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



 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2018

                              ----------                              


                        THURSDAY, JUNE 22, 2017

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10 a.m. in room SD-138, Dirksen 
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
    Present: Senators Blunt, Cochran, Shelby, Alexander, Moran, 
Lankford, Kennedy, Murray, Durbin, Shaheen, Murphy, Manchin, 
and Leahy.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
        GARY GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND BLOOD 
            INSTITUTE
        ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        RICHARD HODES, DIRECTOR, NATIONAL INSTITUTE ON AGING
        NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE
        JOSHUA GORDON, M.D., Ph.D., DIRECTOR, NATIONAL INSTITUTE OF 
            MENTAL HEALTH


                 opening statement of senator roy blunt


    Senator Blunt. The committee will come to order. The 
Appropriations Subcommittee on Labor, Health and Human 
Services, Education, and Related Agencies will come to order.
    Before my opening statement, I want to recognize Melinda 
Bachini, who we had a chance, nine of us did, to meet and talk 
to about her cancer fight and the success she's made there when 
we were out at NIH (National Institutes of Health) a few days 
ago.
    And we are glad you're here, and I was just told that the 
youngest of your six children just got their driver's license, 
so good luck with that.
    [Laughter.]
    Senator Blunt. Good luck with all of that.
    And we were glad to have a chance to meet with her. We're 
glad to have Dr. Collins and the other Institute Directors here 
today. The budget, of course, proposes cuts that I think that 
you can rest assured the committee will find unacceptable. The 
$7.5 billion cut from NIH would, according to analysts, cost 
nearly 90,000 jobs nationwide, result in $15.3 billion of lost 
economic activity. In my home State of Missouri, that equates 
to a loss of nearly 1,700 jobs and $292 million in economic 
activity. The cut is one that I think you can rest assured this 
committee will not take. I certainly fundamentally disagree 
with the proposed funding reduction.
    However, this isn't the first President to propose a 
reduction. President Obama proposed a $1 billion cut in his 
budget last year. We went $3 billion above his proposal. I'm 
not sure we could do anything like that this year, but I also 
mentioned in a hearing earlier this week that when his budget 
was submitted to the Senate, 98 Senators voted against it, and 
1 Senator voted for it. So we have a long history of the 
Congress asserting itself on issues of how to allocate money. I 
believe this committee will do the same thing this year.
    In the last 2 years we were able to increase funding by $4 
billion, with significant encouragement from the whole 
committee, and particularly from Senator Murray, Senator 
Alexander, Senator Durbin, and really the whole committee, we 
had nine of our committee out at NIH recently. I think it was 
the biggest Senate delegation to ever go to NIH. We spent most 
of the afternoon.
    I hope you, Dr. Collins, and your Institute Directors, know 
how much your work is appreciated. In the last 2 years, we have 
increased NIH funding by a little more than 13 percent, and 
we're going to be listening carefully to your presentations 
today.
    But before that, I would like to turn to Senator Murray for 
her opening comments.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Good morning. Thank you, Dr. Collins and the other Institute 
Directors, for appearing before the Subcommittee today to discuss the 
National Institutes of Health's fiscal year 2018 budget request.
    The budget request proposes to cut $7.5 billion from the NIH. 
According to analysis from United for Medical Research, this funding 
reduction could cost nearly 90,000 jobs nationwide and result in a 
$15.3 billion loss in economic activity. In my home State of Missouri, 
that equates to a loss of nearly 1,700 jobs and $292 million. A cut to 
NIH is not a cut to Washington bureaucracy; it is a cut to life-saving 
treatments and cures, affecting research performed all across the 
country.
    I fundamentally disagree with the proposed funding reduction for 
NIH. However, this is not the first President's budget to propose 
reducing NIH funding. Just last year, the Obama Administration proposed 
cutting $1 billion in discretionary funding from NIH. This Committee 
and Congress did not agree, instead, appropriating a $2 billion 
increase for a second year in a row.
    Yet, simply proposing a drastic reduction to medical research is 
the wrong message to send. It's the wrong message for the millions of 
Americans suffering from life-threatening diseases; it's the wrong 
message to the medical research community tirelessly working to develop 
new treatments and cures; and it's the wrong message to the young 
scientists deciding whether medical research is the career path they 
should pursue.
    When I became Chairman of the Labor/HHS Appropriations Subcommittee 
2 years ago, I worked with colleagues on both sides of the aisle, 
including Senators Murray, Alexander, and Durbin, to realign the 
priorities of this bill, putting a renewed focus back on medical 
research funding.
    For over a decade, funding for the National Institutes of Health 
remained stagnant, its purchasing power decreased by 22 percent since 
2003, and grant success rates, in some NIH Institutes, fell to as low 
as 9 percent. This had to change and, over the past 2 years, it has.
    We have increased funding in the past 2 years by $4 billion, an 
increase of 13.3 percent. This is a larger increase for NIH in 2 years 
than in the previous 10 years combined. In the last 2 years, we have 
more than doubled the amount of research funding for Alzheimer's 
disease and started directly funding precision medicine programs. 
Together, these initiatives could transform the way healthcare is 
delivered and help stabilize the long-term viability of Medicare. But 
under the proposed budget, these programs may not move forward as 
envisioned. In fact, Alzheimer's disease funding is cut by $549 million 
and the National Cancer Institute cannot even provide a Precision 
Medicine funding level.
    I am also deeply concerned about several of the specific proposals 
in the budget request, including capping indirect costs and eliminating 
the Fogarty International Center. The funding cut to NIH is so deep 
that it is difficult to determine if these proposals are recommended 
because you truly believe they will gain efficiencies for the agency, 
or if they are proposed because the topline funding levels forced you 
to do so.
    I know each of the witnesses today remains committed to biomedical 
research, just like I do. And, I know we all want to ensure that our 
researchers have the support and funding they need to make the life-
saving breakthroughs that could change so many Americans' lives. I know 
this is a budget they do not want to defend. It's a request no one 
should have to defend.
    Thank you for being here today.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Well, thank you very much, Mr. Chairman.
    Dr. Collins, thank you to you and all of your team for 
being here today. We appreciate all that you do to champion the 
critical work of NIH. You've been a great partner, and I really 
appreciate your leadership and all your teams.
    And I, too, welcome Ms. Bakini. It's good to see you again 
up from Montana.
    And I look forward to having a discussion today about 
really the devastating impact that President Trump's budget 
would have on NIH. As you all know, President Trump has 
proposed cutting NIH by 22 percent, most of it by arbitrarily 
capping indirect costs, resulting in the lowest funding level 
for biomedical research since 2002.
    Three months after releasing this proposal, we still do not 
have basic information from the administration about how NIH 
would implement a $7.5 billion reduction without severe 
consequences for thousands of research facilities and tens of 
thousands of scientists that rely on its grants to support 
their work, facilities like Fred Hutchinson Institute in my 
home State of Washington, just to cite one example, where 
scientists have pioneered bone marrow transplants and today are 
searching for cures to cancer and an HIV vaccine, but because 
of this proposal, could be forced to dramatically scale back 
their efforts to develop cures for patients.
    So these cuts are deeply concerning, which is why I've said 
repeatedly I really hope that both parties will once again 
reject President Trump's budget proposal and continue to work 
together, as we have, to ensure NIH is able to carry out its 
vital work that gives hope to those living with chronic and 
life-threatening disease and bolster economic growth and 
competitiveness.
    But before this discussion can happen, however, I have to 
note that today's hearing takes place in the midst of a very 
pivotal moment for our healthcare system as a whole. As we have 
heard all week, our Republican colleagues appear to be dead set 
on jamming their version of Trumpcare through the Senate in 
just a matter of days.
    This is a bill that has been subject to no hearings, no 
public debate, and no expert testimony. It's a bill so secret 
that apparently until just moments ago many Republican Senators 
were telling press and constituents they couldn't say what was 
in the bill. It was a bill so secret even President Trump's top 
healthcare advisor, Secretary of Health and Human Services, 
told us last week that he didn't know what was in it. It has 
been so secret and closely guarded that not even the 13 male 
Senators who made up the so-called working group could comment 
with certainty on what was in that or when it would be brought 
up or by what procedure. And in fact, it's a bill so secret 
that even the White House Press Secretary couldn't confirm 
whether President Trump or anybody in the White House, for that 
matter, had seen the bill, which begs the question, as I have 
said this week, what are Republican leaders so ashamed of?
    Well, it is becoming very clear now that those who wrote 
the Trumpcare bill knew they wouldn't be able to go back home 
and defend it because based on what we are now learning, this 
bill is going to be the same kind of Trumpcare bill that went 
in the House, and it will have tremendous impact on patients 
and families, higher cost for families, especially seniors and 
people with preexisting conditions. Insurance companies no 
longer will be required to cover basic healthcare, like 
maternity care or mental health services and more. Women would 
lose access to their doctors and to the care they need at 
Planned Parenthood. And tens of millions of people across the 
country would see their Medicaid coverage taken away. That 
means people nationwide who are finally getting treatment for 
substance use disorders like opioid addiction or mental 
healthcare or access to a primary care doctor under Medicaid 
are going to lose that access.
    So as many of my Democratic colleagues have said, this is 
not a healthcare bill, it's an attack on families' health and 
financial security.
    So, again, I just want to reiterate my message to 
Republican leadership: it is not too late to dump this 
Trumpcare bill, it's not too late to make the right choices and 
work with us, as Democrats, to fix our healthcare system.
    As the Chairman and others on this committee should know by 
now, Democrats stand ready, as we always have, to work together 
to actually make healthcare more affordable and accessible for 
patients and families across the country, but we cannot begin 
that conversation until Republican leadership reverses course.
    And lastly I do have to say that after hearing this week 
about so many of my Republican colleagues feeling frustrated 
about this bill's process, who are angered about being shut out 
of this process, are receiving conflicting information, or who 
may be even shocked at the text that was just released, well, 
you have the power to do something about it, not just to 
complain. You can insist on full hearings, open debate, 
increased transparency, because let's be very clear, people 
across the country are really worried about the approach that's 
being taken. They are watching. They're going to be paying 
close attention. And we need to get this right, not what is 
being jammed through the Senate.
    And with that, Mr. Chairman, I'll turn it back to you.
    Senator Blunt. Thank you, Senator Murray.
    We are pleased to have both the Chairman of the full 
committee and the Ranking Member of the full committee with us 
today. I think Chairman Cochran does not have a statement, but 
I think you may, Senator Leahy.
    Senator Cochran. Mr. Chairman, I ask that my statement be 
printed in the record.
    [The statement follows:]
               Prepared Statement of Senator Thad Cochran
    Mr. Chairman, I am pleased to join you to review the fiscal year 
2018 budget request for the National Institutes of Health (NIH).
    A good example of the work funded by the NIH is the Jackson Heart 
Study in my state of Mississippi. Over the past 20 years, this study 
has yielded insight into the causes of and potential treatments for 
cardiovascular disease in African Americans. We are proud of this 
landmark study, and I am hopeful this good work can be expanded when 
the contract is reconsidered later this year.
    I am concerned that the 22 percent funding cut proposed for NIH 
could negatively affect longstanding research endeavors like the 
Jackson Heart Study. I look forward to hearing from Dr. Collins and his 
colleagues about how the NIH can continue its robust support of medical 
research.

    Senator Blunt. Good. Thank you.

                 STATEMENT OF SENATOR PATRICK J. LEAHY

    Senator Leahy. Thank you, Chairman Blunt, Chairman Cochran, 
glad to be here with you, and of course, with Senator Murray. 
And I completely agree with her statement. I think this is an 
important meeting.
    And Dr. Collins, it's good to have you here and your whole 
team. Just for a personal note, my mother, when she was still 
with us, she was first-generation Italian American, and when 
she saw my schedule, that Dr. Fauci was going to be here, she 
would say, ``Say hello to that nice young man.''
    [Laughter.]
    Senator Leahy. Or as you say, ``Say buon giorno.''
    [Laughter.]
    Senator Leahy. But I am worried about the budget. You know, 
this affects all of us. It ignores the fact that you have to 
support the middle class, you have to lift up the most 
vulnerable, and you have to serve our values and interests as a 
Nation. And NIH has been a shining example of serving our 
Nation, but sequestration has had devastating consequences for 
both defense and non-defense programs. I think those 
consequences are going to last for a generation, it will affect 
my children and my grandchildren. And this budget makes it even 
worse, deep budget cuts.
    Those that have drawn the most bipartisan opposition, you 
heard what Senator Blunt said, and others have, about such 
budgets, the most bipartisan criticism has been reductions for 
the National Institutes of Health.
    And I want to commend Chairman Blunt and Ranking Member 
Murray for their efforts to bolster the NIH budget in recent 
years. But this one, this budget that we've been given by the 
White House turns that progress upside-down. It slashes NIH 
resources by $7.2 billion, 21 percent, the lowest NIH budget 
since 2002.
    Well, you know far better than I do that you can't--in 
medical research, you can't say, ``Okay, we'll just turn off 
for a few years those studies and trials and all, but we'll 
come back 5 years from now and pick it back up again.'' You 
just can't do it. You don't hit Pause on studies. You can't 
have ups and downs based on the whims of an anti-science group. 
That hurts the medical research field. I think not only what it 
would do to you, but there's a cap on research that's being 
done around the Nation at universities and other entities.
    I'm not being parochial, but I mention the University of 
Vermont. They receive millions of dollars of NIH grants each 
year. They wrote recently to Director Mulvaney and Secretary 
Price and noted it's unlikely that they could continue their 
research on this budget, and they've been doing cutting edge 
research in cancer, among other things. And I would ask for a 
full copy of the University of Vermont's letter be placed in 
the record, Mr. Chairman.
    Senator Blunt. Without objection.
    [The letter follows:]

    
    
    
    

    Senator Leahy. Thank you. So I think, as vice chairman of 
the overall committee, I'm committed to try to get money back 
in. This science, this is where we can excel, where we can lead 
the world. But not only that, we can make life so much better 
for our own people and people around the world. So I will fight 
for every dollar to get it back that I can.
    And thank you very much, Mr. Chairman.
    Senator Blunt. Thank you, Senator Leahy.
    Director Collins, we're pleased you're here and look 
forward to your opening statement. And when you're through with 
that, we'll go to questions.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Well, thank you. Let me introduce the folks at 
the panel table with me. Over on my left, your right, is Dr. 
Richard Hodes, the Director of the National Institute on Aging. 
Next to him, Dr. Nora Volkow, the Director of the National 
Institute on Drug Abuse. And next to me, Doug Lowy, who is the 
Acting Director of the National Cancer Institute. To my right, 
your left, Joshua Gordon, who is the Director of the National 
Institute of Mental Health, and you've already recognized in 
one comment at least, Dr. Tony Fauci, the Director of the 
National Institute of Allergy and Infectious Diseases. And at 
the far left, on your side, Gary Gibbons, who is the Director 
of the National Heart, Lung, and Blood Institute. We brought 
the ``A Team'' today.
    [Laughter.]
    Dr. Collins. So it's a pleasure and an honor that we were 
able to host many of you on our campus earlier this month, and 
it's a great honor to be here with you today, and I'm 
privileged to continue in this role as NIH Director.
    I want to thank all of you for your sustained commitment to 
NIH, a commitment that will ensure that our Nation remains the 
global leader in biomedical research, with all that it means 
for human health.
    Today, I would like to highlight several areas of 
exceptional scientific opportunity, introduce you to a few 
patients, and also talk about some young researchers who are 
working hard to make these dreams come true, and I'll show a 
few images over there on the screen.
    [The graphic follows:]

    
    

    Dr. Collins. Let's start with an opportunity that shows the 
transformational power of investing in NIH basic science. So 
imagine that you could determine the precise molecular 
structures of proteins like what you see here, proteins 
targeted by pharmaceuticals, and see exactly how they interact 
with each drug. This is starting to happen thanks to a new 
technology called cryo-EM.
    [The graphic follows:]

    
    

    Dr. Collins. This image shows the structure of a protein 
channel, which is indicated in gray mesh, that's the channel 
part, that regulates salt and water balance in the lungs. This 
very protein is misfolded in cystic fibrosis (CF), our Nation's 
most common fatal genetic disease. The genetic mutation that 
causes cystic fibrosis was discovered in my own research lab 
many years ago, but only now is new structural information 
allowing us to design better drugs to help cystic fibrosis 
patients like little Avalyn Mahoney, who will be celebrating 
her second birthday next week.
    Avalyn's life has not been easy. She required surgery for 
an intestinal blockage shortly after birth, but she's doing 
pretty well now. Just a few decades ago, she probably wouldn't 
have made it beyond her teens. No longer.
    Today, we have two targeted drugs for CF, and more to come, 
all building on NIH-support basic research. And we're not done. 
The goal is to turn CF into a 100 percent curable disease. For 
that, we need the next generation of scientific talent.
    Among the early stage investigators tackling this challenge 
is Stephen Aller, of the University of Alabama at Birmingham. 
Trained in both computer science and biology, Stephen plans to 
transform in fundamental ways how we design and deliver drugs 
for all kinds of conditions. In fact, we need that. Treatments 
only exist today for about 500 of the 7,000 diseases for which 
a molecular cause is now known.
    [The graphic follows:]

    
    

    Dr. Collins. Among those in desperate need of a 
breakthrough is sickle cell disease, a life-threatening 
disorder in which red blood cells are deformed in a way that 
clogs small blood vessels. Sickle cell disease is caused by a 
genetic misspelling, and that was essentially understood 60 
years ago, yet even today the only way it can be cured is by a 
bone marrow transplant from an unaffected donor. That can work 
really well for some patients, like Chris Sweet, shown here 
with his family. Chris received a transplant at the NIH 
Clinical Center 6 years ago and is now essentially cured. But 
unfortunately most don't have a well-matched bone marrow donor.
    So what if we could actually correct that sickle 
misspelling in the patient's own blood cells? A few years ago, 
I would have said that's pretty unlikely, but that's all 
changing. NIH's Courtney Fitzhugh is seeking to use a new gene 
editing system called CRISPR to modify bone marrow stem cells 
in people with sickle cell disease. The goal is to fix the 
underlying genetic defect and make the patient's own cells 
healthy. If Courtney and other young scientists can get this to 
work for sickle cell disease, just think about what they might 
do for thousands of others still awaiting a cure.
    [The graphic follows:]

    
    

    Dr. Collins. Now imagine you could develop a detailed 
understanding of the 86 billion neurons in the human brain. 
That's what our BRAIN Initiative aims to do. I know that each 
member of this subcommittee is aware of the enormous toll that 
brain disorders are taking upon our Nation's health and 
economy.
    Alzheimer's disease alone has an estimated economic cost of 
$259 billion this year, and it's projected to exceed $1.1 
trillion by 2050. Let's imagine that using tools and 
technologies created by the BRAIN Initiative you could easily 
identify someone at risk for Alzheimer's and use such advanced 
warning to apply effective ways of preventing this disease 
that's touched so many, including singer Glen Campbell, who was 
here on the Hill with his family just a few years ago to 
advocate for Alzheimer's disease research.
    Well, young investigator Yaki Oki Rose, of Massachusetts 
General Hospital, is among those taking on this challenge. Her 
work is focused on the largest known group of people in the 
world with inherited Alzheimer's, an extended family living in 
the mountains of Colombia. In an effort to uncover subtle 
changes in the brain years before symptoms appear, her team is 
using PET scans to compare the brains of family members who 
carry the Alzheimer's gene mutation with those who do not.
    Clearly, finding Alzheimer's won't be easy, but Yaki and 
other young researchers have the talent and drive to make it 
happen, and you all are part of this. Your emphasis on 
Alzheimer's and related dementias research in fiscal 2016 and 
2017 is enabling progress toward our mutual goal of preventing 
and effectively treating these devastating conditions.
    [The graphic follows:]

    
    

    Dr. Collins. So all of us here are motivated today by a 
sense of urgency to help patients in need of breakthroughs. The 
next generation of innovative and passionate young researchers 
will be the most critical part of achieving that bright future. 
Two weeks ago, NIH announced the Next Generation Researchers 
Initiative, a focused approach to bolster support to early- and 
mid-career investigators like the three you see here. Our 
Nation's health and well-being depend on your strong support 
for them.
    [The graphic follows:]

    
    

    Dr. Collins. So thank you, Mr. Chairman. My colleagues and 
I welcome 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, and it was a pleasure to host many of you at NIH earlier 
this month.
    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 fiscal year 2017 commitment to 
NIH.
    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 believe passionately in our mission. This extends equally to 
the tens 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.
    I would like to provide just a few examples of the depth and 
breadth of the amazing research being supported across the Institutes 
and Centers of NIH.
    The core of our mission remains basic biomedical science. Given the 
exploratory and, hence, unpredictable nature of fundamental discovery, 
basic science is generally not supported in the private sector--but it 
provides the critical foundation for advances in disease diagnosis, 
treatment, and prevention through future clinical applications. 
Virtually none of the substantial gains in reducing human suffering and 
extending longevity over the last century would have happened without 
basic science. NIH's emphasis on fostering innovation to understand 
fundamental biological processes has led to no fewer than 149 Nobel 
Prizes to our grantees, and is leading year by year to new and more 
effective ways to treat complex medical conditions.
    As a current example, the emergence of ``cryo-EM,'' a new form of 
electron microscopy, has dramatically sped up the time needed to 
visualize the exquisite details of biological structures including 
protein-protein and protein-drug complexes. This is a major revolution 
in structural biology that already is transforming drug design.
    Basic research is also fueling new advances in our understanding of 
the brain, which will be critically important for treating diseases 
such as Alzheimer's disease, Parkinson's disease, autism, epilepsy, 
traumatic brain injury, and others. Through the Accelerating Medicines 
Partnership (AMP), a public-private partnership between NIH, the Food 
and Drug Administration (FDA), 10 biotechnology companies, and 
nonprofit organizations, we have joined ranks across sectors to expand 
our understanding of Alzheimer's disease. In one component of AMP, 
researchers are analyzing large-scale molecular data from thousands of 
affected and unaffected human brain samples, including genomic, gene 
expression, and protein measures. With this information, NIH and our 
partners are building new molecular pathways to understand the cause of 
Alzheimer's, and charting a course for entirely new ways to detect and 
treat this devastating disease that go beyond the previous 
understanding of the amyloid and tau proteins. By working with industry 
and sharing data widely in the scientific community, NIH aims to 
shorten the time between these discoveries and the development of new 
strategies for Alzheimer's disease treatment and prevention.
    Rare diseases also represent an area of great need and great 
opportunity, one which NIH continues to be uniquely positioned to 
address. Though such diseases are individually rare, collectively an 
estimated 25 to 30 million Americans are affected. Great advances have 
been made through genomic science in uncovering the cause of rare 
diseases, and that has led to dramatic improvements in diagnosis. But 
of the 6,500 identified rare and neglected diseases for which the 
molecular cause is now known, only about 500 have approved treatments. 
The private sector generally finds it difficult to mount expensive 
initiatives for such small markets--the risks are too high. Finding new 
treatments thus requires NIH to play a lead role--by investing in the 
early stage of therapeutic development to ``de-risk'' such projects. 
While almost all Institutes and Centers at NIH work on rare diseases, 
the National Center for Advancing Translational Sciences (NCATS) has a 
particular focus on this area of opportunity.
    As an example, autoimmune pulmonary alveolar proteinosis (aPAP) is 
a rare, potentially fatal disease marked by a build-up of lipids and 
proteins in the lungs, and leads to respiratory failure. The current 
treatment for severe aPAP is whole-lung lavage, whereby both lungs are 
repeatedly filled and washed with a salt solution. This procedure is 
complicated, dangerous, and must be repeated throughout a patient's 
entire life. NCATS has supported efforts to develop an inhaled 
treatment for aPAP, providing support and expertise to the basic 
research, pre-clinical research and testing, and early-phase clinical 
trials.
    Other transformative technologies are offering dramatic new 
approaches to achieving a truly molecular cure of rare diseases. For 
example, experts are now testing genetic therapy in bone marrow stem 
cells as a curative treatment for sickle cell disease, the first human 
disease understood at the molecular level and the most common inherited 
blood disorder in the United States, affecting over one hundred 
thousand Americans at a yearly cost of hundreds of millions of dollars.
    As a final example, consider how fundamental research over many 
years now promises to transform medicine for patients with advanced 
cancer: immunotherapy. For decades, basic scientists have worked to 
understand how the immune system functions at the molecular level. Now, 
thanks to a series of dramatic advances, we can not only watch the 
immune system at work, we can instruct it--``send it to school.'' In a 
recent breathtaking example, a young woman with widely metastatic 
breast cancer, whose cancer had failed to respond to several rounds of 
chemotherapy, enrolled in an experimental protocol at the NIH Clinical 
Center as a last hope. Her tumor genome was sequenced, and rare immune 
cells in her body with the potential to seek and destroy those cancer 
cells were identified. After those immune cells were massively expanded 
in the laboratory, and then unleashed to go after the cancer, her 
tumors started to recede within days. Now more than a year later, there 
is no evidence of any remaining cancer in her body. She is part of a 
revolution in cancer treatment, all made possible by years of dedicated 
basic research in fields like immunology and genomics.
    So the future has never been brighter for advances in biomedical 
research than right now. Imagine what this feels like for a talented 
and curious new investigator. Early-stage investigators are responsible 
for many of the advances I've told you about today, and our future 
depends on them and their bright ideas. Those young men and women are 
thrilled by the prospect of exploration, and driven to help people. NIH 
is responsible for training these scientists, and for making sure that 
our investment in their careers, and the potential advances they will 
bring to patients, are sustained into the next stage. They are our most 
important resource. If advances in medical research are to continue, if 
research is to lead to breakthroughs that can reduce healthcare costs, 
if the considerable economic return on research is to continue, and if 
America is to continue its global leadership in biomedicine, we need to 
be sure this next generation has the confidence that there will be 
support for them. This is a priority for me.
    Two weeks ago, NIH announced the Next Generation Researchers 
Initiative, a focused approach to bolster support to early- and mid-
career investigators comprised of four components. First, we are 
repurposing funds from NIH's base budget, beginning this fiscal year 
with about $210 million, and ramping to approximately $1.1 billion per 
year after 5 years to support additional meritorious early-stage 
investigators, as well as mid-career investigators (those with less 
than or equal to 10 years as a principal investigator who are about to 
lose all NIH funding or are seeking a second award for highly 
meritorious research). Second, we will track the impact of NIH 
Institute and Center funding decisions for early- and mid-career 
investigators with fundable scores to ensure this new strategy is 
effectively implemented in all areas of research. Third, we will place 
greater emphasis on current NIH funding mechanisms aimed at early- and 
mid-career investigators, such as the NIH Common Fund New Innovator 
Awards the National Institute of General Medicine Sciences Maximizing 
Investigators' Research Award (MIRA), the National Institute of Dental 
and Craniofacial Research Sustaining Outstanding Achievement in 
Research (SOAR) Award, and other special awards from specific 
institutes, with an aim of funding most early-career investigators with 
applications that score in the top 25th percentile. Fourth, we will 
encourage multiple approaches to develop and test metrics that can be 
used to assess the impact of NIH grant support on scientific progress.
    I have provided you with examples of how investments in bright new 
ideas in biomedical research are advancing human health, spurring 
innovations in science and technology, stimulating economic growth, and 
laying the groundwork for the future of the United States biomedical 
research enterprise. We have never witnessed a time of greater promise 
for advances in medicine than right now. Your support has been 
critical, and will continue to be.
    The fiscal year 2018 Budget provides $26.9 billion for NIH, which 
is $7.4 billion below the fiscal year 2017 enacted level. The fiscal 
year 2018 Budget eliminates the Fogarty International Center while 
retaining a total of $25 million in mission-critical international 
research and research related activities within the Office of Director. 
It includes $272 million in discretionary budget authority within NIH 
to preserve key research activities previously carried out by the 
Agency for Healthcare Research and Quality (AHRQ), including critical 
survey activities, support for the U.S. Preventive Services Task Force, 
evidence-based practice centers, patient safety, investigator-initiated 
grants, and researcher training grants. NIH is engaged in many efforts 
to encourage good stewardship practices across all levels of the 
biomedical research enterprise. These include ways to streamline 
administrative processes for investigators, efforts to support new and 
early stage investigators, and a focus on cultivating a world-class 
biomedical research workforce. The fiscal year 2018 Budget includes an 
indirect cost rate for NIH grants that will be capped at 10 percent of 
total cost (currently NIH expends approximately 28 percent of its 
extramural budget on indirect costs). This approach would be applied to 
all types of grants with a rate higher than 10 percent. In addition, 
Federal research requirements for grantees will be streamlined to 
reduce grantee burden through targeted approaches as proposed by NIH.
    This concludes my testimony, and I look forward to answering your 
questions.

                      FOGARTY INTERNATIONAL CENTER

    Senator Blunt. Well, Dr. Collins, again, we're glad you're 
here. I was pleased with the President's decision to continue 
your leadership at NIH, and many of us had advocated for that, 
and we're pleased to see it happen. Your team and what your 
team does is inspiring to all of us.
    We'll have a 5-minute round of questions. I think there are 
a lot of competing things going on today, so we'll try to keep 
that as close to 5 minutes as we can starting with me.
    A couple of areas I want to ask specifically about in the 
President's proposal, one was to eliminate the Fogarty 
International Center. I think particularly with the Zika virus 
response we're going through and have gone through, that Center 
was pretty actively involved. Your thoughts about what the 
Center does as opposed to commenting on necessarily the 
President's view of this.
    Dr. Collins. I appreciate the question. I'm going to ask 
Dr. Fauci to say something about this.
    Senator Blunt. Great.
    Dr. Fauci. Thank very much, Mr. Chairman. The Fogarty 
International Center is truly integral to all that we do both 
directly and indirectly internationally and domestically 
particularly in the arena of infectious diseases, because as we 
know and have testified before this committee so often, 
infectious diseases know no borders.
    There are some cogent examples of how the training of 
international scientific colleagues supported by the Fogarty 
International Center has benefited the United States of 
America, and the two that are most recent are the Ebola 
outbreak and the Zika outbreak, not to mention the long-
standing commitment to HIV/AIDS and the clinical trials that 
are being done in Sub-Saharan Africa. Almost all of these 
trials are led by international scientists who were trained by 
Fogarty grants.
    Now, with regard to Ebola, you might recall that in West 
Africa, in Liberia, Guinea, and Sierra Leone, they had 28,000 
cases and 11,000 deaths. If the Ebola outbreak had gone beyond 
those borders to places like Mali or Nigeria, it could have 
been even a greater catastrophe than it was. When Ebola 
infected individuals went to Mali and to Nigeria, it didn't 
make much press because it was a success in that the 
investigators in those countries were able to handle, identify, 
isolate, contact, trace, and stop Ebola in those countries 
before it started to spread, particularly in Nigeria, which is 
the most populous country in Africa. Each of those 
investigators who helped control Ebola were people who were 
trained by the Fogarty International Center.
    We look upon Fogarty-trained scientists as our true 
colleagues. I refer to them, and I mean that sincerely, as our 
brothers and sisters in the battle against infectious diseases. 
If this were a military metaphor, they would be our closest 
allies. They might wear a different uniform, but they are our 
allies. So the impact of the training that Fogarty supports has 
been extraordinary, and we really need to continue.

    AGENCY FOR HEALTHCARE RESEARCH AND QUALITY INTEGRATION INTO NIH

    Senator Blunt. Another area, the establishment of the 
National Institute for Research on Safety and Quality,--the 
Agency for Healthcare Research and Quality would be 
consolidated into a new--I believe they propose a new institute 
in your organization. One, if you want to comment on that 
generally; and two, if that was going to happen, are there 
alternative ways for those things to be moved into NIH without 
creating a new institute?
    Dr. Collins. So the Agency for Health Research Quality does 
complementary research to NIH particularly focused on health 
safety and health quality, for instance, looking at how to 
prevent health problems such as hospital readmissions, such as 
infections from intravenous catheters. We have strong interest 
in the research they do, and vice versa, and we have close 
connections with them. And we regularly look at our portfolios 
to make sure that we're being complementary and not 
duplicative.
    So if it were the case that AHRQ (Agency for Healthcare 
Research and Quality) was moved into NIH, as is proposed in the 
President's budget, we would figure out how it is that we could 
make the best of that circumstance in order to keep that 
important research going forward.
    Your other question is, would there be other models to 
achieve this other than a new institute? Certainly we could 
consider other models, such as having the portfolio that's in 
AHRQ distributed around amongst the existing institutes who do 
similar research and incorporating the staff that's part of 
AHRQ into the NIH staff without having them set up as a 
separate entity. That would be another option.
    Senator Blunt. I might point out in my last 30 seconds here 
to something I should have mentioned earlier, and it follows up 
on Senator Murray's view that we've tried hard to work 
together. You know, what we've done at NIH in the last 2 years, 
there was no new money to do that, so it was truly a 
prioritization that eliminated programs and consolidated 
programs. And these were programs we had to determine weren't 
doing everything we had hoped they would do so that priority 
could be placed on what you're doing.
    And this is one of those times when Congress really has 
chosen to make decisions that for a lot of Members were really 
hard and for some Members were almost impossible to make, but 
the case you're making is an important case for us to be able 
to understand and talk about.
    Senator Murray.

              INDIRECT COSTS/FACILITIES AND ADMINISTRATION

    Senator Murray. Thank you.
    And thank you again, Dr. Collins, to you and all your team. 
As you have been hearing, there is tremendous concern among the 
research community about President Trump's proposal to cap 
indirect costs. What can you tell us about the status of 
efforts to replace the existing long-standing practice for 
calculating indirect costs with a 10 percent flat fee? Are your 
staff participating in those discussions?
    Dr. Collins. So ``indirect costs'' maybe is a somewhat 
unfortunate term because it's a little hard to know what's 
being referred to. Another alternative is ``facilities and 
administration'' or ``F&A.'' Those indirect costs, which on the 
average right now for NIH are about 28 percent of the grant 
awards in the extramural community, but it varies from 
institution to institution, go to cover such things as the 
facilities, the building, the utilities, the supply of light 
and water, the operations of various administrative services, 
such as human subjects oversight, animal care oversight, and so 
on. Those are not things that can be ascribed to a single 
grant, but they are basically necessary for the institution to 
be able to conduct research.
    Certainly, the proposal to reduce the amount that would go 
from NIH to indirect costs from 28 percent roughly on the 
average to 10 percent has attracted a lot of attention in the 
community because universities who do this work see that as 
potentially quite dangerous for their ability to keep going 
forward.
    We are looking at every possible way that we might be able 
to assist in this conversation by identifying areas in which 
various administrative burdens that we ask institutions to 
follow could be reduced because maybe they're not as necessary 
as they are. So we're looking at our current regulations, for 
instance, about conflict of interest, about animal care, about 
effort reporting. We might in that process be able to identify 
a way to reduce somewhat the burden, but frankly, I don't think 
it would add up to an enormous difference in what we're 
currently asking our grantee institutions to do, and they are 
the ones who do the work. We depend on them.

                      INTRAMURAL RESEARCH PROGRAM

    Senator Murray. Well, what would happen to your intramural 
research program if the costs were kept at 10 percent?
    Dr. Collins. Our intramural program, which you visited 
recently, much of it on the NIH campus, is about 11 percent of 
the overall budget. Calculating indirect costs is a little 
complicated. It's a purely government facility. When that was 
recently looked at, but not that recently, it was about 30 
percent. It was similar to what we would see happening in the 
extramural community. For that intramural program, there would 
be no other potential source of funds. It would make it rather 
hard for me or anyone at this table I think to imagine what we 
would do if that was required to drop to 10 percent given that 
we have the buildings and the electric power and so on.

          IMPACT OF ADMINISTRATIVE COST TO EXTRAMURAL RESEARCH

    Senator Murray. So it would be pretty devastating.
    Dr. Collins. I'm having a hard time imagining how we would 
manage that.
    Senator Murray. Okay. Dr. Lowy, this proposal assumes that 
States or some other benefactor will somehow step in to cover 
the lion's share of indirect costs once NIH abandons that 
responsibility. It's a lot to assume that our States are going 
to pick up what's long been a Federal responsibility, but many 
private institutions don't have access to State resources or 
large trust funds that could cover the difference. What would 
likely happen to those research--places like Fred Hutch or SOC 
or Scripps if they are forced to result their indirect costs to 
10 percent of their grant?
    Dr. Lowy. Senator Murray, it's difficult to speculate 
exactly what would happen, but institutions such as the Fred 
Hutchinson Cancer Research Center have been central to the 
advances that we have made in cancer research.
    For example, Donnall Thomas received a Nobel Prize for the 
research that he conducted with his colleagues at the Fred 
Hutchinson. More recently, Paul Nghiem led the effort to do 
research on the use of immunotherapy for patients with Merkel 
cell cancer, and this has led to a breakthrough for those 
patients who have this disease. It's not as common as melanoma, 
but it is the skin cancer that has the highest mortality rate. 
And recently the FDA approved a cancer immune checkpoint 
inhibitor for treatment of this disease, the first advance in 
many years.
    At the Scripps Institute, for example, they're performing 
breakthrough research on trying to inhibit a particular 
oncogene called Myc that is involved in at least 50 percent of 
human cancer, but we don't yet have interventions that are 
successful for that.
    So these are just some examples of the breakthrough 
treatments that are being developed at these institutions.
    Senator Murray. That would have an impact if the direct 
impact was cut, it would be hard for them to continue that.
    Dr. Lowy. Yes. Certainly they would have difficulty to 
continue their rate of progress.
    Senator Murray. Okay. Thank you very much, Mr. Chairman.
    Senator Blunt. Thank you, Senator Murray.
    Chairman Cochran.

            MINORITY REPRESENTATION IN ALZHEIMER'S RESEARCH

    Senator Cochran. Mr. Chairman, let me join you in 
congratulating our panel here and the participation you're 
bringing to this challenge.
    Dr. Collins, how is the NIH working to ensure that 
minorities are represented at Alzheimer's research activities?
    Dr. Collins. So we are very interested in making sure that 
the resources Congress gives us are utilized in an optimum way 
for health disparities research across all of the fields 
represented by people at this table. You specifically asked 
about Alzheimer's. I'm going to ask Dr. Hodes, who is our key 
person for Alzheimer's research, to address that.
    Dr. Hodes. Thank you very much for the question. In fact, 
in our efforts at Alzheimer's research, very prominent among 
them is attention to disparities, both because all Americans 
have a right to the fruits of research, but also because the 
best understanding of what underlies the processes behind 
Alzheimer's is going to come by understanding how it affects 
individuals of different racial, ethnic, social backgrounds. 
And in fact, a great deal of discovery has shown that even the 
genetic risk factors differ across groups.
    Now, to ensure that we included these populations in 
research, we have active recruitment efforts that are broad. We 
also work through collaboration with some of the existing 
resources. For example, some of the populations who have been 
studied through NHLBI (National Heart, Lung, and Blood 
Institute), including those in your own State, are being 
harmonized with other studies. So we can look across all of 
these, do comparisons about risk factors, causes, and 
ultimately identify interventions that will target on a 
personalized basis across dispersed disparate populations.
    Senator Cochran. Thank you.
    Senator Blunt. Thank you, Chairman.
    Senator Durbin.
    Senator Durbin. Let me first acknowledge, Dr. Lowy, thank 
you for coming to Chicago last October and meeting with the 
directors of Illinois' two NCI (National Cancer Institute)-
Designated Comprehensive Cancer Centers, Lurie Comprehensive 
Cancer Center of Northwestern and University of Chicago 
Medicine Comprehensive Cancer Center. And thanks for your years 
of service as the Acting Director of the NCI. I understand 
you're going to be stepping aside to allow Ned Sharpless to 
take over.
    Your work personally has helped to develop a vaccine 
against cervical cancer, which is a leading cause of cancer 
death among women. It has saved and will continue to save 
countless lives. Our Nation and beyond are forever indebted to 
you for your dedication to research. I hope reports that you 
are going to continue on at NIH in another capacity are true. 
And I just want to thank you on behalf of this committee and 
the people who have been benefited by your great work over the 
years. Thank you, Dr. Lowy.
    Dr. Lowy. Thank you, Senator Durbin.

  INFORMING THE PUBLIC OF NIH'S CONTRIBUTIONS TO RESEARCH DEVELOPMENT

    Senator Durbin. Let me ask you a question, Dr. Collins. If 
I were to ask you whether or not NIH research was part of the 
development of a certain pharmaceutical drug or part of the 
development of a certain medical device, could you trace the 
lineage of the research so that you could tell me a yes or a no 
if NIH was involved?
    Dr. Collins. I think usually we could, and in about 75 
percent or so, the questions of that sort you would ask, the 
answer would be yes, NIH played a role, not necessarily a 
direct proximal role to the ultimate product, but discoveries 
that happened at an earlier point leading to ideas about 
mechanisms, leading to ideas about possible therapeutics, yes, 
you can connect those dots, and those dots almost always 
involve NIH research in some way.
    Senator Durbin. Well, let me tell you why I ask you that 
question. We're all sitting here wearing clothing and suits and 
such, and somewhere there's a label inside, where it's made. 
And we go out to the market and we buy products, and we have an 
identity of the producer and contents.
    And I think it's about time that the NIH had a label that 
is applied to pharmaceuticals and medical devices and other 
things where you can connect the dots. I think it's time the 
American people came to hear the National Institutes of Health 
being referred to on a regular basis as part of the sourcing of 
the great things that are happening.
    You have so many miraculous stories to tell. And I don't 
know if you did a survey across America how many people would 
be able to identify what the letters ``NIH'' stand for. I think 
it's time we do something about it.
    We pass laws about the labels on my suit and the labels on 
products, and I'd like to ask the Chairman and others to think 
about joining me in a bipartisan effort to make sure that 
credit is given where it's due so that Americans come to 
appreciate how you're at the heart of basic research that 
really makes their lives an awful lot better. And so I'm going 
to work on something and I'm going to work with you to make 
sure we do it in the right way.
    Dr. Collins. Well, Senator, I really appreciate your 
emphasizing the importance of this being more widely 
recognized. It is true if you ask people on the streets, ``Do 
you know what NIH is?'' I think the last survey it was less 
than 20 percent. A much higher recognition for NASA (National 
Aeronautics and Space Administration) than there is for NIH, 
and yet obviously a lot of the taxpayers' dollars going into 
what we're trying to do here.
    I would give a quick plug that in August there is a series 
on Discovery called First in Human, which follows a series of 
families that have been treated at the NIH Clinical Center, 
which you all just visited a couple of weeks ago. It is 
powerful. It is three subsequent weeks, 2-hour segments, and 
you will follow and see what happens to these patients and 
their families as they go through what are clearly 
circumstances that are quite desperate. And that's how people 
come to us, because all other options have been ruled out. That 
would be a very good way for America to get a sense about what 
we do and why it matters so much.
    Senator Durbin. Thank you.

                         OPIOID--HEROIN CRISIS

    Dr. Volkow, we're in the midst of an opioid-heroin crisis, 
some places hit harder than others, including the home State of 
my colleague, Senator Shaheen. It is an incredible crisis 
generated by the production of 14 billion opioid tablets a year 
in the United States of America, enough for every adult, every 
adult, to have a 1-month prescription to opioids. That 
production number is approved by the Federal Government each 
year, the Department of Drug Enforcement Administration.
    And then, of course, it gets into the general population 
through scripts written by doctors. CDC (Centers for Disease 
Control and Prevention) has warned these doctors, ``Don't 
overdue it except in extreme cases.''
    I know you're looking closely at this and couldn't join us 
when we visited, but would you comment on the fact that at 
least at this moment the United States Government is complicit 
in the overproduction of opioids?
    Dr. Volkow. Well, I think that in the healthcare system we 
have to recognize our involvement in creating the opioid 
crisis, and it was the result of a well-intentioned initiative 
to treat those patients that were suffering from chronic pain, 
but without the proper education or understanding about the 
tools that we're using to actually treat those patients, which 
was predominantly relying on opioid medications. And as a 
result of that, there was an overprescription that we're 
currently leading. That led to diversion, abuse, and then 
transfer into heroin and synthetic opioids.
    What we are doing from the NIH perspective is taking a 
multipronged approach to address it. Recognizing that the need 
of pain patients was the initial driver, we are aiming to 
actually create public-private partnerships, and this is 
encompassed by the whole NIH, for energizing the development of 
alternative analgesics that are not going to be addictive. So 
that's one of them.
    The other one is again incentivizing the pharmaceuticals 
through these public-private partnerships to the development of 
alternative formulations for the medications that we currently 
have for treating opioid use disorders as well as to developing 
alternative targets for the treatment of addiction of opioids.
    And finally, again, through public-private partnership with 
industry, to develop prevention interventions for overdose as 
well as to develop even more efficient reversal medications 
such as Narcan to address the opioid crisis.
    Senator Durbin. Thank you.
    Senator Blunt. Thank you, Senator Durbin.
    Senator Moran.

        NIH GRANT DOLLARS FOR RESEARCH COMPARED VS SALARIES PAID

    Senator Moran. Chairman, thank you very much.
    Dr. Collins, welcome to you and your fellow Directors at 
NIH. Such a pleasure to hear from you. And I join my colleagues 
in expressing our gratitude for the work that occurs at NIH and 
across the country on behalf of improving the lives and health 
and well-being of millions of Americans and people around the 
globe as well as helping us.
    While we have this healthcare debate going on, it's always 
been my belief that if we can devote additional resources into 
finding cures and delays in treatments of diseases, it's one of 
the suggestions I've made for a long time, we can do a 
significant benefit to the cost of healthcare in the United 
States. And as we have a debate going on about how to pay for 
healthcare, I hope we never forget the opportunity to look at 
why healthcare costs so much in the first place. Who pays? Is 
the different question. That's a challenge for lots of folks. 
But if we can reduce the cost to everyone, all will benefit, 
and I hope that we can spend a lot of attention on that, 
including the continued support for NIH and its mission.
    Let me ask a process question I guess to Dr. Collins. One 
of the things that has been brought to my attention is the way 
that NIH spending occurs in grant support. And I raised this 
with Secretary Price when he was in front of our committee last 
week, but it's my understanding that some research institutions 
make, and particularly universities, make the salaries of their 
researchers contingent upon receiving an NIH grant, and 
instances in which some researchers receive up to 80 percent of 
their salaries as a result of a grant.
    And the question I raise is, is there thought about trying 
to focus the NIH grant dollars on the research as compared to 
the salaries of the researchers such that more money goes 
into--I know you can't have research without the scientists, 
but I also know that universities and other institutions, in my 
view, should be supporting those individuals more or grant 
dollars go to the research. Am I missing something, Dr. 
Collins?
    Dr. Collins. No, I think you've accurately stated the facts 
of the situation. Since World War II, the government, through 
NIH and other funding agencies for science, has sought to try 
to encourage institutions to do scientific research and has 
basically then contracted with those universities to provide 
the full cost of that research being done, and that has 
included in that calculation then the percentage of time of a 
faculty member that's going towards a research project as an 
allowable request when the grant application is submitted.
    And many of the times in some places where faculty are 
essentially doing almost all of their work in research, their 
percent effort over various grants then can climb up to be in 
the neighborhood of 50 or 60 or even 80 percent, although in 
reality on the average it's generally much less than that 
because most researchers have other activities as well. And 
again, we do not pay for other activities of faculty, such as 
teaching or running committees for their institutions.
    It looks as if roughly something between 5 and 10 percent 
of the NIH budget currently goes to pay the salaries for those 
faculty members who are our grantees who are doing that 
research. Institutions would obviously be alarmed at the idea 
that that would no longer be allowable.
    I would point out that there are caps on the level of 
salary that we will pay. A salary cap has been applied by the 
Congress in most of the last many years. But in terms of an 
actual effort to reduce the total percentage, that has not 
previously been tried.
    I would also say, of course, that we are willing to pay the 
salaries of the postdoctoral fellows, the technicians, who are 
working in projects, and some of those would be at 100 percent 
level because that's all they're doing, is doing the research. 
If you add up all the salary coverage, well, it's probably in 
the neighborhood of 35 to 40 percent of our grant extramural 
funding. But in a way, that's our most critical resource, those 
are the people doing the work. They're the ones we have the 
hopes and dreams are going to make that next discovery.
    So, again, hearkening back to the arrangement made after 
World War II, this has seemed so far consistent.
    Senator Moran. Thank you for your answer. I may explore 
with you additional thoughts I have on this topic outside the 
hearing.
    Dr. Collins. I'd be happy to.

                  VETERAN'S AND MENTAL HEALTH RESEARCH

    Senator Moran. Let me ask Dr. Gordon. I chair the 
subcommittee that funds the Department of Veterans Affairs. 
It's a new assignment to me in the appropriations process. 
What's the relationship, I mean--and one of the things I think 
in which the VA (Veterans Affairs) faces some of its greatest 
challenges is in the care and treatment for those who served in 
our military and the consequential effects upon their mental 
health. Too many veterans slip through the cracks, and often 
it's, in my view, it's in the mental health arena. What is it 
that takes place in research at the Department of Veterans 
Affairs that is different or in addition? How is there 
coordination between what happens at NIH and at the VA?
    Dr. Gordon. Thank you very much for the question, Senator 
Moran. We have at the NIMH (National Institute of Mental 
Health), like the NIH in general, a long-standing relationship 
of collaboration with our colleagues at the VA. Many of our 
investigators work with the VA investigators, and many VA 
investigators work with us.
    Specific programs we've focused on over recent times 
include programs in suicide prevention and in PTSD (Post 
Traumatic Stress Disorder) research. In suicide prevention, we 
played an integral part in helping the VA develop research to 
identify those veterans who are at highest risk of suicide so 
that we can help them get into treatment and reduce the suicide 
rates among veterans. That's an ongoing program now that's 
being implemented throughout the Veterans Administration that 
will hopefully help save lives in the near future.
    We also are engaged in research programs, as I mentioned, 
particularly around PTSD, but in general around the mental 
health of veterans. One resource that the Veterans 
Administration has constructed, the Million Veterans Program, 
is an area of active interest which we're engaged with them in 
trying to help our extramural investigators that we fund to use 
that data to better the health of veterans and really all 
Americans.
    Senator Moran. Thank you, Doctor.
    Thank you, Mr. Chairman.
    Senator Blunt. Thank you, Senator Moran.
    Senator Shaheen.

                       SOLVING THE OPIOID CRISIS

    Senator Shaheen. Thank you, Mr. Chairman.
    And Dr. Collins, thank you very much for hosting the 
members of the committee who came to NIH 2 weeks ago. And thank 
you to Chairman Blunt for arranging that visit. I certainly 
learned a lot. It was very impressive to see your work 
firsthand at NIH, and we appreciate everything that you all do.
    Dr. Volkow, thank you for coming to New Hampshire and for 
seeing the challenge that we face with the heroin and opioid 
epidemic. You joined me at Catholic Medical Center, and we 
heard a very compelling presentation about how they were 
dealing with seven patients all with an overdose of carfentanil 
at one time in the emergency room and what kind of challenges 
that presented. And certainly as we look at what's happening in 
New Hampshire, we have got to do more, we have got to provide 
more resources, more help.
    And I know you responded to Senator Durbin about some of 
the things that you're working on. But is there something that 
you think holds the most promise that we ought to be focused 
on, or is this trying to better coordinate everything that 
we're doing?
    Dr. Volkow. I mean, in order to solve the crisis, we need 
an integrated approach working with the other agencies and 
multipronged strategy. So the one that I was describing was 
specifically targeted towards development of medications or new 
therapeutics. But in the meantime, we need to actually act 
rapidly. And one of the big challenges, particularly certainly 
in New Hampshire, but not unique to New Hampshire, is the lack 
of treatment programs that can accommodate for patients with 
substance use disorders or opioid use disorders.
    So in the area of implementation research, one of our 
priorities has been to take advantage of the fact that there 
are healthcare systems throughout the whole United States. So 
how do we integrate the healthcare system into being actively 
involved in the screening, treatment, and follow-up of patients 
with opioid use disorder?
    So in New Hampshire, we were very interested in addressing, 
for example, involvement of emergency departments on treatment, 
involvement of neonatologists on treatments. And many of these 
models are starting to emerge in the States like New Hampshire, 
and we're trying to evaluate them so we can translate it into 
other places. So this area of implementation research, new 
models for treatment of opioid use disorders, is fundamental.

                  BREAKTHROUGHS IN DIABETES TREATMENT

    Senator Shaheen. Absolutely. And I've visited many 
hospitals in New Hampshire, and one of the things that everyone 
cites as being critical to how to respond has been the 
expansion of Medicaid and the ability to get Medicaid dollars, 
and we have many hospitals, community mental health centers, 
that have been able to hire people that are looking at 
expanding and expanding treatment because they're able to count 
on those Medicaid dollars that are available through the 
Affordable Care Act. So as we look at what happens with 
healthcare here, that's one of the real challenges I think we 
face.
    I want to go, and I'm not sure, Dr. Collins, who to direct 
this to, but one of the real chronic diseases that we are 
challenged with in this country is diabetes. I have both a 
personal and a policy interest in Type 1 diabetes. And I think 
there are many people in the country that don't understand 
there is a difference between Type 1 and Type 2 diabetes, that 
Type 1 has nothing to do with lifestyle, it has nothing to do 
with what you've eaten, it has nothing to do with where you 
live, sadly, but it also is increasing at rates that will make 
it hard in the future to afford treatment to make sure we can 
address this disease by--I think the statistic is by 2050, 1 in 
3 Americans will have diabetes either Type 1 or Type 2.
    So can you talk about what research is happening at NIH to 
address Type 1 diabetes and Type 2?
    Dr. Collins. I'd be happy to do that myself because my own 
research laboratory on the NIH campus is primarily focused on 
Type 2 diabetes. We're learning a lot about both Type 1 and 
Type 2 in terms of what the risk factors are, particularly 
using the tools of genomics to identify the pathways that seem 
to be conferring susceptibility. For Type 2, the type that's 
generally coming on later in life, although not that late 
anymore with so much of a problem with juvenile obesity, that's 
pointing us towards new ideas about therapeutics.
    A particularly exciting program we have is a partnership 
with industry called the Accelerating Medicines Partnership, or 
AMP, which has focused one of its components on Type 2 
diabetes, and has brought both sectors together in a way that 
didn't happen before with a whole lot of really interesting 
ideas about new drug targets.
    For Type 1 diabetes, again, we're learning more about the 
genetic susceptibility. We still don't quite know what the 
environmental trigger is, and we presume there must be one 
because not everybody with a susceptibility gets the disease. 
But a particularly exciting advance is the development of an 
artificial pancreas that would make it possible for kids and 
adults with diabetes to have a way of managing their glucose 
and insulin without having these frequent finger sticks and 
injections of insulin, which frankly don't work as nicely as 
one would like.
    Just last year when I spoke to this panel, I predicted that 
we might actually find in the next 10 years an artificial 
pancreas reaching FDA (Food and Drug Administration) approval. 
Well, it actually happened 6 months later, so that's----
    Senator Shaheen. I was going to say it's going to happen a 
lot sooner than 10 years.
    Dr. Collins. Well, there you go. In November 2016, FDA 
approved the first one of these. It's basically a feedback loop 
that samples glucose and then delivers the appropriate dose of 
insulin without the individual having to do the calculation or 
stick their finger. Ultimately, we believe this kind of 
artificial pancreas could be even better if it was made not 
from this kind of machinery, but from your own cells using the 
opportunities we're learning about with stem cells, to take 
your skin cells and turn them into those cells that make 
insulin that maybe aren't doing that anymore for someone with 
Type 1 diabetes but could be convinced to do so. It's a very 
exciting area.
    Senator Shaheen. Well, it is. And thank you very much for 
the work that's ongoing.
    Thank you, Mr. Chairman.

                PRECISION MEDICINE AND CANCER TREATMENT

    Senator Blunt. Thank you, Senator Shaheen.
    I think we may have a few more of our colleagues come, but 
if we don't, Senator Cochran, Senator Moran, and I might have a 
second, third, and fourth round of questions while you're all 
here, and we're fortunate to have that.
    Dr. Lowy, in March, we had a hearing on funding and cancer. 
One of our witnesses, Dr. Tim Eberlein, runs the Siteman Cancer 
Center in St. Louis, and he was talking about the importance of 
precision medicine. One of the things he thought might be 
possible to determine was whether 80 percent of the women that 
currently have chemotherapy after breast cancer surgery would 
have to have that. I think there is some active discussion that 
probably only about 2 out of 10 women benefit from that, but 
how to define that.
    On that topic and generally your immunotherapy advances, 
would you talk a little bit about individual cancers and 
individual people and how they fight those cancers, and how 
you're working to find ways to define what treatment they need, 
and also ways to figure out how they can better, from their own 
unique makeup, fight that cancer?
    Dr. Lowy. Thank you, Senator Blunt. I had the pleasure of 
visiting Dr. Eberlein and his colleagues at Siteman Cancer 
Center last year, and they and many other NCI-Designated Cancer 
Centers are at the forefront of this area of precision 
medicine. The overall goal, as you point out, is to deliver the 
right medication for the right patient at the right time and 
not to overtreat people because we know that overtreatment can 
sometimes actually have serious side effects. Recently, for 
example, with NCI-supported research, it was reported at the 
ASCO meeting that giving people with colorectal cancer less 
treatment, they actually did better than people with more 
treatment.
    An important part of the Precision Medicine Initiative, 
which, thanks to your committee and Congress, has been strongly 
supported, we have been conducting research that is trying to 
understand better how the molecular abnormalities with breast 
cancer and other kinds of cancers can have implications for 
what treatments should different patients be obtaining as we 
try progressively to refine those opportunities and those 
interventions.

                        DEMENTIA AND STROKE RISK

    Senator Blunt. Dr. Gibbons, I think there is some new 
research out that would suggest that having a stroke more than 
doubles the risk of dementia. Could you talk about that a 
little bit? And also in that area, you might further define, as 
people get older, a stroke may not even be apparent, but what's 
the cumulative impact of that? I guess my question is stroke as 
it relates to dementia.
    Dr. Gibbons. Sure. Well, it's an important question you 
raise, Senator, and we now appreciate that there are many forms 
and pathways that promote dementia. You all are very familiar 
with Alzheimer's, but there is another category called vascular 
dementia that can affect maybe one in five of individuals 
affected by that debilitating condition. And indeed, vascular 
dementia can be insidious, as you implied. It may be the 
cumulative effects of vascular disease over time and risk 
factors such as high blood pressure that lead not only to heart 
disease, but also to compromised brain health. And so this is 
an active area of investigation.
    It is actually one area where women as well as African 
Americans appear to be particularly predisposed in terms of the 
cause of dementia. And again it relates to an earlier question 
by Senator Cochran as to why in the Jackson Heart Study we are 
particularly interested in looking at African Americans and the 
causes of dementia, both vascular and Alzheimer's disease.
    In collaboration with our colleagues at the National 
Institute on Aging, and Neurological Disorders and Stroke, we 
are engaged in the SPRINT-MIND trial, which looks at the effect 
of lowering blood pressure in terms of preserving cognitive 
function. So this is an active area of research.
    Senator Blunt. You know, I would think also that's another 
verification of generally my view, and I think the Committee's 
view, that while prescribing funding in some areas is frankly 
helpful to get these funds increased and to make the case, as 
in Alzheimer's, we've gone from I think $631 million to $1.4 
billion in 2 years. But, one, you're better at knowing where 
the pathways are than we are; and two, there's a more than even 
chance, I believe, that you will find something somewhere 
differently than you're looking for it, and there is lots of 
research that suggests that's the case.
    Senator Moran.

               ALZHEIMER DISEASE AND DEMENTIA PREVENTION

    Senator Moran. Chairman, thank you.
    Doctors, perhaps this is for Dr. Hodes, and we've had a 
number of Senators raise the topics about dementia and 
Alzheimer's. What is the current state? One of the things I 
think, and I've told Chairman Blunt this, and we're in 
agreement, that one of the opportunities this subcommittee has 
is to highlight to Americans ways in which they can change 
their lifestyle, dietary intake. What's the status of the 
research in regard to dementia and Alzheimer's today that we 
would want every American to know in regard to their 
activities, behavior, and nutrition and diet?
    Dr. Hodes. Well, it's a very important question. Obviously 
all of us, both individually and societally, want to make sure 
that we're doing all that we can to decrease the risk of 
dementia and cognitive decline. And in fact, it's an important 
enough question that NIH recently commissioned a study on just 
this to ask what the level of evidence is for the kinds of 
interventions which might have that desired effect in reducing 
risk. It was released today, and I think some of your staff may 
have been briefed as recently as yesterday about it.
    The key words were that there is a great deal of 
encouraging, but in most cases inconclusive, evidence for what 
we can do. I can identify three critical areas and the 
implications for what we know now and what we need to do. One 
of them just alluded to was control of hypertension. So there 
is very strong association between hypertension and its control 
and the risk of Alzheimer's disease and dementia.
    As Dr. Gibbons mentioned, one study, SPRINT, was designed 
to look at the impact of aggressive control of blood pressure 
on multiple outcomes. And this is a case where, just as 
described, our Institutes, working together and using some of 
the Alzheimer's funding, have supplemented that study to look 
at its impact on dementia. Those studies are ongoing.
    So it's an area of great promise where clinical trials such 
as SPRINT may give us conclusive evidence. But again I would 
have to point out that the evidence for the importance of 
controlling blood pressure and decreasing stroke and 
cardiovascular disease is so critical that it must be a part of 
our public health imperatives as we communicate.
    Another area is that of physical activity and exercise, 
once again shown to decrease the risk of death, cardiovascular 
disease, and where again there is suggestive evidence that it 
may play a role in decreasing risk of dementia. There are a 
number of studies, including some going on, as you know, at the 
University of Kansas--we had a chance to discuss last year 
there--that are looking directly in randomized clinical trials 
to see what forms of physical activity may make a difference in 
lowering the risk of cognitive decline or dementia.
    The other area is that of cognitive training. And one study 
supported by NIH some years ago showed that cognitive training 
was actually able to induce sustained improvements in cognitive 
function in particular areas as individuals age. That kind of 
study needs to be extended further to see if it actually will 
have an impact on dementia.
    Senator Moran. What's the example of cognitive training? 
What is it that the study suggests one ought to be doing?
    Dr. Hodes. There was a specific study called ACTIVE, that's 
its acronym, that looked at older Americans, men and women, who 
had normal cognitive function and trained them in either speed, 
reasoning, or memory, and then studied them over years to see 
the impact of that training. And it was an extremely positive 
outcome. And it's those individuals who were trained in those 
areas did have improved function over 5 and up to 10 years in 
that domain.
    What this recent National Academies report stresses, 
however, is that there is not yet compelling evidence for any 
of the other activities, including the computer-driven games, 
to identify whether they provide similar outcomes.
    So there are a good number of studies. Currently supported, 
another area where, thanks to the increased funding for 
Alzheimer's research, we're able to look to see what kind of 
cognitive interventions as well as these others may play a 
long-term role in decreasing cognitive decline and dementia.

           RELATIONSHIP BETWEEN DOWN SYNDROME AND ALZHEIMER'S

    Senator Moran. Doctor, thank you. In response to Senator 
Durbin's suggestion that NIH ought to receive more credit for 
its work, I certainly want that to occur. One of the ways that 
Americans would really relate to NIH is, ``Here are the things 
that if you do, the chances of your health improving or being 
maintained, there's a consequence to this behavior,'' and it is 
a way that I think you can tie NIH to everyday Americans and 
their lives, their worry about themselves and their families.
    Let me tie another topic that I care a lot about, Down 
syndrome. We've had conversations in the past in which Down 
syndrome and Alzheimer's, perhaps there's a connection. What's 
the status of our research in Down syndrome? I don't know who I 
should be looking at. I'll keep looking to my right. What's the 
status of that research, and what do we know about the 
relationship between Down syndrome and Alzheimer's?
    Dr. Hodes. Well, it's a very important area of research 
that probably begins with a genetic basis, is the fact that, as 
you know, Down syndrome is associated with a trisomy. There is 
an extra copy of one chromosome, chromosome 21, which happens 
to be the chromosome on which the gene-encoding amyloid protein 
and peptide lie. And reflective of that is in fact that, as we 
have seen an increase in life expectancy with Down syndrome, 
it's a remarkable accomplishment, over 30 years now an average 
life expectancy, not 30, but 50 and 60, that individuals at a 
relatively early age in high proportion are developing 
Alzheimer's-like dementia both in terms of symptoms and in 
terms of brain function and structure.
    So both because this population now is one at a special 
high risk that is deserving of attention and because studying 
this population is likely to inform all we know about 
Alzheimer's research, we have, in collaboration with the Child 
Health Institute, and, again, using some of the funding that 
has been provided over the last fiscal years, initiated 
longitudinal studies in individuals over a range of age with 
Down syndrome to study what is happening in the brain through 
imaging biomarkers to better understand and have a basis for 
ultimately intervening in these people, a highly vulnerable 
population, as well as learning more about the more general 
problems surrounding Alzheimer's type dementia.
    Senator Moran. Thank you very much. Thank you all for being 
so capable of speaking in language and terms that are 
reasonably understandable to me.
    [Laughter.]
    Senator Blunt. Thank you, Senator Moran.
    Senator Alexander.

                   JOB CREATION AND RESEARCH CENTERS

    Senator Alexander. Thank you, Mr. Chairman. First let me 
thank you, Dr. Collins, for what you do for our country. We're 
all excited about the future of the National Institutes of 
Hope, as you call it. We're delighted the President has asked 
you to lead that. And we look forward to your implementation of 
the 21st Century Cures Act, which we all worked on, voted for, 
and even in effect asked NIH, what could we put in there to 
make it easier for you to succeed?
    And I want to salute Senator Blunt, Senator Murray, Senator 
Cochran, Senator Durbin, and Senator Moran for their bipartisan 
support of increasing biomedical research. There is very little 
that's happened in terms of technological change in our country 
since World War II that hasn't had some government research as 
a part of it. We're obviously leading the world in biomedical 
research, and we want to accelerate it, not slow it down.
    Dr. Collins, am I correct that it's a goal of the Trump 
administration to keep more American jobs in the United States?
    Dr. Collins. Yes, that's my understanding as well.
    Senator Alexander. Yes. And we have about 50 major research 
universities, 17 national laboratories, no other country in the 
world has anything like them. Is it true that around those--and 
we spend a lot of money on them. The Office of Science supports 
$5.3 billion for the national laboratories; approximately $28 
billion goes through your agency to universities for research. 
Is it true that around these universities, like Stanford, the 
University of Oklahoma, the Universities of Kansas, Tennessee, 
Missouri, grow complexes of industries who are attracted by the 
research and who, as a result, create jobs around these centers 
of research?
    Dr. Collins. That's absolutely true. If you look at the 
geography of where those places have sprung up, it is very much 
attached oftentimes to a university that's a generator of a lot 
of interesting ideas and a critical mass of visionary 
scientists.

                        LOWERING INDIRECT COSTS

    Senator Alexander. Is it also true that China is making an 
extraordinary investment in new research, and even though they 
have one-fourth our gross domestic product, they may exceed us 
soon in the amount of total funding for research, and that as a 
result, a number of the Chinese scholars at our graduate 
schools and universities are being attracted back home?
    Dr. Collins. That's also true. A recent paper published in 
the JCI pointed out that in 2000, China spent only 12 percent 
of what the U.S. does on biomedical research. By 2015, it was 
75 percent. And I'm not talking about percent of GDP (gross 
domestic product), about actual spendable dollars, and they're 
on track to surpass us in the next 3 or 4 years if those----
    Senator Alexander. Well, this leads me to one of the more 
hair-brained recommendations in the budget that came up to us, 
which is that we lower the amount of indirect costs that are 
allowable for research grants from an average of 28 percent to 
10 percent. This came up when I was Education Secretary 25 
years ago and it produced a huge uproar. Most universities and 
colleges said to us at the time, ``Look, we spend a lot more 
than the average 28 percent on research, and the net effect of 
taking that from 28 to 10 or anything like it would be less 
research, and less research, we've just reminded ourselves, 
means more jobs moving overseas to cluster around the research 
wherever it is in the world.''
    I just did a quick look. The University of Tennessee could 
lose nearly $10 million if that new policy went into place; the 
University of Missouri, $15 million; Kansas, $4 million. People 
think of Harvard and Stanford when they think of indirect 
costs. ``Well, they're rich enough to handle it,'' people say. 
Well, Tennessee, Missouri, Kansas might not be. The only way I 
can think of to make that money up is either higher tuition or 
less research, and less research is not our goal because less 
research means to me more jobs overseas.
    Now, I understand that you may be asked, because of the $27 
or $28 billion that goes through your agency to the 
universities for the kind of research that we're trying to 
increase, not decrease, to report to Secretary Price and to the 
Office of Management and Budget, where I have great suspicions 
that ideas like this originate, of what the effect of this 
would be.
    So may I ask that you put in your report the following? 
Number one, if there is to be any change to this, Congress 
wants to be involved. And I'm going to get in the middle of 
that, and I'll bet I can get a bipartisan group up to make sure 
we are. Number two, will you please ask the universities, 
especially the State universities, how much they would lose in 
funding, how much they contribute to their own administrative 
and facilities costs, outside of the funding you give them, and 
whether there would be more or less research as a result of 
this policy. Include that all in your report, and if it's 
appropriate, let us know about that as well?
    I hope we can nip this idea in the bud. I hope it's one of 
those ideas in the President's budget that's just out there to 
stir up conversation. But it is a thoroughly awful idea, bad 
policy. It would not do what I know the President wants to do, 
which is to create more American jobs, not fewer, more 
research, not less, and this policy would be less.
    And my time is up, but if you want a constructive way to 
get more money out of NIH, look at the National Academies.
    May I take 60 seconds just to finish up?
    Senator Blunt. Yes.
    Senator Alexander. The National Academies has done two 
reports that says more than 40 percent of a researcher's time 
is spent on administrative tasks. My guess is most of those 
come from the Office of Management and Budget, too. So if we 
want to reduce some of those administrative tasks and free up 
more money for research grants that would be a good area to 
work on.
    So maybe I could ask you to be prepared to talk to us about 
that at some time in the future. I don't want to put you on the 
spot now, my time is up, but I wanted to register my strong 
concern about the indirect cost policy and ask that you be very 
specific in polling universities around the country about, 
``How much money would you lose? How much do you put into 
research yourself? And would there be more or less research as 
a result of this policy?''
    Thank you, Mr. Chairman, for your courtesy.
    Dr. Collins. Senator, I'll be happy to work with you on 
that.
    Senator Alexander. Thank you.
    Senator Blunt. Senator Lankford.

                REDUCTION OF ADMINISTRATIVE BURDEN/COST

    Senator Lankford. Thank you. For Senator Alexander as well, 
your extra 60 seconds bled right into my first 60. How about 
that? Because that's actually where I was beginning.
    Let me say first I appreciated all your hospitality in the 
time we could spend at NIH to get a chance to be able to see 
what's going on. We're all looking forward to quite a bit of 
what we saw in research in initial levels and in clinicals 
actually moving out to the general population, getting a chance 
to be able to see that. Everyone would benefit from things like 
universal flu vaccines, the Zika vaccine that is obviously 
progressing, and the AIDS vaccine, which has been progressing 
for a long time and getting closer and closer. Those are 
remarkable discoveries and will help a tremendous number of 
people. What's happening in cancer, mental health, and 
everything else. We very much appreciate the ongoing research 
as it benefits families all over the country and all over the 
world.
    Let me tap into what Senator Alexander was mentioning 
before about administrative costs because I want to zero in on 
just a couple areas. Many areas have already been addressed. 
One is how grants are done and how they're approved. And I want 
to talk specifically between coordination.
    When I talk to grant recipients, they will tell me, ``I go 
apply at NSF and I apply at NIH and I apply anywhere else where 
I think it's close,'' and they're just going after money 
wherever they can get it to be able to do their research. It is 
up to the entities to be able to determine, ``We've got this 
one. You shouldn't take this one. This is closer to what we're 
going to do.''
    And the example I would give you is when we do a law 
enforcement, they can tell you the lane that DEA has, that ATF 
has, and that FBI have. They know, ``That's not ours, that's 
theirs.'' In the research area, that's a little tougher to do.
    So what I'm trying to figure out, not from the grant 
recipients, they're eager to go get the grant money wherever 
they can get it; from our end, how do we help coordinate that 
to make sure that we do have good coordination that we're not 
doubling up on research in other areas, but that we're 
prioritizing that? And then how do we actually get more 
research done by reducing the administrative costs?
    If 40 percent of the costs of what's happening with the 
research dollars are just paperwork that's being completed, 
that's not helping us get to greater discovery. So what can we 
do to simplify the process on the research and reduce the 
burden for the researcher, but also make sure that we're 
coordinating this from a Federal level and being strategic?
    Dr. Collins. Senator, those are two great questions. So 
first of all, just in terms of reducing the administrative 
burden, we're very intensely interested in looking at ways that 
that might be achieved. Senator Alexander already mentioned 
this 42 percent number that came out of that National Academy 
study.
    I should point out that 22 percent of that may be the part 
that we really want the investigators to do because that's 
writing the grant proposal and making sure they've got great 
science ideas and they're putting them forward plus giving us 
annual progress reports so we know what they're actually doing.
    Senator Lankford. I totally agree.
    Dr. Collins. But that still leaves a whole lot of other 
time. And we have some levers that we can pull at NIH to try to 
reduce some of those things, effort reporting, for instance, or 
some of the oversight of conflict of interest, although we need 
to pay attention to that. But some of those levers we don't 
hold, and that would require sort of other discussions to see 
if there are ways systematically to do those reductions.
    Senator Lankford. How do we discover those so we can help 
in that?
    Dr. Collins. I think it would be fine for you all to ask us 
to give you kind of a summary of what the current 
administrative responsibilities are and where those are 
decided. We have a pretty good list of those, if that would be 
useful.
    Senator Lankford. Terrific. I think that would be very 
useful and it would be helpful not only to this committee, but 
to others, HELP included.
    Dr. Collins. And the National Academy recently published a 
report on this, you've referred to it already, that goes 
through a good deal of that information as well, but it's a bit 
lengthy. We could consolidate it if that would be helpful.

           COORDINATION OF RESEARCH EFFORTS BETWEEN AGENCIES

    Senator Lankford. Right. Not to increase your 
administrative burden while we increase others, but we need the 
help.
    [Laughter.]
    Dr. Collins. And in terms of the very real concern about 
not having duplication between different funding agencies, we 
are worried about that and do everything we can to try to nip 
it in the bud if it's starting to happen. We also have much 
better tools now for doing analytics of what's in our portfolio 
and what's in the portfolio of the National Science Foundation 
(NSF) or the Department of Defense's medical research efforts, 
or the Department of Energy's efforts, and we are looking at 
those with increasing intensity now to be able to identify if 
there are unintended duplications. Sometimes it's good to have 
some efforts going on in different ways.
    Certainly, with NSF, we have a lot of areas where we 
specifically coordinate. The BRAIN Initiative, for instance, is 
one where NSF, NIH, and DARPA, and a few other organizations 
have a big role, and we are meeting regularly with them to be 
sure that's going the way it's supposed to. In some other 
areas, we have a pretty good swim lane definition. Take 
genomics. NSF does plants, and the USDA does agricultural 
plants and animals. NIH does those that are relevant to human 
health, and we pretty good tabs on those things. But we do ask 
every investigator, when they send us a grant, they have to 
list their other support. And if we're going to give them the 
grant, we have to look at that and make sure that what they put 
there doesn't sound awfully familiar to what they're asking us 
to do, and we will go and ask them very carefully if that's the 
case.
    So I think for the most part we don't have a lot of 
unintended overlaps. But I think these new tools that we've 
developed may be an opportunity to do an even better job of 
that, and I would love to follow up with you on how we can do 
that.
    Senator Lankford. Yes. And I understand the grant 
recipients have to list where they're getting other fundings, 
but if they're simultaneously applying for other areas, that's 
the area that I see as the weak spot in that, and there has to 
be some way to be able to coordinate to say, ``We've got this 
part of it. You've got this part of it. And we've got to figure 
out who's got what lane because we need all the research done 
and need it done efficiently.''
    Dr. Collins. I'm with you.
    Senator Lankford. Thank you.
    Senator Blunt. Thank you, Senator Lankford.
    Senator Shelby.

   GOVERNMENT AND PRIVATE SECTOR COLLABORATION IN BIOMEDICAL RESEARCH

    Senator Shelby. Thank you, Mr. Chairman. I've been in 
another committee. I'm very sorry.
    Dr. Collins, how much money overall in the U.S., not just 
NIH, but all the governmental agencies, VA, you name it, is 
spent on biomedical research? And how much is spent out of the 
private sector? Whatever it is, it's not enough, I know that.
    Dr. Collins. So the NIH budget, which you all have 
overseen, and thank you for your strong support in a very 
bipartisan way over many decades, this has now led us to $34 
billion for fiscal year 2017. The VA part of this, I don't have 
the number in front of me. It is probably in the neighborhood 
of a billion or two----
    Senator Shelby. Can you furnish some of that for the 
record?
    Dr. Collins. Yes, I would be happy to do that.
    [The information follows:]
  government and private sector collaborations in biomedical research
    (1)  JAMA | The Anatomy of Medical Research: US and International 
Comparisons by Hamilton Moses et al January 13, 2015 (see Figure 2 and 
Figure 3).

    (2)  Research!America | U.S. Investments in Medical and Health 
Research and Development 2013-2015 Fall 2016 (see Sector by Sector 
Analysis on page 4 and Estimated U.S. Medical and Health Research 
Expenditures table on page 8).

    (3)  National Science Board Science & Engineering Indicators 2016 
https://www.nsf.gov/statistics/2016/nsb20161/#/ (see Chapter 4. 
Research & Development: National Trends and International Comparisons 
Figure 4-13).

    (4)  FY18 Presidents Budget Analytics Perspective 18 Research and 
Development.

    Dr. Collins. The private sector actually outspends 
government-supported biomedical research by a factor of two or 
maybe a little bit more than two. You put it all together and 
we're talking about----
    Senator Shelby. Maybe three to one?
    Dr. Collins. Two to one, three to one, in that space. So 
we're talking about an overall spend in the neighborhood of 
$100 billion a year.
    Senator Shelby. And how much of that is complementary? In 
other words, do you coordinate to some degree the investigators 
in the private sector and NIH and other government? Because 
there's a lot of overlap there.
    Dr. Collins. I'm glad you ask, because this has been a 
personal priority of mine to try to identify ways that we could 
avoid the overlap, but also encourage the appropriate 
collaborative projects.
    Senator Shelby. That's important.
    Dr. Collins. And this project----
    Senator Shelby. And how do we do that? How do we do that?
    Dr. Collins. Well, we have a model that's working pretty 
well, which is called the Accelerating Medicines Partnership. 
And this gets the scientists and the scientific leaders from 
the public sector, mostly funded by NIH, and the private 
sector, heads of R&D of Big Pharma, and we get around the table 
and say, ``What are the needs that neither of us can do 
ourselves that would speed up getting treatments to patients?'' 
So those need to be in the precompetitive space; otherwise, the 
industry people get nervous. They don't want to have 
competition finding its way in there. But there's a lot of 
that.
    So we now have a project on diabetes, we have a project on 
Alzheimer's disease, we have a project on rheumatoid arthritis 
and lupus, and we just started a new one on Parkinson's 
disease, all part of this AMP effort, which is joint industry 
at NIH, and we put money into it from both places. There's 
money on the table and skin in the game, and these projects are 
actually I think turning out to be very successful. And we're 
talking about hundreds of millions of dollars going into this.
    Senator Shelby. How much coordination is it regarding 
investigating various challenges we have internationally with 
our international friends or competitors and so forth, in the 
private and public sector?
    Dr. Collins. Well, I'm happy to say----
    Senator Shelby. What you're looking for is a cure for this 
and this, aren't you?
    Dr. Collins. Yes. Yes, indeed. Well, I'm happy that science 
has always been a pretty international enterprise, and most 
scientists have collaborators that are all over the world. 
Certainly when it comes to this industry interaction, Europe 
has a similar kind of effort called IMI, the Innovative 
Medicines Initiative. We work closely with IMI, which is now 
IMI 2, to make sure that what we're doing is complementary with 
what they are doing.
    Until recently, I've served as the chair of the heads of 
international research organizations, which brings together all 
of the funders in the public sector of the world, about 95 
percent of those dollars, to be sure that we are not stepping 
on each other's toes and actually being able to work better 
with each other.

                   UPDATE ON CYSTIC FIBROSIS RESEARCH

    Senator Shelby. Well, that's good to hear.
    Dr. Collins, we've discussed research, I have with you 
privately in here many times, involving cystic fibrosis and 
some autoimmune disease, such as lupus, several times. I know 
NIH has been involved in research in a lot of this. You've made 
a lot of progress. Could you bring us up to date first on 
cystic fibrosis, where we are? We've made progress. Where are 
we going? Of course, we're looking for a cure, I know that.
    Dr. Collins. We are, and I think we're bold enough to say 
we're on the path towards getting there, Senator. You know, the 
cystic fibrosis cause, the genetic glitch, was discovered in my 
own laboratory when I was at Michigan in 1989, but now we are 
here at this moment in history seeing the development of very 
effective targeted drugs. The first one only treated about 5 
percent of patients with cystic fibrosis who had a particular 
misspelling in that gene. But the next one brought us up to 
about 50 percent of patients who can be qualified for that. And 
when you look at what's happening now--and this is a wonderful 
example of academic research leading to advances in the private 
sector now in a company called Vertex. Jeff Leiden, who is the 
CEO of Vertex, was bold enough to say when I saw him a couple 
of weeks ago, ``We're on the path towards curing 100 percent of 
patients with cystic fibrosis, and we're not talking 20 years 
from now either.''
    Senator Shelby. Well, you've extended the life of a lot of 
children----
    Dr. Collins. Oh, yes.
    Senator Shelby [continuing]. In the last year, so that's a 
milestone in itself.
    Dr. Collins. And a hat tip of the biggest sort to the 
Cystic Fibrosis Foundation, who have been incredible supporters 
of this effort from a philanthropic perspective. Those folks 
have just been awesome.
    Senator Shelby. Absolutely. How many children, or people 
you should say, because they become adults more and more, are 
affected by cystic fibrosis?
    Dr. Collins. In the U.S., it's about 30,000 people.
    Senator Shelby. Worldwide, what is it?
    Dr. Collins. Worldwide, again it's primarily in people of 
Northern European backgrounds, so worldwide it's probably about 
100,000.

                        UPDATE ON LUPUS RESEARCH

    Senator Shelby. Okay. What about lupus? Let's talk about 
that. It's difficult, I know.
    Dr. Collins. It's difficult. This AMP project I just 
mentioned has a focus on lupus, and what they've been doing, 
which is really very advanced technologically, is to look at 
kidney biopsies from patients with lupus because, as you know, 
that's one of the major consequences of this disease, is 
affecting the kidney. And what they're doing is looking at the 
immune cells that are in those kidneys to see what's going on, 
not just as a whole bunch of cells together, but one cell at a 
time.
    Senator Shelby. Is this new? This is----
    Dr. Collins. This is brand-new. This is single-cell biology 
applied to lupus in the kidney. And they're discovering there 
are types of immune cells in the kidney that we didn't really 
know were playing a role because they're rather rare, but if 
you look at one cell at a time, you can find them. Now, where 
that's going to take us in terms of new therapeutics, right now 
I can't tell you, but this is another example where industry 
working with academia doing this project has gotten everybody 
pretty excited about what this could lead to.

            DISCOVERY IN BASIC RESEARCH--AUTOIMMUNE DISEASE

    Senator Shelby. Is the money spent overall for all 
autoimmune, so many things related to our autoimmune system, is 
it overlapped? Do you discover things in basic research?
    Dr. Collins. I should ask Dr. Fauci to quickly jump in here 
as the person who's the immunologist at the table.
    Senator Shelby. Yes, sir. I know him.
    Dr. Collins. Because I think the answer is absolutely yes. 
But, please, Tony.
    Dr. Fauci. There is a major effort on autoimmune diseases 
coming from multiple institutes. NIAID is the lead institute on 
this, but there are other institutes that also are pursing the 
concept of the induction of immune tolerance. Autoimmune 
disease is an inappropriate reaction of your own body's immune 
system against your own tissues, and different disease occur 
depending upon what the tissue is, such as lupus, rheumatoid 
arthritis, or autoimmune thyroiditis.
    What we're trying to do is to essentially go back in the 
development of an individual and try to target the cells that 
normally would have been either deleted or suppressed from the 
time you were developing as a fetus. When you develop as a 
fetus, you have cells that have the capability of attacking all 
of your tissues.
    What happens in normal development is that those cells that 
can attack your tissues either get suppressed, deleted, or they 
get tolerized, namely, they don't recognize or they don't 
respond inappropriately to your own tissues. NIAID supports 
research through its Immune Tolerance Network, which is working 
by a number of mechanisms to determine how you can shut off the 
inappropriate immune response without suppressing your 
appropriate immune response.
    Today, the crude approach to autoimmunity is to suppress 
the entire immune system, which unfortunately leads to 
complications like infections and other types of adverse 
events. We'd like to be more precise in targeting autoimmunity 
disease.
    Senator Shelby. And generate a different thing.
    Dr. Fauci. Exactly.

                           GENETICS AND LUPUS

    Senator Shelby. Is kidney failure one of the big things 
dealing with lupus? There are other things, but that's the big 
one?
    Dr. Collins. It's a multisystem disease, as you well know, 
and Senator, you've shared your wife's struggle with this, and 
I hope she's doing well now.
    Senator Shelby. She's doing well, thanks to medical 
research.
    Dr. Collins. That's wonderful. As you know, it affects the 
joints, it affects the kidneys, and it can certainly affect 
other parts of the body, including causing difficulties with 
the brain. So we need to get on top of this and figure out what 
is the best way to intervene and maybe to prevent it 
altogether.
    Senator Shelby. What role does DNA play in this? A lot, I 
guess.
    Dr. Collins. Well, of course, I'm going to say DNA plays an 
important role in absolutely everything----
    [Laughter.]
    Dr. Collins [continuing]. But it would happen to be true in 
this case.
    Senator Shelby. That's why I asked you that question.
    [Laughter.]
    Senator Shelby. You're the father.
    Dr. Collins. So clearly there are genetic susceptibilities 
to lupus. Again, they're not at the present time sufficient for 
us to understand exactly why some people get it and some don't. 
You can see some people are susceptible, but there must be some 
other trigger that happens on top of that. We know that lupus, 
for instance, is particularly common in African American women, 
and we don't entirely understand that. Some of that may be 
genetic, but some of that may be environmental.
    Dr. Fauci. It is likely both genetic and environmental, 
which is often the case when you have diseases that have a 
genetic predisposition. That's one of the things that we see in 
all diseases of autoimmunity, that they have some sort of 
either very strong or maybe a little bit more modest genetic 
predisposition.
    Senator Shelby. There is some link there, isn't it?
    Dr. Fauci. It is a link. It isn't as strong as one gene, 
one disease, but it's certainly a genetic link.
    Senator Blunt. Senator Shelby officially took his two 5-
minute rounds all at once.
    [Laughter.]
    Senator Shelby. I thank the chairman for his indulgence.
    Senator Blunt. No, no, we're getting a chance to ask 
multiple questions.
    Senator Shelby. I think the chairman might have been asking 
those same questions.
    Senator Blunt. No, no. Those were good questions asked.
    Senator Moran.
    Senator Moran. Mr. Chairman, thank you.
    Senator Shelby, while the chairman realized you did that, I 
didn't even notice.
    [Laughter.]

                      PEDIATRIC CLINICAL RESEARCH

    Senator Moran. Perhaps my final question is this, and I 
don't think we have the Director here for this topic 
particularly, but let me hear from you. I've heard from 
parents, advocates of children's hospital directors, the 
difficulties in improving pediatric care. Treatments and new 
drugs are often developed with adults rather than children in 
mind. Establishing pediatric clinical trials is a challenge.
    So I'd like to ask these questions. Considering the 
difficulties facing this patient population, what work is NIH 
doing in research on pediatric issues? And what's standing 
between NIH and pediatric research that might restrict your 
capacity to have greater results and achieve what we're looking 
for?
    Dr. Collins. Well, thanks. You're correct, that the 
Director of the National Institute for Child Health and Human 
Development, Dr. Diana Bianchi, is not at the table, although 
it would be great for you to have a chance to meet her. She was 
recently recruited from Tufts in Boston and is just a terrific 
leader in this space.
    But every Institute at this table has some investments in 
pediatric research because of the way in which little kids 
become grown-up adults, but we also recognize that they're not 
the same as miniature adults, and they need special kinds of 
attention.
    The focus on pediatrics certainly has been a long tradition 
of what NIH has done. I might just ask two of the folks at the 
table to say something about this, maybe Dr. Lowy about 
pediatric cancer, and Dr. Gordon about autism.
    Dr. Lowy. Thank you, Senator Moran. I would like to 
highlight three new programs which the NCI is initiating to 
support pediatric cancer research. As you may know, in the last 
15-year period, there has been a 20 percent decrease in 
mortality rates from children with cancer, but there are two 
serious problems. First, some children who get cancer aren't 
helped. And second, the long-term side effects for children who 
are successfully treated can be devastating.
    So one program that we are initiating is part of the use of 
the Cancer Moonshot funds from the 21st Century Cures bill, 
which is to develop new treatments for children with cancer. 
And as Dr. Collins mentioned, children--childhood cancer is not 
just adult cancer in the small sense, but it's qualitatively 
different, and so it requires a separate kind of research 
effort, et cetera. So that's number one.
    Number two, with our regular appropriation that Congress 
has been generous in giving to NCI, we are also doing what we 
are calling the Provocative Questions Initiative, and that is 
to deal with vexing problems in pediatric cancer research.
    And number three, again, this is with the Precision 
Medicine Initiative, in oncology, developing the pediatric 
MATCH trial, which will be opening in the next few weeks, and 
building on the success of the adult MATCH trial. It's a 
paradigm-shifting trial which first brings the treatment to the 
patient rather than the patient to the treatment. And second, 
based on the molecular abnormalities of the patient rather than 
the kind of cancer that they have.
    Dr. Collins. I just realized I should have also put into my 
quick response something about the ECHO program, which is a new 
initiative at NIH that we're very excited about. So ECHO stands 
for Environmental Influences on Child Health Outcomes. This is 
a trans-NIH effort to try to collect information on more than 
50,000 children in terms of environmental exposures, in terms 
of genetic risk factors, following them over the course of 
time, bringing together cohorts that had previously been 
established but hadn't been connected or subjected to this kind 
of very careful scrutiny and standardized assays.
    Because there are still many things we don't understand 
about the role of the environment maybe even in the prenatal 
arena, maybe especially in the prenatal arena, as well as in 
early childhood in terms of how that affects such things as 
asthma, obesity, neurological development, including autism, 
and basically how it affects whether that child is healthy or 
not. We want to not just study illness, but also health.
    So ECHO, which is now just about a year on, which is 
involving a very large number of components, including IDeA 
States Pediatric Research Network to basically be able to do 
clinical research, is our big investment that's new on the 
scene here to try to answer this kind of a question.
    If you want to very quickly say something about autism. I'm 
sorry I went on too long.
    Dr. Gordon. No, that's okay. So autism is really not just a 
trans-NIH initiative, but it's actually a trans-governmental 
initiative. I chair the Interagency Autism Coordinating 
Committee that involves colleagues from really across the 
government, from the DOD, from Department of Education, of 
course from the NIH and NSF. And our goal is to really try to 
understand and formulate a strategic plan for research around 
autism.
    I would say there are three really exciting ongoing things 
that we're trying to do. First, we're really trying to 
understand what makes a difference in terms of interventions 
during childhood and how that translates into long-term 
outcome.
    The second, we're trying to get a better handle on 
screening, particularly the younger and younger that we can 
identify people at high risk for autism so that we can 
intervene earlier and also so that we can learn more about what 
happens in these early ages.
    And the third is really recent developments in both 
genetics and environmental influences that really suggests 
things are going on actually in the womb, that's really where 
things are starting. So we're learning that we really have to 
understand early neuronal development so that we can really 
understand the risks for autism and do something about them.
    Senator Moran. Thank you for answering that question in a 
timely fashion such that Senator Shelby still owes me.
    [Laughter.]
    Senator Moran. I would conclude, Mr. Chairman, thank you, 
by saying this: one of the light bulbs that went off as you 
were describing this new initiative such as ECHO, one of the 
things that it suggests to me that increasing funding for NIH 
research, science brings new knowledge, which then causes us to 
look in a new area, and a new initiative arises, which suggests 
the resources are growing, the need for resources continue to 
grow.
    Very few things do we get to put the check in the box and 
say we no longer need to look at this, but research allows us 
to say, oh, here's a new way, a new place, a new opportunity 
for us to find information through research and science that 
otherwise didn't exist.
    And so there are lots of reasons I have advocated for 
increased funding of NIH that never occurred to me that just 
your success in finding information breeds the need for more 
resources to find more information.

              ADOLESCENT BRAIN COGNITIVE DEVELOPMENT STUDY

    Senator Blunt. So, Dr. Gordon, before we go to Senator 
Kennedy, there are 19 places, including Washington University 
that are looking at the adolescent brain cognitive development. 
And I wonder if you would give us a little update on what we're 
seeing in those 19 locations.
    Dr. Gordon. I'd be happy to, but that's an initiative that 
Dr. Volkow really spearheaded. We contribute funds and 
intellectual opportunities and also the database, but Dr. 
Volkow might be in a better----
    Senator Blunt. That would be great.
    Dr. Volkow.
    Dr. Volkow. Yes, thanks very much, and thanks, Josh.
    The idea of the ABCD study, the Adolescent Brain Cognitive 
Development, was a concept that now we have the technologies 
that allow us non-invasively to actually image the human brain 
in its structure and its function. And this is a non-invasive 
technology that is widely available across different health 
science centers in the country.
    And we wanted to--so we now have the capabilities to 
actually monitor how the human brain develops from childhood 
through adolescence through adulthood. And the idea is if you 
can get the standards, then like we currently do in pediatrics, 
where you have a norm that tells you whether a child is growing 
faster or slower, we should be able to get what are the normal 
distribution of human brain development. So when a parent comes 
to the physician with a child complaining that the child has 
problems, you can actually determine the extent to which the 
brain is changing.
    This will allow us to understand, for example, the effects 
of early exposure to drugs in brain development, very relevant 
as States are legalizing marijuana, the concept this is not 
harmful. It will allow us to understand, for example, how 
mental illness emerges. Can we detect that early on, on the 
basis of these brain changes? It will allow us to understand 
how physical trauma, like during sports, may negatively 
influence the development of the brain. How alcohol, how 
tobacco, how genes influence the diversity on how our brain 
works.
    This will be a prospective study. It will follow 10,000 
children from ages, 9, 10, until they reach adulthood. And we 
will evaluate not just their brain periodically, but also their 
cognitive performance, their performance at schools, their 
social networks. It will be an open access study, so any 
investigator will be able to analyze and extract data and 
information from that study.
    Senator Blunt. Thank you.
    Senator Kennedy.

             TECHNOLOGY TRANSFER AND POTENTIAL DISCOVERIES

    Senator Kennedy. Thank you, Mr. Chairman.
    And thanks to all of you doctors. I have two brothers in 
the medical field. I've heard them talk for years with respect 
and admiration about NIH, and so I was especially pleased to be 
able to attend the meetings that we had at NIH a few weeks ago 
that Senator Blunt organized. Very, very, very impressed.
    Here's my question. Let's suppose, as you often do, that 
NIH or one of the Institutes develops a new pharmaceutical drug 
or a new vaccine, and obviously it's developed with your 
creativity and intelligence and experience, but the money comes 
from the American taxpayer. And you develop it, it's 
successful, it works. At some point that vaccine or that new 
pharmaceutical drug is turned over to the private sector to 
develop further and market. When that happens, how much in 
terms of royalty or shared compensation does NIH and, more to 
the point, the American taxpayer get?
    Dr. Collins. So the connection between NIH research and the 
development of successful drugs, vaccines, and devices is very 
strong. You can certainly point to NIH-funded discoveries in 
the majority of such instances, upon which the research track 
was traveled.
    In some instances, the NIH funding was for very basic 
science, but it made a light bulb go on that then led a company 
to figure out how to turn that into a treatment. In other 
instances, NIH carries the discoveries further down the line to 
something that is even patentable and then can be licensed out 
to a company to develop a product. If that is done by one of 
our grantees in one of those institutions that we support, 
2,500 of them out there in this country, because of the Bayh-
Dole Act, that institution then holds the intellectual 
property, and if there are royalties that come forward, they 
return back to that institution----
    Senator Kennedy. Pardon me for interrupting----
    Dr. Collins. Please.
    Senator Kennedy [continuing]. But as you know, we're 
limited by time. I'm talking about when it's not one of our 
grantees, it's the NIH itself.
    Dr. Collins. Yes.
    Senator Kennedy. Who negotiates the deal? Do you have a law 
firm you use? Do you use in-house counsel? What is the standard 
royalty? How do we know--how do you know you're getting a good 
deal? I'm not suggesting you're not. Give me the details about 
how you do it.
    Dr. Collins. Sure. So if it's a discovery made by one of 
our own intramural investigators, we have an Office of 
Technology Transfer, which regularly is looking around to see 
if people have made such discoveries, to make sure that they 
claim them appropriately if they have. And then a patent gets 
filed if it seems like it's legitimate that it might ultimately 
be worth something.
    Once that patent is filed, then our Office of Technology 
Transfer, working with the scientists, try to figure out, who 
would be interested in licensing that? And so they put it out 
there. And an industry that steps forward and said, ``We're 
interested,'' then a negotiation begins. I think our 
negotiators are pretty good in terms of figuring out what----
    Senator Kennedy. Are they in-house?
    Dr. Collins. Yes.
    Senator Kennedy. Or do you use outside legal counsel?
    Dr. Collins. Yes, we have our own legal staff in-house. We 
do, I will tell you, employ also consultants, contractors, to 
help us if we have a special area of legal expertise that's 
needed, but we have very strong intramural staff. That has 
resulted roughly each year in the return of about $90 million 
to the NIH from those discoveries that did get licensed and for 
which royalties are now flowing back.
    Senator Kennedy. And again I'm sorry to interrupt you.
    Dr. Collins. No, please.
    Senator Kennedy. I'm down to 1:06, and I want to keep 
within my time. Have you ever had----
    Senator Blunt. Senator Kennedy, you can take a little extra 
time.
    Senator Kennedy. Okay. Thank you.
    Senator Blunt. Everybody else has had----
    Dr. Collins. You're being much more disciplined than your 
colleagues, I think.
    [Laughter.]

                            DRUG DEVELOPMENT

    Senator Kennedy. Thank you. Have any of you ever had the 
development of a pharmaceutical drug or a procedure or a 
vaccine that you looked at and you said, ``This works, it's a 
lead-pipe cinch''? I know maybe you haven't completed all the 
different phases that you need to do to convince the FDA, but 
based on your intelligence, which is considerable, and your 
experience, ``I know this is it,'' have you ever had one of 
those?
    Dr. Collins. Oh, yes, all the time.
    Senator Kennedy. Okay.
    [Laughter.]
    Senator Kennedy. Have we ever thought in those instances, 
I'll call them lead-pipe cinches, I don't know where that 
phrase came from, but a certainty--that might be more 
senatorial--you've got a certainty, have you ever given thought 
instead of farming it out to someone, ``Let's do it 
ourselves''?
    Dr. Collins. Yes. The trick there, Senator, is whether the 
manufacturing process is something that we want to take on. We 
don't make pills in general except in very small amounts for--
--
    Senator Kennedy. Could you sub that out?
    Dr. Collins. You mean instead of to a pharmaceutical 
company, just contract it out. I suppose that's a theoretical 
possibility. I'm going to ask Tony Fauci whether he knows of an 
example where that has been done. The times where we might do 
that would be if it's a rare disease or a neglected disease 
where there just isn't industry interest. Let me say we try 
very hard not to step into the territory where the private 
sector naturally is most capable, and we don't want to mess 
with their success in those circumstances where they're willing 
to take something on, but if they're not, well, Tony, can you 
think?
    Dr. Fauci. We have discussed this, Senator. It's an 
excellent question and something that has crossed our minds 
multiple times. For example--I deal mostly with vaccines.
    Senator Kennedy. Yes, sir.
    Dr. Fauci. To get a vaccine production capability outside 
of the already established pharmaceutical industry is almost 
impossible to do. It's just not out there. And our experience 
has been that it just makes sense in the scenario that you 
described, if we develop the very early stages of a vaccine, 
which we're in the process of doing right now with Zika, and we 
did it with Ebola. In these cases, where you do the concept 
development, you do animal preclinical testing, you do a Phase 
1 trial, and as you say, you're never sure that it's going to 
work until you do the trial, but there are some that you just 
have a feeling is going to work.
    At that stage, you have to develop a relationship with a 
pharmaceutical company because our experience in the past is 
that when we try to get into the pharmaceutical expertise at 
the end of the day, it's much more economical to license the 
product to them, get the kinds of royalties that Dr. Collins 
has spoken about, and let them use their expertise. We 
certainly have considered your model, but it just doesn't work.
    Senator Kennedy. Okay. Well, I want to thank you. I don't 
doubt for a moment that any one of you could go into the 
private sector and quadruple your income, and you know, money 
is not everything, and I think you live that, you don't just 
talk it, and I just want to thank you. I was so impressed with 
the tour and talking to your researchers and your physicians 
and to the patients who were willing to talk to us, and I just 
want to thank all of you.
    Dr. Collins. Thank you, Senator.
    Senator Kennedy. Thank you, Mr. Chairman.
    Senator Blunt. Thank you, Senator Kennedy.
    Senator Shelby.
    Senator Shelby. I will try to take some more time.
    Senator Blunt. This will be your third round.
    [Laughter.]

                         CYSTIC FIBROSIS DRUGS

    Senator Shelby. Leveraging--this slide here, ``Leveraging 
Basic Science,'' can you put that back up there? Where it's 
``Cystic Fibrosis Drugs Are Working''? It shows outside the 
cell, inside the cell, you know?
    Dr. Collins. I'm afraid I can't----
    Senator Shelby. You can't do it. But this is--you're very 
familiar with that.
    Dr. Collins. Yes. We showed that in the opening statement.
    Senator Shelby. Is this the lung?
    Dr. Collins. Well, that diagram on the left, what is that? 
That is actually a photograph at a very high magnification 
using a technique called cryo-EM. It's a protein. That is the 
protein that is responsible for CF. It's there in the lining 
cells of the lung as a channel that moves chloride and salt 
around. And until a few months ago, we didn't really quite know 
what it looks like, and now we do.
    Senator Shelby. And this is where you're talking about 
targeting things rather than perhaps rather than just do the 
shotgun approach.
    Dr. Collins. Exactly. It gives you the opportunity to be 
much more sophisticated in your drug design than just hoping 
you were going to hit something that was going to work.
    Senator Shelby. Dr. Gibbons, you're involved in the lung--
heart, lung, and blood. Do you overlap into cystic fibrosis in 
dealing with the lungs there?
    Dr. Gibbons. Yes, we do, Senator, and----
    Senator Shelby. Would you like to comment on this? I hadn't 
given you a chance, but----
    Dr. Gibbons. Well, certainly, again, Dr. Collins clearly is 
a pioneer in this area. But there are other critical elements 
of the research. For example, he alluded to the fact that 
certain misspellings change how that protein traffics in the 
cell, and a lot of that involved basic cell biology research of 
the lung epithelial cells. Determining where the proteins got 
stuck inside the cells and why was very instrumental in 
understanding how to target them and correct the trajectory of 
that trafficking. So there's always this back-and-forth between 
not only understanding the mutation, but how it affects the 
cell, the cell function, and therefore the organ's function and 
the effect on the patient.
    Moreover, there are other elements of the disease. 
Microbial agents, such as Pseudomonas bacteria, can invade and 
affect the generation of the mucus in the lungs that's so 
important as a barrier function. And so there are other 
treatment strategies----
    Senator Shelby. The accumulation of mucus in the lungs, 
isn't it?
    Dr. Gibbons. That's correct, sir.
    Senator Shelby. And how do you prevent it? Is that correct, 
Doctor?
    Dr. Gibbons. Exactly. And so understanding that in addition 
to influencing how the channel works, there are other 
strategies that can be taken to help the patient.
    Senator Shelby. And as you target the cells there you're 
talking about, what are you--I guess you're trying to suppress 
the mucus some way or get rid of it, I don't know what you do. 
But----
    Dr. Collins. It's a great question. You try every tack you 
can. I mean, one of the drugs that's turned out to be most 
useful in cystic fibrosis, but now 15 years ago, is actually 
something called DNase, which makes that mucus more able to be 
removed, it's not so thick and sticky when you have DNase there 
basically making it more fluid. So that's one approach. And of 
course, there are infections that happen in cystic fibrosis, so 
antibiotics are critical, including those that can be inhaled 
as an aerosol and go right to where the problem is.
    But I think all of us primarily are looking to the time 
where you have a drug that's not just treating the symptoms, 
not just treating the consequences, but actually treating the 
fundamental problem, which is----
    Senator Shelby. The underlying cause.
    Dr. Collins. That's exactly right. And when I talked about 
this, I have to point out that the investigator that I 
highlighted in my conversation briefly about CF was from the 
University of Alabama at Birmingham who is one of those folks 
who is doing this amazing work to look at the structure of the 
protein at the atomic level.
    Senator Kennedy. I think he went to med school at LSU, 
though.
    [Laughter.]
    Dr. Collins. It might be, I don't know.
    Senator Shelby. Dr. Gibbons, what kind of timeline do you 
see as far as--I know it's hard to say it's going to be in 3 
years, 2 years, or what, but you've made so many breakthroughs 
in cystic fibrosis. Now you've made a big one, you think, 
right? Going to the fundamental thing? And if you can target 
that, that will change the game, would it not?
    Dr. Gibbons. Oh, absolutely.
    Senator Shelby. Change the lives, we should say, of so many 
promising young people.
    Dr. Gibbons. Absolutely. It also is perhaps a forerunner 
for other rare diseases that we understand the genetic cause 
of. One that is a high priority for us is sickle cell disease. 
We are excited about the emerging new gene-editing technologies 
that exist where we can actually modify that genetic 
misspelling and turn it back into the correct spelling. This 
kind of therapy was only just a glimmer before, but now I think 
we're on the threshold of bringing it to patients. So we are 
looking forward to rapid advances related to correcting these 
genetic disorders at a fundamental level.
    Senator Shelby. Thank you.
    Thank you, Mr. Chairman.
    Senator Blunt. Thank you, Senator Shelby.
    Well, you can see lots of continued interest in everything 
you're doing, and we're glad you're here.
    Do you have a final comment, Dr. Collins?
    Dr. Collins. I just wanted to say thank you, Mr. Chairman, 
to you and the Members of this committee for your support of 
what all of my colleagues and I believe is at a remarkable 
moment in history.
    And I also wanted to take the moment, if you'll forgive me, 
to allow me to introduce to you the future Senator from 
Michigan, my granddaughter, Bailey Fraker, who is sitting back 
there.
    So, Bailey, stand up.
    Senator Blunt. Wonderful.
    [Applause.]
    Dr. Collins. I dream of a day where she doesn't have to 
worry about the health of herself or her children or maybe even 
of her grandfather, if he's still interested in playing his 
guitar and riding his motorcycle 20 years from now.
    [Laughter.]
    Dr. Collins. But I just want to say thank you to all of you 
for your support.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Blunt. Well, thank you for being here. And we hope 
you're still playing your guitar and riding your motorcycle 
with enthusiasm 20 years from now. Thanks to the Directors for 
also joining us today. The record will stay open for one week 
for additional comments.
    [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
                             indirect costs
    Question. There is significant concern in the research community 
about the proposal to cap indirect costs at 10 percent. First, I think 
the term ``indirect'' is a misnomer--these expenses are part of the 
cost of doing research in America--buying lab equipment, paying 
salaries, and having facilities to work in. Dr. Collins, if we accept 
the proposal to cap indirect costs at 10 percent, what would happen to 
the research system in the United States?
    Answer. The effect on grantees will vary by institution, depending 
on the current indirect cost rate and a variety of other factors. The 
impact will be greater on institutions that have a higher percentage of 
NIH funding compared to total funding from other sources, or a lower 
ability to cover indirect costs from other sources (e.g., donations, 
endowment income, state government, tuition). The Department continues 
to work on specific details of the NIH indirect cost policy for fiscal 
year 2018 and will assess the impact on grantees once the policy is 
finalized.
    Question. Washington University in St. Louis receives over $390 
million a year in NIH-funded research. Under your proposal, they would 
lose $90 million a year in research funding, laying off 1,000 people. 
What discussions did you have with the research community before 
proposing this cap?
    Answer. The extramural NIH research community has provided 
extensive feedback since the Budget release through conferences and 
meetings with professional associations such as the National Council of 
University Research Administrators (NCURA), the Federal Demonstration 
Partnership (FDP), and the Council on Governmental Relations (COGR), as 
well as by email and phone call discussions. Increasing efficiencies 
within NIH remains a priority of the Administration. NIH is working 
with the Department and OMB to identify strategies to streamline 
processes and increase efficiencies within NIH. These strategies to 
reduce grantee administrative burden are informed by direct feedback 
from grant recipients.
    Question. I understand that many nonprofits have caps on indirect 
costs, but they are likely able to do that because: (1) they fund a 
relatively small percentage of research; and (2) NIH's indirect costs 
help offset the cost of their research. I also know the Secretary has 
cited the Gates Foundation's indirect cost rates as an example, yet 
note, that recently Bill Gates issued a statement distancing his 
Foundation's policies from the Administration's. What type of reviews 
of the program did NIH do to come up with the 10 percent cap?
    Answer. The fiscal year 2018 Budget presents an opportunity to 
reexamine how to optimize Federal investment in a way that best serves 
the American people. The Department assessed opportunities within the 
NIH to determine where greater efficiencies may be possible within the 
research project grant mechanism. In addition, HHS also assessed 
strategies used by other non- Federal entities such as foundations and 
private sector organizations to understand how funds for direct and 
indirect research costs are allocated.
                           pediatric research
    Question. Many Institutes at the NIH support pediatric research. 
What are your thoughts on how the NIH can better coordinate and support 
pediatric research across all Institutes and Centers? Specifically, I 
would be interested in your thoughts on the value of a coordinating 
committee and an office on child research to help manage and coordinate 
pediatric research activities trans-NIH similar to offices on women's 
health, sexual and gender minority health and tribal health.
    Answer. Pediatric research continues to be a high NIH priority. The 
NIH's strong basic research portfolio provides the foundation for 
pediatric research in a variety of scientific areas, including 
neurodevelopment, cardiology, lung development, cancer, and behavioral 
and social sciences. In fiscal year 2016, the NIH funded nearly $4 
billion of research grants and projects directed specifically at 
pediatric research. Although the Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD) funds the 
largest proportion of pediatric research within NIH (18 percent) and 
takes a leadership role in many pediatric research efforts that involve 
trans-NIH collaborations, all NIH Institutes and Centers (ICs) support 
various aspects of pediatric research. Each year, NICHD coordinates the 
annual pediatric research report, required by the Children's Health Act 
of 2000 (Public Law 106-310); this report provides an annual update on 
the most significant pediatric research advances across the NIH. NIH 
also publishes annually its Report on Collaborations with Other HHS 
Agencies, which includes several pediatric initiatives.\1\
---------------------------------------------------------------------------
    \1\ Https://report.nih.gov/crs.
---------------------------------------------------------------------------
    In addition, NIH hosts many internal working groups with 
representatives from different ICs that are focused on coordinating 
research efforts on specific conditions, such as Down syndrome, 
muscular dystrophy, autism and mitochondrial diseases. The formation of 
an internal NIH pediatric research working group might improve 
coordination and encourage expanded child health research 
collaborations among the ICs without discouraging investigator-
initiated ideas.
                          alzheimer's disease
    Question. Dr. Collins and Dr. Hodes, recent clinical trial results 
for both disease-modifying and symptomatic treatments for Alzheimer's 
disease have once again been disappointing. In July 2015, the U.S. Food 
and Drug Administration (FDA) released a report on targeted drug 
therapy that highlighted the lack of success to date in bringing 
transformative therapies to market for Alzheimer's disease. The report 
identified basic research gaps that have contributed to subsequent 
failures in clinical development. Additionally, a February 2017 piece 
in The Atlantic explored whether the longstanding ``amyloid 
hypothesis'' is on the brink of success or failure. With more than 5 
million patients waiting for a breakthrough, and millions more 
estimated to be diagnosed in the coming decades, what is the NIH doing 
to connect the dots from the clinical development failures back to its 
basic and clinical research priorities?
    Answer. We share your disappointment and frustration regarding the 
recent reports of failures of promising interventions in clinical 
trials. A major issue, and one that we are now addressing, is that 
previous trials may have been intervening too late in the disease 
process to be effective. Recent breakthroughs in biomedical imaging are 
enabling us to identify and track the earliest pathological stages of 
the disease process, long before clinical symptoms are apparent. These 
discoveries, in addition to discovery of other early biomarkers of the 
Alzheimer's disease process, have opened a ``window of opportunity'' 
for us to target and potentially reverse the disease's underlying 
pathology before cognitive, behavioral, and emotional symptoms appear.
    For example, the Accelerating Medicines Partnership (AMP) was 
established in 2014 to identify and validate novel, clinically-relevant 
therapeutic targets, thereby accelerating the process of bringing new 
medicines to patients. Alzheimer's disease (AD) is one of the first 
conditions on which AMP is focusing. AMP-AD consists of two projects: 
1) a Biomarkers Project that explores the utility of tau imaging 
(another suspected disease-causing agent) and novel fluid biomarkers 
for tracking responsiveness to treatment and/or disease progression, 
and 2) a Target Discovery and Preclinical Validation Project, which 
integrates analysis of large-scale molecular data from human brain 
samples with network modeling approaches and experimental validation, 
with the ultimate goal of shortening the time between discovery of 
potential drug targets and development of new drugs. AMP investigators 
have already identified over 100 novel candidate targets, which are 
currently being evaluated in collaboration with industry partners.
    With respect to the report in The Atlantic specifically questioning 
the amyloid hypothesis, it is important to note that, while amyloid 
remains a viable and dynamic area of study, NIH's Alzheimer's Research 
Funding Database indicates that in fiscal year 2016, NIH's investment 
in amyloid and tau research accounted for only one-third of funded 
projects focused on increasing our understanding of the molecular and 
physiological processes underlying AD pathogenesis. Other funded areas 
of basic research include understanding how brain circuit and synaptic 
dysfunction, immunity and inflammation, and vascular/metabolic factors 
contribute to the development of AD and AD-related dementias.
    Earlier investments in amyloid and tau have resulted in their 
significant representation throughout the drug discovery, preclinical 
development, and clinical research pipeline.
    However, research funding currently covers an extensive and diverse 
range of additional therapeutic targets including ApoE and lipids, 
metabolism and bioenergetics, neurotransmitter receptors, and 
inflammation. NIH has also boosted the non-pharmacological portfolio to 
assess the role of diet, exercise, and cognitive training in preventing 
and alleviating dementia.
                                 ______
                                 
              Questions Submitted by Senator Thad Cochran
                institutional development award program
    Question. Earlier this year, Dr. Jennifer Sasser of the University 
of Mississippi Medical Center testified before this Committee about how 
important the Institutional Development Award program has been to 
ensuring institutions in states like Mississippi can compete on an 
equal playing field for NIH grants. Dr. Sasser is a promising scientist 
still in the early stages of her career. How can the NIH leverage the 
IDEA program toward its new Next Generation Researchers Initiative?
    Answer. NIH has launched the Next Generation Researchers Initiative 
to bolster support for early-stage and mid-career investigators to 
address longstanding challenges faced by researchers trying to embark 
upon and sustain independent research careers. Consistent with this 
objective, the Institutional Development Award (IDeA) program has 
always placed significant emphasis, with corresponding investments, 
toward the professional and scientific development of early- stage 
investigators to facilitate their independence and sustainability as 
biomedical researchers. All four current IDeA Program initiatives have 
an objective of targeting early-stage and/or mid- career investigators:
      (1) Centers of Biomedical Research Excellence (COBRE--Phases I, 
        II, and III). The goal of the COBRE initiative is to strengthen 
        institutional biomedical research capabilities in IDeA states 
        through three competitive, 5-year phases of infrastructure and 
        faculty development of thematic and multidisciplinary research 
        centers. COBRE specifically provides for the development of new 
        and early-stage investigators in Phase I/II and mid- career 
        investigators in Phase II. The Phase III awards are expressly 
        targeted for developing the sustainability of scientific/
        technical core resources with some funds for pilot projects of 
        early-stage and/or mid-career investigators. Of note, receipt 
        of an independent investigator research program grant (RPG) is 
        recognized explicitly by this initiative as a metric of success 
        that results in the `graduation' of a junior investigator from 
        COBRE support. In fiscal year 2016, the NIGMS supported 112 
        COBRE awards, for a total of 122 active COBRE awards.
      (2) IDeA Networks of Biomedical Research Excellence (INBRE). The 
        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 
        (PUIs). INBRE supports institutional research and 
        infrastructure development; research primarily by junior 
        faculty, postdoctoral scientists, and students at PUIs; and 
        outreach to build science and technology knowledge in the 
        states' workforces. In fiscal year 2016, the NIGMS supported 24 
        INBRE awards.
      (3) IDeA Program Infrastructure for Clinical and Translational 
        Research (IDeA-CTR). The 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. IDeA-CTR awards support mentoring and 
        professional development activities for clinically oriented 
        early-stage investigators and mid-career investigators newly 
        embarking on clinical and translational projects. The IDeA-CTR 
        initiative provides for a pilot projects program for supporting 
        research projects of mostly early-stage investigators. In 
        fiscal year 2016, the NIGMS supported seven IDeA-CTR awards, 
        for a total of nine active IDeA-CTR awards.
      (4) Research Co-Funding. IDeA co-funding is provided to eligible 
        applications that have already been judged meritorious by NIH 
        peer-review committees and national advisory councils but are 
        outside the range of applications under consideration for 
        funding by all of the NIH Institutes/Centers (I/Cs). Priority 
        for co-funding is given to new and early- stage investigators. 
        In fiscal year 2016, IDeA co-funded 58 research project grant 
        awards at 17 NIH I/Cs.
           precision medicine initiative--role of physiology
    Question. The NIH Precision Medicine Initiative has focused 
primarily on genetic analysis. However, physiology that may not show up 
in genetics is also an important determinant of a patient's reaction to 
treatment and overall health. The University of Mississippi Medical 
Center, as you know, has long been a national leader in physiology, 
dating back to the famous Dr. Arthur Guyton. How will the Precision 
Medicine Initiative look at the role of physiology in patients' unique 
medical needs?
    Answer. There are four important ways that the All of Us Research 
Program, the patient cohort for the Precision Medicine Initiative, 
plans to look at physiology in the participants:
      (1) Electronic Health Records. We will ask for access to 
        participants' electronic health records (EHRs) to determine if 
        they have any diseases or conditions, or early signs of certain 
        conditions (e.g., heart disease), based on lab tests that have 
        been recorded in the EHR (e.g., cholesterol levels).
      (2) Participant-Provided Information. We will ask participants to 
        fill out surveys with questions that address their lifestyle 
        and habits (e.g., do they smoke) and personal and family 
        medical history. With this information we will be able to 
        identify relationships between certain behaviors that may 
        indicate healthier physiology or more pathologic physiology. We 
        will also compare this information to participants' EHR data to 
        gain greater insight into how diseases manifest and progress, 
        or what kinds of behaviors or lifestyles indicate healthier 
        physiology.
      (3) Physical Measurements and Biospecimens. We will ask 
        participants to visit a clinic to get their physical 
        measurements (i.e., height, weight, waist and hip 
        circumference, blood pressure, and heart rate) as well as 
        collect biosamples (i.e., blood, saliva, and urine). We are in 
        the planning stages to use the biosamples for selected clinical 
        assays that will serve as biomarkers of basic physiology of 
        most organ systems. A few examples of the kinds of tests we are 
        planning to use include cholesterol tests for heart function, 
        creatinine and microalbumin for kidney function, enzymes for 
        liver function, and vitamin D for immune function.
      (4) Digital Health Technologies (mobile Health). Lastly, we will 
        ask participants, over time, to provide personal information 
        based on digital health technologies. For example, if 
        participants have a fitness tracking device, we may ask them 
        for the data to understand how physical activity affects 
        physiologic function. We are also developing new apps that will 
        allow participants to complete cognitive and movement tests and 
        share information about their general well-being by answering 
        questions about their mood or if they experience headaches.
    Importantly, the collective data from all of these sources can be 
integrated to gain a deeper understanding of how this information is 
interrelated, and may provide new ways to identify what factors are 
important for preventing certain conditions.
   precision medicine initiative--federally qualified health centers
    Question. The NIH selected a number of federally Qualified Health 
Centers (FQHCs) to serve as collection sites for the Precision Medicine 
Initiative's million-person research cohort. It is my understanding 
that these FQHCs will each contract with an outside group to provide 
technical assistance in these efforts. Has HHS considered having these 
FQHCs partner with local academic medical centers for this purpose?
    Answer. The All of Us Research Program believes that the nation's 
federally Qualified Health Centers are unparalleled resources for 
engaging diverse, hard-to-reach communities across the U.S. As priority 
healthcare provider organization partners, we established an early 
pilot with six outstanding federally Qualified Health Centers (FQHCs) 
across the U.S. to help us define the best way for incorporating FQHCs 
to help fulfill the promise of All of Us. Conducted through a contract, 
the outcome of this critical pilot will be a set of learnings about the 
potential options and best potential approaches for scaling up FQHC 
involvement in our program. We anticipate the final report with 
learnings in early 2018. We will use this report to guide our 
considerations and roadmap for scaling up FQHC partnerships, which may 
include partnering with academic medical centers.
    In addition to the FQHCs participating in the on-going pilot, it is 
noteworthy that there are several other FQHCs working with Regional 
Medical Centers that are participating in the program. The Illinois 
Precision Medicine Consortium, specifically at the University of 
Illinois at Chicago (UIC), and the California Precision Medicine 
Consortium, specifically the University of California at Irvine (UCI), 
have independently partnered with FQHCs in their areas.
  --The FQHC Mile Square Health Center is currently working with UIC, 
        and there is a future plan for UIC to work with the Alliance 
        Chicago, an organization that unites FQHCs in the Chicago area.
  --The FQHCs working with UCI are:
    --UC Irvine Health Family Health Center, Santa Ana
    --UC Irvine Health Family Health Center, Anaheim
    Our program is deeply committed to integrating federally Qualified 
Health Centers into All of Us and we look forward to finalizing our 
approach to developing robust, scalable partnerships with them.
                                 ______
                                 
               Questions Submitted by Senator Jerry Moran
             essential facilities and administrative costs
    Question. Do you believe that a diversity of universities and 
institutions pursuing life-enhancing biomedical research is valuable 
for the United States to maintain a robust medical research enterprise? 
If so, how are universities and laboratories expected to afford to 
support a new research endeavor if the essential facilities and 
administrative costs are not covered? Will the caps cause research to 
be condensed into only a few universities and result in less geographic 
distribution of biomedical research?
    Answer. Yes, we do believe that a diversity of universities and 
institutions pursing life- enhancing biomedical research is valuable 
for the United States to maintain a robust medical research enterprise. 
The effect of the indirect cost policy on grantees will vary by 
institution, depending on the current indirect cost rate and a variety 
of other factors. The impact will be greater on institutions that have 
a higher percentage of NIH funding compared to total funding, or a 
lower ability to cover indirect costs from other sources (e.g., 
donations, endowment income, state government, tuition). The Department 
continues to work on specific details of the NIH indirect cost policy 
for fiscal year 2018 and will assess the impact on grantees as the 
policy is finalized.
                                 ______
                                 
          Questions Submitted by Senator Shelley Moore Capito
                          alzheimer's disease
    Question. Regarding the National Plan to Address Alzheimer's 
Disease first introduced in 2012 with the goal of preventing or 
effectively treating Alzheimer's by 2025, what progress has NIH made 5 
years into this project and is it your sense that the current 
administration is supporting continuity of this program?
    Answer. Recent and historic levels of investment in Alzheimer's 
disease and related dementias have enabled the Nation to provide more 
robust support for researchers working toward a cure. Their progress 
has already been significant. Since the National Plan was established 
in 2012, NIH-supported investigators have:
  --Helped map the brain's innermost connections and the molecular 
        fabric of Alzheimer's.
  --Deepened our understanding of metabolic changes at the heart of the 
        disease.
  --Detected disease progression through neuroimaging and discovery of 
        novel biomarkers.
  --Used new technologies, through unprecedented multidisciplinary 
        collaborations, to make large data sets available with greater 
        accuracy and speed to the research community.
  --Leveraged new investment in epidemiological research to increase 
        our understanding of the complexity of variation across space 
        and over time in disease incidence and prevalence, with the 
        goal of identifying new clues for prevention.
  --Looked at health disparities in new ways, with studies of genetics 
        and risk factors that may be contributing to higher dementia 
        rates among certain groups.
  --Begun testing technological innovations in the home that aim to 
        increase the ability of older adults to age in place.
    A number of these advances have been made possible through some of 
NIH's flagship programs, which have been created or expanded under the 
National Alzheimer's Project Act (NAPA). They include:
  --Molecular Mechanisms of the Vascular Etiology of Alzheimer's 
        Disease: This consortium aims to improve our understanding of 
        how the vascular system may be involved in the onset and 
        progression of Alzheimer's and related dementias.
  --Alzheimer's Disease Neuroimaging Initiative (ADNI): This long-
        running study has contributed to many important discoveries. 
        For example, work through ADNI has led to the discovery of how 
        Alzheimer's-related brain changes correspond to clinical 
        findings.
  --Alzheimer's Disease Preclinical Efficacy Database: This cutting-
        edge, web-based portal for housing, sharing, and mining of 
        preclinical efficacy data will facilitate data- sharing among 
        researchers in drug development.
  --Model Organism Development and Evaluation for Late-onset AD: This 
        research center is developing improved mouse models of late-
        onset disease.
  --The Collaborative Aging (in Place) Research Using Technology: This 
        multi-NIH institute and joint agency initiative will create a 
        sustainable research infrastructure through which investigators 
        can identify, qualify and collect data on user-friendly and 
        effective technology that will allow older adults to age in 
        place.
  --The Alzheimer 's disease Drug Development Program: Since 2012, NIH 
        has funded nine preclinical drug development projects through 
        this program, including a new immunotherapeutic vaccine; a 
        novel gene therapy that protects nerve cells and improves their 
        function; and a small molecule inhibitor of brain inflammation. 
        These are expected to enter clinical testing within the next 2 
        years.
    We look forward to making continued progress on our goal of 
eliminating the threat of Alzheimer's disease and related dementias 
from the lives of all Americans. The National Plan to Address 
Alzheimer's Disease: 2017 Update is expected to be released shortly, 
and contains detailed information on the recent progress of NIH as well 
as other partner agencies.
                                 ______
                                 
              Questions Submitted by Senator John Kennedy
                             indirect costs
    Question. Director Collins, thank you again for hosting my 
colleagues and me at the NIH a few weeks ago, and thank you for taking 
the time to meet with us today. I wanted to briefly ask about the cap 
on indirect costs that was included in this budget. As you stated in 
your testimony, the NIH currently spends approximately 28 percent of 
its extramural budget on indirect costs. This budget would cap indirect 
costs at 10 percent. Do you think that this cap will negatively affect 
Institutional Development Award (IDeA) states like Louisiana which do 
not receive as much funding for biomedical research?
    Answer. The effect on grantees will vary by institution, depending 
on the current indirect cost rate and a variety of other factors. The 
impact will be greater on institutions that have a higher percentage of 
NIH funding compared to total funding, or a lower ability to cover 
indirect costs from other sources (e.g., donations, endowment income, 
state government, tuition). The Department continues to work on 
specific details of the NIH indirect cost policy for fiscal year 2018 
and will assess the impact on grantees once the policy is finalized.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray
                                  ahrq
    Question. The budget proposes to fold the Agency for Healthcare 
Research and Quality into NIH. As you know, AHRQ's research is focused 
on making healthcare safer and more effective, while NIH is largely 
committed to basic research.
    Dr. Collins, given their somewhat different missions, do you 
believe AHRQ would be a good fit for NIH, and if so, please explain 
why.
    Answer. Yes. The 2018 President's Budget transitions AHRQ to an 
Institute at the NIH--the National Institute for Research on Safety and 
Quality (NIRSQ). If the proposed transition were to occur, NIH would 
take steps to ensure that the important research that AHRQ supports is 
continued at this agency. By capitalizing on the expertise of the AHRQ 
in ensuring that evidence is used to make healthcare safer, higher 
quality, and affordable, the new NIRSQ would be poised to ensure that 
NIH's investments in biomedical science are better translated into 
knowledge and practical tools that can be adopted by physicians and 
other healthcare professionals to benefit patients.
    NIH and AHRQ have complementary missions. NIH's mission is to seek 
fundamental knowledge about human health and disease and to apply that 
knowledge to enhance health, lengthen life, and reduce illness and 
disability. AHRQ's mission is to produce evidence to make healthcare 
safer, higher quality, more accessible, equitable, and affordable, and 
to work within HHS and with other partners to make sure that the 
evidence is understood and used.
    There are similarities in the types of research that is funded. For 
example, while it is a relatively small proportion of the NIH budget, 
both agencies support health services research, comparative 
effectiveness research (CER), and patient safety research. NIH 
regularly examines its portfolio to ensure that NIH and AHRQ's efforts 
are complementary, rather than duplicative.
    The NIH and AHRQ portfolios in these common areas may relate to the 
same health problem, but the questions pursued and the approaches taken 
differ. For example, an NIH CER study will involve a clinical trial 
designed to address a fundamental question about the effectiveness of 
two interventions. AHRQ, on the other hand, will support a research 
review to look at all the available evidence about the benefits and 
harms of each intervention for different groups of people. A case study 
helps illustrate the different approaches. Both NIH and AHRQ have done
    CER on the prevention of sudden death due to heart disease. The 
Sudden Cardiac Death in Heart Failure Trial \2\ exemplifies the 
approach NIH takes. The trial, which involved thousands of patients 
with congestive heart failure, compared the effectiveness of a device 
called an implantable cardioverter-defibrillator (ICD) and an 
antiarrhythmia drug in preventing sudden death from cardiac arrest. The 
study demonstrated that the defibrillator reduced mortality by 23 
percent, whereas the drug had no favorable effect on survival.
---------------------------------------------------------------------------
    \2\ Bardy et al. 2005. Amiodarone or an Implantable Cardioverter--
Defibrillator for Congestive Heart Failure. NEJM 352:225-237. http://
www.nejm.org/doi/full/10.1056/NEJMoa043399.
---------------------------------------------------------------------------
    AHRQ's contribution was to carry out a systematic review of the 
scientific literature resulting from many research studies--including 
the findings from the NIH trial--on the efficacy, effectiveness, and 
safety of ICDs compared to a different type of therapy for arrhythmia. 
AHRQ's research produced an important evidence report \3\ that 
confirmed the value of defibrillators in saving lives in appropriately 
selected patients. The agencies' missions and approaches produced 
complementary research results.
---------------------------------------------------------------------------
    \3\ AHRQ. 2007. Cardiac Resynchronization Therapy and Implantable 
Cardiac Defibrillators in Left Ventricular Systolic Dysfunction. 
Https://www.ahrq.gov/downloads/pub/evidence/pdf/defib/defib.pdf.
---------------------------------------------------------------------------
    Because of their complementary roles and missions, NIH and AHRQ 
have the opportunity for synergistic collaborations. For example, the 
two agencies partner on the U.S. Preventive Services Task Force 
(USPSTF), an independent panel of non-Federal experts that conducts 
scientific evidence reviews of a broad range of clinical preventive 
healthcare services and develops recommendations. AHRQ convenes the 
Task Force and provides scientific, administrative, and dissemination 
support. NIH coordinates with AHRQ/USPSTF to ensure that the Task 
Force's evidence reports and recommendations are informed by the most 
recent NIH-supported research and that the recommendations are clearly 
explained to the public. The NIH's Office of Disease Prevention (ODP) 
also serves as the NIH liaison to USPSTF and works with NIH ICs to 
facilitate NIH scientific review and input. ODP will continue to work 
with AHRQ and the USPSTF to identify opportunities to address evidence 
gaps, monitor progress, and enhance coordination.
                                big data
    Question. One of the greatest challenges facing science today is 
how to manage and effectively use the massive amounts of data. Without 
tools for managing and manipulating data, its value is significantly 
reduced. Likewise, we don't want scientists spending time recreating 
data that exists from other research studies. We directed NIH in the 
2017 omnibus to develop a strategic plan to address these issues.
    Dr. Collins, what's the status of work on the plan and who is 
heading up this effort?
    Dr. Hodes, how are the plan authors coordinating their work with 
your team, given your responsibility for managing the Alzheimer's 
disease data sets?
    Dr. Lowy, what role is NCI playing in developing the data 
infrastructure plan?
    Answer. NIH recognizes the significant opportunities and challenges 
presented by big data in biomedical research and is taking an NIH-wide 
approach to develop a strategy for making biomedical big data 
sustainable, accessible, and usable. Consistent with the 
recommendations of the Advisory Committee to the Director of NIH, the 
National Library of Medicine (NLM) is playing the lead role in 
developing NIH's strategic plan for biomedical big data. It is 
consulting broadly with other NIH Institutes and Centers that are 
active in generating and using big data, including the National 
Institute on Aging, National Cancer Institute, and Center for 
Information Technology. It is also coordinating its efforts with the 
NIH Scientific Data Council and Data Science Policy Council, which 
guide NIH-wide efforts to address the evolving challenges and 
opportunities associated with big data and data science in biomedical 
research and the policy issues associated with scientific data 
management and sharing.
    NIH has made considerable progress in developing its strategic plan 
for big data, which draws upon and synthesizes the experience gained 
from multiple activities. As part of its continued investment in the 
Big Data to Knowledge (BD2K) initiative, managed by the NIH Common 
Fund, NIH is launching the Data Commons Pilot Phase. The Data Commons 
Pilot Phase aims to develop and evaluate cloud-based approaches where 
investigators can store, share, access and use data and tools generated 
from NIH-supported biomedical research. A Funding Opportunity 
Announcement was issued in July 2017 for a Data Commons Pilot Phase 
Consortium tasked with developing plans and prototypes of Data Commons 
cloud solutions and to assess the pilot for cost, utility, efficiency, 
and usability, with awards expected to be issued before the end of the 
fiscal year. NIH's Center for Information Technology is closely 
involved in these efforts and is evaluating the feasibility of 
providing cloud solutions and consistent security approaches to support 
NIH-wide data needs. In addition, NLM's National Center for 
Biotechnology Information is exploring cloud-based approaches for 
providing secure access to high-value data sets, such as the data from 
more than 1.5 million subjects contained in the database of Genotypes 
and Phenotypes (dbGaP). It is considering ways such models could be 
extended to other data types. NLM's own strategic plan, which will 
include an explicit focus on data science and open science, is expected 
to be completed in early 2018 and will also inform the NIH plan for 
biomedical big data. In developing its strategic plan, NLM has convened 
four expert external panels to advise on future directions and 
priorities, including one panel focused specifically on NLM's role in 
data and open science.
    The National Institute on Aging (NIA) is contributing to the NIH 
strategic plan based on its experience with managing Alzheimer's 
disease (AD) data. NIA supports multiple programs involving management 
of big data sets, including the Alzheimer's Disease Neuroimaging 
Initiative, the Genetics of Alzheimer's Disease study, and several 
large complex clinical trials on Alzheimer's disease. Efforts are 
underway to further integrate data sets across NIA-funded centers and 
consortiums. NIA is represented on the NIH Scientific Data Policy 
Council and will use its experience managing and archiving large data 
sets and conducting data harmonization activities to help NLM identify 
consistent approaches to managing big data, including data managed by 
NIH grantees and data coordinating centers.
    The National Cancer Institute (NCI) is contributing to the 
strategic plan by sharing its expertise and the experience gained from 
its work on the Genomic Data Commons (GDC) which was launched in 2016. 
The GDC currently includes genomic data on nearly 15,000 cases and 
nearly 40 disease types, and it is available for free to qualified 
researchers. In addition, NCI is supporting the NCI Cancer Genomic 
Cloud Pilots that aim to incorporate genomic, proteomic, metabolomic, 
clinical, and imaging data in an interoperable environment to change 
the way that cancer researchers can share their data, and accelerate 
cancer research. NCI continues to learn from the development and 
management of this unique resource and will share experiences with NLM 
in the development of the NIH-wide strategic plan.
    These efforts aim to develop and evaluate infrastructure and tools 
for managing and manipulating biomedical big data. They will provide 
insight into approaches for valuing and prioritizing data for long-term 
preservation and will form the basis of NIH's strategic plan for big 
data.
                            mechanism tables
    Question. Please provide updated Mechanism tables reflecting the 
fiscal year 2016 actual, fiscal year 2017 enacted level and fiscal year 
2018 President's Budget for each of the 27 current institutes at the 
National Institutes of Health.
    Answer. The updated mechanism tables requested, covering all of the 
NIH Institutes and Centers, were provided to the Committee on July 19, 
2017. Because of timing of final 2017 appropriations action, the fiscal 
year 2018 President's Budget was based on the fiscal year 2017 
Continuing Resolution.
    [The mechanism tables follow:]

    
    
                                 ______
                                 
              Questions Submitted by Senator Brian Schatz
                          stop pain initiative
    Question. HHS recently committed to pursue a three-part approach to 
opioid misuse and addiction, including finding non-addictive 
alternatives for chronic pain through the NIH.
    Last Congress, I introduced the STOP Pain Act with Senator Hatch, 
which passed into law as part of the CARA package in July 2016. It 
directs the NIH to research chronic pain and non- opioid alternatives 
to treat chronic pain.
    I am calling for a STOP Pain Initiative to be led by the NIH. The 
goal would be to put real dollars behind the goals of the STOP Pain Act 
and to elevate this initiative to the level of the Precision Medicine 
Initiative or the BRAIN Initiative. The opioid crisis is taking too 
many lives to not invest in a new, and well-funded, STOP Pain 
Initiative.
    I know there are multiple efforts going on across the government, 
including the Federal Pain Strategy, the Interagency Pain Research 
Coordinating Committee, and the President's Commission on Combating 
Drug Addiction and the Opioid Crisis.
    Could you share an update about the status of pain research at the 
NIH given these initiatives?
    Answer. Many institutes, centers and offices across the NIH fund 
pain research. In 2016, NIH invested $483 million dollars on pain 
research. As the lead institute for pain, the National Institute of 
Neurological Disorders and Stroke (NINDS) has a designated pain policy 
office to coordinate pain research efforts across NIH through the NIH 
Pain Consortium and across Federal agencies through the Interagency 
Pain Research Coordinating Committee (IPRCC). The NIH Pain Consortium 
is a trans-NIH group representing 25 NIH institutes, centers and 
offices that support pain research. The mission of the NIH Pain 
Consortium is to enhance pain research through collaborative research 
initiatives, pain-related workshops and symposia. Pain research funding 
opportunities initiated by the NIH Pain Consortium Institutes and 
Centers have led to multidisciplinary pain studies that seek to 
understand pain mechanisms, the experience of pain and associated 
treatment challenges.
    The IPRCC has led a number of important pain research initiatives. 
The National Pain Strategy (NPS) released in March 2016, is being 
implemented by the HHS Agencies and other Departments under the 
leadership of the HHS Office of the Assistant Secretary of Health and 
NIH. It recommends approaches to improve understanding, prevention and 
evidence-based treatments of pain. NIH is supporting implementation of 
some of the objectives in the National Pain Strategy along with other 
Federal agencies and external stakeholders. Examples of NIH- supported 
research activities include development, testing and validation of a 
screening tool for chronic pain; and nationwide studies on treatment 
coverage for back pain. Achieving the objectives of this strategy will 
strengthen HHS efforts to reduce harms of opioids.
    The IPRCC and NINDS Office of Pain Policy developed a long-term 
strategic plan to enhance Federal pain research. The Federal Pain 
Research Strategy (FPRS) includes a number of important research 
priorities spanning from basic to clinical research across the 
continuum of pain (acute to chronic) including disparities in pain 
care. A set of priorities specifically focuses on development of novel 
drugs and non-pharmacological treatments for pain. The FPRS 
recommendations are being considered as research priorities by NIH and 
other Federal agencies.
    In recognition of the urgency to address the important public 
health issue of the opioid epidemic and the related chronic pain 
crisis, the NIH recently launched a public-private initiative beginning 
with a series of workshops that were held in June and July 2017. These 
workshops were designed to identify scientific strategies with the 
greatest potential for solutions to the opioid problem. The first 
workshop focused on development of medications for opioid abuse and 
addiction and overdose prevention and reversal. The second workshop 
focused on development of safe, effective, and non-addictive pain 
treatments. The third and final workshop focused on understanding the 
neurobiological mechanisms of pain with the goal of developing novel 
pain treatments.
    Pain is a perception that is hard wired in neural circuits in the 
brain, spinal cord and peripheral nerves. Chronic pain is a 
prototypical disorder of the pain circuit. The NIH BRAIN Initiative is 
a major effort to develop tools to 1) map neural circuits, 2) monitor 
their activity to characterize circuit disorders, and 3) modulate 
circuit activity for health benefit. The advanced neurotechnologies 
from the BRAIN initiative will enable much more powerful approaches to 
diagnose, classify and treat pain. This initiative along with the 
precision medicine `All of Us' initiative will be leveraged to support 
the pain research agenda.
    While many strategies currently are being utilized to reverse the 
epidemic of opioid overdoses, there remains a pressing need to develop 
safer and more effective treatments for pain. Pain research at the NIH 
spans basic, translational and clinical studies on pharmacological and 
non- pharmacological approaches for pain management. Several NIH-
supported investigations are underway to identify compounds for 
pharmaceutical development that target molecules known to be integral 
to pain signaling pathways. For example, persons with a specific gene 
mutation in nerve cells are unable to sense pain (an off-switch), 
others with a different mutation in the same gene suffer from chronic 
painful conditions (an on-switch). Other compounds involved in pain 
signaling are being studied to understand their therapeutic potential 
for pain treatment when used in combination with other drugs. One has 
been shown to ameliorate painful spasms of multiple sclerosis. 
Inflammation plays a role in developing and maintaining chronic pain. 
NIH supports studies on the potential of anti-inflammatory compounds to 
stop acute pain from becoming chronic and to alleviate chronic pain. 
For example, NIH supported basic research that led to a better 
understanding of the role of the inflammatory agents, calcitonin gene-
related peptide in migraine pain and nerve growth factor in 
osteoarthritis pain. Compounds to block activity of these compounds 
currently are in phase 3 clinical trials to treat respectively, 
migraine and osteoarthritis pain.
    NIH recognizes the importance of balancing the need for mitigating 
the harmful effects of opioids while ensuring that people with pain 
receive appropriate care. NIH pain research and strategic planning 
efforts will support the goal of improving the lives of people with 
pain while reducing the reliance on opioids.
                               telehealth
    Question. Telehealth improves outcomes and saves costs in our 
healthcare system. Along with Senators Wicker, Cochran, Cardin, Thune, 
and Warner, I introduced the CONNECT for Health Act to lift outdated 
restrictions on Medicare's reimbursement of telehealth. We have seen 
numerous studies that show that telehealth and remote patient 
monitoring save money and improve outcomes.
    We have spoken previously about telehealth research at the NIH.
    Can you give me an update about what research the NIH is funding in 
terms of telehealth and remote patient monitoring?
    Answer. NIH supports development of telehealth technologies and 
interventions to support the provision of healthcare at a distance. 
Innovation in communication technology, computer science, and medical 
technologies are helping to advance this field in numerous ways, such 
as the development of biosensors. Specifically, the National Institute 
of Biomedical Imaging and Bioengineering (NIBIB) is supporting research 
to address complex health problems such as asthma through the Pediatric 
Research using Integrated Sensor Monitoring Systems (PRISMS) to develop 
sensor-based, integrated health monitoring systems for measuring 
environmental, physiological, and behavioral factors in children. 
Collaborative teams of researchers are developing noninvasive health 
monitoring systems for pediatric asthma research and for other chronic 
diseases in the future. One arm of this collaboration is developing 
both wearable and non-wearable sensors to monitor environmental 
exposure, physiological signals (such as children's activity), and 
behavior in children's natural environments. To date, progress is being 
made in creating a variety of sensors for use by individuals or in 
households that could measure air pollution levels, physical activity, 
breathing patterns, inhaler use, or heart rate.
    The National Heart, Lung and Blood Institute (NHLBI) also supports 
research to bring more science-based, cost-effective telehealth 
approaches to communities that have limited access to healthcare 
facilities and providers, including rural communities. Examples of 
research in this area to improve patient care include a clinical trial 
of telehealth for patients with cystic fibrosis. In this study, remote 
monitoring using phone and Internet will be used to check-in twice per 
week with patients who perform a simple test to measure their own lung 
function (spirometry). Results of the test and a self-report on their 
health status are shared with physicians via a telemonitor. This in-
home approach could replace a typical office visit and will help 
determine if intervening more quickly to treat exacerbations can help 
slow progression of this disease.
    In another example, the HyperLink study found that home blood 
pressure telemonitoring and pharmacist case management achieved better 
blood pressure control compared with usual care during 12 months of 
intervention. Finally, NHLBI is supporting a network to address health 
disparities and to improve the system of care available to treat 
patients with sickle cell disease. The SC-Sickle Cell Statewide Network 
is evaluating a variety of strategies, including telehealth approaches, 
to extend care to patients in rural areas.
    Another example of telehealth research is working to improve the 
informed consent process, a challenge in clinical research. One 
potential solution is the use of ``teleconsent,'' a video system that 
allows research staff to meet and discuss participation in studies with 
potential participants. This National Library of Medicine-funded study 
may address the unique needs of research studies while making studies 
more accessible and efficient.
    These and other telehealth approaches could have an impact on the 
ability to prevent illness or better manage chronic diseases.
                           ethics in research
    Question. I've been concerned about several recent stories of 
potential breaches of human subject protections in research studies. In 
a recent study about testosterone's effects on anemia, the researchers 
failed to tell patients identified to have mild anemia that they had 
it. Even mild anemia can signal further health problems and should be 
treated.
    Could you speak to how you work in your own research to protect 
human subjects, and if you see any areas that need further Federal 
attention?
    Answer. NIH views our responsibility for stewardship of human 
subjects research as being of utmost importance. As such, working with 
the Office for Human Research Protections (OHRP), HHS, we have a number 
of policies and procedures in place to ensure the protection of 
participants in NIH-funded research and these are checked in several 
stages of the lifecycle of the research project.
    Institutions that request NIH funding for human subjects research 
must assure, to OHRP, that they will follow the HHS regulations to 
protect human subjects (45 CFR 46). Before submitting applications for 
grants or cooperative agreements to NIH, the proposed research must 
undergo internal review by institutions and approval by their 
organizational officials. Applications then undergo dual review by NIH, 
first by peer reviewers who are charged with assessing whether the 
design of proposed research includes appropriate protections from 
risks, and that the knowledge to be gained justifies any unavoidable 
risks. Second, Institute and Center Advisory Councils must approve 
applications for grants and cooperative agreements. All concerns 
identified by peer review or by NIH staff in grant applications that 
are approved for funding must be resolved prior to the expenditure of 
Federal funds for studies involving human subjects. NIH Notices of 
Award require that all protections will be implemented, as specified by 
NIH Grants Policy, HHS regulations (45 CFR 46), and FDA regulations as 
applicable.
    In order to receive an NIH award for research involving human 
subjects, institutions must assure that they will comply with all 
regulatory and policy requirements for human subjects research 
protections. Because protecting participants from risks associated with 
research is so important, NIH, institutional review boards (IRBs), and 
research institutions must review all proposed research. IRBs must 
review and approve all proposed studies and informed consent processes 
at least annually, as these Boards are responsible for protecting the 
rights and welfare of human subjects. In addition, clinical trial 
research must include plans for data and safety monitoring, the extent 
of which varies according to the nature, risk, and complexity of the 
research.
    All awardees must submit annual reports to funding NIH Institutes 
and Centers, in which they describe scientific and technical progress 
and any changes to approved research involving human subjects. These 
progress reports must be approved before funding for the project period 
can be allocated.
    Also to ensure that investigators are aware of their obligations to 
research participants, all investigators and all NIH Scientific Review 
Officials and Program staff must complete training in Human Research 
Participant Protections, and individuals involved in clinical trial 
research must complete Training in Good Clinical Practice.
    The combination of the requirements for human subjects research 
forms a safety net of protections that is designed to prevent avoidable 
risks and enhance the potential benefits of NIH-funded research.
                                 ______
                                 
           Questions Submitted by Senator Christopher Murphy
                        extramural partnerships
    Question. Director Collins, I was concerned to learn that the 
proposed budget calls for a significant cut to the National Institute 
on Alcohol Abuse and Alcoholism (NIAAA) from over $483 million in 
fiscal year 2017 to $361 million next year. Given the budget for the 
NIAAA would maintain a full FTE headcount despite the proposed cuts, I 
fear that extramural partnerships would be hurt the most if the overall 
funding were decreased. For instance, funding for the university-based 
Alcohol Research Centers, some of whom are doing innovative genomic 
research to try to discover the genes that predispose people to alcohol 
addiction, could be hurt. As you may know, this Committee expressed its 
support for last year for such efforts and asked the NIAAA for a 
detailed plan on larger-scale genetic screening initiatives. Do you 
believe such genomics based research on addictions is useful, and do 
you believe the NIAAA can proceed with more robust genetic screening 
initiatives with its academic partners in fiscal year 2018 and beyond 
under the current budget proposal?
    Answer. The mission of the National Institute on Alcohol Abuse and 
Alcoholism (NIAAA) is to generate and disseminate fundamental knowledge 
about the effects of alcohol on health and well-being, and apply that 
knowledge to improve diagnosis, prevention, and treatment of alcohol-
related problems, including alcohol use disorder (AUD), across the 
lifespan. Extramural partnerships with research institutions, including 
alcohol research centers, are essential to advancing this mission and 
cultivating a talented and diverse workforce to sustain the biomedical 
research enterprise. In its strategic plan, 2017-2021, NIAAA identified 
key research priorities spanning its broad portfolio to address the 
persistent public health challenges resulting from alcohol misuse in 
our nation, including research to elucidate the genetic factors that 
predispose individuals to, or protect them, from AUD and co-occurring 
mental health disorders.
    NIAAA-supported research has made substantial progress in 
understanding the contributions of genes and gene-environment 
interactions in AUD risk and resiliency; however, many challenges 
remain in identifying the full extent of the role of genes in AUD. 
Recent genome wide association studies (GWAS), studies in which the 
entire genomes of study participants are examined to identify genetic 
variations leading to a particular disorder, have successfully 
identified gene variants that have small associations with risk for 
developing AUD. Much larger GWAS sample sizes are required to enable 
the detection of more substantive genetic associations with AUD risk. 
To achieve the sample sizes needed, NIAAA recently issued a policy 
encouraging applicants to use large scale GWAS approaches and meta-
analyses of the data in their study designs. Complementary to these 
approaches, NIAAA will support the use of next generation sequencing 
technologies to identify gene variants that are rare in a population 
and have moderate to large associations with AUD risk. The knowledge 
generated will provide new insights into the mechanisms that underlie 
AUD pathophysiology and inform individualized prevention, treatment, 
and recovery.
                 inter-agency research on down syndrome
    Question. People with Down syndrome are now living longer than ever 
thanks to medical and scientific advances. However, as this population 
ages, people with Down syndrome have a significantly higher risk of 
developing Alzheimer's disease. The Committee applauds NIH's leadership 
in driving scientific inquiries to better understand this connection 
through the Biomarkers of Alzheimer's Disease in Adults with Down 
Syndrome Initiative, a collaborative effort between NIA and NICHD. 
Given that people with Down syndrome are also at greater risk for other 
conditions like leukemia, autoimmune disorders, and autism, do you see 
other opportunities for inter-agency research on Down syndrome?
    Answer. One benefit of communication and collaborations across NIH 
Institutes and Centers, and with the Down syndrome community, is 
increased coordination of research efforts. Led by the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development 
(NICHD), the public-private Down Syndrome Consortium, which includes 10 
NIH Institutes and Centers, 13 national and international organizations 
whose missions focus on Down syndrome, and individuals with Down 
syndrome and family members, provided valuable input to the 2014 
revision of the NIH research plan on Down syndrome. DS Directions: The 
NIH Down Syndrome Research Plan has had an impact on the field of Down 
syndrome research; in submitting grant applications, many researchers 
have cited one of its objectives, particularly including the call for 
research on many of the comorbidities commonly experienced by people 
with Down syndrome (congenital heart disease, leukemia, and intestinal 
issues, and other developmental disorders). While life expectancy for 
people with Down syndrome who are living in the United States has 
increased dramatically over the last 50 years, these coexisting 
conditions still require more research and, in turn, a wider variety of 
expertise as represented across NIH.
    Members of the Trans-NIH Working Group meet regularly about the 
wide-range of investigator- initiated research projects and other NIH-
supported efforts to improve the health of people with Down syndrome, 
including those with co-existing conditions. The Alzheimer's Biomarker 
Consortium--Down Syndrome (ABC-DS), funded collaboratively by the 
National Institute on Aging (NIA) and NICHD, provides an exciting 
opportunity to improve our understanding of Alzheimer's disease among 
people with Down syndrome, 50 percent or more of whom develop brain 
changes associated with Alzheimer's by age 40. This initiative seeks to 
identify biomarkers and track the progression of Alzheimer's in people 
with Down syndrome, using brain imaging, as well as fluid and tissue 
biomarkers, to help us understand progression of the disease. These 
studies, by two teams of researchers, will include PET brain scans that 
detect levels of tau, to be tested for the first time in people with 
Down syndrome. The teams will make their data and samples freely 
available to qualified researchers worldwide, with the goal of improved 
testing of interventions. In addition, NIH's Alzheimer's research 
agenda continues to be informed by the recommendations of the April 
2013 workshop ``Advancing Treatments for Alzheimer's Disease in 
Individuals with Down Syndrome,'' which was co-sponsored by NICHD and 
NIA, as well as the National Institute of Neurological Disorders and 
Stroke (NINDS), the Down Syndrome Research and Treatment Foundation, 
and Research Down Syndrome.
    Some NICHD-supported research on autism spectrum disorders will 
benefit individuals with Down syndrome who also have autism. A recent 
scientific workshop cosponsored by NICHD and the National Institute on 
Mental Health helped guide research efforts in this area. One recent 
study showed that brain changes at age 6 or 12 months may help predict 
the development of autism spectrum disorders (ASD) by age 2 years among 
infants with a high family risk, an important finding since early 
diagnosis and appropriate intervention can ease symptoms and improve 
social, emotional and cognitive skills. Other NICHD-funded researchers 
have shown that metal toxicant uptake (lead) and deficiency in 
essential elements (manganese, zinc) during fetal development may 
increase ASD risk and severity.
    In addition, NIH assists the research community by providing 
research resources that might otherwise prove cost prohibitive for them 
to support individually. To advance research on Down syndrome, NICHD 
supports a contract for the leading repository of mouse models for Down 
syndrome. The Cytogenic & Down Syndrome Models Resource \4\ at Jackson 
Laboratory maintains and distributes mouse models for Down syndrome, as 
well as the study of chromosomal aneuploidy, and has recently funded a 
new research project to develop new mouse models for Down syndrome. 
Together with NIMH and NINDS, NICHD encourages studies that develop, 
validate, and/or calibrate informative outcome measures for use in 
clinical trials for individuals with intellectual and developmental 
disabilities (IDD), including Down syndrome. And DS-Connect, a Web-
based DS patient registry that was established in 2013 and now includes 
about 3500 participants, provides researchers with a new tool to 
recruit for their research studies. The registry benefits families, 
too; ultimately, the registry will link to biorepositories of tissue 
samples and other resources, making it easier for participants to take 
part in clinical studies for new medications and other treatments for 
Down syndrome and its coexisting conditions.
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    \4\ Http://www.jax.org/cyto/index.html.
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                             down syndrome
    Question. Although Down syndrome has long been viewed as a 
condition that affects children, the life expectancy for people today 
is almost 60 years. NICHD has traditionally been the home for Down 
syndrome research at NIH, but as people with this condition are living 
well into adulthood, how are other Institutes working to integrate 
research on Down syndrome into their portfolios?
    Answer. Through the NIH Working Group on Down Syndrome and the 
public-private Down Syndrome Consortium, the NIH is working across its 
component Institutes and Centers (IC) to coordinate research efforts 
while maintaining the expertise of each IC. A good example was the 
coordinated effort to produce DS Directions: The NIH Down Syndrome 
Research Plan, which NIH published in late 2014. The public-private 
Down Syndrome Consortium, which includes the Trans-NIH Working Group 
(10 ICs), 13 national and international organizations whose missions 
focus on Down syndrome, and individuals with Down syndrome and family 
members, provided valuable input and a link to the Down syndrome 
community during development of the plan. The plan has had an impact on 
the field of Down syndrome research; in submitting their grant 
applications, many researchers have cited one of its objectives.
    Another good example is the recent effort to address Alzheimer's 
disease. Estimates suggest that 50 percent or more of people with Down 
syndrome will develop dementia due to Alzheimer's disease as they age, 
and the National Institute on Aging (NIA) supports several studies of 
Alzheimer's in this population. With the National Institute of Child 
Health and Human Development (NICHD), the NIA supports the Alzheimer's 
Biomarkers Consortium of Down Syndrome (ABC-DS), in which researchers 
from eight sites across the nation are identifying and using biomarkers 
to track disease progression in people with Down syndrome. Other NIA- 
supported studies include a Phase I trial to investigate an 
immunotherapy vaccine in adults with Down syndrome and a project 
investigating the natural history of amyloid deposition in adults over 
age 30 with Down syndrome. NIA is also a member of the trans-NIH 
Working Group on Down Syndrome. Finally, NIH's Alzheimer's research 
agenda continues to be informed by the recommendations of the April 
2013 workshop ``Advancing Treatments for Alzheimer's Disease in 
Individuals with Down Syndrome,'' which was co-sponsored by NICHD and 
NIA, as well as the National Institute of Neurological Disorders and 
Stroke, the Down Syndrome Research and Treatment Foundation, and 
Research Down Syndrome.
    At the other end of the lifespan, NICHD intramural scientists have 
conducted research to understand the neurobiology of Down syndrome and 
optimize fetal outcome through therapy during pregnancy, showing that 
spatial learning in mouse models could be enhanced. Currently, 
intramural researchers at the National Human Genome Research Institute 
are working to test the hypothesis that prenatal treatment of fetuses 
known to have Down syndrome will result in improved brain growth and 
neurocognition. The work, currently being performed in mouse models, 
has shown promising proof of principle by decreasing the time it takes 
for neonatal mice to achieve developmental milestones.
                                 ______
                                 
            Questions Submitted by Senator Joe Manchin, III
                                 nimhd
                              rural health
    Question. In 2016, the America's Health Rankings Report ranked West 
Virginia 43th 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. Rural communities face unique health disparities. To 
address the barriers facing rural communities, including residents of 
West Virginia, NIH supports research aimed at reducing health 
disparities experienced by rural populations, and improving health 
outcomes. In fiscal year 2016, NIH supported more than 500 grants 
focused on rural health for approximately $295 million, with about $24 
million to fund projects in West Virginia. Among the key partners in 
West Virginia that NIH works with to address rural health disparities 
are West Virginia State Department of Health and Human Resources, West 
Virginia University, and Marshall University. NIH encourages the 
scientists of West Virginia to apply for grants related to the health 
disparities experienced by your constituents in West Virginia, 
including diabetes, obesity, smoking, cancer, and substance use.
    NIH is committed to ensuring that research addresses the unique 
strengths and challenges of rural communities. In West Virginia for 
example, NIH supports the West Virginia Clinical and Translational 
Science Institute: Improving Health through Partnerships and 
Transformative Research (WVCTSI), which leads statewide collaborations 
and innovation in clinical and translational research. An important 
facet of the WVCSTI is the Clinical Research Resources and Facilities 
component that will support the Center in: (1) creating a Clinical 
Trials Center of Excellence to provide access to cutting-edge clinical 
trials for West Virginians, (2) facilitating outcomes research, 
predictive modeling, and geospatial analysis, and (3) stimulating 
environmental health research.
    The West Virginia IDEA Network of Biomedical Research Excellence 
(WV-INBRE) is funded by NIH to support a network of partners to develop 
the biomedical research infrastructure and capacity to provide 
biomedical research experiences for undergraduate and graduate 
students, as well as facilitate research progress, mentorship, 
training, and career development for investigators. WV-INBRE focuses on 
chronic diseases such as cancer, diabetes, cardiovascular disease, and 
obesity.
    NIH also supports several programs focused on cancer, 
cardiovascular disease, and other chronic diseases affecting rural 
communities. For example, Screen to Save \5\ 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 \6\ 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 \7\ 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 Exploratory Center of 
Excellence on Health Disparities in Rural Populations \8\ works to 
train faculty interested in rural health, promote community health 
agency partnerships, and examine health promotion programs to improve 
diabetes, hypertension, and prostate cancer outcomes in rural 
communities. NIH's Healthcare for Rural Populations Research Initiative 
\9\ 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.
    Recognizing the unique needs of Appalachian communities, NIH 
partnered with the Appalachian Regional Commission (ARC),\10\ to 
support a series of 1 year service planning grants aimed at combating 
the increase in mortality from injection opioid use among rural 
communities. A NIH-supported study on coronary artery disease (CAD) in 
central Appalachia,\11\ found that more than 98 percent of participants 
had one or more risk factors for the disease. The findings also suggest 
that the use of computerized tomography (CT) scans to detect hardening 
of the coronary arteries might be helpful in identifying people at 
highest risk of CAD, which is important in ensuring individuals get 
preventative care.
    Rural health is an important area of research for NIH in addressing 
the burden of health disparities. Continued collaborations and 
partnerships with scientists and organizations from rural communities, 
such as West Virginia, will help expand NIH's reach in rural 
communities and support our work to combat rural health disparities.
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    \5\ Https://www.cancer.gov/about-nci/organization/crchd/blog/2016/
screentosave-launch.
    \6\ Https://www.nhlbi.nih.gov/health/educational/hearttruth/
partners/grantees.htm.
    \7\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9245732&icde=34114853&
ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
    \8\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9023348&icde=35084347&
ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
    \9\ Https://www.nimhd.nih.gov/programs/extramural/resource-
related.html#healthcare-rural.
    \10\ Https://www.drugabuse.gov/news-events/news-releases/2016/02/
nida-arc-announce-funding-opportunity-research-projects-to- address-
opioid-injection-use-its.
    \11\ Http://www.sciencedirect.com/science/article/pii/
S0091743516300585.
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                    institutional development awards
    Question. The Institutional Development Award (NIH IDeA) program 
has been critical for West Virginia and West Virginia University. It 
brings NIH funding to states that have historically not applied for as 
many NIH grants and helps to build the medical research programs in the 
state.
    West Virginia currently only receives about $2 million in NIH grant 
funding, but through the IDeA program, we have strengthened our 
investments and expanded access to medical research to the rural and 
underserved areas in my state.
    In fact, WVU estimates that the economic benefit of these grants in 
West Virginia is $180 million.
    That is why I have strongly supported funding for this program at 
NIH and why I am disturbed to see that the President's budget would cut 
funding for the National Institute of General Medical Sciences--which 
houses this program--by more than $400 million.
    In addition, the fiscal year 2018 the budget request does not 
appear to specify a funding level for the NIH Institutional Development 
Award program. It was funded at a level of $333.4 million in the fiscal 
year 2017 Omnibus Appropriations bill.
    I believe that we should be expanding this program so that states 
like West Virginia can have the opportunity to build their medical 
research programs.
    Dr. Collins, what impact will the cuts to NIH 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 
2018 funding level is? And can you please speak to the importance of 
funding research at a wide variety of institutions, particularly those 
in poorer, rural states?
    Answer. The National Institutes of Health (NIH) believes 
initiatives like the Institutional Development Award (IDeA) program 
administered by the National Institute of General Medical Sciences 
(NIGMS) are important in ensuring that jurisdictions and institutions 
across the United States are afforded the opportunity to become active 
and significant contributors to this country's biomedical research 
efforts.
    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 in states like West Virginia. NIH anticipates that 
West Virginia investigators will continue to submit proposals and will 
be in open competition with investigators from other IDeA states for 
support for new IDeA awards.
    Funding research at a wide variety of institutions is extremely 
important to ensure that a rich diversity of scientific and 
geographical perspectives are represented and that all available human 
capital is deployed in the critical work of addressing vital biomedical 
research questions and pressing health problems. Oftentimes, local 
investigators are the best equipped and experienced to conduct research 
on local health concerns. In West Virginia for instance, the IDeA-CTR 
award has been focused on the health concerns of the Appalachian 
population. Further, NIH strongly believes that scientific discoveries 
can arise anywhere that 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 biomedical research efforts will increase the 
likelihood of breakthroughs in science and medicine.
                   funding for research institutions
    Question. The Administration's fiscal year 2018 budget request 
recommends cutting reimbursements that fund university-based NIH 
research, suggesting that the government could save billions without 
hurting research.
    I understand that the Association of American Medical Colleges, the 
Association of American Universities, the Council on Government 
Relations, the Association of Public and Land-grant Universities, the 
Association of Independent Research Institutes, and the American 
Council on Education have expressed their united deep concerns about 
this proposal.
    They report that universities would face billions in additional 
expenses for staffing, utilities, facilities, with many discontinuing 
research because it would be outright unaffordable.
    Dr. Collins, as the long-standing Director of NIH, what is your 
expert view about the short and long-term impacts of scaling back 
indirect reimbursements to universities? Would this make it harder for 
institutions like WVU and Marshall in my state to be able to afford to 
do critical medical research?
    Answer. The effect on grantees will vary by institution, depending 
on the current indirect cost rate and a variety of other factors. The 
impact will be greater on institutions that have a higher percentage of 
NIH funding compared to total funding, or a lower ability to cover 
indirect costs from other sources (e.g., donations, endowment income, 
state government, tuition). The Department continues to work on 
specific details of the NIH indirect cost policy for fiscal year 2018 
and will assess the impact on grantees once the policy is finalized.
                                 ______
                                 
              Questions Submitted by Senator Patrick Leahy
                            general funding
    Question. The National Institutes of Health (NIH) is one of the 
Nation's most critical resources for the promotion and preservation of 
public health. Through groundbreaking biomedical research and clinical 
trials, the NIH offers the promise of hope to sick patients and their 
families. The NIH is also instrumental in promoting workforce 
development at institutions across the country in order to continue the 
important work of scientists for generations to come. Without strong, 
continuous resources for biomedical research, our nation's researchers 
will lack the capacity to wage critical projects in their fields. 
Scientific knowledge changes constantly, and biomedical research must 
parallel these advancements. We cannot turn these valuable research 
efforts on and off; our commitment must be sustained.
    Unfortunately, the administration's proposed budget for fiscal year 
2018 imposes a 21 percent cut to the NIH--a reduction of $7.2 billion 
compared to the fiscal year 2017 enacted level--undermining the 
critical work of each and every one of its institutes and centers, as 
well as the thousands of institutions across the country that rely on 
NIH dollars. The administration claims that the NIH is currently 
plagued by ``unnecessary expenses,'' but this is simply untrue The 
billions of dollars in cuts proposed by the administration target 
critical biomedical research labs, projects, equipment, personnel, and 
clinical trials, all of which bring us closer to combatting, 
controlling, and eradicating diseases.
    Please specifically describe the impacts of the administration's 
proposed cuts to the NIH, especially on direct research and clinical 
trials for patients suffering from disease.
    Answer. The Budget presents an opportunity for HHS to reexamine how 
to optimize Federal investments in a way that best serves the American 
people. In addition to requested changes in the reimbursement of 
indirect costs for NIH grants, Federal research requirements for 
grantees will be streamlined to reduce grantee burden through targeted 
approaches as proposed by NIH. HHS is working with NIH to identify 
strategies to streamline processes and increase efficiencies. These 
targeted policies aim to reduce the time and expenses that grantees 
must currently spend to comply with Federal grant requirements.
                             indirect costs
    Question. Under current law, institutions that receive Federal NIH 
grants enter an agreement with the agency to use a proportion of that 
funding for indirect costs, such as the cost of labs and equipment, 
researchers, facility maintenance, and utilities. These funds are 
critical to ``keeping the lights on,'' and ensure that the biomedical 
research intended by the grants can actually be carried out. In my home 
state of Vermont, our largest research institution, the University of 
Vermont (UVM), would lose more than half of what they are currently 
allotted for indirect costs, meaning biomedical research would 
ultimately cease to function at UVM, costing jobs and future medical 
breakthroughs.
    How does the administration's proposal to cap indirect costs at 10 
percent allow smaller institutions to contribute to lifesaving 
biomedical research?
    Answer. The effect on grantees will vary by institution, depending 
on the current indirect cost rate and a variety of other factors. The 
impact will be greater on institutions that have a higher percentage of 
NIH funding compared to total funding, or a lower ability to cover 
indirect costs from other sources (e.g., donations, endowment income, 
state government, tuition). The Department continues to work on 
specific details of the NIH indirect cost policy for fiscal year 2018 
and will assess the impact on grantees once the policy is finalized.
    Question. How do you believe that institutions will be able to 
compensate for the millions of dollars lost as a result of this 
provision through fundraising alone?
    Answer. NIH is working with the Department to streamline process 
and increase efficiencies in order to reduce grantee burden. These 
targeted policies aim to reduce the time and expenses that grantees 
must currently spend to comply with Federal grant requirements, thus 
lowering grantees' indirect costs and mitigating the impact of lower 
reimbursements.
                 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 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 universities 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.
    The administration's proposed cuts to the NIH, including more than 
$300 million to NIGMS will undoubtedly place pressure on the IDeA 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.
    Given the impact of cuts to NIGMS on the IDeA, how does the 
administration suggest institutions continue to operate biomedical 
research centers and labs moving forward?
    Answer. NIH is committed to supporting the Institutional 
Development Award (IDeA) program to further the goal of broadening the 
geographic distribution of NIH funding for biomedical research and 
enhancing the competitiveness of investigators at institutions located 
in states like Vermont. For example, in fiscal year 2016, the IDeA 
Program supported the following awards in Vermont totaling close to $9 
million: 1 IDeA Network of Biomedical Research Excellence (INBRE), 3 
Centers of Biomedical Research Excellence (COBREs), and 5 Co-funded 
awards. In fiscal year 2017, an IDeA Program Infrastructure for 
Clinical and Translational Research (IDeA-CTR) award is being made to a 
collaborative network that involves Maine, Vermont, and New Hampshire 
called The Northern New England Clinical and Translational Research 
Network. NIH anticipates that Vermont investigators will continue to 
submit proposals to the different IDeA initiatives and will be in open 
competition with investigators from other IDeA states for support for 
new IDeA awards.
                                 ______
                                 
               Questions Submitted to Douglas Lowy, M.D.
              Questions Submitted by Senator Patty Murray
                                  nci
         the impact of funding cuts on select diseases--cancer
    Question. Dr. Lowy, I see the budget proposes to reduce cancer 
research by 22 percent, or more than $1.3 billion. The research 
community has been making tremendous strides in the treatment of many 
cancers in recent years.
    What would a reduction on this scale--far more than a billion 
dollars--mean for these efforts and future progress?
    Answer. The proposed budget reduction for fiscal year 2018 would 
require the National Cancer Institute (NCI) to make additional 
strategic choices to prioritize how funding is allocated for NCI 
research and training programs. During fiscal year 2018 NCI would 
minimize new program commitments and give greatest priority to the most 
promising opportunities from our existing portfolio of research.
                                 ______
                                 
               Questions Submitted to Gary Gibbons, M.D.
                Questions Submitted by Senator Roy Blunt
                          heart valve disease
    Question. A recent survey from the Alliance for Aging Research 
found that three out of four adults know little to nothing about valve 
disease. Heart valve disease also affects the very young--babies can be 
born with heart valve problems that usually develop sooner or later 
into heart valve disease. Nearly 600 newborns and infants under the age 
of one die each year from congenital heart valve disease. Dr. Gibbons, 
what has the NHLBI done to address heart valve disease, and where do 
you believe that research gaps remain?
    Answer. Heart valve disease is a complex group of disorders that 
represents an important public health problem. It affects approximately 
five million people in the Unites States each year.
    Although it is much more prevalent among older adults, heart valve 
disease can also be present at birth, affecting children from an early 
age.
    National Heart, Lung, and Blood (NHLBI) funded research helped 
pioneer the development of open heart surgeries for valve repair and 
replacement, and has paved the way for many of the non-surgical 
procedures available today, such as transcatheter aortic valve 
replacement (TAVR).
    While significant progress has been made, more research is needed 
to improve our understanding of these disorders and how to treat them.
    To determine the underlying factors that lead to heart valve 
disorders, the NHLBI supports an extensive research portfolio, 
including our Bench to Bassinet program, which specifically focuses on 
how the heart develops and how congenital heart defects are formed. 
Researchers supported through the program have found several hundred 
genes that, when mutated, may lead to congenital heart disease, 
including valve defects. Identification of these genes and further 
study of their functions is helping us unravel the causes of these 
disorders. NHLBI also supports the development and use of innovative 
new imaging technologies to gain better insights into the causes, 
detection, and prognosis of heart valve disease.
    Additionally, NHLBI continues to support research to understand why 
valves degenerate as people age, and to develop more targeted 
interventions. This includes research on the risks and benefits from 
surgical procedures and non-invasive treatments such as TAVR, so that 
patients and doctors can make informed decisions about a patient's 
treatment options.
    NHLBI's Cardiothoracic Surgical Trials Network (CSTN) provides the 
infrastructure to develop, coordinate, and conduct multiple 
collaborative proof-of-concept studies and interventional protocols to 
improve cardiovascular disease outcomes and is yielding useful 
information for treating valve disease in distinct patient populations. 
Just this year, the American College of Cardiology/American Heart 
Association used CSTN findings to update their guidelines for 
management of valvular heart disease to recommend that patients with 
chronic severe ischemic mitral valve leakage (regurgitation) have their 
mitral valve replaced, rather than repaired during coronary artery 
bypass grafting. For patients with moderate ischemic mitral 
regurgitation, CTSN has found similar outcomes whether the patient had 
surgery to replace the leaky valve or repair it. These types of studies 
are providing patients with more personalized treatment options.
                                 ______
                                 
               Questions Submitted to Anthony Fauci, M.D.
              Questions Submitted by Senator John Kennedy
                                  zika
    Question. Dr. Fauci, it was great meeting with you a couple weeks 
ago at the NIH. I understand that vaccine development for Zika is 
underway and that the Vaccine Research Center developed a DNA vaccine 
candidate that is moving onto the next stage of testing. I read an 
article in which you stated that while this stage of testing is fully 
funded, it is unclear there will be funding for the next phase. Are you 
worried that a $838 million cut to the institute will affect the 
timeline for vaccine development?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) currently supports research on the Zika virus, including 
vaccine development and testing, utilizing the $152 million in 
supplemental funding provided by the Zika Response and Preparedness 
Appropriations Act of 2016 (Public Law No. 114-223). NIAID anticipates 
these funds will be sufficient to support Zika- related activities 
currently planned through fiscal year 2017.
    NIAID is supporting the development of several leading Zika vaccine 
candidates, including the NIAID Vaccine Research Center's DNA-based 
vaccine candidate. NIAID recently launched a multi-site Phase II/IIb 
clinical trial of the DNA-based vaccine candidate in March 2017 
following encouraging results in Phase I testing. This Phase II/IIb 
trial will further evaluate whether the experimental vaccine is safe 
and able to stimulate an adequate immune response, and importantly 
whether it can prevent disease in areas with ongoing mosquito-borne 
Zika virus transmission. The study is expected to conclude in 2019, 
although the exact timing will depend on the intensity of Zika virus 
transmission and the efficacy of the vaccine candidate. A low level of 
Zika transmission may lengthen the amount of time required to obtain 
sufficient efficacy data from the clinical trial. NIAID remains 
committed to further development and testing of Zika vaccine 
candidates.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray
    the impact of funding cuts on select diseases--zoonotic diseases
    Question. Dr. Fauci, at a time when we're experiencing an 
increasing threat from zoonotic diseases, the budget proposes to cut 
research on infectious diseases by almost 24 percent.
    What areas of research are likely to be most affected by a 
reduction of this scale?
    How will flu research be affected by a 21 percent cut to research 
efforts there?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) has a dual mandate to pursue a robust research portfolio in the 
areas of microbiology, infectious diseases, immunology, and immune-
mediated disorders, as well as to quickly launch a research response to 
newly emerging and re-emerging infectious diseases, including zoonotic 
diseases. This dual mandate has been particularly evident in recent 
years as NIAID has accelerated research to address the unprecedented 
Ebola and Zika virus outbreaks. NIAID will continue to prioritize 
efforts to address the perpetual challenge of emerging and re-emerging 
infectious diseases, such as other recent zoonotic disease outbreaks of 
chikungunya virus and yellow fever virus; and potential new outbreaks 
from animal, arthropod, or environmental sources.
    NIAID research supports preparedness for pandemic influenza, 
including the potential for the spread of emerging strains of avian 
influenza, such as an avian H7N9 influenza virus strain that first 
emerged to cause sporadic infections in humans in China in 2013. NIAID 
is conducting and supporting preclinical and clinical studies on 
various investigational pandemic influenza vaccines. Further human 
clinical trials supported by NIAID are planned for 2017. Vaccine 
development to protect against other influenza subtypes with pandemic 
potential also is underway.
    In addition, NIAID's comprehensive influenza research program aims 
to develop a ``universal'' influenza vaccine, or a vaccine that 
provides robust, long-lasting protection against multiple strains of 
influenza. Such a vaccine could eliminate the need to update and 
administer the seasonal influenza vaccine each year and could provide 
protection against newly emerging influenza strains with pandemic 
potential.
    NIAID's support for basic, preclinical, and clinical research on 
influenza that informs the design of new and improved influenza 
countermeasures will remain a priority.
              the role of the fogarty international center
    Question. I was troubled to see that the budget fails to explain 
why the Administration is proposing to eliminate the Fogarty 
International Center, which over the years has shown itself to be a 
modest but wise investment.
    Dr. Fauci, what role did Fogarty graduates play in containing the 
Ebola outbreak 3 years ago?
    How does Fogarty support our efforts to contain pandemics at their 
origin, before they can spread to the United States?
    Answer. The Fogarty International Center (FIC) plays an important 
role in global health by supporting the training and early research 
endeavors of international research professionals. To date, FIC grants 
have enabled foreign institutions and their U.S. academic partners to 
create a cadre of more than 6000 trainee alumni throughout the world. 
Trained Fogarty program graduates drive local efforts to detect and 
address pandemics at their point of origin, contain outbreaks and 
minimize their impact, and they are equipped to conduct high-quality 
basic, clinical, and applied research. Fogarty program graduates 
continue to have access to the technical advice and support of Fogarty 
and NIH.
    For example, during the 2014-2016 Ebola outbreak in West Africa, 
Mali quickly identified and contained the cases thereby preventing the 
spread of Ebola around the country. This capacity was in place in part 
because of Fogarty's longstanding training programs.
    In response to the 2014 Ebola virus outbreak FIC designed and 
initiated the ``Emerging Epidemic Virus Research Training for West 
African Countries with Widespread Transmission of Ebola'' program. This 
program provides grants to U.S. and African institutions to foster 
research training focused on emerging viral epidemics.
                             universal flu
    Question. Dr. Fauci, like you I am very excited about the prospect 
of one day having an influenza vaccine that is able to cover all 
strains of flu. The thought of no longer needing to predict the strain 
of flu that will circulate each year will save us countless dollars and 
lives. However, having talked to experts like you I know that this next 
generation flu vaccine is years away from mass production and use, and 
until then we are going to have to continue to work with the 
technologies we have to protect the American public during the annual 
flu season, which by the way the CDC reported kills as many as 50,000 
Americans a year. Think about that, 50,000 Americans a year!
    Dr. Fauci, are we investing enough as a country on influenza 
research, testing and evaluating our nations influenza vaccine response 
capabilities to ensure an adequate health defense for influenza in the 
short term before we are able to perfect the next generation flu 
vaccine?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) has a longstanding commitment to basic, preclinical, and 
clinical research on influenza. This comprehensive program informs the 
design of new and improved influenza vaccines, diagnostic tools, and 
antiviral drugs to assist in our preparedness for both seasonal and 
pandemic influenza strains. In fiscal year 2016, NIH funding for 
influenza research was $263 million. NIH funding for influenza research 
is estimated to be $272 million in fiscal year 2017. The President's 
budget requests $215 million for fiscal year 2018.
    NIAID supports efforts to gain a basic understanding of how 
influenza strains emerge, evolve, and infect animals and humans. 
NIAID's Centers of Excellence for Influenza Research and Surveillance 
(CEIRS) Program is supporting domestic and international influenza 
researchers studying the factors that control influenza disease 
severity and the emergence and transmission of influenza viruses among 
animals. The CEIRS Program continually monitors cases of animal and 
human influenza worldwide to rapidly detect and characterize viruses 
that may have pandemic potential, such as the avian influenza strain 
H7N9.
    NIAID also is developing and testing the next generation of 
influenza therapeutics, including broad-spectrum antiviral drugs for 
multiple virus families, monoclonal antibodies, inhibitors of an 
influenza surface protein called neuraminidase, and influenza RNA 
polymerase inhibitors. NIAID supported initial Phase I clinical studies 
of peramivir, a novel neuraminidase inhibitor subsequently approved by 
the Food and Drug Administration to treat influenza infection in adults 
in certain circumstances. Three NIAID clinical trials are underway in 
high-risk populations to explore the safety and effectiveness of 
several influenza therapeutic approaches, including human plasma 
containing high levels of anti-influenza antibodies, concentrated 
immunoglobulin with high levels of anti-influenza antibodies, and a 
combination of three licensed antiviral drugs.
    Concerns over vaccine efficacy and the threat of avian influenza 
have highlighted the opportunity for considerable improvement in 
influenza vaccines. In response to the emergence of H7N9 avian 
influenza in China in the spring of 2013, the U.S. Department of Health 
and Human Services produced, tested with NIAID support, and stockpiled 
a vaccine for the virus. In 2017, global influenza surveillance 
identified changes in the circulating H7N9 virus, and researchers 
discovered that the stockpiled 2013 H7N9 vaccine is unlikely to provide 
adequate protection against the current H7N9 strains. An updated H7N9 
vaccine is being produced and will be evaluated for safety and 
immunogenicity in clinical trials by the NIAID Vaccine and Treatment 
Evaluation Units (VTEUs) as soon as it becomes available.
    The change in the H7N9 virus observed in 2017 and the resulting 
effort to develop a new vaccine reminds us of the utility of a vaccine 
that could provide protection against multiple strains of seasonal and 
pandemic influenza virus. A ``universal'' influenza vaccine could 
reduce the need for new or updated vaccines due to changes in 
circulating influenza strains or emergence of novel viruses with 
pandemic potential. NIAID is supporting the development of several 
promising universal influenza vaccine candidates, including a broad-
spectrum BiondVax vaccine anticipated to enter a Phase II clinical 
trial in a NIAID VTEU in 2017. NIAID also recently convened leading 
influenza experts to identify gaps in influenza research and draft a 
research agenda and strategic plan for the development of a universal 
influenza vaccine.
    NIAID remains committed to basic and clinical influenza research to 
inform the development of new rapid diagnostics, therapeutics, and 
vaccines. NIAID will continue to place a high priority on the 
development of a universal influenza vaccine to help address the 
challenge of pandemic and seasonal influenza viruses.
                                 ______
                                 
               Questions Submitted to Richard Hodes, M.D.
            Questions Submitted by Senator Joe Manchin, III
              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 $368 million in 2016 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 $7 billion to NIH overall and more than $700 
million to the National Institute on Aging in particular relative to 
the funding that we included in the fiscal year 2017 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. Recent and historic levels of investment in Alzheimer's 
disease and related dementias have enabled the NIH to provide more 
robust support for researchers working toward a cure. Their progress 
has already been significant. NIH supported investigators have:
  --Helped map the brain's innermost connections and the molecular 
        fabric of Alzheimer's.
  --Deepened our understanding of metabolic changes at the heart of the 
        disease.
  --Detected disease progression through neuroimaging and discovery of 
        novel biomarkers.
  --Used new technologies, through unprecedented multidisciplinary 
        collaborations, to make large data sets available with greater 
        accuracy and speed to the research community.
  --Leveraged new investment in epidemiological research to increase 
        our understanding of the complexity of variation across space 
        and over time in disease incidence and prevalence, with the 
        goal of identifying new clues for prevention.
  --Looked at health disparities in new ways, with studies of genetics 
        and risk factors that may be contributing to higher dementia 
        rates among certain groups.
  --Explored new digital technologies to help support caregivers and 
        patients, in a next generation of care strategies.
    There can be no doubt that the financial costs associated with 
Alzheimer's disease are significant and can be devastating to affected 
families, as well as to society as a whole. Recent numbers published by 
the Alzheimer's Association indicate:
  --Total payments in 2017 for all individuals with Alzheimer's or 
        other dementias are estimated at $259 billion.
  --Medicare and Medicaid are expected to cover $175 billion, or 67 
        percent, of the total healthcare and long-term care payments 
        for people with Alzheimer's or other dementias.
  --Out-of-pocket spending is expected to be $56 billion.
    Total annual payments for healthcare, long-term care and hospice 
care for people with Alzheimer's or other dementias are projected to 
increase from $259 billion in 2017 to more than $1.1 trillion in 2050. 
This dramatic rise includes more than four-fold increases both in 
government spending under Medicare and Medicaid and in out-of-pocket 
spending.
    Furthermore, NIH-supported investigators recently found that 
healthcare expenditures among persons with dementia are substantially 
larger than those for other diseases, and many of the expenses are 
uncovered (uninsured). In their study, they reviewed data from the 
Health and Retirement Study on approximately 1,700 Americans in the 5 
years prior to death, and found that the average total cost of 
healthcare per decedent with dementia ($287,000) was significantly 
greater than that of those who died of heart disease ($175,000), cancer 
($173,000), or other causes ($197,000). Although Medicare expenditures 
were similar across groups, average out-of-pocket spending for patients 
with dementia was 81 percent higher than that for patients without 
dementia; a similar pattern held for informal care. Given the data on 
the economic burden of Alzheimer's disease, investment in research to 
better understand, treat, and cure this disease is vital.
    Previous research has suggested that small delays in disease onset 
would have a significant effect on disease burden, including the 
economic burden of disease, and NIA is currently supporting a project 
that will extend these results by assessing lifetime risks of 
developing Alzheimer's disease based on newly available biomarker 
screening tests, obtaining U.S. projections of numbers of persons with 
preclinical disease, and evaluating the impact of potential 
interventions on these projections.
    NIA is continuing to support research on the social and economic 
implications of Alzheimer's disease, particularly as the U.S. 
population continues to age. For example, the National Health and Aging 
Trends Study (NHATS) and its companion study, the National Study of 
Caregiving (NSOC), are frequently used by scientists to investigate the 
role of dementia in caregiving, including the economic stresses faced 
by caregivers. In addition, the NIA-supported Health and Retirement 
Study includes a new harmonized cognitive assessment protocol (HCAP) 
that will allow the more efficient re-estimation of dementia prevalence 
in the United States and allow us to investigate racial, ethnic, and 
gender disparities in dementia. These important studies will continue 
through fiscal year 2018.
                                 ______
                                 
                Questions Submitted to Nora Volkow, M.D.
                Questions Submitted by Senator Roy Blunt
                         opioid abuse research
    Question. Dr. Volkow, there has been a significant increase in 
prescription drug abuse over the last several years. Can you discuss 
the public/private partnership announced last month with the 
pharmaceutical industry to address this crisis and what you hope comes 
from this partnership?
    Answer. The dramatic increase in prescription drug abuse and 
related overdose deaths in recent years calls for innovative scientific 
solutions. As part of a government-wide effort to address this crisis 
and the Department's Opioid Strategy, the National Institutes of Health 
(NIH) is launching a public- private collaborative research initiative 
to develop new, safe, and effective strategies to prevent and treat 
pain, opioid addiction, and overdose reversal and prevention. The goal 
is to cut in half the time it takes to develop new therapeutics. The 
initial plan for this initiative was recently described by Dr. Collins 
and National Institute on Drug Abuse Director Nora D. Volkow, M.D., in 
the New England Journal of Medicine.\12\
---------------------------------------------------------------------------
    \12\ Volkow, N. D. and F. S. Collins (2017). ``The Role of Science 
in Addressing the Opioid Crisis.'' New England Journal of Medicine.
---------------------------------------------------------------------------
    Three major areas for advancement have been targeted: (1) safe, 
more effective, and non- addictive strategies for chronic pain 
management to prevent abuse of and addiction to prescription opioids; 
(2) new and innovative opioid addiction treatments to reduce drug use 
and support recovery; and (3) overdose reversal and prevention 
interventions to reduce mortality and promote access to treatment. The 
public-private partnership is modeled on recent successful 
partnerships, including the Accelerating Medicine Partnership, that 
demonstrate the power of collaborating across sectors to target various 
conditions, including Alzheimer's disease, diabetes, rheumatoid 
arthritis/lupus, Parkinson's disease, and cancer.
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH recently brought together 
innovative experts from government, industry, and academia for a series 
of three cutting-edge science meetings. Meeting summaries will be 
available at: Https://www.nih.gov/opioid-crisis.
Key Themes from Meeting #1: Medications Development for Opioid Use 
        Disorders and Overdose Prevention & Reversal, June 5, 2017
  --Families need and want the scientific and healthcare communities to 
        have the same level of focus and urgency for developing a cure 
        for addiction as they would for any disease that is taking over 
        50,000 lives each year.
  --Lack of treatment infrastructure for medications is a significant 
        challenge, including reimbursement for medications for opioid 
        use disorders.
  --Incentives are needed to encourage pharmaceutical and biotechnology 
        company investment.
  --There is a need for better surveillance on overdoses and the use of 
        naloxone to reverse them.
  --Technology can help to treat disorders and prevent overdose.
Key Themes from Meeting #2: Development of Safe, Effective, Non-
        Addictive Pain Treatments: June 16, 2017
  --There has been significant progress in target identification and 
        structure based drug development; there are many therapeutics 
        in the pipeline.
  --There is a need to reset expectations of what is achievable with 
        pain treatment.
  --Heterogeneity among patients with chronic pain poses significant 
        challenges in clinical trials; objective biomarkers are needed 
        to improve the speed and efficiency of clinical trials.
  --More basic research is needed on a diverse range of pain 
        conditions, including better animal models.
  --Advances in neuroscience technologies are poised to accelerate 
        development of treatments for pain.
  --There is significant potential value in coordinating across both 
        pharmaceutical and academic research: (a) significant overlap 
        in the targets being pursued by different companies, and (b) 
        common technical challenges that everyone is working on 
        independently.
Key Themes from Meeting #3: Understanding the Biological Mechanisms of 
        Pain, July 7, 2017
  --Linkages between industry and academic researchers can promote the 
        effective use of limited resources.
  --Pain research would benefit from leveraging available neuroscience 
        technologies and encouraging more neuroscientists to enter the 
        pain field.
  --Pain processing is complex throughout the brain and periphery. 
        There is a need for multidisciplinary efforts to understand 
        pain at the molecular, cellular, circuit, and system levels.
  --Standardized, objective biomarkers are needed that will predict the 
        response to treatment in animal models and in humans.
  --Extensive patient phenotyping is needed to develop objective 
        biomarkers which will enable precision medicine approaches to 
        more effectively treat each patient's pain, as well as the 
        factors that impact the patient's experience of pain.
  --There is a need for objective screens based on the neurobiology of 
        pain to accelerate the drug development process.
  --There are research gaps regarding the prolonged effects of chronic 
        pain, long term impacts of treatment (e.g. hyperalgesia due to 
        chronic opioid use), and the transition from acute to chronic 
        pain.
    An NIH action plan is currently being formulated. Promising 
potential action steps include:
  --Develop new formulations, combinations, and means to deliver 
        existing medications to increase treatment effectiveness and 
        support long-term recovery.
    --Medications for opioid addiction (e.g. extended release 
            buprenorphine and naltrexone)
    --Overdose prevention and reversal (e.g. increased potency naloxone 
            for fentanyl and carfentanil overdoses)
    --New technologies (e.g. implants, pumps, neural stimulation) to 
            enhance treatments for pain and opioid addiction, and to 
            prevent/reverse overdose.
  --Accelerate development of new non-addictive pain therapies through:
    --Enhanced data and information sharing collaborative between 
            industry partners and with academic scientists
    --Develop and test a standardized platform for drug-target 
            validation
    --Identify and validate biomarkers for pain and treatment response
    --Nociometer/Pain-meter Development and Testing
    --Rapidly bring to market novel non addictive drugs and devices to 
            treat pain
  --Pilot clinical research networks to:
    --Measure strategies to improve treatment effectiveness for pain, 
            opioid addiction, and overdose prevention/reversal in real-
            world settings.
    --Test new therapies for pain management, especially in high-
            impact, well defined pain populations
    --Understand the transition from acute to chronic pain
    Question. What are the barriers to opioid research and particularly 
conducting research on Schedule 1 drugs?
    Answer. The primary challenges to more research on opioids and 
treatments for opioid addiction are the regulatory barriers associated 
with conducting research on Scheduled drugs. Research on Scheduled 
drugs is subject to the regulatory oversight in the Controlled 
Substances Act (CSA).
    Most prescription opioids--such as oxycodone, hydrocodone, and 
fentanyl--are Schedule II controlled substances. Heroin and many new 
potent synthetic opioids (acryl fentanyl, etc.) are Schedule I drugs.
    The process for conducting research using Schedule I controlled 
substances includes:
  --For all research (involving animal or human subjects), the 
        researcher must obtain a DEA registration for each Schedule I 
        controlled substance. Some states have separate registration 
        requirements that often need to be completed 
        sequentially.\13,14\ Obtaining a DEA registration includes:
---------------------------------------------------------------------------
    \13\ Https://www.txdps.state.tx.us/Internetforms/Forms/NAR-77-
78.pdf.
    \14\ Http://www.ct.gov/DCP/cwp/view.asp?a=1622&Q=500858&PM=1.
---------------------------------------------------------------------------
    --Completing and submitting a DEA application for each Schedule I 
            drug:
      -- The applicable fee is currently $244 for a 1 year 
            registration.
      -- The application includes the research protocol and the amount 
            of drug needed for the study.
    --A DEA investigator conducts a site visit to ensure that diversion 
            controls are in place.
      -- Schedule I substances must be stored in a safe or steel 
            cabinet of substantial construction.
      -- If the safe or cabinet is less than 750 lbs., it must be 
            mounted or secured to something of substantial construction 
            (e.g., bolted to a wall or the floor, or the base imbedded 
            in concrete).
      -- The safe/cabinet should have an inner and outer door with the 
            locks for each door keyed differently.
    --The DEA sends the research protocol to FDA for review. Once 
            received, FDA has 30 days to review and respond to DEA 
            about protocols involving human subjects and 21 days to 
            respond for protocols involving non-human research. 
            However, if more information is needed from the researcher, 
            the DEA investigator will contact the researcher which can 
            extend the time.
    --Once the DEA requirements have been satisfied, the researcher 
            receives a DEA registration number; Registration must be 
            renewed every year.
    --A local IRB approval must accompany the application for 
            registration.
  --When the above steps have been completed, if the drug is not 
        commercially available, it must be obtained through the NIDA 
        Drug Supply Program (DSP).
    --For non-NIH-funded basic research not involving human subjects--
            research that has not undergone a Federal grant review or 
            Investigational New Drug (IND) application review--the 
            research protocol is reviewed for scientific merit by a 
            minimum of two non-government scientists, identified by the 
            DSP, with expertise in the research topic. Investigators 
            must submit a detailed research protocol including:
      -- The specific aims and goals of proposed study;
      -- The experimental design, including number of experiments and 
            experimental subjects and the dosages or concentration of 
            drugs;
      -- Justification of quantities of drug(s) requested;
      -- A document demonstrating that the research is approved by the 
            Animal Care & Use Committee and that adequate care in 
            conducting animal research will be exercised (if 
            applicable); and
      -- Documentation of local IRB approval.
    These regulatory and administrative processes around Schedule I 
drugs pose challenges for researchers and disincentivize research on 
these substances. Researchers report to NIDA that the paperwork and 
delays (often a year or more before a proposed study can be started) 
are a disincentive to studying Schedule I substances.
    Schedule II substances also have high abuse liability but have an 
accepted medical value. They can be as or even more dangerous than 
certain Schedule I substances, yet the process for conducting research 
on Schedule II substances is significantly less burdensome. While the 
diversion control requirements (e.g., storage, access controls) are 
equivalent for Schedule I and II substances, a single DEA registration 
can be obtained authorizing research on any Schedule II substances, and 
no protocol review is required.
    Question. Has your Institute researched whether there are factors 
that predispose or, conversely, protect against opioid abuse and 
addiction?
    Answer. Prevention is a critical component of efforts to combat 
drug use and addiction.
    Research has identified many risk and protective factors that 
influence the likelihood that a person will abuse substances and 
develop an addiction, including both genetic and environmental 
influences. NIDA-funded research has identified several gene variants 
that influence how an individual's body processes and responds to 
opioid drugs. These include variations in the mu- opioid receptor-1 
gene (OPRM1) and the enzyme cytochrome P450 2D6 (CYP2D6). Other genetic 
factors have been linked to differences in pain perception and in 
response to opioid pain relievers, which is directly relevant to the 
problem of opioid addiction since by some estimates up to a third of 
patients chronically-prescribed opioids for pain may be dependent or 
addicted.\15\
---------------------------------------------------------------------------
    \15\ Juurlink, D.N., Dhalla, I.A. Dependence and addiction during 
chronic opioid therapy. J. Med. Toxicol., 8 (4), pp. 393-399 (2012).
---------------------------------------------------------------------------
    An approach to pain treatment that seeks to integrate genetic 
findings is ``pharmacokinomics,'' in which information about 
pharmacogenetics (genetic differences in the response to drugs) and 
pharmacokinetics (how the body processes a drug) is combined to 
optimize opioid dosing to minimize addiction risk.\16\ These methods 
are still in the developmental phase but offer the potential to 
personalize pain medicine with an eye toward addiction prevention.
---------------------------------------------------------------------------
    \16\ Linares, O. A., Daly, D., Stefanovski, D. & Boston, R. C. The 
CYP2D6 gene determines oxycodone's phenotype-specific addictive 
potential: implications for addiction prevention and treatment. Med. 
Hypotheses 82, 390--394 (2014).
---------------------------------------------------------------------------
    Apart from individual genetic and biological risk factors, other 
factors affect risk of substance abuse, such as: present or prior 
history of addiction (e.g., alcohol or nicotine); developmental stage 
(youth are more vulnerable to addiction); mental illness; and a myriad 
of environmental factors. Specific environmental factors include: 
social stressors; patterns of drug use; unemployment and lack of 
economic opportunities; substance use or conflict in the family; lack 
of adequate parental supervision; peers who use drugs; and availability 
of drugs in the community. Individuals in rural areas are more likely 
to abuse opioids, likely due to a range of factors, such as increased 
opioid availability, economic depression, and wider social networks 
facilitating diversion.\17\ Another significant risk factor is early 
initiation of any substance use. Individuals who receive an opioid 
prescription during their teens are more likely to abuse opioids as 
adults.\18\
---------------------------------------------------------------------------
    \17\ Keyes KM, Cerda M, Brady JE, Havens JR, Galea S. Understanding 
the Rural--Urban Differences in Nonmedical Prescription Opioid Use and 
Abuse in the United States. American Journal of Public Health. 
2014;104(2):e52-e59. doi:10.2105/AJPH.2013.301709.
    \18\ McCabe S, West B, Veliz P, et al. Trends in medical and 
nonmedical use of prescription opioids among US adolescents: 1976-2015. 
Pediatrics. 2016;139(4):e20162387.
---------------------------------------------------------------------------
    Research has contributed to the development of numerous prevention 
programs that have been shown to reduce opioid abuse and addiction. The 
2016 Surgeon General's Report on Alcohol, Drugs, and Health provides a 
comprehensive overview of evidence-based prevention interventions.\19\
---------------------------------------------------------------------------
    \19\ Substance Abuse and Mental Health Services Administration 
(US); Office of the Surgeon General (US). Facing Addiction in America: 
The Surgeon General's Report on Alcohol, Drugs, and Health [Internet]. 
Washington (DC): US Department of Health and Human Services; 2016 Nov. 
Available from: Https://www.ncbi.nlm.nih.gov/books/NBK424857/.
---------------------------------------------------------------------------
                                 ______
                                 
          Questions Submitted by Senator Shelley Moore Capito
                            opioid addiction
    Question. The National Institute on Drug Abuse has conducted 
invaluable research that has contributed to the development opioid 
addiction treatments including Probuphine (which is implanted in the 
arm and provides a steady, continuous levels of buprenorphine) and new 
formulations of naloxone designed to combat fentanyl overdoses. 
However, the administration's proposed budget recommends reducing the 
funding for NIDA by $210 million and other anti- addiction resources at 
NIH including the National Institute of Mental Health by $400 million.
    Can you address how these reductions would impact the successful 
implementation of NIH's goals of capitalizing on scientific advances to 
combat opioid addiction and reducing the impact of this epidemic within 
our communities?
    Answer. The opioid overdose epidemic is a serious, ongoing, and 
rapidly evolving public health crisis. Over 33,000 Americans died from 
opioid overdose in 2015 alone. Millions of Americans suffer from opioid 
abuse and addiction, and millions more suffer from chronic pain. The 
urgency and scale of this crisis calls for innovative scientific 
solutions and developing them is a top priority for the Department of 
Health and Human Services, including NIH and NIDA. We will continue to 
prioritize research to develop solutions for this crisis and strive to 
accelerate progress.
    As part of a government-wide effort to address this crisis and 
under the HHS Opioid Strategy, NIH is launching a public-private 
collaborative research initiative on pain and opioid addiction. The 
initial plan for this initiative was recently described by Dr. Collins 
and Dr. Volkow, M.D., in the New England Journal of Medicine and 
includes three major areas for advancement: (1) safe, more effective, 
and non-addictive strategies for chronic pain management to prevent 
misuse of and addiction to prescription opioids; (2) new and innovative 
opioid addiction treatments to reduce drug use and support recovery; 
and (3) overdose reversal and prevention interventions to reduce 
mortality and promote access to treatment.
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH recently brought together 
innovative experts from government (including FDA and CMS), industry, 
and academia for a series of three cutting-edge science meetings. 
Through these meetings, NIH has begun to formulate new approaches and 
recruit additional expertise with the aim of developing new safe and 
effective therapeutics for chronic pain, opioid addiction, and overdose 
in half the time it currently takes. With the conclusion of the three 
scientific meetings, plans are underway to synthesize key themes 
discussed and suggestions provided into a draft strategy. The strategy 
will include major goals of the initiative, action steps, key partners, 
deliverables, timeline, and resources (in-kind and financial costs) to 
fully carry out the proposed action steps. Input on the final draft 
will be solicited from participants including Federal partners as well 
as other relevant stakeholders. Upon final approval of the plan, it 
will be posted on the NIH website at: Https://www.nih.gov/opioid-
crisis.
    Promising potential action steps include:
  --Develop new formulations, combinations, and means to deliver 
        existing medications to increase treatment effectiveness and 
        support long-term recovery.
    --Medications for opioid addiction (e.g. extended release 
            buprenorphine and naltrexone)
    --Overdose prevention and reversal (e.g. increased potency naloxone 
            for fentanyl and carfentanil overdoses)
    --New technologies (e.g. implants, pumps, neural stimulation) to 
            enhance treatments for pain and opioid addiction, and to 
            prevent/reverse overdose.
  --Accelerate development of new non-addictive pain therapies through:
    --Enhanced data and information sharing collaborative between 
            industry partners and with academic scientists
    --Develop and test a standardized platform for drug-target 
            validation
    --Identify and validate biomarkers for pain and treatment response
    --Nociometer/Pain-meter Development and Testing
    --Rapidly bring to market novel non addictive drugs and devices to 
            treat pain
  --Pilot clinical research networks to:
    --Evaluate strategies to improve treatment effectiveness for pain, 
            opioid addiction, and overdose prevention/reversal in real-
            world settings
    --Test new therapies for pain management, especially in high-
            impact, well defined pain populations
    --Understand the transition from acute to chronic pain
                       opioid addiction treatment
    Question. The 21st Century Cures Act last December provided $1 
billion in funding for opioid addiction treatment. Can you address how 
priority funding for a state like West Virginia is supporting 
successful state-based programs like those being implemented in 
Huntington?
    Additionally, what do you see as priorities this Committee should 
be considering to continue this important work?
    Answer. While the State Targeted Response to the Opioid Crisis 
Grants are administered through SAMHSA, NIH has a strong commitment to 
supporting research that builds the evidence base for successful 
strategies to expand access to medications for the treatment of opioid 
addiction. To this end, NIDA posted a Funding Opportunity Announcement 
in April of 2017 to solicit applications for studies evaluating the 
impact of states' efforts to address the opioid crisis using the funds 
authorized under the 21st Century Cures Act.\20\ These projects will 
test the effects of novel approaches for providing medications for 
opioid addiction and the overdose reversal drug naloxone on health 
outcomes including illicit drug use, overdose, and addiction.
---------------------------------------------------------------------------
    \20\ National Institute on Drug Abuse. Expanding Medication 
Assisted Treatment for Opioid Use Disorders in the Context of the 
SAMHSA Opioid STR Grants (R21/R33). RFA-DA-18-005. Available at: 
Https://grants.nih.gov/grants/guide/rfa-files/RFA-DA-18-005.html.
---------------------------------------------------------------------------
    Funded projects will be announced later in 2017, but possible areas 
of research include:
  --Opioid addiction medications provided in emergency departments, 
        pharmacies, inpatient units, and other healthcare settings.
  --Telehealth approaches for providing opioid addiction medications in 
        the general healthcare sector.
  --Models of care in the general health sector that provide a choice 
        of opioid addiction medications to patients.
  --Continuity of care models for those receiving medications for 
        opioid addiction. Models of care and delivery designed to 
        expand the provision of opioid addiction medications in primary 
        care including, but not limited to the following:
    --The Massachusetts Nurse Care Manager Model.
    --The Hub and Spoke Model.
    --The Echo Model.
    --Other evidence-based models.
  --Models of naloxone delivery that offer the opportunity for linkage 
        to medication-assisted treatment (MAT) after receipt of 
        naloxone for overdose.
  --Provision of interim methadone or buprenorphine while patients are 
        waiting for admission to comprehensive treatment programs.
    One ongoing area of concern for the committee's consideration is 
the importance of treatment continuity in addressing opioid addiction. 
Discontinuing medications before the patient is ready poses significant 
risk for relapse and subsequent overdose. The 21st Century Cures 
funding is critical for helping states address the ongoing opioid 
epidemic, but many patients will need ongoing treatment. It is 
important to develop strategies to ensure that patients do not lose 
access to these medications and critical counseling and behavioral 
therapies.
                  medication-assisted treatment (mat)
    Question. Ensuring access to treatment for opioid addiction is 
essential to reversing the number of overdose deaths and the overall 
opioid epidemic. Medication-Assisted Treatment (MAT) plays an important 
role in this treatment. Current treatments such as methadone and 
buprenorphine--while effective in many cases--often require continued 
use for long periods of time, sometimes years, and daily maintenance. 
Is NIDA researching new methods of MATs which would address these 
issues?
    Answer. The urgency and scale of the opioid crisis necessitates 
innovative scientific solutions. As part of a government-wide effort to 
address this crisis and under the HHS Opioid Strategy, NIH is 
supplementing existing research efforts with a public-private 
collaborative research initiative on pain and opioid addiction. In 
April 2017, NIH Director Francis S. Collins, met with research and 
development leaders from the world's leading biopharmaceutical 
companies to discuss new ways for government and industry to work 
together to address the opioid crisis. The initial plan for this 
initiative was recently laid out by Dr. Collins and National Institute 
on Drug Abuse Director Nora D. Volkow, in the New England Journal of 
Medicine.\21\
---------------------------------------------------------------------------
    \21\ Volkow, N. D. and F. S. Collins (2017). ``The Role of Science 
in Addressing the Opioid Crisis.'' New England Journal of Medicine.
---------------------------------------------------------------------------
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH brought together innovative 
experts from government, industry, and academia for a series of three 
cutting-edge science meetings. On June 5, NIH convened the meeting 
Medications Development for Opioid Use Disorders and for Overdose 
Prevention and Reversal, and follow- up activities are in the planning 
stages. One of the main recommendations with potential for short term 
progress is prioritizing development of improved formulations of 
existing medications such as:
  --Long-acting formulations of addiction treatments buprenorphine, 
        methadone, or naltrexone to ensure stable dosing and promote 
        treatment adherence:
    --Depot shots that release a controlled amount of the medication 
            into an individuals' body over time, and
    --Biodegradable polymer implants that release a controlled amount 
            of medication over time but do not need to be surgically 
            removed after treatment,
  --Longer duration depot formulations of the opioid overdose reversal 
        medication such as naloxone which can reduce the danger 
        associated with naloxone wearing off before the danger of 
        overdose has fully abated, due to the long half-life of many 
        opioids.
    We are currently developing a draft strategy that will include 
major goals of the initiative, action steps, key partners, 
deliverables, timeline, and resources (in-kind and financial costs) to 
fully carry out the proposed action steps. Input on the final draft 
will be solicited from participants including Federal partners as well 
as other relevant stakeholders. Upon final approval of the plan, it 
will be posted on the NIH website at: Https://www.nih.gov/opioid-
crisis.
                      non-addicting pain medicines
    Question. Can you share an update on the research to develop non-
addicting pain medicines for people who have to cope with chronic 
debilitating pain? Is there any effort to combat addiction resulting 
from acute pain episodes?
    Answer. The urgency and scale of the opioid crisis necessitates 
innovative scientific solutions. As part of a government-wide effort to 
address this crisis and under the HHS Opioid Strategy, NIH is 
supplementing existing research efforts with a public-private 
collaborative research initiative on pain and opioid addiction. In 
April 2017, NIH Director Francis S. Collins, M.D., Ph.D., met with 
research and development leaders from the world's leading 
biopharmaceutical companies to discuss new ways for government and 
industry to work together to address the opioid crisis. The initial 
plan for this initiative was recently laid out by Dr. Collins and 
National Institute on Drug Abuse Director Nora D. Volkow, M.D., in the 
New England Journal of Medicine \22\ and includes three major areas for 
advancement: (1) safe, more effective, and non- addictive strategies 
for chronic pain management to prevent abuse of and addiction to 
prescription opioids; (2) new and innovative opioid addiction 
treatments to reduce drug use and support recovery; and (3) overdose 
reversal interventions.
---------------------------------------------------------------------------
    \22\ Volkow, N. D. and F. S. Collins (2017). ``The Role of Science 
in Addressing the Opioid Crisis.'' New England Journal of Medicine.
---------------------------------------------------------------------------
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH brought together innovative 
experts from government (including FDA and CMS), industry, and academia 
for a series of three cutting-edge science meetings, two of which 
addressed pain research. On June 16, NIH convened the meeting 
Development of Safe, Effective, Non-Addictive Pain Treatments, and on 
July 7, NIH convened the meeting Understanding the Neurobiological 
Mechanisms of Pain. The combined expertise of the participants was 
focused on identifying the research directions and strategies that are 
most likely to result in rapid progress in development of therapeutics 
for pain without liability for abuse or overdose.
    We are currently developing a draft strategy that will include 
major goals of the initiative, action steps, key partners, 
deliverables, timeline, and resources (in-kind and financial costs) to 
fully carry out the proposed action steps. Input on final draft will be 
solicited from participants including Federal partners as well as other 
relevant stakeholders. Upon final approval of the plan, it will be 
posted on the NIH website at: Https://www.nih.gov/opioid-crisis.
    These efforts are in addition to NIH's ongoing robust support of 
research in this area. NIH's Interagency Pain Research Coordinating 
Committee's Federal Pain Research Strategy was rolled out in June 2017, 
and supports development of safer alternatives to prescription 
medicines for pain care.\23\ Specific areas of focus include:
---------------------------------------------------------------------------
    \23\ NIH's Interagency Pain Research Coordinating Committee: 
Federal Pain Research Strategy. Available at: Https://iprcc.nih.gov/
FPRS/FPRS.htm.
---------------------------------------------------------------------------
  --Development of non-opioid analgesics that target the molecular 
        pathways of pain signaling
  --Development of novel opioid analgesics with reduced potential for 
        addiction and overdose
  --Comparative effectiveness and precision medicine research to 
        identify which treatments will be most effective for a specific 
        patient.
  --Nonpharmacological treatments for pain, including the use of 
        stimulation devices, biofeedback, genetic manipulation, 
        nanotechnology, and behavioral and psychosocial treatments
  --Basic research on the mechanisms of pain
                                 ______
                                 
              Questions Submitted by Senator John Kennedy
                                opioids
    Question. Dr. Volkow, thank you for taking the time to meet with 
our Committee to discuss the NIH's budget request for fiscal year 2018. 
I read that the National Institute of Drug Abuse's (NIDA) request 
included a $210 million cut from fiscal year 2017 allocations. As you 
know, my home state of Louisiana has been hit hard by the opioid 
epidemic, as have many of our states. In your opinion, will NIDA be 
able to curb opioid abuse with this amount of funding?
    Answer. The opioid overdose epidemic is a serious, ongoing, and 
rapidly evolving public health crisis. Over 33,000 Americans died from 
opioid overdose in 2015 alone. Millions of Americans suffer from opioid 
abuse and addiction, and millions more suffer from chronic pain. The 
urgency and scale of this crisis calls for innovative scientific 
solutions and developing them is a top priority for the Department of 
Health and Human Services, including NIH and NIDA. We will continue to 
prioritize research to develop solutions for this crisis and strive to 
accelerate progress.
    As part of a government-wide effort to address this crisis and 
under the HHS Opioid Strategy, NIH is launching a public-private 
collaborative research initiative on pain and opioid addiction. The 
initial plan for this initiative was recently described by Dr. Collins 
and Dr. Volkow, M.D., in the New England Journal of Medicine and 
includes three major areas for advancement: (1) safe, more effective, 
and non-addictive strategies for chronic pain management to prevent 
misuse of and addiction to prescription opioids; (2) new and innovative 
opioid addiction treatments to reduce drug use and support recovery; 
and (3) overdose reversal interventions to reduce mortality and promote 
access to treatment.
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH recently brought together 
innovative experts from government, industry, and academia for a series 
of three cutting-edge science meetings. With the conclusion of the 
three scientific meetings, plans are underway to synthesize key themes 
discussed and suggestions provided into a draft strategy. The strategy 
will include major goals of the initiative, action steps, key partners, 
deliverables, timeline, and resources (in-kind and financial costs) to 
fully carry out the proposed action steps. Input on final draft will be 
solicited from participants including Federal partners as well as other 
relevant stakeholders. Upon final approval of the plan, it will be 
posted on the NIH website at: Https://www.nih.gov/opioid-crisis.
    Promising potential action steps include:
  --Develop new formulations, combinations, and means to deliver 
        existing medications to increase treatment effectiveness and 
        support long-term recovery.
    --Medications for opioid addiction (e.g. extended release 
            buprenorphine and naltrexone)
    --Overdose prevention and reversal (e.g. increased potency naloxone 
            for fentanyl and carfentanil overdoses)
    --New technologies (e.g. implants, pumps, neural stimulation) to 
            enhance treatments for pain and substance use disorder, and 
            to prevent/reverse overdose.
  --Accelerate development of new non-addictive pain therapies through
    --Enhanced data and information sharing collaborative between 
            industry partners and with academic scientists
    --Develop and test a standardized platform for drug-target 
            validation
    --Identify and validate biomarkers for pain and treatment response
    --Nociometer/Pain-meter Development and Testing
    --Rapidly bring to market novel non addictive drugs and devices to 
            treat pain
  --Establish national clinical research networks to:
    --Measure strategies to improve treatment effectiveness for pain, 
            opioid addiction, and overdose prevention/reversal in real-
            world settings
    --Test new therapies for pain management, especially in high-
            impact, well defined pain populations
    --Understand the transition from acute to chronic pain
    Addressing the opioid crisis is a top priority for the Department 
of Health and Human Services, including NIH and NIDA. We will continue 
to prioritize research to develop solutions for this crisis and strive 
to accelerate progress.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray
       the impact of funding cuts on select diseases--drug abuse
    Question. Dr. Volkow, despite the horrible grip the opioid epidemic 
has in so many communities, the budget proposes to cut drug abuse 
research by almost 20 percent or more than $200 million compared to 
this year's funding level. That would come on top of changes to 
Medicaid and the Essential Health Benefits that could restrict access 
to treatment.
    What are the possible impacts of a reduction of that magnitude on 
your research efforts?
    Answer. The opioid overdose epidemic is a serious, ongoing, and 
rapidly evolving public health crisis. Over 33,000 Americans died from 
opioid overdose in 2015 alone. Millions of Americans suffer from opioid 
abuse and addition, and millions more suffer from chronic pain. The 
urgency and scale of this crisis calls for innovative scientific 
solutions. As part of a government-wide effort to address this crisis 
and under the HHS Opioid Strategy, NIH is launching a public- private 
collaborative research initiative on pain and opioid addiction. The 
initial plan for this initiative was recently described by Dr. Collins 
and Dr. Volkow, M.D., in the New England Journal of Medicine and 
includes three major areas for advancement: (1) safe, more effective, 
and non-addictive strategies for chronic pain management to prevent 
misuse of and addiction to prescription opioids; (2) new and innovative 
opioid addiction treatments to reduce drug use and support recovery; 
and (3) overdose reversal interventions to reduce mortality and promote 
access to treatment.
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH recently brought together 
innovative experts from government, industry, and academia for a series 
of three cutting-edge science meetings. Through these meetings, NIH has 
begun to formulate new approaches and recruit additional expertise with 
the aim of developing new safe and effective therapeutics for chronic 
pain, opioid abuse and addiction, and overdose in half the time it 
currently takes.
    With the conclusion of the three scientific meetings, plans are 
underway to synthesize key themes discussed and suggestions provided 
into a draft strategy. The strategy will include major goals of the 
initiative, action steps, key partners, deliverables, timeline, and 
resources (in-kind and financial costs) to fully carry out the proposed 
action steps. Input on final draft will be solicited from participants 
including Federal partners as well as other relevant stakeholders. Upon 
final approval of the plan, it will be posted on the NIH website at: 
Https://www.nih.gov/opioid-crisis.
    Addressing the opioid crisis is a top priority for the Department 
of Health and Human Services, including NIH and NIDA. We will continue 
to prioritize research to develop solutions for this crisis and strive 
to accelerate progress.
                      nida translational research
    Question. It is well documented that it takes years to translate 
the knowledge developed through NIH-support research into actual 
practice in service settings. This ``translational work'' received 
elevated attention at NIDA in the 2000's through its ``Blending 
Initiative.'' This ``Blending Initiative'' included specific 
collaboration with State alcohol and drug agency directors, through the 
National Association of State Alcohol and Drug Abuse Directors 
(NASADAD), to conduct a regular dialogue between NIDA-supported 
researchers and the leaders of the safety net prevention, treatment and 
recovery system. I am concerned with what seems to be lessening 
activity dedicated to this issue. This conversation between researchers 
and State alcohol and drug agency directors is critical because (1) 
leaders of State alcohol and drug service systems benefit from hearing 
about the latest research from the Institute and (2) researchers 
benefit hearing directly from State alcohol and drug agency directors 
regarding their research needs and challenges managing the publicly 
funded system--including challenges related to the opioid issue. This 
type of dialogue can accelerate the lag between scientific discovery 
and practice.
    Can you please outline the specific steps NIDA has taken to hold a 
regular dialogue that connects NIDA-supported researchers with State 
alcohol and drug agency directors to discuss tools to help improve 
services in public sector settings? Are there steps NIDA can take to 
re-energize the Blending Initiative to help improve State systems 
across the country?
    Please provide the proposed fiscal year 2018 budget and the 
previous 5 year final allocations for the following NIDA divisions: 
Epidemiology, Services and Prevention Research Branch; and Clinical 
Trials Network
    Answer. Accelerating the dissemination of research-based drug abuse 
treatment into clinical practice is a priority for the National 
Institute on Drug Abuse (NIDA) and represents the core mission of the 
Blending Initiative, a collaboration between NIDA and the Substance 
Abuse and Mental Health Services Administration (SAMHSA). Established 
in 2001, the Blending Initiative's goal is to reduce the gap that 
exists between the publication of research results and impact on 
treatment delivery.
    Specifically, the Blending Initiative incorporates collaboration 
between clinicians, scientists, and experienced trainers to catalyze 
the creation of user-friendly treatment tools and products and 
facilitate the adoption of research-based interventions into front-line 
clinical settings. Through this initiative, NIDA transferred $1.5 
million per year to SAMHSA to support SAMHSA's Addiction Technology 
Transfer Centers (ATTCs) to develop and disseminate treatment and 
training products based on results from studies conducted by the 
National Drug Abuse Clinical Trials Network (CTN) as well as other 
NIDA-supported research. State alcohol and drug abuse agencies have 
always been a critical partner in this effort to ensure that NIDA-based 
research findings are disseminated and applied in an efficient way to 
ensure widespread adoption. Since 2000, NIDA has supported the 
development of six major training products, convened 14 state- level 
blending meetings in partnership with State alcohol and drug abuse 
offices, and sponsored hundreds of training programs nationwide.
    In order to revitalize the Blending Initiative as described, NIDA 
could expand its dissemination efforts in partnership with SAMHSA and 
State alcohol and drug agency directors to improve services in public 
sector settings. This could include such things as conducting workshops 
and seminars at state-level conferences and meetings, convening webinar 
series targeting and engaging state agency directors or regular 
``roundtable'' in person or virtual meetings to review best practices 
and strategies or solutions to address the opioid overdose epidemic and 
to improve access to medication for persons with opioid addiction in 
public sector settings.

   FUNDING FOR NIDA DIVISION OF EPIDEMIOLOGY, SERVICES AND PREVENTION RESEARCH AND THE CLINICAL TRIALS NETWORK
                                             [Dollars in thousands]
----------------------------------------------------------------------------------------------------------------
                                                                          Fiscal Year
                                             -------------------------------------------------------------------
                                                                                                        2018-
                                                 2013       2014       2015       2016       217-    President's
                                                Actual     Actual     Actual     Actual    Estimate     Budget
----------------------------------------------------------------------------------------------------------------
Division of Epidemiology, Services and          241,661    247,141    265,357    320,608    331,170     263,634
 Prevention Research........................
Clinical Trials Network.....................     44,508     45,291     41,718     41,281     44,264      35,237
----------------------------------------------------------------------------------------------------------------

                                 ______
                                 
              Questions Submitted by Senator Brian Schatz
                              tuberculosis
    Question. Tuberculosis is the leading global infectious killer. It 
takes the lives of 1.8 million people annually around the world. My 
state of Hawaii is one of the most highly burdened states in the United 
States.
    How is the NIH responding to tuberculosis globally and 
domestically, especially in terms of developing faster diagnostics; 
shorter, more tolerable treatments; and effective vaccines to prvent 
the disease?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) remains committed to supporting basic, translational, and 
clinical research that stimulates innovation in the diagnosis, 
treatment, and prevention of tuberculosis (TB). NIAID collaborates with 
other Federal agencies, national and international research 
organizations, philanthropic donors, and industry to address the 
domestic and global challenges posed by TB and its multidrug-resistant 
(MDR) and extensively drug-resistant (XDR) forms. As part of these 
efforts, NIAID plays a key role in the National Action Plan for 
Combating Multidrug-Resistant Tuberculosis.
    NIAID supports fundamental research on Mycobacterium tuberculosis, 
the bacterium that causes TB, to better understand how it causes 
disease and how it develops resistance to the drugs used to treat it. 
NIAID also provides preclinical research support services to 
mycobacterial researchers around the world to delineate the biological 
mechanisms of TB and to advance countermeasure development. These 
activities include the development and evaluation of a broad array of 
TB diagnostic tests, including those capable of detecting TB drug 
resistance. For example, NIAID supported key aspects of the development 
of the Xpert MTB/RIF (Cepheid) test endorsed by the World Health 
Organization. A newer, more sensitive version of the test may help 
detect TB in patients who test negative using other diagnostic tests or 
aid in the challenging diagnosis of TB in children. Another new Xpert 
test version also is being evaluated for the capability to diagnose XDR 
TB. In addition, NIAID's Tuberculosis Research Unit program has helped 
identify biomarkers that define the various stages of infection, such 
as latent, or dormant, versus active disease. NIAID also contributes to 
the global consortia that are mapping the genetic diversity of MDR and 
XDR strains of M. tuberculosis to further aid in diagnostic 
development. To prepare for clinical studies of TB countermeasures, 
NIAID has worked with organizations in India, Brazil, South Africa, 
Indonesia, the Philippines, and South Korea to develop a network of co-
funded research sites to conduct international trials of promising new 
drugs, vaccines, and diagnostics.
    NIAID is funding research to prevent the spread of drug-resistant 
TB by supporting the development and optimization of new and existing 
therapeutics. To date, NIAID support has contributed to more than two-
thirds of 20 investigational TB drugs and drug combinations. NIAID also 
is helping to identify new TB therapeutics by evaluating small molecule 
candidates provided by pharmaceutical companies as part of the TB 
Accelerator, a public-private partnership led by the Bill & Melinda 
Gates Foundation. In addition, NIAID is supporting a clinical trial in 
Peru and South Africa to determine the appropriate dosage of the 
antibiotic levofloxacin in combination with a standard TB antibiotic 
regimen to better treat MDR TB. This trial leverages support and 
infrastructure through the Centers for Disease Control and Prevention 
(CDC). NIAID also supports research designed to make TB treatment 
regimens easier to tolerate. For example, one NIAID-supported study is 
evaluating a novel digital monitoring system for individuals undergoing 
treatments for M. tuberculosis infection that require direct 
observation of the treatment by a medical professional. The goal of the 
system is to make treatment easier and less time consuming for patients 
and healthcare providers. NIAID researchers also are investigating 
whether a 1-month treatment regimen for persons latently infected with 
M. tuberculosis is effective at preventing active TB in at-risk HIV-
infected individuals. If effective, the shorter drug regimen also may 
increase treatment adherence compared to the standard regimen.
    A safe and highly effective TB vaccine will be a critical tool in 
first controlling, and ultimately eradicating the disease. To that end, 
NIAID supports basic, preclinical, and clinical development of 
innovative new vaccine candidates to protect against infection and/or 
TB disease in adults and children. NIAID support has contributed to 
about half of the vaccine candidates currently in clinical development. 
For example, NIAID is conducting a trial to assess the safety and 
immunogenicity of an adjuvanted TB vaccine candidate, ID93. NIAID also 
has released four funding announcements soliciting research to advance 
the science of TB vaccines, including studies on vaccines in 
individuals co-infected with TB and HIV who are at high risk for 
morbidity and mortality.
    NIAID remains committed to supporting the vital research necessary 
to develop new and improved diagnostics, therapeutics, and vaccines for 
TB. NIAID also will continue to advance the biomedical research goals 
and objectives of the National Action Plan for Combating MDR TB by 
engaging with multiple stakeholders, including academic, industry, and 
community collaborators, and by leveraging the clinical trial 
infrastructures established by CDC and the United States Agency for 
International Development.
                                  nida
                       medical marijuana research
    Question. Marijuana research and policy issues continue to be very 
important.
    What are some of the barriers you are facing to funding and 
conducting this research? What do we know about marijuana's potential 
to ease the opioid crisis?
    Answer. There are many open questions related to evolving marijuana 
laws that research can help to address, including how policy changes 
will affect:
  --Use of marijuana and related health outcomes, including mental 
        illness
  --Health outcomes--positive and negative--related to State-level 
        initiatives to permit the medical use of marijuana
  --Usage patterns of other drugs, alcohol, and tobacco
  --Public-safety outcomes related to drugged driving, crime, etc.
  --Potency and cannabinoid content of commonly consumed strains
  --New routes of administration (e.g., vaping, dabbing, edibles)
  --Societal norms and perceptions
    In addition, more research is needed to develop prevention 
interventions that target marijuana use among youth in the context of 
changing norms, to understand the health consequences related to the 
increasing potency of marijuana, to characterize the consequences of 
marijuana use on the developing brain, and to develop new treatment 
strategies for cannabis use disorders.
    NIDA-supported science aims to address these gaps and to help 
inform decisionmaking related to state and Federal marijuana policies. 
In addition, in line with NIDA's mission of reducing the burden of drug 
use and SUDs, ongoing research will continue to explore the therapeutic 
potential of marijuana-derived compounds for pain and addiction.
    Research that utilizes the marijuana plant or its constituent 
compounds is governed by specific regulatory and administrative 
processes that govern research on marijuana. Under the Single 
Convention on Narcotic Drugs (1961), the United States is subject to 
several obligations related to the regulation of marijuana cultivation 
for research.\24\ In addition, under the Controlled Substances Act 
(CSA), marijuana and its constituent compounds are classified as 
Schedule I controlled substances--defined as having high potential for 
abuse and no currently accepted medical use, and no accepted safety for 
use under medical supervision.\25\ As a result of these treaty 
obligations and marijuana's status under the CSA, the Drug Enforcement 
Administration (DEA) with input from the Department of Health and Human 
Services regulates marijuana research and the cultivation of marijuana 
for research purposes through licensing requirements and by 
establishing annual aggregate production quotas. While research on 
marijuana and its constituent compounds is possible, there remains a 
number of barriers, described below, for conducting this research.\26\
---------------------------------------------------------------------------
    \24\ United Nations. Single Convention on Narcotic Drugs. March 
1961. Https://www.unodc.org/pdf/convention_1961_en.pdf.
    \25\ Controlled Substances Act. Vol 21.; 1970. Https://www.gpo.gov/
fdsys/pkg/STATUTE-984/pdf/STATUTE-84-Pg1236.pdf.
    \26\ Stith SS, Vigil JM. Federal barriers to Cannabis research. 
Science. 2016;352(6290):1182-1182. doi:10.1126/science.aaf7450.
---------------------------------------------------------------------------
    The registration process: Researchers have indicated that this 
process creates administrative burdens that can act as disincentives to 
conducting research.
    Single source of marijuana for research purposes: Currently, there 
is one registration for marijuana cultivation in the US--the University 
of Mississippi, which, through a contract with NIDA, supports the 
cultivation and distribution of research grade marijuana for the 
country. While the NIDA supply of marijuana has diversified to include 
different strains with varying concentrations of cannabidiol (CBD) and 
other cannabinoids of interest to researchers, it is both costly and 
time consuming to grow, isolate, and/or refine new products that 
scientists would like to study.
    Given the scope of the ongoing opioid crisis, more research is 
needed to develop non-opioid based medications for pain. Ongoing 
research is actively investigating the potential of cannabinoids for 
this purpose. There is evidence that THC, the main psychotropic 
compound in marijuana, may be effective for treating pain.
                                 ______
                                 
            Questions Submitted by Senator Joe Manchin, III
               research into alternative pain management
    Question. Dr. Volkow, as you know, communities across the country, 
including many in my state of West Virginia, are seeing an alarming 
rise in substance abuse and addiction to prescription opioids. 
Nationally, prescription opioids and heroin killed more than 33,000 
people in 2015. That's 91 people every day. In West Virginia, we lost 
more than 700 people in 2015.
    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, function, and quality of life.
    This is a public health crisis and we have to find a better way.
    That is why I am so worried about the President's Budget Request to 
cut more than $200 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. The opioid overdose epidemic is a serious, ongoing, and 
rapidly evolving public health crisis. As you note, over 33,000 
Americans died from opioid overdose in 2015 alone. Millions of 
Americans suffer from opioid abuse and addiction, and millions more 
suffer from chronic pain. The urgency and scale of this crisis calls 
for innovative scientific solutions. As part of a government-wide 
effort to address this crisis and under the HHS Opioid Strategy, NIH is 
launching a public-private collaborative research initiative on pain 
and opioid addiction. The initial plan for this initiative was recently 
described by Dr. Collins and Dr. Volkow, M.D., in the New England 
Journal of Medicine and includes three major areas for advancement: (1) 
safe, more effective, and non-addictive strategies for chronic pain 
management to prevent misuse of and addiction to prescription opioids; 
(2) new and innovative opioid addiction treatments to reduce drug use 
and support recovery; and (3) overdose reversal and prevention 
interventions to reduce mortality and promote access to treatment.
    To identify the scientific strategies with the greatest potential 
for solutions to the opioid problem, NIH recently brought together 
innovative experts from government, industry, and academia for a series 
of three cutting-edge science meetings. Through these meetings, NIH has 
begun to formulate new approaches and recruit additional expertise with 
the aim of developing new safe and effective therapeutics for chronic 
pain, opioid addiction, and overdose in half the time it currently 
takes. Key themes from each meeting are below:
Key Themes from Meeting #1: Medications Development for Opioid Use 
        Disorders and Overdose Prevention & Reversal, June 5, 2017
  --Families need and want the scientific and healthcare communities to 
        have the same level of focus and urgency for developing a cure 
        for addiction as they would for any disease that is taking over 
        50,000 lives each year.
  --Lack of treatment infrastructure for medications is a significant 
        challenge, including reimbursement for medications for opioid 
        use disorders.
  --Incentives are needed to encourage pharmaceutical and biotechnology 
        company investment.
  --There is a need for better surveillance on overdoses and the use of 
        naloxone to reverse them.
  --Technology can help to treat disorders and prevent overdose.
Key Themes from Meeting #2: Development of Safe, Effective, Non-
        Addictive Pain Treatments: June 16, 2017
  --There has been significant progress in target identification and 
        structure based drug development; there are many therapeutics 
        in the pipeline.
  --There is a need to reset expectations of what is achievable with 
        pain treatment.
  --Heterogeneity among patients with chronic pain poses significant 
        challenges in clinical trials; objective biomarkers are needed 
        to improve the speed and efficiency of clinical trials.
  --More basic research is needed on a diverse range of pain 
        conditions, including better animal models.
  --Advances in neuroscience technologies are poised to accelerate 
        development of treatments for pain.
  --There is significant potential value in coordinating across both 
        pharmaceutical and academic research: a) significant overlap in 
        the targets being pursued by different companies, and b) common 
        technical challenges that everyone is working on independently.
Key Themes from Meeting #3: Understanding the Biological Mechanisms of 
        Pain, July 7, 2017
  --Linkages between industry and academic researchers can promote the 
        effective use of limited resources.
  --Pain research would benefit from leveraging available neuroscience 
        technologies and encouraging more neuroscientists to enter the 
        pain field.
  --Pain processing is complex throughout the brain and periphery. 
        There is a need for multidisciplinary efforts to understand 
        pain at the molecular, cellular, circuit, and system levels.
  --Standardized, objective biomarkers are needed that will predict the 
        response to treatment in animal models and in humans.
  --Extensive patient phenotyping is needed to develop objective 
        biomarkers which will enable precision medicine approaches to 
        more effectively treat each patient's pain, as well as the 
        factors that impact the patient's experience of pain.
  --There is a need for objective screens based on the neurobiology of 
        pain to accelerate the drug development process.
  --There are research gaps regarding the prolonged effects of chronic 
        pain, long term impacts of treatment (e.g. hyperalgesia due to 
        chronic opioid use), and the transition from acute to chronic 
        pain.
    With the conclusion of the three scientific meetings, plans are 
underway to synthesize key themes discussed and suggestions provided 
into a draft strategy. The strategy will include major goals of the 
initiative, action steps, key partners, deliverables, timeline, and 
resources (in-kind and financial costs) to fully carry out the proposed 
action steps. Input on final draft will be solicited from participants 
including Federal partners as well as other relevant stakeholders. Upon 
final approval of the plan, it will be posted on the NIH website at: 
Https://www.nih.gov/opioid-crisis.
    Addressing the opioid crisis is a top priority for the Department 
of Health and Human Services, including NIH and NIDA. We will continue 
to prioritize research to develop solutions for this crisis and strive 
to accelerate progress.
                                 ______
                                 
                          va and nih research
    Question. In 2014, the VA and the National Institutes of Health 
launched a 5-year quality- improvement initiative to explore non-drug 
approaches to managing pain and related health conditions such as PTSD, 
drug abuse, and poor sleep.
    According to the VA, one-third of Veterans in VA care are 
prescribed an opioid, and one-third of those are on long-term opioid 
prescriptions despite the many side effects and the questionable 
efficacy of using these drugs to manage chronic pain.
    That is why this work is so critical.
    Dr. Volkow, can you provide any updates on this initiative and can 
you speak to the need to better understand the complex relationship 
between pain and other health conditions, including mental health 
conditions, and the need to develop non-addictive, non-drug options for 
helping people manage pain?
    Answer. In 2014, the VA and the National Institutes of Health 
launched a 5-year quality- improvement initiative to explore non-drug 
approaches to managing pain and related health conditions such as PTSD, 
drug abuse, and poor sleep. According to the VA, one-third of Veterans 
in VA care are prescribed an opioid, and one-third of those are on 
long-term opioid prescriptions despite the potential for adverse 
effects and the questionable efficacy of using these drugs to manage 
chronic non-cancer pain. This is why developing new, safe, effective, 
non- addictive pain treatments is critical.
    Chronic pain is highly comorbid with mental health problems, such 
as post-traumatic stress disorder and depression; and chronic use of 
prescription opioids for non-cancer chronic pain is higher among and 
increasing faster in patients with mental health and substance use 
disorders than in persons without those diagnoses.\27\ The VA and NIH 
initiative exploring nondrug approaches to managing pain and related 
health conditions includes thirteen research projects totaling 
approximately $21.7 million over 5 years. Some of the research being 
funded by this initiative include:
---------------------------------------------------------------------------
    \27\ Edlund MJ, et al. Trends in use of opioids for chronic 
noncancer pain among individuals with mental health and substance use 
disorders: the TROUP study. Clin J Pain. 2010;26(1):1-8.
---------------------------------------------------------------------------
  --Testing the efficacy of combining transcranial direct current 
        stimulation with cognitive behavioral therapy for the treatment 
        of pain, opioid use, and related health issues;
  --Use of morning bright light treatment to reduce and help manage 
        chronic low-back pain and improve PTSD symptoms, mood, and 
        sleep;
  --The use of mobile devices to display real-time brain activity that 
        veterans with PTSD and TBI can use to induce relaxation and 
        reduce pain symptoms;
  --An integrated program to improve physical function/reduce 
        disability and decrease rates of chronic opioid use of combat-
        injured veterans with multiple traumatic injuries;
  --Mindfulness-meditation-based pain relief; and
  --Complementary/nonpharmacologic health approaches for managing 
        chronic pain.
    The next generation of research from this funding initiative is 
currently underway and is jointly funded by NIH, the Department of 
Defense, and the Veterans Administration Health Services Research and 
Development. The overall goal of this initiative, titled the ``NIH-DoD-
VA Pain Management Collaboratory'', is to develop the capacity to 
implement cost-effective large-scale pragmatic clinical research in 
military and veteran healthcare delivery organizations focusing on non-
pharmacological approaches to pain management and other comorbid 
conditions.
    The NIH intends to commit $2 million in fiscal year 2017 to fund 
one coordinating center. Collectively, the agencies intend to commit 
$3.5-$4.25 million annually to fund approximately 5-7 2-year UG3 
(Planning Phase) awards, and $5.65-$6.65 million/year to fund 
approximately five 4-year subsequent UH3 (Implementation Phase) 
Demonstration Projects, contingent upon budget considerations and 
receiving scientifically meritorious applications.
    To develop non-addictive pain treatments, NIDA is one of multiple 
institutes of the NIH supporting research into novel pain treatments 
with reduced potential for abuse and diversion, including abuse 
resistant opioid analgesics, non-opioid medication targets, and non-
pharmacological treatments. Some of the most promising potential 
therapies include:
  --Non-Opioid Medications: Potential drug targets that could allow for 
        pain relief without the addictive properties or overdose risk 
        of opioids, by targeting different molecular pathways within 
        the nervous system with promising preliminary data include 
        fatty acid binding proteins, the G-protein receptor 55, 
        cannabinoids, and transient receptor potential cation channel 
        A1;
  --Abuse-resistant opioid analgesics: New compounds that target opioid 
        signaling pathways in different ways than traditional opioids 
        may allow for analgesic effects without the rewarding and 
        respiratory-depressing effects of existing opioid 
        medications.\16\
  --Nervous Stimulation Therapies: These include transcranial magnetic 
        stimulation and transcranial direct current stimulation, as 
        well as electrical deep brain stimulation, spinal cord 
        stimulation, and peripheral nerves/tissues stimulation--have 
        shown promise for the treatment of intractable chronic pain. 
        These devises have been approved by the FDA for treatment of 
        other conditions but more research is needed on their 
        effectiveness for pain.
  --Neurofeedback: Neurofeedback is a novel treatment modality in which 
        patients learn to regulate the activity of specific brain 
        regions by getting feedback from real-time brain imaging. This 
        technique shows promise for altering the perception of pain in 
        healthy adults and chronic pain patients and may also be 
        effective for the treatment of addiction.
    Finally, a public-private collaborative research initiative is 
being launched by NIH to develop new, safe, and effective strategies to 
prevent and treat pain, opioid addiction, and overdose in half the time 
it currently takes. The initial plan for this initiative was recently 
described by Dr. Collins and National Institute on Drug Abuse Director 
Nora D. Volkow, M.D., in the New England Journal of Medicine \28\ and 
includes three major areas for advancement: (1) safe, more effective, 
and non-addictive strategies for chronic pain management to prevent 
misuse of and addiction to prescription opioids; (2) new and innovative 
opioid addiction treatments to reduce drug use and support recovery; 
and (3) overdose reversal interventions to reduce mortality and promote 
access to treatment.
---------------------------------------------------------------------------
    \28\ Volkow, N. D. and F. S. Collins (2017). ``The Role of Science 
in Addressing the Opioid Crisis.'' New England Journal of Medicine.
---------------------------------------------------------------------------
    We are currently developing a draft strategy that will include 
major goals of the initiative, action steps, key partners, 
deliverables, timeline, and resources to fully carry out the proposed 
action steps. Input on final draft will be solicited from participants 
including Federal partners as well as other relevant stakeholders. Upon 
final approval of the plan, it will be posted on the NIH website at: 
Https://www.nih.gov/opioid-crisis.
                                 ______
                                 
           Questions Submitted to Joshua Gordon, M.D., Ph.D.
              Questions Submitted by Senator Patty Murray
     the impact of funding cuts on select diseases--mental illness
    Question. Dr. Gordon, what would a cut of almost $600 million or 23 
percent mean for efforts to find more effective treatments for the 44 
million Americans who suffer from mental illness?
    Answer. Mental illnesses are significantly impairing and can be 
life-threatening. In 2015, an estimated 43.4 million U.S. adults 
reported having a mental illness in the past year.\29\ Based on recent 
estimates, mental illnesses accounted for 21.3 percent of all years 
lived with disability in the United States.\30\ These stark statistics 
serve as an important reminder of how essential it is to make continued 
progress in scientific research that will illuminate the causes, and 
corresponding treatments, of mental illnesses.
---------------------------------------------------------------------------
    \29\ Center for Behavioral Health Statistics and Quality. (2016). 
Key Substance Use and Mental Health Indicators in the United States: 
Results from the 2015 National Survey on Drug Use and Health. (HHS 
Publication No. SMA, NSDUH Series H-51). Retrieved from http://
www.samhsa.gov/data.
    \30\ US Burden of Disease Collaborators. The state of US health, 
1990-2010: burden of diseases, injuries, and risk factors. JAMA, 
310(6): 591-608, 2013.
---------------------------------------------------------------------------
               integrating healthcare for mental illness
    Question. Dr. Gordon, during a hearing on mental health in 
February, one of our witnesses, David Johnson, the CEO of Navos Mental 
Health Solutions, noted that the total cost of care per patient could 
be reduced 35 percent in plans that integrated services between primary 
and behavioral healthcare, which is significant. Despite our efforts, 
it does not appear that there has been an appreciable improvement in 
treatment or reduction in prevalence of most forms of mental illness. 
How do we address this problem? Should we rebalance the NIMH research 
portfolio to include more focus on research and training to reduce the 
public health burden of mental illness? In recent years, NIMH has 
prioritized neurobiological mechanisms of mental illness and 
development of pharmaceuticals rather than basic behavioral research 
that could improve our understanding of mental health and lead to 
treatments to address the immediate mental health conditions of the 
population.
    Answer. As the new Director of NIMH, I spent the last year working 
with Institute leadership to refine NIMH priorities and continuing to 
ensure that our research portfolio is balanced. NIMH must invest in 
research that has the potential to improve clinical care over the 
short, medium, and long-term. While it is essential to deeply 
investigate the brain and its interactions with the environment to 
build our knowledge base and search for the truly transformative 
treatments of tomorrow, we must not neglect opportunities to fully 
investigate new treatment targets as they arise. Nor can we forget that 
research is often needed to help currently available, efficacious 
treatments reach all patients who need them.
    For over two decades, NIMH has invested in research to support 
systems of care that integrate mental and physical healthcare--
Collaborative Care. In a Collaborative Care system, patient populations 
are screened and closely tracked in a registry that is used to monitor 
symptoms and inform evidence-based practices. A care manger, a 
psychiatric consultant, and other mental health professionals work 
collaboratively to support mental health treatment within primary care. 
Collaborative Care models have also been shown to improve treatment of 
mental disorders among people with co-occurring medical problems 
treated in primary care settings.\31\ This is critical because 
untreated mental disorders are common in patients seen in primary care 
settings; so much so that primary care is considered the de facto 
mental health service system in the United States. As well, findings 
from over 80 randomized controlled trials robustly support the 
effectiveness of the Collaborative Care model to improve depression, 
anxiety, post-traumatic stress disorder, suicide prevention, and other 
mental disorders in pediatric, adult, and geriatric populations.\32\
---------------------------------------------------------------------------
    \31\ Https://www.ncbi.nlm.nih.gov/pubmed/16675360.
    \32\ Https://www.ncbi.nlm.nih.gov/pubmed/23076925.
---------------------------------------------------------------------------
    From the perspective of NIMH, the science behind Collaborative Care 
is clear: it is an effective model of care delivery. Our current focus 
is assisting other Federal agencies in understanding the evidence and 
allowing it to guide policy decisions.
    The Mental Health Research Network (MHRN) serves as NIMH's 
prototype of a learning healthcare system, and includes large-scale 
pragmatic trials and services research.\33\ The 13 healthcare systems 
that comprise MHRN integrate services to improve the speed, efficiency, 
generalizability, and uptake of mental health research and treatment 
for 13 million beneficiaries across the country. MHRN's population-
based approach to mental healthcare combines expertise in mental health 
research as well as epidemiology, health services, economics, 
disparities, outcomes, and quality assessment. One such study is 
examining the use of electronic medical health records by primary care 
providers to identify appropriate care and control cardiovascular risk 
factors for patients with serious mental illness (SMI).\34\
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    \33\ Http://hcsrn.org/mhrn/en/.
    \34\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9312868&icde=35162345.
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    NIMH also funds research on the detection and treatment of general 
medical conditions in individuals with SMI.\35\ Common modifiable 
health risks associated with premature mortality, such as elevated 
blood pressure, A1C glucose, and BMI, as well as smoking and obesity, 
often go undetected and untreated in individuals with SMI. NIMH is 
funding studies on effective strategies to reduce obesity, improve 
fitness, promote smoking cessation and improve cardiometabolic risks in 
people with SMI.\36,37,38,39\ In August 2016, NIMH funded three large- 
scale trials in youth with SMI to test population-based approaches to 
preventing and reducing cardiometabolic risks at the earliest possible 
opportunity.\40\
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    \35\ Http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
060.html.
    \36\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8764463&icde=22739367.
    \37\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8764228&icde=22739259.
    \38\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8764333&icde=22739523.
    \39\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8763974&icde=22739601.
    \40\ Http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
060.html.
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    Routine screening is essential for early detection of mental 
illnesses and subsequent referral to treatment. In 2016, the United 
States Preventive Services Task Force updated its recommendations 
regarding depression to include screening for depression in the general 
adult population, and especially among persons with chronic illnesses. 
NIMH supports research on effective methods for identifying individuals 
with depression and other mental disorders, and on effective 
interventions for treating mental disorders in both general medical and 
specialty care settings. For example, NIMH funds studies on integrating 
depression screening and care into OB/GYN settings for pregnant women, 
and delivering online therapy for depression and anxiety to adult 
primary care patients.\41,42,43\
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    \41\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9253314&icde=35019783.
    \42\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9046911&icde=35019783.
    \43\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=9086425&icde=35019827.
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                                 ______
                                 
           Questions Submitted by Senator Christopher Murphy
                                  nimh
    recovery after an initial schizophrenia episode (raise) project
    Question. Last year I worked with Senators Alexander, Murray and 
Cassidy to pass a major mental health reform bill as part of the 21st 
Century Cures bill. This bill made a clear statement from the Congress 
about mental health is both important and bipartisan. However, the 
stigma around mental illness continues and I believe that stigma 
extends to the research community. Unfortunately, the administration 
has proposed a cut of about $360 million to the National Institutes of 
Mental Health (NIMH) budget.
    The NIMH budget justification notes that we have made progress in 
reducing untreated psychosis through the Recovery After an Initial 
Schizophrenia Episode (RAISE) project. Specifically it states that 
coordinated specialty care (CSC)--a team-based, multi-component 
treatment program for individuals with first episode psychosis--
produced superior clinical and functional improvements compared to 
typical care, especially among clients with shorter duration of 
untreated psychosis. Despite this success, the budget proposed a 20 
percent cut to this effort.
    Dr. Collins and Dr. Gordon, what is the rationale behind the 
overall cut to NIMH and to this specific initiative? Shouldn't we be 
building on the improvements that were made last year in the Mental 
Health Reform and send a signal to researchers that this is an 
important area by investing in programs that have been shown to be 
effective?
    Answer. The mental health reforms in the 21st Century Cures Act 
promote and support Federal and state mental health and substance 
misuse initiatives, programs, and services. Specifically, the Act 
requires states to use Federal block grant funds on evidence-based 
practices such as coordinated specialty care (CSC), which was examined 
in the NIMH-supported Recovery After an Initial Schizophrenia Episode 
(RAISE) project. As noted in the NIMH budget justification, findings 
from RAISE indicate that CSC for first episode psychosis (FEP) produced 
superior clinical and functional improvements compared to typical care, 
especially among clients with shorter duration of untreated 
psychosis.\44\
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    \44\ Https://www.ncbi.nlm.nih.gov/pubmed/26481174.
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    To build on the successes of RAISE, in May 2016, The National 
Institute of Mental Health (NIMH) reissued funding opportunity 
announcements seeking projects aiming to reduce the duration of 
untreated psychosis.\45,46\ Specifically, NIMH aims to support research 
that tests strategies for reducing the duration of psychosis among 
persons with FEP by eliminating bottlenecks or closing gaps in the 
pathway to CSC services. NIMH currently funds eight such studies aiming 
to reduce the duration of untreated psychosis. Early identification of 
FEP, rapid referral to evidence-based services, and effective 
engagement in CSC are essential to shortening the duration of untreated 
psychosis, pre-empting the functional deterioration common in psychotic 
disorders, and reducing the economic burden of these devastating 
illnesses on society.
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    \45\ http://grants.nih.gov/grants/guide/pa-files/PAR-16-264.html.
    \46\ Http://grants.nih.gov/grants/guide/pa-files/PAR-16-265.html.
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    Additionally, NIMH launched the Early Psychosis Intervention 
Network (EPINET), with the goal of creating a learning healthcare 
system among early psychosis treatment clinics.\47\ EPINET clinics will 
create a common database with information gathered during routine 
clinical encounters, with patients' consent. EPINET will allow 
clinicians and researchers to learn more about the effectiveness of 
early psychosis treatment and accelerate studies of psychosis risk 
factors, biomarkers of illness, and pre-emptive interventions.
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    \47\ 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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    The initial phase of EPINET, which included identification of 
valid, reliable, and feasible measures to support standardized clinical 
assessment and outcome evaluation in early psychosis clinics, was 
completed in January 2017.\48\ The second phase of EPINET is underway 
and aims to identify feasible strategies for harmonizing clinical data 
collection across community-based treatment programs for FEP. An NIMH-
sponsored meeting on data harmonization across CSC programs is planned 
for September 2017. The meeting will bring together key stakeholders, 
including FEP researchers, representatives of state mental health 
authorities, clinical providers and program administrators, and members 
of mental health advocacy groups.
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    \48\ Https://grants.nih.gov/grants/guide/notice-files/NOT-MH-17-
009.html.
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    Overall reductions in the NIMH budget would be distributed across 
all programmatic areas and basic, translational, and clinical 
research--including programs focused on reducing the duration of 
untreated psychosis.
                             warning signs
    Question. Dr. Gordon, we are now a couple weeks removed from a mass 
shooting that injured Rep. Steve Scalise and others. The courage and 
professionalism of law enforcement saved the lives of many Senators, 
Members, staff, and ordinary citizens. We continue to have mass 
shootings perpetrated by individuals with troubled pasts but we also 
know that individuals with mental illness are more likely to be the 
victim of violence than the perpetrator.
    What have we learned about how to recognize the warning signs from 
those who might be at risk to commit an act of violence? What research 
is being done to help those at risk? Lastly, where do we go from here 
to provide better mental health research and services to those in need?
    Answer. Tragic mass shooting events often focus the nation's 
attention on gun violence, mental illness, and the sometimes-difficult 
balance of ensuring personal freedoms while protecting public safety. 
Following the recent shooting that injured Rep. Steve Scalise, the FBI 
reported that the perpetrator did not have a history of mental illness.
    Indeed, individuals with serious mental illness (SMI) are no more 
violent than the general population when symptoms are controlled. 
Notably, violence among people with SMI is more likely to be self-
directed (e.g., suicide) than directed towards others, and people with 
SMI are 11 times more likely than the general population to be victims 
of violence. When substance abuse is combined with untreated SMI, there 
is an increased risk of violence, but risk of violent behavior among 
people with SMI is reduced with appropriate treatment.\49,50\
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    \49\ Https://www.ncbi.nlm.nih.gov/pubmed/9596041.
    \50\ Https://www.ncbi.nlm.nih.gov/pubmed/16061769.
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    Recent, publicized acts of mass violence often involved young 
people whose illness was either not detected and/or not appropriately 
treated. Studies find a substantial delay between the onset of 
psychotic symptoms and the initiation of care; in the U.S., treatment 
is typically delayed between 1 and 3 years.\51,52\ As such, evidence-
supported approaches to early detection to initiate treatment and 
facilitating sustained engagement in effective care are key strategies 
for preventing violent acts among young people with SMI and for 
reducing long-term disability and functional impairment, in general. A 
current NIMH initiative is focused on reducing the duration of 
untreated psychosis.\53,54\ NIMH also funded six studies to develop and 
test interventions to improve the care of persons at clinical high risk 
for psychotic disorders.\55,56,57,58,59,60\ Several of the researchers 
conducting these studies presented their findings at an NIMH and SAMHSA 
co- sponsored meeting in July 2017 on Implementing Early Intervention 
Services for Clinical High Risk for Psychosis in U.S. Community 
Settings: What Do We Know and What Do We Need to Know?
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    \51\ Https://www.ncbi.nlm.nih.gov/pubmed/16143729.
    \52\ Https://www.ncbi.nlm.nih.gov/pubmed/25588418.
    \53\ Https://grants.nih.gov/grants/guide/pa-files/PAR-16-264.html.
    \54\ Https://grants.nih.gov/grants/guide/pa-files/PAR-16-265.html.
    \55\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8789627&icde=22682321.
    \56\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8789633&icde=22682325.
    \57\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8789537&icde=22682326.
    \58\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8786741&icde=22682332.
    \59\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8789569&icde=22682334.
    \60\ Http://projectreporter.nih.gov/
project_info_description.cfm?aid=8786233&icde=22682335.
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    In response to the shooting at Sandy Hook Elementary School in 
Newtown, CT, NIH called for research on the health determinants and 
consequences of violence and its prevention, particularly firearm 
violence.\61,62,63\ In fiscal year 2015, NIH funded nine grants, four 
with a focus on mental health outcomes. One such NIMH-funded study is 
examining emergency department discharge practices that include 
counseling on limiting access to guns during times of mental health 
crisis.\64\ Another NIMH-funded study is exploring the relationship 
between inflammation in the brain and aggression.\65\
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    \61\ Https://grants.nih.gov/grants/guide/pa-files/PA-13-363.html.
    \62\ Https://grants.nih.gov/grants/guide/pa-files/PA-13-368.html.
    \63\ Https://grants.nih.gov/grants/guide/pa-files/PA-13-369.html.
    \64\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=8806202&icde=27520350.
    \65\ Https://projectreporter.nih.gov/
project_info_description.cfm?aid=8887832&icde=27520350.
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    While these and many other NIH-funded studies are promising, 
continued support of research focused on the improvement of services is 
needed to ensure that those most in need receive evidence-based 
treatment. Risk factors for violence among those with mental illness 
are largely the same as for those without mental illness. These risk 
factors include substance abuse, family conflict, early social and 
emotional isolation, school failure, as well as early and persistent 
delinquent behavior among youth. In the future, NIH will continue to 
support research to develop practical tools for clinicians and patients 
to monitor violence risk, allowing them to take action to prevent 
violence, including suicide.

                          SUBCOMMITTEE RECESS

    Senator Blunt. The record will stay open for 1 week for 
additional questions. And the subcommittee will stand in recess 
until June 27th at 10:30 a.m.
    [Whereupon, at 11:29 a.m., Thursday, June 22, the 
subcommittee was recessed, to reconvene at 10:30 a.m., Tuesday, 
June 27.]