. Chairman.
    The perfect--and that is going to be difficult to do. A 
universal flu vaccine would be one that would cover all 
versions of seasonal and any potential pandemic. But the road 
we are taking now is to go step by step. I tend to refer to it 
as universal flu vaccine 1.0, which means that we will not have 
to worry about any H3. The H3N2 that we do each year and we 
have to change it a little from season to season, which is the 
reason why we need to get vaccinated every year, the first 
version will cover all of the H3N2's. The next one will cover 
very likely an H1N1. There are two major groups of influenza 
viruses that have multiple viruses in each group. Getting one 
that covers both groups is getting close to the perfect one.
    So the answer is the end game is that you and I, but most 
likely our children, will be able to get a vaccine early on in 
life, a boost, and then maybe every 10 years or so and not have 
to worry about each year guessing what the next iteration is 
going to be. It is the guess that is the problem because 
sometimes you do not get it right, and even when you do, it 
changes enough that it evades the vaccine. And that is what we 
are trying to avoid.
    Senator Blunt. Well, I may have unlimited time here, and I 
may exceed that. Who knows what may happen?
    [Laughter.]

                       FUTURE OF CANCER RESEARCH

    Senator Blunt. Dr. Sharpless, so I think in the United 
States today there are 15.5 million cancer survivors. In 1971, 
there were 3 million cancer survivors. An incredibly exciting 
time. Immunotherapy, the BRAIN Initiative, and, that I assume 
will have a significant cancer-looking element to it, CRISPR.
    You and I have some time here. Could you take just a few 
minutes, a couple of minutes maybe, and talk about your vision 
of what you hope and believe can happen over the next handful 
of years in the Cancer Institute based on what we see happening 
already?
    Dr. Sharpless. Sure. I think you are really right about 
that. It is a very exciting time in cancer research. I recently 
had a colleague email me. It is like I picked the perfect time 
to lead the National Cancer Institute because there are all 
these exciting things going on. In fact, today is the release 
of the ASCO abstracts. It is sort of like Christmas in our 
field where all the new advances come out and a number of 
exciting advances in a variety of different cancers.
    So I think there really are a lot of opportunities that 
cash in on this observation that cancer is not only one disease 
or 10 diseases but hundreds or thousands of diseases, and each 
one of them needs its own specific treatment.
    So the good news is there is a lot of excitement going on. 
There are a lot of new technologies and new approaches, and a 
lot of that research has been empowered by the funding from 
this committee.
    But I think the bad news about it is that problem is 
somewhat different from what we used to imagine. So we used to 
think of cancer is like one disease and we had the cardiology 
paradigm where we put 800 people on one arm of the trial and 
800 people on the other arm of the trial. That sort of clinical 
trials framework no longer really works. So the modern approach 
to cancer I think has to be somewhat different.
    So the things I thought the NCI should focus on are 
training the workforce so that we have the right kinds of 
cancer researchers. So we need cancer biologists who really 
understand basic immunology because it is excessive 
immunotherapy, and we need cancer researchers who understand 
big data because we are aggregating data at such a furious pace 
to try and use that information to treat cancer patients.
    We need to recommit to basic science. You know, it is not 
enough to make progress against some cancers. We really have to 
make progress against all cancers, and that requires a basic 
biological understanding of all cancers.
    We need to fix the problem of clinical trials. The 
structure of clinical trials in cancer has led them to become 
smaller and more fragmented and much more expensive. And so we 
need to sort of rethink how we do clinical trials. A very 
interesting development there is the NCI-MATCH Trial, which 
will be presented this year at meetings about how we sequence 
patients and identify the mutations in their tumor and then 
allocate them to therapy based on the genetic driver, the 
personalized event that makes their cancer relevant.
    And then lastly, we really need to get serious in cancer 
about organizing our data and aggregating it and linking it so 
that we have the genomic data, the radiology data, the 
histology data, the clinical information--we have that all 
available in a way that is safe and secure, available to the 
research community so we can understand what mutations cause 
what patient to respond to this drug and why they lived that 
long and really get a handle on these bins of rare cancers that 
we have to treat.

                          GENETICS AND CANCER

    Senator Blunt. I was out at FDA not too long ago. They have 
put a cancer team together that I know you are aware of that is 
looking at all they are doing. You know, the thought in that 
discussion came up that within the foreseeable future, there 
just may be something that each individual is prescribed that 
amps up, if you will, whatever their unique fighting capacity 
needs to be on their unique attack that is likely to happen to 
them. That is one look.
    The other look is--I am not sure how the genetic--the 
CRISPR effort works there. But it is an incredibly exciting 
time. Even with immunology, I would think that 5 years ago an 
observation made in passing would not have been made at all. 
This is what we are doing. And there I am sure you are going to 
continue to work on why this does not work on some cancers and 
what you need to find. It may not be possible ever, but right 
now--Dr. Collins, do you want to talk about that?
    Dr. Collins. I appreciate your raising this, why does it 
not work when it does not work.
    And we talked earlier about partnerships, and I wanted to 
point to this as a very successful public-private partnership 
called PACT, the Partnership for Advancing Cancer Therapies. 
Now 12 biotechnology pharmaceutical companies have partnered 
with NIH to ask that question. What are the biomarkers that 
actually tell you that immunotherapy is going to work or it is 
not? Because we have these dramatic success stories. Emily 
Whitehead, this little girl that had failed to respond to the 
traditional treatment for leukemia and who was very much near 
the end, and who with CAR T-cell therapy was not just 
successfully treated, she was cured. She is 5 years out now. 
She looks great and wonderful.
    But it does not work for solid tumors nearly as well. Why 
does it not work for pancreatic cancer? Why does it not work 
for prostate and breast and brain tumors? We need to figure 
that out, and that is what this partnership aims to do. In this 
case no concern about, I think, conflict of interest. It is all 
pre-competitive. It is all out there in public. So in this case 
pharma is contributing both expertise and resources but also 
cash, and it is pretty exciting to see this taking shape under 
the leadership of Dr. Sharpless and his colleagues.
    Dr. Sharpless. Yes. I think that is one of the initiatives 
to really sort of--you know, each of these therapies requires a 
really detailed understanding of how they work to make them 
work in everyone. But it is just leaps and bounds. Every day 
now we are seeing some new area where we have a drug that used 
to work and we are making it work better for a whole new class 
of therapies. And so a lot of good stuff going on.
    However, I think it is also important to note that we do 
still have some cancers, some even reasonably common cancers, 
where we have not made much progress. So glioma, for example, 
glioblastoma, brain cancer, is still a real problem, and I 
think that we really as the NCI have to not only focus on the 
cancers where we are having successes but also perhaps even 
more so on the ones that have been recalcitrant and refractory 
to therapy to date. And so that is an important part of our 
mission as well.

                        ALZHEIMER'S AND DEMENTIA

    Senator Blunt. I think the area of greatest spending, 
certainly the quickest growing spending of Federal health 
dollars would be Alzheimer's and dementia. And Dr. Hodes, if 
you and maybe Dr. Koroshetz both would talk about what we are 
finding there. We have made big investments here. You have 
probably eliminated a lot of things we know do not work. Now, 
how are we doing on the other end of that and the dementia 
impact, too, Dr. Koroshetz, when it comes to you on that? And 
then when you are done, we will go to Senator Hyde-Smith as she 
settles in here.
    Dr. Hodes. Thank you.
    I first want to thank the committee, Congress for the 
increased appropriation of resources towards Alzheimer's 
disease and related dementias. It has had an enormous impact. 
For example, in 2015, we funded 152 awards supporting research 
in this area. 2 years later in 2017, that had increased to 442.
    And importantly, this is reflected with confidence and 
excitement that we heard about across the research community 
seeing the national commitment to sustained resources, a 
renewed energy on the part of new and early stage 
investigators. So of all these new awards we have seen, more 
than a quarter, 27 percent, were to the categories of early 
stage and new investigators who had not received any NIH major 
support previously. An even larger number than that, more than 
a third, 36 percent, had never had any support for Alzheimer's 
and related dementias research. So we are bringing into the 
community not just more dollars and opportunities but the 
energy that comes with new people willing to commit their 
careers and to bring new disciplines into the field.
    This has included an expansion of the number of clinical 
trials currently supported to over 140. And equally important, 
using new techniques of looking at gene expression patterns, 
proteomics, metabolomics, and an amazingly effective 
consortium, AMP, Accelerating Medicines Partnership, around 
Alzheimer's disease to bring public and private science, 
clinical expertise, and financial support together to fund new 
discoveries that have identified the so-called wall of targets 
now--there had been a consensus to find new molecular targets 
not appreciated before that might lead to entirely new 
approaches much needed, in addition to the directions we 
currently take for translation into clinical trials.
    So it is an incredible excitement I think you can 
appreciate. The numbers are only meant to illustrate the 
intensity of excitement there is now. Sustained funding has now 
convinced investigators this is an area in which we can make 
progress, and the pace has increased exponentially.
    Senator Blunt. I think at Washington University they are 
feeling more and more positive about a blood test. Things like 
that that would begin to early identify what was happening with 
amyloids in the brain would be a big step in the right 
direction. Hopefully, we can go out there together and look at 
that sometime.
    Dr. Hodes. Yes.
    Senator Blunt. Dr. Koroshetz.
    Dr. Koroshetz. Thanks to the wisdom of the Congress for 
including what we call the Alzheimer Disease-related dementias 
in this major effort to decrease the public health problem of 
dementia in our country. Most patients who have dementia are 
diagnosed with Alzheimer's disease. Especially in the elderly, 
when one looks at the brain, one more often than not will find 
multiple different things going on. And one of the two areas 
that are most common is the finding of what we call Lewy body 
disease in people who have dementia diagnosed as Alzheimer's. 
They have Alzheimer's changes but also have the signature of 
Parkinson disease, which is synuclein aggregates. So 
understanding the contribution of these synuclein aggregates 
not just to Alzheimer's dementia but also to the dementia that 
occurs in Parkinson's patients who have it for a long time is a 
focus that we have been able to really pursue much more 
aggressively.
    The other area, which is even more common, is the 
combination of vascular disease in people who are diagnosed 
with Alzheimer's disease. And this is, I think, incredibly 
important to understand because we have made strong progress 
over the last 70 years in decreasing the risk of stroke, which 
is the most common consequence of vascular disease in the 
brain, and also incredibly common in people who have dementia 
diagnosed as Alzheimer's.
    So we have been working with the National Institute on 
Aging on projects to be able to track the health of the 
cerebrovascular system in the brain and its contribution to 
dementia with the hope that the things we already know about, 
if we can be more aggressive about them, may actually prevent 
people from going on to develop dementia because we can block 
this contribution of the vascular component.
    Senator Blunt. Exactly.
    Senator Hyde-Smith.
    Senator Hyde-Smith. Thank you, Chairman Blunt.
    And thank you, Dr. Collins, for testifying today and all of 
you for testifying today.

             EXPANDING CLINICAL TRIALS TO UNDERSERVED AREAS

    I have been involved as a volunteer with the American 
Cancer Society for many, many years in Mississippi. So I have 
seen firsthand how new treatments and therapies have 
transformed the prognosis for so many different types of 
cancers. And I am grateful for the role that you have played, 
that NIH has played in so many of those discoveries. What you 
are all doing is so important, and I truly see it changing and 
saving lives. And I am grateful to you for that.
    However, despite these recent innovations in cancer care, 
my State of Mississippi continues to have one of the highest 
cancer mortality rates of any State. For many Mississippians, 
receiving the cutting-edge treatments and participating in a 
clinical trial would mean traveling hundreds of miles from home 
to a cancer center in another State, which is not possible for 
so many of our patients.
    But, Dr. Sharpless, how is the National Cancer Institute 
working to ensure that patients in States like mine, which do 
not have an NCI-designated cancer center, are able to 
participate in clinical trials and benefit from the newest 
discoveries?
    Dr. Sharpless. Senator, thanks for the question.
    I think you raise a really important issue, which is that 
it is in some ways great news we are making all this progress 
against cancer and having those new therapies and new 
approaches, but if we then cannot disseminate them into the 
broader community and implement those therapies in sort of the 
real world, then are we helping people to the extent that we 
could do so?
    So the National Cancer Institute is very concerned about 
how we assure that our advances translate beyond just the NCI-
designated cancer centers, which are a great program but there 
are only 70 of them, and their range is limited.
    One program we have to address this is called the National 
Community Oncology Research Program, or NCORP, which is 50 
NCORP sites that then have each several satellite sites. So 
there are sort of 900 NCORP sites across the country. Between 
the cancer centers and NCORP, we reach virtually the entire 
country. And these sites, in addition to being able to do 
clinical trials, also have catchment areas that have patients 
that are more likely to be rural patients as opposed to urban 
patients and more likely to be underserved minorities. So it is 
a way that we can enroll a demographic that looks more like the 
United States in general. So it is a great program. We have 
just decided to expand its scope somewhat. It is successful and 
we want to build on that.
    And it is also important to note that we can do clinical 
trials in the NCORP program. For example, the NCI MATCH trial 
enrolled 6,000 patients at 1,100 sites. It was the fastest 
accruing trial in the history of the National Cancer Institute, 
and it allowed us to do accrual in the community, which is also 
a real need in cancer research because 5 percent of adult 
oncology patients go on clinical trials. That number needs to 
be higher, and we need to take the trials to them through like 
the NCORP program. So it is one way that we are working to 
address this important issue.

                        ALL OF US PILOT TESTING

    Senator Hyde-Smith. Wonderful, very good.
    And also, I am proud that The University of Mississippi 
Medical Center and the Jackson-Hinds Comprehensive Health 
Center were both chosen as sites in the All of Us research 
program in Mississippi. This program, which seeks to enroll 1 
million American volunteers, will no doubt lead to important 
discoveries that will help doctors identify treatments and 
personalized to patients' lifestyles, individual's environments 
and genetic biology. Jackson-Hinds was only one of only six 
community health centers nationwide chosen to help pilot the 
project beginning in 2016.
    Dr. Collins, as the NIH rolls this program out nationwide 
this year, how have you incorporated lessons learned through 
the pilot at Jackson-Hinds that participated in this?
    Dr. Collins. That is a great question. We did spend the 
last year in a pilot phase of ramping up All of Us, recognizing 
this is probably one of the most ambitious projects that NIH 
has ever mounted, and we needed to have great attention paid to 
the needs of the participants and particularly for their 
security and privacy. And we also made a commitment that this 
was going to be a project that was truly national and it would 
include people who were traditionally not invited to take part. 
People in community health centers oftentimes have not been so 
engaged in research. We wanted to reach out. And Jackson-Hinds 
was in a particularly powerful place to be one of the first 
ones to try and see how this would go.
    I think we have been very encouraged. In the pilot projects 
for All of Us, we enrolled over 26,000 people. That makes it 
one of the biggest studies NIH has done in a long time. And 
that was just the pilot on the way to our million.
    And from the community health centers like Jackson-Hinds, 
we were gratified to hear a lot of interest on the part of 
people who came there for their medical care in getting engaged 
in this kind of research and being included. They wanted to be 
counted too. They wanted the results of this study to be about 
them and therefore, provide information that they could use.
    So I think it has been a wonderful experience. It has been 
a kind of outreach we have not necessarily tried at quite this 
scale before. And now, as of May 6th, we have done the full 
launch, and anybody in the United States can join up, 
joinallofus.org. That is all you need to know.
    Senator Hyde-Smith. Great. Well, we certainly appreciate 
it. All of you.
    Senator Blunt. Thank you, Senator Hyde-Smith.
    Senator Shaheen.

                            TYPE 1 DIABETES

    Senator Shaheen. Thank you, Mr. Chairman.
    I came back because I did not want to go home and tell my 
family that I had this whole panel from NIH in front of me and 
I did not ask you about the prospects of research into a cure 
for type 1 diabetes. I have a granddaughter who has type 1. I 
also co-chair the Diabetes Caucus in the Senate with Senator 
Collins and know how devastating the potential is in this 
country if we do not figure out a cure for this disease. One in 
three by 2050 will have diabetes, and it is one of the most 
expensive, if not the most expensive, chronic diseases that we 
have.
    So can you give me an update on where we are with research?
    Dr. Collins. Senator, I would be happy to and appreciate 
your leadership in this.
    This is another one of these very exciting areas where 
things are now moving very quickly for both type 1 and for type 
2. Much of the excitement surrounds the potential of developing 
an artificial pancreas that would take care of the production 
of insulin when the body has failed to do so at the level it 
needs to. And you already have seen, of course, the FDA 
approving the very first example of an artificial pancreas in 
sort of a closed loop where there is a sensor of what the 
levels of glucose are and then it administers insulin 
accordingly. But this is just the beginning of what I think is 
going to be a remarkable series of advances.
    Ultimately the whole stem cell area is going to be critical 
here as well. We have, after much hard work through the work of 
people like Doug Melton at Harvard, figured out how you can 
take a skin cell from somebody, convince it to become what you 
would call pluripotent and then give it the appropriate set of 
cocktails to convince it to go down the pathway to be a cell 
that makes insulin. But it is your own cell. And so ultimately 
in the view of many of us, that is where we are headed, the 
opportunity to make an artificial pancreas that does not have 
silicon in. It actually has your cells that have been 
reprogrammed to make up for what the other cells that should 
have been doing this were able to do.
    On top of that, I think in terms of prevention particularly 
of type 2 diabetes where we know that this is tightly connected 
to obesity and insulin resistance, increasingly trying out the 
efforts to reduce weight and increase exercise are looking very 
promising over the long term to keep people who are tipping 
over into diabetes from actually getting there.
    A lot of research as well on gestational diabetes and what 
kind of information we can learn when this seems to happen 
during pregnancy. What should be the follow-up to that because 
that clearly indicates a risk for future illness.
    So it is a very exciting time. I could go on much longer, 
but I wanted to reassure you that NIH is deeply in the middle 
of all this and the progress is quite gratifying.

                          ARTIFICIAL PANCREAS

    Senator Shaheen. Well, I appreciate that. And I am excited 
about some of the new developments. I think we need to think 
about how we can reverse the incentives in our healthcare 
system to do more for prevention with type 2 where it really 
makes a difference. And unfortunately, I think we are not 
providing the resources that we need there, and in the long 
term, it is going to cost us more money.
    But I wanted to ask a follow-up because one of the things I 
have heard from the diabetes community is their frustration 
with how long it has taken the FDA to approve an artificial 
pancreas and further developments on that. So we are seeing 
people in the community who are doing what they call bootleg--
and that is probably not a good term--but are basically making 
their own artificial pancreas and feel like that provides more 
relief than they are getting currently, given the system that 
we have and the dependence on insulin and the way that works.
    So can you speak to that? Is that something that you have 
heard about, and are you concerned about what the risk might be 
from that?
    Dr. Collins. I do think there are reasons to be very 
careful about putting in place an artificial pancreas system 
without being absolutely confident that it has the appropriate 
safety mechanisms because we all know that an overdose of 
insulin can put you into a coma and can ultimately lead to 
death. So this needs to be a system that is really well worked 
out. So I understand why the FDA, therefore, has to be pretty 
rigorous in terms of their evaluation of such things.
    I do think, though, that in Scott Gottlieb you have an FDA 
Commissioner who really is dedicated to moving things along as 
soon as the data makes it possible.
    Senator Shaheen. Yes, he has said that. I appreciate that.
    Dr. Collins. We work very closely with FDA under his 
leadership. And some of the things that we can do in terms of 
providing that data is a part of that partnership that we are 
pushing pretty hard right now.
    Senator Shaheen. Well, thank you. Thank you all very much 
for the great work that you are doing.

                     SOCIAL MEDIA AND SOCIALIZATION

    Senator Blunt. Dr. Koroshetz, do you have anybody looking 
at the socialization challenges of the constant exposure to 
social media or the screens as something--the impact that that 
may have on adolescents and others?
    Dr. Koroshetz. So certainly social media is taking over our 
country, and the consequences, whether they are pros or cons, 
are still yet to be determined.
    I think at NIH there are a lot of grantees that are 
actually using social media to advance health research. I think 
it would probably be the National Institute of Mental Health, 
which is looking at the effects on adolescents. But Dr. Volkow 
can mention a really innovative project which will look at this 
and other exposures on the development of children that she has 
just recently--well, almost half finished I guess.
    Senator Blunt. I had a 50-50 shot there I thought.
    [Laughter.]
    Senator Blunt. And I missed it.
    Dr. Volkow. For us, it is important because drug taking and 
experimentation appears in adolescents, and it is a very social 
behavior. And many times it follows peer pressure. And one of 
the things that we have actually tried to understand is how the 
dramatic changes that have happened in the way that teenagers 
are interacting with one another may be influencing their 
behaviors, including drug taking.
    But most importantly, our brains are very neuroplastic and 
they are developing during childhood and adolescence to 
maximize your ability to respond to your environment. So we are 
interested to know if you as an adolescent or as a child get 
exposed massively to the social communication as opposed to the 
one-to-one, how does that influence the development of the 
brain.
    So in September of 2016, we started a study with many of 
our partners at the NIH called the ABCD, Adolescent Brain 
Cognitive Development, where we are aiming to recruit 10,000 
children. We have already recruited 9,500, and we will be 
finishing in September. But to monitor them on the next 10 
years to actually do brain imaging, characterize them 
cognitively, characterize them socially, and measure how 
exposure to social media ultimately influences the development 
of the brain. So this is probably the most notable study that 
we have because it will allow us to understand how this very 
dramatic change on how people are interacting with one another 
may influence the brain.
    We also have research to understand how social media is 
used to actually change the perspectives of teenagers with 
respect to getting exposed to drugs, the likelihood that they 
will take a drug when they see it in social media. So the 
vaping device and the electronic cigarettes, to what extent 
they are being frequently mentioned in social media are 
influencing the probability that a teenager will use them. And 
the same thing with marijuana and the same thing with alcohol.
    So this is a completely new world for all of us, and we do 
not actually, as of now, have an understanding about how it is 
going to influence the human brain and behavior.
    Senator Blunt. Thank you.
    Senator Moran.
    Senator Moran. Chairman, thank you. I am glad the meeting 
is still going. I do not know that you are pleased with my 
arrival.
    [Laughter.]
    Senator Moran. But I am honored to be here. Thank you.
    Senator Blunt. I am always pleased with your arrival.
    Senator Moran. Thank you, Chairman.

                   BIOMARKERS AND ALZHEIMER'S DISEASE

    Dr. Hodes, I am not exactly sure what has been asked and 
answered, but I want to pursue a couple of concepts that are 
now developing in regard to Alzheimer's.
    We have talked about detection and the efforts to use 
biomarkers to identify someone who is at risk or has 
Alzheimer's before they begin showing symptoms. The National 
Institute on Aging just coordinated to propose a biological 
construct which looks at the use of measurable changes in the 
brain to better understand the earliest biological signs that 
lead to symptoms.
    How will this new framework help to drive research forward? 
Does it represent a new understanding of the beginning of the 
disease?
    Dr. Hodes. Thank you.
    The importance of being able to identify the changes that 
accompany Alzheimer's disease and related dementias early, as 
you have emphasized, is critical where we think that the best 
opportunity to intervene at an early point and be able to track 
success or failure of interventions by measuring biomarkers is 
going to be absolutely critical.
    The definition that you refer to is a publication which 
suggested that for the pathologic definition of Alzheimer's 
disease, based on plaques, tangles, and neurodegeneration, 
there is a set of biomarkers that have standardized, would 
allow us to assess across studies both longitudinal studies and 
clinical trials, and in doing so, rigorously harmonize the 
results of multiple efforts, so more quickly understand which 
biomarkers are best predictive of disease and importantly, 
predictive of a response to intervention to treatment or not.
    So the studies that Senator Blunt referred to at Wash U are 
among those. Right now, the biomarkers that are most accessible 
and most widely used are either imaging, which works extremely 
well but is cumbersome and expensive, or cerebrospinal fluid 
analyses which works. But the goal of many now is to establish 
so-called fluid biomarkers that can take the advantage of blood 
and serum and identify either a single molecule or a pattern of 
molecules that will allow us to screen many people, more than 
we currently can through longitudinal studies and through 
interventions.
    Senator Moran. Doctor, thank you.

              RETURN ON INVESTMENT IN BIOMEDICAL RESEARCH

    Let me address this question to Dr. Collins. With the 
leadership of Senator Blunt and others, we have had success in 
large part, I would say, because you all have made a case for 
additional resources within each of your institutes in which 
the public good is demonstrated and the advancements that are 
being made are sufficient for American people to feel 
comfortable that progress is happening and that we are on the 
cusp of developments that will make a difference in their 
lives.
    In the last year since you were here, Dr. Collins, in this 
setting, what can I tell my constituents that has transpired to 
reassure them that their tax dollars are being wisely spent? I 
sometimes head down the track in a town hall meeting explaining 
that there are things that we should spend no money on, things 
we should reduce spending on, and there are things we should 
spend more money on. And by the time I say that sentence, I am 
wondering what my constituents are thinking about a Senator 
from their State who is interested in spending more money on 
anything. Then I use NIH as the example.
    And one of the things that we have been able to do in this 
subcommittee and the Senate is to prioritize our spending. So 
it is making decisions about where to spend more money, not 
just always the thing that I think many Kansans might think 
happens around here, just spending more money on everything.
    So, Dr. Collins, give me the town hall description of how 
successful our spending has been in the year since we last met.
    Dr. Collins. I love to give that description. Thank you for 
the opportunity.
    One thing that I would say is maybe the most important 
discovery that happened in the last year is one we do not know 
about yet because it was a basic science discovery that sort of 
seemed at the time interesting, but we did not realize until 
maybe a year or 2 from now just how profound it might be. We 
talked about CRISPR Cas earlier. When that was discovered, 
nobody had it on their list of the big deal from that year.
    Another big discovery that probably we could mention for 
anybody across this table would be something that has just 
happened in the more therapeutic applications. In my opening 
statement, I told the story of a little boy who should not be 
alive who is walking around and hanging on the monkey bars 
after being diagnosed with spinal muscular atrophy, a fatal 
disease, and which with gene therapy now appears to have had a 
dramatic response.
    I could say, well, let us talk about drug abuse. Just 
yesterday, approval by the FDA of lofexidine, the first non-
opioid way to help people withdraw from opioids, which is an 
effort that NIDA and their colleagues had put together with 
industry.
    With cancer, the advances in cancer immunotherapy, which 
was already pretty good stuff a year ago--oh, my gosh, it has 
gotten so much more exciting now with the additional advances, 
as Ned could no doubt tell you.
    In terms of neurological diseases and advances in aging, 
some of the basic science of aging has also had some 
interesting findings in the last year about the normal process, 
not just when it goes awry.
    And certainly Dr. Fauci would say, well, goodness, where 
were we a year ago in terms of Zika and Ebola and where are we 
now when it comes to such things as a vaccine for the flu, a 
vaccine for HIV, and maybe also ways to deal with that 
antimicrobial resistance problem, which have come a long way in 
that last year.
    So my town hall speech has already gone on too long, but I 
think you get the sense there is a long list of things we could 
point to in just this last year.
    And in case anybody thinks, well, that is fine but is it 
really worth the money, it is also the greatest return on 
investment of anything that the government spends money on, 
$8.38 of return in 5 years from every dollar that you all 
allocate to NIH because of what happens in terms of its 
economic impact.
    Senator Moran. You do, Dr. Collins, what I do in my town 
hall meetings in wrapping up and concluding and then I have 
another few paragraphs as well.
    Dr. Collins. Guilty.
    Senator Moran. But you have a great story to tell and I 
appreciate you reminding us of those successes. Thank you.
    Senator Blunt. Thank you, Dr. Collins and the Institute 
directors with you today.

                     ADDITIONAL COMMITTEE QUESTIONS

    The record will stay open for 1 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 to Francis S. Collins, M.D., Ph.D.
                Questions Submitted by Senator Roy Blunt
                         personalized medicine
    Question. Dr. Collins, over the past 3 years, this Subcommittee has 
provided $650 million in funding for personalized medicine initiatives, 
including the recently launched ``All of Us'' program. At the same 
time, the National Human Genome Research Institute has continued other 
important genomics research efforts. As the NIH advances the ``All of 
Us'' program, which is a large personalized medicine initiative, how 
are you ensuring that you continue to leverage and support the genomics 
expertise and facilities currently in place across the country?
    Answer. The NIH thanks the Subcommittee for its support of 
personalized medicine initiatives overall, and for its support of the 
All of Us Research Program in particular. The field of precision 
medicine is a major area of growth across the U.S., and the All of Us 
Research Program will dramatically advance the fields of personalized 
medicine and precision health through integrating a wide variety of 
environmental, behavioral, and biological information at an 
unprecedented scale. The program launched nationally on May 6, 2018, 
after establishing a major consortium of academic researcher 
institutions, healthcare provider organizations, technology experts, 
community partners, and participants. The program leveraged the 
expertise of the genomics community through the Genomics Working Group 
of the All of Us Research Program Advisory Panel which issued a report 
in December 2017.\1\ This Working Group included expertise from 
academia, industry, and NIH, including the National Human Genome 
Research Institute. The report provides information on the pros and 
cons of different approaches and options for corresponding 
implementation plans, and encompasses effective strategies to generate, 
analyze, and manage genomic data at the scale of All of Us. The program 
recently issued a funding announcement for Genome Centers to generate 
genotype and whole genome sequence data from participants' biosamples. 
The program anticipates funding up to two Genome Center awards in 
fiscal year 2018, with analyses to begin this fall with a goal of 
ramping up to 200,000 genotypes and whole genome sequences annually. 
This is a scale only feasible because of the outstanding achievements 
of the U.S. genomics research community. The program has been able to 
make major advances in its genomics approach not only through the 
world-class genomics expertise in its consortium and Advisory Panel, 
but also through the on-going interactions of its senior leadership 
with the broader community through frequent participation in events and 
workshops held by organizations across the country, as well as its 
strong relationships with Institutes and Centers across NIH, including 
leveraging the expertise within the National Human Genome Research 
Institute.
---------------------------------------------------------------------------
    \1\ Considerations Toward a Comprehensive Genomics Strategy. 
Available at: https://allofus.nih.gov/sites/default/files/
gwg_final_report.pdf.
---------------------------------------------------------------------------
                            opioids vaccine
    Question. The fiscal year 2019 budget proposes a coordinated 
strategy with two primary aims to combat the opioid epidemic in our 
country. One of those aims is to accelerate the development of new, 
non-addictive pain therapies with the goal of making a wide-range of 
therapeutics accessible to those who need them as quickly as possible. 
Can you describe what types of non-addictive pain therapies are 
currently in the NIH research pipeline, and how quickly can these 
therapies can be developed and distributed to the market?
    Are there any vaccine candidates being considered?
    Answer. NIH is particularly excited about the new Helping to End 
Addiction Long-term (HEAL) Initiative. HEAL will bolster research 
across NIH in an effort to improve the treatment of chronic pain by (1) 
exploring biomarkers that predict the transition from acute to chronic 
pain, (2) identifying new targets for treating chronic pain using 
neurotechnologies developed through the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the 
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, 
and (3) building the evidence base on the effectiveness of nondrug and 
integrated pain treatments. In addition, the Initiative will pursue 
public-private partnerships to develop new non-addictive pain medicines 
by sharing data on past and present research projects, and matching 
researchers with a selection of potentially promising but abandoned 
pharmaceutical industry compounds to explore their effectiveness for 
the treatment of pain. Finally, NIH will develop a clinical trials 
network for pain, allowing multiple new and repurposed compounds to be 
tested for effectiveness simultaneously.
    The Initiative will tap into the expertise of the NIH Pain 
Consortium,\2\ a trans-NIH consortium made up of NIH institutes that 
fund pain research. Funded projects are investigating the entire range 
of therapeutics development- from preclinical safety and efficacy 
testing and early phase human trials to health services research. 
Currently, the consortium members are working on developing more 
effective and less addictive treatments for chronic pain. For example, 
a study using a molecular imaging technology called x-ray 
crystallography has revealed the molecular structure of the receptors 
that mediate drugs' effects; this information is already leading to the 
development of safer medications to treat pain.
---------------------------------------------------------------------------
    \2\ https://www.painconsortium.nih.gov/About/Members.
---------------------------------------------------------------------------
    NIH-funded research is developing medications with properties that 
affect opioid receptors to produce analgesia with reduced risk of 
addiction and misuse. Some of these exhibit novel properties as a 
result of their combined activity at different opioid receptors (mu, 
delta, and kappa). Compounds with combined activity at the mu and delta 
receptors or at all three receptors can induce strong analgesia without 
producing tolerance or dependence in animal models. In addition, the 
discovery of adjunct medications that can be combined with opioids to 
reduce the needed dose has the potential to result in lower potential 
for dependence and addiction. Innovative methods are being explored for 
drug delivery to increase specificity and efficacy and to reduce 
analgesic side effects, as well as modified formulations to enhance 
delivery.
    NIH supports an initiative called the Blueprint Neurotherapeutics 
Program for small molecule drug discovery and development. For example, 
NINDS funds studies through this program that aim to develop non-
addictive kappa opioid receptor antagonists for migraine and a safe, 
non-opioid analgesic that can be taken orally to reduce diabetic nerve 
pain.
    NIDA continues to fund development of anti-opioid vaccines capable 
of generating an immune response that would prevent opioids from 
entering the brain, thereby blocking both their euphoric effects and 
their dangerous respiratory depressant properties. Current projects 
include:
  --Optimization and preclinical testing of a practical heroin-HIV 
        vaccine \3\
---------------------------------------------------------------------------
    \3\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9110917&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=20&csb=default&cs=ASC&pball=.
---------------------------------------------------------------------------
  --Preclinical development of vaccines against heroin, oxycodone, 
        hydrocodone, and fentanyl \4,5,6,7\
---------------------------------------------------------------------------
    \4\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9444613&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=11&csb=default&cs=ASC&pball=.
    \5\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9330137&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=26&csb=default&cs=ASC&pball=.
    \6\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9461410&icde=39707102.
    \7\ Olson ME, Janda KD. Vaccines to combat the opioid crisis: 
Vaccines that prevent opioids and other substances of abuse from 
entering the brain could effectively treat addiction and abuse. EMBO 
Rep. 2018 Jan;19(1):5-9.
---------------------------------------------------------------------------
    Results from preclinical models thus far have shown that these 
vaccine candidates are capable of producing an immune response that 
blocks opioid effects.32 While none have yet advanced to clinical 
trials, the heroin vaccine candidate developed by the Walter Reed Army 
Institute of Research in collaboration with NIDA has been in-licensed 
by Opiant Pharmaceuticals for further development.\8\
---------------------------------------------------------------------------
    \8\ https://www.opiant.com/pipeline/heroin-vaccine/.
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                                 ______
                                 
             Questions Submitted by Senator Lamar Alexander
                        fda enforcement actions
    Question. In April 2018, at my request, the Federation of State 
Medical Boards issued a report on regenerative and stem cell therapy 
practices. The report included information on the regulatory history of 
regenerative medicine and recommendations for state medical boards.
    The report described how ``some clinics . . .  are engaged in the 
provision of treatment modalities that lack evidence . . .  or use what 
have been described as `tokens of scientific legitimacy' to lend 
credence to treatments offered or the quality of a clinic and its 
associated professionals.'' According to the report, these tokens 
include ``patient or celebrity testimonials and endorsements, clinician 
affiliations or memberships in academic or professional societies, and 
registrations in clinical trials, among others.''
    Last week, the Food & Drug Administration (FDA) filed two 
complaints in Federal court seeking permanent injunctions to stop two 
stem cell clinics from marketing products without FDA approval. The 
National Institutes of Health runs clinicaltrials.gov and includes a 
disclaimer that not all studies on the website have been evaluated by 
the U.S. Federal Government.
    What steps can NIH take to make sure patients visiting 
clinicaltrials.gov are aware of any enforcement or regulatory actions 
taken by FDA? Is there any other legislative action Congress can take 
to help NIH address this issue?
    Answer. Research participant safety is of utmost importance to NIH. 
The ClinicalTrials.gov website currently includes information to help 
potential participants learn more about the potential benefits and 
risks of participating in a trial and always recommends talking with 
trusted healthcare professional before starting a trial. NIH is taking 
several steps to increase transparency and clarify information on 
clinicaltrials.gov including:
  --Adding more prominent disclaimers explaining that listing a study 
        does not mean it has been evaluated by the U.S. Federal 
        Government
  --Adding a question about whether the product being tested is under 
        FDA oversight
  --Continuing to evaluate and improve other resources to help 
        potential participants identify questions they may want to 
        consider when deciding whether to participate in research and 
        encouraging them to consult with their healthcare provider on 
        such decisions
    NIH is committed to continuing to improve these resources to help 
ensure people understand important issues to consider before 
participating in a clinical trial and working closely with FDA to 
determine best strategies for educating the public on FDA activities 
and providing information on FDA oversight of clinical research.
    NIH does not believe additional legislative action is needed at 
this time. As noted, NIH is committed to working with FDA to identify 
ways to improve communication about FDA actions, including enforcement 
or regulatory actions that may be relevant to information on 
ClinicalTrials.gov.
                                 ______
                                 
             Questions Submitted by Senator James Lankford
                               stem cells
    Question. As you know, despite years of research and use of tax 
dollars, there is currently no validated, successful patient treatment 
from embryonic stem cells. Additionally, alternatives to embryonic stem 
cell research exist. In 2012, the Nobel Prize in Physiology or Medicine 
was awarded to two researchers for their discovery of induced 
pluripotent stem (iPS) cells, which mimic the qualities of embryonic 
stem cells but do not use embryos in any way. Similarly, NIH has had 
great success in treating and curing more than 70 diseases using adult 
stems cells and iPS cells.
    Despite that, in 2009, President Obama issued E.O. 13505, which 
gave HHS and NIH authority to use human stem cells, including embryonic 
stem cells, in research. E.O. 13505 revoked a previous EO from 
President Bush that outlined ethical principles for stem cell research.
    Because the research has yet to yield positive results, have you 
considered a plan to stop embryonic stem cell research or limit such 
research if the cell line is not already included on the NIH Human 
Embryonic Stem Cell Registry?
    Answer. NIH funds a range of stem cell research, using human and 
non-human adult stem cells, induced pluripotent stem cells (iPSCs), and 
since 2001, human embryonic stem cells (hESCs). NIH stem cell research 
must be conducted in accordance with the NIH Guidelines for Human Stem 
Cell Research, which detail stringent criteria for voluntary informed 
consent by which the NIH Director determines the eligibility for use of 
specific hESC lines in NIH-funded research. NIH-funded stem cell 
research is exploring applications in regenerative medicine, drug 
screening, and the study of the molecular pathways in biological 
development and human disease. Projects studying how undifferentiated 
stem cells become specialized cells with specific functions in the body 
have produced knowledge that is essential for developing regenerative 
medicine treatments. For example, NIH-supported researchers have 
established protocols for development of specific cell type from hESCs: 
e.g., pancreatic beta cells (which were effective in a mouse type 1 
diabetes model), dopaminergic neurons (tested in a mouse Parkinson's 
model), liver hepatocytes, and cardiomyocytes. NIH-supported 
researchers are using hESCs to study cells with particular diseases, 
such as neurons with a Niemann Pick type C1 mutation, which causes a 
progressive neurological disease. NIH-supported researchers have also 
used hESCs to develop organoids, including intestine, colon, and 
kidney, to model organ-specific diseases.
    Several investigational cell therapies developed from hESCs are 
currently in FDA-regulated clinical trials for spinal cord injury, 
macular degeneration, and type 1 diabetes. The first trial using an 
investigational cell therapy from iPSCs is taking place in Japan for 
macular degeneration; an NIH intramural investigator also plans to file 
an IND this year for using a product from human iPSCs for macular 
degeneration.
    One can never be certain where the next cure or treatment will come 
from, and maximizing researchers' access to diverse tools, methods, and 
experimental systems is critical for enhancing the likelihood of 
success in advancing the NIH mission. Therefore NIH will continue to 
support highly meritorious research with NIH-approved hESCs.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray
                                big data
    Question. The Committee directed NIH in the fiscal year 2017 
omnibus to develop a strategic plan to address these issues, which was 
recently released. Now that NIH has a plan, what's the timeline for its 
implementation?
    Answer. The NIH Strategic Plan for Data Science \9\ (subsequently 
referred to as ``the Plan'') describes NIH's Overarching Goals, 
Strategic Objectives, and Implementation Tactics for modernizing the 
NIH-funded biomedical data-resource ecosystem. The Plan was developed 
by the NIH Scientific Data Council, and reflects input from HHS, 
scientists, policymakers, scientific and professional societies, the 
general public, and leadership and staff from NIH and its constituent 
Institutes and Centers.
---------------------------------------------------------------------------
    \9\ https://datascience.nih.gov/sites/default/files/
NIH_Strategic_Plan_for_Data_Science_ Final_508.pdf.
---------------------------------------------------------------------------
    NIH is mapping out the Plan's implementation and expects activities 
will intensify over the next year. Implementation of key areas are 
already underway, including the NIH Data Commons Pilot and NIH's cloud-
marketplace initiative. In addition, targeted training and career 
development opportunities to enhance the biomedical data science 
workforce are in preparation, such as data science fellowships. NIH 
also is in the process of aligning data science-related funding 
opportunity announcements to help ensure support for databases, 
knowledgebases, and tools development are addressed in the most 
efficient and cost-effective way. Other Plan goals, such as developing 
data standards, are in early discussion and will require additional 
research, planning, and interaction with the community to determine the 
scope and context of future guidance.
    As NIH moves forward, the Scientific Data Council, a sub-committee 
of the NIH Steering Committee composed of Institute and Center 
directors and deputy directors, as well as key NIH subject matter 
experts, will have an active role in overseeing execution of the Plan. 
The NIH Chief Data Strategist, currently being recruited, will 
collaborate closely with the Scientific Data Council, Data Science 
Policy Council, and other key NIH stakeholders to lead implementation 
of the NIH Strategic Plan for Data Science. We anticipate that full 
implementation plans will be in place within the next year, with a 
majority of Implementation Tactics launched in the same timeframe.
    Question. Given the scale of this undertaking, what does NIH see as 
the biggest potential barriers to achieving the plan's vision?
    Answer. During development of the Plan, a number of data science 
challenges for NIH were characterized (see pages 4-5 of the Plan). Some 
of the most pressing barriers to achieving the Plan's vision are 
summarized below:
  --The exponential expansion of data quantity and complexity is 
        increasing costs of data infrastructure, storage and 
        management, including data access, integrity, and privacy 
        considerations.
  --The siloed nature of the current data ecosystem is a challenge for 
        data integration, standardization, and interoperability. 
        Implementation of FAIR (Findable, Accessible, Interoperable, 
        and Reusable) principles will enhance stewardship by improving 
        the sustainability of data resources supported through NIH 
        investments.
  --The funding mechanisms currently used by NIH incentivize tool 
        development and primary analysis of data but are less 
        compatible with data resource maintenance and sharing. A key 
        objective of the Plan is to tailor the funding mechanisms to 
        the desired outcomes for NIH-supported data resources.
  --Novel bridges between academic research institutions, NIH, and the 
        technology industry are needed to enhance development and 
        dissemination of efficient and effective data resources and 
        analytical tools. Flexible funding strategies, including 
        expanded use of Other Transaction Authority, would assist in 
        building these bridges.
  --A new generation of trained biomedical data science experts will be 
        essential to bringing the vision elaborated in the Plan to 
        fruition. However, the discrepancy in pay scales between the 
        technology industry on the one hand and academics and 
        government on the other presents a challenge for recruiting and 
        retaining talent in data science for biomedical research.
    As noted in the response to Question 1, NIH is working to overcome 
these challenges and implementing new programs and initiatives to 
address these barriers.
    Question. Are there cases where researchers are reluctant or face 
challenges sharing their data, or they delay releasing that data for 
years until they've published their findings? What do you do in these 
situations? Do you see an opportunity to revise policy to address this 
issue?
    Answer. The current culture of data sharing is moving towards 
openness and transparency. Consistent with these efforts, the NIH 
encourages and expects the sharing of data from supported research 
through policies and practices. For example, under the NIH Genomic Data 
Sharing \10\ (GDS) Policy, investigators seeking NIH funding for 
genomics projects are expected to submit a Genomic Data Sharing Plan as 
part of the application for funding, which includes the data submission 
and release timeline. NIH recognizes that different types of genomic 
data undergo different levels of processing, and the expectations for 
data submission and data release are based on those levels. However, in 
general, data are released to NIH-designated data repositories for 
access by other investigators no later than 6 months after the initial 
data submission begins, or at the time of acceptance of the first 
publication, whichever occurs first, without restrictions on 
publication or other dissemination.
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    \10\ https://osp.od.nih.gov/wp-content/uploads/NIH_GDS_Policy.pdf.
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    In some cases, restrictions or limitations on the data may exist 
that prevent broadly sharing the data. For example, based on the 
informed consent provided by the research participants, there may be 
limits on who may use the data or for what purposes the data may be 
used. Other restrictions may stem from legal issues or limitations 
placed on downstream data use by the study populations who participated 
in the research, for example tribal populations. In some cases, it may 
not be appropriate for researchers to share genomic data. In such 
cases, NIH may grant an exception to the typical data sharing 
expectations and allow for an alternative genomic data sharing plan. An 
example of an alternative data sharing plan might be the sharing of 
summary-level information only. Summary-level information is study data 
that has been aggregated across the study population (as opposed to 
sharing data at the level of each individual study participant).
    NIH recognizes that investigators often do not want to share their 
data until they have had the opportunity to publish their own findings. 
However, at the same time, NIH has a strong interest in increasing the 
impact and rigor of research studies it funds. Therefore, the NIH 
officially announced in March 2017 \11\ that researchers may cite their 
interim research products and claim them as products of NIH funding in 
order to increase the impact and rigor of a research study. Interim 
research products can be cited anywhere other research products are 
cited in the NIH grant application. An example of such a product is a 
preprint publication, which is a complete and public draft of a 
scientific document that typically has not yet undergone peer review. 
NIH encourages investigators to use interim research products, such as 
preprints, to speed dissemination and enhance the rigor of the 
research.
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    \11\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
050.html.
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    NIH also has addressed specific data sharing challenges through 
targeted policy development. For example, the NIH Policy on the 
Dissemination of NIH-Funded Clinical Trial Information \12\ promotes 
broad dissemination of summary-level results from NIH-funded clinical 
trials by establishing the expectation that researchers will register 
the trials in and submit the results information to ClinicalTrials.gov. 
Under this Policy, NIH expects the results information to be submitted 
no later than 1 year after the trial's primary completion date.
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    \12\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-
149.html.
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    Another example policy is the NIH 2003 Data Sharing Policy, which 
expects that investigators submitting a research application requesting 
$500,000 or more of direct costs in any single year include a plan for 
sharing their final research data or state why they cannot. In this 
Policy, NIH expects the timely release and sharing of data to be no 
later than the acceptance for publication of the main findings from the 
final dataset. The specific time will be influenced by the nature of 
the data collected. However, despite guidance on implementation, there 
is not a structured format for the plans, and policy compliance has 
been inconsistent.
    The NIH is evaluating its existing data sharing policies with an 
eye on furthering the current culture of data sharing. From November 
2016 to January 2017, NIH sought public comment on how scientific data 
generated from NIH-funded research should be managed, and to the 
fullest extent possible, made publicly available through a Request for 
Information: Strategies for NIH Data Management, Sharing, and 
Citation.\13\ This public comment solicitation also specifically asked 
the public for the greatest barriers and challenges associated with 
data sharing. Input \14\ from the public, which included universities, 
associations, companies, and publishers, noted specific barriers to 
data sharing, such as establishing a culture of sharing that would 
appropriately incentivize and encourage data sharing, the need for 
community-based standards for long-term preservation or sustainability 
of data, data preparation and submission, and the costs and resources 
associated with data management and sharing, e.g., data curation, 
personnel, infrastructure. Suggestions to resolve some of these 
barriers included providing incentives (e.g., citation of datasets and 
attribution for sharing data) to help to change the culture of data 
sharing. Respondents felt that the use of community-based standards, as 
well as the ability to budget for data management and sharing in NIH 
funding applications and proposals, would help mitigate some of the 
resource barriers associated with data management and sharing.
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    \13\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
015.html.
    \14\ https://osp.od.nih.gov/wp-content/uploads/
Public_Comments_Data_Managment_
Sharing_ Citation.pdf.
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    The NIH intends to continue ongoing outreach and community 
engagement on existing policies and practices to refine the 
implementation of existing policies and to develop new policies when 
warranted to achieve the goal of encouraging a culture of data sharing.
    Question. Given the scale of investments Congress is making in 
Alzheimer's disease, the data we are generating may be used to 
accelerate major scientific breakthroughs. Has NIA looked at its 
existing data sharing policies to determine how they are working? Do we 
know what percentage of grant recipients fulfil their data sharing 
obligations at the end of their projects?
    Answer. NIA does not currently keep an overall tally of compliance 
with data-sharing plans. With that said, a number of NIA initiatives 
related to Alzheimer's disease (AD) and related dementias have data-
sharing plans built in, and in those situations sharing of data is used 
as a criterion for continued funding from year to year. Major programs 
that operate under these terms include the Accelerating Medicines 
Partnership for AD initiative (AMP-AD); the Model Organism Development 
and Evaluation for Late-Onset AD (MODEL-AD) initiative; and the 
Alzheimer's Disease Neuroimaging Initiative (ADNI). We are currently 
exploring the feasibility of and possible mechanisms for tracking 
compliance more globally across research project grants.
    Question. The committee has prioritized a biomedical research 
ecosystem that is amplified by sustainable, interoperable, accessible, 
and usable research data, including Alzheimer's research data. How do 
you ensure that data sharing is prioritized at the start of the NIH 
grant process? Is there a process to make sure researchers are 
preparing to share their data from the start? What are the most 
frequent comments you hear from researchers about why they can't share 
their data?
    Answer. Effective data sharing relies upon appropriate 
identification, adoption, and crediting of good data management and 
sharing practices. Thus, NIH encourages data sharing consistent with 
the FAIR (Findable, Accessible, Interoperable, Re-usable) data 
principles. For example, in order to facilitate access by qualified 
investigators to genomic data for the study of Alzheimer's disease, NIH 
funded the creation of The National Institute on Aging Genetics of 
Alzheimer's Disease Data Storage Site \15\ (NIAGADS), currently 
maintained at the University of Pennsylvania. NIAGADS along with other 
National Institute for Aging (NIA) approved sites make genomic data and 
associated phenotypic data available to qualified investigators in the 
scientific community for secondary analysis in accordance with 
standards established by the NIA and the NIH Genomic Data Sharing (GDS) 
Policy.
---------------------------------------------------------------------------
    \15\ https://www.niagads.org/.
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    NIH policies on data sharing typically expect that a plan is 
submitted with a funding application, indicating for example what data 
will be shared, and how, when, and where it is expected to be shared. 
These policy expectations suggest that researchers and institutions 
should be thinking through these issues during the planning phases of 
their applications.
    For example, the implementation of the NIH GDS Policy sets the 
expectation that applications for funding that propose the generation 
of large-scale human or non-human genomic data include a Genomic Data 
Sharing Plan in the Resource Sharing Plan section of the grant 
application. Applicants are expected to describe the data type(s) and 
repository for data deposition. Applicants proposing to generate human 
data should also provide information addressing data submission and 
release timelines, Institutional Review Board assurance of the genomic 
data sharing plan, the appropriate uses of the data, and if 
appropriate, a request for a data sharing exception, prior to award. 
Those proposing to generate non-human data also need to address the 
data submission and release timelines prior to award. The Genomic Data 
Sharing Plan is approved by the funding NIH Institute or Center. In 
addition, for the NIH Policy on the Dissemination of NIH-Funded 
Clinical Trial Information, applicants proposing to conduct clinical 
trials must submit a plan for the dissemination of the trial 
information.
    NIH continues to discuss, with public input, the value of data 
sharing and what information is most helpful to include in a plan for 
managing and sharing data that ensures shared data are findable, 
accessible, interoperable, and reusable (the FAIR principles).\16\ NIH 
and the National Science Foundation held a joint workshop on the Value 
of Data Sharing in October 2017.\17\ Some consistent themes included in 
plans for data management and sharing among various Federal funders 
include describing the types of data to be shared; what tools may be 
needed to analyze shared data; what standards apply to the collected 
data; how, where, and for how long data will be available; and whether 
any barriers to data sharing exist.
---------------------------------------------------------------------------
    \16\ https://www.force11.org/group/fairgroup/fairprinciples.
    \17\ https://osp.od.nih.gov/2017/12/18/data-destiny-debrief-nih-
nsf-workshop/.
---------------------------------------------------------------------------
    Through responses to the Request for Information: Strategies for 
NIH Data Management, Sharing, and Citation,\18\ the public indicated 
that barriers to data sharing include the resources and repositories 
needed to manage and share data, the need for data standards to ensure 
that data is reusable and reproducible, and incentives. NIH continues 
to gauge ways to address these barriers in the process of evaluating 
its existing data sharing policies and practices.
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    \18\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
015.html.
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                          alzheimer's vaccine
    Question. In 2000, the NIH set aside $50 million over 5 years to 
support research on new ways to treat Alzheimer's disease with a 
special emphasis on the development of a vaccine to prevent the 
disease. While the first generation of Alzheimer's vaccines were 
developed shortly thereafter, in 2008 these studies were halted due to 
patient safety concerns. Can you describe what the NIH has done in 
recent years--or plans to do in the future--to support development of a 
vaccine to treat the more than 5 million Americans currently living 
with Alzheimer's?
    With the most recent omnibus funding bill bringing total 2018 
funding to $1.8 billion, does the NIH plan to fund research for an 
Alzheimer's vaccine in fiscal year 2019?
    The Alzheimer's Association has made a commitment to prevent or 
effectively treat Alzheimer's disease by 2025. We're less than 6 years 
away from that target, and in spite of continued Congressional 
increases to the NIH budget, safe and effective treatments are still 
out of reach. Can you describe the current research being done, and if 
you believe there are any gaps in research that could be addressed in 
fiscal year 2019?
    Vaccines have been one of the most effective and impactful 
medicines in history. Is vaccine research a priority for NIH's 
Alzheimer's research goals, and if not, why?
    Answer. Vaccination is one of many treatment modalities currently 
under study for both prevention and treatment of Alzheimer's disease 
and related dementias (AD/ADRD). For example, the Alzheimer's 
Prevention Initiative Autosomal Dominant Alzheimer's Disease (API-ADAD) 
study is exploring ``preventive immunotherapy'' among members of an 
extended Colombian family that carries a genetic mutation placing many 
members at greatly increased risk of developing the disease. Another 
study, the Dominantly Inherited Alzheimer's Network (DIAN) trial, 
evaluates the safety, tolerability, and effectiveness of several drugs, 
including two vaccines, and will determine if they can prevent, delay, 
or even reverse Alzheimer's disease changes in the brain. NIA also 
supports a large cooperative agreement to complete preclinical safety 
and efficacy testing for AV-1959D, a cutting-edge DNA vaccine. DNA 
vaccines use pieces of DNA from specific pathogenic proteins to 
stimulate an immune response and offer potential technical and safety 
advantages over conventional protein/adjuvant vaccines. All of these 
studies remain important priorities within our AD/ADRD portfolio and 
will remain active in fiscal year 2019.
    With respect to current AD/ADRD research and gaps, NIA has 
leveraged the extraordinary influx of funding directed at these 
diseases to build a series of bold and innovative research programs, 
infrastructure, and new partnerships that are enabling some of the 
Nation's leading scientists to tackle the problem of AD/ADRD at an 
unprecedented scale and pace. High-priority research and infrastructure 
programs that are currently underway include:
  --Alzheimer's Clinical Trial Consortium (ACTC), to accelerate and 
        expand trials of AD/ADRD therapies;
  --Resilience-AD, a new program bringing together experts from 
        multiple disciplines to understand why some high-risk 
        individuals remain dementia free;
  --Molecular Mechanisms of the Vascular Etiology of Alzheimer's 
        Disease (M\2\OVE-AD) Initiative, exploring how metabolic and 
        vascular risk factors such influence brain aging and AD 
        pathology and identifying blood-based markers of the disease;
  --Alzheimer's Biomarker Consortium--Down Syndrome (ABC-DS), in which 
        researchers use biomarkers to track disease progression in 
        people with DS, a uniquely vulnerable population at high risk 
        for developing AD;
  --The Model Organism Development and Evaluation for Late-onset AD 
        (MODEL-AD) project to develop better animal models of late-
        onset AD;
  --Approximately 140 active clinical trials of interventions to 
        prevent, treat, or manage symptoms of AD/ADRD and to enhance 
        caregiver well-being;
  --Development of new therapeutics, including some that target 
        molecules other than beta-amyloid; and
  --Harnessing the power of big data to identify existing drugs or 
        combinations currently used to treat other conditions that 
        could be effective for the treatment of AD/ADRD.
    Gaps continue to exist around development of caregiver support 
interventions; implementation of a national recruitment strategy that 
ensures inclusion of diverse populations in AD/ADRD research; 
understanding gene-environment interactions that increase risk or 
confer resilience against AD/ADRD; infrastructure development, 
including big data infrastructure; workforce training across the 
spectrum of research; and harmonization and distribution of data from 
large datasets. NIH considers each of these a priority area for fiscal 
year 2019, and NIA has begun to implement strategies to fill these 
gaps, with a number of relevant Funding Opportunity Announcements 
issued or approved in concept by the National Advisory Council on 
Aging.
                      next generation researchers
    Question. Ensuring a strong pipeline of the best and brightest U.S. 
scientists is of paramount importance. To this end, the Fred Hutchinson 
Cancer Research Center in Seattle participates in the Coalition for 
Next Generation Life Science, which seeks to increase transparency of 
life science career prospects by providing new data and information to 
help students make informed choices about their science careers. What 
steps is the NIH taking to ensure young and mid-career investigators 
remain engaged in academic research?
    The National Academies of Sciences, Engineering, and Medicine 
released a report in April on the next generation of biomedical and 
behavioral researchers and recommended that NIH increase by five-fold 
the number of individual research fellowship (F) awards and career 
development (K) awards available to support postdoctoral researchers. 
It also recommended that NIH create a Next Generation Researcher 
Innovation Fund to support innovative pilot projects that seek to 
improve and accelerate transitions into independent careers. Which of 
these recommendations or others in the report, do you anticipate NIH 
adopting or considering?
    Answer. NIH is currently assessing the recommendations of the 
National Academies Next Generation Researchers Initiative (NGRI) 
committee, convened in early 2017, to study and recommend solutions to 
any barriers that may extend periods of training, time to independence, 
or impede sustained success in research. As you noted, a final report 
titled, ``Next Generation of Biomedical and Behavioral Sciences 
Researchers: Breaking Through'' was released in April 2018. As these 
recommendations are being considered, NIH is also awaiting a related 
report from a working group of the Advisory Committee to the Director 
focused on the next generation of researchers, expected in June 2018. 
NIH expects to incorporate guidance from both groups to prioritize 
further actions to bolster the careers of early-stage investigators.
    Within the NIH Office of the Director, the Office of Extramural 
Research's Division of Biomedical Research Workforce conducts regular 
evaluations of outcomes of NIH training and career development 
programs. These activities help us assess strategies that are 
successful in promoting continued engagement in academic research. NIH 
has, and continues to grow, an evidence-base to support positive 
impacts of individual postdoctoral fellowship (F) awards and individual 
career development (K) awards on subsequent, sustained research 
careers. NIH is currently considering how to optimize the benefits and 
outcomes of these awards for early stage researchers.
    NIH appreciates the recommendation to increase the number of F and 
K awards. NIH will carefully consider the cost to benefit ratio of 
increasing their numbers as well as other options, such as enhancing 
stipends, salary, or research support offered with each award, to 
maximize their impact on successful research careers.
    In addition, as we consider the National Academies' and Advisory 
Committee to the Director Working Group's recommendations, we will work 
with the NIH Institutes and Centers to consider expansion of other 
programs that have been particularly successful for early stage 
investigators, including:
  --NIH Director's New Innovator Award Program (DP2), which supports 
        early-stage investigators of exceptional creativity who propose 
        bold and highly innovative new research approaches with the 
        potential to have a major impact on broad, important problems 
        in biomedical and behavioral research.
  --The Maximizing Investigators' Research Award (R35) supports early-
        stage investigators to enhance their ability to take on 
        ambitious scientific projects, spend time on research, and 
        reduce the time spent writing grant applications.
  --The NIH Pathway to Independence Award (K99/R00) program to 
        facilitate a timely transition of outstanding postdoctoral 
        researchers to independent, tenure-track, or equivalent faculty 
        positions and help researchers to launch competitive, 
        independent research careers.
  --The Director's Early Independence award (DP5), as part of the NIH 
        Common Fund's high-risk high reward initiative, aims to support 
        more bold and innovative research activities with the 
        opportunity for rapid progress. Specifically, this program 
        accelerates the entry of exceptional junior scientists into an 
        independent research career by forgoing the traditional post-
        doctoral training period. These select investigators have 
        established a record of scientific innovation and research 
        productivity as well as demonstrated unusual leadership, drive, 
        and maturity,
  --The High Priority, Short-Term Project/Bridge Awards (R56) supports 
        early-stage investigators by providing limited, interim 
        research support to gather additional data for revised grant 
        applications.
                               salary cap
    Question. The Administration's fiscal year 2019 budget request 
proposes limiting the percentage of an investigator's salary that can 
be paid with grant funds at 90 percent of total salary. Like the fiscal 
year 2018 proposal to cap facilities and administrative costs, limiting 
salary support is proposed under the guise of identifying 
``efficiencies.'' Congress firmly rejected the proposal to cap F&A in 
the final fiscal year 2018 omnibus because these infrastructure costs 
are integral to conducting successful research. Perhaps to an even 
greater degree, researchers who develop ideas, articulate research 
questions, design studies, and conduct experiments and clinical trials 
are essential to quality research and the pursuit of life-saving 
treatments and cures. Would NIH agree that if Federal support for 
principal investigators' salaries is cut, in addition to resources 
being redirected from other activities to cover salaries, wouldn't this 
send a message to those interested in entering academic research that 
they may not be fully supported?
    Answer. Because Federal research funds are limited, reductions in 
the NIH contributions to the salary of researchers on NIH grants leaves 
more funds for additional scientists along with the equipment and 
resources they need to carry out their critically important work. This 
may also provide funds that may be used to fund additional grants.
    NIH is aware of varying degrees of salary support for its funded 
scientists. In some institutions, scientists are expected to seek 
external grant funds to support most of their salaries. Other 
institutions provide most, if not all, of the salary support.
    Based on a NIH enumeration study,\19\ the NIH supports 
approximately 313,049 full-time and part-time positions, or the 
equivalent of 121,465 full-time employed individuals each year. We 
believe that approximately half of these full-time researchers are 
affected by the salary cap. Institutions may choose to increase 
tuition, utilize funds from their endowments, or solicit state level 
support to absorb some of the costs engendered by the salary cap. Some 
stakeholders have voiced concern that stringent salary caps may lead to 
disincentives for certain highly-skilled clinician scientists who may 
be well-positioned to conduct the kind of science solicited by NIH. The 
selective pressures on such individuals may lead to a lower number of 
them willing to engage in NIH-funded research. The NIH is cognizant of 
these potential effects, but in no way intends for the policies 
included in the President's Budget to hinder the critically important 
biomedical research funded by NIH.
---------------------------------------------------------------------------
    \19\ Pool, Lindsay R., et al. ``Size and characteristics of the 
biomedical research workforce associated with U.S. National Institutes 
of Health extramural grants.'' The FASEB Journal30.3 (2015): 1023-1036.
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                      national academy of medicine
    Question. According to the 2015 National Academy of Medicine report 
Improving Diagnosis in Healthcare, eliminating diagnostic errors is a 
``moral, professional, and public health imperative.'' Are there steps 
that NIH can take to invest in basic research on improving diagnosis in 
medicine, consistent with the findings of the National Academy of 
Medicine report? Given NIH's disease-specific institute missions, are 
there structural barriers, either administrative or legislative, that 
would need to be addressed for successful advancement of basic research 
by NIH in improving diagnosis in medicine?
    Answer. NIH invests in basic research on improving diagnosis in 
medicine, primarily through the National Library of Medicine (NLM). Of 
the approximately $30 million NLM expects to spend on extramural 
research projects in fiscal year 2018, about 1/3 supports investigator-
initiated research projects in clinical/healthcare informatics and 
data. NLM-funded researchers have examined safety-related issues such 
as the unintended consequences of physician order entry, data mining of 
clinical data repositories, and tools for inpatient monitoring using 
evidence from the electronic health record (EHR). Current NLM research 
projects which are consistent with the recommendations of the National 
Academies study are: ways to monitor clinical workflow to detect 
adverse events, workflow capture to improve trauma resuscitation 
outcomes, terminology services to make orders consistent and reduce 
avoidable CT imaging, extraction of typical and atypical disease 
progression patterns from multi-site EHRs, and patient medical history 
representation, extraction and inference from EHRs. NLM's intramural 
research program also emphasizes analysis of large health data sets to 
enable discoveries that can inform diagnosis. In addition, the 
intramural research program supports work on health information/data 
standards and text processing that can improve the consistency of the 
terminology used in EHRs to support large scale analysis and extract 
meaning from narrative text, such as clinical notes, to support 
research on diagnosis. NLM's expanding portfolio of data science 
research will emphasize needs of precision medicine initiatives and 
organizations like OHDSI (Observational Health Data Sciences and 
Informatics) to characterize completeness, assure accuracy, and 
mitigate bias in large heterogeneous data sets. One challenging area is 
the need for large data sets of personal health data from individuals 
for fundamental research. Restrictions and concerns about access, 
confidentiality, permissions and bias in the data remain a challenge 
and are important areas for future research.
                                 ______
                                 
                Questions Submitted by Senator Jack Reed
                           bioethical issues
    Question. Gene editing research such as the NIH's Somatic Cell 
Genomic Editing program holds the potential for curing diseases and 
significantly improving lives; however, we will need to contend with 
serious bioethical concerns as we continue to make advances in this 
research. Can you explain how NIH is staying ahead of bioethical issues 
as the research continues to progress? How is NIH coordinating these 
efforts with other Federal agencies, both within and outside of HHS?
    Answer. Gene editing technologies are powerful tools that enable a 
broad range of applications, including investigating gene function, 
developing better animal models to study specific human diseases, and 
developing new strategies to reduce the spread of malaria and other 
infectious diseases by vectors such as mosquitoes (through an 
application called a gene drive). Gene editing technologies are also 
already being used in clinical trials to potentially treat genetic or 
acquired diseases, ranging from infectious diseases to cancer.
    The bioethical issues associated with gene editing depend on the 
specific application of the technology, that is, how the gene editing 
technology is being used and for what purpose. Applications such as 
somatic gene therapy, human germline modification, and gene drives to 
eradicate disease all have different bioethical considerations. In many 
cases, the bioethical concerns raised by these technologies are similar 
to those first raised at the advent of recombinant DNA technology and 
human gene therapy and are well explored and integrated into current 
oversight structures. For instance, NIH supports gene therapy research, 
including gene editing approaches, in somatic cells in humans. Somatic 
cells are not involved in reproduction, so changes in somatic cells are 
not inherited by subsequent generations. The well-established oversight 
frameworks and FDA regulatory authority over human gene therapy trials 
would apply to clinical research involving gene editing. In fact, gene 
editing applications have already been in the clinic for several years 
in trials involving different types of technologies targeting such 
diseases as HIV infection, cancer, and several genetic disorders such 
as Hemophilia B.
    The potential use of gene editing to modify the human germline such 
that changes would not only affect an individual, but subsequent 
generations, has been a subject of ethical debate. NIH has participated 
in multiple activities of the National Academies of Sciences, 
Engineering, and Medicine (NASEM) focused on issues related to gene 
editing. The 2017 NASEM report, Human Genome Editing: Science, Ethics, 
and Governance,\20\ supported basic research and gene therapy in 
somatic cells but recommended a cautious approach to heritable gene 
editing in clinical studies.\21\ Given the ongoing concerns in this 
space, NIH will not fund any use of gene editing technologies in human 
embryos (NIH Director's statement, April 28, 2015).\22\ There are also 
legislative and regulatory prohibitions including the ``Dickey-Wicker'' 
amendment attached to the annual appropriations bill for the Department 
of Health and Human Services, which prohibits the use of NIH funds for 
``(1) the creation of a human embryo or embryos for research purposes; 
or (2) research in which a human embryo or embryos are destroyed, 
discarded, or knowingly subjected to risk of injury or death greater 
than that allowed for research under applicable Federal regulations.''
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    \20\ https://www.nap.edu/catalog/24623/human-genome-editing-
science-ethics-and-governance.
    \21\ https://www.nap.edu/catalog/24623/human-genome-editing-
science-ethics-and-governance.
    \22\ https://www.nih.gov/about-nih/who-we-are/nih-director/
statements/statement-nih-funding-
research-using-gene-editing-technologies-human-embryos.
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    Potential bioethical issues exist for gene drive technology, which 
allows for the spread of desired traits through populations of 
organisms at a faster rate than what typically occurs in nature. This 
approach could potentially provide a means to address environmental or 
public health problems (e.g., control of invasive species or vector-
borne infectious diseases like malaria), but there are potential 
ethical concerns, especially related to possible effects on the 
environment. To engage in a robust conversation and to address ethical, 
scientific, and safety issues, NIH funded in part a 2016 NASEM study 
\23\ on responsible conduct of gene drive research. In a Director's 
Statement (June 7, 2016), NIH accepted the report, which included 
support for continuing basic and applied research in gene drives while 
holding off on release of gene drive modified organisms into the 
environment at this time.\24\
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    \23\ http://nas-sites.org/gene-drives/.
    \24\ https://www.nih.gov/about-nih/who-we-are/nih-director/
statements/statement-national-academy-sciences-report-gene-drives-non-
human-organisms.
---------------------------------------------------------------------------
    As new gene editing technologies come to fruition, NIH continues to 
be prepared to investigate their ethical, legal, and social 
implications (ELSI). For example, the National Human Genome Research 
Institute (NHGRI), has a Congressionally-mandated, 5 percent set-aside 
in its extramural budget to fund ELSI research. In anticipation of 
myriad bioethical issues, NHGRI's ELSI portfolio covers research to 
explore the downstream implications of emerging genomic technologies.
    How is NIH coordinating these efforts with other Federal agencies, 
both within and outside of HHS?
    Answer. NIH has been closely engaged with other Federal agencies, 
both inside and outside of HHS, on bioethical issues associated with 
gene editing. NIH works closely with the Food and Drug Administration 
(FDA) on issues related to gene editing through fora such as the NIH/
FDA Joint Leadership Council, in which there is a dedicated effort to 
coordinate gene editing activities.
    NIH continues to participate in many NASEM activities, including 
the ongoing Human Genome Editing Initiative, which involves many 
components across the U.S. Government and beyond.\25\ As noted above, 
NIH also supported a NASEM study on gene drives, which involved other 
funders including the Defense Advanced Research Projects Agency, the 
Foundation for the National Institutes of Health, and the Bill & 
Melinda Gates Foundation. NIH continues to coordinate with these 
funders to promote the safe and ethical conduct of gene drives 
research.
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    \25\ http://nationalacademies.org/gene-editing/index.htm.
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    NIH also engages in bioethics conversations in international fora, 
including discussions of the ethics of gene editing at the fourth 
``Unite to Cure Conference'' in April 2018, which was hosted at the 
Vatican to discuss the bioethics of gene editing and other 
biotechnologies with physicians, researchers, and religious thought 
leaders from across the globe. NIH will continue to engage in such 
discussions, both inside and outside the government, and both 
domestically and internationally.
                                 ______
                                 
           Questions Submitted by Senator Christopher Murphy
               center for excellence in genomic sciences
    Question. As you know, I represent a State that has two significant 
academic medical research institutions--Yale University and the 
University of Connecticut. The University of Connecticut, via a 
collaboration with the Jackson Labs, has in recent years made 
significant investments in genomics research, a field that Yale has 
done work in as well. As the technology and tools to do genomics 
research and screening have become more widespread, more universities 
like UConn have aspired compete for Federal funding.
    As you know, the largest of such awards at the National Human 
Genome Research Institute is called the Center for Excellence in 
Genomic Sciences (CEGS) program. Each 5-year CEGS grant supports a 
multi-investigator, interdisciplinary team to develop innovative 
genomic approaches to address a particular biomedical problem and is 
funded at up to $1.75 million annually.
    The CEGS program was launched back in 2001 with two awards. 
Additional rounds of awards in subsequent years eventually expanded 
that number to 10 centers. However, at present there are only 8 CEGS 
awards active in the U.S. spread among only 7 research institutions. 
Furthermore, only 20 institutions total have ever received one of these 
awards in the past 17 years. I understand the importance of 
institutional knowledge at these universities but am also concerned 
that the same players may get these awards while other universities, 
like UConn, are left with little chance to compete for these larger 
awards.
    Do you have any suggestions on how NIH might address this problem?
    Answer. The Centers of Excellence in Genomic Science (CEGS) were 
established in 2001. Three CEGS awards were made that year, including 
one to Yale University. NHGRI generally makes one to two CEGS awards 
per year, although in 3 years we made three or four awards. In the 18 
years that the program has existed, NHGRI has issued 23 awards, to 20 
institutions. The group of 20 institutions that has benefited from the 
CEGS program is quite geographically and institutionally diverse.
    The CEGS program generally makes awards for 5 years, and only eight 
institutions have renewed for another 5 years. Awards currently in 
their first 5 years of funding are located at Harvard Medical School, 
Stanford University, the University of Washington/Altius Institute for 
Biomedical Sciences, the University of Chicago, the University of 
California Berkeley, and the University of Pennsylvania. Those in 
renewals are located at Yale University, the University of Washington/
Arizona State University, Tempe, Stanford University, the University of 
Southern California, Harvard Medical School, Johns Hopkins University, 
and the Dana Farber Cancer Institute. NIH recognizes the importance of 
allowing as many different institutions as possible to benefit from 
such funding, and, as referenced below, institutions in Connecticut 
have received various awards from NHGRI. As stated in the CEGS Funding 
Announcement \26\ ``The total length of support for any Center under 
this program will not exceed 10 years''. This limit was put in place to 
encourage diversity of funding recipients.
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    \26\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-436.html.
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    Applications to renew enter the same competitive pool as 
applications from institutions applying for CEGS funding for the first 
time, and not all requests to renew are successful. NHGRI encourages 
all eligible institutions to consider submitting CEGS applications. 
NHGRI also strongly recommends that applicants contact program staff 
early in the application development process, to increase their chances 
of success.
    Research institutions interested in receiving grant money for 
genomics research are not limited to applying to the CEGS program; they 
may also choose from a range of funding opportunities with varying 
award sizes provided by NHGRI and other NIH institutes. Outside of the 
CEGS program, NHGRI in recent years has issued awards comparable in 
size to a CEGS award to genomics researchers from Yale University, the 
University of Connecticut, and Jackson Laboratory for Genomic Medicine 
in Farmington, Connecticut. The total NHGRI dollars going to Yale and 
the University of Connecticut in each fiscal year 2017 and fiscal year 
2018 are $7 million per fiscal year, and at least $5.6 million will be 
awarded in fiscal year 2019. A few examples of awards to those 
institutions are listed below. Several smaller awards have also been 
awarded to Yale University and the University of Connecticut.
  --In fiscal year 2018, Brenton Graveley at the University of 
        Connecticut School of Medicine was awarded $1,815,769 
        ($8,624,902 total for fiscal year 2018-fiscal year 2021) for a 
        Genomic Community Resource Award to develop A Comprehensive 
        Functional Map of Human Protein-RNA Interactions.
  --In fiscal year 2016, Richard Lifton at Yale University received a 
        renewal of a Center for Mendelian Genomics Award, which is part 
        of NHGRI's largest funding program, the Genome Sequencing 
        program. This award started in 2011; the current 4-year renewal 
        award is co-funded by NHGRI and the National Heart, Lung, and 
        Blood Institute (NHLBI). In fiscal year 2018, NHGRI is 
        contributing $1,947,043, and will contribute another $2,425,542 
        in fiscal year 2019.
  --In fiscal year 2017, Charles Lee at the Jackson Laboratory for 
        Genomic Medicine in Farmington, CT, received $2,868,077 for 
        fiscal year 2017 and $1,986,604 for fiscal year 2018, for An 
        Integrative Analysis of Structural Variation for the 1000 
        Genomes Project, which NHGRI has funded since 2013.
    Examples of other NHGRI programs (in order from largest to smallest 
budgets) include the Genome Sequencing Program (GSP), the Genomic 
Community Resources Program, the Electronic Medical Records and 
Genomics (eMERGE) program, and general investigator-initiated (R01 and 
R21) research grants. These programs include geographically diverse 
grantees pursuing work on both the basic and clinical sides of the 
research spectrum. Additionally, NHGRI is not the only, or even the 
largest, funder of genomic research at NIH. The National Institute on 
Aging (NIA), the National Cancer Institute (NCI), and the National 
Institute of Mental Health (NIMH) are examples of other institutes that 
provide funding for this type of research. Some other non-NHGRI 
programs that offer funding for large scale genome sequencing are the 
Gabriella Miller Kids First Pediatric Research Program (GMKF) (Common 
Fund) and the Trans-Omics for Precision Medicine (TOPMed) program 
(NHLBI). Interested parties may look to these and other institutes/
programs as possible sources of funding as well.
          national institute on occupational health and safety
    Question. As you mentioned in your testimony, the administration's 
budget request proposes to move the National Institute on Occupational 
Health and Safety (NIOSH), which is currently located in the Centers 
for Disease Control and Prevention, into the National Institutes of 
Health. The 2019 budget also proposes a significant reduction in 
funding for NIOSH activities from $335 million to $200 million.
    As you know, NIOSH currently has multiple responsibilities in the 
areas of occupational health, including research, training of 
occupational health professions and professionals, and implementing 
research into practice with our Nation's businesses, manufacturers, 
forestry, and agricultural sectors.
    Could you provide a list of NIH's current research or training 
activities in the field of occupational health and safety, and provide 
the NIH's underlying statutory authorities that would enable NIH to 
implement NIOSH's core mission and its activities?
    Statutory authority for NIH activities is found in section 301 and 
title IV of the Public Health Services Act
    Answer. The fiscal year 2019 Budget proposes consolidating certain 
HHS research programs into three new institutes within the NIH. The 
Budget provides $380 million for the activities of the Agency for 
Healthcare Research and Quality (AHRQ), which would be renamed the 
National Institute for Research on Safety and Quality. The National 
Institute for Occupational Safety and Health (NIOSH), including the 
Energy Employees Occupational Illness Program (EEOCIPA), currently 
administered by the Centers for Disease Control and Prevention, and the 
National Institute on Disability, Independent Living, and 
Rehabilitation Research (NIDILRR), currently administered by the 
Administration for Community Living, are also proposed for 
consolidation into the NIH.
    NIH currently does not track its research or training activities in 
the field of occupational health and safety but could do so in the 
event of a consolidation. The Budget proposal assumes that existing 
statutory authorities for NIOSH's core mission and activities would be 
amended to make them available to NIH along with the necessary funding.
    Consolidating targeted research programs from across HHS--AHRQ/
NIRSQ, NIOSH, NIDILRR--into NIH allows high priority research programs 
to benefit from focused resources and NIH research infrastructure. NIH 
will continue to implement strategies to increase operational 
efficiencies and administrative reforms.
                       clinical trials definition
    Question. NIH has expanded the definition of clinical trials 
through a set of case studies to include both fundamental basic and 
health-related research, which will have a significant impact on and 
consequences for principal investigators and research projects. 
Although there were a number of revisions in response to concerns from 
research universities and associations, issues remain unresolved. 
Congress included language in the fiscal year 2018 Omnibus to suspend 
NIH's new definition of clinical trials and called on NIH to revamp the 
policy with input from the scientific community. With that in mind, 
could you answer the following questions:
    What steps has NIH taken to satisfy the requirement in the fiscal 
year 2018 Omnibus bill that directs NIH to consult with the basic 
science research community about the implementation of the new clinical 
trials definition?
    Has NIH considered creating a new or alternative framework to 
ClinicalTrials.gov for reporting basic science research involving human 
subjects?
    The new clinical trials definition will include small-scale 
mechanistically driven clinical studies involving human subjects. These 
studies cannot inform a change in clinical practice, and yet the new 
definition will impose tremendous costs associated with registration, 
training, continuing education, record keeping, and special reports 
under the assumption that these are clinical trials. Is NIH concerned 
that the new policy will provide a disincentive for this type of 
research with human subjects?
    Answer. As the largest public funder of clinical trials in the 
United States, currently investing more than $3 billion each year, the 
National Institutes of Health (NIH) takes its stewardship of the 
nation's clinical trial enterprise very seriously. Therefore, NIH must 
ensure that supported trials investigate a mission-relevant question 
that is of high priority, do not needlessly duplicate previously 
conducted trials (in contrast to providing needed replication), and 
have the highest likelihood to advance knowledge and improve health. To 
achieve this goal, several challenges in the design, efficiency, and 
reporting of clinical trials need to be addressed. In combination, 
these targeted reforms are intended to ensure stewardship and 
transparency in the scientific enterprise. The NIH definition of a 
clinical trial, is focused on fostering this stewardship and 
transparency to assure the public that scientists will report the 
results of research with human participants--in a timely manner--
regardless of how different scientists might classify them.
    NIH recognizes the concerns expressed by the research community and 
has spent the past few years continuing to solicit input and work with 
the community to chart the best path forward for achieving the aims 
outlined in NIH's stewardship reforms. Moreover, NIH has taken several 
steps to satisfy the requirement in the fiscal year 2018 Omnibus bill 
that directs NIH to consult with the basic science research community 
regarding its policy on the Dissemination of NIH-Funded Clinical Trial 
Information.\27\ For example, NIH leadership met with interested 
stakeholders on May 2 to discuss their concerns, and NIH leadership met 
with Senate and House staff to review those discussions and propose 
plans, including:
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    \27\ https://Federalregister.gov/d/2016-22379.
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  --Issuing a Guide Notice stating that for basic science trials that 
        meet the October 2014 NIH definition of a clinical trial NIH 
        will delay enforcement of the NIH policy \28\ on registration 
        and reporting posted in the Federal Register on September 16, 
        2016.
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    \28\ https://www.Federalregister.gov/documents/2016/09/21/2016-
22379/nih-policy-on-the-dissemination-of-nih-funded-clinical-trial-
information.
---------------------------------------------------------------------------
  --Issuing a Guide Notice describing flexible, lenient implementation 
        of other clinical stewardship and transparency policies as they 
        apply to basic science studies that meet the October 2014 NIH 
        definition of a clinical trial.\29\
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    \29\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-
015.html.
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  --Issuing a basic science parent Funding Opportunity Announcement 
        (FOA) in early fiscal year 2019 for fundamental human studies 
        that meet the NIH definition of clinical trials. This enables 
        the agency to combine the transparency we all agree on with the 
        recognition that these types of studies often occur outside of 
        the clinic.
  --Issuing a targeted Request for Information (RFI) to consult with 
        researchers and the public to determine the reporting standards 
        best suited to fundamental research with human participants. 
        NIH is also interested in soliciting comments to consider 
        alternative frameworks for reporting basic science research 
        involving human subjects.
    As stated in the policy issued on September 16, 2016,\30\ NIH 
recognizes that additional effort is required to register and report 
the results of research studies. Nonetheless, reporting the results of 
scientific work is integral to the scientific method. The benefits of 
timely registration and reporting will, in the long run, accrue to the 
investigators as well as to the public, patients, and the enterprise 
because transparency will improve future research designs and maximize 
the public's investment--and their trust--in research. Equally 
important, it will help investigators fulfill the ethical obligation 
they have to research participants, namely to ensure that the findings 
from their participation contribute to generalizable knowledge and the 
advancement of public health.
---------------------------------------------------------------------------
    \30\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-
149.html.
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                           pulmonary fibrosis
    Question. Unfortunately, like many Americans, my family was touched 
by pulmonary fibrosis years ago when my uncle passed away from this 
devastating disease. Estimates are that about 200,000 people are 
affected in the United States, there are 50,000 new cases each year, 
and 40,000 people die from the disease each year.
    In this era of precision medicine, is the NIH and the National 
Heart, Lung and Blood Institute applying precision medicine approaches 
to tackling this disease? How can patient registry's, such as the 
registry created by the Pulmonary Fibrosis Foundation, play a role in 
NIH precision medicine efforts relating to this group of diseases?
    Answer. Pulmonary fibrosis, which causes progressive scarring of 
lung tissue, can run in families, but the exact cause of the disease is 
not well understood. The National Heart, Lung, and Blood Institute 
(NHLBI) supports a vigorous research program on pulmonary fibrosis to 
improve understanding of the disease and identify better treatments. In 
2014, a NHLBI workshop report, ``Future Directions in Idiopathic 
Pulmonary Fibrosis'' recommended continued support for precision 
medicine efforts including genomic and molecular studies.\31\ Examples 
of NHLBI efforts include:
---------------------------------------------------------------------------
    \31\ https://www.ncbi.nlm.nih.gov/pubmed/24160862.
---------------------------------------------------------------------------
  --NHLBI-funded researchers have used whole-exome sequencing--scanning 
        all of the protein-coding genes in the genome--to better 
        understand genetic factors involved in idiopathic pulmonary 
        fibrosis (IPF). They analyzed data from >250 patients who had 
        pulmonary fibrosis with little or no family history, and found 
        that variation in three genes (TERT, RTEL1 and PARN) is 
        associated with a risk of IPF.\32\ All three genes had 
        previously been implicated in familial PF and are involved in 
        the maintenance of telomeres (a region at the end of 
        chromosomes that protects the ends chromosome from damage). 
        Shorter telomere length also has been associated with higher 
        mortality in three IPF patient cohorts.\33\
---------------------------------------------------------------------------
    \32\ https://www.atsjournals.org/doi/abs/10.1164/rccm.201610-
2088OC.
    \33\ https://www.ncbi.nlm.nih.gov/pubmed/24948432.
---------------------------------------------------------------------------
  --The NHLBI-funded IPF Clinical Research Network (IPFnet) conducted a 
        trial to investigate whether the antioxidant N-Acetylcysteine, 
        when used in combination or with immunosuppressant drugs, is 
        effective in patients with IPF. Analysis of the trial results, 
        combined with genetic data from the participants, showed that 
        N-acetylcysteine monotherapy improved clinical outcomes in 
        patients who carry a particular mutation in the Toll-
        interacting protein (TOLLIP) gene.\34\
---------------------------------------------------------------------------
    \34\ https://www.ncbi.nlm.nih.gov/pubmed/26331942.
---------------------------------------------------------------------------
  --Genomic and molecular studies have revealed small bits of RNA, 
        called microRNAs, as a potential form of therapy. MicroRNA-29 
        appears to play a key role in preventing fibrosis in the lung. 
        Researchers at Yale are collaborating with industry to create a 
        similar--but more stable--version of microRNA-29 that can 
        potentially be used as a therapy for IPF. Their current efforts 
        to develop such a therapy have shown promise in mouse models. 
        The same researchers \35\ also have identified a 52-gene 
        signature \36\ in the blood that can be used to develop a risk 
        profile for recently diagnosed IPF patients, which may help 
        identify IPF patients who will benefit most from a given 
        therapy.
---------------------------------------------------------------------------
    \35\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9270067.
    \36\ https://www.ncbi.nlm.nih.gov/pubmed/28942086.
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  --In research funded through NHLBI's LungMAP \37\ and Lung Repair and 
        Regeneration Consortium, as well as a program project 
        grant,\38\ researchers performed the first single-cell RNA 
        sequencing analysis of epithelial cells in pulmonary 
        fibrosis.\39\ This revealed aberrant lung epithelial cells that 
        appear to be in an ``indeterminate'' state of differentiation 
        (cell fate) not seen in normal lung development. This work also 
        provides sequencing data that can be utilized by other 
        researchers conducting future IPF research.
---------------------------------------------------------------------------
    \37\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9062494.
    \38\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9111936.
    \39\ https://www.ncbi.nlm.nih.gov/pubmed/27942595.
---------------------------------------------------------------------------
    NHLBI encourages IPF investigators to utilize existing clinical 
resources, including the Pulmonary Fibrosis Foundation's patient 
registry and NHLBI's lung tissue repository,\40\ when submitting grant 
applications. By leveraging these longitudinal patient data and 
biosample repositories, alongside the collection of additional genetic 
and genomic information, clinical researchers have a greater potential 
to predict risk, disease progression, and response to therapy--
information that is necessary to develop precision medicine approaches 
to treating IPF.
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    \40\ https://www.nhlbi.nih.gov/science/lung-tissue-research-
consortium-ltrc.
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                          psychotic disorders
    Question. Despite advancements for many diseases, I continue to 
hear from constituents frustrated by the slow pace of development of 
new medicines to treat psychotic disorders such as schizophrenia. The 
absence of biomarkers and specific molecular targets, as well as the 
complexity of the brain, create enormous challenges for drug discovery.
    What steps can the National Institute of Mental Health (NIMH) be 
taking to spur development of innovative therapies to treat these 
devastating disorders? Is NIMH examining the viability of a public-
private partnership to advance discovery of new medicines?
    Answer. NIMH supports innovative approaches aimed at improving 
treatment for individuals living with schizophrenia and other psychotic 
disorders through research on novel therapeutics, biomarkers to inform 
therapeutics development and treatment, and services and interventions 
to optimize existing evidence-based treatments.
    NIMH supports early-stage therapeutic discovery and development for 
the treatment of mental illnesses across the drug development pipeline, 
including first-in-human and early efficacy trials.\41\ The NIMH Drug 
Discovery and Clinical Therapeutics Program supports research to design 
and develop novel therapeutics agents for the treatment of mental 
illnesses and supports the NIH National Cooperative Drug/Discovery/
Development Groups (NCDDG) program for the Treatment of Mental 
Disorders.\42\ The NCDDG encourages public-private partnerships to: 
accelerate the discovery of pharmacological agents targeting novel 
molecular processes implicated in the pathophysiology of mental 
illnesses; facilitate the development and validation of predictive 
assays for developing novel therapeutics for mental illnesses; support 
early phase human clinical testing to rapidly assess the safety and 
efficacy of promising drug candidates; and, facilitate the development 
and validation of new clinical measures or biomarkers suitable for use 
in human proof of concept trials of novel therapeutics. As an example, 
the NIMH Psychoactive Drug Screening Program provides the research 
community with access to broad screening capabilities in the form of 
pharmacological and functional assays to stimulate innovative research 
and development efforts including potential therapeutic agents for the 
treatment of psychiatric disorders.\43\ In addition, NIMH supports 
research on the development and testing of novel drug compounds for 
their potential to improve cognition in people with schizophrenia. 
These compounds modulate cholinergic signaling in the brain, which 
plays an important role in arousal, attention, memory, and motivation. 
Two of these compounds are at the stage of safety and tolerability 
testing in human subjects.\44,45\ This line of research aims to 
ameliorate neurocognitive dysfunction, which is a hallmark of 
schizophrenia and a significant contributor to disability associated 
with schizophrenia.
---------------------------------------------------------------------------
    \41\ https://www.nimh.nih.gov/research-priorities/therapeutics/
index.shtml.
    \42\ https://www.nimh.nih.gov/about/organization/dnbbs/molecular-
cellular-and-genomic-neuroscience-research-branch/drug-discovery-and-
clinical-therapeutics-program.shtml.
    \43\ https://www.nimh.nih.gov/funding/grant-writing-and-
application-process/concept-clearances/2017/the-nimh-psychoactive-drug-
screening-program-pdsp.shtml.
    \44\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9339822&icde=32296266.
    \45\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9140071&icde=32296291.
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    To inform novel therapeutics development, NIMH continues to fund 
research aimed at identifying biomarkers and charting trajectories of 
psychotic disorders. Through the NIH Neuroscience Blueprint, which uses 
state-of-the-science brain imaging technologies to acquire and broadly 
share data about the structural and functional connectivity of the 
human brain, NIMH co-funds two NIH Human Connectome Projects (HCP) 
focused on psychosis. One project examines brain anatomical and 
functional connectivity in individuals with early psychosis.\46\ The 
second project tests quantitative models of local and long-range neural 
mechanisms to understand abnormal visual perception in psychosis.\47\ 
These projects aim to identify neural correlates of clinical symptoms 
observed in psychosis and could pave the way for novel treatment 
development. In addition, NIMH supports the North American Prodrome 
Longitudinal Study (NAPLS), a nine-site consortium combining brain-
based biological and clinical markers to predict the onset of psychosis 
in vulnerable populations and chart trajectories of mental illness. An 
improved predictive algorithm and better understanding of biological 
mechanisms underlying psychosis onset could inform patient 
stratification for clinical trials of novel preventive treatments.\48\ 
NIMH also supports the Early Psychosis Intervention Network (EPINET) to 
create a common database of information gathered during routine 
clinical encounters to inform effective early psychosis care and 
accelerate research into psychosis risk factors, biomarkers of 
psychosis risk and onset, and pre-emptive interventions.\49\
---------------------------------------------------------------------------
    \46\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9108511&icde=32296915.
    \47\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9109802&icde=32296932.
    \48\ http://campuspress.yale.edu/napls/.
    \49\ https://www.nimh.nih.gov/funding/grant-writing-and-
application-process/concept-clearances/2015/early-psychosis-
intervention-network-epinet-a-learning-healthcare-system-for-early-
serious-mental-illness.shtml.
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    In addition to seeking pathways to novel interventions, NIMH is 
also committed to improving implementation of current evidence-based 
practices for the treatment of psychosis. Antipsychotic medications 
provide substantial benefits to many patients, and consistent 
medication use is associated with lower rates of relapse and re-
hospitalization. Through the Small Business Innovation Research and 
Small Business Technology Transfer (SBIR/STTR) program, NIMH supports 
research to help patients maintain treatment through efforts that 
improve medication adherence, medication monitoring, and the use of 
technologies to enhance interventions.\50,51,52,53,54\ In addition, the 
Advanced Laboratories for Accelerating the Reach and Impact of 
Treatments for Youth and Adults with Mental Illness (ALACRITY) Research 
Centers aims to improve the effectiveness, delivery, and quality of 
evidence-based services in diverse settings for individuals with 
serious mental illness, including psychotic disorders.\55,56,57\ 
Through the Early Psychosis Prediction and Prevention (EP3) initiative, 
NIMH supports several projects to develop and test interventions to 
improve cognitive and social skills for persons at clinical high risk 
for psychotic disorders.\58,59,60,61\ NIMH recently issued a funding 
opportunity announcement to support a large-scale initiative focused on 
testing the effectiveness of interventions that target early symptoms 
associated with clinical high risk for psychosis (i.e., problems in 
thinking, mood, and social functioning suggestive of a pre-psychosis 
risk state).\62\
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    \50\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9254370&icde=39687639.
    \51\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9201433&icde=39687639.
    \52\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9128708&icde=39687639.
    \53\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9361111&icde=39687639.
    \54\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9201713&icde=39687639.
    \55\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9374695&icde=39592663.
    \56\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9485776&icde=39592663.
    \57\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9486324&icde=39592663.
    \58\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9345577&icde=22682326.
    \59\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9304884&icde=22682332.
    \60\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9302540&icde=22682334.
    \61\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9302539&icde=22682335.
    \62\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
211.html.
---------------------------------------------------------------------------
    NIMH will continue to fund research on psychotic disorders to 
identify and develop the breakthrough treatments of tomorrow, as well 
as to optimize and implement the effective treatments of today. In 
pursuit of its mission to transform and understand treatment of mental 
illnesses, NIMH will continue public-private partnerships through the 
NCDDG and consider other partnerships that support excellent science 
and the NIMH mission.
                        neurological conditions
    Question. As you may know, the 21st Century Cures Act authorized 
the CDC to implement a national neurological conditions surveillance 
system. I worked on this section with Sen. Isakson because despite the 
fact that estimates indicate that one in six Americans lives with a 
neurologic condition, many condition-specific figures are severely 
outdated. For instance, the last national study of prevalence and 
incidence of Multiple sclerosis was done in 1975 and data on the 
prevalence of Parkinson's disease is based on a 1985 study.
    How would a neurological disease registry help provide a foundation 
for evaluating and understanding aspects of neurological conditions? 
How could such a surveillance system accelerate neurological research?
    Answer. For many neurological diseases, there are no recent, 
reliable data on the incidence, prevalence, geographical distribution, 
and demographics in the U.S. population, nor for changes over time. 
Such information can be useful in several ways. These data are 
essential to understand the societal burden of neurological disorders, 
which is an important factor that NIH and the research community must 
consider in setting research priorities, along with scientific 
opportunity. Such data are also crucial for designing public health 
programs. In some cases, these data may provide clues to risk factors 
and potential environmental influences that more targeted studies may 
follow up, such as reported differences in geographical distribution in 
multiple sclerosis and the association of some cases of Parkinson's 
disease with occupational exposure. Data on frequency of diseases also 
can demonstrate the effectiveness of research on public health; for 
example, in stroke, for which we do have good data, there has been a 70 
percent decline in the age adjusted death rate, reflecting the 
cumulative benefits of decades of research.
    Although potentially useful, surveillance of neurological disorders 
presents formidable challenges, especially in a healthcare system that 
does not have a single central record system. There are hundreds of 
diseases of the brain and nervous system, many of which are difficult 
to diagnose correctly. Some disorders, like chronic pain, are among the 
most common of all diseases, and the many rare genetic diseases 
collectively have an enormous burden despite being individually rare. 
Together, neurological diseases affect people of all ages, who may be 
treated via family physicians, various medical specialties, hospitals, 
nursing homes, or by self-care. All of this makes tracking very 
difficult because the optimal strategy is different for different 
diseases. The 21st Century Cures Act acknowledged the difficulty, 
noting that the surveillance system may initially address a limited 
number of neurological diseases.
                                 ______
                                 
            Questions Submitted by Senator Joe Manchin, III
                             superfund site
    Question. Dr. Collins, as you may know, Minden, West Virginia has 
been listed as a Superfund site by the EPA since 1984 because the small 
rural community was contaminated with PCBs by an industrial facility 
related to coal mining.
    I am gravely concerned about the reports stating that cancer rates 
are significantly higher in Minden than the rest of Fayette County and 
the rest of the State.
    The National Toxicology Program ranks PCBs as ``reasonably 
anticipated to be human carcinogens'' and the EPA has classified PCBs 
as a probable human carcinogen. Both designations indicate that there 
is substantial likelihood that extended exposure to PCB contaminated 
sites could result in cancer.
    Yet, the EPA has found that PCB exposure from the superfund site is 
not responsible for these high cancer rates or for a cancer cluster in 
this small, rural Appalachia town. That is why it is so critical that 
we conduct additional research to fully understand the potential causal 
connection between PCB exposure and cancer rates.
    Dr. Collins, will you commit to directing the National Toxicology 
Program at NIH to promptly prioritize further research on PCB exposure 
and the link to cancer?
    Further, will you work with me and the other members of this 
Committee to ensure that the National Institute of Environmental Health 
Sciences has the resources needed to conduct this critical research?
    Answer. Thank you for your questions, and I appreciate your sharing 
information about the situation with the Superfund site in Minden, West 
Virginia. The National Institute of Environmental Health Sciences 
(NIEHS) is home to the National Toxicology Program (NTP), which is 
dedicated to testing and evaluating substances in the environment. 
NIEHS and NTP have a long history of funding research into the health 
effects associated with exposure to polychlorinated biphenyls (PCBs). 
NTP has conducted extensive rodent studies with component PCBs to try 
to understand how these components interact in the body to cause 
cancer. Other NIEHS investments in this area cover relationships 
between exposure to PCBs and risks of developmental disorders, immune 
responses, obesity, metabolic disorders and diabetes, and neurological 
problems. Given their current and past research activities, NIEHS and 
NTP are well positioned to advise and share information with other 
agencies involved in answering scientific questions about PCB exposure 
levels in affected populations.
                              rural health
    Question. In 2017, the America's Health Rankings Report ranked West 
Virginia 46th in overall health. This low ranking is driven by high 
obesity rates, high rates of smoking, and high rates of drug related 
deaths. We're also 48th highest in cancer deaths and 49th highest in 
the number of West Virginians with diabetes.
    West Virginia has, in many ways, been left behind as medical 
advances have saved lives in other places. In fact, I have heard from 
West Virginians who want to participate in clinical trials, but are 
forced to leave the state to do so.
    Dr. Collins, what is NIH doing to bridge this gap in health 
outcomes?
    How do you ensure that the medical research that you do benefits 
people in poor, rural communities?
    How can we better expand access to research studies and then to 
successful treatments to rural Americans, particularly in states like 
mine where the disease burden is so high?
    Answer. NIH recognizes the unique health disparities that rural 
communities face, and as such, rural health is an important area of 
research for the agency. Through diverse collaborations and 
partnerships with communities, academic institutions, and state 
agencies, NIH supports and conducts rural health research to improve 
health outcomes and reduce rural health disparities with a special 
emphasis on populations in poor, rural communities. NIH's rural health 
research focuses on key areas of concern to you and rural residents and 
are aimed at addressing health disparities that rural populations in 
West Virginia and around the U.S. experience.
    In fiscal year 2017, NIH supported more than 500 rural health-
related grants for approximately $259 million. NIH is committed to 
ensuring that there are opportunities for poor rural Americans to 
access the benefits of research and that research addresses the unique 
strengths and challenges of rural communities. NIH supports several 
programs focused on cancer, cardiovascular disease, and other chronic 
diseases disproportionately affecting rural communities. For example, 
Screen to Save \63\ is a colorectal cancer outreach and screening 
initiative aimed at increasing cancer screening rates for individuals 
in rural communities, particularly among racial and ethnic minority 
populations. The Heart Truth Community Action Program \64\ initiative 
engages and empowers women to learn about risk factors for heart 
disease and steps they can take to live a heart-healthy life. The 
Strong Hearts, Healthy Communities \65\ program works to reduce rural 
disparities in cardiovascular disease through community-based 
interventions (e.g., nutrition and physical activity classes) in ten 
underserved, rural towns. NIH's Healthcare for Rural Populations 
Research Initiative \66\ aims to enhance the resources and 
infrastructure underlying healthcare access and quality for rural 
populations, including methods for improving oral health in rural 
school-based cavity prevention programs.
---------------------------------------------------------------------------
    \63\ https://www.cancer.gov/about-nci/organization/crchd/blog/2016/
screentosave-launch.
    \64\ https://www.nhlbi.nih.gov/health/educational/hearttruth/
partners/grantees.htm.
    \65\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9245732&icde=34114853.
    \66\ https://www.nimhd.nih.gov/programs/extramural/resource-
related.html#healthcare-rural.
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    Recognizing the unique needs of Appalachian communities, NIH 
supports the Kids SIPsmartER \67\ project, a school-based, behavior and 
health literacy curriculum aimed at improving sugar-sweetened beverages 
(SSB) behaviors among middle school students in medically underserved 
Appalachian counties in southwest Virginia. The program uses a two-way 
short service message strategy to engage caregivers in SSB role 
modeling and supporting home SSB environment changes. The primary aim 
is to assess changes in SSB behaviors among 7th grade students at 
schools receiving Kids SIPsmartER; evaluate changes in secondary 
student outcomes such as BMI and quality of life; changes in caregiver 
outcomes; and maintenance of outcomes. The overall goal is to establish 
an effective, scalable, and sustainable multi-level strategy to improve 
SSB behaviors and reduce SSB-related health inequities and chronic 
conditions in rural Appalachia.
---------------------------------------------------------------------------
    \67\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9495908&icde=39783928.
---------------------------------------------------------------------------
    Several West Virginia institutions are also engaged in rural health 
research, including the West Virginia State Department of Health and 
Human Resources, West Virginia University, West Virginia School of 
Osteopathic Medicine, CAMC Health Research Institute, and Marshall 
University. In one West Virginia-based project for example, NIH 
supports the West Virginia University Stroke Center of Biomedical 
Research Excellence (WVU Stroke CoBRE),\68\ a part of the WVU Center 
for Basic and Translational Stroke Research, which works to identify 
and treat the known risk factors for stroke among Appalachian 
populations. Research conducted by the WVU Stroke CoBRE focuses on 
stroke prediction, causes, prevention, acute treatment and 
rehabilitation. The Stroke CoBRE also has an intensive mentoring 
program for junior investigators. The WVU Stroke CoBRE recently became 
a formal part of the StrokeNet clinical trial consortium which will 
allow the Center to conduct multi-centered clinical trials to enhance 
its rapid translation of basic research into clinical trials and 
studies.
---------------------------------------------------------------------------
    \68\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9313278&icde=39683671.
---------------------------------------------------------------------------
    The Rural West Virginia Responds to Opioid Injection Epidemics: 
From Data to Action \69\ project seeks to eliminate the opioid epidemic 
and associated infectious diseases in West Virginia through 
collaborations with communities and public health agencies. The project 
will create an evidence-based roadmap to coordinate and improve 
screening, prevention, and treatment for HIV and other insular 
injection drug use-associated diseases; develop and test a novel 
strategy to rapidly identify the emergence of HIV in rural communities; 
and deploy and evaluate an integrated service delivery model to enhance 
delivery of evidence-based services, screening strategies, and 
treatment.
---------------------------------------------------------------------------
    \69\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9412006&icde=39683671.
---------------------------------------------------------------------------
    Continued collaborations and partnerships with scientists and 
organizations from rural communities, such as many in West Virginia, 
will contribute to NIH's reach in rural communities and support our 
work to combat rural health disparities.
                    institutional development award
    Question. The Institutional Development Award (NIH IDeA) program 
has been critical for West Virginia. It brings NIH funding to help 
build the medical research programs in underserved states.
    West Virginia currently only receives about $20 million in NIH 
grant funding, but WVU estimates that the economic benefit of these 
grants in West Virginia is $180 million and the IDeA program has been 
critical for expanding access to medical research in my State.
    The IDeA program received $350 million in the bipartisan fiscal 
year 2018 Omnibus Appropriations bill, but the budget would cut funding 
for the National Institute of General Medical Sciences--which houses 
this program--by more than $935 million, and this program was not even 
specifically listed.
    I believe that we should continue to strongly support this program.
    Dr. Collins, what impact the proposed cuts to NIH funding would 
have on this important program?
    Can you tell me why this program was not specifically listed in the 
budget and what the recommended fiscal year 2019 funding level is?
    Can you please speak to the importance of funding research at a 
wide variety of institutions, particularly those in rural, underserved 
states?
    Answer. The Budget recognizes that importance of funding the 
highest priority scientific discoveries while also maintaining fiscal 
responsibility of Federal resources. The IDeA Program will continue to 
fulfill its congressional mandate of broadening the geographic 
distribution of NIH funding for biomedical research and enhancing the 
competitiveness of investigators at institutions located at eligible 
states and jurisdictions at the fiscal year 2019 funding level.
    Consistent with other NIH Institutes, the fiscal year 2019 National 
Institute of General Medical Sciences (NIGMS) Congressional 
Justification only included the total program level. Individual NIGMS 
program details were not provided, also consistent with other NIH 
Institute Congressional Justifications.
    Prior to the increase of the budget caps and the fiscal year 2018 
enacted levels, the fiscal year 2019 President's Budget was built on 
the fiscal year 2018 Annualized CR level which reduced the NIGMS budget 
by 2.29 percent. Like the overall NIGMS Program level, the fiscal year 
2019 President's Budget for the IDeA Program would be reduced by 2.29 
percent from the fiscal year 2018 Annualized CR. When comparing fiscal 
year 2019 President's Budget over the fiscal year 2018 enacted level, 
the overall NIGMS total program level and the IDeA program would be 
reduced by 7.6 percent.
    The IDeA Program managed by NIGMS is a long-term interventional 
capacity-building program targeting states and jurisdictions that have 
consistently trailed in obtaining significant NIH support. The intent 
of the program is to transform institutions with infrastructure, human 
resource, and economic challenges to become more competitive biomedical 
research enterprises through various distinct but complementary 
initiatives. Some benefits of the IDeA Program in the eligible states 
and jurisdictions include:
  --Builds active biomedical research environments in IDeA states and 
        improves access to modern, state-of-the-art biomedical research 
        for students, researchers, and the general public.
  --Ensures that states without medical schools have an opportunity to 
        develop research capacity for conducting basic, translational, 
        and clinical research.
  --Provides opportunities to address health disparities in medically 
        underserved groups residing in IDeA states.
  --Promotes SBIR/STTR programs, technology transfer, entrepreneurship, 
        and public-private partnerships that could lead to the 
        formation of bio-related industries, potentially benefitting 
        the local economy.
  --Encourages collaborations and leveraging among IDeA research 
        resource centers to capitalize on each other's unique 
        capabilities to solve complex research questions and encourages 
        consolidation of research resources with complementary 
        technologies to improve efficiency and crate economies of 
        scale.
  --Enhances the competitiveness of institutions by providing 
        opportunities for talented and highly motivated undergraduate 
        students to participate in research training and pursue 
        research careers in the biomedical sciences.
  --Develops best practices, training tools, workflows, databases, and 
        analysis tools that assist clinical and translational 
        researchers to develop and perform clinical and translational 
        protocols to address important questions in multiple areas of 
        biomedical science quickly and efficiently.
    Funding research at a wide variety of institutions is extremely 
important to ensure that a rich diversity of scientific and 
geographical perspectives is represented and that all available human 
capital is deployed in the critical work of addressing vital biomedical 
research questions and pressing health problems. Local investigators 
are often the best equipped and experienced to conduct research on 
local health concerns. Further, NIH strongly believes that scientific 
discoveries can arise anywhere where there are well-trained and 
determined investigators working in adequately resourced environments. 
Ensuring that all jurisdictions and institutions across the United 
States are afforded the opportunity to become active and significant 
contributors to this country's research agenda increases the likelihood 
of breakthroughs in science and medicine.
              medical research can save money--alzheimer's
    Question. I am someone who is very concerned about the Federal 
debt, but I have always supported strong funding for NIH because it is 
an investment that saves lives, preserves America's role as a global 
innovator, and has the potential to save a lot more money in the future 
if we're able to reduce the costs of treating expensive diseases.
    Alzheimer's disease, for example, cost West Virginia's Medicaid 
program $394 million in 2017 and this cost is expected to increase as 
the number of people with the disease increases. The Alzheimer's 
Association estimates that the cost of caring for people with 
Alzheimer's and dementia will rise from $236 billion to $1.1 trillion 
in 2050. In short, we can't afford to not invest in medical research.
    That is why I share my colleagues concern about the President's 
budget cuts of more than $2.2 billion to NIH overall and more than $1.1 
billion to the National Institute on Aging in particular relative to 
the funding that we included in the fiscal year 2018 Omnibus.
    Dr. Hodes, as the Director of the National Institute on Aging, can 
you please speak to the research that your agency is doing on 
Alzheimer's disease?
    Do you believe that investments in this research now is a fiscally 
responsible choice given the astronomical costs that our country is 
likely to face as our Nation ages?
    Answer. NIA has leveraged the extraordinary influx of funding 
directed at Alzheimer's disease and related forms of dementia (AD/ADRD) 
to build a series of bold and innovative research programs, 
infrastructure, and new partnerships that are enabling some of the 
Nation's leading scientists to tackle the problem of AD/ADRD on an 
unprecedented scale and pace. High-priority research and infrastructure 
programs that are currently underway include:
  --Alzheimer's Clinical Trial Consortium (ACTC), to accelerate and 
        expand trials of AD/ADRD therapies;
  --Resilience-AD, a new program bringing together experts from 
        multiple disciplines to understand why some high-risk 
        individuals remain dementia free;
  --Molecular Mechanisms of the Vascular Etiology of Alzheimer's 
        Disease (M\2\OVE-AD) Initiative, exploring how metabolic and 
        vascular risk factors such influence brain aging and AD 
        pathology and identifying blood-based markers of the disease;
  --Alzheimer's Biomarker Consortium--Down Syndrome (ABC-DS), in which 
        researchers use biomarkers to track disease progression in 
        people with DS, a uniquely vulnerable population at high risk 
        for developing AD;
  --The Model Organism Development and Evaluation for Late-onset AD 
        (MODEL-AD) project to develop better animal models of late-
        onset AD;
  --Approximately 140 active clinical trials of interventions to 
        prevent, treat, or manage symptoms of AD/ADRD and to enhance 
        caregiver well-being;
  --Development of new therapeutics, including some that target 
        molecules other than beta-amyloid; and
  --Harnessing the power of big data to identify existing drugs or 
        combinations currently used to treat other conditions that 
        could be effective for the treatment of AD/ADRD.
    Other current priorities include development of caregiver support 
interventions; implementation of a national recruitment strategy that 
ensures inclusion of diverse populations in AD/ADRD research; 
understanding gene-environment interactions that increase risk or 
confer resilience against AD/ADRD; infrastructure development, 
including big data infrastructure; workforce training across the 
spectrum of research; and harmonization and distribution of data from 
large datasets.
    The financial costs associated with AD/ADRD to affected families 
and to society are considerable. Data published by the Alzheimer's 
Association estimate total payments in 2018 for all individuals with 
AD/ADRD at $277 billion, much of which will be paid by Medicare and 
Medicaid. NIH-funded researchers found that, in the last 5 years of 
life, total health and long-term care spending for people with dementia 
was more than $250,000 per person, greater than costs associated with 
death from other major chronic diseases. Average out-of-pocket spending 
for patients with dementia was 81 percent higher than for patients 
without dementia. Caregiving costs, including loss of wage income due 
to caregiving responsibilities, are also significant.
    NIH-supported researchers estimate that delaying onset of AD for 5 
years would result in 41 percent lower prevalence and 40 percent lower 
cost of AD by 2050. Given these findings, research to ameliorate not 
only the physical and mental burdens of these diseases but also the 
economic burden is not only fiscally responsible, it is crucial to the 
health of our economy.
                                 ______
                                 
            Questions Submitted by Senator Patrick J. Leahy
    Institutional Development Award (IDeA)
    Question. The IDeA program, operated by the National Institute of 
General Medical Sciences (NIGMS) at the National Institutes of Health 
(NIH) has long been a fundamental source of support for institutions 
that participate in biomedical research. With a focus on health-related 
research, specifically in rural and medically underserved communities, 
IDeA is critical in the goal of supporting researchers' work to uncover 
lifesaving methods to combatting disease. In my home State of Vermont, 
IDeA awards have contributed to advances in genetic research, new 
medical technologies, and vaccine and drug developments.
    With the help of IDeA awards, the University of Vermont, our 
State's largest research institution, developed the Vermont Genetics 
Network, the Vermont Center for Immunology and Infectious Diseases, the 
Vermont Center for Neuroscience, and the Vermont Center on Behavior and 
Health. IDeA grants have also expanded the employment of STEM 
professionals in several other institutions of higher education across 
the State. These institutes have contributed to some of the world's 
most groundbreaking medical understanding on how to cure lung and heart 
disease and on understanding the effect of brain disorders on learning 
and development.
    I am concerned that the administration's proposed cuts to NIH and 
NIGMS will undoubtedly place pressure on the IDeA program by reducing 
the amount of grant dollars awarded for institutional biomedical 
research. This means less opportunities for our Nation's institutions 
to develop lifesaving treatments to debilitating disease.
    What are the benefits of the IDeA program in building capacity in 
states that might not otherwise receive NIH funding, including a 
description of not only how this program has benefited not just local 
communities, but also helped advance the national dialogue on 
biomedical and translational research?
    Answer. The overarching mission of the Institutional Development 
Award (IDeA) Program is inclusive Biomedical Research Capacity-
building--to develop and strengthen biomedical science research 
programs in States/Jurisdictions of the country that are 
underrepresented in the NIH portfolio, to enable increased engagement 
and participation of these states in scientific areas that are 
supported by NIH, and to promote biomedical research capacity and 
capabilities in these states that are competitive and sustainable. 
Benefits of the IDeA program in states/jurisdictions receiving IDeA 
funding include the following:
  --Through targeted professional development efforts, the IDeA Program 
        grows and nurtures the pool of next generation scientific 
        leaders and innovators.
  --The IDeA program develops and enhances the research facilities and 
        resources in these states/jurisdictions, thereby enabling 
        investigators to expand their contributions to scientific 
        discovery, innovation, and learning.
  --Inclusive and sustainable biomedical workforce development pathways 
        are established and formalized that equip local human resources 
        with the appropriate intellectual and technical scientific 
        skills. Biomedically skilled human capital, in turn, can serve 
        as the nidus or help attract the formation of bio-related 
        industries, potentially benefitting the local economy.
  --Through meaningful engagement of the local community, both the 
        scientific research community and the community at-large form 
        important partnerships that begin to address vital and urgent 
        scientific questions and regional health priorities.
    Within the past year, some of the important contributions made by 
investigators and other highlights/impacts emanating from the IDeA 
Program initiatives include the following:
  --Vermont IDeA Network of Biomedical Research Excellence (INBRE) \70\ 
        researchers characterized the processing of a protein in 
        neurons called progranulin, a mechanism that impacts the 
        neuropathology of frontotemporal dementia (FTD), a 
        neurodegenerative disorder characterized by progressive changes 
        in personality, behavior, and/or language. FTD is the second 
        most common cause of early-onset Alzheimer's disease. This 
        finding was published in the scientific journal Molecular 
        Neurodegeneration.
---------------------------------------------------------------------------
    \70\ The IDeA Network of Biomedical Research Excellence (INBRE) 
initiative enhances, extends, and strengthens the research capabilities 
of biomedical research faculty in IDeA states through a statewide 
program that links a research-intensive institution with primarily 
undergraduate institutions.
---------------------------------------------------------------------------
  --A New Mexico Centers of Biomedical Research Excellence (COBRE) \71\ 
        team reported on a collaborative intervention to increase 
        awareness on risk of falls for Zuni Native American community. 
        The innovative collaborative approach can produce dramatic 
        improvements in clinical outcomes, health related quality of 
        life, and reductions in healthcare costs. The Zuni Health 
        Initiative (ZHI), an integrated model of community, family and 
        clinic-based education, life style modification and healthcare 
        will facilitate the translation of validated national 
        guidelines for screening and treatment of chronic disease and 
        reduce health disparities in this high-risk population of Zuni 
        American Indians.
---------------------------------------------------------------------------
    \71\ The Centers of Biomedical Research Excellence (COBRE) 
initiative develops and strengthens institutional biomedical research 
capabilities in IDeA states through three 5-year phases of 
infrastructure and faculty development of multidisciplinary research 
centers focused on a specific biomedical science theme.
---------------------------------------------------------------------------
  --A report from Advances in Physiology Education reported on North 
        Dakota INBRE's impact on undergraduate research at rural 
        primarily undergraduate institutions (PUIs) over a 12-year 
        period. Participation of the PUIs in the ND INBRE generated a 
        more robust research culture at the undergraduate institutions. 
        The number of faculty participating in undergraduate research 
        increased two- to four-fold. The high level of student success 
        (550 participants) is supportive of the concept that 
        undergraduate research (350 posters presented) is a value-added 
        component of the INBRE initiative that will help prime the 
        pipeline for the next generation of health professionals in 
        research, service, and teaching.
  --A COBRE team from Vermont carried out research on adverse effects 
        associated with using commercially available cigarettes and 
        explored the effects of reducing potential for addiction in 
        highly vulnerable populations (socioeconomically disadvantaged 
        smokers, individuals with psychiatric conditions). Three 
        manuscripts were published that reported the following: (1) 
        significant positive association between using commercially 
        available high nicotine yield cigarettes and risk of nicotine 
        dependence and continuing to smoke during pregnancy in a 
        nationally representative sample of U.S. women of reproductive 
        age (published in Preventive Medicine), (2) reducing the 
        nicotine content of cigarettes significantly reduces the 
        addiction potential of cigarette smoking in adults highly 
        vulnerable to tobacco addition (smokers with psychiatric 
        disorders or socioeconomic disadvantage) (published in JAMA 
        Psychiatry), and (3) dependence severity has no moderating 
        influence on the ability of reduced nicotine content cigarettes 
        to lower the addiction potential of smoking, and minimal 
        effects on relief from craving/withdrawal or smoking topography 
        (published in Preventive Medicine).
  --INBRE researchers from Alaska reported on the ability of the arctic 
        ground squirrel, a seasonal hibernator, to resist brain damage. 
        Investigating how oxygen glucose deprivation induces tolerance 
        has very important translational implications in ischemic brain 
        injury in stroke patients (reported in Journal of 
        Neurochemistry).
  --Investigators supported through the Kentucky INBRE elucidated the 
        role of a Zika capsid (membrane) protein in brain damage and 
        published their results in Nature.
  --Shayna Bennett, an alumna of Johnson State College in Vermont, was 
        named an awardee of the 2018 National Science Foundation 
        Graduate Research Fellowship Program (GRFP). The program 
        supports graduate students with high potential to be leaders in 
        STEM research. The program supports NSF's goal of developing a 
        workforce that leads the world in advancing science and 
        engineering research. While Shayna was an undergraduate student 
        at Johnson State College, she was funded by the Vermont INBRE 
        to conduct biomedical research from 2014-2015. The experience 
        influenced her decision to pursue a graduate degree in a STEM 
        research field. She is currently a first-year doctoral student 
        in applied mathematics at the University of California Merced.
  --A report at the Advances in Physiological Education demonstrated 
        how the Kansas INBRE annual symposium, a 10-institute 
        collaboration, improved undergraduate education. The 16-year 
        undertaking has supported 1,000 students. Survey results 
        indicate that students and mentors alike find the symposium to 
        be beneficial and enriching of the student experience, with 
        almost 80 percent of student respondents indicated that their 
        participation in the symposium fostered appreciation of 
        research. The KA-INBRE symposium provides a terrific 
        opportunity for students to gain experience in collecting, 
        preparing, and communicating research in a professional 
        environment.
  --An Arkansas COBRE team published their findings on the effects of 
        radiation on normal tissues and certain age-related diseases 
        vis-a-vis aging stem cells and the ability of tissues to 
        regenerate and repair, drive inflammation, and oxidative 
        stress. The report focused on ABT-263, a molecule initially 
        developed as an anti-cancer therapy drug, which could 
        effectively deplete senescent (aging) cells. The depletion 
        appeared to reduce premature aging of the bone marrow due to 
        irradiation and rejuvenated the function of stem cells in 
        normally aged mice (reported in Nature Medicine).
  --Investigators supported through the Louisiana IDeA-Clinical and 
        Translational Research (CTR) \72\ award found that Mycoplasma 
        genitalium is an etiologic agent of cervicitis in HIV-infected 
        women, providing a potential mechanism for enhanced HIV 
        transmission to an uninfected partner. M. genitalium is an 
        emerging sexually transmitted pathogen implicated in 
        inflammatory syndromes of the female reproductive tract 
        (reported in Journal of Infectious Disease).
---------------------------------------------------------------------------
    \72\ The IDeA Program Infrastructure for Clinical and Translational 
Research (IDeA-CTR) initiative develops network infrastructure and 
capacity in IDeA-eligible states to conduct clinical and translational 
research focused on health concerns that affect medically underserved 
populations and/or that are prevalent in IDeA states.
---------------------------------------------------------------------------
  --Montana IDeA researchers collaborated on a report on the 
        transmission of a pathogen from animals to humans (zoonotic 
        transmission). This work provides a foundation for 
        transdisciplinary investigation of spillover and synthetic 
        theory on zoonotic transmission (reported in Nature Reviews 
        Microbiology).
  --A New Hampshire COBRE team reported on a plant-based nanotechnology 
        that could generate an antitumor immune response. The effect 
        was observed to be systemic and durable, resulting in immune-
        memory and protection from recurrence (reported in Nature 
        Nanotechnology).
                          tick-borne diseases
    Question. The spread of tick-borne diseases, such as Lyme disease 
(Lyme), to humans have been increasing in Vermont and many other 
northern states. While reports of Lyme in Vermont used to be rare in 
the early 1990s, it is now common to see over 400 confirmed cases 
reported in a year. This trend has proven to be true for other 
northeastern and upper Midwestern States as well, as the number of 
reported cases of Lyme has tripled and the number of high-risk counties 
has increased by more than 300 percent since the late 1990s. Ticks, and 
thus Lyme and other tick-borne diseases, have expanded their geographic 
range and are now being found in places where there were not seen 20 
years ago. It is estimated that 20 percent of the population that live 
in areas where Lyme is common are unaware that they live in high-risk 
areas for tick-borne diseases.
    Given the ever-growing threat of tick-borne diseases, what efforts 
are NIH pursuing to better detect or cure tick-borne diseases such as 
Lyme?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) maintains a diverse research portfolio on Lyme disease and 
other tick-borne diseases and encourages development of diagnostics, 
therapeutics, and vaccines to combat these infections. As part of this 
effort, NIAID engages in important collaborations with Federal 
partners, Lyme disease experts, patients, and others as a member of the 
Department of Health and Human Services Tick-Borne Diseases Working 
Group created by the 21st Century Cures Act.
    NIAID supports basic research on how Borrelia species, including B. 
burgdorferi and B. mayonii, infect the host, multiply, and ultimately 
cause Lyme disease. Basic research also is underway for a variety of 
tick-borne infections such as anaplasmosis, babesiosis, tick-borne 
encephalitis, and others. Findings of these early-stage studies will 
help to identify targets for additional diagnostic tests, treatments, 
and vaccines for these infections. For example, NIAID grantees are 
using real-time imaging to track the spread of bacteria that cause Lyme 
disease and to monitor treatment effectiveness in infected mice. NIAID 
scientists also have developed a novel tick infection model for 
flaviviruses that could be used to evaluate tools to combat the deadly 
Powassan and tick-borne encephalitis viruses.
    NIAID is committed to discovering better ways to diagnose Lyme 
disease that would enable more informed treatment decisions. In 
collaboration with the Centers for Disease Control and Prevention and 
others, NIAID is working to develop novel diagnostics including next 
generation molecular tests. NIAID-supported scientists are working to 
identify biomarkers that could allow for earlier and more rapid 
diagnosis, accurate indication of disease stage and progression, 
indications of successful treatment, and ability to distinguish between 
Lyme and other tick-borne infections. NIAID scientists and extramural 
researchers recently developed a novel tool, the TBD-Serochip, to help 
differentiate several tick-borne infections. This test is designed to 
discriminate between eight major tick-borne pathogens in the United 
States, including species of Anaplasma, Babesia, and Borrelia.
    NIAID also supports Lyme disease prevention research, including 
efforts to develop effective vaccines. NIAID is funding research 
exploring the adaptation of a successful canine Lyme disease vaccine 
for potential use in humans. Other NIAID-supported studies are pursuing 
vaccine strategies to limit Lyme disease transmission, including oral-
bait vaccines targeting wildlife reservoirs of B. burgdorferi and 
efforts to target proteins in tick saliva that are critical for 
effective transmission of Lyme bacteria.
    NIAID is committed to supporting basic, translational, and applied 
research on tick-borne diseases, including studies on the pathogens, 
the ticks that transmit them, and their vertebrate hosts. Through 
ongoing research support, as well as collaborations with Federal and 
public partners, NIAID will continue to advance the development of 
vaccines, therapeutics, and diagnostics for Lyme and other tick-borne 
diseases.
                                 ______
                                 
               Questions Submitted to Anthony Fauci, M.D.
              Questions Submitted by Senator Patty Murray
                combatting antibiotic resistant bacteria
    Question. How has the threat posed by antibiotic resistant bacteria 
changed since you helped write the National Action Plan a few years 
back? Is the situation worse, better or unchanged?
    Answer. The National Institutes of Health (NIH) continues to 
prioritize research to address the public health threat of 
antimicrobial resistance. The National Institute of Allergy and 
Infectious Diseases (NIAID), part of the NIH, plays a lead role in 
addressing the goals of the National Action Plan for Combating 
Antibiotic-Resistant Bacteria (CARB), including the development of 
diagnostics, therapeutics, and vaccines for drug-resistant bacteria. 
The Progress Report: CARB Years 1 and 2 \73\ outlines NIAID-supported 
efforts, along with those of Federal CARB partners, toward achieving 
the goals of the National Action Plan for CARB. While our understanding 
of antibiotic-resistant bacteria--and how to combat them--has improved 
since the development of the National Action Plan for CARB, the 
emergence and re-emergence of drug-resistant bacteria continue to pose 
a threat to the public health. NIH and its CARB partners are committed 
to sustaining our critical efforts to develop countermeasures and 
strategies to address the ongoing challenge of antibiotic-resistant 
pathogens.
---------------------------------------------------------------------------
    \73\ https://aspe.hhs.gov/system/files/pdf/258516/
ProgressYears1and2CARBNationalActionPlan.
pdf.
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    Question. What is the status of efforts to fund clinical trials to 
test new antibiotics and diagnostics to quickly identify bacterial 
pathogens?
    Answer. NIAID supports a comprehensive research portfolio on 
antimicrobial resistance, including clinical trials to test new 
diagnostics, treatments, and vaccines. NIAID is funding highly 
meritorious research projects on antimicrobial resistance focused on 
developing: (1) clinical diagnostics; (2) tools to facilitate discovery 
of novel therapeutics; and (3) prevention strategies. These awards will 
build on successes in NIH-supported CARB research, including prior 
support for more than 35 clinical studies through the NIAID 
Antibacterial Resistance Leadership Group (ARLG), which oversees 
clinical research to reduce the public health threat of antibacterial 
resistance. The ARLG has undertaken studies investigating diagnostic 
devices, optimized treatment regimens, new drugs, and projects on 
antimicrobial stewardship. NIAID also supports basic and preclinical 
research to identify promising antibacterial products that may move 
into clinical trials. NIAID continues to collaborate with the 
Biomedical Advanced Research and Development Authority (BARDA) on CARB-
X, a unique public-private partnership dedicated to accelerating the 
development of innovative antibacterial products from target/candidate 
identification and characterization through Phase 1 clinical trials. 
NIH also continues to partner with BARDA to support the CARB diagnostic 
challenge seeking to identify innovative, rapid point-of-need 
diagnostics to combat the development and spread of drug-resistant 
bacteria, as well as increase antibiotic stewardship. These efforts are 
critical to generating a robust pipeline of candidate antibiotics and 
diagnostics to support clinical testing of promising products against 
drug-resistant organisms.
    Question. Does NIH expect these efforts to help reduce the number 
of drug-resistant infections and deaths that occur each year, or is 
that too much to expect?
    Answer. The ultimate goals of NIAID-supported research on 
antimicrobial resistance, ranging from basic research to identify 
targets for antimicrobial products to applied research and clinical 
trials to test new diagnostics, treatments, and prevention strategies, 
are to help reduce the number of drug-resistant infections and deaths 
and to increase antibiotic stewardship. As one example, NIAID 
scientists have been using next generation sequencing to study the 
evolution of community acquired methicillin-resistant Staphylococcus 
aureus (MRSA) strains to help identify how these strains developed and 
to understand why those strains have become more prevalent. This 
research, which collected MRSA isolates from patients in many 
geographic regions, may inform new strategies to limit community 
acquired MRSA infections throughout the United States. NIAID also has 
evaluated a new drug to treat Neisseria gonorrhoeae, a bacterium that 
is increasingly resistant to currently used drugs, in clinical trials 
through the Sexually Transmitted Infections Clinical Trials Group and 
the Phase 1 Clinical Trial Units for Therapeutics. Based on these early 
studies, which found the investigational gonorrhea therapeutic to be 
well-tolerated and effective, the drug will advance to later-stage 
clinical trials. NIH anticipates that its ongoing CARB research and 
partnerships across government, as well as new activities enabled by 
increases to CARB research funding in fiscal year 2018, will continue 
to support progress against antibiotic-resistant bacterial infections.
                         universal flu vaccine
    Question. NIH recently announced the phase 2 clinical trial of a 
potential universal flu vaccine. How long is that trial expected to 
last, and does NIAID have other vaccine candidates in the pipeline? If 
so, when might we see trials for candidates begin?
    Answer. The National Institutes of Health (NIH) is prioritizing the 
development of universal influenza vaccines that would represent a 
groundbreaking advance in influenza preparedness by allowing for 
durable protection against multiple influenza strains. The National 
Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, 
has outlined its research priorities for a universal influenza vaccine 
in a strategic plan published online on February 28, 2018, by The 
Journal of Infectious Diseases. As one example of research consistent 
with the strategic plan, NIAID recently launched a Phase 2 clinical 
trial of an experimental universal influenza vaccine called M-001. The 
vaccine, which was developed and produced by BiondVax Pharmaceuticals, 
is designed to stimulate an immune response against peptide sequences 
shared among many different influenza strains. The clinical study will 
be conducted at NIAID-funded Vaccine and Treatment Evaluation Units 
(VTEUs) and is estimated to be completed in early 2019. The VTEUs also 
are planning to initiate Phase 1 clinical studies to inform the 
development of universal influenza vaccines, including a study to 
evaluate whether the addition of a novel adjuvant to an existing pre-
pandemic H5N1 influenza vaccine can enhance the breadth of the immune 
response to different influenza strains.
    NIAID is studying additional strategies to create a universal 
influenza vaccine, several of which have advanced to early-stage 
clinical trials. For example, NIAID Vaccine Research Center scientists 
have initiated Phase 1/2 studies of a universal influenza vaccine 
approach that includes an investigational DNA-based vaccine followed by 
a licensed seasonal influenza vaccine ``boost'' to improve the potency 
and durability of seasonal influenza vaccines. NIAID also developed a 
ferritin nanoparticle-based vaccine approach that showed promise in 
animal testing and is being evaluated in early-stage clinical trials. 
In another strategy, NIAID scientists developed a vaccine made from 
non-infectious virus-like particles (VLPs). This VLP-based vaccine 
candidate incorporates four subtypes of the viral hemagglutinin protein 
into one vaccine. This candidate broadly protected against multiple 
influenza virus subtypes in animal models and may advance to clinical 
trials in the future. NIAID is supporting a number of preclinical 
studies to evaluate additional universal influenza vaccine candidates. 
In addition, NIAID funds basic research to better understand how the 
immune system responds to influenza infection or vaccination, and 
efforts to develop new assays and reagents to evaluate the efficacy of 
novel influenza vaccines.
    NIAID will continue to support the development of a robust pipeline 
of candidate universal influenza vaccines that may advance to 
evaluation in clinical trials. The availability of a universal 
influenza vaccine would eliminate the need to update and administer the 
seasonal influenza vaccine each year and could provide protection 
against newly emerging influenza strains, including those with pandemic 
potential. NIAID efforts to achieve this important goal will be 
facilitated by the generous support of the Congress in providing $100 
million dedicated to research on universal influenza vaccines in NIH's 
fiscal year 2018 budget.
                            opioid epidemic
    Question. What share of NIDA's roughly $1.4 billion budget for 
fiscal year 2018 will be devoted to opioid-related efforts, be it 
prevention, clinical trials or the development of new therapeutics?
    Answer. We are unable to provide this information until fiscal year 
2018 concludes, but we will provide the information when it becomes 
available.
    Question. When can we expect to see the agency's strategic plan for 
the opioids initiative, and will it include specific targets and 
milestones for what we're trying to achieve?
    Answer. The research plan for the Helping to End Addiction Long-
term (HEAL) Initiative \74\ is available online. Setting specific 
targets and milestones is difficult due to the unpredictable nature of 
scientific inquiry, so at this time, specific targets are not included. 
The overall goals of the HEAL Initiative are preventing addiction 
through enhanced pain management and improving treatment for opioid use 
disorder.
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    \74\ https://www.nih.gov/research-training/medical-research-
initiatives/heal-initiative/heal-initiative-research-plan.
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    Question. The fiscal year 2019 budget proposes a coordinated 
strategy with two primary aims to combat the opioid epidemic in our 
country. One of those aims is to accelerate the development of new, 
non-addictive pain therapies with the goal of making a wide-range of 
therapeutics accessible to those who need them as quickly as possible. 
Can you describe what types of non-addictive pain therapies are 
currently in the NIH research pipeline, and how quickly can these 
therapies can be developed and distributed to the market?
    Answer. NIH is particularly excited about the new Helping to End 
Addiction Long-term (HEAL) Initiative. HEAL will bolster research 
across NIH in an effort to improve the treatment of chronic pain by (1) 
exploring biomarkers that predict the transition from acute to chronic 
pain, (2) identifying new targets for treating chronic pain using 
neurotechnologies developed through the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the 
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, 
and (3) building the evidence base on the effectiveness of nondrug and 
integrated pain treatments. In addition, the Initiative will pursue 
public-private partnerships to develop new non-addictive pain medicines 
by sharing data on past and present research projects, and matching 
researchers with a selection of potentially promising but abandoned 
pharmaceutical industry compounds to explore their effectiveness for 
the treatment of pain. Finally, NIH will develop a clinical trials 
network for pain, allowing multiple new and repurposed compounds to be 
tested for effectiveness simultaneously.
    The Initiative will tap into the expertise of the NIH Pain 
Consortium,\75\ a trans-NIH consortium made up of NIH institutes that 
fund pain research. Funded projects are investigating the entire range 
of therapeutics development- from preclinical safety and efficacy 
testing and early phase human trials to health services research. 
Currently, the consortium members are working on developing more 
effective and less addictive treatments for chronic pain. For example, 
a study using a molecular imaging technology called x-ray 
crystallography has revealed the molecular structure of the receptors 
that mediate drugs' effects; this information is already leading to the 
development of safer medications to treat pain.
---------------------------------------------------------------------------
    \75\ https://www.painconsortium.nih.gov/About/Members.
---------------------------------------------------------------------------
    NIH-funded research is developing medications with properties that 
affect opioid receptors to produce analgesia with reduced risk of 
addiction and misuse. Some of these exhibit novel properties as a 
result of their combined activity at different types of opioid 
receptors (mu, delta, and kappa). Compounds with combined activity at 
the mu and delta receptors or at all three receptors can induce strong 
analgesia without producing tolerance or dependence in animal models. 
In addition, the discovery of adjunct medications that can be combined 
with opioids to reduce the needed dose has the potential to result in 
lower potential for dependence and addiction. Innovative methods are 
being explored for drug delivery to increase specificity and efficacy 
and to reduce analgesic side effects, as well as modified formulations 
to enhance delivery.
    NIH supports an initiative called the Blueprint Neurotherapeutics 
Program for small molecule drug discovery and development. For example, 
NINDS funds studies through this program that aim to develop non-
addictive kappa opioid receptor antagonists for migraine and a safe, 
non-opioid analgesic that can be taken orally to reduce diabetic nerve 
pain.
    It is difficult to estimate the time to market for these various 
alternatives, but NIH is establishing a Clinical Trial Network to 
accelerate the development of novel non-addictive chronic pain 
medications and devices by optimizing analgesic trial design, targeting 
appropriate patient populations for trials, and engaging research 
expertise at existing clinical sites.
    Question. Are there any vaccine candidates being considered?
    Answer. NIDA continues to fund development of anti-opioid vaccines 
capable of generating an immune response that would prevent opioids 
from entering the brain, thereby blocking both their euphoric effects 
and their dangerous respiratory depressant properties. Current projects 
include:
  --Optimization and preclinical testing of a practical heroin-HIV 
        vaccine \76\
---------------------------------------------------------------------------
    \76\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9110917&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=20&csb=default&cs=ASC&pball=.
---------------------------------------------------------------------------
  --Preclinical development of vaccines against heroin, oxycodone, 
        hydrocodone, and fentanyl \77,78,79\
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    \77\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9444613&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=11&csb=default&cs=ASC&pball=.
    \78\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9330137&icde=39707102 
&ddparam=&ddvalue=&ddsub=&cr=26&csb=default&cs=ASC&pball=.
    \79\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9461410&icde=39707102.
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    Results from preclinical models thus far have shown that these 
vaccine candidates are capable of producing an immune response that 
blocks opioid effects.\80\ While none have yet advanced to clinical 
trials, the heroin vaccine candidate developed by the Walter Reed Army 
Institute of Research in collaboration with NIDA has been in-licensed 
by Opiant Pharmaceuticals for further development.\81\
---------------------------------------------------------------------------
    \80\ Olson ME, Janda KD. Vaccines to combat the opioid crisis: 
Vaccines that prevent opioids and other substances of abuse from 
entering the brain could effectively treat addiction and abuse. EMBO 
Rep. 2018 Jan;19(1):5-9.
    \81\ https://www.opiant.com/pipeline/heroin-vaccine/.
---------------------------------------------------------------------------
    Question. The budget emphasizes that the NIH will work with the FDA 
and pharmaceutical partners to build a public-private partnership to 
accelerate the development of new non-addictive pain therapies. Can you 
describe what these partnerships will look like, and how small 
biopharmaceutical companies who may be working on novel approaches 
might be able to participate?
    Answer. As part of the NIH HEAL Initiative, NIH will pursue public-
private partnerships to accelerate the development of non-addictive 
pain medicines by sharing data on past and present research projects, 
as well as matching researchers with a selection of potentially 
promising but abandoned pharmaceutical industry compounds to explore 
their effectiveness for the treatment of pain. Companies of all sizes 
can participate in this initiative.
                                 ______
                                 
               Questions Submitted to Richard Hodes, M.D.
                Questions Submitted by Senator Roy Blunt
                          alzheimer's vaccine
    Question. Dr. Hodes, vaccines have been one of the most impactful 
medicines in history. Is there the scientific possibility that a 
vaccine would work in Alzheimer's?
    What is the state of the research in this area?
    Is NIA planning to fund any vaccination programs in fiscal year 
2018?
    Answer. Vaccination, a form of immunotherapy, using your body's own 
immune system to help fight disease, is one of many treatment 
modalities currently under study for both the prevention and treatment 
of Alzheimer's disease (AD). While we have every reason to hope that we 
will see positive results from these studies, our cautious optimism is 
tempered by the acknowledgement that previous vaccine trials have been 
largely unsuccessful. For example, in 2002 a trial of AN1792, the first 
vaccine to target deposition of beta-amyloid, a pathological hallmark 
of the disease, ended early because dangerous brain inflammation 
occurred in some patients. More recently, industry-supported clinical 
trials of passive immunization (i.e., direct transfer of antibodies 
that attack beta-amyloid) with the monoclonal antibodies bapineuzumab 
and solanezumab produced disappointing results.
    However, these studies were initiated in individuals who were 
already showing clinical symptoms of the disease, and more recent 
vaccine studies are targeting at-risk individuals much earlier in the 
disease course, before symptoms appear. For example, the Alzheimer's 
Prevention Initiative Autosomal Dominant Alzheimer's Disease (API-ADAD) 
study is exploring ``preventive immunotherapy'' among members of a 
large extended family that carries a genetic mutation placing many 
members at greatly increased risk of developing the disease. Another 
study, the Dominantly Inherited Alzheimer's Network trial, evaluates 
the safety, tolerability and effectiveness of several drugs, including 
two vaccines, and will determine if they can prevent, delay, or even 
reverse Alzheimer's disease changes in the brain. The Alzheimer's 
Prevention Initiative APOE4 Trial (API APOE), or Generation 1 study, is 
determining the safety and efficacy of two drugs targeting beta-
amyloid, including an active immunotherapy injection, in older adults 
at genetic risk of the disease, while the Anti-Amyloid treatment in 
Asymptomatic AD Trial (A4 Trial) is evaluating a passive vaccine in 
clinically normal older adults with evidence of AD pathology on 
screening positron emission tomography imaging who are at risk for 
developing dementia.
    NIA also supports a large cooperative agreement to complete 
preclinical safety and efficacy testing for AV-1959D, a cutting edge 
``DNA vaccine.'' DNA vaccines use pieces of DNA from specific 
pathogenic proteins to stimulate an immune response and offer potential 
technical and safety advantages over conventional protein/adjuvant 
vaccines.
    More broadly, NIA supports research on underlying mechanisms of the 
immune system in the brain. For example, one study is exploring immune-
mediated mechanisms underlying clearance of beta-amyloid from the brain 
and central nervous system, while others are investigating possible 
immunotherapies targeting tau, another pathological hallmark of AD. All 
of this important work will be active in fiscal year 2018 and 2019.
                           trans-angiogenesis
    Question. In May 2013, the NIH hosted the NIH Trans-Angiogenesis 
Workshop. In March 2016, the NIH released a meeting summary, which 
included an outline of clear steps needed to bring angiogenesis 
research forward. The resources needed included:
  --Develop potential partnerships with pharmaceutical companies for 
        the development of new drugs that require investigations using 
        structural biology approaches and medicinal chemistry.
  --Develop cross-disciplinary NIH resources to increase research on 
        the molecular understanding of angiogenesis across therapeutic 
        fields, such as cancer, diabetes, obesity, and cardiovascular 
        diseases.
  --Develop a biomarker identification project that moves beyond 
        prognostic biomarkers to the development of validated 
        predictive biomarkers of clinical benefit (or lack of benefit) 
        and biomarkers of toxicity.
  --Improve the translation of basic research angiogenesis focused 
        findings across disciplinary fields to clinical applications.
  --Organize a cross-disciplinary meeting of basic science, 
        translational and clinical scientists and clinicians where NIH 
        grantees would be required to present their research.
  --Create trans-NIH Program Project Grants and Specialized Centers of 
        Clinically Oriented Research for angiogenesis research.
    Could you please provide the Subcommittee an update on the progress 
on these issues?
    Answer. Angiogenesis is the process of new blood vessel formation 
and growth that is vital for normal embryonic development, new blood 
vessel formation, and wound healing. Insufficient, excessive, or 
aberrant angiogenesis may have significant clinical consequences in 
diseases such as stroke, myocardial infarction, peripheral arterial 
disease, cancer, chronic inflammation, and retinopathy.
    Multiple NIH Institutes fund angiogenesis-related research aimed at 
improving the understanding of normal and abnormal angiogenesis and 
translating findings into therapeutic interventions.
    Because angiogenesis research applies to many diseases, the trans-
NIH workshop was convened to provide leaders in angiogenesis research 
an opportunity to examine the diverse nature of the sciences involved 
across the field, to identify current gaps, and to explore potential 
advantages in integrating basic, translational, and clinical research 
in the prevention and treatment of angiogenesis-related diseases.\82\ 
NIH has continued to address research gaps and focus on priorities 
identified by the workshop. Here are a few examples:
---------------------------------------------------------------------------
    \82\ https://prevention.cancer.gov/news-and-events/meetings-and-
events/trans-nih-angiogenesis-workshop/meeting-summary.
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                    basic and translational research
    Research supported by the National Heart, Lung, and Blood Institute 
(NHLBI) has contributed to a better understanding of angiogenesis 
mechanisms at the molecular and cellular level.\83\ Signaling pathways 
and regulation of angiogenesis have been better defined,\84\ as has the 
role of inflammation and metabolism of cells that line the interior 
surface of vessels in angiogenesis.\85\ For example, researchers found 
that changes in endothelial cell glucose, fatty acid, and protein 
metabolism may function as a ``metabolic switch'' for angiogenesis. 
Further investigation of these pathways is ongoing to identify 
biomarkers of endothelial cell health and disease and to discover 
potential ways to alter defective angiogenesis.
---------------------------------------------------------------------------
    \83\ http://circres.ahajournals.org/content/120/11/1713/tab-
supplemental.
    \84\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966612/.
    \85\ https://www.ncbi.nlm.nih.gov/pubmed/29795441.
---------------------------------------------------------------------------
    Recognizing that cancers need a blood supply to grow and spread, 
the National Cancer Institute (NCI) provides support for research on 
elucidating the cellular mechanisms that give rise to the creation of 
new blood vessels and the therapeutic potential of anti-angiogenesis 
drugs. One area of particular interest is the action of vascular 
endothelial growth factor (VEGF) and other signaling molecules that 
stimulate angiogenesis. Since the discovery of VEGF almost 30 years 
ago, these proteins have become a major target for therapy; drugs that 
inhibit VEGF have become an intensively studied--and in some cases, 
successful--approach to block abnormal angiogenesis.
    Yet, some cancers are also resistant to these inhibitors. 
Researchers are examining the basic mechanisms of resistance in 
glioblastoma, with a focus on VEGF and stromal-cell derived factor 1 
(SDF-1), a protein involved in tumor growth and metastasis.\86\ NCI 
also supports basic research into tumor microenvironments, which may 
help illuminate future therapeutic pathways. Examples include a project 
examining the role of low oxygen, acidity, and depleted nutrient levels 
in the tumor microenvironment, and the effects these factors may have 
on glioblastoma angiogenesis,\87\ as well as a study on how immune 
system activity promotes angiogenesis in melanoma tumor 
microenvironments.\88\
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    \86\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=8997986.
    \87\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9274829.
    \88\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9236367.
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    Angiogenesis research is also relevant to stroke, as collateral 
blood vessels around a blocked vessel can provide an alternative path 
for blood flow to the brain. Researchers funded by the National 
Institute on Neurological Disorders and Stroke (NINDS) are exploring 
the molecular and genetic mechanisms that determine the number and size 
of collateral vessels around major arteries, as well as the remodeling 
of these vessels after a stroke. Researchers also are exploring the 
role of angiogenic pathways in brain blood vessel stability and the 
risk for hemorrhage, as well as in processes that support protection 
and recovery of brain tissue following a stroke. Additionally, NINDS-
funded investigators are exploring avenues to improve the effectiveness 
of angiogenesis inhibitors for treating brain cancers such as 
glioblastoma. Ongoing work is investigating the molecular mechanisms 
that lead to therapeutic resistance, and tumor recurrence and 
progression.
    Angiogenesis research is also important to eye health. Diabetes and 
the most common type of age-related macular degeneration (AMD) can 
cause vision loss due to abnormal blood vessels in the retina. 
Researchers funded by the National Eye Institute (NEI) have 
demonstrated that gene therapy can be used effectively to block 
proteins in the VEGF pathway to reduce vision loss in animal 
models.\89\ This proof of concept supports a novel treatment for 
angiogenesis-related retinopathy.
---------------------------------------------------------------------------
    \89\ https://www.ncbi.nlm.nih.gov/pubmed/29730824.
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                           clinical research
    The NCI hopes to expand the successes of angiogenesis inhibitors in 
treating cancer and currently supports clinical trials of these agents 
to treat glioblastoma, pancreatic cancer, metastatic breast cancer, 
prostate cancer, ovarian cancer, colorectal cancer, lung cancer, liver 
cancer and other solid tumors. Many of these trials involve the 
therapeutic agent bevacizumab (Avastin), a monoclonal antibody directed 
against VEGF.
    The NHLBI also funds significant clinical research relating to 
angiogenesis. This includes a planning grant for a clinical trial 
testing an anti-angiogenesis drug to treat hereditary hemorrhagic 
telangiectasia, a genetic disorder that involves abnormal blood vessel 
formation and can result in hemorrhage and stroke.
    NHLBI has also supported, research to develop pro-angiogenic 
factors to treat ischemic diseases that restrict blood supply. Such 
efforts have not yielded reproducible and sustained success in late-
stage clinical trials.\90\ While the use of pro-angiogenic stem cells 
may offer more promise, its clinical application is still limited.\91\
---------------------------------------------------------------------------
    \90\ https://journals.lww.com/cardiovascularpharm/Abstract/2014/
08000/Identifying_and_
Overcoming_Obstacles_in_Angiogenic.1.aspx.
    \91\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869986/.
---------------------------------------------------------------------------
    The Eunice Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD) supports a range of intramural and extramural 
research projects on aspects of angiogenesis, specifically on 
development of the utero-placental interface, placenta formation, and 
early development of the vascular system. In addition to investigator-
initiated research, NICHD also supports clinical research aimed at 
achieving healthier pregnancy outcomes through its Maternal Fetal 
Medicine Units network. Recently, similarities in the pathology of 
cardiovascular disease and preeclampsia, a dangerous spike in a 
pregnant woman's blood pressure, prompted NICHD-supported researchers 
to conduct a preliminary study of a commonly used cardiovascular drug 
in high-risk pregnant women in their second trimester. While the risk 
of preeclampsia was unchanged in women who received a placebo, women 
who received this drug did not develop preeclampsia.\92\
---------------------------------------------------------------------------
    \92\ https://www.ncbi.nlm.nih.gov/pubmed/?term=26723196.
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    A noninvasive retinal imaging approach called optical coherence 
tomography (OCT) has emerged as an effective tool to view the layers of 
the retina as well as any fluid leakage--a useful biomarker for AMD and 
for responses to treatment.\93\ Over the past decade, the introduction 
of anti-angiogenesis drugs, such as Avastin, Lucentis, and Eylea has 
revolutionized treatment of AMD, slowing the disease and even reversing 
vision loss in some cases. However, monthly treatment injections are 
expensive and not always needed. OCT is also used for treatment 
decisions for other angiogenesis-related causes of blindness, such as 
diabetic retinopathy.
---------------------------------------------------------------------------
    \93\ https://www.ncbi.nlm.nih.gov/pubmed/29077605.
---------------------------------------------------------------------------
                           trans-nih efforts
    Question. Several NIH Institutes are involved in a Neuroscience 
Blueprint initiative--Neurobiology of Small Blood and Lymphatic Vessels 
in Health and Disease. This initiative will support the development of 
innovative tools and technologies to explore heterogeneity of small 
blood and lymphatic vessels in the central nervous system (CNS), as 
well as human studies to identify targets, biomarkers, and mechanisms 
specific to CNS small blood and lymphatic vessels. This initiative 
emerged from a trans-NIH scientific workshop on the role of small 
vessels in health and disease across different organ systems in the 
body.\94\ While not specifically focused on angiogenesis research, it 
may support angiogenesis projects.
---------------------------------------------------------------------------
    \94\ https://www.ncbi.nlm.nih.gov/pubmed/27815267.
---------------------------------------------------------------------------
    Because angiogenesis plays an essential role in health and is 
implicated in a wide range of diseases and disorders, the NIH will 
continue to support a full spectrum of research in this area, including 
development of pro- and anti-angiogenic therapies.
                                 ______
                                 
             Questions Submitted to Norman Sharpless, M.D.
                Questions Submitted by Senator Roy Blunt
            cancer research & treatment in rural communities
    Question. The network of National Cancer Institute-designated 
cancer centers and comprehensive cancer centers play an important role 
in our national efforts to prevent, diagnose, and treat cancer. As 
someone from a rural state who understands the difficulty in access to 
cancer treatments in rural and remote areas, Dr. Sharpless, can you 
describe how existing resources are used to help those Americans in 
rural and underserved communities?
    How do NCI-designated cancer centers ensure those in rural 
communities can benefit from clinical trials and breakthrough cancer 
treatments?
    Answer. Rural communities face disadvantages compared with urban 
areas, including higher poverty, lower educational attainment, and lack 
of access to health services. These challenges contribute to higher 
incidence of certain cancers and worse cancer-related outcomes in low-
income, underserved rural populations. New data has shown that--for the 
first time--cancer death rates are higher in rural areas than in urban 
areas. This shift has been demonstrated by two studies--one by NCI 
researchers \95\ and one led by researchers from the Centers for 
Disease Control and Prevention (CDC).\96\
---------------------------------------------------------------------------
    \95\ https://www.ncbi.nlm.nih.gov/pubmed/28600296.
    \96\ https://www.cdc.gov/mmwr/volumes/66/ss/ss6614a1.htm.
---------------------------------------------------------------------------
    There are several areas where the National Cancer Institute (NCI) 
plays a significant role in advancing rural cancer prevention and 
control research. Key areas include working with NCI's Community 
Oncology Research Program (NCORP) and NCI-Designated Cancer Centers to 
build on their experience with community outreach and developing 
partnerships with local organizations. To inform NCI's efforts to 
better address cancer disparities in rural communities, NCI is also 
convening researchers, community representatives, and providers to 
discuss these important issues. In May 2018, NCI hosted a diverse group 
of speakers from across these disciplines to discuss collaboration and 
coordination for rural cancer control. The objectives of the meeting 
were to (1) identify gaps in rural cancer research and practice; (2) to 
build partnerships across the country to address challenges and 
disseminate solutions; and (3) to highlight and identify methods to 
address competing and common agendas of clinics/providers, researchers, 
and community/patients.\97\
---------------------------------------------------------------------------
    \97\ https://cancercontrol.cancer.gov/research-emphasis/meetings/
arcc-meeting.html.
---------------------------------------------------------------------------
    NCI has a broad and growing range of research in this area and will 
continue to work with the cancer community and others to refine and 
reinvigorate our cancer control efforts in rural areas across the 
country. NCORP is a crucial part of NCI's efforts to prevent, diagnose, 
and treat cancer in rural populations.\98\ NCORP's mission is to bring 
clinical trials and cancer care delivery research to people where they 
live, with a special focus on rural communities. NCORP is comprised of 
seven research bases; 46 community sites, 12 of which are designated as 
minority/underserved; \99\ and more than 900 component sites across the 
country.\100\ NCORP community and component sites, which are comprised 
of public hospitals, physician practices, academic medical centers, and 
other groups that provide healthcare services in community settings, 
play an important role in accruing patients to NCI-supported research 
studies and clinical trials, including the groundbreaking NCI Molecular 
Analysis for Therapy Choice (NCI- MATCH) precision medicine cancer 
treatment trial.
---------------------------------------------------------------------------
    \98\ https://ncorp.cancer.gov/.
    \99\ NCORP minority/underserved sites have a patient population 
that is of at least 30 percent racial/ethnic minorities or rural 
residents.
    \100\ https://ncorp.cancer.gov/findasite/map.html.
---------------------------------------------------------------------------
    NCI-Designated Cancer Centers also play an increasingly important 
role in rural cancer control. There are currently 70 NCI-Designated 
Cancer Centers located in 36 States and the District of Columbia. These 
cancer centers develop and translate scientific knowledge from 
promising laboratory discoveries into breakthrough treatments for 
cancer patients. Each year, approximately 250,000 patients receive 
their cancer diagnosis at an NCI-Designated Cancer Center, and an even 
larger number of patients are treated for cancer and/or enrolled in a 
clinical trial at these centers.\101\ Cancer centers applying for NCI-
designation are required to describe the geographic area they intend to 
serve, and are encouraged to describe how the center plans to extend 
its reach beyond this catchment area to bring the center's expertise to 
bear on wider populations, including rural populations.\102\
---------------------------------------------------------------------------
    \101\ https://www.cancer.gov/research/nci-role/cancer-centers.
    \102\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-095.html.
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    To incentivize cancer center engagement in rural health, NCI has 
provided supplemental funding to 15 cancer centers to collect 
additional data concerning their catchment area population and align 
local measures with national ones, enabling more direct comparisons 
across centers and with national surveillance data. To extend this 
commitment, in fiscal year 2018, NCI plans to support NCI-Designated 
Cancer Centers in further developing their rural cancer control 
research capacity.
    In addition to the programs described above, NCI recently released 
a standalone Funding Opportunity Announcement (FOA) inviting 
applications for research aimed at improving the reach and quality of 
cancer care in rural populations.\103\ Depending on receipt of 
sufficiently meritorious applications, NCI intends to fund up to 10 
awards in fiscal year 2018.
---------------------------------------------------------------------------
    \103\ https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-18-
026.html.
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                            pediatric cancer
    Question. Dr. Sharpless, we hear a lot about the need for more 
research on childhood cancer, often from families who have lost a child 
to cancer. What is the National Cancer Institute doing to improve 
outcomes for children with cancer, and to address the factors that make 
childhood cancers unique?
    Answer. Pediatric cancer research remains a top priority for the 
National Cancer Institute (NCI), and each year the Institute identifies 
the best research opportunities to build upon the foundation of basic 
science, further develop the scientific understanding of genetic 
drivers of childhood cancers, identify effective therapies, and enhance 
the quality of life for pediatric cancer survivors.
    NCI recognizes cancers that strike infants, children, teens and 
even young adults are different from those that affect adults, and that 
they require specific research. Additionally, even when long-term 
survival is achieved, many survivors of childhood cancer experience 
serious long-term adverse effects from the disease or its treatment. 
Future discoveries made through additional research are needed so that 
new, more effective, and less toxic treatments for cancers that affect 
children and young adults can be developed.
    Recognizing that childhood cancers are distinct from adult cancers, 
NCI supports numerous targeted programs aimed at advancing research in 
pediatric oncology. These efforts include:
  --The Children's Oncology Group (COG),\104\ part of NCI's National 
        Clinical Trials Network (NCTN), develops and coordinates 
        pediatric clinical trials across more than 200 member 
        institutions. In addition to conducting late-phase clinical 
        trials, the COG receives NCI support for the Phase 1 and Pilot 
        Consortium,\105\ which conducts early-phase trials and pilot 
        studies to rapidly introduce new anticancer agents into 
        pediatric care.
---------------------------------------------------------------------------
    \104\ https://www.childrensoncologygroup.org/.
    \105\ https://www.childrensoncologygroup.org/index.php/phase-1-
home.
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  --The Pediatric Oncology Branch (POB) \106\ in NCI's Center for 
        Cancer Research, part of NCI's intramural research program, 
        conducts high-risk, high-impact basic, translational, and 
        clinical research.
---------------------------------------------------------------------------
    \106\ https://ccr.cancer.gov/Pediatric-Oncology-Branch.
---------------------------------------------------------------------------
  --The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) 
        Trial,\107\ launched in July 2017, tests molecularly targeted 
        therapies in children and adolescents with advanced cancers who 
        have few other treatment options. This nationwide trial is open 
        to children and adolescents from 1 to 21 years of age and 
        currently has eight treatment arms.
---------------------------------------------------------------------------
    \107\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/pediatric-match.
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  --Other efforts include the Pediatric Preclinical Testing Consortium 
        (PPTC),\108\ the Therapeutically Applicable Research to 
        Generate Effective Treatments (TARGET) \109\ program, the NCI 
        Experimental Therapeutics (NExT) Program,\110\ the Childhood 
        Cancer Survivor Study (CCSS),\111\ the Pediatric Provocative 
        Questions (PQ) Program,\112\ the Pediatric Brain Tumor 
        Consortium (PBTC),\113\ the Pediatric Cancer Immunotherapy 
        Trials Network (CITN),\114\ and the New Approaches to 
        Neuroblastoma Therapy (NANT) \115\ Consortium.
---------------------------------------------------------------------------
    \108\ http://www.ncipptc.org/.
    \109\ https://ocg.cancer.gov/programs/target.
    \110\ https://next.cancer.gov/.
    \111\ https://www.cancer.gov/types/childhood-cancers/ccss.
    \112\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-217.html.
    \113\ https://www.pbtc.org/.
    \114\ https://ctep.cancer.gov/MajorInitiatives/
cancer_immunotherapy_trials_network.htm.
    \115\ http://www.nant.org/.
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    In addition to these well-established programs, the Institute is 
enthusiastic about the scientific opportunities provided by the Cancer 
MoonshotSM to stimulate further investigation of pediatric cancers. 
Current programs supported by the Cancer MoonshotSM include the Fusion 
Oncoproteins in Childhood Cancers (FusOnC2) Consortium, which will seek 
to develop models of, and therapeutic agents for, fusion-driven 
childhood cancer; \116\ the Pediatric Immunotherapy Translational 
Science Network, which will aim to identify targets for immunotherapy 
treatments for pediatric patients; \117\ and the Rare Tumor Patient 
Engagement Network,\118\ which aims to study rare tumors, including 
pediatric tumors, and develop a network of clinical trials.
---------------------------------------------------------------------------
    \116\ https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-17-
049.html.
    \117\ The foundation of this initiative began in 2017, with the 
release of two FOAs to establish the Pediatric Immunotherapy Discovery 
and Development Network (PI-DDN): https://grants.nih.gov/grants/guide/
rfa-files/RFA-CA-17-051.html; https://grants.nih.gov/grants/guide/rfa-
files/RFA-CA-17-050.html.
    \118\ https://ccr.cancer.gov/research/cancer-moonshot.
---------------------------------------------------------------------------
    NCI is committed to addressing the unique scientific challenges and 
opportunities that pediatric cancers pose in ways that lead to better 
outcomes for children with cancer. NCI continues to demonstrate this 
commitment through its ongoing support for childhood and adolescent 
cancer research efforts, through a continued investment in basic 
research and other crosscutting research efforts, and through its 
collaborations with the childhood cancer community.
    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.\119\ Research on pediatric cancers will continue to be 
a top priority.
---------------------------------------------------------------------------
    \119\ http://www.cancer.gov/researchandfunding/areas/childhood.
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                indefinite delivery/indefinite quantity
    Question. It is my understanding that NIH is using more Indefinite 
Delivery/Indefinite Quantity (ID/IQ) awards, which can provide several 
advantages: (1) greater competition in the procurement process; (2) 
smaller well-defined program tasks; (3) tighter financial control on 
each program task; and (4) incremental milestone driven funding. 
However, many small, not-for-profit contractors have a difficult time 
justifying the large commitment of time and resources when contracts 
are small and delayed. Therefore, the return-on-investment for 
contractors is becoming harder to justify. Can you discuss the issues 
NIH faces with ID/IQ contracts and why they are not being more 
regularly awarded?
    Answer. NIH makes regular use of Indefinite Delivery/Indefinite 
Quantity (ID/IQ) contracts and continues to look for more opportunities 
to establish new or use existing ID/IQs. We carefully consider small 
business opportunities when establishing or using the ID/IQs. The 
advantages of establishing multiple award ID/IQs far outweigh the 
challenges. However, one challenge is once the contracts are awarded, 
new vendors tend to be unable to pursue NIH business for a period of 
time because so much of the ordering is limited to the existing 
contractors. Additionally, due to bid protests, NIH tends to award 
contracts to a large number of contractors rather than limiting the 
awardees to a smaller, more manageable pool. This tends to make the 
competition at the task order level less efficient. Small companies 
often feel the investment of time and energy expended when pursuing an 
ID/IQ is potentially wasted when the competition for individual task 
orders involves so many competitors and requires additional resources 
to receive the order. One last issue is the inability to award flexible 
orders when issuing task orders against multiple award ID/IQs. The firm 
nature of the orders often cause the NIH program to consider other 
arrangements such as a Blanket Purchase Agreement (BPA) against a GSA 
Schedule contract.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray
                          functional genomics
    Question. Fred Hutch researchers recently received NCI funds to 
continue work on an approach termed functional genomics, in which they 
focus directly on a patient's tumor cells. The approach can be applied 
toward different types of cancer, to pinpoint which drugs work best for 
an individual patient's tumor and identify drug resistance. With this 
new infusion of funding, researchers will have the opportunity to 
identify new drug targets in difficult to treat cancers and collaborate 
with various partners to help oncologists deliver individually tailored 
therapies to cancer patients. Can you tell me more about NCI's plans to 
support this type of highly targeted treatment?
    Answer. The National Cancer Institute (NCI) is supporting a wide 
range of cancer genomic programs focused on understanding how cancer 
develops, the molecular changes that drive cancer, and the vast tumor 
heterogeneity within and across cancers. Precision oncology is rooted 
in a deep understanding of the genetic and functional changes that 
occur in cancer cells and the tumor microenvironment. NCI is committed 
to supporting research in genomics and other disciplines to increase 
our understanding of the complexity of cancer biology to advance 
precision oncology.
    The NCI Center for Cancer Genomics (CCG) unifies NCI's activities 
in cancer genomics by aiming to synthesize research in different fields 
of cancer genomics. CCG's programs and collaborations generate cancer 
genomic and clinical data, and, importantly, make these data available 
for widespread use by the research community. Using a collaborative 
``team science'' approach, CCG engages in three complementary sub-
disciplines within cancer genomics: structural genomics, functional 
genomics, and computational genomics. Structural genomics identifies 
alterations in cancer that contribute to cancer growth, metastasis, and 
recurrence. Functional genomics studies the role of cancer genes, 
mutations, and pathways, and develops therapeutic strategies to target 
them. Computational genomics uses statistical and computational 
approaches to derive insight from big data on cancer. By testing 
hypotheses derived from structural genomics research, and by generating 
new ideas from experiments in cancer cells, functional genomics 
research reveals patterns in cancer biology that can be translated into 
novel therapies for precision cancer care.
    To translate genomic insights to the clinic, the findings must be 
tested in models of cancer to understand the functional impact of 
insults to the genome. In addition to supporting investigator-initiated 
grants and other extramural research in this area, NCI provides 
resources to the extramural community to support their research on the 
molecular changes that drive cancer. One example is The Cancer Genome 
Atlas (TCGA),\120\ which contains the genomes of more than 30 types of 
cancer and catalogues thousands of genetic alterations in cancer cells 
that could be targets for existing or new therapies. Another example is 
the Genomics Data Commons (GDC), a unified data system for sharing 
genomic and clinical data launched in 2016. The GDC centralizes, 
standardizes, and makes data from large-scale NCI programs more 
accessible and useful to scientists and clinicians. One measure of the 
importance of this resource is that non-profit and for-profit 
organizations are now offering their data sets for sharing through the 
GDC.
---------------------------------------------------------------------------
    \120\ Collaboration with the National Human Genome Research 
Institute.
---------------------------------------------------------------------------
    One program geared towards bridging the knowledge gap between data 
generated from large-scale genomic studies and the underlying etiology 
of cancer development, progression, and/or metastasis is the Cancer 
Target Discovery and Development (CTD) \96\ Network. The CTD \96\ 
Network is accelerating the use of molecular data to speed the 
translation of basic science findings to clinical trials. Through 
validation studies that rely on bioinformatics analysis of genomic 
data, high-throughput screening of small molecules, and research that 
involves cancer models or other tools, the CTD \96\ Network supports 
research to capitalize on a growing volume of data to identify new 
cancer vulnerabilities and treatments.
    The initial phase of CTD \96\ Network generated 19 novel 
bioinformatic tools which enable the identification of therapeutic 
targets, gene and molecular networks, and driver mutations (genetic 
changes that drive the development of cancers), and chemical 
sensitivities. These tools are available to the scientific community 
and can be accessed through the CTD \96\ analytical tools page.\121\ 
During the first phase, the Network has been highly successful and 
published over 60 manuscripts with preclinical and clinical 
relevance.\96\ The results from some studies have provided supporting 
evidence for the initiation of several clinical trials.\122\ Highlights 
of progress during this first phase include the discovering the 
mechanism of action of a compound that selectively inhibits the growth 
of breast cancer stem cells, and the discovery of novel, rare driver 
mutations in pancreatic cancer and confirmation of their importance 
through validation studies in model systems.
---------------------------------------------------------------------------
    \121\ https://ocg.cancer.gov/programs/ctd2/analytical-tools.
    \122\ https://ocg.cancer.gov/programs/ctd2/publications.
---------------------------------------------------------------------------
    The second phase of the CTD \96\ Network (multi-year awards funded 
in fiscal year 2017) is exploring cancer complexity in terms of various 
types of heterogeneity, that is differences in genetic characteristics 
within each patient (i.e., across tumor tissue, the tumor 
microenvironment, and normal tissue), as well as genetic differences 
within each tumor (i.e., different tumor cells may have different 
genomic characteristics and molecular drivers). Projects seek to 
understand the potential impacts of heterogeneity (i.e., acquired 
resistance to chemo and immunotherapies) and develop efficient 
strategies to overcome treatment resistance. Through active 
collaboration and the sharing of data and resources with the cancer 
research community, each of the twelve funded Centers within the CTD 
\96\ Network will utilize functional and computational genomic 
approaches to contribute to the understanding of mechanisms of cancer 
and potentially accelerate the development of clinically useful 
markers, targets, and therapeutics for precision oncology.
    Complimenting these efforts, NCI is supporting development of the 
Human Tumor Atlas Network (HTAN) as part of the Cancer Moonshot.\SM\ 
The HTAN is planned to be a 5-year pilot consortium focused on 
generating comprehensive, multidimensional tumor atlases (detailed 
mapping of molecular and cellular characteristics) describing key 
transitions in the development of cancer that will inform future cancer 
research and, ultimately, clinical decisionmaking. The HTAN efforts 
build upon and extend the efforts of TCGA. The HTAN will draw upon the 
lessons learned from TCGA, address its limitations, and use evolving 
state-of-the-art information technology and other emerging technologies 
to achieve its goal. Additional efforts supported by the Cancer 
Moonshot,\SM\ such as those focused on cancer immunology and 
immunotherapy, will increase our knowledge of genetic changes that 
occur in cancer cells and the tumor microenvironment to enable use of 
precision immunotherapy for both adult and pediatric cancer patients.
    Currently ongoing Precision Oncology trials that utilize molecular 
characterization to inform treatment choice include the NCI Molecular 
Analysis for Therapy Choice (NCI-MATCH) Trial and the Pediatric MATCH 
Trial. For these trials, rather than selecting therapies based on where 
a tumor originated in the body, the focus is on evaluating the 
effectiveness of treating cancer based on specific genetic changes. In 
2017, the adult NCI-MATCH Trial achieved its enrollment goal, nearly 2 
years ahead of schedule. The trial involves more than 6,000 patients 
from all 50 States. NCI also successfully opened enrollment for the 
Pediatric MATCH Trial in 2017. Other NCI precision medicine trials 
include the Lung Cancer Master Protocol (Lung-MAP) Trial, the Adjuvant 
Lung Cancer Enrichment Marker Identification and Sequencing Trials 
(ALCHEMIST), and Molecular Profiling-Based Assignment of Cancer Therapy 
(NCI-MPACT) Trial.
    NCI's investment in cancer genomics programs such as the CTD \96\ 
and the HTAN will inform future precision medicine trials and build 
upon the results of ongoing trials in this paradigm changing approach 
to precision oncology for cancer patients.
                          nci-funded research
    Question. Dr. Sharpless, cancer immunotherapy is one of the great 
success stories of NCI-funded research. After decades of basic 
research, patients today are receiving immunotherapy treatments for a 
growing number of cancers, including melanoma, lung cancer, lymphoma, 
leukemia, head-and-neck cancer, and more. Many of these patients 
previously had few other treatment options. Some who had even very 
advanced cancer are now doing extremely well. And, we are just getting 
started. What is being done to educate healthcare providers about the 
principles of immunotherapy and how to manage the toxicity? And what 
efforts is NCI taking to retrain laboratory scientists to advance the 
immunotherapy field?
    Answer. Immunotherapy, a treatment that uses a patient's own immune 
system to help fight diseases including cancer, is a major focus of 
National Cancer Institute (NCI)-supported research that spans basic 
science to clinical applications. NCI-supported researchers publish 
their research results in peer-reviewed journals, and frequently 
present their research at professional conferences, including the 
annual meetings of the American Association of Cancer Research (AACR) 
and the American Society of Clinical Oncology (ASCO). For example, at 
the June 2018 meeting of ASCO, NCI-supported researchers participated 
in a two-day seminar entitled ``Cancer Immunotherapy Today: Maximizing 
Patient Outcomes,'' co-hosted by ASCO and the Society for Immunotherapy 
of Cancer (SITC).\123\ This session provided continuing education to 
clinical oncologists, nurses, pharmacists, and the entire medical team 
on effectively providing the most up-to-date and comprehensive 
immunotherapy options to their patients, and included guidance on 
patient selection and managing toxicities.
---------------------------------------------------------------------------
    \123\ https://www.sitcancer.org/events/event-
description?CalendarEventKey=796e7e32-bba9-
4712-9491-daed98d7a3c8&Home=%2fevents%2fcalendar.
---------------------------------------------------------------------------
    NCI supports training for immunotherapy investigators across the 
research spectrum, from basic to translational to clinical research. 
NCI's Center for Cancer Research (CCR) supports an Immunotherapy 
Fellowship for physicians who have completed a medical oncology 
fellowship program and who seek specialized training in immunotherapy, 
including the design and facilitation of clinical trials.\124\ 
Immunotherapy researchers are encouraged to apply for NCI-supported 
training awards.\125\ Different awards are available to pre- and post-
doctoral researchers, clinical fellows, established investigators, and 
non-tenured early-career stage faculty.
---------------------------------------------------------------------------
    \124\ https://www.cc.nih.gov/training/gme/programs/
immunotherapy.html.
    \125\ https://www.cancer.gov/grants-training/training/funding.
---------------------------------------------------------------------------
    NCI's intramural Center of Excellence in Immunotherapy (CEI) 
focuses on creating opportunities for immunologists in the intramural 
and extramural communities to exchange information and to facilitate 
collaborations. To that end, CEI sponsors an annual series of meetings 
on cancer-related immunology research, with the next meeting entitled 
``Frontiers in Basic Immunology'' \126\ planned for September 2018. 
Prior meetings included the 2017 ``Cancer and Immunology and 
Immunotherapy: From Conception to Delivery,'' meeting and the 2016 
``Immunotherapy Biomarkers 2016: Overcoming the Barriers'' meeting. 
Videos of the presentations and discussions are freely available 
online.\127\
---------------------------------------------------------------------------
    \126\ https://ncif-staging.ncifcrf.gov/Events/Conferences/
Frontiers/.
    \127\ https://ncif-staging.ncifcrf.gov/Events/Conferences/
Frontiers/PastConferences.aspx.
---------------------------------------------------------------------------
    In addition to these resources, NCI plans to support new training 
and education efforts in fiscal year 2018 including supplemental 
training awards for cancer immunotherapy, and additional funding to 
support the development of a consortium. The consortium will engage 
external partners that will develop standardized educational content 
for oncology care providers and deliver the content nationwide.
    NCI will continue to encourage the dissemination of research 
advances and the career development of the immunotherapy research 
community.
                                 ______
                                 
                Questions Submitted to Nora Volkow, M.D.
                Question Submitted by Senator Roy Blunt
                              chronic pain
    Question. Dr. Volkow, unfortunately, much of the opioid crisis we 
are experiencing today can be linked to opioid prescriptions to treat 
chronic pain. Your Institute has studied the effectiveness and risks 
associated with long-term opioid use for chronic pain, but what 
research is currently ongoing related to new and alternative options to 
treat chronic pain other than opioids?
    Answer. In fiscal year 2017, NIH spent $516 million on pain 
research ranging from cell and molecular mechanisms of acute and 
chronic pain to safe, effective therapy development, to large scale 
clinical trials. The portfolio includes many research projects that 
address the pressing need to develop new non-opioid, non-addictive, 
pain treatments. Research studies range from early-stage drug target 
discovery focusing on molecular pathways of pain signaling, including 
exploration of receptors and channels as potential non-addictive 
analgesic targets to testing in behavioral models. A number of targets 
identified through NIH basic science, such as nerve growth factor 
receptor and pain-related ion channels, are now being pursued in 
industry-sponsored clinical trials for non-addictive treatments. NIH 
supported early development of calcitonin receptor gene protein, a 
compound recently approved for migraine treatment.
    A tissue--based tool for screening potential migraine drugs is 
under development and a library of small molecules is being leveraged 
to screen candidates for optimization as analgesics. Tissue engineering 
and regeneration to create tissue scaffolding and microenvironments to 
promote wound healing, joint cartilage, and intervertebral disc 
replacements is being applied to relieve pain. Neural stimulation 
technologies for chronic, intractable pain are being improved. For 
example, wearable ultrasound devices and implantable micro-stimulators 
are being tested on peripheral and central nervous system targets to 
relieve pain.
    Evaluation and dissemination of complementary and integrative 
health approaches is a crucial component of quality pain management. 
NIH-supported studies include mechanism-based clinical studies on 
cognitive behavior therapy, exercise, yoga, acupuncture, massage, 
fitness, and mindfulness practices are an important component of the 
NIH Federal pain research portfolio.
                                 ______
                                 
             Question Submitted by Senator Joe Manchin, III
               research into alternative pain management
    Question. Dr. Volkow, communities across the country are seeing an 
alarming rise in substance abuse and addiction to prescription opioids. 
Opioids killed more than 42,000 Americans in 2016. That's 115 people 
every day. In West Virginia, we lost more than 909 people to a drug 
overdose in 2017.
    So many of these people who become addicted started taking these 
drugs because their doctor prescribed them for pain even though--
according to the CDC--there is little evidence that opioids improve 
chronic pain.
    This is a public health crisis and we have to find a better way. I 
am proud to have worked with my colleagues to dedicate an additional 
$500 million to NIH for research on opioid addiction, the development 
of opioid alternatives, pain management, and addiction treatment.
    That is why I am so worried about the President's Budget Request to 
cut more than $500 million from the National Institute on Drug Abuse.
    Dr. Volkow, what research is being done to develop non-addictive 
alternative pain management options for patients--particularly those 
dealing with long-term, chronic pain who are currently being prescribed 
opioids despite the lack of evidence of their effectiveness?
    What impact would the proposed budget cuts have on NIDA's ability 
to do continue to do this research?
    Answer. Chronic pain is a complex neurological condition, driven by 
many biological, environmental, social, and developmental factors. To 
this end, NIH supports a range of activities to advance research on 
understanding and treating pain.
    Chronic pain is a disorder of brain circuits, and the 
neurotechnologies emanating from the trans-NIH Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative enable 
scientists to explore these circuits to advance diagnostics and 
therapeutics. Similarly, the Stimulating Peripheral Activity to Relieve 
Conditions (SPARC) program at the NIH Common Fund supports novel means 
to alter peripheral nerve pathways to relieve pelvic pain and has 
promise for application to other pain conditions.
    Complementary and integrative health approaches address the 
biopsychosocial nature of chronic pain and its treatment. NIH supports 
numerous clinical studies on cognitive behavioral therapy (CBT), 
exercise, yoga, acupuncture, massage, fitness, and mindfulness 
practices. For example, trials showed that mindfulness-based stress 
reduction with CBT and yoga improved function and reduced low back 
pain.
    The NIH Health Care Systems Research Collaboratory supports large-
scale, pragmatic clinical trials focused on the management of patients 
with multiple chronic conditions, including pain. One study is 
evaluating multidisciplinary approaches to pain management in the 
primary care setting in patients who are currently on long-term 
opioids. This large-scale trial aims to develop integrated pain care 
approaches to reduce pain and opioid use in patients enrolled in a 
large healthcare system. The NIH, Department of Defense and Department 
of Veterans Affairs Pain Management Collaboratory's goal is to develop 
the capacity to implement cost-effective large-scale clinical research 
in military and veteran healthcare delivery organizations focusing on 
non-pharmacological approaches to pain management and other comorbid 
conditions.
    To accelerate the development of novel non-addictive chronic pain 
medications and devices, NIH is establishing a Clinical Trial Network 
to optimize analgesic trial design, target appropriate patient 
populations for trials, and engage research expertise at existing 
clinical sites. A related initiative is to pursue, through the Network, 
development and validation of biomarkers of pharmacodynamic response 
and biomarkers for treatment response to optimize patient 
stratification based on phenotyping and thus allow smaller sample size 
and improve assay sensitivity for screening novel analgesics. These 
efforts provide a valuable set of clinical research resources which 
will allow researchers to identify effective pain medications more 
quickly.
    The NIH Common Fund is currently in the planning stages of a broad 
scale clinical study to identify a set of objective biomarkers to 
predict which patients will transition to chronic pain after an acute 
pain event. This program, known as Acute to Chronic Pain Signatures 
Program, will collect longitudinal data from two large patient groups 
that have acute pain associated with a surgical procedure or an acute 
musculoskeletal trauma such as a bone fracture. Neuroimaging, genetic 
and molecular data, sensory testing, and psychosocial assessments from 
patients will be collected for months after the acute pain event and 
analyzed to explore transition or resilience characteristics to help 
predict which patients will recover and which patients will develop 
long-lasting pain. Identifying such markers will help to predict which 
people might be at risk for developing chronic pain, reducing reliance 
on opioids thereby, guide precision medicine approaches to prevent 
chronic pain, and by doing so, reducing our reliance on opioids.
    The current state of the science, emerging technologies, and 
mobilization of the research community holds great promise for advances 
in evidence-based, quality pain care.

                          SUBCOMMITTEE RECESS

    Senator Blunt. The subcommittee stands in recess.
    [Whereupon, at 11:38 a.m., Thursday, May 17, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]


              MATERIAL SUBMITTED SUBSEQUENT TO THE HEARING

    [Clerk's Note.--The following outside witness testimony was 
received subsequent to the hearing for inclusion in the 
record.]
 Prepared Statement of Christopher P. Austin, M.D., Director, National 
              Center for Advancing Translational Sciences
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National Center 
for Advancing Translational Sciences (NCATS) of the National Institutes 
of Health.
    NCATS is dedicated to understanding and transforming translation, 
defined as the process of turning scientific, medical, and public 
health observations in the laboratory, clinic, and community into 
interventions that improve the health of individuals and the public. At 
a time of unprecedented science discoveries, our collective ability to 
translate research findings into health benefits often is too slow and 
ineffective. Developing a new drug requires on average 10 to 15 years 
and more than $2 billion given the high prevalence of failure along the 
translational pipeline. We must deliver the promise of science to 
patients in an accelerated and more efficient manner. NCATS studies and 
supports translation on a system-wide level as a scientific and 
operational problem, addressing roadblocks that impede or preclude 
promising advances.
                   accelerating clinical translation
    The largest portion of NCATS' budget is dedicated to its Clinical 
and Translational Science Awards (CTSA) Program. Through this program, 
NCATS supports a national network of medical research centers, called 
hubs, that collaborate locally, regionally, and nationally to foster 
innovation in clinical researcher training, patient engagement, and new 
research tools and processes. There are multiple initiatives within 
this program, including the Trial Innovation Network that is composed 
of the hubs as well as Trial Innovation Centers and a Recruitment 
Innovation Center. Through this network, researchers are identifying 
and implementing ways to improve the clinical trial process, including 
participant recruitment and other aspects of clinical trial conduct.
    The process of obtaining ethics approval from multiple 
institutional review boards (IRBs) to conduct a clinical research study 
at multiple institutions is a longstanding challenge that can lead to 
significant delays in study activation. To address this problem, NCATS 
supported the development of a single IRB reliance platform for 
multisite clinical studies, enabling study sites to rely on a single 
IRB of record. The platform, known as the Streamlined, Multisite, 
Accelerated Resources for Trials (SMART) IRB, includes resources such 
as umbrella agreements, guidance documents, and consultation services 
that investigators nationwide can access to harmonize and streamline 
IRB review for their own multisite studies. SMART IRB is serving as a 
roadmap to help implement the NIH policy released in June 2016 that 
requires all NIH-funded multisite clinical studies to use a single IRB.
    Providing the resources to train, cultivate, and sustain future 
leaders of the biomedical research workforce is another key CTSA 
Program emphasis. The program supports a coordinated, national effort 
to help ensure a pipeline of trained translational investigators who 
can move basic research findings into applications for improving health 
outcomes as novel therapies, diagnostics, and preventives. Program 
grantees have developed clinical and translational sciences training 
resources, including educational core competencies, best practices for 
training mentors, and curriculum materials. These tools are freely 
available, and many institutions nationwide are using them.
    Engaging patients at all stages of translation is crucial; their 
perspectives as members of the research team provide insights, focus, 
urgency and connectivity that can be instrumental in making the 
development, testing and deployment of new interventions more 
effective. NCATS supports the Rare Diseases Clinical Research Network 
(RDCRN) and requires each consortia member to include patient groups as 
full partners on their research teams, an approach that helps achieve 
greater success. The RDCRN Coalition of Patient Advocacy Groups 
develops and shares best practices, and the RDCRN website includes a 
contact registry for patients who may be interested in participating in 
RDCRN clinical studies. Rare diseases, which cumulatively affect 
approximately one in 10 people in the U.S., are in crucial need of 
innovative translational technologies, and are thus a crucial NCATS 
focus.
    Measurable outcomes can help determine whether a new translational 
process is actually an improvement. NCATS' Discovering New Therapeutic 
Uses for Existing Molecules program matches academic investigators with 
pharmaceutical companies that have compounds that were found to be 
ineffective in treating specific diseases. Repurposing these compounds 
for potentially treating other diseases saves time in the drug 
development process because significant foundational work already has 
been completed. NCATS helps to further accelerate this process by 
providing collaboration agreement templates that now are being used 
broadly in the research community and by supporting researchers with 
new ideas for how existing compounds can be repurposed.
                finding new therapies for clinical study
    NCATS also is dedicated to removing pre-clinical translational 
science roadblocks. Through its Therapeutics for Rare and Neglected 
Diseases (TRND) program, the Center works to ``de-risk'' potential 
therapeutics so that private sector companies may be more inclined to 
acquire them to finish their development.
    Despite promising results in clinical trials outside of the U.S., 
work on further developing a gene therapy for the rare pediatric 
disease aromatic L-amino acid decarboxylase (AADC) deficiency was 
seemingly insurmountable. Through TRND, NCATS teamed with a private 
sector partner, Agilis Biotherapeutics, to convert promise into 
reality, jointly creating a manufacturing process for a therapy that 
complies with FDA regulations, and obtaining the required pre-clinical 
data. In addition to getting this potentially lifesaving therapy to 
patients, this project established technological and regulatory models 
that will accelerate development of other rare disease gene therapies.
    The NCATS Cures Acceleration Network (CAN) supports high-risk, 
innovative programs to advance the development of high-need cures and 
reduce significant barriers between research discovery and clinical 
trials. Through the CAN-funded Tissue Chip for Drug Screening program, 
NCATS is working on new methods for predicting both safety and efficacy 
of experimental drugs using engineered ``chips'' that contain human 
cells and model human organs. Current methods such as animal and cell 
models are not always reliably predictive and can result in wasted time 
and effort. In addition to developing these chips for testing potential 
drugs, NCATS soon will send tissue chips to the International Space 
Station (ISS) for research on the effect of microgravity on these model 
organs. Microgravity can accelerate aging and have other effects 
relevant to diseases on Earth, making the ISS a unique and significant 
research environment.
    New drug development for currently untreatable diseases has been 
greatly limited because known chemical structures affect only 10 
percent of potential drug targets within the human body. With CAN 
support, NCATS plans to launch its Automated Synthesis Platform for 
Innovative Research and Execution (ASPIRE) program to bring together 
chemistry, robotic engineering, biological activity testing, and 
artificial intelligence. Tools developed through ASPIRE will minimize 
the time chemists spend on tedious and repetitive tasks, freeing them 
up for more complicated pursuits such as designing, synthesizing, and 
testing compounds for diseases that currently have no treatment.
          adaptability to tackle emerging public health needs
    With its unique collection of programs, initiatives and resources, 
NCATS has the capacity and capability to address public health crises. 
For example, a team of researchers from NCATS and the Icahn School of 
Medicine at Mount Sinai developed a miniaturized assay for high-
throughput screening to find compounds that block the ability of Ebola 
virus-like particles (VLPs) to enter and infect cells. A screen using 
2,816 compounds identified 53 drugs with entry-blocking activity 
against Ebola VLPs.
    In another example, investigators from Johns Hopkins University and 
Florida State University collaborated with NCATS experts on drug 
repurposing and high throughput screening to identify rapidly two 
classes of existing compounds that potentially can be used to fight 
Zika. These compounds were effective either in inhibiting the 
replication of the Zika virus or in preventing the virus from killing 
brain cells. All data have been made available through public 
databases, allowing these compounds to be further studied by the 
broader research community.
    NCATS also is well-positioned to help combat the current national 
epidemic of opioid abuse. The Center's high-throughput screening 
facility could be used to test potential opioid abuse therapeutics, and 
CTSA Program-supported researchers could help identify opioid patients 
and rapidly enroll them in multisite clinical trials.
                               conclusion
    Through its programs and initiatives described above, and others, 
NCATS is improving health through smarter science in unprecedented 
ways, with the ultimate goal of getting more treatments to more 
patients--and to the public at large--more quickly.
                                 ______
                                 
Prepared Statement of Dr. James F. Battey, Jr., M.D., Ph.D., Director, 
   National Institutue on Deafness and Other Communication Disorders
    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's fiscal year 2019 budget request for the 
National Institute on Deafness and Other Communication Disorders 
(NIDCD) of the National Institutes of Health (NIH).
    NIDCD conducts and supports research and research training in the 
normal and disordered processes of hearing, balance, taste, smell, 
voice, speech, and language. NIDCD focuses on disorders that affect the 
quality of life of millions of Americans in their homes, workplaces, 
and communities. The physical, emotional, and economic impact for 
individuals living with these disorders is tremendous. NIDCD continues 
to make investments to improve our understanding of the underlying 
causes of communication disorders, as well as their treatment and 
prevention. It is a time of extraordinary promise, and I am excited to 
be able to share with you some of NIDCD's ongoing research and planned 
activities on communication disorders.
          preventing hearing loss caused by common cancer drug
    NIDCD intramural researchers have discovered why cisplatin and 
other popular and effective platinum-based chemotherapy drugs cause 
ototoxicity--damage to the delicate cells in the inner ear which can 
lead to hearing loss. In previous studies, researchers have focused on 
why the inner ear is more vulnerable to cisplatin ototoxicity than 
other areas in the body. The NIDCD research team, however, studied the 
cause of cisplatin ototoxicity from a different perspective; they 
explored if cisplatin remains in the inner ear continuing to cause 
damage for a longer time than in other areas of the body. The 
scientists found that, both in mice and humans, cisplatin remains in 
the inner ear long after it is already eliminated from other areas of 
the body. These results suggest that the inner ear readily takes up 
cisplatin, but it has little ability to remove the drug.
    In mouse and human tissues, the research team saw the highest 
accumulation of cisplatin was in a part of the inner ear called the 
stria vascularis, which is responsible for maintaining the positive 
electrical charge in inner ear fluid that certain cells need to detect 
sound. The research team determined that the accumulation of cisplatin 
in the stria vascularis portion of the inner ear contributed to 
cisplatin-related hearing loss.
    This research suggests that if we can find ways to avoid cisplatin 
from entering the stria vascularis during treatment with cisplatin, we 
might be able to prevent the hearing loss that goes along with it. As 
hearing loss is often associated with isolation, depression, and other 
conditions, helping to preserve hearing in individuals who are required 
to undergo cancer treatment with these chemotherapy drugs would greatly 
contribute to maintaining the quality of their lives.
             treating hereditary deafness with gene editing
    Hearing problems in infants and children can delay the development 
of voice, speech, and language skills. Approximately 80 percent of 
hearing loss is due to genetic factors, and treatment options for 
genetic deafness are limited. A research team, supported in part by 
NIDCD, used a mouse model of human genetic deafness to design a 
potential treatment approach.
    Mutations in a particular gene, TMC1, are known to cause hereditary 
deafness in both humans and mice. The mutation causes the death of 
sensory hair cells in the cochlea of the inner ear. These hair cells 
transform sound waves into electrical signals that the brain recognizes 
as sound. To prevent hair cell death and the resulting progressive 
hearing loss in mice with the TMC1 mutation, the scientists used the 
CRISPR-Cas9 gene-editing system to remove the mutation and disable the 
gene.
    The researchers developed a novel approach to deliver the gene-
editing complex into the inner ears of newborn mice. They packaged the 
gene-editing complexes in lipids (fats) that form structures called 
liposomes. The liposome-packaged complexes move readily through cell 
membranes into cells. Eight weeks later, substantially more hair cells 
survived in ears of treated compared to untreated mice. The treatment 
also significantly reduced progressive hearing loss. This novel 
strategy may help scientists develop new therapies for hearing loss 
caused by inherited genetic mutations.
       taste, balance, and more--a proton channel with many roles
    Our ability to taste helps us choose and enjoy nutritious foods and 
avoid foods that have been spoiled by bacteria. On our tongue, sensory 
taste cells respond to chemicals that are released from food and drink. 
Taste cells respond to these chemicals via protein receptors and 
channels that are specific to certain taste molecules. For instance, to 
detect sourness in food, specialized channels let protons (Hydrogen 
atoms) that are released from acidic sour-tasting foods enter proton-
sensitive, ``sour'' taste cells on the tongue.
    The identity of this ``sour detector'' protein has been elusive. 
Now, NIDCD-supported scientists have located a protein called OTOP1 and 
determined that it forms a channel that allows protons to enter taste 
cells on the tongue. They have also confirmed that human OTOP1 forms a 
channel with properties similar to those of the mouse OTOP1 protein. 
When OTOP1 gene was altered in mice, the scientists observed that taste 
cells had significantly fewer protons going into them. This evidence, 
together with other supporting studies on OTOP1, suggests that OTOP1 is 
the long-sought after sour taste receptor. The next step to test this 
theory will be to record whether mice that lack OTOP1 respond to sour 
tastes. Studies like this one, that increase our understanding about 
how we taste, may help scientists learn to restore a sense of taste to 
those who have lost it due to disease or injury.
    This study may help us understand far more than just how we detect 
taste. OTOP1 is also required for the vestibular (balance) system in 
the inner ear to detect gravity, so it is important for helping us keep 
our balance. OTOP1 is also expressed in many other body tissues, 
including fat, heart, uterus, breast, and the nervous system. Since we 
know that OTOP1 functions as a proton-sensitive channel, what we learn 
from this taste study may help us understand cell signaling in these 
other tissues, too. When protons enter cells, they change the acid/base 
(pH) concentration. So, a better understanding of OTOP1 could also help 
us understand other body processes that involve changes in pH, such as 
pain sensation, fat metabolism, and pH changes seen in cancer cells.
      personalized voices for people with severely impaired speech
    Approximately 2.5 million Americans and millions more people 
worldwide have a severe speech impairment since birth or as a result of 
a neurological disorder that occurred later in life, such as a stroke. 
For these people, communicating is a daily challenge that relies upon 
their use of a computer to generate their voice. While these devices go 
a long way toward helping people with a voice disorder express 
themselves, the synthetic voices produced are usually a poor 
representation of a natural human voice. In addition, the lack of 
diversity in available synthetic voices means that many people must use 
the same generic voice.
    Through a Small Business Innovation Research Program grant, NIDCD 
voice scientists have moved research from the lab into real-world 
application. Researchers are in the second phase of developing a 
personalized text-to-speech augmentative and alternative communication 
(AAC) device called VocaliD. This device involves blending the speech 
of two individuals--a donor and the recipient. First, a recording is 
made of whatever vocal sounds the recipient is still able to make. The 
next step is accomplished with the help of a volunteer voice donor. For 
the best results, the donor should match the recipient in terms of 
gender, age, region of origin, and other characteristics. By 
commercializing VocaliD, NIDCD scientists have refined the technology, 
automating certain steps and making the entire process of creating 
personalized, synthetic voices faster and more efficient. These 
improvements will advance speech synthesis while humanizing machine-
mediated spoken interaction for AAC devices and beyond.
                                 ______
                                 
Prepared Statement of Diana W. Bianchi, M.D., Director, Eunice Kennedy 
   Shriver, National Institute of Child Health and Human Development
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development 
(NICHD) of the National Institutes of Health (NIH).
                       achieving lifelong health
    Understanding human development, both normative and atypical, is at 
the core of NICHD's mission. As our name reflects, NICHD supports and 
conducts a wide range of research, including but not limited to 
pediatric research, on all phases of human development to maturity, 
with the goal of achieving optimal health, cognitive, and physical 
function.
    Child Health.--The epidemic of opioid use disorder and its 
consequences is among the most serious public health threats in this 
country today. Among those exposed to opioid use are the thousands of 
infants born to women with the disorder. Every 15 minutes, a baby is 
born with Neonatal Opioid Withdrawal Syndrome (NOWS) in the United 
States; to date, NOWS has cost about $2 billion in additional costs for 
Medicaid-financed deliveries.\1\ Symptoms of NOWS, also known as 
Neonatal Abstinence Syndrome (NAS), often do not begin until after 
infants have been discharged from the hospital. Their needs are placing 
huge stresses on the healthcare and foster care systems nationwide. To 
address this problem, NIH launched a new study called the Advancing 
Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) to 
evaluate treatment options and improve clinical care of affected 
infants. The study is a collaboration between NICHD's Neonatal Research 
Network and the new IDeA States Pediatric Clinical Trials Network 
(within the Office of the NIH Director's Environmental Influences on 
Child Health Outcomes program), with sites located in rural and 
medically underserved communities. This joint research effort will use 
the reach of both networks to assess the prevalence of NOWS, understand 
current approaches to managing these cases, and develop protocols for 
conducting large scale studies to inform clinical care, so that these 
babies may get a better start in life.
---------------------------------------------------------------------------
    \1\ Winkelman, T.N., Villapiano, N., Kozhimannil, K.B., Davis, 
M.M., Patrick, S.W., Incidence & Costs of Neonatal Abstinence Syndrome 
among Infants with Medicaid: 2004-2014, Pediatrics published online: 
March 23, 2018 (doi: 10.1542/peds.2017-3520).
---------------------------------------------------------------------------
    One of NICHD's longest standing research priorities is to improve 
the lives and health of people with intellectual and developmental 
disabilities, such as Down syndrome. NICHD leads the public-private 
Down Syndrome Consortium, which includes 11 NIH Institutes and Centers, 
13 national and international organizations whose missions focus on 
Down syndrome, and individuals with Down syndrome and family members. 
Consortium members provided valuable input to DS Directions: The NIH 
Down Syndrome Research Plan. Among the plan's major objectives is the 
call for research on the co-existing conditions commonly experienced by 
people with Down syndrome. For example, studies show that virtually all 
middle-aged adults with Down syndrome exhibit the neuropathological 
hallmarks of Alzheimer's disease, 50 percent of whom will develop this 
type of change to the brain by age 40. Funded jointly by NICHD and the 
National Institute on Aging, a new project, the Alzheimer's Biomarker 
Consortium--Down Syndrome (ABC-DS), seeks to identify biomarkers and 
use brain imaging to help us understand the progression of the disease. 
In addition, the research teams will make their data and samples freely 
available to qualified researchers worldwide, with the goal of 
accelerating the testing of potential interventions, which in turn may 
have widespread implications for Alzheimer's and other conditions. In 
fiscal year 2018, NICHD will lead a major new initiative to explore the 
risk and resilience of people with Down syndrome to common, co-existing 
conditions such as autism, cancer, and cardiovascular disease.
    NICHD's research on child health explores basic biological 
processes that control healthy or atypical development, translational 
research, behavioral and social science, and clinical studies. Basic 
research studies provide fundamental knowledge essential to 
understanding causes of structural and functional birth defects. NICHD 
has long provided the evidence base informing the panel of conditions 
included in newborn screening tests to help diagnose and treat infants 
early. Further, in collaboration with NHGRI, the Newborn Sequencing in 
Genomic Medicine and Public Health (NSIGHT) is exploring the challenges 
and opportunities associated with sequencing the entire genome of a 
newborn infant to advance our understanding of undiagnosed disorders. 
And, although it is widely recognized that children are not small 
adults, only five of the 80 drugs most frequently used in newborns and 
infants have been labeled for pediatric use to date. However, progress 
is being made under The Best Pharmaceuticals for Children Act, 
reauthorized by Congress for the fourth time in summer 2017, which 
charged NIH/NICHD with leading a trans-NIH effort on pediatric 
therapeutic needs. This year, through its Pediatric Trials Network, 
NICHD tested a commonly used combined antibiotic (piperacillin-
tazobactam), finding the dose of this combination drug that is safe for 
infants who acquire severe infections in the hospital. NICHD-supported 
researchers also recently reported that children who are engaged during 
shared reading experience a boost in the area of the brain that is 
involved in language development, comprehension, memory, and problem 
solving; understanding how reading shapes a child's brain can help 
educators and parents develop and use effective early learning 
strategies.
    Maternal Health.--The World Health Organization defines maternal 
mortality as the death of a woman while pregnant or within 42 days 
after the pregnancy ends due to causes related to or aggravated by the 
pregnancy. Between 1987 and 2013, maternal mortality in the United 
States increased from 7.2 to 17.3 per 100,000 live births, the only 
developed nation in which the rates have been rising since 2000. NICHD 
supports a wide range of research efforts to counter this disturbing 
trend. For example, NICHD-supported researchers studying placental 
abruption (a dangerous condition that occurs when the placenta 
separates from the uterus before birth) found that women who had a 
placental abruption were about twice as likely to have abnormal levels 
of specific proteins in their blood. These results may help identify 
women at risk in the future.
    NICHD is supporting two major projects to gather unprecedented 
amounts of information about pregnancy. Its ongoing Human Placenta 
Project, designed to provide insights into placental health 
noninvasively and in real time, continues to yield new data to improve 
maternal health and pregnancy outcomes. Another effort launched this 
year, PregSource is a longitudinal, crowd-sourced, citizen science 
registry that will expand our knowledge about women's typical 
experiences during pregnancy and after birth, the effects of pregnancy 
on women's lives, and special health challenges some women face. In 
addition, many pregnant or breastfeeding women must either take 
prescription medications to ensure their own health or are urged to 
take medications to benefit the baby's health outcomes. As part of the 
21st Century Cures Act legislation, NICHD was asked to lead the newly 
mandated Federal Task Force on Research Specific to Pregnant Women and 
Lactating Women. Although pregnant women in the United States take 
between three and five prescription medications, usually for serious 
health conditions, very few of these therapies have been tested during 
pregnancy. Almost nothing is known about the transfer of medications 
into breast milk, nor the risks and benefits of breastfeeding while on 
medication. The Task Force's report and recommendations are due to the 
Secretary of Health and Human Services and Congress by September 2018, 
which will shed light on this understudied issue.
    Rehabilitation.--About 5 percent of children aged 5 to 17 in the 
United States live with disability. Conditions such as brain injury, 
cerebral palsy, or spina bifida can impede children's education and 
future potential to lead productive lives. The 2016 NIH Research Plan 
on Rehabilitation, led by the National Center for Medical 
Rehabilitation Research (NCMRR) at NICHD and the trans-NIH 
Rehabilitation Working Group, set out priority areas for medical 
rehabilitation research and assistive technologies to improve the lives 
of people of all ages. Multiple funding opportunities have been 
published to encourage scientists to submit applications on topics such 
as sleep disorders during medical rehabilitation; grants recently have 
been awarded on the biomechanics of movement and regenerative medicine. 
Another priority is to support research that will improve function for 
individuals with limb loss, yet the lack of data on the number of 
individuals who experience limb loss and the types of procedures or 
devices they receive to enable them to return to optimal function at 
home, school and work, has presented a barrier to research in this 
area. This year, NCMRR, in partnership with the Department of Defense, 
will solicit applications for a nationwide Limb Loss Registry to enable 
researchers the data they need to develop new devices and track health 
and functional outcomes.
    Helping Young Scientists.--To continue to foster groundbreaking 
health research, NICHD's commitment to investing in the next generation 
of researchers has been unwavering. For example, the Institute holds an 
annual young investigators conference to facilitate the training of 
physician scientists. The conference focuses on developing the skills 
needed by young clinician investigators who are working in any of the 
areas within NICHD's mission. We are also analyzing long-term success 
as a function of different types of training awards so that training 
resources can be directed to provide the maximum return on investment. 
To help young investigators get started with testing hypotheses and 
performing original research and to make maximum use of public 
investment, NICHD makes data and other research resources available 
through the Data and Specimen Hub (DASH), which offers de-identified 
data from clinical research on pregnancy, infant care, child health, 
HIV/AIDS, and other topics. Currently, the repository includes data 
from 63 studies, and more than 12,000 users have visited the site, 
including many young investigators who are exploring possible research 
collaborations; future plans include linking hundreds of thousands of 
residual biospecimens to the de-identified data.
                               conclusion
    To capitalize on the many scientific areas within NICHD's mission, 
and to determine scientific priorities, the Institute is engaging in a 
new strategic planning process, with input from a wide array of 
stakeholders, and in collaboration with NIH and scientific leadership. 
As the new plan emerges, NICHD will continue its life-changing research 
efforts to improve the lives of children and families.
                                 ______
                                 
    Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T, A.T.S, 
     Director, National Institute of Environmental Health Sciences
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Environmental Health Sciences of the National Institutes 
of Health (NIH).
                   team science for health solutions
    Human beings are faced with an increasingly complex environment in 
which we experience thousands of exposures--both healthy and 
hazardous--on any given day over the course of our lifetimes. Although 
advances in knowledge and technology enable individual scientists to 
delve deeper than ever into how such exposures may impact our health, 
the use of diverse, multidisciplinary teams of scientists to 
investigate complex problems offer the promise of accelerated discovery 
to prevent disease and improve health. A 2015 report by the National 
Research Council concluded that ``Several strands of research and data 
suggest that team science can rapidly advance scientific and 
technological innovation by increasing research impact, novelty, 
productivity, and reach.'' Such outcomes are directly in line with the 
imperatives of Optimize NIH and ReImagine HHS to increase efficiency, 
maximize talent, and accelerate innovation.
    Team science, in the NIEHS context, is the collaborative effort of 
researchers from diverse scientific disciplines, often in partnership 
with communities that have relevant experience or perspectives, to 
solve public health problems that arise from environmental exposures. 
NIEHS continues to build on a long tradition of interdisciplinary 
approaches that engage a range of scientific and community stakeholders 
in creating the knowledge to inform public health decisionmaking. I 
will describe some of the ways in which we implement team science 
approaches as we work to fulfill the mission of the NIEHS--to discover 
how the environment affects people in order to promote healthier lives.
                 centers, consortia, and collaborations
    NIEHS both conducts team science intramurally and supports team 
science through a variety of center, consortia, and interagency 
collaborations. We use the centers framework to capitalize on the 
diverse talent at universities and create a supportive environment for 
multidisciplinary science and community engagement. NIEHS-supported 
centers include those focusing on areas such as Environmental Health 
Sciences, Breast Cancer and the Environment, Environmental Health 
Disparities, Children's Environmental Health and Disease Prevention, 
and Oceans and Human Health. These centers provide a centralized hub to 
support research, training, and scientific exchange among investigators 
across disciplines and often in partnership with patient advocacy or 
other community organizations. Each center must also conduct research 
translation, provide information and education, and engage with 
interested patient groups and communities.
    The centers are highly productive and last year generated numerous 
significant discoveries, including how omega-3 fatty acids contained in 
fish oil could be used to treat asthma patients; that dementia is 
linked to a certain genetic variation combined with exposure to air 
pollution, and an impaired sense of smell in such persons may serve as 
an early warning sign; that children with asthma may be more likely 
become obese later in childhood or adolescence; links between exposure 
to seasonal harmful algal blooms and elevated risk of amyotrophic 
lateral sclerosis (ALS); and potentially safer alternatives to 
bisphenol A (BPA), to name just a few.
    Consortia are another way that NIEHS supports team science that 
extends beyond a single institution to create a network of linked 
expertise to focus on a complex environmental health problem or set of 
related issues. NIEHS led the Gulf Long-term Followup (GuLF) Study and 
the 5-year, $25.2-million Deepwater Horizon Research Consortia, both of 
which partnered researchers with communities to investigate health 
effects stemming from the oil spill, including the long-term mental 
health impacts of the spill on coastal residents, especially women and 
children; the resilience of individuals and communities; and whether 
seafood in the Gulf was safe for human consumption. These research 
partnerships continue to yield new insights: a 2017 study linked a 
range of health problems in workers who were exposed to dispersants 
used to clean up the oil spill.
    Research needs identified by the Deepwater Horizon consortia 
provided further momentum for the creation of the NIH Disaster Research 
Response (DR2) program, which comprises a national framework for 
research on the medical and public health aspects of disasters and 
public health emergencies. Led by the NIEHS and the National Library of 
Medicine, DR2 has rapidly grown into a Federal interagency effort with 
broad engagement in the goal of understanding how to be prepared for 
disasters and how to limit any negative disaster-related health 
effects. Examples of such research include human health studies to 
assess effects of exposures on first responders, worker volunteers, and 
community members; characterizing chemical hazards in floodwaters and 
identifying post-flood molds; and assessing risks to vulnerable people 
such as those with asthma from wildfire pollution. DR2 tools and 
trainings were used last year to enable critical data collection and 
analysis, and inform response to the devastating Hurricanes Harvey, 
Irma, and Maria. In addition, NIEHS awarded time-sensitive research 
grants specifically aimed at hurricane response research.
    NIEHS is leading the Nation's coordinated science response to 
another type of environmental threat--the potential for serious human 
health impacts from exposure to PFAS, the collective name for per- and 
polyfluoroalkyl substances, chemicals widely used over the past 50 
years in food packaging, lubricants, water-resistant coating, and fire-
fighting foams, and other manufacturing. Although some have been phased 
out, these endocrine-disrupting chemicals continue to be found in 
drinking water supplies in multiple States, and NIEHS-funded research 
suggests links to health effects on immune and thyroid function, fetal 
growth and development, risk of cancer and obesity, and others. NIEHS 
helped to organize a recent meeting of 16 Federal agencies that focused 
on exchanging information on PFAS exposure science, health science, and 
remediation and treatment of contaminated areas, and generated 
opportunities for collaborative research. The National Toxicology 
Program Laboratory Branch, one of the NIEHS research components of this 
interagency program, is also responding to public demand for more and 
faster information on the threat posed by PFAS through its Rapid 
Evaluation and Assessment of Chemical Toxicity (REACT) program. 
Outcomes of these collaborative efforts will help to target research 
and inform decisionmaking by both government and communities.
    Perhaps the most prominent environmental hazard demanding a team 
science approach from across a broad spectrum of disciplines is lead 
exposure. NIEHS-supported science established the knowledge base for 
lead's major health impacts. But although we understand the primary 
outcomes of lead poisoning, particularly neurodevelopmental damage in 
children, the need continues for research to make clear exactly how 
lead works in the body to cause damage so that successful interventions 
can be developed. An NIEHS-funded study using lead in baby teeth as a 
marker of exposure found associations between lead levels just before 
and after birth with the risk for and severity of autism in later 
childhood. Another study of children whose mothers took multivitamins 
during pregnancy suggested they were 30 percent less likely to develop 
autism. The concerns are not just for children however; a recent study 
estimated that low-level lead exposure (<5mg/dL blood) is responsible 
for more than 400,000 deaths each year in the United States, some 
250,000 of which from cardiovascular disease in adults. Combined with 
the estimated half million children still exposed beyond the CDC 
reference level, the health, economic, and societal consequences of 
lead exposure remain great. NIEHS and our grantees are continuing to 
respond to this threat through research, training for workers involved 
in lead cleanup and remediation, and engaging with our Federal partners 
on the President's Task Force on Environmental Health Risks and Safety 
Risks to Children to develop a Federal Lead Strategy.
                       connecting the data points
    No matter what the environmental health issue is, it has become 
increasingly clear that finding solutions demands a strong commitment 
to team science--data science, sharing, and integration offer the 
promise of incredible breakthroughs in preventing disease and promoting 
health, but require unprecedented levels of engagement, coordination, 
and standardization across a rapidly evolving scientific landscape. 
NIEHS has been working to foster data collaborations through support of 
training grants in the Big Data to Knowledge (BD2K) initiative, 
partnership with the NIH Data Commons, development of an NIEHS Data 
Commons, convening of National Academies workshops, establishment of an 
Office of Cyberinfrastructure, and prioritization of data science and 
integration goals across our developing Strategic Plan.
    To conclude, environmental health problems present large, costly, 
and complex issues for our society that demand the focused attention of 
multidisciplinary teams of scientists. NIEHS will continue to provide 
the critical support and leadership necessary for such teams to succeed 
in discoveries that will prevent disease and promote the health of the 
American people.
                                 ______
                                 
  Prepared Statement of Patricia Flatley Brennan, Director, National 
                          Library of Medicine
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Library of Medicine of the National Institutes of Health (NIH).
        accelerating biomedical discovery & data-powered health
    The National Library of Medicine (NLM) plays an essential role in 
catalyzing basic biomedical science through its cutting-edge data 
science and informatics research, comprehensive information systems, 
and extensive research training programs. As the world's largest 
biomedical library, NLM acquires, organizes, and delivers up-to-date 
biomedical information across the United States and around the globe. 
Millions of data scientists, health professionals, and members of the 
public use NLM's electronic information sources every day to translate 
research results into new treatments, products, and practices; provide 
useful decision support for health professionals and patients; and 
support disaster preparedness and response.
    Leveraging its 180-year history of organizing and disseminating 
biomedical literature, NLM is committed to the application of emerging 
data science capabilities to challenges in biomedical research and 
public health. It will do this by expanding its data and information 
resources and providing leadership in both the acquisition and analysis 
of data for discovery. It will expand its core biomedical literature 
and genomic collections to include a broad array of health, clinical, 
and biological data types and make these data findable, accessible, 
interoperable, and reusable (FAIR) for research. NLM will enhance its 
research programs to systematically characterize and curate data 
describing complex health phenomena and to devise new methods to 
uncover the knowledge held in data. It will restructure its biomedical 
informatics training programs to address data science as they continue 
to foster excellence and support a diverse workforce. NLM will develop 
an efficient organizational structure to accommodate emerging 
directions in research and services.
          research in biomedical informatics and data science
    NLM's research programs support pioneering research and development 
to advance knowledge in biomedical informatics and data science. Its 
research portfolio spans such areas as artificial intelligence, 
computational biology, clinical decision support, public health 
surveillance, visualization, and discovery mining in digital data sets. 
This research encompasses areas of high importance to NIH and society 
at large, and for audiences ranging from clinicians and scientists to 
consumers and patients.
    Research in data science produces novel analytical approaches and 
visualization tools that help scientists accelerate discovery from data 
and translate these findings to clinical solutions. It also aims to 
solve problems consumers face in accessing, storing, using, and 
understanding their own health data and to produce tools that make 
precision medicine discoveries available and more understandable to 
patients. Biomedical informatics research is yielding advanced 
analytical methods and tools for use against large scale data generated 
from clinical care, leading to fuller understanding of the effects of 
medications and procedures as well as individual factors important in 
the prevention and treatment of disease processes.
    Recognized as a leader in clinical information analytics, NLM 
conducts intramural research in areas such as medical language 
processing, high-speed access to biomedical information, analysis and 
use of high quality imaging data, advanced technology for emergency and 
disaster management, health data standards; and analysis of large 
databases of clinical and administrative data to predict patient 
outcomes and validate findings from clinical research studies. 
Leveraging extensive machine learning experience and field-based 
projects, NLM is now advancing analytical tools and deep learning 
techniques for application in image analysis research.
    NLM's biomedical informatics research also addresses issues in 
computational biology. Research creates new ways to represent and link 
together genomic and biological data and biomedical literature and 
produces analytic software tools for gaining insights in areas such as 
genetic mutational patterns and factors in disease, molecular binding, 
and protein structure and function.
         biomedical information systems for research and health
    NLM develops and operates a set of richly linked databases that 
promote scientific breakthroughs and play an essential role in all 
phases of research and innovation. Every day, NLM receives up to 12 
terabytes of new data and information, enhances their quality and 
consistency, and integrates them with other NLM information. It 
responds to millions of inquiries per day from individuals and computer 
systems, serving up some 100 terabytes of information, including 
genomic, chemical, and clinical trial data, as well as citations to 
more than 25 million journal articles in PubMed and more than 4.7 
million full-text articles in PubMed Central.
    NLM also offers sophisticated retrieval methods and analysis tools 
to mine this wealth of data, many of which grow out NLM's research and 
development programs. For example, NLM tools are used to mine journal 
articles and electronic health records (EHRs) to discover adverse drug 
reactions, analyze high throughput genomic data to identify promising 
drug targets, and detect transplant rejection earlier so interventions 
to help clinical research participants can begin more quickly. Data 
analysis tools also support complex analyses of richly annotated 
genomics data resources, yielding important molecular biology 
discoveries and health advances for applications to clinical care. Such 
applications demonstrate how the benefits of big data critically depend 
upon the existence of algorithms that can transform such data into 
information.
    As a major force in health data standards for more than 30 years, 
NLM's investments have led to major advances in the ways high volume 
research and clinical data are collected, structured, standardized, 
mined, and delivered. In close collaboration with other HHS agencies 
and the Veterans Administration, NLM develops, funds, and disseminates 
clinical terminologies designated as U.S. standards for meaningful use 
of EHRs and health information exchange. The goal is to ensure that EHR 
data created in one system can be transmitted, interpreted, and 
aggregated appropriately in other systems to support healthcare, public 
health, and research. NLM produces a range of tools to help EHR 
developers and users implement these standards and makes them available 
in multiple formats, including via application programming interfaces 
(APIs).
              engaging the public with health information
    NLM uses multiple channels to reach the public with health 
information, including development of consumer-friendly websites, 
direct contact, and human networks that reach out to communities. 
Direct-to-consumer information is made available in lay language 
through MedlinePlus, which covers more than 1000 health topics. EHR 
systems can connect directly with MedlinePlus to deliver information to 
patients and healthcare providers at the point of need in healthcare 
systems. In collaboration with NIH Institutes and Centers (ICs) and 
other partners, NLM produces the print and online NIH MedlinePlus 
magazine, and its Spanish counterpart, NIH Salud.
    The National Network of Libraries of Medicine (NNLM) engages 6,500 
academic health sciences libraries, hospital libraries, public 
libraries, and community-based organizations as valued partners in 
conducting outreach to ensure the availability of health information, 
including from NLM services. The NNLM provides a community-level 
resource for NIH's All of Us program, ensuring a point of presence in 
almost every county in the US. NNLM partners with local, State, and 
national disaster preparedness and response efforts to promote more 
effective use of libraries and librarians and ensure access to health 
information in disasters and emergencies. NNLM also plays an important 
role in increasing the capacity of research libraries and librarians to 
support data science and improve institutional capacity in management 
and analysis of biomedical big data.
                               conclusion
    To conclude, through its research, information systems and public 
engagement, NLM supports discovery and the clinical application of 
knowledge to improve health. Its programs provide important foundations 
for the field of biomedical informatics and data science, bringing the 
methods and concepts of computational, informational, quantitative, 
social, behavioral, and engineering sciences to bear on problems 
related to basic biomedical and behavioral research, healthcare, public 
health, and consumer use of health-related information.
                                 ______
                                 
   Prepared Statement of Anthony S. Fauci, M.D., Director, National 
              Institute of Allergy and Infectious Diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Allergy and Infectious Diseases (NIAID) of the National 
Institutes of Health (NIH).
    NIAID has a dual mandate to maintain and grow a robust basic and 
clinical research portfolio in the areas of microbiology, infectious 
diseases, immunology, and allergy as well as to launch a swift research 
response when infectious diseases emerge and re-emerge. NIAID makes 
vital contributions to developing diagnostics, therapeutics, and 
vaccines by supporting medical countermeasures specific to single 
pathogens as well as platform technologies that can be deployed to 
target multiple pathogens. Also, NIAID research that has responded to 
ongoing public health threats has been a key component of U.S. 
biodefense preparedness.
                    research on infectious diseases
    Influenza, Including Universal Influenza Vaccine Development. NIAID 
supports basic, translational, and clinical research to address the 
constant threat of seasonal and pandemic influenza. Concerns over the 
efficacy of seasonal influenza vaccine, and the threat of pandemics 
such as posed by H7N9 influenza, highlight the need for a new 
generation of influenza vaccines. NIAID recently convened influenza 
research experts from around the world at a workshop that led to the 
development of a Strategic Plan for a Universal Influenza Vaccine. 
NIAID's Strategic Plan outlines research priorities in three areas 
important for understanding the formidable challenges posed by 
influenza and advancing the development of universal influenza 
vaccines. These research areas are: 1) transmission, natural history, 
and pathogenesis of influenza infection; 2) influenza immunity and 
factors correlated with immune protection; and 3) vaccine approaches to 
elicit broad, protective immune responses.
    NIAID is pursuing the research agenda outlined in the Strategic 
Plan, including research on cohorts of infants to determine how 
influenza vaccinations and natural influenza infections may affect 
immunity to influenza infection or immunization later in life. These 
cohort studies will provide vital information to facilitate the design 
of broadly protective influenza vaccines. NIAID also is supporting the 
development of several universal influenza vaccine candidates. One 
strategy pursued by NIAID Vaccine Research Center scientists uses a 
platform to display portions of an influenza surface protein--
hemagglutinin--that do not easily mutate and are relatively constant 
among influenza strains. A separate NIAID-supported approach uses non-
infectious virus-like particles that display four types of influenza 
hemagglutinin in one vaccine. Another NIAID-funded strategy employs 
several influenza fragments recognized by the immune system that are 
common to different influenza virus strains. Each of these vaccine 
strategies aims to produce broad and durable immune responses that 
would be effective against multiple influenza strains.
    Zika. NIAID research has led to the rapid development of 
diagnostics, candidate vaccines, and therapeutics to address the public 
health threat of Zika virus disease, especially Zika virus-related 
congenital abnormalities. NIAID scientists developed a DNA-based Zika 
vaccine that is now being tested in a large-scale clinical trial in 
Zika-endemic regions. NIAID is developing other candidate Zika 
vaccines, including a live, attenuated vaccine that targets both Zika 
virus and the related dengue virus. In addition, NIAID is partnering 
with other NIH Institutes and the Fiocruz Institute in Brazil to 
support the Zika in Infants and Pregnancy cohort study, which is 
assessing the risks of Zika infection in expectant mothers and tracking 
infant outcomes for at least 1 year.
    Other Vector-borne Diseases. NIAID supports research to address 
mosquito-borne diseases such as dengue, malaria, chikungunya, and 
yellow fever, and tick-borne diseases such as Lyme disease. NIAID 
scientists developed a candidate dengue vaccine, TV003, that targets 
all four sub-types of dengue virus. TV003 currently is being tested in 
a large-scale clinical trial in Brazil. An NIAID-supported malaria 
vaccine, PfSPZ, contains a weakened form of the mosquito-borne malaria 
parasite. Recent clinical trials showed PfSPZ protects people against 
multiple malaria strains and prevents infection in a malaria-endemic 
region. NIAID also is supporting a clinical trial of a vaccine designed 
to trigger an immune response to mosquito saliva. This vaccine aims to 
prevent multiple mosquito-borne diseases by blocking their transmission 
from infected mosquitoes.
    HIV/AIDS. NIAID research has led to powerful HIV treatment and 
prevention tools that improve the lives of individuals living with HIV 
and that have the potential to eventually end the HIV/AIDS pandemic. 
NIAID is supporting new HIV vaccine studies, including the Imbokodo 
trial in sub-Saharan Africa that is evaluating a vaccine candidate 
designed to protect against multiple global HIV strains. NIAID also is 
developing broadly neutralizing antibodies that can block most subtypes 
of HIV found worldwide. VRC01 is one such antibody that is currently 
being evaluated by passive infusion in two ongoing HIV prevention 
trials in individuals at high risk of HIV infection. Another broadly 
neutralizing antibody protected against infection in a monkey model of 
HIV. Further study in this model showed that a mixture of two broadly 
neutralizing antibodies could treat already infected animals. Enabled 
by the HOPE Act, NIAID also is building on its pioneering clinical 
trials of organ donation between HIV-infected individuals by launching 
a multi-site clinical trial of kidney transplantation in this 
population. NIAID continues to pursue additional methods to combat HIV, 
including microbicide-based approaches such as a vaginal ring infused 
with an anti-HIV drug, and long-acting injectable drugs to prevent and 
treat HIV.
    Tuberculosis. NIAID supports research to address tuberculosis (TB) 
including the challenges of TB/HIV co-infection and increasing drug 
resistance. NIAID also leads the research component of the National 
Action Plan for Combating Multidrug-Resistant TB. NIAID scientists and 
collaborators have developed a new diagnostic tool that detects 
resistance to key antibiotics used to treat TB and may facilitate a 
point-of-care diagnostic approach to guide TB therapy. In addition, an 
NIAID clinical trial of HIV-infected individuals demonstrated that a 1 
month course of preventive TB medication was as safe and effective as a 
nine-month regimen. Patients were more likely to complete the short 
regimen, suggesting it may be a preferred TB prevention strategy.
    Antimicrobial Resistance. NIAID plays a critical role in research 
components of the National Strategy for Combating Antibiotic-Resistant 
Bacteria (CARB). NIAID is collaborating with the Biomedical Advanced 
Research and Development Authority (BARDA) on the CARB 
Biopharmaceutical Accelerator, or CARB-X, a global public-private 
partnership to advance the preclinical and early clinical development 
of promising antibacterial drugs and other products. In addition, NIAID 
funds multiple clinical trials to evaluate novel antibiotics or 
optimize the use of current antibiotics. One recent study found that 
two common, inexpensive antibiotics can effectively treat methicillin-
resistant Staphylococcus aureus skin abscesses. NIAID also supports 
clinical trials to develop zoliflodacin, a novel antibiotic for 
gonorrhea, an increasingly drug-resistant infection.
          research on immunology and immune-mediated disorders
    NIAID research has led to transformational advances in our 
understanding of the immune system and to new ways of treating and 
preventing immune-mediated diseases. For example, NIAID research on 
mechanisms of T-cell activation led to the development of ``checkpoint 
inhibitors,'' a new class of immunotherapy drugs for cancer.
    Food Allergy. NIAID research investments have led to important 
advances in the prevention and treatment of food allergies. NIAID 
convened an expert panel to build on the findings of pivotal food 
allergy studies by developing new clinical guidelines to help prevent 
peanut allergy in at-risk infants. NIAID-supported researchers also 
have found that combining oral immunotherapy with the asthma drug 
omalizumab may be an effective strategy to simultaneously desensitize 
children with multiple food allergies.
    Stem Cell Transplants for Treatment of Autoimmune Diseases. Two 
recent NIAID-supported clinical trials found that intensive 
immunosuppression followed by transplantation of a patient's own stem 
cells was an effective treatment for progressive and life-threatening 
autoimmune diseases. The Scleroderma: Cyclophosphamide or 
Transplantation (SCOT) trial showed that stem cell transplantation 
improves survival and quality of life for people with severe 
scleroderma when compared with routine immunosuppression. The HALT-MS 
trial demonstrated sustained remission in most people with relapsing-
remitting multiple sclerosis for 5 years following transplantation.
                               conclusion
    NIAID research continues to drive rapid progress in the development 
of vaccines, therapeutics, and diagnostics that improve human health 
and enhance our ability to respond rapidly to emerging and re-emerging 
infectious diseases. NIAID-supported science and innovation will 
continue to pave the way to solutions for many of the formidable health 
challenges facing the Nation and the world.
                                 ______
                                 
Prepared Statement of Gary H. Gibbons, M.D., Director, National Heart, 
                       Lung, and Blood Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National Heart, 
Lung, and Blood Institute (NHLBI) of the National Institutes of Health 
(NIH).
    This year, the NHLBI commemorates its 70th anniversary and a legacy 
of achievements across the broad spectrum of research--including basic 
science, epidemiology studies, implementation research, training, and 
landmark clinical trials--that have helped people all over the world 
live longer, healthier lives. Moving forward, the Institute remains 
committed to leveraging scientific opportunities and working in 
partnership with the public and private sector to prevent and treat 
heart, lung, blood, and sleep disorders.
         investing in basic research today for tomorrow's cures
    The NHLBI's continued investments in fundamental discovery science 
provide the foundation for tomorrow's medical breakthroughs. This 
includes the NHLBI's support for research on the circadian rhythm (the 
body's daily internal clock), how it is regulated, and its relationship 
to the risk of chronic disease. Well known to cardiologists, blood 
pressure rises and falls on a daily rhythm, reaching its peak in the 
early morning--which is also when the risk for heart attacks and other 
cardiovascular events is greatest. Moreover, disruption of circadian 
rhythms has been shown to contribute to obesity, diabetes, and other 
conditions that can increase the risk of heart, lung, blood, and sleep 
disorders. Recent discoveries from basic research--including work on 
fruit flies recognized with the 2017 Nobel Prize in Medicine--have 
revealed new insights on the genetic and molecular pathways underlying 
circadian rhythms that are opening new doors to prevention and 
treatment.
    To leverage these discoveries, the NHLBI has partnered with the 
National Institute of Diabetes and Digestive and Kidney Diseases on a 
program to better understand how circadian-dependent mechanisms 
contribute to obesity and to the risk of heart and lung disorders 
linked to obesity. Such research may help identify novel therapies that 
act on the circadian rhythm to prevent or manage these disorders.\2\ As 
researchers learn more about the basic pathways underlying circadian 
function, they may also gain new insights into treating sleep disorders 
such as sleep apnea.
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    \2\ https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-17-
020.html.
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               the power of data to personalize medicine
    The goal of precision medicine is to give healthcare providers the 
tools to better predict health and preempt chronic disease, and to 
tailor treatment strategies to a patient's unique characteristics. To 
accomplish this, the NHLBI's Trans-Omics for Precision Medicine 
(TOPMed) program is integrating clinical, genomic, and other data from 
diverse cohort studies, including the NHLBI's long-standing Framingham 
Heart Study and Jackson Heart Study, which continue to help us 
understand who is vulnerable to chronic diseases and why. To date, 
TOPMed has generated whole-genome sequences from 120,000 individuals in 
these studies, which we expect will identify new genetic risk factors 
for disease and new molecular targets for therapy.
    Data from TOPMed will be included in a pilot of the new NIH Data 
Commons, a public-private partnership to bring research findings into a 
cloud-computing environment to enhance data sharing. This effort will 
give researchers access to data from hundreds of studies, creating new 
opportunities for collaborative research, innovation, and discovery.
                      reducing health disparities
    Despite declines in overall death rates from cardiovascular disease 
(CVD), many populations in the United States, whether defined by race, 
gender, geography, or other factors, continue to experience a high 
burden of CVD and other chronic diseases. Increasingly, it is clear 
that place matters. Where people live, work, and play affects their 
susceptibility to disease and their health outcomes.
    A 2017 study of more than 3,000 counties found a high burden of CVD 
throughout the U.S. heartland, from Kentucky to Oklahoma, with 
mortality rates in the highest-burden counties up to four times higher 
than in the lowest-burden counties.\3\ New CDC data also shows that 
rural Americans face a higher burden of chronic obstructive pulmonary 
disease (COPD) than urban Americans and are dying from it at higher 
rates.\4\ Many communities face economic, cultural, and geographic 
barriers to disease awareness, prevention, and treatment, reflected in 
a high burden of CVD risk factors such as high blood pressure, smoking, 
low physical activity, and high-calorie diets.
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    \3\ https://jamanetwork.com/journals/jama/fullarticle/2626571.
    \4\ttps://www.cdc.gov/mmwr/volumes/67/wr/mm6707a1.htm.
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    These data help inform efforts to reduce health disparities through 
implementation research. For example, a recent NHLBI-funded study shows 
the power of using non-traditional settings to adapt and implement 
healthcare interventions for high-risk communities. In the study, blood 
pressure screenings and pharmacist referrals at barbershops helped 
reduce high blood pressure among African American men in the Los 
Angeles area.\5\ In alignment with the comprehensive Federal COPD 
National Action Plan, other research seeks to improve COPD care in 
medically underserved areas. One recent study found that a set of 
simple affordable diagnostic tools can help primary care providers 
identify patients with COPD and follow up with appropriate 
treatment.\6\
---------------------------------------------------------------------------
    \5\ https://www.ncbi.nlm.nih.gov/pubmed/29527973.
    \6\ https://www.ncbi.nlm.nih.gov/pubmed/27783539.
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    The NHLBI is expanding its implementation research programs. The 
STIMULATE initiative seeks investigator-initiated proposals to overcome 
barriers to implementation of proven interventions, and DECIPHeR will 
create opportunities to integrate intervention trials into the NHLBI's 
long-running observational studies of minority populations.
         sickle cell disease: from better treatments to a cure
    While the NHLBI supports implementation research programs in sickle 
cell disease (SCD) that are helping develop and test approaches to 
improve patient outcomes, fundamental discoveries in stem cell biology 
and genomics are converging toward a cure. SCD is a genetic blood 
disorder that affects 100,000 Americans and millions worldwide. It is 
caused by a genetic mutation that causes the body's red blood cells to 
take on a sickled shape and obstruct blood flow, leading to severe 
frequent pain, organ damage, and other debilitating effects.
    More than 50 percent of adults with SCD have significant pain more 
than three days per week, and about 40 percent take opioid pain 
medications daily. The NHLBI supports research to investigate 
mechanisms of pain in SCD and the potential for non-opioid treatments. 
This research will assist in addressing the Nation's devastating opioid 
epidemic, by helping ensure that individuals with SCD and other types 
of chronic pain can acquire effective relief without over-reliance on 
opioids.
    In addition to managing pain and other complications of SCD, it is 
possible to cure SCD with a bone marrow transplant. However, this 
procedure requires that the patient have a healthy, immunologically 
matched marrow donor, which is not an option for most patients.
    Advances in gene-editing technologies, such as CRISPR, are offering 
new hope for a cure that works for all patients. By using the patient's 
own bone marrow stem cells, researchers can replace the faulty SCD gene 
or edit the misspelled gene and transplant the corrected cells back 
into the patient, without the risk of immune rejection. NHLBI 
intramural scientists are leading cutting-edge research and clinical 
trials in this area.
    Curing this disease within the decade is not something the NIH can 
do alone. The NHLBI Cure Sickle Cell initiative is bringing together 
patients, patient advocacy groups, healthcare providers, academic 
researchers, and industry to accelerate development of a widely 
available SCD cure.
                               conclusion
    Medical breakthroughs and improvements in public health that once 
seemed impossible are now within reach due in large part to the NHLBI's 
seven decades of investing in excellent science. The Institute remains 
committed to funding investigator-initiated discovery science, training 
and building a talented diverse scientific workforce to help address an 
array of research needs, forming new strategic partnerships, and 
promoting the implementation of evidence-based care. Through these 
multi-pronged efforts, the NHLBI will continue to stimulate the 
scientific advances needed to further reduce suffering from heart, 
lung, blood, and sleep disorders.
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     Prepared Statement of Roger I. Glass, M.D., Director, Fogarty 
                          International Center
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the Fogarty 
International Center (FIC) of the National Institutes of Health (NIH).
                              introduction
    The idea that the U.S. could benefit from international 
collaborative research was central to the creation of the Fogarty 
International Center in 1968. Fogarty's namesake, Rhode Island 
Congressman John E. Fogarty, foresaw that U.S. citizens would reap the 
benefits of international discoveries and that global health was a 
smart investment for the U.S. and the world. Fifty years later, 
Congressman Fogarty's vision remains a guiding force as Fogarty 
continues to provide leadership in strengthening the research workforce 
here and abroad to ensure that the best and brightest minds are 
harnessed solve complex health challenges that affect us all.
    Well-trained scientists have never been more critical to protecting 
the health of Americans and populations around the world. Infectious 
diseases like Ebola and Zika have traveled across borders, and diseases 
formerly found only in other countries are now present in the U.S. 
Therefore, it is imperative that we train scientists in developing 
countries to detect pandemics at their point of origin, contain 
outbreaks, and minimize their impact. In addition, the ability to 
collaborate with scientists abroad can generate valuable knowledge 
about diseases such as Alzheimer's Disease and cancer.
    Fogarty supports research and research training programs for U.S. 
and low- and middle-income country (LMIC) scientists. These programs 
are built on long-standing partnerships between U.S. and LMIC academic 
institutions. Fogarty programs also extend the reach and 
competitiveness of U.S. universities, where there is high demand for 
international research opportunities. Currently, Fogarty supports over 
500 research and training programs involving 100 universities. Roughly 
80 percent of Fogarty grants are awarded to U.S. institutions and all 
Fogarty awards involve U.S. researchers.
            strengthen and sustain the biomedical workforce
Global Health Security
    Emerging epidemics such as Ebola demand a critical mass of in-
country scientists with relevant research expertise and skills. In 
2016, Fogarty initiated the Emerging Epidemic Virus Research Training 
for West African Countries with Widespread Transmission of Ebola 
program. These grants fund collaborations between U.S. and African 
research institutions in Guinea, Liberia, and/or Sierra Leone to plan 
capacity building programs for Fogarty's Global Infectious Disease 
Research Training Program, with a focus on emerging viral epidemics. 
This support enables scientists on the front lines in these countries, 
which were ground zero for Ebola, to design training programs that 
increase expertise in Ebola, Lassa fever, and other emerging viral 
diseases. For example, Yale University, in partnership with the 
University of Liberia, will develop a training program focusing on 
predictive transmission modeling and epidemiological research. Fogarty 
has also awarded a grant to Tulane University, the Vanderbilt Institute 
for Global Health, and the University of Sierra Leone. Together, these 
institutions will advance research focused on efficacy studies of novel 
and existing therapeutics for endemic viral hemorrhagic fevers like 
Lassa fever, while simultaneously building capacity on how to conduct 
higher-level clinical trial research during an epidemic like Ebola.
    An in-house team of Fogarty-supported scientists develop and use 
advanced computational models to study the emergence, evolution, and 
transmission of pathogens to help predict future pandemics, provide 
actionable information early in outbreaks, and protect the U.S. 
population from these threats. For example, these researchers and their 
collaborators recently modeled the global migration of Zika virus and 
their potential for causing large outbreaks in the U.S. They have also 
studied the transmission dynamics and evolution of influenza viruses in 
humans, domestic animals, and migratory birds to help predict future 
pandemics.
Combatting Common Disease Threats
    Fogarty also supports training of scientists in LMICs, many of whom 
have become leaders in academic institutions and ministries of health 
in their home countries and serve as critical partners for U.S. 
scientists. Notably, many health challenges facing Americans are most 
effectively addressed through research conducted in a global context, 
where diseases are often highly prevalent or where the study of unique 
genetic predispositions can inform how we detect and prevent certain 
diseases that affect U.S. citizens.
    HIV/AIDS. Key scientific discoveries in HIV/AIDS treatment and 
prevention have been made by Fogarty-supported trainees and former 
trainees, including interventions to reduce mother-to-child 
transmission of HIV, using HIV treatment to prevent new HIV infections, 
and novel approaches to address HIV/TB coinfection. Fogarty-trained 
scientists in South Africa are now studying broadly neutralizing 
antibodies, which can kill multiple strains of the virus that causes 
AIDS. Produced by only about 20 percent of people with HIV, these 
antibodies show up too late to be able to stop disease progression in 
the people who make them. However, scientists are exploring their 
potential to prevent HIV in others--either through a vaccine that would 
coax the body to generate similar types of antibodies or via passive 
immunization in which an antibody product would be given directly.
    Alzheimer's Disease. Columbia is home to the largest known family 
with an inherited, early-onset form of Alzheimer's. Testing new 
therapies on healthy individuals who are at a high risk for the 
disease, like those in this family, is providing valuable clues for 
understanding how to prevent it. Members of this family are now 
participating in a trial to determine if a drug provided by a U.S.-
based company can stave off the decline in memory and brain function 
associated with the disease. Fogarty-supported research training helped 
to build a strong neuroscience research community in Colombia, which 
set the stage for this potentially game-changing research.
                                research
    Brain Disorders. Fogarty's Global Brain and Nervous Systems 
Disorders Research across the Lifespan Program supports cutting-edge 
research in LMICs on nervous system development, function, and 
impairment throughout life. The program allows U.S. investigators to 
gain experience working in LMICs, expanding the research workforce in 
these settings by developing long-lasting international partnerships. 
This research network spans over 45 countries and has contributed to 
the creation of new interventions, new tools for clinical assessment, 
and new laboratory methods.
    Hydrocephalus--excessive accumulation of fluid in the brain--is one 
of the most common birth defects in the U.S. The traditional treatment 
for hydrocephalus is the surgical placement of a shunt, which often 
involves complications like mechanical failure, obstruction, and 
infection. Global Brain-supported researchers working in Uganda 
developed a new treatment for infant hydrocephalus. They combined 
endoscopic third ventriculostomy and choroid plexus cauterization (ETV/
CPC) into one treatment, where a small hole drains fluid from the brain 
and heat is applied to brain tissue to reduce fluid production. Both 
procedures have been practiced separately, but scarce resources in 
Uganda inspired researchers to combine the two practices. This 
combination treatment has helped to avoid shunt dependence in most 
Ugandan infants treated for this condition. Notably, ETV/CPC is now 
being practiced in the U.S.
    Influenza. The Multinational Influenza Seasonal Mortality Study 
(MISMS) is an international effort led by FIC to model the epidemiology 
and evolutionary dynamics of influenza in human, swine and avian 
populations. With funding from DHHS since 2007, MISMS has developed a 
network of over three-hundred influenza experts in forty-five countries 
and studied a broad range of topics, including: the global circulation 
of influenza virus; cross-species transmission; pandemic preparedness; 
control strategies; transmission dynamics; historical pandemics; 
disease burden; and seasonality.
    Mobile Health. Mobile technologies present exceptional 
opportunities and new tools for improving health outcomes. A mobile 
health tool conceived by a Fogarty grantee for HIV patient care in 
Uganda is now being used to help patients use their phones to adhere to 
strict medication regimen at a lower cost for conditions like opioid 
addiction, tuberculosis, and hepatitis C. Fogarty-supported researchers 
from the U.S. and Zambia are developing a simple diagnostic test for 
malaria that uses a few drops of blood and tiny magnetic beads to 
accurately detect the parasite that causes the disease. This new, 
inexpensive test improves malaria detection and reduces drug resistance 
by treating only those who have the disease.
                               conclusion
    Fogarty investments are enabling researchers to take science to 
where the problems are most acute, conduct research, and develop 
solutions in the places where diseases are especially challenging. This 
is the unique niche that Fogarty will continue to fill in fiscal year 
2018 and beyond.
                                 ______
                                 
Prepared Statement of Joshua A. Gordon, M.D., Ph.D., Director, National 
                       Institute of Mental Health
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Mental Health (NIMH) of the National Institutes of Health 
(NIH). I am excited to discuss NIMH's efforts to accelerate scientific 
progress that will improve our understanding of mental illnesses, 
fueling transformative care for the greatest public health impact.
             funding impactful science to alleviate burden
    To help millions of Americans suffering from a mental illness, NIMH 
continues to ardently pursue its mission to transform the understanding 
and treatment of mental illnesses. In 2016, approximately 44.7 million 
U.S. adults suffered from a mental illness; of these, an estimated 10.4 
million U.S. adults experienced serious mental illnesses (SMI). To 
balance the challenge of alleviating the burden of mental illnesses 
now, while supporting research that will inform future treatments and 
interventions, NIMH prioritizes excellent and impactful science and 
strives for a diverse research portfolio of short-, medium-, and long-
term investments. For example, in the short term, efforts in suicide 
prevention research, such as screening and predicting risk in emergency 
departments, could result in significant decreases in suicide events. 
In the medium term, research on techniques to manipulate neural 
circuits could be applied to the treatment of mental illnesses in 
humans. In the long term, computational and theoretical approaches to 
psychiatry are needed to refine treatments.
                 early identification and intervention
    Each year, thousands of adolescents and young adults in the United 
States experience first episode psychosis. To explore methods for 
establishing early intervention programs to help people with psychosis, 
NIMH launched the Recovery After an Initial Schizophrenia Episode 
(RAISE) project, which clearly demonstrated that when coordinated 
specialty care was provided early in the disease, outcomes for 
individuals were superior to usual care, including symptom reduction, 
improvement in school and work functioning, and increased quality of 
life. Based on these findings, the Centers for Medicaid & Medicare 
Services extended Medicaid coverage for coordinated specialty care, and 
the Substance Abuse and Mental Health Services Administration (SAMHSA) 
set aside 10 percent of its Mental Health Block Grant allocation for 
each State to support evidence-based programs that target first episode 
psychosis. Today, over 200 CSC programs operate in 49 States.
    Suicide is a potential consequence of mental illnesses and one of 
the leading causes of mortality in the United States. Suicide rates 
have increased since 1999, and nearly 45,000 Americans died from 
suicide in 2016. Recent studies show that most individuals who die by 
suicide have had recent contact with a healthcare provider, and that 
early identification of those at risk for suicide is key to prevention. 
To address this major public health concern, NIMH partners with the 
National Action Alliance for Suicide Prevention and supports its Zero 
Suicide initiative to support healthcare systems reduce suicide events. 
Another example of NIMH-funded work in this area is the ED-SAFE 
project, which demonstrated that universal screening for suicide risk 
among adults in emergency departments (EDs) doubled the rate of 
detection, and ED-initiated interventions for high-risk adults 
decreased suicide attempts by as much as 30 percent.
    In addition, researchers in the NIMH Division of Intramural 
Research Programs developed a brief pediatric suicide risk screening 
instrument; the four-item Ask Suicide Screening Questions (ASQ) is now 
used in medical facilities around the world. Additional examples of 
NIMH-funded research include the Emergency Department Screen for Teens 
at Risk for Suicide (ED-STARS) study, which uses innovative approaches 
to suicide screening and assessment for youth in EDs. NIMH also 
supports collaborative research hubs, which aim to reduce the high 
suicide rates among American Indian and Alaska Native youth.
    Similarly, NIMH recognizes the importance of early identification 
and intervention strategies for individuals with autism spectrum 
disorder (ASD). NIH-funded research has identified ASD risk markers 
within the first 12 months of age; early signs of behavioral 
differences correspond with genetic and environmental risk for ASD that 
appear to act before birth and alter the very early stages of brain 
development. However, a critical gap exists in translating these 
methods into practical screening tools that could be widely used to 
identify ASD early in life. NIMH plans to launch an initiative aimed at 
developing and validating new screening methods for ASD for use in 
infants (0-12 months of age) which could lead to novel transformative 
treatments that improve outcomes.
     developing effective and transformative treatments of tomorrow
    NIMH supports efforts to systematically and rapidly employ `lessons 
learned' from research findings and clinical practice to improve 
patient care. To help narrow the gap between research and practice, the 
Mental Health Research Network (MHRN), a learning healthcare system 
that includes large-scale practical trials and services research, uses 
electronic health records large and diverse healthcare systems to 
improve delivery of effective treatments. The NIMH Early Psychosis 
Intervention Network (EPINET) is another learning healthcare system, 
which will focus on early psychosis treatment clinics by linking 
clinical sites. Like other learning healthcare models, the aim of 
EPINET is to share and compare data that will narrow the time gap for 
feedback and can help guide practice and ultimately improve mental 
healthcare. In addition, NIMH-funded research on mobile health 
(mHealth) technologies includes smartphone and texting approaches to 
help treat and monitor patients with mental illnesses. These methods 
are examples of how NIMH-funded research create opportunities for 
continuous evaluation and improvement of care.
    It is ever important that we continue to support research focused 
on developing tools that can be used to study and treat mental 
illnesses. For example, NIMH co-leads the cutting-edge NIH Brain 
Research through Advancing Innovative Neurotechnologies (BRAIN) 
Initiative. Maps of whole brains in action, the ability to identify 
thousands of brain cells at a time, and innovative brain scanners are 
just a few of the advances funded by this groundbreaking effort. In the 
past 3 years, research under the Initiative has advanced so rapidly 
that now many of the previously funded individual projects will receive 
expanded support to achieve the ambitious goals of the BRAIN 
Initiative.
    Specifically, NIH recently announced funding for 110 new awards for 
the BRAIN Initiative. The new round of awards includes the BRAIN 
Initiative Cell Census Network (BICCN), aimed at providing researchers 
with comprehensive references of diverse brain cell types to generate 
the knowledge necessary for understanding brain disorders, including 
mental illnesses. Additionally, new BRAIN Initiative research awards 
aim to address neuroethical issues associated with human brain 
research. Through the innovative studies supported by the BRAIN 
Initiative, researchers will be able to produce a revolutionary, 
dynamic picture of the brain that will lend to new ways to treat, cure, 
and even prevent mental illness.
    Finally, NIMH has supported successful efforts to map the genes 
that predispose individuals to schizophrenia and other SMIs. Thanks to 
these efforts, we now know of hundreds of locations in the genome 
associated with risk for SMI. Each of these locations represents an 
important clue into the neurobiology of SMIs and holds promise as a 
potential therapeutic target. Current efforts, including the 
PsychENCODE consortium, which studies the relationship between genetic 
risk and protein expression in the brain, and an initiative that uses 
convergent neuroscience approaches to elucidate how these risk factors 
alter the function of neurons and circuits in the brain, are aimed at 
translating these genetic discoveries into new knowledge and novel 
treatments.
    NIMH will continue to vigorously support research using novel 
approaches to enhance biological understanding, translation of 
evidence, services and intervention delivery, and therapeutics 
development, all aimed at reducing the tremendous burden shouldered by 
individuals and families living with mental illnesses.
                                 ______
                                 
  Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN Director, 
                 National Institute of Nursing Research
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 Budget request for the National 
Institute of Nursing Research (NINR) of the National Institutes of 
Health (NIH).
                              introduction
    The mission of NINR is to promote and improve the health of 
individuals, families, and communities. In pursuit of this mission, 
NINR has set forth a bold, innovative scientific agenda in our 
strategic plan, ``Advancing Science, Improving Lives.'' The plan, which 
incorporates long-standing focus areas of nursing science and 21st 
century solutions for improving the Nation's health, encompasses four 
focus areas, including symptom science, wellness, self-management, and 
end-of-life and palliative care; along with continued development of a 
21st-century nurse scientist workforce, and finding ways in which 
technology and innovation can contribute across all these areas. I 
appreciate this opportunity to share some examples of NINR's research.
       symptom science: promoting personalized health strategies
    Through its focus on symptom science, NINR supports research to 
develop new knowledge in biology and behavior to improve our 
understanding of symptoms such as fatigue, pain, and sleep disturbance. 
For example, NINR-supported investigators found a potential connection 
between the use of opioids to treat pain and the rate of healing for 
chronic wounds. They found that patients who had never received opioids 
healed more rapidly, and that patients receiving higher opioid doses, 
because they had a larger wound size or painful co-occurring 
conditions, had slower wound healing in comparison with those receiving 
lower doses or no opioids. Their findings raise important 
considerations on potential connections between symptoms, biological 
factors, and clinical management of pain and chronic wounds.
           wellness: promoting health and preventing illness
    In promoting wellness, NINR strives to build the science to 
understand and prevent chronic conditions, reduce burden for patients 
and caregivers, and eliminate health disparities. A recent NINR-
supported study found that family caregivers of persons with 
Alzheimer's and related dementias (ADRD) reported an average of seven 
new or worsening symptoms and signs in the care recipient, such as 
confusion, decreased activity, and agitation, over a six-month period. 
Understanding the range of symptoms that caregivers must respond to 
when caring for loved ones with ADRD can guide the development of 
future educational materials and interventions. Other NINR-supported 
researchers are testing: a family-focused intervention to reduce the 
risk of type 2 diabetes and cardiovascular disease in Hispanics; the 
effectiveness of an intervention to reduce the rate of obesity in rural 
Alaska Native children; and an intervention to increase physical 
activity and reduce falls in older adults.
       end-of-life and palliative care: the science of compassion
    As the lead Institute for end-of-life research at NIH, NINR 
supports research to inform high quality care for individuals and their 
caregivers, improve management of pain and other advanced symptoms, and 
facilitate decisionmaking at all stages of illness, including at the 
end of life. With our support of the Palliative Care Research 
Cooperative (PCRC) group, we continue to build the science of end-of-
life and palliative care by expanding this extensive network of over 
400 multidisciplinary palliative care scientists to include over 160 
clinical trial research sites across the U.S. NINR recently expanded 
its Palliative Care: Conversations Matter initiative, which aims to 
raise awareness of pediatric palliative care, by developing a new Web 
feature profiling different members of the pediatric palliative care 
team, including a chaplain, a child life specialist, a nurse, a nurse-
scientist, a pediatrician-researcher, and a social worker. This 
resource gives families insight into the array of providers and 
services available to support them and gives providers a glimpse into 
how teams work together.
          supporting a 21st century nursing science workforce
    NINR has long-recognized the importance of supporting scientists at 
all career levels, particularly those at an early career stage. NINR 
supports a variety of training opportunities for scientists and 
trainees. In addition to funding extramural trainees, NINR sponsors a 
Symptom Methodologies Research Boot Camp, focused on precision health 
methodologies and the latest advances in various `omics' such as 
genomics and microbiomics. NINR's Summer Genetics Institute provides a 
foundation in molecular genetics to improve research and clinical 
practice for graduate students, faculty, and clinicians. NINR also 
provides on-line video training resources on its website to support an 
innovative workforce, from students to early- and mid-career 
scientists.
                               conclusion
    Thank you for this opportunity to share some of NINR's recent 
accomplishments. We look forward to continuing to support nursing 
research to advance science, improve lives, and envision new pathways 
to improve health.
                                 ______
                                 
 Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National 
                    Human Genome Research Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National Human 
Genome Research Institute (NHGRI) of the National Institutes of Health 
(NIH).
                       the forefront of genomics
    NHGRI is, and always has been, at the forefront of genomics 
research. NHGRI led the U.S. contribution to the Human Genome Project, 
which was completed in 2003, and has since embarked on evermore 
ambitious endeavors, including the dissemination of genomic 
technologies, knowledge, and expertise throughout the NIH, into the 
private sector, and around the world. NHGRI accomplished this by 
driving cutting-edge research, developing new methods and approaches, 
and studying the impact of genomics on society with the goal of 
improving the health of all humans through genomic advances. The 
current pace of genomics is breathtaking, and we are approaching a 
transitional time in which there will be rapid uptake of genomics in 
medicine for prevention, diagnosis, and treatment of disease.
    To prepare to lead the next phase of genomics, NHGRI officially 
launched a new strategic planning process in early 2018. This 2-year 
effort will generate a `2020 Vision for Genomics' and position the 
Institute to lead genomics research and its applications to human 
health into the next decade.
    Our strong tradition of audacious thinking and effective strategic 
planning has led to advances that today are enabling some of the most 
high-profile initiatives in biomedical research. Examples include the 
NIH All of Us Research Program, which seeks to build the largest, most 
diverse dataset of its kind for health researchers, and the Cancer 
Moonshot initiative, which aims to accelerate cancer research and to 
improve our ability to detect, prevent, and treat cancer. The NHGRI-
funded Electronic Medical Records and Genomics (eMERGE) Network, now in 
its third phase, has served as an invaluable pilot for precision 
medicine research studies, like All of Us, by developing the tools and 
approaches for using genomic information coupled with data in 
electronic medical records to study human health and disease, including 
prevention. The Cancer Genome Atlas (TCGA), equally funded by NHGRI and 
the National Cancer Institute (NCI), generated comprehensive maps of 
key genomic changes in 33 types of cancer and made all the generated 
data publicly available to the research community; this program 
provided a foundation upon which the molecular bases of cancer continue 
to be defined, revealing new approaches for cancer treatments. In 
addition, efforts like TCGA and the Cancer Moonshot heavily rely on the 
dropping costs of genome sequencing, which has been greatly facilitated 
by NHGRI's technology development research programs.
    As noted earlier, the uptake of genomic medicine approaches will 
increase rapidly in the coming years, and NHGRI is committed to laying 
the groundwork for these changes. An example effort that will be 
underway in fiscal year 2019, if funding allows, is the Clinical 
Sequencing Evidence-Generating Research Program (CSER), which aims to 
generate and analyze evidence for the use of genome sequencing in 
clinical care and to address barriers to genomic medicine 
implementation. This program has a targeted focus on recruiting 
ancestrally diverse and underserved populations, recognizing that the 
full benefit of genomic medicine will not be realized unless all of the 
diverse populations in the United States benefit equitably from genomic 
advances.
    Compared to even a decade ago, genomics is now associated with a 
much greater breadth and depth of research activities. Furthermore, 
influenced by NHGRI's leadership, virtually every NIH Institute and 
Center now funds genomics research to some extent, and a significant 
amount of genomics research is funded beyond NIH. Recognizing that 
going forward, a majority of genomics research will be funded by others 
in the U.S. and internationally, NHGRI aims to identify, lead, and 
support areas of genomics that are paradigm-setting, that enable novel 
applications, and that expand the field--all with a focus on 
applications to human health and disease. In doing so, NHGRI will 
directly stimulate and achieve highly impactful and generalizable 
progress in genomics that will benefit the efforts of others for years 
to come.
                                research
    Our foundational work in technology development, coupled with new 
approaches for elucidating genome function, is fueling discoveries of 
how genomic variation relates to human health and disease; in turn, 
this knowledge is increasingly being applied to patient care through 
pilot projects that study the implementation of genomic medicine.
    In fiscal year 2019, if funding allows, NHGRI's longstanding Genome 
Sequencing Program will continue its fundamental work to identify 
genomic variants associated with disease and to provide resources for 
the research and clinical communities to discover the genomic 
underpinnings of disease. The Centers for Common Disease Genomics 
(CCDGs) are conducting an in-depth genomics study of roughly 10 common 
diseases, including cardiovascular disease and developmental disorders, 
to identify genomic variants that either increase or decrease risk 
associated with those diseases. Using the generated data, the sites 
intend to develop improved and novel analysis methods and study designs 
across the entire program. So far, the CCDG sites have generated over 
50,000 whole-genome sequences and over 38,000 whole-exome sequences 
(the protein-coding portions of the genome); the size of such studies 
is needed to generate the statistical power that will allow reliable 
conclusions about these diseases to be derived.
    Many of NHGRI's principal accomplishments have centered on 
unraveling the complexities of the genome and giving researchers open 
access to valuable data. For example, the Encyclopedia of DNA Elements 
(ENCODE) Project is creating a catalog of all the parts of the human 
genome that are functional (i.e., that play an active biological role). 
All of the generated ENCODE data are made freely available, providing 
every scientist rapid access to this unique and valuable information 
for their research. In fact, ENCODE's value in biomedicine can be 
readily appreciated by the widespread use of these data: there are more 
than 2,000 scientific publications from research groups that have used 
ENCODE data for their published work.
    Another treasure trove of data for the biomedical research 
community was generated by the NHGRI-led Common Fund project GTEx 
(genotype-tissue expression), which began in 2008 and aimed to 
establish a database and accompanying tissue bank to allow scientists 
to study the relationship between genomic variation and gene 
expression. In October 2017, Nature published a collection of papers 
highlighting discoveries from the program. The analyses include data 
for thousands of tissue samples and demonstrated how gene regulation 
differs across individuals and tissue types.
    NHGRI has also been building its portfolio in genomic medicine, 
piloting projects that seek to explore how to integrate genome 
sequencing within clinical care and begin to build an evidence base 
demonstrating its effectiveness. One example is the Newborn Sequencing 
in Genomic Medicine and Public Health (NSIGHT) program, which began in 
2013 to study the opportunities and challenges in the use of genome 
sequencing for the care of newborns. NSIGHT has shown ways in which 
newborn sequencing can be critical for saving lives by increasing the 
speed of diagnosis. For example, one of our NSIGHT grantees, whose work 
was recently featured in Time magazine, is using genome sequencing to 
provide diagnoses and suggest treatment changes for critically ill 
infants in the neonatal intensive care unit in a timeframe that can 
make life-altering differences.\7\ Notably, this group recently set a 
Guinness World Record for the fastest genomic diagnosis--19.5 hours.
---------------------------------------------------------------------------
    \7\ Park, A. (2017) Genetic Testing is Providing New Hope for 
Babies Born with Mysterious Ailments. Time. http://time.com/4951200/
genetic-testing-providing-hope-babies-ailments/.
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                               conclusion
    As is clear from our research portfolio, NHGRI does more than fund 
the discovery of knowledge and create new technology--we have catalyzed 
cultural changes across biomedical research. We have demonstrated an 
unrelenting commitment to data sharing, our `team science' approach has 
fostered a spirit of collaboration among scientists, and we have 
provided researchers with access to shared tools and data to transform 
genomic advances into health discoveries. As NHGRI delves into 
strategic planning in fiscal year 2019 and beyond, we will collaborate 
with experts in the field to identify the cutting-edge areas across our 
diverse research domains that the Institute should champion and support 
in the coming decade. We will also continue to tackle the 
underrepresentation of minorities in genomics research to be sure that 
the knowledge gained through the Federal investment in genomics 
benefits all.
    NHGRI believes that advances in genomics research are transforming 
our understanding of human health and disease, and we are excited to 
continue accelerating breakthroughs, improving patient care, and 
advancing genomics in society.
                                 ______
                                 
Prepared Statement of Jill Heemskerk, Ph.D., Acting Director, National 
           Insitute of Biomedical Imaging and Bioengineering
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the 
National Institutes of Health (NIH).
    The mission of NIBIB is to improve human health by leading the 
development of biomedical technologies and accelerating their 
application. NIBIB supports research that integrates engineering with 
the physical and life sciences to develop emerging technologies that 
can be applied to a broad range of biomedical and healthcare problems. 
Building partnerships with industry, academia, and other Federal 
agencies is a high priority for the institute. A few examples from the 
many exciting NIBIB-funded research efforts that are leading to better, 
faster, and less costly ways to advance public health are shared in 
this testimony.
                    on the spot food allergy testing
    Eating out can be a challenge for people with allergies. Diners 
must rely on knowing what ingredients contain the allergens they must 
avoid, and on restaurants to serve dishes that exclude them. 
Recognizing this widespread public health problem, researchers have 
developed a system called integrated exogenous antigen testing (iEAT). 
The purpose of the iEAT system is to give those who suffer from food 
allergies a rapid, accurate device that allows them to personally test 
foods in less than 10 minutes. The device is small enough to fit on a 
keychain and can test for common allergens such as gluten, milk, or 
nuts. The device contains a disposable testing chamber, so once a test 
is completed the chamber can be replaced and the device used again. 
After developing and testing a prototype of the device, the research 
team granted a license to a local start-up company to make iEAT 
commercially available. In the future the device could be adapted to 
test for other allergens or substances.
                 cuff-less blood pressuring monitoring
    A person's blood pressure is one of several key indicators of 
health, but the inflatable cuff device used to measure blood pressure 
is largely the same as it was 100 years ago. Measuring blood pressure 
while in a doctor's office gives physicians a limited view since blood 
pressure can vary throughout the day. Researchers are developing a new 
``cuff-less'' method to accurately measure blood pressure more 
frequently and without the need for special equipment. One group is 
making progress using a modified smart phone case with built-in sensors 
and an app to capture blood pressure by pressing a finger on the 
phone's home button. The ability to monitor blood pressure on an 
ongoing basis could help alert people to potential problems and more 
consistently monitor their blood pressure if they are at risk or are 
taking medications. This could help reduce the risk of cardiovascular 
disease through improved management of blood pressure.
                        clearing out blood clots
    Blood clots that form in the deep veins of the legs are called deep 
vein thrombosis and can be quite painful, and even fatal if a clot 
dislodges from the wall of the vein and travels to the heart or lungs. 
Currently, intravascular treatments use devices inserted into the vein 
to trap clots, but they have limitations including damage to the blood 
vessel wall. In some patients, clot-thinning medication is required, 
which can have a range of side effects. A new approach to overcome 
these limitations uses a surgical tool that is inserted into a vein and 
directs ultrasound waves directly at clots to break them up into tiny 
pieces. It is targeted and therefore minimizes damage to blood vessels; 
and because the broken pieces are tiny, patients do not need to use 
blood thinning medication following the procedure. In addition to using 
ultrasound, researchers are adding injectable microbubbles that vibrate 
when exposed to the ultrasound waves. This helps to further break up 
the clot. This tool is portable and is estimated to cut the declotting 
procedure time by more than half, from 10 hours to four hours. So far, 
the tool has only been tested in synthetic blood vessels, and more 
study is needed to bring this treatment to patients.
                nanovaccines weaponized to battle tumors
    A new vaccine designed to stimulate a multi-pronged immune response 
can stimulate the immune system to specifically attack a tumor, while 
simultaneously inhibiting the suppression of the immune system, which 
often occurs in people with cancer. The researchers also developed a 
way to shrink the vaccine molecule so that it can more easily reach the 
parts of the immune system to activate it. Using colon cancer that had 
spread to the lungs as a test case for this approach, the nanovaccine 
successfully blocked lung tumor growth in a mouse model. Further 
testing revealed that mice receiving the nanovaccine had a significant 
increase in a type of immune cell that can target cancerous cells. 
Another potential benefit of this approach is that it mounts an anti-
tumor immune response that circulates through the system, and therefore 
is particularly valuable for finding and inhibiting metastatic tumors 
growing throughout the body.
            solving a common heart disease with engineering
    Ischemic cardiovascular disease is a result of impaired blood 
circulation to tissues and organs and is the leading cause of death and 
disability in the U.S. Damage to small blood vessels is difficult to 
treat and can result in heart failure, stroke, or other arterial 
diseases. To address this problem, researchers developed a way to grow 
new blood vessels using 3D printed patches. The specially designed 
patches are seeded with cells and implanted into damaged areas. Once 
implanted, the patches induced the growth of new blood vessels. This 
early stage, basic research is an example of interdisciplinary teams 
including engineers, biologists, and clinicians combining their 
expertise and collaborating to solve health problems.
                    advances from nibib laboratories
    While the majority of NIBIB's budget supports research projects 
throughout the U.S., NIBIB also supports a small, but robust program 
within its Intramural Research Program (IRP). These investigators are 
working to create optical imaging technologies that provide 
unprecedented high resolution and speed to study living cells in real 
time. Others create ``theranostic'' imaging probes--based on 
nanomaterials--that combine therapeutic and diagnostic capabilities to 
improve early diagnosis, monitor therapeutic responses, and guide drug 
discovery and development.
    In one example, researchers developed a new radiotracer to help 
diagnose prostate cancer. Prostate cancer is the fifth leading cause of 
death worldwide and is especially difficult to diagnose, particularly 
early on. While prostate cancer is relatively easy to treat in its 
initial stages, it is prone to metastasis and can quickly become 
deadly. The research team developed a radiotracer that could identify 
prostate cancer at all stages. This new tracer is one of the first 
dual-receptor target tracers, which target more than one biomarker, to 
be studied in humans. This new method improves on the current practice 
that can lead to many false positive results and cause the patient to 
undergo unnecessary treatments or painful biopsies. A successful Phase 
I clinical trial with a small group of patients to establish safety and 
identify any possible side effects was recently completed.
                               conclusion
    Advances in technology are catalyzing the development of solutions 
to previously intractable disorders and improved approaches to 
biomedical research. As these examples illustrate, this type of 
research requires many disciplines to work together. This integration 
of disciplines is what defines NIBIB's approach. NIBIB is committed to 
supporting such teams of researchers to solve major biomedical 
challenges that will improve the health of all Americans.
                                 ______
                                 
   Prepared Statement of Richard J. Hodes, M.D., Director, National 
                           Institute on Aging
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute on Aging (NIA) of the National Institutes of Health (NIH).
                     aging: a universal risk factor
    Each one of us is susceptible to the effects of aging, which 
remains the most powerful driver of chronic diseases and disabilities 
that affect older adults. As the number of Americans ages 65 and older 
soars in the coming decades--from an estimated 46.2 million in 2014 to 
82.3 million in just 26 years, according to projections from the U.S. 
Census Bureau--it is increasingly urgent that we pursue a comprehensive 
national effort to understand aging, to develop interventions that will 
help older adults enjoy robust health and independence, and to support 
American elders' active engagement with their families and communities.
    At the NIH, the NIA leads this effort. We support genetic, 
biological, clinical, behavioral, and social research related to the 
aging process, healthy aging, and diseases and conditions that increase 
with age. We also support training of the next generation of 
researchers in geriatrics and related fields. In addition, we are the 
lead Federal agency supporting research on Alzheimer's disease and 
related forms of dementia (AD/ADRD).
         research on alzheimer's disease and related dementias
    In a recent analysis based on 2010 data, 5.5 million Americans were 
projected to have Alzheimer's disease by 2018. It's true that several 
studies, including the long-running Framingham Heart Study, have 
identified declines in the incidence and prevalence of dementia since 
the 1970s, possibly associated with increased educational attainment 
among study populations. However, if current population trends 
continue, these numbers will increase significantly as the number of 
older Americans rises--unless we learn how to prevent or effectively 
treat the disease.
    Since passage of the National Alzheimer's Project Act in 2011, an 
extraordinary influx of funding directed at AD/ADRD has made it 
possible for NIH, led by NIA, to begin building a series of bold and 
innovative research programs, infrastructure, and new partnerships 
aimed at laying the foundation for precision medicine for AD/ADRD. NIA 
and other NIH Institutes are harnessing the tremendous power of big 
data to gain insight into the basic biology of AD/ADRD, as well as 
factors that may confer resilience to these diseases; accelerating the 
discovery of the next generation of new targets and biomarkers through 
the open science research model of the Accelerating Medicines 
Partnership for AD (AMP-AD); and establishing new translational 
infrastructure programs to enable rapid sharing of data and research 
models and enhancing research rigor and reproducibility.
    NIA currently supports over 140 active clinical trials of 
interventions to enhance cognitive health in older individuals and to 
prevent, treat, or manage symptoms of AD/ADRD. These studies range from 
studies of emerging therapeutics developed in academic centers and the 
small business community, to studies of the cognitive effects of drugs 
commonly used for other conditions, to clinical trials involving 
lifestyle interventions such as exercise, dietary change, and cognitive 
training. Investigators with AMP-AD have identified over 100 potential 
new drug targets for AD/ADRD, and over 30 projects for development of 
novel therapeutics against a variety of targets are under way in NIA's 
Alzheimer's Disease Translational Research Program. NIH has also 
established the Alzheimer's Clinical Trial Consortium (ACTC), 
consisting of 35 sites across the United States, to support trials 
across the full spectrum of AD/ADRD. The ACTC will also spur innovation 
in trial design and recruitment, with a specific focus on inclusion of 
communities underrepresented in AD research.
    We have made important progress. For example, an NIA-supported 
international research team used cryo-electron microscopy to visualize 
the structure of individual tau fibrils (a pathological hallmark of 
several forms of dementia) for the first time. The high-resolution, 
exquisitely detailed images helped explain why tau-based therapies have 
been difficult to develop--its components are so tightly bound together 
as to be impermeable--but also suggested possible new avenues for 
therapy. Other investigators analyzed Medicare data and noted an 
association between use of cholesterol-lowering statin drugs and 
reduced risk of AD. Intriguingly, the reduction in risk varied across 
sex, race, and particular statin used, suggesting that the right statin 
type for the right person at the right time may provide a relatively 
inexpensive means to lessen the burden of AD.
    Our continuing efforts have been informed by input from researchers 
and advocates worldwide through key scientific conferences, including 
periodic Summits on Alzheimer's Disease (most recent: March 2018) and 
Alzheimer's Disease-Related Dementias (most recent: 2016, with the next 
Summit planned for 2019). A Summit in October 2017 also brought 
together experts to discuss dementia care and the unique needs of 
caregivers of persons with AD/ADRD.
                        advancing aging research
    Recognizing aging as the most powerful risk factor for diverse 
diseases and frailties, NIA supports research into the underlying 
biological mechanisms of aging. For example, the trans-NIH Geroscience 
Interest Group, established by the NIA and joined by most NIH 
Institutes, promotes research on the links between aging biology and 
etiology of chronic diseases. NIA also supports research on diet and 
healthy aging, as well as two multi-investigator interventions testing 
programs to identify and validate compounds that extend life and 
improve health in laboratory animals. Ongoing collaborations with the 
National Institute of Allergy and Infectious Diseases and the National 
Cancer Institute continue to expand our understanding of the aging 
immune system and the role of aging in the etiology of cancer.
    NIA's longtime flagship studies in aging remain vibrant with 
opportunities to apply new technologies and thinking to their treasure 
troves of data. The Baltimore Longitudinal Study on Aging, 60 years old 
in 2018, continues to break new ground in identifying the longitudinal 
physical and cognitive changes that define aging; elucidating the 
factors that affect the rate of age-related change; and understanding 
the relationship between advancing age and chronic disease. BLSA 
investigators are particularly interested in ``exceptional agers''--
those rare individuals who live well into their eighties with few 
health problems. This year the Health and Retirement Study (HRS) will 
complete 25 years of data collection and will mark the occasion with 
several enhancements, including deployment of an improved approach to 
assessing cognitive impairment and dementia and expanded collection of 
objective health measures, including blood-based assays capturing the 
aging of the immune system and related molecular and cellular age-
related changes. This project and others are designed to reveal the 
biological pathways through which differences among social and 
demographic groups can affect health.
    NIA-supported investigators are looking at better ways to translate 
what we know into clinical practice that will help improve the health 
and well-being of older Americans. For example, starting in fiscal year 
2019, NIA will support demonstration projects leading to pragmatic 
trials--clinical trials that are conducted under ``real-world'' 
conditions, as opposed to the tightly controlled conditions of a 
traditional trial--for a variety of age-related diseases and 
conditions, including care of persons with dementia in long-term 
settings. The National Advisory Council on Aging has also recently 
approved in concept a new initiative to explore ``deprescribing'' 
strategies for older adults with multiple chronic health conditions. 
This research, which will begin in fiscal year 2019, will address 
inappropriate prescribing of medication, which is estimated to affect 
20 percent of older adults, one-third of individuals in long-term care 
facilities and over half of the persons with advanced dementia in 
nursing homes.
              empowering the next generation of scientists
    As the number of older Americans continues to grow, we must foster 
the development of the next generation of scientists whose research 
will lead to improved care and more effective treatment for older 
patients with complex medical conditions. To encourage emerging 
scientists, NIA supports an advantage in pay line for new and early-
stage investigators. The Paul Beeson Career Development Awards in Aging 
Research program, sponsored by the NIA, the National Institute of 
Neurological Disorders and Stroke, and private partners, continues to 
produce leaders in the fields of aging and geriatrics research. A 
recent Funding Opportunity Announcement led to awards for four new 
training programs for joint MD-PhDs in the social sciences relevant to 
aging. Finally, the Butler-Williams Scholars Program (formerly the NIA 
Summer Institute) remains a vibrant and vital institution at NIA.
    Thank you. I welcome your questions.
                                 ______
                                 
Prepared Statement Of Stephen I. Katz, M.D., Ph.D., Director, National 
      Institute of Arthritis and Musculoskeletal and Skin Diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of 
the National Institutes of Health (NIH).
                    niams research impacts everyone
    NIAMS is the primary Federal agency for supporting medical research 
on diseases of the bones, joints, muscles, and skin. As such, our work 
touches the lives of nearly every American. A 2018 publication by the 
Centers for Disease Control and Prevention notes that an estimated 23 
percent (54 million) of Americans have been diagnosed with some form of 
arthritis, including osteoarthritis, rheumatoid arthritis, gout, and 
fibromyalgia; 24 million of whom have symptoms severe enough to hinder 
activities they want or need to do. This problem is expected to grow as 
our population ages; 78.4 million adults will have arthritis by 2040 if 
current trends continue. When arthritis is combined with other bone and 
joint conditions such as neck and low back pain, osteoporosis, and 
musculoskeletal injuries, the total cost of medical care and lost wages 
is estimated to be $874 billion annually. Diseases in the NIAMS 
research portfolio also have a global impact. In 2015, low back and 
neck pain was the leading cause of disability worldwide, while skin 
diseases such as eczema and psoriasis ranked fifth.
    NIAMS is enhancing health, lengthening life, and reducing illness 
and disability by supporting basic and translational research and 
clinical trials that will inform medical practice; training the next 
generation of bone, joint, muscle, and skin scientists; and 
disseminating health information and the findings from the studies it 
supports to all Americans. For the remainder of my statement, I will 
describe a few of the many recent research activities that are 
benefiting people today and enabling future advances.
                   research advances funded by niams
    My first two examples focus on the risks and benefits of steroids, 
which an estimated 1 percent of the entire U.S. population takes as 
chronic therapy. A team of researchers studying the effects of repeated 
steroid injections for knee pain found that people who received shots 
every twelve weeks for 2 years showed worsening joint damage and no 
long-term reduction in pain compared with those who received saline 
injections. While this study did not evaluate the benefits of steroid 
injections into the knee for short-term pain relief, it does not 
support their long-term use for treatment of symptomatic knee 
osteoarthritis. Another group of investigators looked at the mechanisms 
by which steroids preserve muscle function for boys who have Duchenne 
muscular dystrophy. Using cells and a mouse model, the team determined 
that a weekly dosing regimen increases the activity of two genes 
involved in muscle cell repair, while daily dosing activates pathways 
that cause muscle to shrink and weaken. Their discovery explains the 
seemingly contradictory results of previous studies into the drugs' 
effects. If these observations from cell cultures and mice also occur 
in patients, this study could directly inform how steroids are 
prescribed to maximize their therapeutic benefits while minimizing 
their negative effects.
    After decades of investigating Pompe disease, a rare, life-
threatening condition that cripples the muscles, NIAMS-funded 
researchers have developed a gene-transfer approach that shows promise 
in mice. While the study's main goal was to test whether the strategy 
would prevent the animals from developing an immune response, it also 
demonstrated that this gene therapy could potentially replace standard 
care. These results directly contributed to an investigational new drug 
approval by the Food and Drug Administration to move this approach into 
clinical trials. Gene therapy also holds promise for people who have 
the rare and life-threatening skin disease recessive dystrophic 
epidermolysis bullosa, which causes fragile, blistering skin. In a 
phase 1 clinical trial, investigators collected skin biopsies from four 
patients and used a harmless virus to correct the gene for the 
defective skin protein in the patients' cells. Next, they coaxed the 
genetically modified cells to grow into sheets of skin about the size 
of a deck of playing cards. Then, the new skin was grafted back onto 
patients to speed healing of the open wounds that characterize the 
disease. After 12 months, half of the two-dozen grafts were still 
covering patients' wounds. Investigators will continue monitoring these 
patients and are recruiting people for a phase 2 clinical trial.
    NIAMS research is also developing techniques to help clinicians 
identify which patients are likely to have more severe or rapidly 
progressing disease. For example, researchers found that positron 
emission tomography (PET), a technique that can visualize the body's 
metabolic processes, could be used to distinguish between patients who 
have large vessel vasculitis or other diseases with similar symptoms. 
PET may also help clinicians predict which patients are at highest risk 
of disease relapse. Another study examined children with juvenile 
myositis, a disease where the muscles are attacked by antibodies in the 
patients' blood. The investigators found that children with a certain 
type of antibody experience worse muscle disease and more severe 
weakness. This finding also explains why these children show less 
benefit from existing therapies and opens a possibility for better 
treatments. Other researchers discovered blood markers that may 
distinguish the subset of people who have systemic sclerosis that are 
at risk of developing interstitial lung disease (the leading cause of 
death for these patients). This advance also may lead to new therapies.
    Other studies of basic cellular processes hold promise for people 
who suffer from skin diseases. Investigators determined that a 
molecular pathway involving the protein JAK1 is involved in chronic 
itch. They then tested whether an existing drug that blocks JAK 
signaling could help people who do not respond to other treatments 
(e.g., some cases of atopic dermatitis). Their results were promising 
although further clinical studies are needed to confirm the findings. 
Additional teams of researchers are examining how microbes on the skin 
may influence a person's susceptibility to atopic dermatitis. A pair of 
studies, focusing on the role of the bacterium Staphylococcus aureus in 
driving the disorder, suggest that reducing S. aureus by increasing 
beneficial skin bacteria could be an effective treatment.
    NIAMS-funded research is also having an impact beyond arthritis and 
musculoskeletal and skin diseases. For example, psoriasis has been 
linked to an increased risk of developing type 2 diabetes. A new 
finding that the risk of diabetes is highest for those with the most 
severe psoriasis sheds light on the causes of both diseases and 
provides compelling evidence that certain patients should receive 
targeted diabetes prevention strategies. Other investigators are 
showing that while early antiretroviral therapy saves HIV patients' 
lives, it also damages their bones, emphasizing the importance of 
developing bone-preserving strategies for this population. Weight loss 
due to bariatric surgery, another life-saving intervention, also is 
associated with bone loss, and researchers are beginning to understand 
the role that glucose metabolism plays in bone health. This discovery 
could lead to targeted prevention and treatment strategies for 
osteoporosis, the skeletal complications of bariatric surgery, and 
diabetic bone fragility. Still other research is explaining why muscle 
breaks down in cancer patients (a process known as cachexia). A number 
of molecular pathways and targets underlying the muscle wasting process 
have been discovered recently, and investigators are beginning to 
identify existing drugs or new targets to stop this from occurring.
                     looking to a promising future
    The wide reach of NIAMS-funded research is allowing people affected 
by diseases within our mission to benefit from large multi-agency 
programs such as the Cancer Moonshot Program and the Regenerative 
Medicine Innovation Project supported by the 21st Century Cures Act. 
Moving forward, investigators will examine connections between 
immunotherapies for cancer and autoimmune disease and will continue to 
be encouraged to apply for funding for research on bone, joint, muscle, 
and skin regeneration. NIAMS, along with the National Institute of 
Allergy and Infectious Diseases, continues to lead the Accelerating 
Medicines Partnership (AMP) in rheumatoid arthritis and lupus which is 
working to identify and validate promising biological targets for those 
diseases. With guidance from NIAMS, three other Institutes, and the NIH 
Common Fund, the trans-NIH Molecular Transducers of Physical Activity 
in Humans program continues to make progress developing a database that 
researchers can use to elucidate changes that take place in our bodies 
in response to exercise and how those changes relate to human health.
    In fiscal year 2019, NIAMS plans to continue support for its 
Research Innovations for Scientific Knowledge (RISK) funding 
opportunities, which allow investigators from around the country to 
submit cutting edge, unconventional, innovative research proposals for 
up to 3 years of funding. To help bolster the next generation of 
researchers, the Institute also continues to encourage early 
established investigators who have successfully renewed their first 
NIAMS research project grant to apply for a supplemental funding 
program to aid the transition of their individual research project into 
a broader, more robust and resilient research program.
                                 ______
                                 
    Prepared Statement of George F. Koob, Ph.D., Director, National 
               Institute on Alcohol Abuse and Alcoholism
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute on Alcohol Abuse and Alcoholism of the National Institutes of 
Health (NIH).
             burden of alcohol misuse in the united states
    Alcohol misuse has profound effects on the health and well-being of 
individuals, families, and communities. Approximately 15 million people 
in the United States have alcohol use disorder (AUD), a chronic 
relapsing brain disease related to alcohol misuse. 88,000 lives are 
lost to alcohol-related causes annually, making alcohol the third 
leading preventable cause of death in the United States. Alcohol misuse 
cost the U.S. almost $250 billion in 2010. Guided by its 2017-2021 
strategic plan, the National Institute on Alcohol Abuse and Alcoholism 
(NIAAA) supports research and initiatives to generate and disseminate 
fundamental knowledge about the effects of alcohol on health and well-
being, and apply that knowledge to improve the diagnosis, prevention, 
and treatment of alcohol-related problems, including AUD, across the 
lifespan.
             advancing translational and clinical research
    For nearly five decades, NIAAA has supported cutting-edge research 
to reduce the toll that alcohol misuse takes on human health and well-
being. The Institute's vast portfolio of translational and clinical 
research has led to more effective interventions to prevent and treat 
alcohol misuse and related conditions, provided support for integrating 
prevention and treatment services into mainstream healthcare, and paved 
the way for the development of novel strategies to address medical 
conditions associated with alcohol misuse.
Alcohol Treatment Navigator\SM\
    In any given year, less than 10 percent of individuals diagnosed 
with AUD receive treatment. Although effective behavioral interventions 
and medication-assisted treatment are available, in addition to mutual 
help groups, people often do not know the full extent of their options 
or where to turn for help. In October 2017, NIAAA launched the Alcohol 
Treatment Navigator\SM\ (alcoholtreatment.niaaa.nih.gov), a 
comprehensive online resource to help people search for professionally-
led, evidence-based alcohol treatment. The Navigator educates consumers 
about AUD and treatment options, provides 10 recommended questions to 
ask a potential provider, and suggests five signs of higher quality 
treatment to recognize. It also provides instructions for searching 
several existing online directories of licensed professional 
therapists, accredited alcohol treatment programs, and board-certified 
addiction medicine physicians. With the Navigator, adults searching for 
AUD treatment will be better able to find care that meets their unique 
needs, friends and family members will feel empowered to help an adult 
loved one struggling with AUD, and healthcare providers can feel more 
confident in screening their patients for AUD knowing there is a tool 
to share with those who need a referral to treatment. Given that 
treatments for AUD work better for some people than others, NIAAA will 
continue to support research on the neurobiological mechanisms that 
underlie AUD to identify novel medication targets that could ultimately 
expand the number of effective treatment options.
Addiction Medicine in Routine Healthcare
    Many individuals with AUD often seek primary care for a health 
problem related to alcohol misuse rather than for the misuse itself, 
indicating a need for addiction medicine approaches in routine medical 
practice. NIAAA provides primary care and other healthcare providers 
with tools to help them become more proficient in conducting alcohol 
screening and evidence-based interventions, including medication-
assisted treatment. The Institute is also partnering with the National 
Institute on Drug Abuse, the Substance Abuse and Mental Health Services 
Administration, and others to improve physician training in the 
diagnosis, prevention, and treatment of alcohol and other substance 
misuse and to expand the range of healthcare providers appropriately 
trained in identifying and addressing these problems.
Alcohol-Associated Liver Diseases
    In the United States, about half of liver disease deaths are 
attributable to alcohol misuse. NIAAA will continue to invest in 
clinical and translational research to develop treatments for alcohol-
associated liver diseases such as alcoholic hepatitis, a deadly form of 
liver disease for which there are no treatments approved by the Food 
and Drug Administration (FDA). The Institute aims to strengthen its 
research programs in alcoholic hepatitis through the establishment of a 
clinical and translational network to streamline the design, 
initiation, and conduct of clinical trials, reduce administrative 
redundancy, and optimize the use of scientific innovations. NIAAA is 
collaborating with the FDA to identify appropriate clinical trial 
endpoints for studies investigating novel treatments for alcohol-
associated liver diseases as well as safe, effective therapies for AUD 
in liver disease patients.
Fetal Alcohol Spectrum Disorders
    Prenatal alcohol exposure is a leading preventable cause of 
developmental abnormalities that contribute to a broad range of 
lifelong physical, cognitive, and behavioral challenges known as Fetal 
Alcohol Spectrum Disorders (FASD). Among NIAAA's extensive portfolio in 
FASD research are studies to establish more accurate FASD prevalence 
estimates. A new NIAAA-supported study of more than 6,000 first-graders 
across four U.S. communities (Midwest, Rocky Mountain, Southeast and 
Pacific Southwest) has found that as many as 1-5 percent of first-grade 
children have FASD. This finding provides further evidence that FASD is 
a significant public health problem in the U.S. and strategies to 
expand screening, diagnosis, prevention, and treatment in communities 
are needed to address it.
                     emerging public health issues
    Changing patterns in alcohol consumption, shifts in the burden of 
alcohol-related disease, and shifts in the demographic composition of 
the U.S. pose new challenges for alcohol prevention and treatment. 
Identifying and addressing emerging public health issues early can 
lessen the societal burden and associated costs.
Increases in Alcohol-Related Emergency Department Visits
    A new study found that the rate of alcohol-related emergency 
department visits in the U.S. increased by nearly 50 percent between 
2006-2014, especially among women and older adults. About 15 percent of 
the visits involved substances in addition to alcohol. Alcohol 
interacts with a variety of prescription and illicit drugs, including 
opioid pain relievers, which dramatically increase the risk of overdose 
deaths and may partially explain the increased prevalence of emergency 
department visits also observed for alcohol and medication 
interactions. The relationship between alcohol and pain is another area 
of interest including how chronic alcohol misuse increases sensitivity 
to pain, and how pain drives alcohol misuse. NIAAA is supporting 
epidemiological studies to determine the associations between alcohol 
and opioid misuse as well as basic research to elucidate the 
neurobiological mechanisms through which alcohol, opioids, and pain 
interact.
Extreme Binge Drinking
    A recent NIAAA study based on 2012-2013 data found that that nearly 
32 million adults in the U.S. (13 percent of the population aged 18 and 
older) engaged in extreme binge drinking, i.e., consuming alcohol at 
levels two or more times the binge thresholds, in the past year. 
Extreme binge drinking was associated with an elevated likelihood of 
emergency department visits and other adverse consequences. NIAAA is 
forming a working group of external experts to better understand the 
social and cultural determinants of extreme binge drinking to inform 
the development of improved interventions.
Alcohol Misuse Among Women
    A growing body of evidence indicates that women who drink are at 
increased susceptibility to short- and long-term alcohol-related 
consequences, and alcohol use and misuse are increasing more 
significantly among women than men. NIAAA encourages basic, clinical, 
and translational research on the biological bases of sex differences 
in the development of AUD and associated consequences, factors that 
increase risks for AUD and co-occurring disorders, and improved 
diagnosis and evidence-based interventions that consider the unique 
needs of women.
Alcohol Misuse Among Older Adults
    As people age, they tend to be more sensitive to alcohol's effects, 
and are more likely to experience health conditions exacerbated by 
alcohol misuse as well as alcohol-medication interactions. An analysis 
of data from 1997-2014 showed an increase in drinking and binge 
drinking among adults aged 60 and older, particularly among women. 
NIAAA-supported studies are focused on identifying and reducing 
unhealthy alcohol use among older adults as well as elucidating how 
alcohol contributes to age-related changes in the brain. For example, a 
recent study of older adults with AUD has shown accelerated declines in 
various brain regions and circuits, including in the frontal cortex 
which may lead to accelerated impairments in cognitive function.
                               conclusion
    Advances in alcohol research have expanded our knowledge of the 
effects of alcohol on health and resulted in numerous evidence-based 
preventive and treatment interventions. Still, more work needs to be 
done to reduce the burden of alcohol misuse in our Nation. With its 
fiscal year 2019 budget, NIAAA will continue to invest in basic, 
clinical, and translational research to address existing and emerging 
public health concerns and cultivate the biomedical research workforce 
to harness the contributions and perspectives of the broadest range of 
investigators.
                                 ______
                                 
  Prepared Statement of Walter J. Koroshetz, M.D., Director, National 
             Institute of Neurologcial Disorders and Stroke
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Neurological Disorders and Stroke (NINDS) of the National 
Institutes of Health (NIH). NINDS research improves the diagnosis, 
treatment, and prevention of brain diseases and other nervous system 
disorders, and the Institute is the world's largest supporter of basic 
research to understand the normal brain, which drives progress against 
disease throughout the public and private sectors.
                the challenge of neurological disorders
    According to the Centers for Disease Control and Prevention, in the 
United States: traumatic brain injury (TBI) is the leading cause of 
death and disability in children and young adults and a major problem 
for the elderly (falls), about 795,000 strokes occur each year, 
epilepsy affects 3 million adults plus nearly half a million children, 
dementia is a growing public health challenge, and chronic pain is 
perhaps the most common of all medical problems, and a major factor in 
the opioid crisis. Parkinson's disease, multiple sclerosis, amyotrophic 
lateral sclerosis, cerebral palsy, and hundreds of other disorders, 
common and rare, also affect the brain, spinal cord, and nerves of the 
body. Because of the multiplicity of brain disorders and the 
extraordinary complexity of the brain, neurological disorders present 
the most daunting challenges in all of medicine. For most of these 
diseases, treatments are still far from adequate.
                progress against neurological disorders
    Historically, progress against neurological disorders has been 
slow, but the pace appears to be accelerating, with encouraging 
advances against several neurological disorders in recent years. As NIH 
has driven medical progress in general, NINDS basic research has 
provided the foundation for these recent advances against neurological 
diseases, and the Institute's translational and clinical research have 
also made major contributions. A few recent examples illustrate:
  --Stroke.--Two decades ago, NINDS-supported research showed that tPA 
        therapy can restore blood flow to the brain following a stroke. 
        For the first time, stroke became a treatable emergency, and 
        the care system organized to take advantage. Building on NINDS 
        funded research, clinical trials in 2015 showed that timely 
        intervention with intravascular devices can directly clear a 
        blocked brain artery in severe strokes when tPA does not 
        restore blood flow, with striking clinical benefit. In 2018 the 
        NINDS DEFUSE 3 clinical trial reported that a brain imaging 
        method can identify people who may respond well beyond the 
        current restricted time window for this intervention, now up to 
        16 hours, so many more people with strokes may benefit.\8\ 
        These recent results again transform emergency stroke 
        treatment, and stroke care systems are now making these 
        catheter-based treatments available in both urban and rural 
        communities.
---------------------------------------------------------------------------
    \8\ N Engl J Med. 378:708-718 2018.
---------------------------------------------------------------------------
  --TBI.--The 2018 FDA marketing authorization of the first blood test 
        to help in the diagnosis of concussion exemplifies the 
        extensive NIH and DoD cooperation on TBI. NINDS funded the 
        foundational basic science and clinical studies to the 
        successful research team, and DoD supported the subsequent 
        development and testing. The test could reduce the cost and 
        radiation exposure from thousands of unnecessary CT scans.
  --New Drugs.--Pioneering NIH-supported basic and translational 
        research, and subsequent private sector development, led to FDA 
        approval of the first disease-modifying drugs for two rare 
        pediatric diseases, spinal muscular atrophy (SMA) and Batten 
        disease. The FDA also approved the first drugs for primary 
        progressive multiple sclerosis, for movement problems 
        associated with Huntington's disease, and a drug for 
        amyotrophic lateral sclerosis (ALS). And researchers reported 
        promising results for migraine, adrenoleukodystrophy, Niemann-
        Pick disease, and several other disorders.
  --Dementia.--A long-term NIH study with more than 15,000 people found 
        that middle aged Americans who have vascular risk factors, 
        including diabetes, high blood pressure and smoking, are more 
        likely to suffer from dementia later in life.\9\ The findings 
        add to a growing body of evidence linking cardiovascular health 
        to brain health. The hope is that managing vascular risk 
        factors in middle age may slow or prevent the development of 
        dementia, and there are hints that may be happening.\10\
---------------------------------------------------------------------------
    \9\ JAMA Neurology 74:1246-54 2017.
    \10\ New England Journal of Medicine 374:523-32, 2016.
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                        driving future progress
    NINDS will continue to emphasize investigator-initiated research 
with rigorous peer review because of its proven track record. 
Complementing this core strategy, the Institute calls for research 
proposals to address unmet public health needs or exceptional 
scientific opportunities. Among the notable activities for the coming 
year:
  --The Opioid Crisis.--Through a series of workshops and discussions 
        in 2017, Federal agencies, the scientific community, and 
        industry forged a partnership to accelerate the development of 
        safe and effective, non-addictive treatments for pain. NINDS 
        leads two key priorities of the plan-- development of 
        biomarkers (objective indicators) of pain and of a clinical 
        trials network to use biomarkers for the development of non-
        addictive pain treatments. Together with the NIH Pain 
        Consortium and the NIH Director's Common Fund, NINDS is also 
        targeting the key question of why acute pain leads to chronic 
        pain for some people, well after the original cause of pain has 
        been resolved.
  --ADRDs.--Through the National Alzheimer's Project Act (NAPA), 
        Congress recognized the impact of not just Alzheimer's, but 
        also Alzheimer's disease-related dementias (ADRDs). 
        Frontotemporal dementia (FTD) is the most common dementia in 
        people younger than 60, and Lewy body and Parkinson's dementias 
        also have a major impact. The most common ADRD, Vascular 
        Cognitive Impairment and Dementia (VCID), like stroke, affects 
        brain blood vessels. VCID is so intertwined with Alzheimer's 
        disease that most elderly people with dementia have a 
        combination of the two. NINDS leads several new and ongoing 
        initiatives to understand and develop treatments for the ADRDS, 
        working closely with the National Institute of Aging (NIA), 
        which provides funding to a suite of these NINDS-led programs. 
        NINDS also leads the ADRD summits that occur every third year, 
        as mandated by NAPA.
  --AMP PD.--NINDS, Celgene, Verily, Pfizer, GlaxoSmithKline, Sanofi, 
        the Michael J. Fox Foundation (MJFF), and the Foundation for 
        NIH are launching the Accelerating Medicines Partnership for 
        Parkinson's Disease (AMP-PD). This new addition to the NIH AMP 
        program will identify and validate biomarkers and new 
        therapeutic targets for Parkinson's disease, leveraging a 
        treasure trove of data and resources supported over the past 
        several years by NINDS, MJFF, and others.
  --Pediatric Concussion.--An NINDS initiative will develop biological 
        measures of persistent symptoms following pediatric concussion, 
        which addresses the highest research priority identified by a 
        2016 NIH scientific workshop on pediatric concussion.
  --Biomarkers.--The lack of reliable biomarkers for most neurological 
        disorders heightens the challenges of developing treatments and 
        dissuades private sector investment. An NINDS initiative will 
        support the advanced development and validation necessary to 
        bring potential biomarkers to clinical practice, complementing 
        the extensive early phase biomarkers discovery research that is 
        already underway.
  --BRAIN Initiative.--NINDS is an enthusiastic leader of the Brain 
        Research through Advancing Innovative Neurotechnologies (BRAIN) 
        Initiative. The Initiative is developing and applying new 
        technologies to understand how circuits of interconnected nerve 
        cells in the brain enable us to perceive, act, think, and 
        learn, and what goes wrong in brain disorders. Remarkable new 
        tools now enable researchers to identify all of the individual 
        brain cell types, monitor activity of thousands of cells in a 
        circuit at once in real time, precisely manipulate cells' 
        activity, and non-invasively monitor and stimulate the human 
        brain with increasing precision. As the Initiative continues, 
        engaging these new opportunities to enhance research on pain 
        and addiction is a high priority.
    Finally, NINDS continues its longstanding emphasis on investigator-
initiated basic research, which is yielding remarkable advances on many 
fronts in addition to circuits. Among the many findings this year, for 
example, research discovered unexpected links between bacteria and 
brain blood vessels, new roles of non-nerve cells in the brain, 
insights about how genes orchestrate brain development, the role of 
undetected seizure-like activity in Alzheimer's disease, how the gut 
conveys information to the nervous system, mechanisms of memory, and 
novel ways that nerve cells respond to stress. Which findings from 
basic research will launch the next advances against disease is not yet 
apparent. However, NIH basic research will surely continue to be the 
wellspring of progress for both the public and private sector.
                                 ______
                                 
Prepared Statement of Jon R. Lorsch, Ph.D. Director, National Institute 
                      of General Medical Sciences
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of General Medical Sciences (NIGMS), a component of the 
National Institutes of Health (NIH).
    The NIGMS focuses on promoting and supporting fundamental or 
``basic'' biomedical research that increases scientific knowledge about 
how living systems work, from individual molecules to cells, organs, 
whole organisms, and populations. The Institute's priority is to 
support investigator-initiated research, based on the principle that 
the best scientific ideas, directions, and approaches stem from 
scientists themselves. Thus, NIGMS aims to enable creative, innovative, 
and ambitious research conducted by individuals and teams of 
investigators to promote scientific discovery and medical advancement.
    One indication of the success of the Institutes' strategy is the 
number of Nobel Prizes awarded to NIGMS grantees. Of the 153 Nobels 
given for NIH-funded research, over half--87--have been for work 
supported by NIGMS. This year, the Nobel Prizes in both chemistry and 
in physiology or medicine were awarded to multiple NIGMS grantees. The 
2017 Nobel Prize in chemistry was awarded to a NIGMS grantee and two 
others for the development of cryo-electron microscopy (cryo-EM), a 
technique that simplifies and improves the imaging of biomolecules. 
Similarly, the 2017 Nobel Prize in physiology or medicine was awarded 
to three NIGMS grantees for their work on molecular mechanisms 
controlling circadian rhythms, more commonly known as ``biological 
clocks.'' Biological clocks influence a variety of physiological 
responses such as alertness, hunger, metabolism, fertility, and mood; 
clock dysfunction is associated with various disorders, including 
insomnia, diabetes, and depression. These awards serve as yet another 
testament to how investing in the study of fundamental biological 
processes can yield important insights into the principles that 
underlie human biology, health, and disease.
    Because scientific breakthroughs generally cannot be predicted in 
advance and often originate from unexpected or disparate strands of 
knowledge, a cornerstone of NIGMS' strategic plan is to support a broad 
and diverse portfolio of fundamental research. This strategy builds the 
strongest possible foundation on which breakthroughs can arise.
    nigms strategic priority: new funding approaches to accelerate 
                   scientific progress and discovery
    In order to enhance the efficiency and productivity of fundamental 
biomedical research, the NIGMS has developed a new mechanism to fund 
scientists. The Maximizing Investigators' Research Award (MIRA) seeks 
to transform how fundamental biomedical research is supported by 
providing individual investigators with a heightened level of both 
scientific stability and flexibility.\11\ These awards allow 
investigators to follow new research directions and insights in real-
time, while simultaneously providing an extra year of support as part 
of a more coordinated scientific program (versus single project) focus. 
In addition, the peer review process for MIRA applicants reviews early 
stage investigators (ESIs) independently from established investigators 
(EIs), thus allowing each group of applicants to be examined relative 
to their own peer group. Since the creation of the program, the NIGMS 
has awarded 231 MIRAs to EIs and 192 MIRAs to ESIs. The MIRA program is 
especially beneficial for ESIs, as evidenced by the increase in the 
number of ESI applications from 393 in 2015 (prior to MIRA) to 649 in 
2017. The number of ESIs funded by the Institute per year has nearly 
doubled in the same time period. The NIGMS will continue to monitor the 
progress and outcomes of the MIRA program as it evolves.
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    \11\ https://www.nigms.nih.gov/research/mechanisms/MIRA/pages/
default.aspx.
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    Because some areas of biomedical investigation require groups of 
investigators to synergistically work together to solve complex 
problems, the NIGMS recently developed and implemented a new team-
science support mechanism known as the Collaborative Program Grant for 
Multidisciplinary Teams.\12\ This investigator-initiated funding 
opportunity supports multidisciplinary teams of researchers to work 
toward a shared goal that has the potential to have a major impact on 
one or more fields of biomedical research. Because this program only 
funds highly integrated research teams working toward a common 
objective, it will promote and enable a type of collaborative science 
that can't easily be supported through other kinds of research grants. 
Further, these new awards possess an optional component that allows for 
support of pilot projects by early-stage investigators to develop 
research in the team's area(s) of expertise with a goal of helping the 
junior researchers obtain independent funding.
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    \12\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-340.html.
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    nigms strategic priority: develop and sustain a highly skilled, 
         diverse, and productive biomedical research workforce
    The NIGMS plays a leading role in supporting the career development 
and training of the next generation of scientists, including the 
development of institutional research capacities in regions across the 
country in which the levels of NIH support have been historically low.
    Given the rapidly evolving landscape of science and medicine, the 
Institute is working to catalyze the modernization of graduate 
education. Recently, the NIGMS issued a new funding opportunity 
announcement (FOA) for its pre-doctoral T32 training grants \13\ that 
focuses on addressing several key issues such as: shifting the emphasis 
from simply teaching scientific ``facts'' to teaching both scientific 
and professional skills; developing the acumen needed to become 
rigorous and responsible scientists; supporting a safe, inclusive and 
diverse training environment; promoting the use of evidence-based 
teaching and mentoring practices; and enhancing student career 
development. Over the next several years, the NIGMS will work to 
implement this revised T32 program and will carefully evaluate its 
outcomes. In addition, the NIGMS is also working to ensure that 
emerging issues can be quickly incorporated and addressed in the 
training process, as appropriate. For example, the Institute has 
recently supported the development of open-access curricular training 
modules in areas related to improving the rigor and reproducibility of 
biomedical research. These modules are available on the NIGMS 
website,\14\ with more modules due to be added this year. The goal is 
to generate useful resources for graduate training programs.
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    \13\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-341.html.
    \14\ https://www.nigms.nih.gov/training/pages/clearinghouse-for-
training-modules-to-enhance-data-reproducibility.aspx.
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    Through its Institutional Development Award (IDeA) program, the 
NIGMS provides targeted support to help broaden the geographic 
distribution of biomedical research funding by enhancing the 
competitiveness of investigators located at academic institutions in 
States having a historically low level of NIH support. The IDeA Centers 
of Biomedical Research Excellence (COBRE), for instance, support 
thematic, multidisciplinary centers that expand and develop faculty 
research capabilities and research infrastructure, in part through the 
development of core technology facilities needed to carry out modern 
multidisciplinary collaborative research. Another important aspect of 
the IDeA program is its support of medical research for rural and 
underserved communities. The IDeA Clinical and Translational Research 
Network (CTR), for instance, provides support for clinical and 
translational research that addresses conditions that have been 
traditionally higher among certain regions, populations or communities, 
including (but not restricted to) cancer, cardiovascular disease, and 
substance abuse disorders.
    Because developing a well-trained research workforce begins with 
early outreach and education, the NIGMS was proud to welcome the NIH 
Science Education Partnership Awards (SEPA) to the Institute in 
2017.\15\ SEPA supports diversity in the workforce by providing 
opportunities for students (specifically at the pre-kindergarten to 
grade 12 levels) from underserved communities to learn about careers in 
basic or clinical research. Ten of the fourteen SEPAs in IDeA States 
are currently in partnerships with IDeA COBREs or IDeA Networks of 
Biomedical Research Excellence (INBREs). An Institute goal is to fund 
at least one SEPA in every State.
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    \15\ https://www.nigms.nih.gov/Research/DRCB/SEPA/Pages/
default.aspx.
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   nigms strategic priority: create and share cutting-edge tools and 
                               resources
    Given that technology plays a critical role in biomedical research, 
the NIGMS continues to place a high level of significance on supporting 
the development and dissemination of innovative, new technologies that 
have the potential to transform research. To this end, the NIGMS 
supports a multi-phased funding strategy that consists of support for 
an initial proof-of-concept phase for a given technology followed by 
potential support for a second prototype refinement phase. These phases 
can then lead to the adoption and expansion of the technology via 
commercialization through small business innovation research or small 
business technology transfer (SBIR/STTR) grants. Technologies can also 
be applied toward answering specific scientific questions through their 
incorporation into regular research project grants or, once 
sufficiently mature, through their incorporation into resources 
supported by the Institute's Biomedical Technology Research Resources 
(BTRR) program.\16\ Programs such as the BTRR form an important part of 
the NIGMS' portfolio as the Institute seeks to ensure broad access 
across the research community to cutting-edge technological resources. 
For example, synchrotron-based technologies, an extremely powerful 
source of X-rays, are critical for structural biology research; more 
than 90 percent of all three-dimensional structures of biological 
molecules in the Protein Data Bank \17\ were determined using data from 
synchrotrons. The NIGMS recently shifted its support for these 
important resources from research grants to a mechanism focused on 
user-access, utility and efficiency of operations. A similar model will 
be used to support the new national cryo-electron microscopy centers.
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    \16\ https://publications.nigms.nih.gov/btrrs/searchresults.asp.
    \17\ https://www.rcsb.org/.
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                               conclusion
    Mr. Chairman, in this statement, I have tried to highlight just a 
few examples of how NIGMS' programs maximize the scientific returns on 
the taxpayers' investments in fundamental biomedical research. As the 
scientific enterprise and national clinical landscape continue to 
evolve, the NIGMS looks forward to continuing to meet and address both 
the challenges and opportunities associated with this dynamic 
environment, and in so doing, to the many more advances that will 
emerge from institutions, laboratories, research teams, and individual 
investigators across the Nation. We thank you for your continued 
support and for this opportunity to describe some of the new 
initiatives at NIGMS.
                                 ______
                                 
  Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P., Director, 
    National Institute of Diabetes and Digestive and Kidney Diseases
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the 
National Institutes of Health (NIH).
           combating chronic disease to improve human health
    NIDDK supports research on diseases and conditions affecting the 
health and well-being of millions of Americans. Its mission spans 
diabetes and other endocrine and metabolic diseases; digestive and 
liver diseases; kidney and urologic diseases; blood diseases; obesity; 
and nutrition disorders. Though diverse in nature, most of these 
diseases and conditions are chronic, consequential, and costly. For 
example, diabetes, kidney disease, and digestive diseases alone run 
into hundreds of billions of dollars yearly for medical care, 
disability, loss of work or productivity, and other costs. Obesity is 
at high prevalence among U.S. adults and youth and is a risk factor for 
many of these chronic and sometimes deadly health problems. The 
challenges are vast, and the needs urgent. Through research and related 
activities, NIDDK continues to seek out ways to prevent, treat, and 
cure chronic diseases and conditions to improve human health and 
quality of life.
                                research
    To foster discovery important to combating chronic disease, NIDDK 
supports a multi-faceted scientific portfolio spanning basic to 
translational to clinical studies, while also creating and leveraging 
partnerships that can fortify and accelerate research. For example, in 
basic research, scientists have used a specialized microscopy technique 
to develop a three-dimensional picture of a cellular protein that is a 
target for certain diabetes drugs. Because this protein is also a 
member of a protein ``family'' targeted by about 40 percent of 
pharmaceutical drugs on the market today, the intricate knowledge 
gained from this work is not only important for diabetes but will 
inform the search for new drug treatments and refinement of current 
ones for other diseases. New findings in mice may also open up new 
therapeutic avenues important to prevention of obesity and type 2 
diabetes: One research group has identified a group of brain cells 
that, upon activation, induces rapid binge eating and weight gain, 
while another has found that bones secrete a hormone that both 
suppresses appetite and regulates blood sugar levels. Studies in mice 
have also revealed a more complex view of the kidney's role in salt and 
water balance and blood pressure regulation and suggest new areas of 
investigation for human hypertension. NIDDK-supported scientists have 
also been able to produce human intestinal ``organoids''--small bundles 
of cells that model various aspects of the small intestine and its 
functioning, facilitating study of certain digestive system diseases 
and disorders and creating potential for tissue replacement therapy.
    In fiscal year 2019, NIDDK will build upon research accomplishments 
such as these and upon other research avenues and continue its support 
for basic studies of both normal and disrupted biological functions and 
systems. For example, the ReBuilding a Kidney (RBK) consortium will 
continue efforts to enable tissue repair or replacement in kidney 
disease; already, RBK scientists have found that selecting the proper 
substrate for growth and structural support is critical to creating 
blood supply in a ``kidney on a chip.'' Recent studies have shed light 
on the multiple levels of complex interactions that contribute to how 
human gut microbes affect health, from molecules produced by the 
microbes themselves to differences in human diet; a 2017 workshop on 
best practices for studies of diet and gut microbiome will help inform 
rigor and reproducibility in future efforts in this aspect of research 
on the gut microbiome, which is rapidly emerging as an important 
contributor to digestive diseases, obesity, nutrition, and many other 
chronic diseases and conditions.
    Similarly, NIDDK-supported translational and clinical studies have 
yielded fruit. For example, in the translation of genetic discovery to 
treatment, NIDDK-supported scientists developed a personalized 
treatment plan for a child suffering from a severe anemia after 
discovering that the cause was a rare mutation affecting a protein 
already available in a therapeutic form. New findings about the impact 
of being diagnosed with diabetes before age 20 include that youth with 
type 2 diabetes are more than twice as likely as peers with type 1 
diabetes to have or be at high risk of a diabetes health complication 
by age 21. The Multidisciplinary Approach to the Study of Chronic 
Pelvic Pain (MAPP) Research Network has yielded important new insights 
into the nature and course of the urologic chronic pelvic pain 
syndromes interstitial cystitis/bladder pain syndrome (IC/BPS) and 
chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), such as new 
knowledge about the prediction of and bodily patterns of pain. NIDDK-
supported scientists have also developed the first method for 
calculating the average rate of blood filtration by the individual 
functional units in the human kidney, an important measure of kidney 
health. Discoveries such as these can now be harnessed into new 
research toward interventions or into other actions to improve health.
    NIDDK will continue its support of research that, in partnership 
with human volunteers, can elucidate causes of and treatments and cures 
for chronic diseases and conditions and ways to implement those 
findings. For example, the third phase of the Diabetes Prevention 
Program Outcomes Study, spearheaded by NIDDK with several NIH partners, 
will study outcomes that are of increasing concern in an aging 
population with a high burden of pre-diabetes and diabetes. These 
include evaluating the potential benefit of the diabetes drug metformin 
on the development of cardiovascular disease and cancer. Gestational 
diabetes has long-term health impacts for affected mothers and 
children, and NIDDK will continue to capitalize on new findings and 
efforts to better understand this condition and identify ways to 
improve outcomes. Efforts will continue in development and testing of 
artificial pancreas systems for treatment of type 1 diabetes. NIDDK 
will also continue support for many clinical research efforts to 
address overweight and obesity, including major ongoing studies to 
assess the health risks and benefits of weight-loss surgery in 
extremely obese adolescents. The new Kidney Precision Medicine Project 
will pursue innovative efforts to elucidate the heterogeneity of kidney 
disease in human study participants, which could lead to novel and 
tailored treatments for both acute and chronic kidney disease. NIDDK 
will sustain its long-term investment in the Drug-Induced Liver Injury 
Network (DILIN) so that it may continue its highly productive and 
informative efforts to characterize liver injury from herbal and 
dietary supplements and prescription and over the counter drugs.
    To help tackle complex challenges and move discovery forward, NIDDK 
continues to forge effective partnerships with other NIH ICs and 
Offices, other Federal agencies, and private organizations. For 
example, the NIH Nutrition Research Task Force chaired by NIDDK and co-
chaired by the National Heart, Lung, and Blood Institute (NHLBI), 
National Cancer Institute (NCI), and Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD) has sought 
input from across NIH and external stakeholders and is developing the 
first NIH-wide strategic plan on nutrition. The public-private 
Accelerating Medicines Partnership-Type 2 Diabetes (AMP-T2D) project, 
spearheaded by NIDDK with partners from industry and nonprofit 
organizations, continues to exceed expectations in terms of progress 
and will continue augmenting content and access to genetic and clinical 
data on diabetes and related traits made available through its 
Knowledge Portal.
                                 other
    Indivisible from research are the minds and hands that generate new 
ideas and bring forth results. NIDDK will continue to foster and grow a 
diverse biomedical research workforce that can meet, with innovation 
and creativity, the challenges posed by chronic diseases and 
conditions. NIDDK supports several special training opportunities 
spanning high school to medical school to attract students, including 
those underrepresented in science and medicine, to NIDDK research 
areas. Mentorship opportunities offered by NIDDK's Network of Minority 
Health Research Investigators, which celebrated its 15th anniversary in 
2017, focus on junior investigators and will continue to promote a 
diverse research pipeline. NIDDK will also continue efforts to help the 
new generation of biomedical researchers realize their potential, such 
as priority funding strategies for those early in their careers. NIDDK 
is also pursuing multiple efforts to enhance rigor and reproducibility 
in research. Simultaneously, NIDDK will continue disseminating health 
and scientific information through multiple venues to educate and 
inform the public, healthcare providers, and researchers about new 
developments germane to chronic diseases and conditions.
                               conclusion
    In closing, NIDDK has a robust and vigorous commitment to research 
and related activities to combat chronic diseases and conditions. This 
is reflected in its five guiding principles: maintain a vigorous 
investigator-initiated research portfolio, support pivotal clinical 
studies and trials, preserve a stable pool of new investigators, foster 
research training and mentoring, and disseminate science-based 
knowledge through education and outreach programs. Through research, 
NIDDK hopes to advance progress toward new and improved prevention, 
treatment, and curative strategies.
                                 ______
                                 
  Prepared Statement of Norman E. Sharpless, M.D., Director, National 
                            Cancer Institute
    Mr. Chairman and Members of the Committee, I am pleased to present 
the President's fiscal year 2019 budget request for the National Cancer 
Institute (NCI) of the National Institutes of Health (NIH). With the 
resources that this subcommittee provides, NCI supports a broad array 
of biomedical research to advance scientific discovery, reduce the 
burden of cancer, and help all people live longer, healthier lives.
NCI Progress under the 21st Century Cures Act
    In the Cures Act, Congress authorized $1.8 billion across seven 
fiscal years for the Cancer Moonshot. The fiscal year 2018 Consolidated 
Appropriations Act provided the second Cures Act installment of $300 
million. Guided by the recommendations of a Blue Ribbon Panel convened 
to identify research priorities, NCI awarded fiscal year 2017 funding 
in ten promising areas of cancer research targeted for rapid 
translation into new treatment and prevention. NCI will fund all 
remaining Blue Ribbon priorities during fiscal year 2018.
    One example of NCI's commitment to the progress envisioned in the 
Cures Act is the promising area of immunotherapy--activating a 
patient's immune system to attack cancer cells. To accelerate the 
development of immunotherapy strategies for cancer patients, in the 
fall of 2017, NCI launched a public-private partnership with NIH and 
pharmaceutical companies, known as the Partnership for Accelerating 
Cancer Therapies, or PACT. The Foundation for the National Institutes 
of Health will manage and coordinate PACT, and the Food and Drug 
Administration will play an essential advisory role. Twelve 
pharmaceutical companies are now members of PACT.
    A centerpiece of PACT is NCI's $54 million investment of Cures Act 
funds across 5 fiscal years to establish four Cancer Immune Monitoring 
and Analysis Centers and a Cancer Immunologic Data Commons. Together, 
the centers and data commons will operate as a network to identify 
mechanisms of response and resistance to cancer therapy and to support 
adult and pediatric immunotherapy trials.
    NCI created the immunotherapy network to speed discovery of 
molecular signatures associated with immune response and to predict 
whether immunotherapy will benefit individual patients. The network 
will identify biological markers of disease and response to treatment 
that researchers and clinicians can use to design optimum treatment 
strategies for cancer patients. The entire cancer research community 
can access data from analysis conducted by the four centers and use 
this resource to further their research on cancer cures. Other 
priorities of the NCI immunotherapy network and the 12 PACT partners 
include establishing a set of standardized biomarkers for testing in 
research studies, harmonizing assays to strengthen data 
reproducibility, fostering data comparability across clinical trials, 
and reducing duplication of effort, thereby allowing researchers to 
conduct more high-quality clinical trials for children and adults with 
cancer.
    In addition to support for PACT, NCI also awarded Cures Act funding 
to other promising research on harnessing the immune system to attack 
cancer. The goal of this research is to expand the initial successes in 
immunotherapy to a much wider range of cancers, to a broader range of 
patients experiencing the same form of cancer, and to cancers that have 
been most resistant to cure.
Appropriations for Other Cancer Research Priorities
    While the 21st Century Cures Act deserves prominence in any 
discussion of NCI's current cancer research priorities, as a component 
of our total budget, fiscal year 2017 Cures Act funding represented 
about 5 percent of NCI's total cancer research appropriation. It is 
therefore important to emphasize the breadth of other research that 
NCI's appropriation conducts.
    As the detailed narrative accompanying NCI's budget request 
demonstrates, sustained progress that will benefit cancer patients 
relies on many forms of research, including:
  --basic research, such as genetics, cell biology, immunology, and 
        structural biology
  --translational and clinical sciences to prevent, screen, and 
        diagnose cancer, and to develop and test drugs, biomarkers, 
        imaging technologies, diagnostics, and radiotherapies
  --population sciences, including epidemiological, environmental, and 
        behavioral studies.
    These areas constitute the bedrock of NCI cancer research. 
Continued funding across all these disciplines is essential to 
understanding the causes and mechanisms of cancer, preventing cancer, 
strengthening cancer screening, developing and refining cancer 
therapies, and improving cancer survivorship. Many of these disciplines 
will experience profound changes based on the new understanding of 
cancer that is driving precision oncology and to tailor treatments to 
individuals. Others will continue to depend on more traditional 
approaches to research.
    The research resources that NCI makes available to the cancer 
research community is another mechanism of growing importance to cancer 
science. Examples of NCI research resources include:
  --The Biopharmaceutical Development Program (BDP) produces novel 
        antibodies and proteins when they cannot be manufactured 
        elsewhere. For example, researchers turned to the BDP to 
        manufacture a monoclonal antibody (ch14.18) necessary for a 
        clinical trial to proceed. The antibody is now the standard of 
        care for children with certain types of neuroblastoma.

    During fiscal year 2018, NCI will use the capability of the BDP to 
        expand production of CAR T-cells for use in immunotherapy 
        trials. The BDP will help meet the growing demand for 
        experimental therapies to serve adult and pediatric patients in 
        intramural and extramural clinical trials. CAR T-cell therapy 
        is an immunotherapy treatment in which a patient's T-cells (a 
        type of immune cell) are modified in the laboratory so they 
        bind to cancer cells. Millions of CAR T-cells are grown in the 
        laboratory and then given to the patient by infusion, where 
        they bind to an antigen on cancer cells and kill them.
  --NCI's Experimental Therapeutics (NExT) program advances 
        breakthroughs in new cancer therapies by shortening the 
        timeline for drug discovery, development, and approval. 
        Researchers with promising cancer drug development projects can 
        apply to NExT for assistance to overcome the challenges they 
        face along the path to drug approval.

    Vanderbilt University's recent progress developing therapies to 
        inhibit a protein known as Mcl-1 is an example of the 
        breakthroughs that NExT helps to foster. After engaging NExT 
        scientists to resolve therapeutic development challenges, 
        Vanderbilt is now collaborating with Boehringer Ingelheim to 
        develop drugs to treat a range of cancers known to overexpress 
        the Mcl-1 protein.
  --NCI's RAS Initiative supports the development of therapies for 
        tumors that contain mutations in the RAS family of oncogenes. 
        One-third of all cancers involve RAS gene mutations. Through 
        the RAS Initiative, NCI generates standardized reagents, 
        assays, and datasets and provides them to scientists worldwide 
        to support research on RAS oncogenes.
  --The Cancer Genome Atlas (TCGA)--a collaboration between NCI and the 
        National Human Genome Research Institute--is a resource of 
        comprehensive, multi-dimensional maps of key genomic changes in 
        33 types of cancer. The publicly-available TCGA dataset--
        containing 2.5 petabytes of data--has contributed to more than 
        a thousand cancer studies. An NCI priority for fiscal year 2018 
        is to update TCGA data with new details on patient therapeutic 
        response, outcome, and survival, and to support additional 
        clinical research based on the new data.
  --Launched in June of 2016, NCI's Genomic Data Commons (GDC) is a 
        unified data system for sharing genomic and clinical data. The 
        GDC centralizes and standardizes data from large-scale NCI 
        programs, and makes it more accessible and useful to scientists 
        and clinicians. One measure of the importance of this resource 
        is that non-profit and for-profit organizations are now 
        offering their data sets for sharing through the GDC.
    I also want to highlight our progress with the NCI Molecular 
Analysis for Therapy Choice (NCI-MATCH) Trial and the Pediatric MATCH 
Trial, two cornerstones of NCI's Precision Medicine Initiative. Rather 
than selecting therapies based on where a tumor originated in the body, 
these trials test the effectiveness of therapies that target specific 
genetic changes. In 2017, the adult NCI-MATCH Trial achieved its 
enrollment goal nearly 2 years ahead of schedule. The trial involves 
more than 6,000 patients from all 50 States at more than 1,000 
institutions.
    NCI opened enrollment for the Pediatric MATCH Trial during fiscal 
year 2017. This is a phase 2 clinical trial for children and 
adolescents with certain advanced solid tumors that have not responded 
to treatment or have progressed on standard therapy. The study is led 
jointly by NCI and the Children's Oncology Group, a clinical trials 
group including more than 9,000 childhood cancer experts across 3 
continents that is part of the NCI-sponsored National Clinical Trials 
Network. The Pediatric MATCH trial is taking place at 200 participating 
children's hospitals, university medical centers, and cancer centers 
across the United States.
    Thanks to support from Congress over many years, NCI research in 
these and other areas has yielded important results that have 
contributed to steady decreases in cancer mortality. Sustained 
Congressional support for NCI and the national cancer program has led 
to new diagnostics, treatments, and prevention strategies, improved our 
ability to manage the symptoms of cancer and the side effects of cancer 
treatments, and allowed us to more effectively monitor the prevalence 
of cancers and the factors associated with cancer risk.
    NCI-led cancer research on prevention and treatment is paying off: 
translating into a more than 25 percent reduction in cancer death rates 
since 1991. Yet despite steady progress, too many Americans face a 
cancer diagnosis, and far too many still die from the disease. There 
will be more than 1.6 million new cases of cancer in the United States 
in the coming year and more than 600,000 will likely die from cancer.
    Thus, much work remains to meet the needs of those suffering from 
cancer, those at risk of cancer, and the growing population of cancer 
survivors. The resources proposed in this fiscal year 2019 budget will 
allow NCI to continue to conduct our cancer research mission in ways 
that deliver important results for the patients we serve.
                                 ______
                                 
Prepared Statement of David Shurtleff, Ph.D., Acting Director, National 
            Center for Complementary and Integrative Health
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National Center 
for Complementary and Integrative Health (NCCIH) of the National 
Institutes of Health (NIH).
    The mission of NCCIH is to define, through rigorous scientific 
investigation, the safety and effectiveness of complementary and 
integrative health approaches, which are a group of practices and 
products that originate outside of conventional medicine. This diverse 
group of health practices includes natural products such as dietary 
supplements, plant-based products, and probiotics, as well as mind-body 
approaches such as yoga, massage therapy, meditation, mindfulness-based 
stress reduction, spinal manipulation, and acupuncture. According to a 
2012 National Health Interview Survey (NHIS), Americans are spending 
approximately $30.2 billion a year on complementary approaches to 
improve their overall health, manage symptoms of chronic diseases, and/
or counter the side effects of conventional medicine. However, the 
scientific research base surrounding the safety and efficacy of these 
practices is limited. Therefore, NCCIH is committed to providing the 
American public with valuable information about these practices, while 
also investigating how specific complementary approaches can be 
integrated into conventional medical care.
       exploring nonpharmacologic approaches for pain management
    NCCIH is devoting significant resources to understand the basis of 
pain and how complementary and integrative health approaches can be 
utilized in pain management. Pain is a major public health problem and 
is the most common reason Americans turn to complementary and 
integrative health practices. Data from the 2012 NHIS found that an 
estimated 25.3 million adults in the U.S. (11.2 percent) experience 
daily pain with nearly 40 million adults (17.6 percent) experiencing 
severe levels of pain. The use of highly addictive opioids as a primary 
pain management strategy in the U.S. is helping to fuel the growing 
opioid misuse epidemic. Improved strategies for pain management may 
lead to a decreased reliance on opioids for patients suffering from 
pain. NCCIH supports research to better understand the biologic 
mechanisms of pain and to identify effective nonpharmacologic 
approaches to reduce the duration and intensity of pain.
    Research supported at NCCIH is focused on understanding the role of 
the brain in perceiving, modifying, and managing pain, with the long-
term goal of improving clinical management of chronic pain through the 
integration of pharmacologic and nonpharmacologic approaches. Recently, 
scientists discovered a new class of sensory nerve cells that respond 
to high-threshold (intense) mechanical stimuli, such as hair pulling. 
This work provides insights into how our bodies encode and transmit 
pain sensations. Another study mapped the regions of the brain 
activated during pain to establish a ``pain signature'' and found that 
specific regions of the brain respond to pain intensity, while other 
regions mediate the psychological effect, and yet another region showed 
increased activity related to pain relief. This work not only provides 
insights into how pain is interpreted but could lead to the development 
of new methods to detect, quantify, or target pain.
    NCCIH-supported research is also advancing understanding of the 
mechanisms of action of mind and body interventions and determining 
their effectiveness for treating pain. One study investigated the 
effect of acupuncture on carpal tunnel syndrome and found that it 
affected activity within brain pain centers, decreased associated pain 
symptoms, and improved overall wrist function. Mindfulness meditation 
is another promising area of research. Numerous studies have shown that 
mindfulness meditation helps relieve pain, but the mechanism through 
which meditation exerts this effect is not well known. New study 
results demonstrate that mindfulness meditation activates the same 
region of the brain as opioids; however, it reduces pain independently 
of opioid neurotransmitter mechanisms. These results suggest that 
greater pain control could be achieved through the combination of 
mindfulness meditation and opioid-signaling-induced pharmacologic 
approaches. NCCIH-supported research has also shown that mindfulness-
based stress reduction and cognitive behavioral therapy can improve 
functioning and reduce chronic low back pain in young and middle-aged 
adults and may provide patients with skills for long-term management of 
pain. Studies have demonstrated that these approaches resulted in 
substantial cost savings over usual care.
    Based on these and other promising results, NCCIH is leading a new 
multi-agency partnership between the NIH, Department of Defense (DoD) 
and Department of Veterans Affairs (VA). This initiative, called the 
NIH-DoD-VA Pain Management Collaboratory (PMC), addresses the need to 
focus on ``advancing better practices for pain management,'' which is 
outlined in HHS's five-point strategy to combat the opioid crisis. The 
PMC will focus on developing, implementing, and testing cost-effective, 
large-scale, real-world research on nondrug approaches for pain 
management and related conditions in military and veteran healthcare 
delivery organizations. The PMC launched in fiscal year 2017 and the 
agencies plan to fund 11 two-year UG3 (Planning Phase) awards, and up 
to 10 four-year subsequent UH3 (Implementation Phase) Demonstration 
Projects, contingent upon successful completion of the short-term pilot 
and feasibility studies In addition, a PMC Coordinating Center has been 
established at Yale University and the Veteran's Administration 
Hospital in Connecticut to provide leadership and serve as a resource 
for the projects by providing innovative tools and best practices. 
Types of approaches being studied include mindfulness/meditative 
interventions, movement interventions (e.g., structured exercise, tai 
chi, yoga), manual therapies (e.g., spinal manipulation, massage, 
acupuncture), psychological and behavioral interventions (e.g., 
cognitive behavioral therapy), integrative approaches that involve more 
than one intervention, and integrated models of multi-modal care. The 
results of these studies may inform new pain management practices 
within the DoD and VA and support the use of nondrug approaches for 
pain management in the general population
                 advancing research on natural products
    According to the 2012 NHIS, nearly one in five U.S. adults use 
botanical supplements and other non-vitamin, non-mineral dietary 
supplements, such as fish oil/omega-3 fatty acids and probiotics. 
Adverse events related to dietary supplements are estimated to 
contribute to 23,000 emergency department visits in the U.S. each year. 
To better inform consumers and their healthcare providers, NCCIH 
supports rigorous research on the biological mechanisms of the benefits 
and potential harmful effects of natural products with the goal of 
improving the body of knowledge available to healthcare providers and 
patients.
    NCCIH is supporting a Center of Excellence to determine how best to 
study potential adverse interactions between natural products and 
conventional medications. The goal is to develop a definitive approach 
to determine the clinical relevance of supplement-drug interactions to 
inform design of future research and, ultimately, decisionmaking about 
using natural products and medications together.
    In fiscal year 2015, NCCIH partnered with NIH's Office of Dietary 
Supplements (ODS) to establish the Centers for Advancing Research on 
Botanical and Other Natural Products (CARBON) Program. Through this 
program, researchers recently identified two chemicals found in grapes 
that could significantly reduce depression-like behaviors in mice. The 
systems targeted by these compounds are not the same as current 
pharmaceutical antidepressants and may provide novel insights into the 
biology of depression and could lead to new therapeutic agents. The 
program is also developing new methods for chemical characterization of 
natural product mixtures, biological profiling assays, and creating new 
informatic tools to rigorously analyze and share data.
    NCCIH is also supporting research on cytisine, a natural product 
for smoking cessation. Despite promising results from clinical trials 
conducted outside the U.S., cytisine has not yet been approved for use 
in the U.S. NCCIH supported a series of pre-clinical studies on 
cytisine through a strategic collaboration with Achieve Life Sciences, 
Inc., OncoGenex Pharmaceutical, Inc., other NIH ICs, and private 
research organizations. Phase 2 clinical studies will further assess 
cytisine as a smoking cessation treatment. This continuing public-
private partnership may lead to the wide availability of a new option 
to address the major public health issues associated with tobacco use.
                               conclusion
    As a responsible steward of resources, NCCIH supports 
scientifically meritorious basic, mechanistic, clinical, and 
translational research. The Center focuses on areas with the greatest 
potential impact by prioritizing research topics that show scientific 
promise and are amenable to rigorous scientific inquiry. We leverage 
strategic partnerships to build the scientific evidence needed on the 
safety and efficacy of complementary health approaches and disseminate 
evidence-based information to the American public.
                                 ______
                                 
    Prepared Statement of Dr. Paul Sieving, Director, National Eye 
                               Institute
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National Eye 
Institute (NEI) of the National Institutes of Health.
                     fifty years of vision research
    It may have been a hot day on August 16, 1968, when President 
Johnson signed Public Law 489 to create the National Eye Institute, but 
on March 21, 2018, the biggest blizzard of the season threatened a 
reception hosted by Congressman Pete Sessions to celebrate NEI's 50th 
anniversary. However, snow didn't deter over 100 vision research 
stakeholders, National Institutes of Health scientists, patients, and 
members of Congress from coming out to recognize the vision-saving 
progress made in the past half century. While my statement usually 
covers the latest advances, I want to start by reflecting on some of 
our remarkable research progress, which has advanced clinical vision 
care.
    Over the past 50 years, NEI has funded research of nine Nobel Prize 
winning scientists, including discovery of the molecular mechanisms by 
which specialized neurons in the retina detect photons of light 
entering the eye and initiate biochemical and electrical signals to the 
brain that convey vision. The key light-detecting protein, rhodopsin, 
became the first cell membrane-bound protein studied by x-ray 
crystallography and imaged to reveal the protein structure in three 
dimensions. This paved the way for the study of other molecules in 
diseases in and beyond the eye. NEI-funded Nobel laureates also made 
landmark neuroscience discoveries of how brain circuits form and self-
organize in the visual cortex. This has revolutionized treatment for 
amblyopia, a disorder in which the brain favors visual information 
coming from one eye over the other. The first use of antiviral 
chemotherapy was developed for the eye to treat herpes outbreaks on the 
cornea. In ground-breaking work, NEI scientists discovered the first 
tumor suppressor gene, retinoblastoma, which transformed all of cancer 
biology. Conversely, in the past decade, the ocular adaptation of a 
cancer drug that blocks growth of abnormal blood vessels treats two of 
the leading causes of blindness: age-related macular degeneration (AMD) 
and diabetic retinopathy, stopping disease progression, and in many 
cases, reversing vision loss for medical benefit to thousands of 
patients.
    In its early years, NEI pioneered new methodology for conducting 
placebo-controlled, multi-center clinical trials, which led to vision-
saving laser surgery to treat diabetic retinopathy, AMD, and glaucoma. 
Large trials identified dietary supplements demonstrated to slow 
progression to end-stage AMD. Trials compared effectiveness of 
different therapies for AMD, diabetic retinopathy, and an inflammatory 
eye condition called uveitis, to inform patients and their doctors of 
options for personalized treatment. Elevated fluid pressure in the eye, 
called ocular hypertension, is a precursor for glaucoma, especially in 
African Americans who have a disproportionate burden of this disease. 
1,500 patients participated in the Ocular Hypertension Treatment Study, 
including 400 African American participants, which led to new treatment 
guidelines that can reduce incidence in African Americans by 50 
percent. A 20-year follow-up study is currently underway to assess the 
long-term impact. More recently, the first application of genomics 
methods led NEI scientists to uncover new genetic components for AMD, 
opening the door to new treatments. Before NEI was established, a major 
cause of lifelong blindness was retinopathy-of-prematurity (ROP), a 
disease caused by abnormal development of retinal blood vessels in low 
birth weight babies born very prematurely. Technology to identify and 
treat ROP has improved dramatically over the years and a recent NEI 
trial demonstrated that premature infants can be screened for ROP 
remotely via telemedicine, expanding access to specialists in rural and 
underserved communities.
                   recent progress in vision research
    NEI-supported vision research remains on the forefront of medicine, 
from regenerative medicine to replace neural tissue lost due to retinal 
degeneration; to advancing retinal prosthetics, including the Argus II 
artificial retina which was approved by FDA through the Humanitarian 
Device Exemption pathway; and pioneering the application of gene 
therapy to correct blinding disease-causing mutations. One landmark 
occurred in December 2017, when the FDA approved the first ever gene 
therapy in the U.S. to correct a retinal degeneration, Leber Congenital 
Amaurosis, which causes blindness in infants and children. The genetic 
mutation had earlier been discovered by an NEI scientist in 1993, but 
researchers had to invent the tools to turn that discovery into a gene 
therapy. Having set this precedence for all of medicine, the path from 
gene discovery to clinical trial is now being expedited with vision 
loss mutations in a dozen genes currently being addressed in pre-
clinical and clinical studies.
    Also in December, FDA approved two new drugs for glaucoma, the 
first new medications for this disorder in 18 years. This new class of 
drugs lowers pressure in the eye through novel targets that are 
different from existing medications. An ongoing clinical trial is 
testing a combination therapy of the newer and older drugs used 
together, which may prove more effective than either drug alone. This 
research represents the culmination of over 25 years of NEI basic 
research on molecules that control the contractile machinery of cells, 
which regulate the flow of fluid out of the eye.
    Idiopathic intracranial hypertension (IIH), which primarily affects 
obese young women, causes the buildup of pressure on the optic nerve, 
leading to vision loss in nearly 10 percent of patients. The recently 
completed IIH Treatment Trial of 165 patients showed that for mild 
vision loss, intervention with acetazolamide plus diet was superior to 
diet alone for reducing vision loss and improving quality of life. 
However, neither intervention was effective for patients with moderate 
to severe vision loss. NEI is funding a new three-arm trial testing 
different surgical interventions to relieve pressure and protect the 
optic nerve in 180 IIH patients with more severe vision loss.
                         seeing into the future
    The NEI Audacious Goals Initiative (AGI) seeks to restore vision 
through neuroregeneration in the eye and visual system. This 
fundamental regenerative medicine approach was initiated in 2013 and is 
advancing rapidly. NEI has established two collaborative consortia of 
research teams working on different facets of the challenge: one on 
functional imaging, and a second for discovery science to identify new 
regeneration factors by looking in model systems. For example, unlike 
adult mammals, zebrafish can regenerate their retina after injury, 
which led NEI researchers to identify a key regeneration factor, 
present in newborn mice, and through manipulating this factor, they 
caused new neurons to form in adult mice. Scientists also found that 
exosomes secreted from stem cells protect a type of retinal cells, the 
ganglion cells, which are damaged by glaucoma. Exosomes are now being 
examined for potential therapeutic effect. Exosome-treated rats lost 
only a third of their retinal ganglion cells following optic nerve 
injury, compared with 90 percent loss in untreated rats. NEI is now 
reviewing proposals for a third AGI consortium, to develop animal model 
systems to facilitate translation of discovery research into the 
clinic.
    NEI just launched new stem cell trials for retinal vein occlusion 
(RVO)--the second leading retinal vascular cause of vision loss after 
diabetic retinopathy, and for limbal stem cell deficiency (LSCD). In 
RVO, the vessels draining blood from retinal tissue become clotted, 
leading to leaking and bleeding and ultimately starving the neurons of 
oxygen. The trial will test the safety, feasibility and efficacy of 
injecting stem cells derived from the patient's own bone marrow into 
their eyes. Corneal limbal cells, are responsible for renewing the 
front layer of the transparent cornea. In thousands of patients with 
LSCD, loss of these cells causes visual impairment from chronic 
inflammation, abnormal blood vessel growth, and opaque corneas. The 
21st Century Cures Act Regenerative Medicine Program is supporting an 
NEI project to treat LSCD. Researchers identified a limbal cell marker, 
ABCB5, which has allowed them to isolate, purify and expand limbal stem 
cells in the lab in sufficient quantities for transplantation. This 
summer, NEI scientists are about to launch the first clinical trial 
using induced pluripotent stem cells-derived retinal tissue to treat 
the dry form of AMD. Skin cells taken from AMD patients will be 
manipulated in the lab for about 3 months, then transplanted back into 
the same patients, thereby minimizing rejection of foreign tissue that 
affects many types of transplant therapies.
    In 2017, NEI launched a 3D Retina Organoid Challenge Competition 
(3D-ROC), with the goal of developing functioning ``mini-retinas'' in a 
culture dish from human adult stem cells. In September, NEI awarded the 
$90,000 prize for the Phase I Ideation Stage, to a team that developed 
the concept of building a retina by screen-printing adult neural 
progenitor-derived retinal cells in layers that mimic the structure of 
the human retina. The system is designed to be scalable, efficient, and 
reproducible, enabling high throughput screening for drug testing. In 
February 2018, NEI launched Phase II, which soon will award up to $1 
million in prizes for developing this work to the critical stage of 
functional prototypes of human retinas.
    In January, NEI announced the launch of a new strategic planning 
process, under the auspices of the National Eye Advisory Council. The 
5-year plan will be developed with significant community input, 
centered around scientific program working groups. It will also align 
with the NIH Strategic Plan and requirements laid out in the 21st 
Century Cures Act, including research to address health disparities.
                                 ______
                                 
    Prepared Statement of Martha J. Somerman, DDS, Ph.D., Director, 
         National Institute of Dental and Craniofacial Research
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute of Dental and Craniofacial Research (NIDCR) of the National 
Institutes of Health (NIH).
    The mission of NIDCR is to improve dental, oral, and craniofacial 
health through research, research training, and the dissemination of 
health information. A recent study looking at personal healthcare 
spending in the United States by condition estimates that Americans 
spend $66.4 billion annually on the treatment of oral disorders and 
another $48.7 billion for general dental care and preventive services. 
Together, the total surpasses the costs of treatment related to a 
common condition among Americans--diabetes--by more than $13 
billion.\18\ NIDCR leads the effort to reduce this burden by supporting 
basic, translational, and clinical research and research training to 
improve dental, oral, and craniofacial health. By promoting the timely 
translation of those findings into practice NIDCR helps advance 
treatment and prevention strategies for all Americans.
---------------------------------------------------------------------------
    \18\ Dieleman J. US Spending on Personal Health Care and Public 
Health, 1996-2013. JAMA. 2016; 316(24):2627-2646.
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    To prioritize emerging areas of scientific inquiry that are ripe 
for significant advances over the next decade, we launched a long-term 
strategic initiative called NIDCR 2030. As part of this bold, forward-
looking plan, NIDCR will support research that integrates oral health 
into overall health and uncovers the common risk factors and underlying 
biological mechanisms of health and disease throughout the body. This 
knowledge will inform the development of new preventative and 
therapeutic interventions to improve dental, oral, and craniofacial 
health--as well as the health of the whole body.
          pioneering a gene therapy to treat chronic dry mouth
    For most people who survive head and neck cancers, successful 
treatment with radiation therapy comes at a high price--significant 
loss of salivary gland function, leading to chronic dry mouth and its 
adverse health effects. Radiation therapy works by killing malignant 
tumor cells, but it does not discriminate among cell types. It also 
kills saliva-producing cells, which causes saliva production to shut 
down. This can lead to problems chewing, tasting, talking, and 
swallowing food, and significantly increases the risks for dental 
decay, tooth loss, and oral infections. NIDCR supports research to 
unravel the complex molecular and cellular processes involved in 
salivary gland function and fluid secretion. These investments have 
inspired the development of a gene therapy to treat chronic dry mouth 
caused by radiation treatment. The therapy delivers specific DNA 
sequences into the surviving salivary gland cells, resulting in the 
production of specialized tube-shaped proteins called aquaporins, which 
allow water to flow out of the salivary gland cells. Studies in mouse 
models showed that the gene therapy generated enough aquaporin proteins 
to restore salivary flow. This research led to a clinical trial 
conducted on the NIH campus that is currently recruiting patients to 
test the gene therapy treatment in people whose salivary glands have 
been damaged by radiation therapy for head and neck cancer. Results 
from the first phase of the study are encouraging and suggest that this 
approach could be a promising treatment. Building on these studies, 
another clinical trial is being planned to see if the therapy can also 
be used to restore salivary function in individuals whose chronic dry 
mouth is caused by Sjogren's syndrome, an autoimmune disorder that 
damages salivary glands.
   developing innovative techniques to advance regenerative medicine
    A major priority for NIDCR is advancing regenerative medicine 
research to improve the lives of those with dental, oral, and 
craniofacial conditions or diseases. A significant challenge in 
regenerating load-bearing tissues such as joint cartilage is 
engineering and growing tissues that are as strong and flexible as the 
body's natural ones. The cartilage that makes up joints, such as the 
temporomandibular joint in the jaw, must be extremely resilient to 
withstand a lifetime of repetitive movement and mechanical stress. To 
overcome this obstacle, NIDCR-supported scientists are developing 
techniques to generate functional tissues in the laboratory for 
regenerative medicine therapies. These scientists developed a device 
that physically pulls on single layers of cartilage cells while they 
are being grown on a flat, supportive matrix, resulting in tissues with 
strength and elasticity that more closely resembles natural cartilage. 
Using this technique results in engineered cartilage that is more 
resilient to wear and tear, making it especially useful as a potential 
replacement for damaged cartilage in highly mobile joints. Future uses 
could include the development of better treatment options for 
temporomandibular joint and muscle disorders (TMD) and joints damaged 
by osteoarthritis. Further development of this novel cartilage growth 
technique, and its expansion to other cell types could open the door to 
exciting possibilities for the engineering and generation of more 
durable and flexible tissues for use throughout the body.
                finding pain relief in unexpected places
    Chronic pain is a major health problem that affects almost one-
quarter of the U.S. population.\19\ Opioids are often prescribed to 
alleviate chronic pain, although they carry a strong risk for 
addiction. Identifying new effective and non-addictive pain treatments 
remains a priority for NIDCR, especially in regard to TMD, a group of 
conditions that can cause severe and chronic pain in the jaw and 
muscles of the head and neck. In 2005, NIDCR launched OPPERA (Orofacial 
Pain, Prospective Evaluation and Risk Assessment)--a multi-site 
population-based study--to identify the biopsychosocial and genetic 
risk factors that cause TMD. Early OPPERA studies found an association 
between the gene for epidermal growth factor (EGFR) and the development 
of chronic pain in patients with TMD. Drugs that block the activity of 
EGFR are currently being used to inhibit tumor growth in some types of 
cancer. Strikingly, there have been case reports of cancer patients 
reporting a significant reduction in pain when treated with EGFR-
blocking drugs. Taking these observations into the laboratory, NIDCR-
funded investigators used a mouse model to show that EGFR-blocking 
drugs alleviate inflammatory and neuropathic pain. These drugs function 
by blocking the activity of EGFR in neurons that receive and interpret 
sensory stimuli--such as pain--in the body. This intriguing finding 
could lead to the development of more effective treatments for chronic 
pain that also reduce the risks for addiction.
---------------------------------------------------------------------------
    \19\ Gereau RW, et al. A pain research agenda for the 21st century. 
J Pain. 2014; 15(12):1203--1214.
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 advancing treatments for hpv-positive and hpv-negative oropharyngeal 
                                cancers
    Oropharyngeal cancers form in the middle part of the throat, 
including the back of the mouth, base of the tongue, and the tonsils, 
and are often caused by HPV (human papilloma virus), the same virus 
that causes cervical cancer. These cancers are known as HPV-positive 
(HPV+) oropharyngeal cancers. Experts estimate that 60 to 70 percent of 
newly diagnosed oropharyngeal cancers in the United States are likely 
to be HPV+, especially among young men and women. Although people 
exposed to the HPV virus are more likely to develop oropharyngeal 
cancer, paradoxically, HPV+ cancers respond much more successfully to 
chemotherapy than HPV-negative (HPV-) cancers. A collaboration of 
clinicians and basic science researchers funded by NIDCR are studying 
the biomolecular reasons for this difference in treatment outcomes to 
see if there is a way to separate out the HPV+ beneficial response to 
treatment and then apply it to HPV-negative (HPV-) oropharyngeal 
cancers. To do this they looked closely at the activities of 
cisplatin--the most commonly used chemotherapy for many cancers--which 
is better at killing HPV+ cancer cells than HPV-cancer cells. The team 
discovered an HPV protein called E7 that enhances the effectiveness of 
cisplatin treatment, and then developed a small protein fragment 
(peptide) called E2F5 that mimics the HPV protein E7 without the HPV 
infection. Combining this novel peptide with cisplatin treatment in 
HPV-negative patients led to improved outcomes, similar to those of 
HPV+ patients. Next steps will be to clear the FDA requirements for 
producing the E2F5 peptide and establishing treatment protocols for 
clinical trials.
                                 ______
                                 
Prepared Statement of Eliseo J. Perez-Stable, M.D., Director, National 
          Institute on Minority Health and Health Disparities
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute on Minority Health and Health Minorities of the National 
Institutes of Health (NIH).
    advancing the science of minority health and health disparities 
                                research
    Today, revolutionary advances in biomedical science, such as the 
emergence of genomics, precision medicine, and health information 
technology hold greater promise to improve our Nation's health than has 
ever before been possible. We are on the cusp of major scientific 
advances that will change how we think about minority health and health 
disparities. The mission of the National Institute on Minority Health 
and Health Disparities (NIMHD) is to lead scientific research to 
improve minority health and reduce health disparities. To accomplish 
this, NIMHD plans, coordinates, reviews, and evaluates NIH minority 
health and health disparities research and activities; conducts and 
supports research in minority health and health disparities; promotes 
and supports the training of a diverse research workforce; translates 
and disseminates research information; and fosters innovative 
collaborations and partnerships. As part of its charge to improve 
minority health and reduce health disparities, NIMHD is currently 
developing the 2018-2022 Trans-NIH Minority Health and Health 
Disparities Strategic Plan in collaboration with the other NIH 
Institutes and Centers and with input from community partners and key 
stakeholders. Once completed, this strategic plan will provide a 
blueprint to advance the direction and goals of minority health and 
health disparities research.
    As the science of minority health and health disparities research 
evolves, a critical multidisciplinary approach is needed to focus on 
research studies that facilitate scientific advances to improve 
minority health and to reduce health disparities. Minority health 
research is the scientific investigation of distinctive health 
characteristics and attributes of minority racial and/or ethnic groups 
who are underrepresented in biomedical research in order to understand 
population health outcomes. Health disparities research is a field of 
study devoted to gaining greater scientific knowledge about the 
influence of health determinants, understanding the role of different 
pathways leading to disparities, and determining how findings 
translates into interventions to reduce health disparities. In order to 
ensure that all populations have an equal opportunity to live healthy 
and productive lives, NIMHD leads advancement in minority health and 
health disparities research and promotes a diverse scientific workforce 
reflective of the population.
                                research
    Advancing the science of minority health and health disparities 
requires scientific vision; that means building and developing 
evidence-based information that takes into account the social 
determinants of health and the places where we live, learn, work, and 
play. To meet the demands of keeping up with biomedical advances, NIMHD 
is strengthening research in minority health and health disparities; 
increasing opportunities for investigator-initiated research; 
strengthening the evaluation and reporting of minority health and 
health disparities research; and supporting the expansion of workforce 
diversity.
    NIMHD promoted the fields of minority health and health disparities 
by developing and posting NIMHD's Research Framework, a transformative 
scientific agenda which addresses the complex influences on health and 
health disparities. Specifically, the Research Framework reflects an 
evolving conceptualization of factors relevant to the understanding and 
promotion of minority health and to the understanding and reduction of 
health disparities. The framework focuses on how these influences 
affect individuals, families, communities and society at large. It 
serves as a vehicle for encouraging NIMHD- and NIH-supported research 
that addresses the complex and multi-faceted nature of minority health 
and health disparities and guides researchers on where on the 
scientific spectrum their research fits.
    NIMHD's increased emphasis on the science of minority health and 
health disparities has evolved into the three focused areas of clinical 
and health services research, integrative biological and behavioral 
research, and community health and population sciences. The Clinical 
and Health Services Research area generates new knowledge to improve 
health outcomes and quality of healthcare for minority and underserved 
populations within the context of everyday clinical practice. It 
examines the development of preventive, diagnostic and therapeutic 
healthcare interventions that can contribute to reducing health 
disparities and how precision patient-clinician communication may 
reduce health disparities. Moreover, it supports clinical research that 
generates new knowledge to improve health outcomes and quality of 
healthcare. For example, researchers found that childhood cancer 
survivors who reported greater well-being rated religion and 
spirituality of high importance, accessed specialized cancer services 
more regularly, and expressed a greater level of healthcare self-
efficacy.
    The Integrative Biological and Behavioral Research area examines 
research on how biological and behavioral mechanisms and pathways 
influence resilience and susceptibility to adverse health conditions 
that disproportionately affect racial and ethnic minority populations, 
persons of less privileged socioeconomic status, and other health 
disparity populations. Research examples in this area include genomic 
and epigenomic risk and protective factors; human microbiome 
contributions to health and disease; and mechanisms through which 
behavioral risk and protective factors influence the development of 
adverse health conditions by triggering adverse biological pathways. 
For example, research found that changes in DNA, as a consequence of 
environmental factors, can be used to accurately estimate gestational 
age. This novel measure of gestational age may be a useful tool in 
addressing persistent higher rates of low birth weights for some 
minority populations.
    The Community Health and Population Sciences research area focuses 
on community engaged research and large studies of populations in a 
defined geographic area that reflect overall health of minority and 
underserved population groups. Community engagement refers to the 
active participation of community members in contributing to the 
research process in a partnership with investigators. Studies within 
this area examine causes, prevention, screening, early detection, and 
management of disease such as epidemiologic studies that identify and 
describe disease burden and risk factors in disparity populations; 
behavioral, sociocultural, and environmental influences on disease 
risks and outcomes; and research integrating the multiple determinants 
of health at the biologic, behavioral, and contextual levels and their 
interactions. In a study examining the perspective of older breast 
cancer survivors toward physical activity, researchers found that 
physical activity programs should focus on cancer treatment related 
concerns and include strength training.
    Innovative partnerships and collaborations are instrumental and 
essential to improve minority health and reduce health disparities. 
NIMHD supports research partnerships across NIH and the Federal 
Government with a goal to create synergistic research approaches to 
improve public health for health disparity populations. Partnerships 
conducted and supported by the NIMHD have created innovative studies 
into how to promote screening for breast, prostate, and pancreatic 
cancers; examine how children's experiences affect brain development; 
investigate the effects of environmental exposures--including physical, 
chemical, biological, social, behavioral, natural and built 
environments--on child health and development; understand the sources 
of persistent health disparities in overall longevity, cardiovascular 
disease, and cerebrovascular disease; and to eventually eliminate 
health disparities in dental care and oral/pharyngeal cancer.
                building a diverse biomedical workforce
    At the core of NIMHD's transformative scientific agenda is its 
commitment to building institutional research capacity and a diverse 
cadre of minority health and health disparities researchers. The 
Centers of Excellence program creates collaborative hubs for minority 
health and health disparities research among research institutions and 
local communities, which support early-career scientists as well as 
established investigators. The Research Centers in Minority 
Institutions program builds research capacity, supports a new 
generation of researchers from underrepresented populations through 
pilot funding, and funds established scientists to conduct cutting edge 
science in basic, behavioral or clinical research topics. The Research 
Endowment program provides funds to low resource academic institutions 
with a diverse student body and faculty to support endowments that will 
help to support a training or research capacity program to promote 
minority health and health disparities research.
    NIMHD is committed to supporting and developing a diverse 
biomedical workforce. We support training grants across the spectrum of 
experience from pre-doctoral awards through mid-career awards. 
Moreover, NIMHD has enhanced opportunities for early-stage 
investigators by: expanding awards to help senior postdoctoral fellows 
and junior faculty-level candidates to become competitive for major 
grant support; providing fellowships to help less experienced 
researchers to become productive, independent investigators; and 
restructuring the NIMHD Health Disparities Research Institute to 
support career development for promising early-career minority health 
and health disparities research scientists.
                               conclusion
    NIMHD continues to advance the science of minority health and 
health disparities by building upon evidence-based research; developing 
researchers from underrepresented populations and retaining their 
diverse insights; and enhancing programs that create research 
infrastructure and train a diverse scientific workforce. Through this 
scientific research agenda, NIMHD's mission and vision will lead to 
discoveries that will promote health equity and ultimately improve 
minority health and reduce health disparities.
                                 ______
                                 
   Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal 
                Deputy Director, Office of the Director
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the Office of the 
Director (OD) of the National Institutes of Health (NIH).
    The OD promotes and fosters NIH research and research training 
efforts in the prevention and treatment of disease through the policy 
oversight of both the extramural grant and contract award functions, 
the Intramural Research program, and through the coordinating efforts 
of several cross-cutting program offices responsible for stimulating 
specific areas of research throughout NIH to complement the ongoing 
efforts of the Institutes and Centers. The OD also develops policies in 
response to emerging scientific opportunities employing ethical and 
legal considerations; coordinates the communication of health 
information to the public and scientific communities; provides 
oversight and management of peer review policies; and coordinates 
information technology across NIH. The OD also provides the core 
administrative and management services, such as budget, human 
resources, property management, procurement services, ethics oversight, 
committee management, and the administration of equal employment 
policies and practices.
    The fiscal year 2019 budget request will also support activities 
managed by the OD's operational offices. The OD Operations is comprised 
of several OD Offices that provide advice to the NIH Director, policy 
direction and oversight to the NIH research community, and administer 
centralized support services essential to the NIH mission. In addition 
to the Common Fund (CF) administered by the Division of Program 
Coordination, Planning, and Strategic Initiatives, two additional 
research programs, Environmental Influences on Child Health Outcomes 
(ECHO) and the All of Us Research Program, are coordinated within the 
OD. The functions and initiatives of the OD's research offices and 
programs are described in detail as follows:
 division of program coordination, planning, and strategic initiatives
    DPCPSI (Division of Program Coordination, Planning, and Strategic 
Initiatives) provides leadership for identifying, reporting, and 
funding trans-NIH research that represents important areas of emerging 
scientific opportunities, rising public health challenges, or knowledge 
gaps that merit further research and would benefit from collaboration 
between two or more ICs, or from strategic coordination and planning.
    DPCPSI includes major programmatic offices that coordinate, and 
support research and activities related to HIV/AIDS, women's health, 
behavioral and social sciences, disease prevention, dietary 
supplements, and research infrastructure. DPCPSI serves as a resource 
for the ICs and OD for portfolio analysis by developing, using, and 
disseminating data-driven approaches and computational tools. DPCPSI 
serves as the focal point for coordinating research to advance the 
health and wellbeing of sexual and gender minorities and for American 
Indians and Alaska Natives, and coordinating tribal consultation 
activities for the NIH.
    The Office of Research Infrastructure Program (ORIP) provides 
support for research into model systems of human diseases and a variety 
of research infrastructure needs. ORIP supports a number of 
repositories of animal models, biological materials, genetic stocks, 
and human biospecimens. ORIP also makes grant awards to fund the 
purchase of expensive state-of-the-art scientific instruments and to 
update animal research facilities. ORIP supports training and career 
development for veterinarian-scientists engaged in biomedical research 
and contributing to interdisciplinary research teams addressing topics 
at the intersection of human/animal populations and the environment.
    The Office of Aids Research (OAR) plays a unique role at NIH by 
serving as a model of trans-NIH planning and management, vested with 
primary responsibility for overseeing all HIV/AIDS-related research 
supported by the NIH. OAR coordinates the scientific, budgetary, 
legislative, and policy elements of the NIH HIV/AIDS research program. 
OAR's response to the HIV/AIDS epidemic requires a unique and complex 
multi-institute, multi-disciplinary, global research program. This 
diverse research portfolio demands an exceptional level of scientific 
coordination and management of research funds to identify the highest-
priority areas of scientific opportunity, enhance collaboration, 
minimize duplication, and ensure that precious research dollars are 
invested effectively and efficiently.
    The Office of Behavioral and Social Sciences Research (OBSSR) 
furthers the mission of the NIH by emphasizing the critical role that 
behavioral and social factors play in health, healthcare and well-
being. OBSSR serves as a liaison between NIH and the extramural 
research communities, other Federal agencies, academic and scientific 
societies, national voluntary health agencies, the media, and the 
general public on matters pertaining to behavioral and social sciences 
research. OBSSR's vision is to bring together the biomedical, 
behavioral, and social science communities to work more collaboratively 
to solve the pressing health challenges facing our Nation. OBSSR also 
coordinates and helps support the NIH Basic Behavioral and Social 
Science Opportunity Network, a trans-NIH initiative to expand the 
agency's funding of basic behavioral and social sciences research.
    The Office of Research on Women's Health (ORWH) has worked to 
ensure the inclusion of women in NIH clinical research, to advance and 
expand women's health research, and to promote advancement of women in 
biomedical careers. ORWH is the focal point for NIH women's health 
research and works in partnership with the NIH ICs to incorporate a 
women's health and sex differences research perspective into the NIH 
scientific framework. ORWH activities are guided by the NIH Strategic 
Plan for Women's Health Research. This strategic plan outlines six 
goals to maximize impact of NIH research effort. The NIH strategic plan 
for women's health and sex differences research serves as a framework 
for interdisciplinary scientific approaches.
    The Office of Disease Prevention (ODP) is responsible for 
assessing, facilitating, and stimulating research in disease prevention 
and health promotion, and disseminating the results of this research to 
improve public health. In fiscal year 2019, ODP will release a new 
strategic plan which outlines the priorities that the Office will focus 
on over the next 5 years and highlights ODP's role in advancing 
prevention research at the NIH. The Office of Dietary Supplements (ODS) 
is within the ODP organizational structure. The mission of ODS is to 
strengthen knowledge and understanding of dietary supplements by 
evaluating scientific information, stimulating and supporting research, 
disseminating research results, and educating the public to foster an 
enhanced quality of life and health for the U.S. population.
    The Office of Strategic Coordination (OSC) and the Common Fund 
(CF)- OSC manages the Common Fund (CF), which functions as a ``venture 
capital'' space where high-risk, innovative endeavors with the 
potential for extraordinary impact can be supported. CF supports 
approximately 30 programs that focus on areas of emerging scientific 
opportunities, rising public health challenges, and knowledge gaps that 
deserve special emphasis; that would benefit from strategic 
coordination and planning across NIH Institutes and Centers (ICs); and 
that are designed to address specific, high-impact goals and milestones 
within a 5- to 10-year timeframe. Collectively, these programs 
represent strategic investments aimed at solving problems or building 
resources to affect research throughout the entire biomedical research 
enterprise. Most CF programs consist of a series of integrated 
initiatives that collectively address a set of goals aiming to 
transform the way research is conducted, the way that health and 
disease are understood, and/or the way that diseases are diagnosed or 
treated.
           environmental influences on child health outcomes
    Launched in fiscal year 2016, the Environmental Influences on Child 
Health Outcomes (ECHO) program supports multiple synergistic, 
longitudinal studies by leveraging, harmonizing, and combining existing 
and new data from 83 maternal/pediatric cohorts to create one ECHO-wide 
Cohort with 50,000 participants. Researchers will investigate the 
effects of a broad range of early life environmental exposures (e.g., 
physical/chemical, societal, psychosocial, behavioral, biological) on 
five key pediatric outcomes with high public health impact: pre-, peri-
, and postnatal outcomes; upper and lower airway conditions; obesity; 
neurodevelopment and positive health.
    The intervention component of ECHO is the IDeA States Pediatric 
Clinical Trials Network, with a goal to provide access for rural and 
medically underserved children to participate in state-of-the-art 
clinical trials. This network builds institutional capacity, provides 
professional development to researcher and their teams, and leverages 
partnerships with outside academic institutions. In fiscal year 2019, 
having built its infrastructure, ECHO Cohorts will disseminate research 
findings, and the IDeA States Pediatric Network will continue to 
conduct one or more clinical trials.
                       all of us research program
    The All of Us Research Program, launched in fiscal year 2016, is an 
ambitious effort to gather data on the biological, environmental, and 
behavioral influences on health and disease over many years from one 
million or more people living in the United States. All of Us will 
serve as a national research resource to inform thousands of studies, 
covering a wide variety of health conditions and enabling 
individualized prevention and treatment options for patients.
    Since July 2016, All of Us achieved several key implementation 
milestones, including initial study protocol approval, establishment of 
a state-of-the-art biobank to process and store biological samples from 
patients, and construction of a big data IT system to store data for 
research purposes. Working together with a consortium of Federal, 
academic, and industry partners, All of Us began participant enrollment 
for its beta testing phase in May 2017, and, as of March 25, 2018, more 
than 35,000 participants are currently enrolled, of whom over 20,000 
have completed the full protocol.
    The program will begin full-scale, nationwide participant 
enrollment in the spring of 2018.
                                 ______
                                 
Prepared Statement of Dr. Nora Volkow, Director, National Institute on 
                               Drug Abuse
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2019 budget request for the National 
Institute on Drug Abuse (NIDA) of the National Institutes of Health 
(NIH).
               drug use and addiction research priorities
    As a part of NIH, the Nation's premier biomedical research agency, 
NIDA's mission is to advance the science on the causes and consequences 
of drug use and addiction and to apply that knowledge to improve 
individual and public health. NIDA-supported research has transformed 
our understanding of how biological, social, and environmental factors 
contribute to substance use disorders (SUD), generating new knowledge 
that fosters the development of smarter means for preventing and 
treating SUDs.
    Substance use and SUDs represent a constant and dynamic threat to 
the health and well-being of our Nation. Their combined toll is more 
than $740 billion a year in healthcare, crime, and lost productivity; 
but dollars barely capture the devastating human cost of addiction to 
individuals, families, and communities. In 2016 alone, over 63,000 
Americans died because of an unintentional drug overdose. Over 42,000 
of these deaths are attributable to opioids, due in large part to the 
spread of powerful synthetic opioids such as fentanyl and its 
analogues. Other challenges include the disconcerting rise in 
fatalities associated with cocaine and methamphetamine use, as well as 
the rise of new synthetic drugs and delivery systems, such as e-
cigarettes, that are changing how people perceive and use drugs.
    Despite these complex challenges, this is a time of great 
opportunities. In the last few years we have seen huge technological 
advances and new research applications, from deep sequencing to precise 
gene editing tools, and from more powerful brain imaging technologies 
to mobile health platforms and electronic health records.
    NIDA's commitment to leveraging these advances through synergistic 
collaborations with Federal, community, and industry partners has been 
codified in the 2016-2020 Strategic Plan, which charts our path forward 
according to four broadly defined goals designed to:
  --Understand the complex multilevel interactions influencing drug use 
        trajectories.
  --Accelerate the development of treatments for SUDs.
  --Address real-world complexities including comorbidities and poly-
        drug use.
  --Advance bi-directional translation from basic to clinical and 
        applied research.
                          research highlights
    I'd like to highlight several high priority research areas that 
NIDA is pursuing, the most prominent of which is addressing the opioid 
crisis with medications development and implementation research efforts 
as well as assessing the impact of adolescent drug use on brain 
development and behavior that will build the evidence for personalized 
prevention.
                             opioid crisis
    Millions of Americans are suffering from an opioid use disorder 
(OUD). The urgency and scale of this crisis calls for innovative 
solutions:
    Medications Development.--The Division of Therapeutics and Medical 
Consequences supports synthesis and preclinical evaluation of potential 
therapeutics, clinical trial design and execution, and preparing 
regulatory submissions of medications. While there are current 
treatments available to reverse opioid overdose and treat opioid use 
disorder, the continued epidemic underscores the need for improved 
treatment options. In addition to current projects, new projects on 
reformulating drugs are underway and supported by NIDA grants and 
contracts. For example, NIDA support is accelerating the development of 
extended release formulations of existing medications used to treat OUD 
(methadone, buprenorphine, and naltrexone), as well as new medications 
to prevent and reverse overdoses from synthetic opioids or from drug 
combination (alcohol and heroin).
    Criminal Justice.--Juvenile Justice Translational Research on 
Interventions for Adolescents in the Legal System (JJ-TRIALS) is guided 
by the philosophy that all juvenile offenders can benefit from 
evidence-based drug use and HIV-related prevention, screening, and 
treatment interventions. JJ-TRIALS builds on the strong foundation of 
our past work with criminal justice populations and includes three 
interrelated research efforts: (1) a national survey of existing 
practices within the juvenile justice system, (2) a large-scale, multi-
site randomized study of data-driven strategies to improve justice 
systems' capacity to identify unmet substance use service needs, and 
(3) a pilot study examining the capacity to form partnerships with 
public health providers to address HIV and sexually transmitted 
infection risk behaviors.
    Rural Communities.--In rural areas, a lack of treatment 
infrastructure and poor access to care hamper efforts to stem the tide 
of opioid addiction. Together with SAMHSA, CDC, and the Appalachian 
Regional Commission (ARC), NIDA is funding research to reduce the 
adverse outcomes of injection opioid use in rural communities. Initial 
projects focused on epidemiology, infrastructure, and policy issues to 
lay foundation for future research and planning efforts throughout 
Appalachia, while subsequent projects are testing the effectiveness of 
community response models and best practices in responding to opioid 
injection epidemics that can be implemented in similar rural 
communities across the US.
    Developing Alternative Pain Treatments With Reduced Abuse 
Potential.--In addition to these strategies to reverse the opioid 
overdose epidemic, we must develop more effective and less addictive 
treatments for chronic pain; NIDA is working with the NIH Pain 
Consortium to promote research in this key area. Funded grants span the 
entire range of the therapeutics development spectrum from preclinical 
safety and efficacy testing and early phase human trials, to health 
services research. Worth highlighting in this context are new molecular 
imaging technologies like x-ray crystallography that revealed the 
molecular structure of the receptors that mediate drugs' effects, 
information that is already leading to the development of safer 
medications to treat pain including the potential for developing an 
opioid pain medication devoid of addictive effects.
               adolescent drug use and brain development
    A deeper understanding of how biological, environmental, social, 
and developmental factors interact and contribute to SUD risk is 
critical for developing better prevention and treatment strategies. 
This is particularly true when trying to understand how early onset 
drug use impacts developmental processes. To address this high priority 
need, NIDA has launched, jointly with other NIH institutes, centers, 
and offices the Adolescent Brain and Cognitive Development (ABCD) 
study, the largest long-term study of brain development and child 
health in the United States. Approximately 10,000 children ages 9-10 
will be studied at 21 research centers across the country; they will be 
followed into early adulthood with brain-imaging, genetic, 
neuropsychological, behavioral, and other health assessments. The 
results will expand our understanding of how drugs can disrupt a young 
person's life trajectory. As of March 2018, more than 8,300 
participants were enrolled in the study and close to 30 terabytes of 
data--about three times the size of the Library of Congress 
collection--had been obtained from the first 4,500 participants.
                        prevention and treatment
    Substance use disorders present a fascinating phenomenon: they are 
wholly preventable but when they strike, they can be utterly 
catastrophic. Hence, it is important to reassess our stance vis a vis 
prevention and treatment as often as possible and in response to new 
developments including the need for prevention strategies to protect 
against opioid initiation that is rising among young adults (early 
twenties).
    Prevention and Treatment.--NIDA supports integrated approaches to 
understanding and developing strategies to addressing the interactions 
between individuals and environments that contribute to substance use 
by fielding the annual Monitoring the Future survey of adolescent 
students. NIDA also supports the National Drug Early Warning System 
(NDEWS) network to survey emerging trends related to illicit drug use. 
The Division also supports research on integrating prevention and 
treatment services into healthcare and community systems to reduce the 
burden of drug problems across the lifespan. Ongoing research is 
exploring SUD treatment in the criminal justice system, including 
studies on implementation of medication-assisted treatment (MAT) and 
seek, test, treat, and retain (STTR) strategies for people with SUDs 
who are also at risk for HIV. NIDA also funds research into the 
efficacy of screening, brief intervention, and referral to treatment 
(SBIRT) in primary care settings for reducing drug use including opioid 
use disorders. Our research also examines the implementation of 
evidence-based universal as well as tailored prevention interventions 
and treatment services in real-world settings. For instance, NIDA is 
funding researchers to partner with States as they use the State 
Targeted Response funding from the 21st Century Cures Act to test 
approaches for expanding access to MAT for opioid use disorder and 
naloxone for the reversal of opioid overdoses.
    The NIDA Clinical Trials Network (CTN) is a collaborative 
partnership with clinicians, researchers, and participating patients 
that cooperatively develops, tests, and delivers new treatment options 
to patients with SUD including opioid addiction. The CTN studies 
behavioral, pharmacological, and integrated treatment interventions in 
rigorous, multisite clinical trials across a network of community-based 
treatment settings. Current CTN-funded trials include studies on how to 
implement buprenorphine in emergency departments and by primary care 
physicians, engagement of pharmacists for prescribing and monitoring 
buprenorphine to patients with an OUD and the effectiveness of a 
combination pharmacotherapy regimen to treat methamphetamine use 
disorder, among others.
    Our efforts to develop effective addiction treatments respond to 
urgent needs while facing significant challenges. For example, despite 
remarkable advances in recent years, our menu of effective addiction 
treatments still presents critical gaps. Most notably, there continues 
to be a dire need for therapies to help treat addiction to stimulant 
drugs, like cocaine and methamphetamines or to help treat addiction to 
marijuana. As a result, NIDA is committed to evaluating the potential 
of emerging new therapies for SUDs, including pharmacological and non-
pharmacological (e.g. psychosocial, biofeedback, brain stimulation 
technologies). For example, NIDA's IRP is collaborating with partners 
in the pharmaceutical industry to study a potential medication to 
decrease methamphetamine craving and collaborating with Italian 
researchers to test the efficacy of transcranial Magnetic Stimulation 
(TMS) for treatment of cocaine use disorders. The IRP is also exploring 
interventions to reverse the impact of prefrontal cortex deficits 
caused by cocaine or heroin use and to develop clinically useful 
indicators (biomarkers) of addiction severity or treatment efficacy 
that will support the development of more effective treatments.
                               conclusion
    Substance use and its attending disorders are complex conditions. 
The fiscal year 2019 budget request will allow NIDA to support cutting-
edge research that leverages the most powerful technologies and latest 
emerging opportunities to expand our understanding of drug use and 
addiction in order to enhance prevention and treatment, help address 
public health emergencies, and improve the health of the public.