[Senate Hearing 116-]
[From the U.S. Government Publishing Office]




 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2020

                              ----------                              


                        THURSDAY, APRIL 11, 2019

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

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR
ACCOMPANIED BY:
        ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        GRIFFIN P. RODGERS, M.D., M.A.C.P., DIRECTOR, NATIONAL 
            INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
        JON LORSCH, PH.D., DIRECTOR, NATIONAL INSTITUTE OF GENERAL 
            MEDICAL SCIENCES
        DOUGLAS LOWY, M.D., ACTING DIRECTOR, NATIONAL CANCER INSTITUTE
        NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE


                 opening statement of senator roy blunt


    Senator Blunt. The Appropriations Subcommittee on Labor, 
Health and Human Services, Education, and Related Agencies will 
come to order.
    This is always a good hearing for us. I think, in the 4 
years that Senator Murray and I have worked on this committee 
together, we clearly have made NIH one of our priorities, and 
we're glad it has been.
    We have increased funding by $9 billion, a 30 percent 
increase over 4 years, and hopefully we are not done with that 
process yet, but hearing what you are doing with that money 
always helps encourage us to not only make those dollars 
available, but even more.
    We have seen real progress in vaccine research from Ebola 
to Zika, we have seen the development of blood tests to detect 
different kinds of cancer earlier than had been before, the 
first-ever drug used specifically for postpartum depression has 
been developed during this period of time. Obviously, what is 
happening in immunotherapy, which at our first hearing was 
something that had to be explained to all of us and even a few 
of your colleagues, as it was developing in the amazing way it 
has already.
    I think we have seen ways that you have found to encourage 
young researchers and hopefully we will be able to hear a 
little more about that today, as well.
    In my home State of Missouri, research has demonstrated 
that interactive therapy can reduce rates of childhood 
depression, a discovery of an enzyme responsible for the spread 
of cancer, and we have seen research supported that aimed at 
improving the scaling-up of immunotherapy and how to make that 
more available in a more affordable way for more people.
    I am disappointed of course, that the 2020 budget request 
would cut the agency by 13 percent. I am confident that this 
committee will not do that, but we will talk to you today about 
the reasons that we should continue in the direction we are in, 
rather than head in another way.
    I am deeply concerned about an issue that I have seen 
develop, and I hope Dr. Collins, you have a chance to talk 
about that too. It is something that the research community 
needs to take more seriously, and that is that foreign 
governments are initiating systematic ways to influence our 
research, and frankly, to take advantage of our research by 
stealing it.
    There is a Chinese Government program to recruit NIH 
(National Institutes of Health) funded researchers to encourage 
them to steal intellectual property; cheat the peer review 
system; establish shadow laboratories in China; and help the 
Chinese Government obtain confidential information about NIH 
research grants. That cannot continue to happen, and I look 
forward to hearing your discussion of that issue.
    Obviously, there is an important balance here, of 
protecting our research from both foreign threats and other 
kinds of piracy and having the kind of collaborative 
environment you want to have to bring the best people into that 
research community you can. I know that is a challenge, and I 
have seen some challenges that you have faced even recently on 
that topic of who should be there and where they should be, but 
we benefited from them, they have benefited from us. This is a 
system that has worked, and we need to be sure we continue to 
protect it. Not everyone is well-intentioned.
    I know there is an ongoing FBI investigation, and that it 
is investigating specifically what the Chinese government is 
trying to do to undermine our research structure. This is a 
serious threat to all of the things that make that structure 
work.
    The NIH Advisory Committee has recommended several steps, 
including implementing a broad education campaign about the 
requirements to disclose foreign sources of funding, and 
developing enhanced cybersecurity protocols.
    And while I appreciate those recommendations, I think that 
NIH has to be sure that the research community is fully aware 
of the threats, and more importantly, how to combat those 
threats.
    NIH has sent only one letter to the community on the 
subject, but I am going to let you talk about that a little 
more either in your prepared remarks, or later in questions. It 
is a vulnerable environment. It is a critically important time 
to look to the future. A number of individuals that are part of 
the so-called Thousand Talents program may be few, but I think 
we should not just assume that that is the only program out 
there trying to do exactly the same thing, either.
    So, Dr. Collins, certainly, I am pleased with the 
relationship you have had with this committee, with your 
leadership, I admire the team that you and your colleagues have 
put together. I am excited about the opportunity of the moment 
and glad you are here with us again today.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Good morning. Thank you, Dr. Collins and the Institute Directors, 
for appearing before the Subcommittee today to discuss the National 
Institutes of Health's fiscal year 2020 budget request.
    As Chairman of this Subcommittee, re-prioritizing funding for the 
National Institutes of Health after a decade of stagnation has been my 
number one priority. Over the past 4 years, we have increased funding 
by $9 billion or 30 percent.
    This increase has funded significant progress on vaccines for Ebola 
and Zika, developed blood tests to detect different types of cancer, 
and led to the first-ever drug specifically for postpartum depression. 
In my home State of Missouri, NIH research has demonstrated that 
interactive therapy can reduce rates of childhood depression, 
discovered an enzyme responsible for the spread of cancer, and 
supported research aimed at improving cancer immunotherapy.
    I am disappointed the fiscal year 2020 budget request cut the 
agency by $4.9 billion or 13 percent. This is not a choice I will make 
when we write the fiscal year 2020 Labor/HHS appropriations bill.
    While my commitment to biomedical research remains strong, I am 
deeply concerned about an issue I think NIH and the entire research 
community needs to take more seriously. Foreign governments are 
initiating systematic programs to influence the American research 
enterprise.
    There is a Chinese government program to recruit NIH-funded 
researchers to steal intellectual property, cheat the peer-review 
system, establish shadow laboratories in China, and help the Chinese 
government obtain confidential information about NIH research grants.
    I understand and support the need to balance protecting against 
foreign threats with the collaboration and open access that has long 
been prioritized in the medical research community. And in almost every 
case, talented foreign researchers have benefited the U.S. research 
community and moved medical research forward. As I have said many 
times, I believe that any foreign student coming to the United States 
for advanced education should be able to stay in the U.S. after that 
training is complete.
    However, we must recognize that not everyone is well intentioned. 
We know from an ongoing FBI investigation that the Chinese government 
is trying to undermine the U.S. research infrastructure. This is a 
serious threat to NIH peer-review system, to universities and research 
institutions' intellectual property, and to corrupting a system that 
has long been held as the gold standard in research worldwide.
    The NIH Advisory Committee has recommended several steps, including 
implementing a broad education campaign about the requirement to 
disclose foreign sources of funding and developing enhanced 
cybersecurity protocols. While I appreciate the Advisory Committee's 
recommendations, I do not think NIH has made the research community 
fully aware of the exact threats they face, and more importantly, how 
to combat them. In fact, NIH has only sent one letter to the community 
on the subject. The research community needs to understand that this is 
a serious, immediate, and specific threat, and that some foreign 
governments will use any means necessary to obtain a competitive 
advantage over the U.S.
    In this vulnerable environment, I think it is prudent for NIH to be 
even more cautious about ensuring systems and protocols are in place to 
protect the research community. But I am unconvinced that is happening 
now.
    Moving forward, I want to see clear steps taken to ensure all NIH 
grantees are trained to understand their roles and responsibilities 
within current policy. NIH needs to evaluate their peer-review system 
and internal controls through a lens that takes into account national 
security threats. And, finally, those who inappropriately share 
information from the peer-review process or illegally share 
intellectual property need to be held accountable.
    While the number of individuals that are part of China's Thousand 
Talents program may be few, this program has uncovered a systematic 
flaw. We must take this threat seriously and NIH should take definitive 
steps today to maintain the integrity of the NIH system.
    Thank you.

    Senator Blunt. I would like to turn to Senator Murray for 
her opening comments.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Well thank you very much, Mr. Chairman. Dr. 
Collins, good to see you and all of your team. Thank you to all 
of you for being here today and for the work you are doing.
    The National Institutes of Health is perhaps the best 
example of an issue, where members on both sides of the aisle 
have been able to come together. We have repeatedly worked in a 
bipartisan way to provide increased investment in research that 
improves the health and well-being of people, invests in our 
local communities, and supports our Country's continued 
leadership in science.
    NIH is the largest funder of basic research in the world 
and I am very proud that Chairman Blunt, thank you, and I, and 
others on this committee have been able to increase its budget 
by $9 billion over the last 4 years, despite opposition, by the 
way, from the Trump Administration.
    Now we are here today to talk about President Trump's 
latest budget, and it stays true to form and proposes severe 
cuts across the spectrum of healthcare activities. In his 
budget, President Trump proposes steps that would undermine 
healthcare protections for 130 million people in this country 
living with a pre-existing condition. It strips healthcare away 
from tens of millions of people and we should not forget he is 
arguing in court for a ruling that would do all of that and 
more.
    President Trump's budget proposes slashing the Centers for 
Disease Control and Prevention, including their work on birth 
defects and disabilities, their efforts to combat antibiotic 
resistant pathogens, and emerging infectious diseases and more. 
It slashes funding for the healthcare workforce training 
programs at a time when our Nation is facing a healthcare 
provider shortage, particularly in our rural areas, and it 
proposes eliminating funding for the Teen Pregnancy Prevention 
Program and cutting funding for rural health and maternal and 
child health.
    And at a time of remarkable possibility in medical 
research, a time where we can and should continue leading the 
world in medical discovery, the Trump administration wants to 
cut funding for NIH.
    President Trump's budget offers one small step forward for 
pediatric cancer research and a marathon sprint backward for 
everything else.
    While he proposes increasing pediatric cancer research by 
$50 million, he proposes cutting $100 million, twice that 
amount, from diabetes research. He proposes cutting $300 
million, six times that amount, from Alzheimer's research, and 
he proposes cutting over $1 billion, 20 times that amount, from 
efforts to discover treatments for every other kind of cancer. 
In fact, for every new penny President Trump proposes for 
pediatric research, he proposes cutting a dollar from NIH. He 
would cut funding from just about everything, which would mean 
delaying, or even missing opportunities to find treatments and 
cures that could save lives, like a universal flu vaccine, or a 
vaccine for HIV.
    President Trump's damaging budget is wildly out of step 
with the sentiments of Congress, thankfully, and the American 
people, and I feel confident working with our chairman that we 
will once again reject it.
    Now, I do want to say that with that support for NIH, 
however, comes the expectation that NIH will lead in all the 
fields in which it is involved, including setting the highest 
standards for the behavior of the research community it funds.
    Last summer, the National Academies of Science, 
Engineering, and Medicine released a report that found sexual 
harassment is common in all three fields.
    Dr. Collins, you and I have had numerous discussions about 
this. The report found that almost half of women in medical 
school or enrolled as a graduate student in a college of 
medicine, and more than half of women faculty in academia 
reported having experienced some form of sexual harassment.
    The Academies recommended Federal research agencies require 
institutes to report when people on grants have violated sexual 
harassment policies or have been put on administrative leave 
due to harassment allegations. A recommendation the National 
Science Foundation has since adopted.
    NIH needs to step up and demonstrate greater leadership in 
holding its partners and extramural grantees accountable, as 
well. It is not acceptable for NIH to defer to its grantee 
institutions or other agencies to address harassment, rather 
than actually requiring them to report when it happens in 
research settings, or by researchers funded by NIH grants, 
especially when NIH's funding gives the agency such sway with 
the research community.
    Harassment undermines scientists and researchers 
professional and educational obtainment and erodes the 
integrity of the research enterprise. It makes survivors feel 
inferior or that they do not belong, and it draws promising 
young scientists away from research at great cost to our Nation 
and our scientific advancement.
    I expect more from NIH on this issue, and Chairman Blunt 
and, Dr. Collins, I would like to work with you both on 
direction that requires NIH to take meaningful action to 
address harassment that occurs in both intramural and 
extramural settings, including implementing recommendations 
from the Academies report, some of which the National Science 
Foundation has already done.
    Thank you, Mr. Chairman.
    Senator Blunt. Thank you, Senator Murray. As Senator Murray 
pointed out, the committee has worked hard on this together, as 
Senator Durbin, Senator Alexander, great advocates, along with 
Senator Shaheen, and Senator Moran, but the two people at the 
top of the committee have also been incredibly important in 
encouraging us to move forward.
    I might point out that it is not just the current budget, 
the past administration actually proposed cutting NIH research 
at a time or two, and never proposed, as far as I know, 
increasing it, at least it did not get increased. So, we have 
sort of had a bipartisan determination to correct a bipartisan 
failure to move forward for a long time. We are going to 
continue to do that and one of the reasons we will be able to 
do that is the great leadership of the Chairman, who joined us 
today.
    And Chairman Shelby, do you have some comments?

                 STATEMENT OF SENATOR RICHARD C. SHELBY

    Senator Shelby. Thank you. Thank you, Chairman Blunt, 
Ranking Member Murray.
    First, I would like for my written statement to be made 
part of the record.
    Senator Blunt. Without objection.
    Senator Shelby. And I will be very brief. I am going to 
tell you, and I agree with those Senator Blunt and Senator 
Murray, this is an important hearing. What you do is more 
important than most of what we do in America. I am not 
interested in cutting your budget, I am interested in 
increasing it; so, are they. We are going to have a big 
struggle this year, dealing with the budget, but I think this 
is a great investment for America, for the world, for humanity, 
what you do.
    Sitting at the table here, all of you distinguished in your 
own right; we are fortunate to have you, to have your 
dedication and we are going to stay with you, and we are going 
to continue to do it.
    I believe it is not only a financial investment, which is 
good for the economy, it is the leading scientist at cutting 
edge of scientific research that you had. We all benefit from 
it immensely.
    Thank you, Mr. Chairman.
    [The statement follows:]
            Prepared Statement of Senator Richard C. Shelby
    Dr. Collins, I want to thank you and your colleagues for coming 
today to give us updates on the great work that you are doing at the 
National Institutes of Health (NIH).
    I have enjoyed our conversations in the past about the importance 
of research, and I applaud the job that you have done as Director of 
the NIH.
    Research institutions in Alabama have done some wonderful 
advancements with the funding they receive from the NIH.
    Not only do our institutions in Alabama reap the benefits by 
attracting the brightest minds to perform the research, but the Alabama 
economy as whole capitalizes on the above average wages of researchers 
and the buying power they add to local businesses.
    It is important to Alabama and the rest of the country that we 
continue to increase funding for medical research at the NIH. America 
needs to remain at the forefront of advanced medical research, and 
investigators want to know that Congress is committed to pursuing new 
treatments and cures.
    Thank you all for coming today, and I look forward to asking you 
some important questions.

    Senator Blunt. Well, thank you, Chairman.
    Again, Dr. Collins, welcome to you and the directors of 
several of the institutes that are with you today. We look 
forward to hearing what they have to say as well, but if you 
would like to start with your opening statement, this would be 
the time to do that.

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

    Dr. Collins. Well, thank you.
    Let me introduce the people at the table. On my left, your 
right, starting over at the end, someone well known to this 
particular panel of Senators. We estimate this might be about 
his 400th hearing, Dr. Tony Fauci, Director of the National 
Institute of Allergy and Infectious Diseases.
    Next to him our Director of the National Institute on 
Aging, Richard Hodes. Then next to me, Dr. Griffin Rodgers, 
Director of the National Institute of Diabetes, Digestive and 
Kidney Diseases. On my right, Jon Lorsch, Director of the 
National Institute of General Medical Sciences. Next Doug Lowy, 
who has stepped back into the role as now Acting Director of 
the National Cancer Institute, as Dr. Sharpless has moved over 
to FDA (Food and Drug Administration) just in the last few 
days. And then on the end of the table, Dr. Nora Volkow, 
Director of the National Institute on Drug Abuse. I am honored 
to have these colleagues with me today for what I hope is going 
to be a really important exchange of ideas and information.
    So, Chairman Blunt and full committee Chair Shelby, Ranking 
Member Murray, members of the subcommittee, I want to thank you 
most sincerely for your strong and consistent, and bipartisan 
support of NIH. In fiscal year 2019 we received a most welcome 
increase of $2 billion, enabling us to continue our mission of 
turning scientific discovery into healing and hope, and we will 
have a chance to tell you about some of those things in the 
course of this hearing.
    I take very seriously the comments that were raised by the 
Chairman about foreign influence, and by the ranking member 
about sexual harassment. These are issues of incredible 
intensity and importance and I hope we can discuss some of 
those in the course of the questions.
    But I wanted to introduce you today to just a few of the 
millions of people who over the years have made medical 
research progress possible by volunteering to take part in NIH 
funded research. Instead of focusing on the researchers, I am 
going to focus on our really important partners, the people who 
take part in these clinical studies, and tell you something 
about three examples of them.
    [The graphic follows:]

    
    

    Let's begin with Richard Hockfelder. Six years ago, this 
retired aerospace engineer had a blood test called hemoglobin 
A1c that showed that he was at high risk of developing 
diabetes, a pre-diabetes diagnosis. So, he took some 
preventative steps like cutting down on carbohydrates and 
exercising more to get his health back on track and that work 
really well.
    [The graphic follows:]

    
    

    Now he could have kept that success to himself but instead 
he decided to help others and he joined NIH's All of Us 
research program, which is building an unprecedented resource 
to explore what health approaches work best for each 
individual, and why. This is precision medicine on a scale we 
have never attempted before.
    [The graphic follows:]

    
    

    We are making great progress toward enrolling our goal of 1 
million or more people. And you can see from the graph where we 
are in less than a year, more than 200,000 people have, in 
fact, begun enrollment, and about 50 percent of those are from 
traditionally underrepresented racial and ethnic minority 
groups. Because we want very much to have an opportunity with 
this resource to understand health disparities, it is a very 
diverse population.
    [The graphic follows:]

    
    

    Now all the information that they contribute of various 
types, will go into a highly secure database that researchers 
can get access to, to make discoveries. Success is going to 
depend on involvement of people from all walks of life, so we 
encourage you to join too. All you have to do is go to 
joinallofus.org, and anybody in our country can join this 
effort. And we do hope by the next 3 years to take this already 
quarter of a million and bring it to a million people. This is 
unprecedented. It is already the largest study that we have 
mounted in a very long time and we are only a quarter of the 
way there.
    [The graphic follows:]

    
    

    Let me turn to another example of somebody who has 
volunteered to help us with research. This is Frank Stevens. 
Frank belongs to a community with unique biological 
characteristics that has been offering to volunteer for 
research for years, but too often has not really had that 
opportunity. I am talking about individuals with Down Syndrome. 
We need to do better for them.
    [The graphic follows:]

    
    

    Frank actually did testify before Congress in October 2017, 
that is where this picture is taken. Now Down Syndrome usually 
results from having an extra chromosome 21, each year about 
6,000 babies are born with this condition in the U.S., and the 
average life span has doubled in recent years, but these folks 
still face significant health challenges. They include an 
increased risk of heart defects, of leukemia, of immune 
problems, of autism, and Alzheimer's disease.
    [The graphic follows:]

    
    

    On the other hand, interestingly, Down Syndrome individuals 
have a lower risk of coronary artery disease and a lower risk 
of solid tumors, even when you age-match. We do not know why 
that is and it would be very important to figure that out.
    So, because of this studying Down Syndrome may hold the key 
not only to helping those who have the condition, but also to 
understanding common diseases in all people. And this is a good 
example how rare diseases can inform about things that go well 
beyond that particular condition. NIH is stepping our efforts 
to do just that.
    [The graphic follows:]

    
    

    This should come as good news to Frank and his Mom, you see 
here vacationing, and his mom Cornelia, actually herself, has 
already shown signs of Alzheimer's disease. Frank faces a 
greatly increased risk of that because of his Down Syndrome, 
but his Mom already has it, and he wants to try to help her as 
well. As Frank once put it, ``My extra chromosome provides a 
blueprint for medical research that could reveal answers to 
this heartbreaking disease.''
    [The graphic follows:]

    
    

    Well speaking of heartbreaking diseases, I told this 
subcommittee last year that we might be on the verge of a cure, 
I used the C word, cure, for sickle cell disease. A life-
threatening genetic disorder that bends red blood cells into a 
sickled shape because of a mistake in the gene that codes for 
one of the hemoglobin proteins, and they are bending then into 
this sickled shape that blocks blood vessels, causing 
excruciating pain in a sickle cell crisis, and damage to 
organs, which sadly shortens the lives of people with this 
condition, substantially.
    So, we talked about last year, maybe we are on the brink of 
something, today I am thrilled to say, I think we have reached 
a remarkable milestone.
    [The graphic follows:]

    
    

    Let me introduce you to Janelle. Janelle Stevenson is one 
of the brave research participants who has helped make this 
happen and whose story was recently featured on CBS's 60 
Minutes. Throughout her young life, as you can see, she was 
often hospitalized, even at, Christmas; you see there with 
Santa Claus next to her bed and has experienced over the course 
of her 20 years, just about the worst pain that a human can 
imagine from these crises.
    [The graphic follows:]

    
    

    But she decided to take a bold step for herself and for 
others with this condition and signed up for a gene therapy 
trial at the NIH Clinical Center. This trial, her own bone 
marrow stem cells were removed; modified to compensate for that 
sickle mutation, and then infused back into her body where they 
began producing healthy red blood cells. The transformation has 
been pretty incredible.
    Here is Janelle, sitting alongside her father, Ray wearing 
her white jujitsu uniform. And here she is--remember this is 
somebody who was pretty much almost bedridden before this 
procedure [Video shown].
    So, our Nation needs a lot more stories like this, but that 
one certainly heartening to anybody who has wondered are we 
going to come to an answer for that first molecular disease, 
sickle cell. We have known about it for more than 100 years and 
now, a molecular cure for that molecular disease in a very 
rigorous research protocol, and the treatment was challenging 
to endure, but you can see this is working.
    The promise is now real for the nearly 100,000 Americans 
who suffer from this devastating disease.
    [The graphic follows:]

    
    

    So, we need a lot more stories like this through the 
generosity and courage of people like Richard, Frank, and 
Janelle, along with your strong and sustained support. NIH 
research is making it possible for these kinds of stories to 
emerge every day and the world can look forward to a healthier 
and happier future.
    So, thank you, Chairman. We 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.
    Before I discuss NIH's Budget request for the upcoming fiscal year 
and some of the exciting scientific opportunities on the horizon, I 
want to express my gratitude to the leadership and members of this 
Subcommittee. In fiscal year 2019, NIH received an increase of $2 
billion.I can promise you that we are investing those resources in 
groundbreaking research as quickly as we can.
    Biomedical research at NIH seeks to push forward the frontier of 
knowledge, from basic science to translational research to clinical 
trials, and success relies on vision, risk-taking, and a tireless 
pursuit of the next scientific question. NIH will continue to invest in 
people, programs, infrastructure, and technology with these goals in 
mind, consistently striving for breakthroughs that culminate in 
improvements in human health and wellbeing. From harnessing new 
technologies to supporting the next generation of researchers, NIH will 
invest its resources to ensure that the U.S. remains at the forefront 
of innovation and discovery.
    The fiscal year 2020 President's Budget provides $34.4 billion for 
NIH, seeking to fund the highest priority scientific discoveries while 
also maintaining fiscal stewardship of Federal resources. This Budget 
will prioritize biomedica l research to confront our Nation's greatest 
medical challenges, including the opioid crisis, precision medicine, 
and pediatric cancer.
    As in previous years, the Budget proposes to streamline Federal 
research by consolidating activities of the Agency for Healthcare 
Research and Quality (AHRQ) into a new National Institute for Research 
on Safety and Quality (NIRSQ) within the NIH. The Budget provides NIRSQ 
$256 million to support its activities to improve the quality, safety, 
effectiveness, and efficiency of healthcare.
    America's continuing leadership in biomedical research requires 
infrastructure and facilities capable of housing safe, reproducible 
research in compliance with all laws and regulations and conducive to 
cutting edge research. NIH buildings include inpatient hospital beds, 
Biosafety containment facilities, biomedical research laboratories, 
animal holding facilities, and even a utility plant. NIH's backlog of 
maintenance and repair now exceeds $1.8 billion.
    NIH is aggressively using fiscal year 2019 funding to address some 
of this backlog and ensure our facilities are both safe for patients 
and conducive to cutting-edge research and research support. The fiscal 
year 2020 Budget invests in NIH's facilities by again proposing $200 
million to support multiple biomedical research infrastructure 
priorities at NIH-owned sites.
    One of my personal priorities since joining NIH has been to develop 
and support the next generation of biomedical researchers. In August 
2017, NIH launched the Next Generation Researchers Initiative to 
address the challenges faced by researchers trying to embark upon and 
sustain independent research careers. I am pleased to report that NIH 
met its ambitious goal of funding 1,100 early-stage investigators in 
fiscal year 2018. In fact, we funded 1,287, the largest number in 
history. The fiscal year 2020 Budget includes a dedicated fund of $100 
million in the Office of the Director to support the prioritization of 
meritorious applications to support early stage investigators that have 
never been funded by an award, or current NIH- supported researchers at 
risk of losing support. NIH remains committed to the development, 
support, and retention of our next generation of investigators.
    This is a remarkable time in biomedical research. Truly exciting, 
world class science is taking place through NIH support, and leading to 
breakthroughs in multiple areas. I would like to provide just a few 
examples of the depth and breadth of the amazing research the fiscal 
year 2020 Budget supports.
    The fiscal year 2020 Budget continues to invest in Precision 
Medicine. Less than 1 year ago, NIH formally launched national 
enrollment for the All of Us Research Program. This program is on pace 
to enroll one million or more U.S. volunteers in an ambitious effort to 
accelerate health research and medical breakthroughs. With this 
Committee's long-standing support, we are closer than ever to building 
the most diverse biomedical data resource of its kind. By analyzing 
individual differences in lifestyle, environment, and biology, 
researchers will uncover paths toward delivering precision medicine, an 
emerging approach for disease prevention and treatment.
    As of April 7, 2019, more than 212,000 people have begun the 
enrollment process, and more than 129,000 have completed all the steps 
in the protocol. The All of Us Research Program is committed to 
engaging individuals from all walks of life, including those who may 
not have been asked to participate in research previously, and more 
than 75 percent of participants are from communities that have been 
underrepresented in biomedical research. This diversity has the power 
to revolutionize standards for inclusivity in research and for 
generalizability of biomedical research findings across many 
communities, with the ultimate goal of spurring discoveries that bring 
the promise of precision medicine to all of us. The fiscal year 2020 
Budget provides $313 million to support the All of Us Research Program.
    Millions of Americans across the Nation have been devastated by 
opioid misuse, addiction and overdose. To help bring scientific 
solutions to this crisis, and to provide safe and effective options for 
the more than 25 million Americans who suffer from daily chronic pain, 
NIH launched the Helping to End Addiction Long-term (HEAL) Initiative. 
This Committee made a historic investment of $500 million in our work 
in fiscal year 2018 and built upon that investment in fiscal year 2019 
with an additional investment of $500 million. Through HEAL, NIH will 
build on basic science discoveries to accelerate the development of 
novel medications and devices to treat all aspects of the opioid 
addiction cycle, including chronic use, withdrawal symptoms, craving, 
relapse, and overdose. NIH has launched a series of new studies to test 
both new non-addictive medications and non-pharmacologica l strategies 
for pain management, with the goal of targeted treatments for the 
millions of Americans living with chronic pain. The fiscal year 2020 
Budget continues the special investment of $500 million that was 
started in fiscal year 2018, and supports a total of $1.3 billion for 
opioids and pain research across NIH, ensuring that we continue to 
respond aggressively to the crisis of pain and addiction in our 
communities.
    Cancer is the leading cause of death from disease among children 
and adolescents in the United States. Although substantial progress has 
been made in the treatment of several types of childhood cancer, 
progress against other types has been limited. Even when long-term 
survival is achieved, many survivors of childhood cancer may experience 
long-term adverse effects from the disease or its treatment. More 
research is needed to develop new, more-effective, and safer treatments 
for childhood cancer. The President recently launched an initiative to 
support pediatric cancer research. The fiscal year 2020 Budget provides 
$50 million for a data initiative that will support the development of 
new, more effective, and safer treatments for childhood cancers, and 
will facilitate aggregation of data to create a federated, 
comprehensive, and shared resource to support childhood cancer 
research.
    First identified in 1981, AIDS is one of humanity's deadliest and 
most persistent epidemics. Although significant progress has been made 
in the fight against new infections and AIDS deaths, the HIV/AIDS 
pandemic continues around the world. The development of a safe and 
effective HIV vaccine remains a key component to realizing an end to 
the HIV/AIDS pandemic. The NIH-wide HIV research program will continue 
to sustain the accomplishments already made and secure future advances 
to prevent the spread of HIV; improve health outcomes for persons with, 
at risk for, or affected by HIV; and ultimately to find a cure for HIV. 
The fiscal year 2020 Budget includes $6 million for NIH to support the 
President's Ending HIV Epidemic Initiative. The NIH-funded Centers for 
AIDS Research and AIDS Research Centers are leveraging critical 
relationships with local and State public health services, communities, 
and research institutions to develop and refine evidence-based, 
community-specific strategies that will help guide this initiative.
    The fiscal year 2020 Budget continues to invest in research 
progress toward the important but scientifically challenging effort to 
develop a universal influenza vaccine. NIH-supported research is 
helping advance understanding of how influenza strains emerge, evolve, 
infect, and cause disease. These research results are informing design 
of new and improved therapies, diagnostics, and vaccines. Influenza 
viruses pose an ever-present public health threat and place substantial 
health and economic burdens on the U.S. and the world. The fiscal year 
2020 Budget will accelerate research progress to achieve the end goal 
of a universal influenza vaccine, which is vital to protecting millions 
of people from infection and mitigating the public health threat posed 
by influenza viruses.
    NIH is at the vanguard of biomedical research, leading the world in 
support of groundbreaking science. Thank you again for inviting NIH to 
testify today. We look forward to answering your questions.

                           FOREIGN INFLUENCE

    Senator Blunt. Thank you, Dr. Collins.
    Why don't we talk a little bit about the efforts you have 
made on the concern about foreign involvement, about duplicate 
labs in other countries, and information being shared that 
should not be, and then what we are going to do about it.
    Dr. Collins. I would be glad to do that. We are deeply 
concerned about the evidence which has been growing and which 
we have become increasingly aware of over the course of more 
than a year, that there are instances, egregious instances, 
where our funding of grants in this country is being taken 
advantage of by individuals who are not following the 
appropriate rules. This is utterly unacceptable.
    We have had multiple opportunities to interact with the 
FBI, who have been investigating this vigorously. Some of this 
is classified information, some of it is not. And as a result 
of that have uncovered what has now led to more than 55 
investigations that are ongoing of institutions where we 
believe there may be investigators who are double dipping, 
receiving foreign government money without disclosing it, or in 
some instances, diverting intellectual property that was 
rightly the property of the institution where they are working, 
to China. Or, maybe most egregiously at all because it violates 
such an important principle for us, taking grants that they are 
asked to review as part of the peer review process and 
distributing those to another country even before those grants 
have gone through the full review process, giving therefore an 
opportunity for somebody else's ideas to be stolen.
    Knowing the seriousness of this, I did something 
unprecedented and wrote--first time since I have been NIH 
director, to every one of our grantee institutions, and that is 
more than 10,000, a very strongly worded letter saying this is 
an issue they all need to take with great seriousness, and if 
they are not aware of what their own faculty are doing in terms 
of these kinds of relationships, need to begin to find that 
out.
    I think there was initially some surprise and maybe even 
denial that that could be happening in these institutions. I 
think we are past that now and we are now seeing statements 
from some of those institutions, very strongly worded to their 
own faculty saying, we realize we have a problem too. There 
increasing instances where faculty members have been fired, 
have been asked to leave the institution, many of them then, 
returning back to their previous foreign base. And I should say 
while China has certainly been mentioned a lot, this is not 
only China.
    So, actions are being taken and you will see more evidence 
of that in the press, and particularly in the coming week or 
two, to show just what is now necessary in order to respond to 
this. We will not rest until we have looked at every possible 
example. We have to depend on the universities as our partners 
in this, but we are driving this process as vigorously as we 
can.
    Senator Blunt. Within those 55 instances, how many 
different institutions would that involve?
    Dr. Collins. That is 55 institutions.
    Senator Blunt. 55 different grantee institutions?
    Dr. Collins. Yes, and basically, we are triggered by noting 
in a grantee that there is a publication that comes out that 
seems to involve a lot of authors and a lot of other 
institutions that were not mentioned in their grant 
applications. Now, maybe that is an appropriate collaboration; 
I am not going to tell you that every one of these 
investigations is going to reveal something bad happened, but 
some of them will.
    Senator Blunt. Well, we clearly benefit from having people 
from other countries here; to have their skill level here. 
Frankly I think we benefit to have them, if they want to stay 
here, to let them stay here.
    Dr. Collins. Absolutely.
    Senator Blunt. It is difficult to look at this from the 
point of view of where somebody comes from, but no matter where 
they come from, if they are involved in this, we are going to 
have to obviously be at a higher level of on-guard, than we 
have been.
    Dr. Collins. Mr. Chairman, I am totally with you, as are my 
colleagues. I am glad you raised, though, the concern though 
that we not carry this to the point where anybody who is a 
foreign national begins to feel like they are under suspicion, 
even if they are honorable contributors to our workforce, 
because almost all of those folks are. We need to be careful 
that we do not step into something that almost seems a little 
like racial profiling.
    I think Chinese scientists working in the U.S. have already 
written some letters to Science Magazine to express their 
concern about not being swept into this same framework where 
everybody is under suspicion, because the vast majority of 
these folks have been incredibly important and honorable 
contributors to our workforce.
    Senator Blunt. Now, there is a research synergy that you 
achieve by bringing people together from totally different 
preparation, styles, and everything else into that research 
moment, I think.
    Dr. Collins. Yes. Diversity contributes to productivity in 
every way, and all kinds of diversity that is true, including 
gender diversity, including people from different socioeconomic 
backgrounds, and from different countries.
    Senator Blunt. Yes. I am sure we are going to have lots of 
questions. Let's try to stay with the 5-minute time, but we 
can, anybody that wants to stay beyond their first round, we 
will get to as many questions as we can possibly get in between 
now and the time we are done.
    Senator Murray.

                              DATA COMMONS

    Senator Murray. Thank you very much, Mr. Chairman.
    You know, many research organizations are now exploring the 
best ways to create research data commons. Private sector 
communities of companies and extramural research institutions 
like, science bound networks, Penn State, and Google's 
datacoms.org have demonstrated success, while other Federal 
agencies are already further along than NIH in successfully 
establishing data commons, like the National Science Foundation 
big data innovation hubs. It is really important that we learn 
from them, as well as from some less successful attempts at 
driving data instruction, like CA Bigg, which saw very little 
traction in the community and was widely criticized.
    So, Dr. Lorsch, let me start with you. What is NIH doing to 
avoid reinventing the wheel, and how is NIH planning to 
leverage data commons work that is already being done 
extramurally?
    Dr. Lorsch. Thank you very much Senator. That is a very 
important question. If we can connect disparate types of data, 
so, say data from the Jackson Heart Study with data from Dr. 
Hodes' Alzheimer's disease databases, the power of that could 
be enormous in terms of generating new ideas, new connections 
between these diseases, or in that case, between cardiovascular 
health and dementias, for example. That might lead to new ideas 
about treatments that could be possible or earlier detection 
strategies.
    This is what we call interoperability, making data that is 
in different languages, essentially, able to talk to each other 
so the scientists can use that data for these kinds of 
discoveries.
    We are working very closely right now with our partners in 
academia, as well as experts in the tech industry, particularly 
through the STRIDES Initiative, which is an arrangement with 
Google and Amazon that we have right now, to develop ways to 
connect the high-value data sets that NIH has, the Jackson 
Heart study, for example and Alzheimer's data together, to 
create this interoperability.
    We are definitely looking at past examples, both successful 
and unsuccessful, to help guide us, and we are definitely 
taking a lot of input from experts, particularly in the tech 
industry through that STRIDES initiative.

                      DATA SCIENCE IN OTHER FIELDS

    Senator Murray. Okay. Dr. Collins, what is the agency doing 
to really encourage and support data science training in other 
scientific fields beyond those like genomics and neuroscience, 
which really have embraced this?
    Dr. Collins. I appreciate that you are raising this issue, 
and John Lorsch has been very much a leader in the space.
    You see here our website, which will show you our strategic 
plan for data science, which has been a way in which we have 
tried to put together a lot of ideas. I totally take your point 
about not reinventing wheels that have already been tried 
either successfully, or otherwise. So, I think we are pretty 
well invested in that.
    And certainly, a big part of this is training. We are 
seeking to bring more fellows to NIH to bring the skill sets 
that exist in Silicon Valley and get them excited about 
biomedical research, because that is where a lot of the talent 
is. We are recruiting a chief data strategist, probably 
somebody from the private sector, to help us with that kind of 
culture change and recruiting of talent that we know we need. 
We need our bench to be a lot deeper, we aim to get it there.
    Senator Murray. Okay, good. Thank you. I really appreciate 
it.

                         NCI AWARD PERCENTAGES

    Dr. Lowy let me turn to you. While Congress has been 
providing the NIH, including the National Cancer Institute, 
with more funding each of the past 4 years, the odds of 
securing a grant from NCI (National Cancer Institute) have 
actually been getting more difficult. Can you tell us what is 
driving that trend and what its significance is, and do you 
expect it to continue?
    Dr. Lowy. Thank you very much, Senator Murray. Thanks to 
the generosity of Congress, we have received an increase in our 
appropriation for the last several years, approximately 17 
percent through 2018, to the regular appropriation during that 
time. During that time we have increased the number of awards 
made for investigator initiated research by about 20 percent, 
the number of new people in the awards system and the NCI by 20 
percent, and so this is, I think, very much in line with what 
you and your colleagues have had in mind.
    On the other hand, we have had over that period a 50 
percent increase in the number of grant applications, and so it 
has not been possible to keep up with the number of awards that 
we would like to make, although we are very pleased we have 
been able to make more.
    It has led to the success rate for investigator-initiated 
research going from 15 percent down to a little bit below 12 
percent during that time period, and we certainly hope that we 
will be able to increase the success rate going forward. For 
example, this year we are planning to put in more money to the 
RPG (Research Project Grant) pool than even with the generosity 
of Congress is, has added to the NCI regular appropriation.
    Senator Murray. Okay thank you, very much. I appreciate 
that.
    Senator Blunt. Senator Shelby.

                       PUBLIC SECTOR PARTNERSHIPS

    Senator Shelby. Thank you.
    Dr. Collins, you previously said that the private sector 
research outspends public sector research three to one; three 
to one. To prevent overlap, investigators in the public and 
private sector, I believe, should coordinate research where 
they can so that efforts would not be duplicated so much. I 
know there is an accelerated medicines partnership, AMP, going 
on, you have talked about it before. Would you give us an 
update on this and how we are working together to get the good 
results?
    Dr. Collins. I am happy to talk about that. Yes, I think it 
is a great opportunity to bring the best and brightest of skill 
sets in terms of scientists and also the areas of expertise. 
NIH is in the basic science in translational arena, but we do 
not make pills and the industry does, and we have to figure out 
how to do that hand-off so that this ecosystem really 
flourishes.
    I get invited each year to a meeting of the heads of 
research and development of the largest pharmaceutical 
companies; we just met this past weekend. And we have 
developed, I think, a very functional working relationship 
there to identify opportunities for shared collaborative 
precompetitive efforts, and AMP that you just mentioned, the 
Accelerating Medicines Partnership, is one of those which I 
think has been particularly successful.
    This allowed us to come together around several diseases, 
and that includes Alzheimer's disease, and rheumatoid 
arthritis, and lupus, and diabetes, and basically to work 
together to identify whether there were areas that we could as 
a group do, that neither could do alone, yet make all the data 
available. We have to do that, we are NIH.
    In those projects which are now almost 5 years along, we 
have met every milestone, and everybody who is involved would 
say we have accelerated the progress in finding new treatments 
for those diseases.
    Everyone is a little different in terms of the particular 
science that is being supported. My colleagues here are a part 
of that so, Dr. Rogers oversees the NIH part of the diabetes 
effort, Dr. Hodes oversees the part of the Alzheimer's effort, 
Dr. Carter, who is not here, the rheumatoid arthritis and 
lupus, and we have just started a new one on Parkinson's. And 
we are talking about a new one on schizophrenia where we 
desperately need some new ideas, and industry after being a 
little reluctant before, is now looking as if they could 
embrace that, too. There is a separate project on cancer 
immunotherapy called PACT, which is a relationship we have with 
industry.
    I think we are finding ways, obviously recognizing we have 
different goals, to make that happen and that is a personal 
priority for me to be sure we do not miss those opportunities.

                            CYSTIC FIBROSIS

    Senator Shelby. What about cystic fibrosis? Where are you 
going there, and where do you hope to go? You have come a long 
way.
    Dr. Collins. Well, this is also something I have a personal 
passion about, having had the opportunity to co-discover the 
gene for cystic fibrosis exactly 30 years ago. And now to see, 
although it took 30 years and I wish it had been faster, the 
emergence of highly effective, triple therapy with a very well 
designed molecular-based drugs that looks as if something like 
90 percent of people with cystic fibrosis are now going to have 
a treatment that allows them to live out what could be almost 
normal lives. Which is an amazing thing to be able to say.
    It took a huge amount of work from NIH funded resources to 
try to figure out exactly what the mechanism is for this 
disease, and what kind of drug might work, and then a close 
partnership with a company called Aurora which then became 
Vertex, and now here we are. And it is incredibly gratifying to 
see that for all those kids and families that have been waiting 
for this all this time.
    Senator Shelby. Doctor, you have been very involved in the 
National Center for Advancing Translational Sciences, and so 
forth.
    Dr. Collins. Yes.

                        RURAL HEALTHCARE ACCESS

    Senator Shelby. Could you elaborate on how NIH is 
implementing this program to address healthcare access and 
delivery in rural areas across the country?
    Dr. Collins. So NCATS, the National Center for Advancing 
Translational Sciences, is one of our newest entities. I have 
been very excited to see this emerge, trying to identify ways 
that we can help research projects that sometimes get stuck in 
the valley of death actually move across for benefit to people 
out in the clinics and the hospitals.
    NCATS also runs the CTSAs, the Clinical and Translational 
Science Awards, which is this network of 57 centers across the 
country. But we are aware that those are generally located in 
more urban settings and there is an opportunity and a 
responsibility to reach out to rural communities.
    NCATS has out right now, a notice of interest out there to 
think about how to link up in that way. One possibility is to 
link up with the idea states clinical trial research networks, 
which are also often times more in an opportunity where there 
is a rural setting. And also, to see if there is a way to work 
in the pediatric clinical trial network which is also been put 
forward as part of the effort to deal with the opioid crisis.
    So, we have a lot of connections here that are being built. 
There was a meeting at the University of Florida to talk about 
this two days ago, I am waiting to hear what the results of 
that were.

                             FUNDING LEVELS

    Senator Shelby. Doctor, lastly, could you explain how NIH 
determines funding levels for research within its larger 
funding number, because all of us advocate for certain diseases 
that touch us and touch our friends and family, and 
constituents in many ways.
    Dr. Collins. In the minus 21 seconds I have, let me see 
what I can do to outline.
    [Laughter.]
    Senator Shelby. Well, I think I am over.
    Dr. Collins. It is a critically important question. All of 
us around this table work with that issue virtually every week 
trying to be sure we have our priorities set. I might point you 
to the strategic plan that we put forward a couple of years 
ago, which tries to go through in a very clear fashion how 
those priorities get set.
    May I say, we appreciate the fact that the Congress 
generally does not give us a lot of recommendations about 
specific disease areas, because we think science is in the best 
place to make those decisions along with what the public health 
need is, and that is what we try to do every day.
    Senator Shelby. Mr. Chairman, could I just, not a question, 
make a request? Dr. Vickers invited you to be the keynote 
lecturer, I am sure all over the world, but in Birmingham and 
at the lecture, Academic Leadership Medicine, Academic 
Leadership Series. I hope if you can work that out you would 
go; you have been there before. They asked me to do this and I 
told them I would follow their request.
    Dr. Collins. I will be there.
    [Laughter.]
    Senator Shelby. Okay. Thank you.
    Senator Blunt. That is the right answer, I am sure.
    [Laughter.]
    Senator Blunt. Senator Durbin.
    Senator Durbin. Once again proving all politics is local.

                   RESEARCH INTEGRITY AND STEWARDSHIP

    Dr. Collins, it was about 5 years ago when I visited the 
NIH and you and I had a conversation which informed and 
inspired me about 5 percent real growth a year in funding on 
medical research. The education of a United States Senator is a 
daunting task, and I thank you for taking the time to explain 
to me how consistency is as important as amounts.
    It is a new challenge to you too, in this day and age, to 
justify the amount that is being added each year when I look at 
the record. And I want to give special shout-outs to our 
Chairman here, Senator Blunt, Senator Murray, who just in both 
authorizing and appropriating committees, has been a national 
leader on the subject, and Senator Alexander who is retiring. I 
am hoping that someone with his skill and determination will 
replace him to continue this battle, but since fiscal year 2014 
we have seen the 30.6 percent increase in NIH funding, a 40.6 
percent increase in Department of Defense medical research and 
a 33 percent increase in VA (Department of Veterans Affairs) 
medical research. The CDC (Centers for Disease Control and 
Prevention), 7.4; I wish it could have been more because it is 
a deserving agency.
    But when you answer the question of the Chairman about the 
integrity of the research undertaking and endeavor, 
particularly our concern about falsification of data or the 
stealing of information, I think it really goes to the heart of 
this. Those of us who deeply believe in what you are doing and 
believe it is one of the most important parts of our public 
lives, really need to count on you, as well, to join in in 
proclaiming that integrity is not being compromised and money 
is being well spent. Our critics are going to be watching to 
find evidence to the contrary.
    Would you like to comment on that?
    Dr. Collins. I could not agree more. Let me say, I 
appreciate your beginning your comments about this importance 
of predictable, steady trajectory for support that has been 
such a source of encouragement, particularly to young 
investigators who are seeking to know whether they had a path 
for their careers.
    And frankly, things were looking pretty tough for them, 6 
or 7 years ago as we had lost a fair amount of purchasing 
power. Now to have this, 4 years in a row of a steady upward 
trajectory, has changed the dynamic completely in the 
institutions that I go and visit, where the postdocs, and the 
graduate students, and the junior faculty are now really fired 
up about the opportunity.
    But you are right, this puts great responsibility on us to 
be stewards of every dollar of that and if we find misuse of 
that information, to move swiftly to make sure that that is 
quickly stopped. We are doing everything I think we can in that 
regard, with help from our institutions to root out that 
problem and I think we have made a lot of progress, but we are 
nowhere near done.

                     AMYOTROPHIC LATERAL SCLEROSIS

    Senator Durbin. I would like to get more specific and 
personal in this next question. Tuesday morning a young man 
from Chicago named Brian Walleck, and his wife Sondra came in 
to see me. A year and a half ago, 18 months ago, he was 
diagnosed with ALS, Lou Gehrig's disease, and they wanted to 
come and talk to me about their determination to try to spark 
more interest, more research, more focus on this disease.
    Sadly, the life expectancy of those diagnosed is not long 
and they fear that many of the people who are the most 
passionate advocates will not be here long enough to fight the 
good fight and see good results.
    What can you say to the couple and others that face this 
particular disease?
    Dr. Collins. This is a particularly critical and 
heartbreaking condition, as you well know. We have redoubled 
our efforts to try to take advantage of some of the newer 
discoveries to come up with clinical applications. There is a 
consortium now called CReATe, which is Clinical Research in ALS 
and Related Disorders for Therapeutic Development.
    We have been heartened by the success, which, I think I 
talked to this committee last year of a gene therapy for the 
infantile version of ALS called spinal muscular atrophy, which 
actually has worked quite well. And now the question is could 
that same approach be successful, at least for some individuals 
with ALS where we know what the genetic mutation is, and there 
are families where that is the case.
    That is a big area of focus at the present time, but not 
the only one. So, we at least now have a consortium to put all 
the ideas that we can come up with into this space. It is a 
very hard problem, but I think our chances are better now than 
ever to make some real forward motion and maybe even some 
breakthroughs.

                     MATERNAL AND INFANT MORTALITY

    Senator Durbin. Thank you. My last point is this, as we are 
dazzled by your work and the breakthroughs in cystic fibrosis 
and other things, we also face the grim reality that this great 
Nation, this United States of America, maternal and infant 
mortality rates are absolutely unacceptable, particularly among 
some segments of our population. We cannot forget the basics 
here, and I know you are not, and I hope that you will be able 
to tell us--I have run out of time now, but in some other 
context, the work that is being done in these two particular 
areas.
    Dr. Collins. I would be glad to for the record, give you 
quite a summary of all the things that are happening there, 
particularly supported by National Institute of Child Health 
and Human Development which also covers maternal health. We 
agree that is a very high priority.
    Senator Blunt. Thank you, Senator Durbin.
    Senator Moran.

                            PEDIATRIC CANCER

    Senator Moran. Thank you, Mr. Chairman. Dr. Collins, thank 
you and your colleagues for joining us today and for the work 
that you and your team across the country, do.
    Let me start with Dr. Lowy. Doctor, the President has 
proposed a Pediatric Cancer Research Initiative, safer 
treatments for children, and better data.
    What can you tell me about the challenges we face in 
fighting cancer among children, as compared to adults? Are 
there sufficient numbers of children who were willing to 
participate in clinical trials? What are the issues that are 
unique to childhood cancers?
    Dr. Lowy. Thank you Senator Moran. One of the most 
important things to understand is that children who have cancer 
are not just small people who have adult cancer, but childhood 
cancer is qualitatively different. Whereas adult cancer has 
many mutations, often there are just are a few mutations that 
arise in children with cancer.
    In addition, while there is a tremendous amount of interest 
in cancer treatment for adult cancer, there is less involvement 
in the private sector, so that NCI has a particular obligation 
to do research in this area, and we have substantially 
increased the amount of research that we do in this area over 
the last few years.
    The particular proposal from the President is really along 
the lines of something that Senator Murray was asking about, 
which is how to efficiently and constructively aggregate data. 
And the goal as we envision it is to take pediatric cancer as 
an example, where some of the information is still quite 
siloed, and by aggregating it and pulling it together with an 
interoperable system, to be able to address important questions 
in pediatric cancer.
    Fortunately, in the terms of participation in clinical 
trials, a high percentage of children with cancer participate 
in that and a lot of that is through the Children's Oncology 
Group sponsored by the National Cancer Institute, and because 
all childhood cancers are rare cancers this is actually an 
international effort that is part of the COG.

                          ALZHEIMER'S DISEASE

    Senator Moran. Thank you. Thank you very much.
    Dr. Hodes, we have recently seen a number of late stage 
clinical trials focused on addressing Alzheimer's, that have 
shut down, highlighting the difficulty in achieving meaningful 
progress in combating Alzheimer's. What is your view on the 
current state of Alzheimer's research? Where is the future 
potential? And, maybe that is the questions.
    Dr. Hodes. Well, beginning with the failures in recent 
clinical trials, of course all of us are deeply disappointed at 
them, and these are efforts that are generally been targeted at 
amyloid protein individuals who already have symptoms. There 
are cases where there is very strong evidence to think that 
this amyloid pathway still may be important, in particular, in 
some of the early onset familial cases, but also by targeting 
earlier in disease, and so we are pursuing those specific 
areas.
    But in addition, thanks very much to the increased funding 
that has come from Congress over past years, our understanding 
of the processes underlying Alzheimer's has improved 
enormously. Last year, for example, some 32 new genes were 
identified, more than had previously identified all around.
    This has led to the ability to identify from those genes, 
bioinformatics, sys-biology, new targets. The number of targets 
is illustrated, Francis, we actually have a visual to look at. 
This is meant to show at stages from drug discovery, drug 
development, the phase one/two trials, the phase three trials, 
starting at the left the early stage of discovery, each of 
those bars represents a different kind of target currently 
under study. You can see the number of targets whether its 
inflammation or protein trafficking or proteostasis, that we 
are discovering more and more about as potential avenues.
    So, the more targets we approach, the greater the 
probability and individuals with particular syndromes that we 
are going to have success. Out of some 35 clinical trials now 
ongoing, 13 are targeting amyloid, the rest have this multitude 
of targets.
    So, a new generation of investigators, new science is 
leading us to this multitude of opportunities to make sure we 
have the way paved for a multitude of approaches to Alzheimer's 
disease.

                      NEXT GENERATION RESEARCHERS

    Senator Moran. Dr. Collins, the new set of scientists, the 
next generation, I cannot think of the young lady's name on 
your screen years ago, but you highlighted her as somebody we 
are going to lose because of the instability in research 
funding. And while I suppose we are always looking for the 
concrete evidence that the funds have resulted in a cure or a 
treatment, perhaps in the interim, between now and when we find 
all those cures and treatments, you can reassure me that the 
investment led by this subcommittee has made a difference in 
keeping, retaining, and encouraging young people to pursue 
careers in science and research.
    Dr. Collins. I can, and I appreciate the question very 
much. Yes, that was a young woman as a graduate student at MIT 
who was about ready to give up.
    That was a while ago and look at this curve which shows you 
our ability, thanks to you, to be able to ratchet up the awards 
that we have given to early stage investigators, that is people 
who have not previously been a principal investigator on an NIH 
grant. In 2013, that was a little less than 600, last year we 
challenged all the institutes to try to really push this 
forward and get us to 1100, we got to 1,287, by far the largest 
in history. We have made this a priority and every one of those 
individuals represents somebody with a lot of energy, a lot of 
innovative ideas. This is the most important investment we 
could make.
    Senator Moran. Senator Shelby would have asked had he not 
run out of time, but on his behalf, I would ask if you would 
come to Kansas.
    [Laughter.]
    Senator Blunt. Thanks Senator Moran.
    Senator Shaheen.
    Dr. Collins. I am going to be on a lot of airplanes here, I 
can tell.
    [Laughter.]
    Senator Shaheen. Well thank you, Chairman and Senator 
Murray for holding this important hearing, and thank you Dr. 
Collins and to all of you, for the amazing work that you do.

                            OPIOID EPIDEMIC

    I want to begin with you Dr. Volkow, because as I know you 
are aware, we have a horrible epidemic in this country of 
substance misuse, and in New Hampshire we have been 
particularly hard-hit. I appreciate your coming up and meeting 
with some of the folks in New Hampshire who address this 
challenge.
    Can you talk about what you are doing at NIDA (National 
Institute on Drug Abuse) that might give us some hope that 
there are additional medications, there are additional 
therapies on the way that might be able to help us address this 
epidemic?
    Dr. Volkow. I think my microphone is not working, so can I 
borrow yours?
    Indeed, this has become an area of priority area, and not 
just for NIDA but for the whole NIH and multiple institutes are 
working on it. And we have different strategies of research 
that are relevant to actually address a crisis.
    With respect to medication development, for example, it has 
been a unique opportunity to bring in the expertise from the 
NCATS (National Center for Advancing Translational Sciences) 
Institute, the translational institutes, but also even from the 
expertise that comes from the NIAID Institute as it relates to 
that development of immunotherapies for addiction.
    There are some exciting projects that are likely to bring 
us more rapidly alternatives like extended release formulation 
that improve the compliance of patients with their medications. 
We are also very interested in developing new tools that can be 
more effective in reversing overdoses that we are seeing, and 
people are reporting a higher dose of naloxone is needed to 
reverse overdose, when individuals are overdosing with drugs 
like fentanyl.
    In the field of expanding access to treatment, we now know, 
and we do not need to do anymore research, that medications are 
extraordinarily effective in preventing relapse, and in 
preventing the overdosing, and in preventing infectious 
diseases, including hepatitis C, or in outcomes in Neonatal 
Abstinence Syndrome, but they are not being used.
    The part of the problem is stigma, but another part of it 
is that we do not have sufficient infrastructure. So, we are 
working with researchers to develop models of care that they 
can advance the healthcare system, on the one side, and adjust 
the setting on the other one. These two systems have been 
almost like different universes. So, we are using the funding 
that we are getting to bring them together and figure out how 
we can come with models of care that will treat the individual 
and sustain them in care.
    And then a third.
    Senator Shaheen. There has been an issue in New Hampshire, 
as you know.
    Dr. Volkow. Yes, I know, and it is also a unique 
opportunity. We look at it in terms of preventing overdoses 
targeting both of them, as well as taking advantage, you just 
made me think, because New Hampshire has been incredible in 
terms of coming up with community solutions.
    Senator Shaheen. Right.
    Dr. Volkow. So, my perspective is how do we learn from 
those community solutions so that we can apply them to other 
States. We have an initiative called the HEALing Communities 
study that aims to do that.
    And finally, an extremely important aspect that we have to 
keep in mind when we are addressing the crisis is research for 
prevention. And why is that so? Because if we do not prevent 
opioid use disorders, or we do not do interventions to prevent 
other addictions, we will be changing one for the other.
    So, we have a very broad portfolio that covers these three 
different buckets.
    Senator Shaheen. Thank you very much.

                           DIABETES RESEARCH

    Dr. Rodgers, as you know, diabetes is one of the most 
expensive diseases in this country, and I was very disappointed 
to see that the President's budget actually called for a $280 
million decrease in funding for NIDDK (National Institute of 
Diabetes and Digestive and Kidney Diseases).
    I wonder if you could--I do not think this committee will 
go along with that. I think we appreciate that investment in 
addressing diabetes research will help us in the long term to 
be more cost-effective, as well as to address the challenge 
that folks with diabetes face.
    Can you talk about some of the breakthroughs that you are 
looking at now in terms of the artificial pancreas, which is 
really the most hopeful innovation to help folks with Type I, 
in particular?
    Dr. Rodgers. Absolutely, thank you for the question. Yes, 
the FDA recently approved what have been truly breakthroughs 
for treatment of patients with type 1 diabetes, such as the 
first hybrid, artificial pancreas and the next generation of 
continuous glucose monitors that no longer require a finger 
stick for calibration, or that those are fully implantable.
    I am happy to report that supported and the Special 
Diabetes Program have contributed to testing of all of these 
FDA approved therapies, and we continue to support cutting-edge 
research in this area. We are supporting advances in artificial 
pancreas in four very large, international clinical trials now, 
conducted at academic medical centers. Research using our 
special business funds is developing the next generation of 
management technologies.
    The goal is to provide the patient and their healthcare 
provider with different options to decide what is the best 
artificial pancreas that could be used for that individual.
    Senator Shaheen. Well, thank you very much. I am out of 
time, but I hope that our healthcare system and our health 
insurance companies will be willing to cover these kinds of 
innovations so people can actually benefit from them.
    Dr. Rodgers. I agree.
    Senator Shaheen. Thank you.
    Senator Blunt. Thank you Senator Shaheen.
    Senator Capito.
    Senator Capito. Thank you. Thank you, Mr. Chairman and 
thank you Dr. Collins and everybody for being here.

                        FUNDING NEW RESEARCHERS

    The first question I was going to ask Dr. Collins, I think, 
has been asked a couple of times. We were really lucky to get 
Dr. Marie Bernard to come. Dr. Hodes was supposed to come but 
doing what he should be doing with his family, and one of the 
doctors in the room, researchers in the room expressed his 
concern about talented young scientists being frustrated with 
not being able to get into the queue.
    So, you gave us the statistics of past had been 600, and 
now 1287, is that?
    Dr. Collins. That is correct. That was for last year and we 
are going to aim to make a very good result this year. We are 
already starting to count these up and make sure that any 
investigator who scores in sort of, the top 25 percent as a 
first-time applicant, ought to have a very good chance, a very 
high chance of getting funded.
    Senator Capito. Would you say those are geographically 
pretty much spread across the country then?
    Dr. Collins. They are, as much as our grant portfolio is in 
general, and of course there are institutions that send more 
grants and others that send fewer, and the IDeA (Institutional 
Development Award) program helps us by balancing that.
    Senator Capito. Right. Right. Thank you.

                   COORDINATING ALZHEIMER'S RESEARCH

    Dr. Hodes, we did have a great visit and you were, as I 
said, well represented by Dr. Bernard.
    One of the things that we talked about during the visit to 
West Virginia University was the work that is being done with 
the other institutes at NIH in conjunction with NIA, the 
National Institute of Aging, on different aspects of 
Alzheimer's. For instance, it was mentioned like a possible 
connection of low blood pressure and decreased cognitive 
impairment.
    Can you talk about what kind of coordinating, you are doing 
at the Institute of Aging when you are looking and researching 
across the spectrum of NIH?
    Dr. Hodes. Thank you. It is a very important question and 
part of the success that we are going to have in addressing 
Alzheimer's disease, or other complex problems, of course, 
would be to recruit the best talent from a diverse area of 
science and expertise. So, along the lines of previous 
conversation, over the past 4 years about one quarter of all of 
the awards have gone to new and early stage investigators. 
About one third have gone to new-to-the-field investigators who 
never even applied for research in Alzheimer's before, and last 
year a particular program, for example, invited grantees of all 
institutes whose research was not Alzheimer's directed, but who 
proposed a supplement to bring their creativity, their 
technology, their genius to the field to do so, and last year 
awarded some 300 supplements.
    This we expect, and we are following up upon, will bring 
these people into the field. We directly fund the research on 
Alzheimer's and related dementias across all the institutes of 
NIH, so about $200 million last year actually supported awards 
to other institutes that are relevant to Alzheimer's and 
related dementias.
    Senator Capito. Yes, I think that obviously brings an 
economy of scale a bit, but knocks down, I am sure like 
everybody else has, silos. I am sure NIH has had silos, not as 
many maybe.
    Dr. Collins. Yes, past tense.
    Senator Capito. Past tense. Yes.
    Dr. Collins. We hope to knock them all down and we did 
pretty well, but we are still watching for them to try to come 
back.
    Senator Capito. Right. Great.

                  NEONATAL ABSTINENCE SYNDROME BABIES

    Dr. Volkow, as you know, my fellow Senator from New 
Hampshire, I know you have been to West Virginia. How many 
times now, two or? Three times and thank you for that visit; 
those visits that the NAS (neonatal abstinence syndrome) 
babies, Lily's Place and others, we do not know what the long-
term effects of all of this is, I do not think. I think a lot 
of it may be in the science of the person's--as the child 
grows, their own health, but there are always external factors 
that are going to be impacting this, what kind of education, 
family life, etc. etc.
    What are you doing with the NAS babies in terms of 
pharmacological research and specialized treatment strategies?
    Dr. Volkow. Yes, and this is one of the priority areas for 
the HEAL initiative, to actually develop better treatment 
interventions that will improve the outcomes for the infants 
and that will lead us to understand better what are the 
consequences on the one hand, for a newborn that has during 
pregnancy their mother was taking opioids, but importantly, as 
they grow up in an environment where the mother may still be 
taking drugs and be subjected to a social deprivation.
    So, on one hand one strategy is can we develop better 
treatments for Neonatal Abstinence Syndrome, and we typically 
treat them with, for example, morphine. Now, it is said that if 
you treat them with that small dose buprenorphine you 
significantly decrease the number of days that they actually 
have to be given the medication.
    Just like we had also shown before that if you treat the 
mother with buprenorphine, as opposed to methadone, you 
decrease almost by half the number of days that you actually--
the infant that is born out of that mother will have with her 
withdrawal symptoms.
    We are also funding research, and again, this is in 
partnerships with other institutes, including the National 
Institute of Child Health and Human Development about non drug 
interventions, and this has emerged out of root grass of 
communities that have had to deal with the problem. And, for 
example there is recognition now that physical contact of the 
infant with the mother, could actually decrease the amount of 
morphine that is necessary to control withdrawal. So, we are 
funding research to develop the evidence about what are the 
optimal interventions.
    And finally, as it relates to your question about what is 
going to happen with these children. There has been already 
some research that shows that in infants that are born out of 
mothers who were exposed to opiates, if you provide a 
supportive environment those children grow up to not have 
evidence of cognitive impairments.
    But we are actually in the planning phases of launching a 
very, very large study that will follow close to 8,000 infants 
as they go from infancy to adolescence to evaluate how exposure 
to drugs influences brain development trajectories.
    Senator Capito. Yes, I mean that sounds very powerful and 
the troubling part is, it has to be a long-term study to be 
able to see the effect and by that time, the effect has taken 
hold.
    Thank you so much for your good work. Thank you.
    Senator Blunt. Thank you Senator Capito.
    Senator Lankford.
    Senator Lankford. Thank you, Mr. Chairman. Thank you all.
    A quick story. I was sitting on an airplane about 3 months 
ago, sitting next to a gentleman flying back to Oklahoma. He 
leaned over, introduced himself as a fellow Oklahoman and we 
chit chatted for a while, and I said, what brings you to 
Washington? He said, ``I come often. I am in an NIH trial, and 
I have been for years'' and he smiled, and he said, ``And, I am 
still here.''
    And from watching his smile and chit-chatting with him on 
the two-hour flight back home, it reminded me again of how many 
people that are still around, just like he said, because of the 
work that you are doing.
    So, thanks for continuing that work and for helping folks 
that, literally for him, as you know, he had been through 
everything to be able to get to your desk, to be able to get to 
that spot. So, we appreciate it very much.

                             BRAIN MAPPING

    Dr. Collins give me an update on the brain mapping. I want 
to walk through several things we talked about in the past. We 
have obviously made significant investments into that. I missed 
the very opening statement of this in a previous thing that I 
had to be able to get to as well this morning. Tell me where we 
are on brain mapping.
    Dr. Collins. I would love to talk about this. This project, 
which began 4 years ago has very ambitious goals to really 
understand, what are the cell types in the brain? There are 86 
billion of those cells, so that is a pretty big challenge. And 
how are they connected together and how do the circuits in the 
brain do the amazing things that they are capable of, and how 
can that go awry and result in disorders like Parkinson's 
disease or epilepsy, or a long list of others?
    We, after 4 years, I would say have met or exceeded every 
one of the milestones that was put in place when the original 
plan for the 10-year program was put forward.
    So, you are asking the question at an appropriate moment. 
Right now, we are having a meeting of all the brain 
investigators at the Marriott at Wardman Park, and this evening 
I will chair a panel that will look at the plan now that is 
being revised, we can call it brain 2.0, of what we might be 
able to accomplish given the platform that has already been 
built.
    It is exciting from what we have already learned in terms 
of new principles about how brain actually does what it does. 
It is exciting by the people that have come into it, and the 
latest couple of rounds of grant awards, more than half of them 
were engineers, who would not necessarily be coming to NIH with 
grant applications, but they are fired up about this too. And 
that interdisciplinary part of this is part of the reason that 
I think it is turning out to be so successful.
    Senator Lankford. Okay, thank you. Well, we will want to 
get a detailed update because we want to make sure it stays on 
track, obviously, but this is a massive project, as you 
detailed before.
    Dr. Collins. Yes.

                      NONADDICTIVE PAIN TREATMENT

    Senator Lankford. You have brought together folks from the 
outside and from private companies to be able to talk about 
alternatives to opioids and developing a nonaddictive pain 
treatment.
    How are the outside groups, private entities, 
pharmaceutical companies, cooperating with you? Is that group 
still together, still working?
    Dr. Collins. Actually, quite well. We have in fact, put in 
place a combination of scientific expertise from academia from 
NIH and from industry, and we are now trying to prioritize what 
may be, is many as 60 or 70 possible therapeutics that would be 
nonaddictive treatment for pain, but which have been slowly 
moving through the pipeline.
    We at NIH are setting up a clinical trial network for 
people with chronic pain syndromes so that these can be tried 
out in a rigorous way, and companies are willing to contribute 
those.
    Senator Lankford. They are staying engaged?
    Dr. Collins. They are staying engaged.
    Senator Lankford. Okay, that was the risk at the beginning, 
to say you are bringing together competitor groups to be able 
to say we have got to sit down and solve this right now, 
together, so.
    Dr. Collins. Yes, I met with the 20 pharmaceutical 
companies that have the largest budgets last weekend and they 
were all on board.

                          DUPLICATIVE RESEARCH

    Senator Lankford. Okay, thank you. Let me read a GAO report 
real quick and I want to be able to get a follow-up from you.
    Their statement was, they talked about VA, CDC, NSF 
(National Science Foundation), DoD, NIH and they said, ``Each 
lack a comprehensive information on health research funded by 
the other agencies, which limits their ability to identify 
potential areas of duplication in the health research they 
fund.''
    They made that comment just looking at the broad picture of 
all of the research that is happening in multiple different 
areas, the Appropriations Committee appropriates.
    How is it working to be able to cooperate with VA, DoD, 
especially large programs, NSF, to make sure, because as you 
would know, grant folks are requesting of everybody. So, they 
will have a slightly different name for similar research and go 
to as many institutions as they can to be able to see if they 
cannot find money to do the research on it.
    How are we doing being able to avoid the duplication and 
communication on agencies?
    Dr. Collins. Senator it is a great question and it is 
something we are quite invested in. We have a whole office of 
portfolio analysis that has now been working at coming up with 
tools to allow us to look, very complicated research portfolios 
what are the areas of overlap?
    We have done that kind of analysis comparing NIH to NSF, 
comparing NIH to the DoD programs, comparing NIH to ARC. It is 
very informative to be able to see that in a visual form, and 
we have in few instances identified places where there was 
duplication and acted upon it.
    We have not yet done this as much for VA, but that is next 
on the agenda. As long as we have access to the abstracts for 
the grants that are being funded, we can do this right away.
    Senator Lankford. You are breaking down silos at NIH. The 
challenge is going to be for us to break down silos in medical 
research across multiple agencies to make sure researchers can 
meet with each other, and we know we've got similar research 
and we are sharing that information, and we are not duplicating 
it.
    I will have a question for the record that I will follow up 
with you, I know you had an interchange with Representative 
Harris on fetal tissue research. HHS is in the process of doing 
a review of all fetal tissue right now and I know there is 
somewhat of a pause going on as they are waiting for that to be 
responded on, but I will do some follow up with some questions 
for the record with you on that as well.
    Dr. Collins. I will be glad to answer for the record.
    Senator Lankford. Thank you.
    Senator Blunt. Thank you, Senator Lankford. We will 
probably have a chance for a second round, if you want to stay.
    Senator Baldwin.
    Senator Baldwin. Thank you, Mr. Chairman.

                 NEXT GENERATION RESEARCHERS INITIATIVE

    Dr. Collins, you and I share a passion on a personal 
priority of investing in our Nation's next-generation of 
researchers. I think most everyone on the subcommittee knows 
from my retelling the story that I was raised by my 
grandparents, and my grandfather was an NIH-funded scientist, a 
biochemist. So, I grew up understanding the importance of the 
contributions of our researchers to biomedical leadership.
    In 2013, I had a particularly powerful meeting with a high 
school student. He was a bone cancer survivor from Fond du Lac, 
Wisconsin, and his name is Ian and Ian told me that cancer 
research helped save his life. He decided at that point that he 
wanted to grow up to be a scientist and to help others who had 
the disease. But he was concerned that it would not be possible 
for him to break in as a new researcher due to NIH funding 
cuts.
    Ian inspired me to author the Next Generation Researchers 
Act with my colleague, Susan Collins, to improve NIH 
opportunities for our new and early-stage researchers.
    I am proud to report to you that Ian has graduated from 
college and is now working in a lab with a scientist at 
Huntsman Cancer Institute in Salt Lake City, Utah studying 
pediatric cancers like osteosarcoma.
    I applaud NIH's progress in implementing my Next-Generation 
Research's Initiative to help support future scientific leaders 
like Ian. In fact, as you noted, NIH funded 1287 early-stage 
investigators in 2018, as part of this work, the largest number 
in history.
    I would love it if you could elaborate on NIH's work to 
implement this initiative since it was signed into law back in 
2016, and your plans for implementing it moving forward, and 
any comments you might have about the National Academies 
Consensus Study Report on the Next Generation of Biomedical and 
Behavioral Sciences researchers.
    Dr. Collins. Well Senator, I really appreciate the way you 
have drawn attention to this critical issue, and we have named 
our initiative the Next Generation Researchers Initiative after 
what you authored, because we were totally in sync with this as 
one of our highest priorities.
    When Ian asked you the question how we were funding, 
according to the graph here if it was 2013, less than 600 
early-stage investigators, and that was a time where it was 
challenging for somebody trying to get their career started to 
have confidence that there was going to be a path forward.
    And notice what has happened since then, thanks to the 
strong support of this committee, and to our prioritizing 
early-stage investigators as the most important applicants that 
we see, and yes, we are now in 2018, up to 1287. We aim to try 
to keep a level in that space going forward. I think that is a 
pretty healthy number. This is not one of those where we want 
to go up and then go back down again, because there is plenty 
of remarkable talent out there.
    So, in addition to, of course, trying to be sure that we 
are doing this in a fashion that attracts really talented 
people, we also are focused on diversity. We want to have more 
women in this category, because we still have not achieved the 
point where our grantee pool is what it could be, given that 
PhD's now are being granted 50-50 to men and women, yet we 
still as first-time applicants to NIH, it is about 30 percent 
that are women.
    We are coming up with ways to try to make this pathway seem 
more appealing, and for us to be more welcoming, and of course 
that means dealing with the sexual harassment issues that 
Senator Murray rightly brought up earlier.
    We did support that report from the National Academy and we 
have strong agreement with many of its recommendations in terms 
of what we need to be doing to sustain this, but as I briefly 
said earlier, I am perceiving, and Ian is a great example, of a 
good deal of the change in the enthusiasm and excitement out 
there in institutions of young graduate students, postdocs, 
junior faculty really see, okay this is a good time to be in 
science, not a time where we have to worry about our future 
quite as much as we did 5 or 6 years ago. So, thank you for the 
way you have supported this.
    Senator Baldwin. Well, thank you.
    I have been concerned that President Trump's budget would 
cut NIH funding by over $4 billion, as years of budget cuts are 
one of the primary factors in discouraging historically, young 
scientists from getting into the field or forcing them to leave 
the field to pursue careers in other countries or in other 
realms. Yet, no investment in my mind promises greater returns 
for America than our investment in biomedical research.
    Will the Next Generation Researchers Initiative deliver on 
its promise and be able to continue to hit such ambitious 
milestones as you are describing, under the administration's 
proposal to reduce overall funding for the NIH?
    Dr. Collins. Well of course, everything we do depends on 
the overall support that we have available. This Congress, and 
this particular subcommittee has been very attentive to that 
and the opportunities that we have had over these 4 years of 
seeing our budgets go up by a total of 30 percent, have made a 
lot of these things possible.
    We always though, have to adjust based upon the resources 
that we have. I will tell you of the institutes at this table 
and the others who are not here, this funding of early-stage 
investigators is one of our highest priorities. We will seek to 
make that happen to the level that we can with the resources 
we've got.
    Senator Baldwin. Thank you and Chairman Blunt and Ranking 
Member Murray, I oppose the President's budget request to slash 
funding for NIH, and I look forward to working with both of you 
to increase funding both for NIH and for a special focus on the 
Next Generation Researchers Initiative in the fiscal year 2020 
budget.
    Senator Blunt. Well thank you, Senator Baldwin.
    Senator Alexander.
    Senator Alexander. Thank you, Mr. Chairman. Dr. Collins and 
your team welcome.
    First I want to once again salute Chairman Blunt and 
Senator Murray, and others who have worked over the last 4 
years for such steady progress in funding for the National 
Institutes of Health. One reason we have done that is because 
we had such great confidence in your leadership and that of 
your team that you would spend the money well. So, it is a 
testimony to you and very important.

                     OTHER TRANSACTIONAL AUTHORITY

    In the opioid's legislation, we did something that you had 
asked us to do when we talked about 21st century cures. That 
was to give you other transactional authority so you could deal 
with such things as a nonaddictive pain medicine.
    The committee that Senator Murray and I are ranking on, we 
recently had a hearing on pain and that exacerbated-- that 
reminded us that when we limit the supply of the most effective 
pain medicine, opioids, to millions of Americans, that causes a 
lot of worry among people who live with pain every day, and 
there are millions of them.
    So, my question is, what have you been able to do with the 
other transactional authority that we gave you to help find new 
nonaddictive painkillers?
    Dr. Collins. It was very helpful, in fact essential, to 
have that kind of authority to move quickly in this space of 
putting together an unprecedented public/private partnership to 
try to speed up the development of those nonaddictive pain 
medicines.
    As I mentioned a couple minutes ago, we are working now 
with pharmaceutical companies who were willing to put forward 
compounds, we are calling them assets, but basically, they are 
untested drug compounds that are ready for clinical trials but 
have been slow moving through that pipeline.
    We then need to do a very quick review of how to prioritize 
these, we cannot test 60 of them, but we might be able to 
ultimately run trials on a dozen or so. Which means we need to 
have a process of review that is very streamlined, and it needs 
to be supported in a way that would be very hard to do with a 
traditional grant mechanism.
    The other transaction authority is exactly the tool that we 
have needed in that space; it has been essential, and so we are 
grateful for it.
    Senator Alexander. Good. Well, there is--I have an even 
higher sense of urgency about the nonaddictive pain medicine 
and treatment and accelerating our effort for that.
    Let me go back to April 2016, you testified before this 
subcommittee and made 10 bold predictions of what might be able 
to happen in the world of medical miracles over the next 
several years. A lot of them are happening, and you have 
mentioned them today. Are you ready to update your 10 bold 
predictions for the next 10 years?
    [Laughter.]
    Dr. Collins. I probably could do that. It would be kind of 
fun because there were some things that I do not think I put 
down in 2016 that I could now be pretty enthusiastic about. So, 
for instance, in 2016, I do not think I would have been bold 
enough to say that we would be curing sickle cell disease, and 
yet we are now seeing in at least three clinical trials that 
NIH is supporting, examples of individuals who are cured.
    Senator Alexander. Is that because of CRISPR?
    Dr. Collins. That is, CRISPR is in there, and other kinds 
of gene therapy making this possible. Some of the things we put 
down at that point, I thought were a bit overly optimistic, and 
yet maybe I underestimated how quickly things would go. We 
earlier talked about the artificial pancreas and, you know, I 
put that one down and a year later FDA approved the first one.

                         REGENERATIVE MEDICINE

    Senator Alexander. That is pretty common, right.
    Well, what about regenerative medicine? The juvenile 
diabetes folks say that the next step is regenerative medicine 
might help actually change the cells so you would not have to 
use the device. Is that possible?
    Dr. Collins. I think that is the ultimate goal. Maybe Dr. 
Rodgers would like to make a quick comment, to go from what is 
currently a technology that is like a servo mechanism with some 
nonhuman materials, into a human version of an artificial 
pancreas derived from stem cells.
    Senator Alexander. But the impact of that would be 
astonishing, wouldn't it?
    Dr. Collins. Profound, and it would be your own cells so 
this would not be a transplant, it is basically----
    Senator Alexander. So, you would not have to prick for your 
blood every day?
    How would that work Dr. Rodgers?
    Dr. Rodgers. Well, that is a great question. Cell 
replacement therapy is certainly an area that we are also, in 
addition to the artificial pancreas technology looking for a 
curative therapy. The goal here would be to stimulate the 
person's own beta cells, those cells that are lost due to 
autoimmune disease, and get them to replicate to expand them. 
Or alternatively, use of the remaining cells, such as the alpha 
cells that make glucagon, and trick them into actually becoming 
beta cells so that insulin can then be produced as well.
    One thing that we are doing in that space, using these 
islets, the cells that make insulin, is actually putting them 
on a chip. I have actually brought a copy of one to illustrate 
for the committee. These islet cells are put on this chip 
together with cells that replicate the pancreas environment 
blood vessels, as well as components of the immune system. In 
that, you can mimic the disease on a chip.
    The potential of this is that we may be able to test 
therapies in advance and save some of the expense and time 
associated with testing novel technologies in humans and get 
those that are likely to fail out of the way. So, we really 
have a lot of enthusiasm about this type of work.
    Senator Alexander. Thank you. My time is up.
    But I look forward to you updating your bold predictions, 
Dr. Collins.
    Dr. Collins. You are on.
    Senator Blunt. Alright. We will look forward to the list of 
bold predictions.
    Dr. Fauci, I am going to take 5 minutes here, and I have 
three questions and maybe we can deal with all of them in 5 
minutes. One, is measles. What do you think is happening and 
how concerned we should be about it?
    Two, the antibiotic resistance, the fungus that we are 
having problems, big problems in a couple places in the country 
now. Then, three would be the President's HIV 10-year 
prediction to not have transmission, or not have this as a 
problem anymore.
    So, start with measles.

                                MEASLES

    Dr. Fauci. Thank you, Mr. Chairman. Measles is really a 
formidable problem that is growing. It is a completely 
avoidable problem, which is the reason why we in the scientific 
and public health field are so frustrated by it.
    If you look at the year 2000, we here in the United States 
had essentially eliminated measles. By elimination, it means 
that there are no transmissible cases in the country over a 12-
month period. Yet over the last several years there has been 
increasing numbers of cases of measles, and I will explain in a 
moment why that is occurring.
    The problem right now, this past 3 months of 2019, we have 
had 465 cases of measles in the United States, which is more 
than we saw all of last year. And the cause of that is very 
clear, it is individuals in the community who are not 
vaccinating their children, leaving a vulnerable group such 
that when someone comes in from the outside, from another 
country where measles might be rampant and into the community, 
that if you have that veil of protection that you need when you 
need a certain critical percentage of the population is 
vaccinated, and for measles that means between 93 and 95 
percent.
    But look at what is going on now, in the State of 
Washington, in the Rockland County, New York and very, very 
importantly, in the middle of New York City in the Williamsburg 
section, where the Hasidic Jewish community goes down to around 
70 percent protection, which means that veil of community 
immunity is gone.
    That is the reason why we are having this outbreak. It is 
very frustrating, because measles is one of the most 
transmissible viruses known to man and we have a vaccine 
against measles, which is one of the most effective vaccines 
known to man, and yet those two are not coming together with 
this hesitancy to get vaccinated.
    So, our goal and our purpose now, is to try and educate 
people to understand the importance of not only protecting 
their own children but protecting the community. That is 
measles.

                          CANDIDA AURIS FUNGUS

    The fungus that you alluded to; it is called Candida auris. 
Fungi in general that we see are mostly, I would not say 
benign, but relatively easily treatable. The problem with this 
fungus that is now come out about 500 or so cases, is that we 
are seeing in hospitals particularly, a fungus that is rather 
resistant, if not completely resistant to the antifungal 
agents.
    This is particularly important for individuals who are 
immuno-suppressed, people on cancer chemotherapy, or people who 
have underlying immunosuppression. You have read about it in 
the front page of the New York Times, but this is becoming a 
problem that we have to address, and it falls under the big 
umbrella of the anti-microbial resistance.

                                  HIV

    Third, the President's announcement at the February 7th 
State of the Union Address about ending the HIV epidemic as we 
know it in the United States, and this is based on something 
that has happened for many years largely supported by this 
committee, is the development of the tools to do just that.
    We have drugs right now as you well know, I have spoken to 
you about this, that if you treated an individual who is HIV 
infected and bring down the level of virus to below detectable 
level, not only do you save that person's life but you make it 
essentially impossible for that person to transmit the virus to 
someone else.
    And then there is preexposure prophylaxis or PREP, which 
means that if you are at high risk of getting infected and you 
take one pill a day, you can decrease by 97 percent the 
likelihood that you actually will acquire infection.
    You put those two things together and you look at the map 
of the United States, why it is so unique. We have 3,007 
counties in the United States, in 48 of those counties, plus 
the Washington District of Columbia, plus San Juan, more than 
50 percent of all the infections in the United States come from 
that very restricted group.
    So, the plan is to take this demographically and 
geographically concentrated area, and as I say, put a full 
court press on getting into the community and implementing each 
of those.
    So, I will stop there, and I give you back 10 seconds.
    [Laughter.]
    Senator Blunt. Well, that is back to the observation 
earlier that you have testified before, you have three 
questions, exactly have timed them out and land on time.
    Senator Murray.

                           SEXUAL HARASSMENT

    Senator Murray. Thank you very much and Dr. Collins I know 
you are aware of a recent study in the Journal of American 
Medical Association, which found the gender differences, you 
talked a minute ago about that, in the amount of NIH funds 
awarded to first time female, and male principal investigators 
that favored men receiving larger grants than women. And data 
shows that in academic medicine, which for years has trained 
just as many women as men, the percentage of women in the 
workforce decreases at every career stage, such that women make 
up only 25 percent of the professorate.
    And your conversation with Senator Baldwin indicates you 
are aware of a study that also found that women held fewer 
grants, submitted fewer applications, and were less successful 
at renewing grants than their male counterparts.
    So, in light of the National Academy's report last summer, 
which showed that sexual harassment is rampant in academic 
science and undermines women's professional attainment, in some 
cases, leaving women to leave the scientific workforce 
entirely, the cumulative effect results in significant damage 
to research integrity and a considerable loss of talent in our 
country.
    So aside from its economic and potential scientific impact 
that loss of talent actually represents a significant cost to 
our taxpayers. It has been estimated that each newly minted 
Ph.D. costs $500,000, and of course it is a personal loss to 
women who feel pushed out of the field they love.
    So, given all that, can you comment on actions that NIH is 
taking to address this attrition of women from the biomedical 
workforce?
    Dr. Collins. I would be happy to. This is a very critical 
issue and there are multiple factors, but certainly the 
realization of how prominent and pervasive sexual harassment 
has been leads us to push even harder to address this issue. It 
is unacceptable, it is morally indefensible, and it drives 
talented women away from the workforce who could make wonderful 
contributions.
    If you look at this graph, it sort of shows you what has 
happened as far as the percent of various types of grants that 
are going to women. You can see in the career awards, which are 
generally people early in their independent phase we are doing 
better over time, we are actually doing better with research 
project grants, but the curve is way too slow in terms of its 
upward movement. That ought to be 50 percent, and it is not 
that there is a discrimination against women who apply for 
grants, if you look at the likelihood of getting funded, men 
versus women, it is almost exactly the same. The problem is we 
are not getting the applications.
    Senator Murray. They do not apply.
    Dr. Collins. And that is clearly an indication that there 
is something about our environment that is not welcoming, it 
does not feel like to many women, a place they really want to 
be. There are lots of factors in there in addition to the 
sexual harassment issue, there are family issues, and there are 
the issues about who has responsibilities for other parts of 
the community that people are coming out of. There is this sort 
of concern that if you look around, where are the mentors.
    I believe we really need, not just to try to address the 
things that are the most egregious as far as the sexual 
harassment, but also the gender harassment. The way in which 
our culture encourages women, often times to think they do not 
belong there by subtle comments that are made, usually by men. 
We have to change that, the best way to change that is to get 
more women into leadership positions.
    Senator Murray. I am looking at your panel, it's great, 
but----
    [Laughter.]
    Dr. Collins. Well, yes, look at our panel, just take a 
snapshot here, this is a good example of what we need to 
change.
    We are actually looking at our intramural program right now 
to try to see, are we doing enough there to provide 
opportunities for talented women to rise through the ranks or 
are we too ossified by people who get into a position and stay 
there too long.
    We are taking this with great seriousness. I grant you, we 
should have done so sooner, and I am apologetic to those who 
think we have not done enough. We are determined to do better.
    Senator Murray. Okay, I appreciate that. Thank you very 
much and of course, we all have to participate, and appreciate 
your taking this seriously, look forward to working with you on 
it. I think we are losing talent from an early age and it gets 
worse as we go on. We have to make sure we have all of our 
talent at the table. So, thank you.
    Dr. Collins. I agree with you.

                       METHAMPHETAMINE DEPENDENCE

    Senator Murray. Dr. Volkow, my last question. There is a 
lot of hope in my home State that opioid-related overdoses may 
have peaked, but we have been seeing an alarming increase in 
methamphetamine overdoses now, and as you know there is no FDA 
approved treatments for methamphetamine dependence.
    Can you tell me what NIDA's efforts to development 
treatment for methamphetamine addiction is right now?
    Dr. Volkow. Well, you are asking me a question that 
actually literally makes me extraordinarily anxious and keeps 
me awake at night, because we are seeing the numbers of 
mortality increasing for methamphetamine and cocaine too, and 
even though we funded research to come up with treatments none 
of them have reached the outcomes that are actually necessary 
to get them approved and show them effective.
    However, what is very exciting in the whole area and 
possibility, relates to immunotherapies, and in fact, where we 
have done the greatest advance is developing monoclonal 
antibodies for capturing the drug so that the drug gets 
sequestered in the blood and never gets into the brain 
obviating any pharmacological effects, happens to be for its 
application on methamphetamine.
    So, we have brought those antibodies already into humans, 
and what we are trying to work right now is the extent to, 
which by partnering with some of the scientists who are part of 
the NIAID Institute and the Cancer Institute, on developing 
longer lived, the monoclonal antibodies extent to which we 
could apply them. Because they work, they capture it, the 
problem is they are not long-lasting, so you have to repeatedly 
immunize.
    So, this is one of our priorities as it relates to 
medications.
    In parallel of course, we are funding research in terms of 
behavioral interventions to try to actually improve the 
outcomes on individuals that are suffering from methamphetamine 
addiction.
    Senator Murray. Okay. Thank you very much, I really 
appreciate it. And thank you to all of you for being here 
today. I appreciate the great work you do.
    Senator Blunt. I have just a couple of more things as we 
finish up here.

                           YOUNG RESEARCHERS

    Dr. Lorsch, we talked about young researchers. I think you 
have also been experimenting with longer research times for 
grants. Would you talk about that and talk about whether there 
is any impact that your appropriation stream has on being able 
to do that?
    Dr. Lorsch. Thank you very much, Senator. We have developed 
a new program called Maximizing Investigators Research Awards, 
or MIRA, which has several goals, but one as you said, is to 
give a longer and more stable funding stream to investigators. 
We hope that by doing that, and by also giving them more 
freedom to basically follow their noses as their research 
evolves, we will allow them to do more ambitious research and 
to get faster to discoveries through this process.
    There are two parts of it; one is the established 
investigator part, and the other is the early-stage 
investigator part.
    The early-stage investigator part is actually particularly 
exciting right now because since the program started in 2016, 
we have seen a doubling of the number of early-stage 
investigators that we fund at the Institute, primarily through 
the MIRA program. We have seen a 60 percent increase in the 
number of applications from early-stage investigators. So, they 
are clearly speaking with their feet that this is the way they 
want to see science supported.
    And what is particularly exciting is we are actually 
funding them at a younger age, so all 3 years of the program, 
the median age of funding for early-stage investigators in MIRA 
is 37, whereas it is 38 for early-stage investigators funded 
through RO1s and we are hoping that trend is going to continue.
    What I will say for the record, is that one of my strategic 
goals for the Institute is to try to push that age of funding 
for MIRA down to 35. I think 37 is still too late to be getting 
your first grant award.
    Senator Blunt. Well, thank you for that.

                     NON-ADDICTIVE PAIN MEDICATION

    Dr. Volkow, you know we have had a 30 percent increase in 
NIH and we are all pleased about, and during that same period 
of time we have had a 1300 percent increase in money going to 
the opioid fight.
    I do not know that we have talked yet today about 
alternative research to have pain medicine that is not 
addictive. Do you have any more you want to add to that?
    Dr. Volkow. There are two components to it, one of them is 
in terms of the basic science that Francis was speaking of that 
allowed us to identify completely novel treatment targets, 
molecules or immunotherapies for management of pain.
    And then those interventions that do not rely on biologics 
or medicine, and that includes behavioral interventions to 
evaluate the extent that they can improve the outcomes, as well 
as an area that is very exciting in the whole area of brain 
diseases, is the use of neuromodulation technologies like 
magnetic resonance, transcranial magnetic resonance 
stimulation, or direct electrical stimulation, to modify 
certain areas of the brain, in means to improve outcomes.
    The research, for example, there are several papers that 
have shown positive effects for various chronic pain conditions 
that offers an opportunity. There is also, as part of the HEAL 
initiative, a project that is going to be evaluating 
comprehensive models of care, just as the CDC recommends for 
the management of chronic pain, that will determine the extent 
for which they are effective and optimize our understanding 
about what are the active ingredients and how to sustain them. 
And too, at the end recognize that chronic pain is an 
extraordinary, difficult condition to treat, and that it is 
terrigenous and that we may require to do what is done in 
cancer, personalize intervention.
    So, doing that research that will enable us to get there 
will be very important in helping patients suffering from 
severe chronic pain conditions.
    Dr. Collins. I just want to weigh in for a minute here and 
say how incredibly helpful it was for the Congress to identify 
this as an area, both of great need and of great opportunity, 
and the $500 million that you put into the budget beginning in 
fiscal year 2018 has made it possible for us to solicit truly 
bold ideas across all of NIH.
    We now have 20 of our institutes engaged in this, more than 
40 different funding opportunity announcements, some of which 
have already received grants, have been reviewed and are 
starting to be funded; some of which are still out there for 
solicitations. By the end of this fiscal year we will have put 
the largest infusion of research into finding nonaddictive 
alternatives for pain that has ever happened at NIH, in 
addition to funding a very large amount of efforts to try to 
help how to manage opioid use addiction, which is obviously our 
National crisis.
    We could not have done this at this scale without your 
help, and it has made all the difference.

                                 SEPSIS

    Senator Blunt. Good. I do not remember the first time I 
noticed that somebody's cause of death was sepsis. It does not 
seem to me it was that long ago, but it does seem to me that I 
see that often now.
    What are we trying to do there, and is that an NIH issue 
that you are dealing with?
    Dr. Collins. It is. Maybe I will ask Dr. Lorsch to say a 
little bit about the basic science part, and Dr. Fauci about 
the clinical efforts, because those are hand in hand.
    Dr. Lorsch. Thank you very much. Sepsis research is 
supported jointly by three main institutes, one is NIGMS, one 
is Dr. Fauci's Institute, NIAID, each of which fund about a 
third of sepsis research, and Heart, Lung, and Blood funds 
about a quarter of it and the remainder is Child Health and Dr. 
Rodger's institute.
    I became concerned a couple of years ago that the pace of 
research in the basic part of sepsis understand the mechanisms 
underlying the condition was not fast enough. So I put together 
a working group of our advisory council, which right now is 
examining our portfolio and the field and how it fits in with 
the rest of what NIH is funding, and they will be making 
recommendations to us at the May council meeting that we will 
have next month.
    Particularly they are going to be looking at the balance of 
research in animal models versus in humans. We are concerned 
that perhaps there is too much emphasis on looking at sepsis-
like conditions in mice and not enough in actual human 
condition. And we are also looking at ways we can leverage 
clinical trials networks that are funded by other institutes 
that are already enrolling critically ill patients who may 
develop sepsis.
    And perhaps, Dr. Fauci wants to say a little bit about 
that.
    Dr. Fauci. Thank you, Mr. Chairman. The effort against 
sepsis as Dr. Lorsch has mentioned, is really multifaceted, 
because you have a micro-organism, a pathogen that triggers a 
process that is a physiologic and pathological process that 
leads to what we now know as sepsis. It is not just the microbe 
and it is not just the response; it is a combination of the 
two.
    NIAD's role is to study specifically the microbe itself, 
the virilism of the microbe, the processes that trigger these 
physiological and patho-physiological events, as well as 
treatment.
    And as Dr. Lorsch mentioned, we have a clinical trials 
network that we look at these patients, it is very difficult to 
actually study them, because when they come in it is such an 
acute situation that you have to move very quickly when you are 
doing a clinical trial. But we are working with other 
institutes, including the National Heart, Lung and Blood 
Institute, to do this kind of synergy of multiple approaches to 
what is a very complex and heterogeneous problem.
    Senator Blunt. Well, Senator Murray, we are about to finish 
here, is there anything that we should have asked that we did 
not ask Dr. Collins?
    Dr. Collins. You did a pretty fine job of covering a lot of 
the landscape with the folks who are here. And again, I have to 
say how much it has impressed me over the years about how much 
the members of this subcommittee have become so deeply 
knowledgeable about what we do.
    These conversations always end up being full of really rich 
details and digging into areas that we love to talk about. So, 
many thanks to you for all of the ways in which you have spent 
your time on these issues, and of course, we would love to 
invite you back out to NIH any time because we always have new 
things to show you.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Blunt. All right. The record will stay open for one 
week for additional questions.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
         Questions Submitted to Francis S. Collins, M.D. Ph.D.
                Questions Submitted by Senator Roy Blunt
                    china's thousand talents program
    Question. I'm very concerned that the NIH research community is not 
being adequately informed of the threats they are facing from foreign 
government programs specifically designed to undermine U.S. research. 
What specific steps are being taken to: (1) better inform the research 
community of the specific threat; (2) ensure there is disclosure of 
foreign collaborations and affiliations; and (3) implement controls to 
protect the integrity of the peer review system?
    Answer. NIH shares your concern about foreign government programs 
that are designed to undermine U.S. research. NIH is committed to 
working with other agencies and offices, including law enforcement, as 
well as with the extramural community, to identify and confront the 
risks these programs pose and to combat them. As described further 
below, NIH is employing a multi-pronged approach addressing individual 
situations and developing proactive programs to address these threats.
Informing the Research Community
    NIH's efforts to inform and engage the research community are 
proceeding across multiple platforms. For example, multiple 
communications to the research community over the last several years 
have focused on the imperative that applicants and recipients inform 
NIH of foreign support, and the obligations and certifications of 
reviewers to protect the confidentiality of grant applications, study 
section deliberations, preliminary scoring and reviews. For example, an 
NIH Guide Notice \1\ issued in March 2018 reminded applicants and 
recipients of the requirement to disclose to their institution 
significant financial interests, which can include support coming from 
foreign governments or other foreign entities; the institution 
determines financial conflicts of interest that must be reported to NIH 
and managed on an ongoing basis by the institution. On August 23, 2018, 
the NIH Director took the unusual action of issuing a comprehensive 
statement on protecting the integrity of U.S. Biomedical Research. The 
Director also took the unprecedented step of issuing a letter to 
officials at approximately 10,000 recipient institutions. This letter 
informed the research community that the agency is aware that some 
foreign entities have mounted systematic programs to influence NIH 
researchers and peer reviewers, as well as to take advantage of the 
long tradition of trust, fairness, and excellence of NIH supported 
research activities. Furthermore, NIH convened a working group of the 
Advisory Committee to the NIH Director on Foreign Influences on 
Research Integrity. This panel was comprised of leaders in higher 
education, members of the extramural community, and experts in 
security, and was charged with assisting the Advisory Committee in 
making recommendations to the agency, which are currently being 
implemented.
---------------------------------------------------------------------------
    \1\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-
160.html.
---------------------------------------------------------------------------
    In order to address specific cases brought to the attention of the 
agency, NIH has contacted nearly sixty institutions regarding concerns 
about scientists who may have failed to disclose foreign affiliations 
or significant financial interests stemming from foreign-based entities 
or governments. This approach has proven highly effective in both 
communicating concerns to the extramural research community, 
engendering partnerships to develop best practices, and gaining 
compliance with Federal and NIH grants requirements and policies. NIH's 
efforts have been widely reported within the science and popular press, 
e.g., by the Houston Chronicle,\2\ Science Magazine,\3\ and The Cancer 
Letter,\4\ which is expanding our impact. We are actively engaging the 
research community and in turn, they are actively partnering with us. 
For example, Penn State University,\5\ M.D. Anderson,\6\ and the 
University of California San Diego \7\ have posted new guidelines for 
faculty. Professional societies such as the American Society for 
Biochemistry and Molecular Biology \8\ are acting to share our concerns 
across the research community. We appreciate all the members of the 
research community who proactively work with us to address these 
matters.
---------------------------------------------------------------------------
    \2\ https://www.houstonchronicle.com/news/houston-texas/houston/
article/MD-Anderson-fires-3-scientists-over-concerns-13780570.php.
    \3\ https://www.sciencemag.org/news/2019/04/universities-will-soon-
announce-action-against-
scientists-who-broke-nih-rules-agency.
    \4\ https://cancerletter.com/articles/20190426_3/.
    \5\ https://www.research.psu.edu/international_affiliations.
    \6\ https://www.mdanderson.org/newsroom/md-anderson-addresses-
national-threat-of-foreign-
influence-.h00-159302256.html.
    \7\ https://medschool.ucsd.edu/vchs/research-services/hssppo/
review/Pages/Foreign-Involvement-.aspx.
    \8\ http://policy.asbmb.org/2019/01/02/updates-from-the-nih-
advisory-committee-to-the-directors-december-meeting/.
---------------------------------------------------------------------------
    Furthermore, NIH regularly communicates with grantees to provide 
training and compliance support for issues involving conflict of 
interest requirements at NIH-led conferences such as the NIH Regional 
Seminars. This information is also communicated by NIH through 
professional organizations such as the Federal Demonstration 
Partnership, Society for Research Administrators, American Association 
of Universities, Council on Governmental Relations, Association of 
Public & Land Grant Universities, and the National Council of 
University Research Administrators. There have been a number of special 
meetings involving these groups and others to address the recent 
concerns on foreign influence. In addition, NIH recently developed an 
online training module on Financial Conflict of Interest as a resource 
for both NIH staff and the extramural community. NIH's outreach and 
engagement have facilitated extensive faculty outreach at research 
organizations as well as led to developing and sharing best practices.
    Moving forward, as Dr. Collins said during the Senate Appropriation 
hearing, ``We will not rest until we've looked at every possible 
example. We have to depend on the universities as our partners in this, 
but we are driving this process as vigorously as we can.'' Additional 
institutions will be contacted when new discoveries are made. NIH will 
continue to remind the extramural research community of the need to be 
transparent regarding other support, financial conflicts of interest 
and foreign components, to better address research threats.
    Finally, NIH is actively partnering with other Federal departments 
and agencies to address concerns related to undue foreign influence on 
the biomedical research enterprise. These Federal partners include the 
Central Intelligence Agency, Federal Bureau of Investigation, HHS 
Office of Inspector General, Department of Defense, Department of 
State, and the National Science Foundation.
Ensuring Disclosure of Foreign Collaborations and Affiliations
    NIH requires institutions, as the applicants for and recipients of 
NIH funding, to ensure that individual investigators make all 
appropriate disclosures to their institution regarding other support, 
affiliations, and financial interests, whether or not they are 
employees of the institution. Institutions, in turn, must ensure that 
all applications and reports submitted to NIH are complete and 
accurate.
    Prior to making an award, NIH requests and reviews updated ``other 
support'' information for the program director/principal investigator 
and other key personnel identified in the grant application to ensure 
that updated information on all financial resources, whether Federal or 
non-Federal, foreign, commercial or institutional, available in direct 
support of an individual's research endeavors, are known and considered 
prior to award. This includes foreign financial support. NIH uses this 
information to ensure that sufficient levels of effort are committed to 
the project, there is no scientific, budgetary, or commitment overlap, 
and only the funds necessary to the approved project are included in 
the grant award.
    In addition, NIH applicants and recipients must request and receive 
approval for the inclusion of any foreign components of an NIH award. A 
foreign component is the performance of any significant scientific 
element or segment of the project outside of the United States, either 
by the recipient or by a researcher employed by a foreign organization, 
whether or not grant funds are expended.
    Among other obligations, the applicant organization must certify, 
and in some cases submit assurances, that they comply with the public 
policy requirements provided in the NIH Grants Policy Statement. These 
requirements are intended to ensure that recipient organizations handle 
their Federal awards responsibly. While NIH maintains oversight of our 
awards, we entrust our recipient organizations with the responsibility 
and accountability for successfully administering their grant award, 
including prudent fiscal management and other requirements spelled out 
in the NIH Grants Policy Statement.
    NIH will take action and has taken action where appropriate under 
its authority to address such concerns as part of its proper oversight, 
compliance, and stewardship roles. As an example, when NIH identifies 
noncompliance with the terms and conditions of award, it may take 
actions consistent with the regulatory requirements found in 45 CFR 
75.207 and 75.371 for grants and FAR 52.227-11 for contracts. Depending 
on the severity and duration of the noncompliance, NIH may decide to 
take one or more actions, which are also described in the NIH Grants 
Policy Statement, Section 8.5, Specific Award Conditions and Remedies 
for Noncompliance, including imposing specific award conditions, 
disallowing costs, withholding future awards for the project or 
program, suspending the award activities, making a referral for 
suspension or debarment, or terminating the award.
Protecting the Integrity of the Peer Review System
    All participants in the NIH peer review system are responsible for 
promoting integrity. Maintaining integrity--including obligations of 
reviewers to keep application information confidential and secure, 
consistent with their certifications--in the peer review process is 
essential for ensuring robust exchange of scientific opinions and 
providing reliable input to NIH about which research projects it should 
support and maintaining public trust in science.
    In recent years, NIH has taken numerous steps to protect the 
integrity of the peer review process. In addition to issuing several 
Guide Notices and blogs on the confidentiality and integrity of peer 
review, NIH has referred many cases to the HHS Office of Inspector 
General for consideration of further action, including referrals for 
debarment or suspension, as well as removed the affected individuals 
from peer review service. Also, in the end of 2018, reviewer conflict 
of interest certifications were converted to completely electronic 
format, enabling more thorough assessment of compliance across the 
agency and in cases of individual breaches.
    The NIH Office of Extramural Research (OER) has expanded its 
internal training for NIH Scientific Review Officers (SROs) to raise 
their awareness of integrity concerns. OER held three interactive 
training sessions on peer review integrity in the last year, each event 
drawing hundreds of SROs. These events covered case studies largely 
based on actual events and stimulated lively discussion of the best 
course of action in each scenario. The NIH is also working to implement 
recommendations from the NIH Advisory Committee to the Director on 
Foreign Influences on Research Integrity that focus on peer review 
integrity. Further, NIH continues to explore new technologies and ideas 
to protect the integrity of the peer review process. For example, a new 
dashboard is being developed to assist the Office of the Director in 
identifying data needed to review possible peer review integrity 
violations. Finally, policies for permissions to access certain 
information are being re-assessed. Taken together, these efforts to 
communicate internally and externally, as well as modernize controls, 
are raising the profile on peer review integrity concerns and reducing 
risks.
                    research on social media impacts
    Question. Dr. Collins, as a father of a 14 year old, I understand 
the role that cell phones, social media, and video games play in an 
adolescent's life. There is a lot of competing research available that 
shows the potential mental and emotional effects that media may play. 
Conversely, media also may be a resource to find social and emotional 
support for teens. Can you discuss what role NIH is playing in this 
research? Specifically, can you provide a few examples of what type of 
studies you are doing?
    Answer. NIH is vigorously pursuing this area of research. Several 
NIH Institutes and Centers, including the Eunice Kennedy Shriver 
National Institute of Child Health and Human Development (NICHD), are 
researching the effects of increasing use of media by children and 
adolescents. New evidence shows that screen time use is growing with 
unknown long-term effects on health and development. Early data from 
the NIH-funded Adolescent Brain Cognitive Development (ABCD) study 
shows that only 37 percent of children in the study met the less than 
two hours per day of recreational screen time recommended by American 
Academy of Pediatrics (AAP) guidelines. According to the AAP, 95 
percent of teens have access to a smartphone, and 45 percent say they 
are online ``almost constantly.'' In April 2019, the World Health 
Organization issued new guidelines stating that to grow up healthy, 
``children under five must spend less time sitting watching screens,'' 
emphasizing that screen time should be replaced with interactive non-
screen-based activities.
    NIH is committed to learning more about this issue. Just last year, 
NICHD hosted a workshop on media exposure and early child development, 
bringing together experts in this new field to share their individual 
perspectives regarding research gaps. Recommendations from some of the 
workshop panelists included developing meaningful measures of the 
impact of exposures to media, conducting neuroimaging research to look 
at the effects on developing brains, and parent education approaches. A 
recent NICHD-funded study found that exposure to media violence is a 
strong predictor of aggression and that parental monitoring is a 
significant factor against aggressive behavior. At the same time, 
social media can have positive effects; through its Adolescent Trials 
Network, NICHD is exploring the use of an interactive smartphone app as 
an intervention to help prevent the spread of HIV. Another study funded 
in 2018 is exploring whether books presented on a screen or with 
interactive enhancements confer the same benefits to a child's reading 
skills and socio-emotional development as print books. Screens also 
have been associated with delayed or insufficient sleep, which can lead 
to a number of chronic medical conditions in children and adolescents; 
another NICHD-funded study is exploring whether the light emitted by 
screens and other mechanisms affect children's circadian clocks.
    The ABCD \9\ is a longitudinal study of close to 12,000 children 
beginning at age 9-10 and continuing through adolescence and into early 
adulthood to understand how the experiences of adolescence shape brain, 
cognitive, social, and emotional development. When the children are 9 
and 10, they are asked questions about how much time they spend on 
different activities related to digital media (e.g., watching TV, 
playing video games, on social media, texting, video chatting). As they 
get older, they will be asked more in-depth questions about technology 
use. These data can then be correlated with other assessments within 
the study such as structural and functional MRI and measures related to 
mental health, cognition, and sleep, as well as be tracked over time as 
they mature. This comprehensive data set, led by the National Institute 
on Drug Abuse and supported by NICHD, the National Institute on Alcohol 
Abuse and Alcoholism, and the National Cancer Institute (NCI), will be 
disaggregated by sex, racial/ethnic group, and socioeconomic status, to 
allow researchers to address numerous questions related to adolescent 
brain development, thus informing future prevention and treatment 
efforts and public health strategies.
---------------------------------------------------------------------------
    \9\ https://abcdstudy.org/.
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                                 ______
                                 
          Questions Submitted by Senator Shelley Moore Capito
                           pulmonary fibrosis
    Question. I have a question for you about pulmonary fibrosis, a 
devastating disease that affects many people in my State. A major area 
of interest in pulmonary fibrosis-related research is patient-centered 
clinical research--research that directly addresses issues of most 
importance to those suffering from the disease. This would include 
studies looking at reducing hospitalizations, improving symptoms, and 
prolonging life. For example, researchers are currently examining the 
chronic cough that pulmonary fibrosis patients cite as one of the 
symptoms that most affects their quality of life.
     In the context of pulmonary fibrosis, what are the NIH and the 
NHLBI doing to support clinical researchers focused on patient-centered 
outcomes, and how they are promoting the use of novel data sources such 
as real-world registries, wearables and other technology?
    Answer. The NHLBI continues to support a wide array of clinical 
trials and fundamental research studies as part of a multi-pronged 
approach to identify and enhance treatments for patients who suffer 
from pulmonary fibrosis (PF).
    In the fundamental discovery science area, NHLBI-funded researchers 
are studying the mechanisms of lung fibrosis. One research team 
recently found that fibrotic cell invasion in PF could be driven by a 
problem with immune checkpoints, which are cell surface proteins that 
keep immune responses in check. These same proteins are hijacked by 
cancer cells to evade the immune system, and are the target for a new 
class of cancer drugs, suggesting that similar drugs could be used to 
treat PF.\10\ Another group's research suggests that toxic byproducts 
of oxygen consumption (reactive oxygen species) may contribute to lung 
injury in idiopathic PF (IPF), which has led to a clinical trial of a 
potential new drug.\11\
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    \10\ https://www.ncbi.nlm.nih.gov/pubmed/30763282.
    \11\ https://clinicaltrials.gov/ct2/show/NCT03865927.
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    NHLBI supports trials evaluating a number of other potential 
therapies that target different aspects of pathology in IPF. Two multi-
site clinical studies are investigating a combination of therapies that 
target autoantibodies--which stimulate the immune system to attack the 
body's own tissues; in PF, certain autoantibodies are known to cause 
acute breathing exacerbations.\12\ NHLBI's Pulmonary Trials Cooperative 
supports an ongoing study of antimicrobial therapy to reduce the risk 
of hospitalization and death from PF.\13\ Additionally, NHLBI's Centers 
for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases 
(CADET) program conducts preclinical research to help translate new 
understanding of disease mechanisms into better treatment for lung 
diseases, and is a developing potential new therapeutics for PF.
---------------------------------------------------------------------------
    \12\ https://clinicaltrials.gov/ct2/show/NCT03286556
and https://clinicaltrials.gov/ct2/show/NCT01969409.
    \13\ https://clinicaltrials.gov/ct2/show/NCT02759120.
---------------------------------------------------------------------------
    The NHLBI also strongly encourages investigators to utilize patient 
registries, such as the Pulmonary Fibrosis Foundation's registry, 
whenever appropriate to identify, recruit, and retain patients for 
clinical research, including intervention trials and studies to better 
understand the disease process. Several current funding opportunities 
allow PF researchers to leverage existing registries and resources.
    The NHLBI also encourages PF researchers to contribute and use 
whole genome sequencing data that is available through our Trans-omics 
for Precision Medicine (TOPMed) program. TOPMed is one of three massive 
datasets that researchers will be able to access and query during a 
pilot phase of the NIH Data Commons, a cloud-computing environment that 
is part of the NIH Science and Technology Research Infrastructure for 
Discovery, Experimentation, and Sustainability (STRIDES) initiative. 
The NHLBI is also developing another resource called Data Storage, 
Toolspace, Access and analytics for biG-data Empowerment (DataSTAGE) 
that will integrate TOPMed and other datasets with analytical tools to 
provide computing power that will help researchers explore precision 
medicine for PF and other disorders.
    The NHLBI and other Institutes continue to support the development 
of technologies to ameliorate symptoms such as cough in patients with 
chronic lung diseases, including PF, in part through our small business 
research programs. For example, researchers supported by the National 
Institute on Aging (NIA) are developing a wearable monitoring device to 
better assess patients with chronic respiratory disease.\14\
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    \14\ https://projectreporter.nih.gov/
project_info_details.cfm?aid=9465334.
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    The NHLBI also recognizes that aging has a significant impact on 
disease progression in patients with fibrotic lung diseases, and that 
there is a need for improved methods and tools to account for the 
interplay between aging and fibrosis. To this end, the NHLBI developed 
an initiative aimed at Deciphering the Molecular Landscape of Lung 
Aging in Humans,\15\ which is supporting four projects, including a 
Normal Aging Lung Atlas that will catalog dynamic gene expression 
changes in aging lung tissue at the single-cell level.\16\
---------------------------------------------------------------------------
    \15\ https://grants.nih.gov/grants/guide/rfa-files/rfa-hl-19-
012.html.
    \16\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9657483.
---------------------------------------------------------------------------
                           vascular dementia
    Question. Vascular dementia is the second most common form of 
dementia, after Alzheimer's disease, affecting almost a third of people 
over age 70. The NIH just completed the first randomized clinical trial 
demonstrating that lowering of systolic blood pressure significantly 
reduces the occurrence of mild cognitive impairment, which is an 
established risk factor and often a precursor for dementia.
    As the incidence of dementia continues to rise, what is NHLBI doing 
to understand the connection between heart health and brain health--
e.g. vascular dementia? What can people do to prevent it?
    Answer. Cardiovascular disease (CVD) is increasingly recognized as 
an important contributor to cognitive impairment and dementia. 
Fortunately, the science also suggests that maintaining a healthy heart 
can help maintain a healthy brain. A recent Alzheimer's Disease-Related 
Dementias (ADRD) Summit at NIH included a discussion of vascular 
dementia and how to continue to move the field forward.\17\
---------------------------------------------------------------------------
    \17\ https://meetings.ninds.nih.gov/?ID=21149.
---------------------------------------------------------------------------
    NIH is already leveraging several of its long-established cohort 
studies to better understand the connections between heart disease and 
dementia. NHLBI's Framingham Heart Study began 70 years ago, and has 
since expanded to include three generations of participants. The study 
has found that many of the risk factors for dementia are the same as 
those for heart disease, such as high blood pressure, cigarette 
smoking, lack of physical activity, obesity, and diabetes. A recent 
NIH-supported analysis of Framingham data found that high blood 
pressure during mid-life increases the risk of dementia later, 
suggesting that there are potential cognitive benefits from managing 
blood pressure in mid-life.\18\
---------------------------------------------------------------------------
    \18\ https://www.ncbi.nlm.nih.gov/pubmed/29117954.
---------------------------------------------------------------------------
    Several NIH cohort studies focused on minority populations have 
added new objectives to better understand the connection between 
vascular risk factors and brain health. NHLBI's Jackson Heart Study of 
CVD in African Americans was renewed in August 2018, and new clinical 
exams beginning in 2020 will include tests of cognitive function as 
well as brain imaging. Additionally, the National Institute of 
Neurological Disorders and Stroke (NINDS) is supporting projects that 
leverage data from cohort studies such as the Reasons for Geographic 
and Racial Differences in Stroke (REGARDS) study and the Northern 
Manhattan Study (NOMAS). To better understand and prevent risk of 
vascular brain disease in women, participants from the NHLBI-supported 
Women's Health Initiative are part of the Women's Health Initiative 
Strong & Healthy (WHISH), trial which is testing whether increasing 
physical activity will reduce the risk of CVD and cognitive decline in 
older women.\19\
---------------------------------------------------------------------------
    \19\ https://whish.stanford.edu/about/.
---------------------------------------------------------------------------
    In the basic research arena, the Molecular Mechanisms of the 
Vascular Etiology of Alzheimer's Disease (M\2\OVE-AD) Consortium, 
developed by the NIA in collaboration with NINDS, brings together six 
multi-disciplinary research teams to use a variety of computational and 
animal model approaches to better understand the complex molecular 
mechanisms by which vascular and metabolic risk factors influence the 
development of Alzheimer's and related dementias, with the ultimate 
goal to identify therapeutic targets and biomarkers.\20\
---------------------------------------------------------------------------
    \20\ https://www.nih.gov/news-events/news-releases/decoding-
molecular-ties-between-vascular-disease-alzheimers.
---------------------------------------------------------------------------
    It is now known that brain changes typically begin years--if not 
decades--before people show symptoms, which suggests that a window of 
opportunity exists to prevent, slow, or delay the onset of cognitive 
decline. A recent analysis of the Framingham Heart Study examined 
whether adherence to the American Heart Association's (AHA) 
Cardiovascular Health Guidelines was associated with improved brain 
health. The analysis found a lower risk of incident stroke, dementia, 
cognitive decline, and brain atrophy among participants who adhered to 
the AHA recommendations, which includes maintaining a healthy body mass 
index, healthy diet, nonsmoking status, normal total cholesterol, 
normal blood pressure, and physical activity.\21\
---------------------------------------------------------------------------
    \21\ https://www.ahajournals.org/doi/full/10.1161/
strokeaha.115.012608.
---------------------------------------------------------------------------
    A 2017 National Academies of Sciences report supported by NIH 
concluded that there is encouraging but inconclusive evidence for 
several potential approaches to guard against cognitive decline and 
dementia, including blood pressure management for people with 
hypertension, increased physical activity, and cognitive training.\22\ 
Recent NIH-funded studies add to the weight of evidence that aggressive 
treatment of hypertension may protect against cognitive decline. The 
NIH-funded Systolic Blood Pressure Intervention Trial (SPRINT) trial 
investigated whether aggressive systolic blood pressure reduction--down 
to less than 120 mm Hg, rather the prior target of 140 mm Hg--could 
reduce the risk of heart attack, stroke, and death in people over age 
50 who have hypertension. A sub-study, the SPRINT Memory and Cognition 
IN Decreased Hypertension (MIND) trial, evaluated whether this 
aggressive treatment would also lower the risk of dementia. These 
studies were stopped early because the treatment clearly protected 
against CVD. After about 5 years of follow-up in SPRINT MIND, there was 
no significant change in dementia risk, perhaps because of the study's 
shortened duration. However, there was almost 20 percent lower risk of 
mild cognitive impairment, a well-established precursor of 
dementia.\23\
---------------------------------------------------------------------------
    \22\ http://www.nationalacademies.org/hmd/Reports/2017/preventing-
cognitive-decline-and-
dementia-a-way-forward.aspx.
    \23\ https://jamanetwork.com/journals/jama/fullarticle/2723256.
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                                 ______
                                 
            Questions Submitted by Senator Cindy Hyde-Smith
                            opioid addiction
    Question. Dr. Collins, how is NIH investing in research to identify 
genetic components that may make particular individuals more 
susceptible to opioid addiction? What is the current status of the 
science in this area? Are additional funds needed to expand this 
research?
    Answer. Many individuals affected by OUD have a family history of 
addiction to opioids or other substances, however, research to date 
indicates that OUD does not have a clear pattern of inheritance. The 
increased risk among members of an affected family is likely due in 
part to shared genetic factors, but it is also likely related to 
environment and other non-genetic influences that are shared by family 
members.
    Separating the complexities of genetic and non-genetic factors that 
affect OUD risk is a crucial pillar of efforts to stem the tide of the 
opioid crisis and advances NIH's broader goals of understanding the 
mechanisms underlying addiction to inform effective prevention and 
treatment strategies. Accordingly, NIH has fostered a robust and 
multidisciplinary research portfolio to examine the genetic 
underpinnings of OUD. There are currently 67 active NIH-funded projects 
focused on opioid addiction and genetics, as identified in NIH's public 
database, RePORTER. Some of these projects are highlighted below.
    One of the common tools in NIH's arsenal to investigate the role of 
genetics in disease is a genome-wide association study, or GWAS. A GWAS 
involves examining genetic variations (genotypes) across the complete 
sequences of DNA, or genomes, of many different people to find genetic 
variants associated with a disease or trait (phenotypes). There have 
been six GWAS projects studying OUD phenotypes that identify several 
single nucleotide polymorphisms (SNPs), or variations in a single DNA 
nucleotide, as potentially significant. These variations are being 
examined to validate their association with OUD. The National Institute 
on Drug Abuse's Genetics Consortium, founded in 1999 to coordinate 
efforts of investigators studying substance use disorders and addictive 
behaviors, is currently conducting its own GWAS, which includes samples 
from more than 10,000 people. Recent work in psychiatry genetics 
suggest that sample sizes larger than 10,000 are needed to identify 
genome wide significant results.
    In addition, NIDA is seeking to leverage resources of commercial 
companies to identify genetic variants for prescription opioid misuse 
and has issued a Request for Information via FedBizOpps to identify 
companies that can execute such an initiative (Solicitation 
75N95019R00053: Addressing the Opioid Crisis: Genetic Variants for 
Prescription Opioid Abuse).
    Current Status of the Science: While research in this field is 
still underway, there is already a body of evidence that suggests a few 
key themes in the complex interplay between genetics and addiction:
  --The dose of methadone needed to successfully treat OUD is affected 
        by genetic variations in the mu opioid receptor gene and in the 
        gene for the enzyme that metabolizes methadone.\24,25,26\
---------------------------------------------------------------------------
    \24\ Smith AH, Jensen KP, Li J, et al. Genome-wide association 
study of therapeutic opioid dosing identifies a novel locus upstream of 
OPRM1. Mol Psychiatry 2017;22:346-52.
    \25\ Crist RC, Doyle GA, Nelson EC, et al. A polymorphism in the 
OPRM1 3'-untranslated region is associated with methadone efficacy in 
treating opioid dependence. The pharmacogenomics journal 2018;18:173-9.
    \26\ Dennis BB, Bawor M, Thabane L, Sohani Z, Samaan Z. Impact of 
ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose 
and treatment response in patients with opioid addiction: a systematic 
review and meta-analysis. PloS one 2014;9:e86114-e.
---------------------------------------------------------------------------
  --Genetic variations in the mu opioid receptor gene are also 
        associated with risk for heroin addiction and with severity of 
        heroin addiction.\27,28,29,30\
---------------------------------------------------------------------------
    \27\ Schwantes-An TH, Zhang J, Chen LS, et al. Association of the 
OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to 
Substance Dependence in a Collaborative de novo Meta-Analysis of 
European-Ancestry Cohorts. Behavior genetics 2016;46:151-69.
    \28\ Hancock DB, Levy JL, Gaddis NC, et al. Cis-Expression 
Quantitative Trait Loci Mapping Reveals Replicable Associations with 
Heroin Addiction in OPRM1. Biological Psychiatry 2015.
    \29\ Zhang Y, Picetti R, Butelman ER, Ho A, Blendy JA, Kreek MJ. 
Mouse model of the OPRM1 (A118G) polymorphism: differential heroin 
self-administration behavior compared with wild-type mice. 
Neuropsychopharmacology : official publication of the American College 
of Neuropsychopharmacology 2015;40:1091-100.
    \30\ Xu J, Lu Z, Xu M, et al. A heroin addiction severity-
associated intronic single nucleotide polymorphism modulates 
alternative pre-mRNA splicing of the ? opioid receptor gene OPRM1 via 
hnRNPH interactions. J Neurosci 2014;34:11048-66.
---------------------------------------------------------------------------
  --Copy Number Variations (CNVs) (or variability in the number of 
        times a sequence of DNA is repeated) are associated with opioid 
        dependence. In one sequence, a chromosomal deletion is 
        associated with being protective against opioid dependence, and 
        duplication of the same part of the chromosome increased risk 
        for opioid dependence.\31\
---------------------------------------------------------------------------
    \31\ Li D, Zhao H, Kranzler HR, et al. Genome-wide association 
study of copy number variations (CNVs) with opioid dependence. 
Neuropsychopharmacology 2015;40:1016-26.
---------------------------------------------------------------------------
  --Variations in genes that code for proteins associated with the 
        signaling of glutamate, a widespread neurotransmitter in the 
        brain, have also been associated with development of opioid 
        addiction and regulation of opioid withdrawal.\32,33,34\
---------------------------------------------------------------------------
    \32\ Nelson EC, Agrawal A, Heath AC, et al. Evidence of CNIH3 
involvement in opioid dependence. Mol Psychiatry 2016;21:608-14.
    \33\ Reti IM, Crombag HS, Takamiya K, et al. Narp regulates long-
term aversive effects of morphine withdrawal. Behavioral neuroscience 
2008;122:760-8.
    \34\ Crombag HS, Dickson M, Dinenna M, et al. Narp deletion blocks 
extinction of morphine place preference conditioning. 
Neuropsychopharmacology 2009;34:857-66.
---------------------------------------------------------------------------
  --A gene coding for a protein that is important for the way neurons 
        form connections with one another regulates opioid tolerance 
        and opioid-induced hyperalgesia.\35\
---------------------------------------------------------------------------
    \35\ Donaldson R, Sun Y, Liang D-Y, et al. The multiple PDZ domain 
protein Mpdz/MUPP1 regulates opioid tolerance and opioid-induced 
hyperalgesia. BMC Genomics 2016;17:313.
---------------------------------------------------------------------------
    Question. Are additional funds needed to expand this research?
    Answer. Investing in research is fundamental, and NIH will continue 
to explore opportunities to expand the scope and impact of genetic 
research on OUD. For example, an expert panel convened by the NIDA 
Genetics Consortium recently highlighted the value in conducting a GWAS 
on opioid naive surgical patients to identify genetic variants 
associated with persistent opioid use and other opioid-related 
outcomes. This would be an opportunity to potentially identify genetic 
variants among surgical patients who become opioid dependent.
                                 ______
                                 
             Questions Submitted by Senator James Lankford
                        fetal tissue/stem cells
    Question. During an appropriation hearing in the House of 
Representatives, Rep. Andy Harris asked you about the ongoing fetal 
tissue research at NIH, but there were some outstanding questions from 
his line of questioning. I share Rep. Harris' concern over the use of 
fetal tissue research at NIH and would like more information as it 
relates to ongoing studies that use fetal tissue research.
    From my understanding, you recently extended a fetal tissue 
contract with the University of California San Francisco (UCSF).
    From where is the tissue obtained that UCSF is providing to NIH?
    Answer. UCSF obtained fetal tissue as it became available from 
elective and legal abortions performed at the UCSF clinic in San 
Francisco and that would otherwise be discarded. Per the June 5, 2019, 
statement from the Department of Health and Human Services, the 
contract expired on June 5, 2019, and there will be no further 
extensions.\36\
---------------------------------------------------------------------------
    \36\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
department-of-health-and-human-services.html.
---------------------------------------------------------------------------
    Question. How old are the fetuses that were obtained from UCSF that 
are used in the study?
    Answer. The contract required the delivery of humanized mouse 
models. The contractor proposed the collection of human fetal tissue in 
order to create the humanized mouse models. NIH did not specify 
gestational age of the tissue being collected. As noted above, this 
contract expired on June 5, 2019, and there will be no further 
extensions.
    Question. Why was the decision made to extend this contract before 
HHS finished its audit of fetal tissue research?
    Answer. The contract with UCSF had an option year that needed to be 
exercised prior to the completion of the HHS audit. The contract was 
extended to ensure continuity of service until the audit is completed 
and a final decision was made about the contract. As noted above, this 
contract expired on June 5, 2019, and there will be no further 
extensions.
    Question. How many studies is NIH conducting with fetal tissue?
    Answer. The Estimates of Funding for Various Research, Condition, 
and Disease Categories (RCDC) provides official NIH figures on research 
spending by category. For fiscal year 2018, RCDC lists 200 grants and 
projects that involve research with human fetal tissue.\37\ Please also 
see the June 5, 2019, statement from the Department of Health and Human 
Services about NIH-supported research using human fetal tissue.
---------------------------------------------------------------------------
    \37\ https://report.nih.gov/categorical_spending.aspx.
---------------------------------------------------------------------------
    Question. The research conducted by the NIH affords invaluable 
knowledge and understanding of the infectious diseases we face today. 
Indisputably, NIH funding is vital to improving healthcare and 
protecting American lives. That being said, we must ensure that we hold 
taxpayers' dollars with highest regard and direct our limited resources 
to projects that not only better our country but reflect the will of 
the people.
    As revealed by the Select Panel on Infant Lives investigation, 
Planned Parenthood officials have admittedly changed abortion 
procedures to procure intact fetal body parts for sale. The fact that 
an industry has been created around the sale of aborted baby parts is 
deeply disturbing, and I firmly believe we must do all that we can to 
ensure taxpayers' dollars are used responsibly and ethically when it 
comes to federally funded research involving fetal tissue.
    What steps has NIH taken to partner with hospitals to procure fetal 
tissue that has been donated after a spontaneous abortion or 
miscarriage as opposed to tissue that is acquired after an elective 
abortion?
    Answer. NIH funded a major effort through five tissue bank programs 
to collect and examine tissue donated from women who had spontaneous 
abortions or ectopic pregnancies. The results were published in the 
Journal of the American Medical Association in 1995.\38\ From over 
22,000 obstetric admissions, tissue from 1,250 spontaneous abortions 
and 247 ectopic pregnancies was obtained. Most of the specimens 
recovered consisted of maternal or extraembryonic tissue. Of the 
embryonic collections, less than 1 percent would have been useful for 
clinical use. 71 percent of embryonic samples were degenerated; 79 
percent had bacterial contamination (despite use of aseptic collection 
techniques); and 40 percent had chromosomal abnormalities.
---------------------------------------------------------------------------
    \38\ https://jamanetwork.com/journals/jama/fullarticle/385456.
---------------------------------------------------------------------------
    Question. Has NIH considered limiting its procurement of fetal 
tissue obtained this way? If not, please explain why.
    Answer. NIH-funded research summarized above has established that 
fetal tissues from miscarriages (spontaneous abortions) and ectopic 
pregnancies are not feasible sources for research. Please also see the 
June 5, 2019, statement from the Department of Health and Human 
Services about NIH-supported research using human fetal tissue.\39\
---------------------------------------------------------------------------
    \39\ https://www.hhs.gov/about/news/2019/06/05/statement-from-the-
department-of-health-and-human-services.html.
---------------------------------------------------------------------------
    Question. Since President Obama's Executive Order 13505 ``Removing 
Barriers to Responsible Scientific Research Involving Human Stem 
Cells'' in March 2009, NIH has had wide access to human embryonic stem 
cells. As you know, this EO revoked a previous EO from President Bush 
that outlined ethical principles for stem cell research.
    As you know, some may claim that because stem cells themselves are 
not human embryos, there is no need to limit the amount available. But 
because the cells come from human embryos, NIH has an ethical 
obligation to value and honor the human life that contributed to such 
cells.
    While I have received some information on the types of research in 
which NIH uses ``human embryonic stem cells (hESCs)'', I am unaware of 
any validated, successful patient treatment from embryonic stem cells.
    Additionally, as you know alternatives to embryonic stem cell 
research exist. In 2012, the Nobel Prize in Physiology or Medicine was 
awarded to two researchers for their discovery of induced pluripotent 
stem (iPS) cells, which mimic the qualities of embryonic stem cells but 
do not use embryos in any way. Similarly, NIH has had great success in 
treating and curing more than 70 diseases using adult stems cells and 
iPS cells. Despite this, it is my understanding that NIH continues to 
expand its embryonic stem cell research to cell lines not already 
included on the NIH Human Embryonic Stem Cell Registry.
    How many new cell lines has NIH added to its Registry since EO 
13505 was enacted?
    Answer. Executive Order 13505 directed NIH to issue new guidance on 
research with human stem cells, including human embryonic stem cells 
(hESCs).\40\ NIH subsequently issued the NIH Guidelines for Human Stem 
Cell Research (Guidelines) on July 7, 2009.\41\ The Guidelines 
established strict new criteria for the NIH Director to determine the 
eligibility of the use of specific hESC lines in NIH-funded research. 
The NIH Director has approved 398 hESC lines for use in NIH-supported 
research under this policy, including 10 of the 21 cell lines that were 
also eligible for use under the policy of the prior administration. The 
NIH Director has also determined that 70 hESC lines are not eligible 
for use in NIH-supported research, primarily due to inadequacies in the 
embryo donation consent process.
---------------------------------------------------------------------------
    \40\ https://www.govinfo.gov/content/pkg/FR-2009-03-11/pdf/E9-
5441.pdf.
    \41\ https://stemcells.nih.gov/policy/2009-guidelines.htm.
---------------------------------------------------------------------------
    Question. Why has NIH chosen to add more cell lines to its registry 
instead of using cells already on the registry?
    Answer. Part of the stated purpose of the Executive Order was `` . 
. . to expand NIH support for the exploration of human stem cell 
research.'' So, NIH developed a new policy, which included stricter new 
requirements regarding the embryo donation process. Under current 
policy, hESCs can only be used by NIH funded researchers if the embryos 
were created using IVF for reproductive purposes, no longer needed by 
the parents, and the embryos were donated by those parents with 
voluntary, written, informed consent. NIH also included new 
requirements that certain information be given to the potential donors 
during the consent process, such as what will happen to the embryos, 
and how long they have to change their minds.
    Some of the newer hESC lines have characteristics that are more 
suitable for clinical use, including reduced exposure to animal 
products and viruses. Some are also more flexible in their ability to 
form different tissue types. There are more than 100 hESC lines 
approved under the current policy that have mutations associated with 
particular diseases, providing useful cell models for studying those 
diseases.
    Question. Why has NIH not used IPS cells for research instead of 
using hESCs?
    Answer. NIH funds a range of stem cell research, using induced 
pluripotent stem cells (iPSCs) as well as hESCs. In fiscal year 2018, 
NIH awarded $468 million for human iPSC research and $278 million for 
hESC research. NIH is currently funding a significant amount of pre-
clinical research using iPSCs. For example, an investigator in the 
National Eye Institute's intramural program is developing an iPSC-
derived cell therapy for age-related macular degeneration.\42\ There 
are also other investigational cell therapies developed from human 
induced pluripotent stem cells (hiPSCs) in clinical trials now (not 
funded by NIH) for age-related macular degeneration, graft versus host 
disease, and Parkinson's disease.
---------------------------------------------------------------------------
    \42\ https://irp.nih.gov/pi/kapil-bharti.
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                                 ______
                                 
              Questions Submitted by Senator Patty Murray
                         chief data strategist
    Question. For the past 3 years, this committee has urged NIH to 
focus on developments in data science as it relates to biomedical 
research. What is possible to achieve by harnessing the vast amount of 
data produced in science is still unknown. But what we do know, is with 
proper leadership, vision, and tools, big data has the potential to 
help scientists unlock infinite breakthroughs and discoveries in 
biomedical research. At the direction of this committee, in May 2018 
NIH released a strategic plan for data science, which includes 
recommendations to advance data infrastructure and data stewardship in 
support of the data ecosystem at NIH and improve NIH's expertise in 
this space.
    After a year of efforts to recruit for the new CDS position, NIH 
still has not filled this role.
    What is the status of the job search for the Chief Data Strategist? 
Please include details on the recruitment, number of applicants and 
interviews, significant next steps, and timeline for completion. Are 
there specific obstacles to filling this role that NIH needs to 
address?
    Answer. The recruitment for the NIH Chief Data Strategist is 
currently open for receiving applications, until filled. The 
recruitment for this position opened on May 9, 2018. To date, NIH has 
received 59 application packages which met the basic qualifications for 
the position, held rating meetings, and conducted interviews. An 
external search firm was secured to work in concert with the search 
committee to seek and encourage highly qualified candidates to apply. 
Over 20 ads were placed online with periodicals, data science 
organizations, and diversity associations. Currently, a video is being 
produced to highlight the data science activities at NIH, which will be 
released to encourage candidates to apply to this position. The 
recruitment timeline is currently open ended.
    Data science is a burgeoning field of study, involving both private 
sector and academic leaders. The NIH is hoping to fill this position 
with an individual who has the knowledge and unique skill set needed to 
accelerate NIH progress in data science and to expand collaborations 
worldwide. As you note, it has been exceedingly challenging to attract 
someone that would bring the unique combination of knowledge and skills 
to the position. Federal salary limits are one limiting factor and the 
constraints related to financial holdings that result from Federal 
employment are another. The NIH is committed to filling this position 
as soon as possible and is determined to fill the position with the 
ideal candidate.
    Question. Since the recruitment process is taking a considerable 
amount of time, what is NIH doing during this interim period, prior to 
hiring a CDS, to move the work forward?
    Answer. Executive leadership of data science efforts at the NIH 
continues to be provided by the Interim Associate Director for Data 
Science, a position temporarily being filled by the Principal Deputy 
Director, NIH. The Scientific Data Council, co-chaired by the Director, 
National Institute of General Medical Sciences, and the Director, 
National Institute of Biomedical Imaging and Bioengineering, is also 
providing advice and oversight to ensure forward movement on trans-NIH 
data science activities. Other executive staff, including the Directors 
of the Center for Information Technology and the National Library of 
Medicine have been playing key roles in moving forward critical data 
science efforts. The Director of the NIGMS Division of Biomedical 
Technology, Bioinformatics, and Computational Biosciences is providing 
essential leadership for, and helping to fully operationalize, the 
Office of Data Science Strategy (ODSS). Other Office of the Director 
staff are also playing key roles for activities that are being led and 
funded by ODSS. While we have not yet been able to fill the Chief Data 
Strategist position, we have made significant progress in implementing 
components of the NIH Strategic Plan for Data Science.
    Question. Given the challenges of bringing someone with the 
appropriate skills, vision and background into the CDS position, what 
alternatives is NIH exploring?
    Answer. As noted above, NIH contracted with an external search firm 
to work closely with the search committee to seek and encourage highly 
qualified candidates to apply. Over 20 ads were placed online with 
periodicals, data science organizations, and diversity associations. A 
video is being produced to highlight the data science activities at NIH 
which will be released to encourage candidates to apply to this 
position. In the meantime, NIH leadership is considering whether other 
NIH employees could fill this vacancy on a temporary basis.
    Question. Has NIH consulted with organizations that face similar 
challenges, such as DoD, NASA, and universities attempting to solve 
some of the same cutting edge data challenges?
    Answer. Yes. Through both formal interagency processes and informal 
leadership and staff level conversations, NIH consults and shares 
information with other Federal research agencies facing similar 
challenges. As part of the search for the CDS, we have also engaged in 
extensive outreach, including to other Federal agencies, e.g., 
Department of Energy and the National Science Foundation.
    We are continuing efforts to find the best candidate for this 
critical position at NIH. Some important new approaches we will be 
taking are listed below:
  --NIH is about to launch a social media and marketing campaign for 
        the CDS position--possibly as early as the week of May 28. You 
        may see Twitter and Facebook posts from NIH, Dr. Collins, the 
        CDS Search Committee co-chairs, and various other NIH-related 
        handles. NIH is also asking other Federal government agencies 
        to help amplify our posts. An executive search firm will be 
        helping NIH cross-promote on LinkedIn.
  --NIH has produced a final cut of a 5-minute video about the 
        position. View on YouTube here: https://youtu.be/92arhggy4xI.
  --Dr. Collins will use his blog to highlight the important of this 
        position to NIH's future with an embedded version of the video.
  --An easier-to-use URL for the position is now available: 
        www.nih.gov/CDS http://www.nih.gov/CDS.
  --NIH will make additional efforts to identify and capitalize on NIH 
        leadership that have personal connections with Silicon Valley 
        and other tech company executives/VIPs who may have good 
        candidates to recommend.
  --A slide will be provided for use by NIH leadership in any 
        presentations they are making to the tech community.
  --A 30 second teaser video, based on the YouTube video linked above, 
        will be released as part of a social media marketing campaign 
        to attract candidates.
    Question. Last year, the Committee assumed that implementation of 
certain components of the strategic plan--including developing 
performance measures and specific milestones for the plan's 
objectives--was delayed due to the open job search. What, if any, steps 
in the strategic plan have been implemented to date?
    Answer. The NIH has moved forward in implementing multiple 
components of the NIH Strategic Plan for Data Science. Currently, a 
team of NIH employees detailed to the ODSS is coordinating the efforts 
of nearly thirty implementation working groups with members 
representing nearly all NIH Institutes and Centers. ODSS has also 
established a Technical Implementation Working Group composed of high-
level data science experts across NIH to advise the Office on technical 
matters related to implementation tactics. A non-exhaustive summary of 
current activities aligned with each goal of the strategic plan is 
provided below:
    Goal 1: Support a highly efficient and effective biomedical 
research data infrastructure.
  --ODSS executed a contract with BioTeam, Inc. to develop a basic 
        needs requirement document that would directly inform the 
        infrastructure development of a NIH-wide data ecosystem that 
        meets FAIR principles. The contractor is currently in the 
        process of collecting data ecosystem use cases and conducting a 
        gap analysis across high-profile NIH data systems. A final 
        report is anticipated in September 2019.
  --ODSS is providing technical assistance to the NIH Office of Science 
        Policy (OSP) in the review of current policies regarding Data 
        Access Committees to streamline and increase the efficiency of 
        review.
  --The National Center for Biotechnology Information and CIT have 
        developed an initial strategy for a trans-NIH approach to user 
        authentication and authorization for access to data sets. This 
        technical solution will be developed into a testable prototype 
        in the next few months.
  --The STRIDES Initiative, a NIH partnership with industry-leading 
        cloud service providers (currently, Google and Amazon) to 
        provide discounted cloud storage and compute access to 
        biomedical researchers, continues to migrate high-value data 
        sets to cloud platforms. ODSS is providing oversight of this 
        CIT-managed initiative and has engaged nearly 40 data programs 
        in both the intra- and extra-mural communities. NIH is 
        developing the policies and procedures for making this 
        innovative partnership available to all NIH-funded biomedical 
        researchers in order to accelerate scientific discoveries 
        leading to new health technologies.
    Goal 2: Promote modernization of the data-resources ecosystem.
  --A strategic plan implementation team co-led by NLM and NIGMS 
        developed new funding opportunity announcements (FOAs) that 
        will address the objective of separating support for databases 
        and knowledgebases and sets forth appropriate resource criteria 
        and review criteria that must be met in order to receive NIH 
        support. These FOAs are currently under review with an 
        anticipated release date this summer.
  --This April, NIH held a workshop to share criteria for 
        trustworthiness of data repositories and to educate biomedical 
        data managers on the CoreTrustSeal certification requirements. 
        Information from the workshop will be used to promote 
        sustainable and trustworthy data infrastructures in the 
        biomedical arena. In a related effort, NLM conducted a 
        comprehensive analysis of criteria for open-access data sharing 
        repositories that receive NIHsupport and will soon publish a 
        public request for information to solicit additional input on 
        draft criteria.
  --The NIH Scientific Data Council is reviewing how NIH could 
        potentially integrate existing clinical data elements with the 
        industry-adopted fast healthcare interoperability resources 
        (FHIR) specification to enable the exchange of healthcare, 
        clinical and basic research data across different systems.
    Goal 3: Support the development and dissemination of advanced data 
management, analytics, and visualization tools.
  --ODSS is engaged in planning a workshop to bring systems integration 
        specialists from the private sector so that NIH data scientists 
        can learn the latest approaches to the optimization of data 
        analysis tools and algorithms.
  --NSF and NIH/ODSS will hold a workshop in June to discuss 
        opportunities for joint funding of data science research 
        programs, with a particular emphasis on AI/ML approaches to 
        solving complex data analysis problems in biology and medicine.
  --ODSS executed a contract with FigShare, providing NIH-funded 
        researchers with access to online open access repository where 
        researchers can preserve and share their research outputs, 
        including figures, datasets, images, and videos.
    Goal 4: Enhance workforce development for biomedical data science.
  --Please refer to NIH's description of efforts in data science 
        workforce development addressed in the response to a specific 
        question for the record on this topic.
    Goal 5: Enact appropriate policies to promote stewardship and 
sustainability.
  --The NIH OSP recently completed its analysis of public comments on 
        proposed provisions for a draft data management and sharing 
        policy. OSP is in the process of incorporating the public 
        feedback and will release a draft policy statement for further 
        public consultation.
    Question. The Committee included $30 million to support the Chief 
Data Strategist's work in fiscal year 2019. What is the status of NIH's 
plan for this funding?
    Answer. The NIH has engaged in a multi-step planning process to 
identify the most pressing trans-NIH needs for the data science funding 
provided by Congress. The $30 million is being used to advance the 
trans-NIH data ecosystem--that is, we are working to make currently 
siloed data storage and workspaces connect (interoperable) by 
establishing standards, building infrastructure and tools to allow 
different data repositories to talk to each other, and defining common 
data elements and standards.
                dpcpsi/office of strategic coordination
    Question. The Data Commons Pilot Phase was initiated under the New 
Models of Data Stewardship program, implemented in support of the 
Strategic Plan for Data Science. This project was supposed to run 
through fiscal year 2020 and was tasked with developing a four-year 
roadmap for the data commons. What is the status of this roadmap, how 
is NIH implementing the associated recommendations, and what are the 
next steps for this initiative?
    Answer. The NIH Data Commons Pilot, part of the Common Fund's New 
Models of Data Stewardship program, aimed to accelerate new biomedical 
discoveries by developing and testing a cloud-based platform where 
investigators could store, share, access, and interact with digital 
objects (data, software, etc.) generated from biomedical and behavioral 
research. By connecting the digital objects and making them accessible, 
the Data Commons was intended to foster novel scientific research that 
wasn't possible before, including hypothesis generation, discovery, and 
validation. The program supported the NIH Strategic Plan for Data 
Science \43\ goal to develop new, cutting-edge methods for storing, 
sharing, and analyzing NIH supported datasets in the cloud.
---------------------------------------------------------------------------
    \43\ https://datascience.nih.gov/strategicplan.
---------------------------------------------------------------------------
    From 2017-2018, researchers funded as part of the NIH Data Commons 
Pilot Phase Consortium (DCPPC) tested the best ways to build and 
implement the cloud-based platform described above. They iteratively 
experimented with a series of key capabilities needed for the Commons 
to operate and meet standards for being FAIR--findable, accessible, 
interoperable, and reusable. Three different and high-value test case 
data sets helped in setting policies, processes, and architecture for 
the Data Commons Pilot Phase.
    Development of a roadmap for modernizing the biomedical data 
science ecosystem requires trans-NIH coordination, most appropriately 
managed by the NIH Office of Data Science Strategy (ODSS). Therefore, 
ODSS is developing a broad, trans-NIH data ecosystem strategy informed 
by the tools and best practices developed by the DCPPC. The Common Fund 
will continue to test, evaluate, and refine a subset of deliverables 
from the Data Commons Pilot Phase, working with Common Fund programs to 
establish a cloud-based data ecosystem for Common Fund datasets.
                 dpcpsi/office of data science strategy
    Question. Research organizations are exploring the best ways to 
create research data commons. Private sector communities of companies 
and extramural research institutions, like Sage Bionetworks, Penn 
State, and Google's datacommons.org have demonstrated success. Even 
other Federal agencies have successfully established data commons, such 
as the National Science Foundation big data innovation hubs, and are 
further along than NIH. Furthermore, we must ensure NIH is also 
learning from less successful attempts at driving data infrastructure, 
such as caBIG, which saw little traction in the community and was 
widely criticized. As good stewards of taxpayer investments, what is 
NIH doing to avoid ``reinventing the wheel'' and how is NIH planning to 
leverage data commons work already being done extramurally?
    Answer. NIH appreciates the opportunity to highlight how we are 
building upon the advances in academia and industry to create a highly 
integrated biomedical research data ecosystem. A principle stumbling 
block across data science is the compartmentalization of data--from 
biomedical research data, disease specific data, health records and 
data resulting from clinical trials. These data silos impede discovery 
of commonalities across diseases and inhibit a cross-disciplinary 
understanding that will rapidly accelerate innovation in the biomedical 
research enterprise. Our goal at NIH is to leverage data and 
information from different studies and across diseases to empower 
investigators to ask new questions and make new discoveries to improve 
human health.
    To do so, NIH is investing in many data commons efforts, including 
NHGRI ANVIL, NCI Cancer Research Data Commons, All-of-Us Research 
Program, NIMH Data Archive, NHLBI Data STAGE and others.\44\ We have 
recently completed a NIH Data Commons Pilot study and we have 
undertaken a comprehensive analysis of this, and the other commons 
efforts listed above, to learn from our past and current efforts and to 
determine successful approaches with existing capabilities.
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    \44\ NHGRI AnVIL is designed to be an interoperable resource for 
the genomics community to co-locate data, storage and computing with 
commonly used services for analyzing and sharing data.
    NCI Cancer Research Data Commons is a virtual, expandable 
infrastructure to provide secure access to cancer-specific data to 
allow researchers to analyze, share and store their work, in a cloud 
environment.
    NIMH Data Archive is a collaborative resource that contains human 
subjects research data for Autism research
    NHLBI Data STAGE is a digital environment that allows for access to 
NHLBI datasets and innovative data analysis capabilities, in a cloud 
environment.
    All-of-Us Research Program provides a cloud-environment to gather 
and serve data from one million or more people living in the United 
States.
---------------------------------------------------------------------------
    NIH is also working with leading industry partners, including 
Google and Amazon, and academic collaborators, to leverage those 
experience, expertise and technologies as we work to connect high-value 
NIH data systems. An early example of this is the cross-NIH effort to 
create an industry-standard system that will allow any NIH researcher a 
single-entry point to NIH data resources, with the appropriate 
security-enabled data access.
    In addition, the National Center for Advancing Translational 
Sciences' (NCATS) Biomedical Data Translator program is building an 
informatics platform that aims to bridge the current symptom?based 
diagnosis of disease with research?based molecular and cellular 
characterizations through interrogation of relationships across the 
full spectrum of data types (e.g., disease names, clinical signs and 
symptoms, to organ and cell pathology, genomics, and drug effects). The 
Translator is not a database but rather is focused on identifying data 
integration and inclusion barriers and exploring inferential or 
predictive models that would provide new insights into biology, health, 
and disease. The Translator will find and connect existing data, 
provide previously unknown insights into diseases and possible 
treatments, and make inferences and predictions even when data are 
missing to translate basic data science to clinical and public health 
practices.
    Together these, and other efforts articulated in the NIH's 
Strategic Plan for Data Science, aim to maximize the value of the data 
generated through NIH-funded efforts to enable biomedical discovery and 
innovation. Doing so is critical for keeping the United States at the 
forefront of biomedical research and ensuring continued advances toward 
improving the Nation's health.
    Question. Beyond the efforts in NIGMS, what is the NIH doing to 
encourage, support and incorporate computational science training in 
other scientific fields beyond those like genomics and neuroscience 
which have already embraced it?
    Answer. NIH is committed to training the next generation of 
researchers across biomedical related disciplines, including computer 
science. Twelve of the agency's Institutes, Centers, and Offices (ICOs) 
support a funding opportunity, the Mentored Quantitative Research 
Career Development Award (K25), to attract investigators whose 
quantitative science and engineering research has thus far not been 
focused on questions of health and disease. This funding opportunity 
supports professionals with quantitative (e.g., mathematics, 
statistics, economics, computer science, imaging science, informatics, 
physics, chemistry) and engineering backgrounds to integrate their 
expertise with NIH-relevant research. Another cross-NIH effort, 
Predoctoral Training in Advanced Data Analytics for Behavioral and 
Social Sciences Research--Institutional Research Training Program 
(T32), is funding training opportunities for predoctoral students in 
data analytics for behavioral and social science research and is 
supported by a number of ICOs. Other trans-NIH funding opportunities 
are being planned to broaden the expertise of the extramural biomedical 
community and will be released in the coming months. Additionally, the 
National Library of Medicine recruits data scientists to work in their 
institute through several coordinated postdoctoral training programs, 
and has a joint program with the National Institute of Dental and 
Craniofacial Research to recruit computer scientists to postdoctoral 
studies in the dental field. Other ICOs across NIH recruit 
computational experts to work in their intramural research programs 
based on the lab's specific needs.
    Training programs for NIH staff and extramural researchers who are 
putting data into Science and Technology Research Infrastructure for 
Discovery, Experimentation, and Sustainability Initiative are currently 
being offered. These trainings target general use of the cloud 
platforms as well as generic [mock/dummy] tool and dataset use in cloud 
environments.
    NIH has also initiated several fellowships to expand the expertise 
of the NIH internal workforce, by bringing computationally-savvy 
individuals to work in NIH offices. For example, through Coding it 
Forward's Civic Digital Fellowship and the NIH Office of Intramural 
Training and Education Graduate Data Science Summer Program, ODSS will 
bring 23 data scientists to NIH campus this summer to be placed in 
offices and laboratories throughout the agency. Other programs led by 
NIH to bring computational experts into the Federal workforce include 
the Emerging Leaders in Data Science Fellowship, led by NIAID, and the 
Big Data Scientist Training Enhancement Program, co-led by NCI and the 
Department of Veterans Affairs.
                              rare cancers
    Question. At least 95 percent of 400 known forms of cancer meet the 
American Cancer Society criteria of affecting fewer than 6 Americans 
per 100,000 per year, yet in 2018 nearly 80 percent of cancer patients 
with no approved targeted therapeutic for their cancer have a rare 
cancer. Many of these cancer patients are faced with decades-old 
treatment protocols that include harsh chemotherapies which are 
frequently ineffective for their cancers. What are NIH, NCI and NCATS 
doing to develop more therapeutics for these neglected rare cancers?
    Almost 1 in 3 new cancer diagnoses is for a rare cancer. However, 
rare cancers suffer from critical gaps in funding, available data, and 
basic and translational science. In 2017, over 148 forms of rare cancer 
received no direct funding from NIH, and that gap in spending is 
associated with a lack of FDA-approved targeted therapies available for 
those cancers. Simultaneously, just 34 out of 380 forms of rare cancer 
received almost 40 percent of NIH funding that was directed to rare 
cancers. What is being doing to encourage greater support for research 
into rare cancers?
    I understand 95 percent of all cancers are rare forms, and 
increased use of molecular subtyping can lead to more accurate 
diagnoses of those precise forms. But that is only if this subtyping is 
done. I understand molecular diagnostics are seldom used for the 
majority of patients and data on cancer subtypes is rarely shared among 
researchers and physicians. What can be done to improve molecular 
analysis for patients, and to permit patients to anonymously and 
publicly share their data with researchers and drug developers?
    A key to understanding and developing targeted cancer treatments is 
the ability to research tumor cell lines, yet cells lines for rare 
cancers are frequently difficult to obtain, especially for smaller 
companies, due to high costs or licensing restrictions. When they are 
available, they sometimes do not share the genetic profiles of the 
cancers they are meant to represent. Why is that? How can we change 
that to accelerate research to save lives in the near-term?
    Treatment for pediatric cancers carries a tremendous burden for 
survivors throughout their childhood and adult lives, frequently due to 
the use of caustic chemotherapy agents. There is only one currently 
available targeted therapy that is specifically approved for a 
childhood cancer, neuroblastoma. What is being done to ensure that 
childhood cancers receive appropriate levels of funding for 
translational research that turns basic science into new therapies?
    Over 550,000 Americans were newly diagnosed with a rare cancer in 
2018, but SBIRs, which are a major source of translational funds to 
bridge the drug development 'valley of death', primarily fund common 
cancers. In fact, in the 5-year span between 2013 and 2017, 262 forms 
of cancer, all rare, did not receive any directed funding--that's over 
65 percent of all types of rare cancer. What is being done to ensure 
that SBIR funding is addressing the critical translational gap for 
these neglected rare cancer patients?
    Over half a million Americans were newly diagnosed with a rare 
cancer in 2018. For over 100 of those cancers, there are no available 
datasets in the most significant microarray repository in the world, 
GEO. Unfortunately for those patients whose cancers are not 
represented, they have an almost 7-fold decreased likelihood of having 
a targeted therapy. What is being doing to ensure that all forms of 
cancer have significant dataset presence in publicly available data 
repositories?
    Answer. Rare cancers all qualify as rare diseases, which are 
diseases or conditions affecting fewer than 200,000 people in the U.S. 
The National Center for Advancing Translational Sciences (NCATS) has 
several programs and initiatives focusing on rare diseases, including 
rare cancers. Specifically, the Office of Rare Diseases Research (ORDR) 
is dedicated exclusively to accelerating treatments and research to 
benefit rare disease patients.
    Advancing research on rare cancers is an important focus across the 
NCI portfolio as well. As our understanding of cancer expands, we now 
know it is not one disease, but hundreds, if not thousands, of cancer 
types and subtypes--a collection of rare diseases. A quarter of all 
cancer deaths each year are due to rare cancers. Although new 
treatments are always being developed, finding new effective treatments 
for rare cancers is challenging for many reasons. Additionally, this 
translational and clinical research is only possible due to NCI's 
sustained investment in basic science that advances understanding and 
progress for all cancer types, including rare cancers.
    Question. What are NIH, NCI and NCATS doing to develop therapeutics 
for these neglected rare cancers?
    Answer. Several NCI-supported research efforts aim to advance and 
accelerate the development of targeted cancer therapies for rare cancer 
types and subtypes diagnosed in children and adults. The following 
narrative describes some of the major NCI initiatives that may benefit 
rare cancer patients, but it is not an exhaustive list of the 
Institute's investments in rare cancer research.
    The cancer research community continues to recognize that cancer is 
made up of a collection of hundreds, if not thousands, of subtypes 
defined by these characteristics. NCI-supported research like The 
Cancer Genome Atlas \45\ and the Pediatric TARGET (Therapeutically 
Applicable Research to Generate Effective Treatments) Initiative,\46\ 
as well as the Pediatric Cancer Genome Project led by Washington 
University and St. Jude Children's Research Hospital,\47\ have been 
critical to advancing this field. As a result of these efforts and 
other relevant research, ``cancer'' is increasingly recognized as a 
collection of rare cancer subtypes, each of which will likely require a 
somewhat different treatment. NCI's ongoing efforts include research to 
support the development and evaluation of precision approaches to 
cancer therapy--including targeted chemotherapy and immunotherapy, and 
combination therapy approaches based on the molecular profile of the 
cancer.
---------------------------------------------------------------------------
    \45\ https://cancergenome.nih.gov/.
    \46\ https://ocg.cancer.gov/programs/target.
    \47\ https://www.stjude.org/research/pediatric-cancer-genome-
project.html.
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    As part of the Cancer Moonshot, NCI launched the Rare Tumor Patient 
Engagement Network in fiscal year 2018, leveraging the unique resources 
of the NCI intramural research program and the NIH Clinical Center to 
bring together national and international investigators, patients, 
advocacy groups, and industry to comprehensively study rare tumors and 
provide exceptional patient care. Under the umbrella of this effort, 
NCI has also launched the Moonshot Pediatric, Adolescent, and Young 
Adult Rare Tumors (MyPART) Network, a collaboration of scientists, 
patients, family members, advocates and healthcare providers to find 
treatments for rare cancers.\48\ The MyPART Network will collect 
samples like blood, saliva, and biopsy tissue from people with rare 
tumors to study how rare tumors grow, share data from rare cancer 
samples with other scientists, build new ways of testing new 
treatments, and design new clinical trials for rare cancers.\49\ 
Another component of this rare tumors initiative, the NCI Comprehensive 
Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) within the 
intramural program aims to advance the understanding of rare adult 
central nervous system (CNS) cancers by establishing and fostering 
patient-advocacy-provider partnerships and networks to improve 
approaches to care and treatment. Although all primary adult CNS tumors 
can be considered rare, NCI-CONNECT is starting with 12 types, each 
with less than 2,000 patients diagnosed a year. NCI-CONNECT intends to 
address these challenges and unmet needs by connecting patients, 
providers, researchers and community organizations to work in 
partnership.\50\
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    \48\ https://ccr.cancer.gov/research/cancer-moonshot.
    \49\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor/about/
what-is-mypart.
    \50\ https://ccr.cancer.gov/neuro-oncology-branch/connect.
---------------------------------------------------------------------------
    The NCI-MATCH Trial \51\ is an important research program for rare 
cancers for which there is not a standard of care or cancers that no 
longer respond to standard treatment. This nationwide trial, which has 
enrolled patients in all 50 States, analyzes patients' tumors to 
determine whether they contain gene abnormalities for which a targeted 
drug exists and then assigns patients to treatment based on the 
abnormality. Using this approach, the NCI-MATCH trial holds promise for 
improved treatment options for both common and rare cancers. The trial 
originally had ``set aside'' 25 percent of screening accrual to be for 
rare cancers, to ensure that more common cancers were not over-
represented. Ultimately 62.5 percent of the over 6,000 patients 
screened for MATCH represented rare cancers. However, even with 6,000 
patients screened, some trial arms did not complete accrual due to the 
low frequency of a particular variant in the population. Thus, patients 
continue to be enrolled in these trial arms through the Rare Variants 
Initiative. Launched in May 2017, the Rare Variants Initiative casts a 
wider net for patients through collaborations with additional 
commercial and academic partners that will help find patients with 
uncommon genetic variants and let their doctors know they may be 
eligible for the MATCH trial.
---------------------------------------------------------------------------
    \51\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
nci-supported/nci-match.
---------------------------------------------------------------------------
    The mission of the NCI Experimental Therapeutics (NExT) Program 
\52\ is to advance clinical practice and bring improved therapies to 
patients with cancer by supporting the most promising new drug 
discovery and development projects. For those institutions 
collaborating with NCI, NCI may leverage its scientific expertise and 
various contract and grant resources toward the implementation and 
development of submitted projects. The NCI will partner with successful 
applicants to facilitate the milestone-driven progression of new 
anticancer drugs (small molecules, biologics) and imaging agents 
towards clinical evaluation and registration.
---------------------------------------------------------------------------
    \52\ https://next.cancer.gov/entryToPipeline/default.htm.
---------------------------------------------------------------------------
    Additionally, NCATS supports the Tissue Chip for Drug Screening 
Program, which is an innovative program that enables the development of 
microphysiologic systems to develop human tissues on bioengineered 
chips. This program seeks to better understand human disease, model 
human organs and organ systems, and potentially serve as toxicology and 
drug screening systems. Many rare disease indications have been 
included in the tissue chip program, including tuberous sclerosis, 
which is a rare disease that leads to benign tumor growth in the brain. 
This program is planning to support development of chips that can be 
used to inform potential clinical trials on rare diseases and, in 
conjunction with NCI, rare cancers will be included as part of the 
research focus.
    NCATS also supports the Therapeutics for Rare and Neglected 
Diseases (TRND) and the Bridging Interventional Development Gaps 
(BrIDGs) programs. TRND supports pre-clinical development of 
therapeutic candidates intended to treat rare or neglected disorders 
with the goal of enabling an Investigational New Drug application 
(IND). TRND works in collaboration with external partners, such as 
academia and industry on these projects, and TRND provides scientific 
expertise and resources to further therapeutic development. Researchers 
working on rare cancers are eligible for assistance from this program. 
Similarly, BrIDGs assists researchers in advancing promising 
therapeutic agents thought late-stage pre-clinical development toward 
an IND and clinical testing. Currently, these programs are working on 
several rare cancer-related projects, including work on pancreatic 
cancer and core binding factor (CBF) leukemia.
    Notable NCATS programs led through the ORDR relevant to rare 
cancers include:
  --The Rare Diseases Clinical Research Network (RDCRN) \53\ provides 
        cooperative awards to multi-center multi-disciplinary consortia 
        who study three or more related rare diseases at a time. This 
        program has supported research into >250 rare diseases since 
        its inception, including some rare cancer-related diseases and 
        conditions. Applications for new consortia members are 
        currently being considered and awards will be announced around 
        June-July 2019. Some of the applications being considered 
        include rare cancers and cancer-related conditions that may be 
        funded in collaboration with NCI.
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    \53\ https://ncats.nih.gov/rdcrn.
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  --The Bench-to-bedside (B2B) grant program \54\ is run by the NIH 
        Clinical Center (CC), and NCATS ORDR supports four B2B awards 
        each year for rare disease indications. These grants are for 
        intramural/extramural partnerships leveraging the CC and other 
        resources to facilitate translating bench research toward 
        clinical trials. Several rare cancer-related B2B grants have 
        been supported through this program over the past 15 years. 
        Some examples of rare cancer and cancer-related B2B awards 
        include, but are not limited to: T-cell adoptive therapy for 
        viral infection after stem cell transplantation and CAR-
        modified CD8+ memory stem cells targeting B-cell malignancies, 
        among others.
---------------------------------------------------------------------------
    \54\ https://clinicalcenter.nih.gov/ccc/btb/.
---------------------------------------------------------------------------
  --The Toolkit for Patient-focused Therapies Development (``Toolkit'') 
        \55\ and the Rare Diseases Registry program (RaDaR) \56\ assist 
        patients and patient groups, who play a large role in 
        therapeutics development and research for rare diseases, 
        including rare cancers. Toolkit and RaDaR provide advice, 
        tools, templates and best practices for initiating and 
        furthering rare disease research programs and registries, 
        respectively. Toolkit and RaDaR are web-based freely accessible 
        resources that anyone can access and use.
---------------------------------------------------------------------------
    \55\ https://rarediseases.info.nih.gov/toolkit.
    \56\ https://registries.ncats.nih.gov/.
---------------------------------------------------------------------------
  --The Scientific Conferences (R13 and U13) Grant program \57\ 
        provides small grants to help co-fund scientific conferences 
        and meetings. Priority areas for NCATS include translational 
        sciences and rare diseases, including rare cancers. In the past 
        several years, grants have included conferences on rare cancers 
        and cancer-related indications, including, but not limited to, 
        cholangiocarcinoma, cancer vaccines, RASopathies, and cancer 
        immunotherapy, among others.
---------------------------------------------------------------------------
    \57\ https://grants.nih.gov/grants/funding/r13/index.htm.
---------------------------------------------------------------------------
    Question. What is being doing to encourage greater support for 
research into rare cancers?
    Answer. The NIH and the NCI rely heavily on scientific peer review, 
in which highly trained outside scientists initially review 
investigator-initiated research proposals and score them based on 
factors such as scientific merit, potential impact, likelihood of 
success, and disease burden. Thereafter, the National Cancer Advisory 
Board conducts a review of the research proposals. NCI does not 
establish predetermined targets for a specific disease area or research 
category, and does not set preestablished funding levels for cancer 
types or specific areas of cancer research. It is important to note 
that NCI and NIH do not consider disease burden to be limited to how 
many people are diagnosed with a disease or condition, but rather uses 
a broader lens to capture the impact of a health condition as measured 
by mortality, morbidity, financial cost, and other indicators. 
Accordingly, NIH's Institutes and Centers support special initiatives 
based on public health need, including burden of disease. Comprehensive 
portfolio analysis and programmatic evaluation are also critical to 
these programmatic decisions and development of special initiatives. 
Examples span common and rare cancers, such as NCI's RAS Initiative, 
which focuses on molecular alterations in the RAS family of genes and 
pathways, responsible for driving the development and progression of 
several common and rare cancers. Other examples include the Cancer 
Moonshot, which is supporting research relevant across cancer types and 
scientific areas, and NCI's proposed Childhood Cancer Data Initiative.
    In addition, the Institute strives to balance strategic efforts to 
address public health needs with its basic scientific research 
portfolio. Basic research, which represents approximately half of the 
NCI research portfolio, is vital to achieve progress in the cancer 
types for which little or no progress has been made. Decades of basic 
research investments from NCI and NIH have demonstrated the value of 
basic research as a foundation for clinical advances, even though the 
basic research may lack a direct initial connection to a specific 
disease, the serendipitous discoveries of basic research illuminate 
pathways for future clinical breakthroughs.
    Question. Molecular diagnostics are seldom used for the majority of 
patients and data on cancer subtypes is rarely shared among researchers 
and physicians. What can be done to improve molecular analysis for 
patients, and to permit patients to anonymously and publicly share 
their data with researchers and drug developers?
    Answer. Detailed molecular characterization of tumors has 
demonstrated the heterogeneity of cancer and can identify genetic 
alterations that may allow for the selection of targeted therapies for 
patients based on the unique profile of a patient's tumor. This is the 
basis for the NCI-MATCH trial mentioned above. However, it is important 
to point out that targeted therapies currently only exist for a small 
number of known genetic alterations.
    Although comprehensive genomic profiling is technically feasible, 
its current application in clinical practice is fragmented and there 
are barriers to wide-spread profiling. These barriers include cost, 
lack of standardized genomic profiling panels and tumor collection, 
insufficient evidence of broad-based clinical utility, and lack of 
infrastructure to harmonize and share data across the clinical and 
research community.
    The NCI is addressing several of these barriers. Precision medicine 
clinical trials like NCI-MATCH and others seek to provide the evidence 
of clinical utility of treating a patient based on a unique 
characteristic of the patient's tumor regardless of the type of tumor. 
In addition, other NCI research supported through the Cancer Moonshot's 
direct patient engagement efforts,\58\ including the Rare Tumor Patient 
Engagement Networks mentioned above, will support molecular 
characterization of patients' tumors, directly engage patients to 
participate in clinical trials, and share tumor profiling data with the 
research community and the individual patient participants through a 
secure linked network of databases.
---------------------------------------------------------------------------
    \58\ https://www.cancer.gov/research/key-initiatives/moonshot-
cancer-initiative/implementation/patient-engagement.
---------------------------------------------------------------------------
    The NCI has established the Cancer Research Data Commons as a part 
of a larger National Cancer Data Ecosystem to support precision 
medicine. The Data Commons will provide an information platform to 
support the integration of genetic information about patients and their 
tumors with data on how the tumors respond to therapy. The Data Commons 
will also incorporate additional data such as imaging and clinical data 
from patients to identify approaches to cancer care that will improve 
patient outcomes. Other NCI efforts include the development of a cancer 
data aggregator to link various data types across the Data Commons and 
ultimately allow for analysis of multimodal data sets; and an encrypted 
unique patient identifier to link patient level data while protecting 
personally identifiable information. The former is critically important 
to address patient privacy issues that exist with publicly sharing 
their data.
    Cost is an important issue outside of the scope of the NCI mission. 
However, NCI notes that in March 2018 CMS took an important step in 
addressing this barrier by finalizing a National Coverage Determination 
that covers diagnostic laboratory tests using Next Generation 
Sequencing for patients with advanced cancer.\59\
---------------------------------------------------------------------------
    \59\ https://www.cms.gov/newsroom/press-releases/cms-finalizes-
coverage-next-generation-
sequencing-tests-ensuring-enhanced-access-cancer-patients.
---------------------------------------------------------------------------
    Question. A key to understanding and developing targeted cancer 
treatments is the ability to research tumor cell lines, yet cells lines 
for rare cancers are frequently difficult to obtain, especially for 
smaller companies, due to high costs or licensing restrictions. When 
they are available, they sometimes do not share the genetic profiles of 
the cancers they are meant to represent. Why is that? How can we change 
that to accelerate research to save lives in the near-term?
    Answer. As a public sponsor of biomedical research, NIH, including 
the NCI, is committed to supporting national and international efforts 
that encourage the sharing and dissemination of important research 
resources. NIH also recognizes the need to support reasonable incentive 
structures that facilitate commercial development or translation of 
basic research findings. Restricted availability of unique research 
resources, upon which further studies depend, can impede the advance of 
research. Conversely, sharing biomaterials, reagents and data in a 
timely manner has been an essential element to stimulate rapid research 
progress on many model organisms for biomedical research. The NIH is 
interested in continuing to ensure that the research resources 
developed with NIH funding are made readily available in a timely 
fashion to the research community for further research, development, 
and application, which will further the research enterprise and 
accelerate the development of products and knowledge of benefit to the 
public.
    With regard to rare cancers specifically, low incidence rates of 
rare cancers mean both patients and researchers face unique challenges. 
To address these concerns, NCI supports development of several research 
resources and makes them available to the extramural research community 
for use in investigator-initiated research projects and NCI-supported 
programs. Such resources include the Human Cancer Models Initiative 
(HCMI) \60\ and the NCI Patient-Derived Models Repository (PDMR).\61\ 
Many of NCI's resources are catalogued on the Resources for 
Researchers\62\ website which provides information on how to obtain the 
resources.
---------------------------------------------------------------------------
    \60\ https://ocg.cancer.gov/programs/HCMI.
    \61\ https://pdmr.cancer.gov/, https://www.cancer.gov/news-events/
cancer-currents-blog/2018/nci-pdmr-cancer-research-models.
    \62\ https://www.cancer.gov/research/resources.
---------------------------------------------------------------------------
    The HCMI is a collaborative international consortium that is 
generating 1,000 novel, next-generation, cancer models from patient 
tumors that are clinically and molecularly characterized. HCMI-
developed models and related genomic and clinical data are available as 
a community resource without excessive intellectual property (IP) 
constraints. The NCI is contributing to the initiative by supporting 
four Cancer Model Development Centers (CMDCs) at the Broad Institute, 
Cold Spring Harbor Laboratory, Weill Cornell Medicine, and Stanford 
University. These cancer models will serve as valuable resource for 
translational cancer research and will contribute to developing 
innovative therapeutic strategies, identifying novel diagnostic 
markers, and individualizing patient treatment plans. In addition, the 
initiative will make resources such as protocols used for model 
development, SOPs, and other model-associated support available to aid 
the research community to generate additional models. There are 
currently 19 models available through the HCMI searchable catalog.\63\
---------------------------------------------------------------------------
    \63\ https://hcmi-searchable-catalog.nci.nih.gov.
---------------------------------------------------------------------------
    The PDMR is mainatained by the Frederick National Laboratory for 
Cancer Research and is a national repository of patient-derived 
xenografts developed from patients with solid tumors. These models are 
clinically-annotated with molecular information available in an easily 
accessible database for the extramural community. Since the launch of 
the PDMR in early 2017, 166 public models have been developed from 163 
unique patients, and new models continue to be added for cancer types 
already existing in the repository. Several new cancer types are now 
available in the PDMR collection, including some rare cancers. These 
new cancer models are of high value to the research community and 
include: several gynecologic cancers (ovarian, vaginal, carcinosarcoma, 
and cervical), small cell lung cancer (a subtype of lung cancer that is 
a rare disease), Hurthle cell neoplasm (a rare and often aggressive 
form of thyroid cancer), Osteosarcomas, chondrosarcoma, squamous cell 
skin carcinoma, Merkel cell carcinoma (a rare and aggressive form of 
skin cancer), mesothelioma (a rare type of lung cancer). The primary 
goal of this repository is to make a publicly available archive and 
repository of tumor samples and models that are fully characterized 
from a molecular and clinical perspective, and that are easily 
accessible to the extramural community at a very modest cost.
    NCI also supports pediatric cancer cell lines and models to address 
key challenges in the development of new therapies for children with 
cancer (all childhood cancers are considered rare diseases). NCI's 
Preclinical Testing Consortium (PPTC) \64\ develops reliable 
preclinical testing data for pediatric drug candidates that can be used 
to inform new agent prioritization decisions. The PPTC consists of a 
Coordinating Center and five Research Programs that perform in vivo 
testing of pediatric anticancer drug candidates for a particular cancer 
(sarcoma and renal, neuroblastoma, osteosarcoma, leukemia, and brain 
tumors). The PPTC collaborates with pharmaceutical companies and 
academic drug developers to systematically test candidate agents 
against well-credentialed panels of genomically characterized childhood 
cancer models to identify those investigational agents most likely to 
have clinical activity against childhood cancers. For example, in 2011, 
the PPTC developed a model for a subtype of pediatric low-grade 
astrocytoma (PLGA, a type of brain tumor) with a mutation in a gene 
called BRAF and identified a targeted therapy, selumetinib, for 
additional research. Building upon these findings, the PBTC conducted a 
Phase 1 trial of selumetinib.\65\ In this trial, children with BRAF-
mutated PLGAs responded to treatment by showing tumor shrinkage. Based 
on these promising findings, the trial is now in a Phase 2 expansion 
with results from several cohorts reported in 2017 showing that 
selumetinib is active for patients with two subtypes of BRAF-mutated 
PLGAs.\66\
---------------------------------------------------------------------------
    \64\ http://www.ncipptc.org/.
    \65\ https://clinicaltrials.gov/ct2/show/NCT01089101.
    \66\ http://ascopubs.org/doi/abs/10.1200/
JCO.2017.35.15_suppl.10504.
---------------------------------------------------------------------------
    Question. What is being done to ensure that childhood cancers 
receive appropriate levels of funding for translational research that 
turns basic science into new therapies?
    Answer. Pediatric cancer research remains a top priority for the 
NCI. Each year the Institute identifies the best research opportunities 
to build upon the foundation of basic science, further develop the 
scientific understanding of genetic drivers of childhood cancers, 
identify effective therapies, and enhance the quality of life for 
pediatric cancer survivors.
    When considering the Institute's investments in any category of 
disease research, NCI does not make decisions about funding based on 
predetermined targets for a specific disease area or research category. 
Rather, NCI relies on technical and scientific peer review, in which 
highly trained outside investigators perform an initial review of 
research proposals and evaluate them on factors such as scientific 
merit, likelihood of success, and potential impact. Thereafter, the 
National Cancer Advisory Board, which includes members with pediatric 
oncology expertise, also conducts a review of the research proposal. 
NCI leadership further evaluates proposals to consider factors such as 
scientific novelty and overall representation of the research topic 
within the NCI portfolio.
    Recognizing that childhood cancers are distinct from adult cancers, 
NCI supports numerous targeted programs aimed at advancing research in 
pediatric oncology. These efforts include:
  --The Children's Oncology Group (COG),\67\ part of NCI's National 
        Clinical Trials Network (NCTN), develops and coordinates 
        pediatric clinical trials across more than 200-member 
        institutions. In addition to conducting late-phase clinical 
        trials, the COG receives NCI support for the Phase 1 and Pilot 
        Consortium,\68\ which conducts early-phase trials and pilot 
        studies to rapidly introduce new anticancer agents into 
        pediatric care.
---------------------------------------------------------------------------
    \67\ https://www.childrensoncologygroup.org/.
    \68\ https://www.childrensoncologygroup.org/index.php/phase-1-home.
---------------------------------------------------------------------------
  --The Pediatric Oncology Branch (POB) \69\ in NCI's Center for Cancer 
        Research, part of NCI's intramural research program, conducts 
        high-risk, high-impact basic, translational, and clinical 
        research.
---------------------------------------------------------------------------
    \69\ https://ccr.cancer.gov/Pediatric-Oncology-Branch.
---------------------------------------------------------------------------
  --The NCI-COG Pediatric MATCH Trial,\70\ launched in July 2017, tests 
        molecularly targeted therapies in children and adolescents with 
        advanced cancers who have few other treatment options. This 
        nationwide trial is open to children and adolescents from 1 to 
        21 years of age and currently has eight treatment arms.
---------------------------------------------------------------------------
    \70\ https://www.cancer.gov/about-cancer/treatment/clinical-trials/
nci-supported/pediatric-match.
---------------------------------------------------------------------------
  --Other efforts include the Pediatric Preclinical Testing Consortium 
        (PPTC),\71\ the Therapeutically Applicable Research to Generate 
        Effective Treatments (TARGET) \72\ program, the NCI 
        Experimental Therapeutics (NExT) Program,\73\ the Childhood 
        Cancer Survivor Study (CCSS),\74\ the Pediatric Provocative 
        Questions (PQ) Program,\75\ the Pediatric Brain Tumor 
        Consortium (PBTC),\76\ the Pediatric Cancer Immunotherapy 
        Trials Network (CITN),\77\ and the New Approaches to 
        Neuroblastoma Therapy (NANT) \78\ Consortium.
---------------------------------------------------------------------------
    \71\ http://www.ncipptc.org/.
    \72\ https://ocg.cancer.gov/programs/target.
    \73\ https://next.cancer.gov/.
    \74\ https://www.cancer.gov/types/childhood-cancers/ccss.
    \75\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-217.html.
    \76\ https://www.pbtc.org/.
    \77\ https://ctep.cancer.gov/MajorInitiatives/
cancer_immunotherapy_trials_network.htm.
    \78\ http://www.nant.org/.
---------------------------------------------------------------------------
  --The Childhood Cancer Data Initiative proposed in the President's 
        Budget will seek to leverage existing Federal authorities to 
        effectively and efficiently coalesce different types of data 
        currently collected for pediatric cancer cases across the wide 
        variety of entities that produce and maintain it. As childhood 
        cancers represent less than 1 percent of all new cases of 
        cancer diagnosed in the United States each year, NCI recognizes 
        the need to study the basic biology of pediatric cancers to 
        develop relevant preclinical models and support clinical trials 
        that are accessible to every child with cancer. Furthermore, it 
        is critical that the data garnered from these studies is 
        aggregated and appropriately shared. In addition, the 
        integration of longitudinal data from pediatric cancer patients 
        into adulthood, and the ability to compare adult and pediatric 
        data broadly will have a profound impact upon our understanding 
        of the etiology of cancer and our ability to advance research 
        that can lead to new and better treatments.
    For decades, the foundations of both childhood and adult cancer 
treatment were surgery, chemotherapy, and radiation therapy. Recently, 
immunotherapy, in which a patient's own immune system is harnessed to 
fight cancer, has emerged as a new pillar of cancer treatment. While 
some immunotherapy approaches have been effective in treating certain 
pediatric cancers, many immunotherapy treatments being developed for 
adult cancers will likely not be applicable to childhood cancers. 
Therefore, this area remains a critical research focus.
    Recent clinical advances in immunotherapy include the 2017 FDA-
approval of Keytruda (pembrolizumab), a checkpoint inhibitor, for 
pediatric and adult patients with classical Hodgkin lymphoma that 
cannot be cured with existing treatments, as well as pediatric patients 
with solid tumors that have specific genetic features known as mismatch 
repair deficiency and high microsatellite instability. This approval is 
significant because targeting genetic characteristics, rather than 
where the cancer originates in the body, creates new options for 
patients who might otherwise not be considered candidates for a drug. 
NCI is now sponsoring early-phase clinical trials of pembrolizumab in 
children with aggressive brain tumors.
    In 2017 the FDA also approved KymriahTM 
(tisagenlecleucel), a chimeric antigen receptor (CAR) T-cell therapy, 
for children with acute lymphoblastic leukemia (ALL). This NCI-
supported discovery was first published in the New England Journal of 
Medicine in 2014. NCI is currently sponsoring nine clinical trials of 
CAR T-cell therapy in pediatric patients with other types of 
cancer.\79\
---------------------------------------------------------------------------
    \79\ https://clinicaltrials.gov/ct2/results?cond=&term=CAR+T-
cell&type=&rslt= &recrs=b&recrs=
a&recrs=f&recrs=d&age_v=&age=0&gndr=&intr=&titles=&outc=&spons=National+
Cancer+
Institute&lead=&id=&cntry=&state=&city=&dist=&locn=&strd_s=&strd_e=&prcd
_s=
&prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=.
---------------------------------------------------------------------------
    In April 2019, selumetinib was awarded Breakthrough Designation by 
the FDA,\80\ following Orphan Drug Designation in February 2018,\81\ 
for treatment of neurofibromatosis type 1 (NF1), a rare pediatric 
disease that can cause malignant tumors. Although Breakthrough 
Designation does not guarantee final approval of the drug for this 
purpose, it is promising news for the future of this rare pediatric 
disease. NCI's POB led the Phase I and II trials of selumetinib, 
through an intramural and extramural collaboration. Early results from 
the phase II trial are promising--72 percent of the 50 pediatric 
patients between the ages of 2 and 18 enrolled in the trial are 
responding to the treatment. Not only are some patients seeing their 
tumors shrink more than 50 percent, but many patients report less pain 
intensity and pain interference, as well as increased strength and 
range of motion.\82\ If this trajectory continues, selumetinib will be 
the first drug ever approved for this disease.
---------------------------------------------------------------------------
    \80\ https://ccr.cancer.gov/news/article/mek-inhibitor-selumetinib-
granted-breakthrough-
designation-by-fda-to-treat-neurofibromatosis-type-one-in-pediatric-
patient.
    \81\ https://ccr.cancer.gov/news/article/fda-grants-orphan-drug-
status-to-selumetinib-for-neurofibromatosis-type-1-nf1-treatment.
    \82\ https://meetinglibrary.asco.org/record/159508/abstract.
---------------------------------------------------------------------------
    Innovative clinical trials would not be possible without the basic 
research conducted to understand the biological mechanisms of disease 
and to identify molecular targets for therapies. The NTRK family of 
genes is one such example. Describing the role of this family of genes 
was first made possible as a result of a basic science discovery in the 
1980's at NCI's Frederick National Laboratory for Cancer Research by 
Dr. Mariano Barbacid. Dr. Barbacid was not studying pediatric cancers, 
or any particular cancer type--he was on the hunt for unique genetic 
drivers of cancer, called oncogenes. At the time, he could not have 
anticipated that his discovery would eventually lead to an effective 
therapy for rare cancers diagnosed in children and adults.
    This discovery led to the development of an NTRK inhibitor, LOXO-
101 or larotrectinib, which works against unique fusion oncoproteins 
that drive certain pediatric and adult cancers. In May 2018, FDA issued 
larotrectinib an orphan drug status and Priority Review, and in 
November 2018, FDA granted accelerated approval to larotrectinib. This 
is the second FDA approval for a precision cancer therapy that is based 
on a particular genetic alteration, rather than the site in the body in 
which a cancer occurs. Larotrectinib was evaluated in both the NCI 
adult and pediatric MATCH phase II clinical trials.
    Investigators are hopeful that the story of crizotinib (Xalkori) 
will be similar. Crizotinib was first developed to target a protein 
produced by the oncogene MET but was later found to inhibit cancer-
causing forms of the ALK gene, found in anaplastic large cell lymphomas 
(ALCL), certain neuroblastomas, and some non-small cell lung cancers 
(NSCLC). ALCL and neuroblastoma both occur in pediatric patients; the 
connection between ALCL and ALK was established in 1994, while the 
identification of ALK as a driver of neuroblastoma occurred in 2008. 
Crizotinib was first approved for NSCLC in March 2016, and it is part 
of the NCI adult and pediatric MATCH trials. In 2018, the FDA granted 
breakthrough approval of the drug for ALCL, and COG launched a phase 
III trial with crizotinib in combination with chemotherapy for high-
risk neuroblastoma patients.
    NCI will continue to support basic, translational, and clinical 
research to help develop new and less toxic therapies for children with 
cancer. NCI is also committed to supporting cancer survivorship 
research to better understand and develop interventions to address the 
late effects of cancer and its treatment in childhood, and adolescent 
and young adult (AYA) cancer survivors. NCI is currently implementing 
new research efforts in this area and is also supporting efforts to 
enhance biospecimen collection and biobanking efforts with an emphasis 
on pediatric cancer types and subtypes for which treatments have been 
least effective. Both activities are aligned with provisions of the 
Childhood Cancer STAR Act directed toward NCI.
    Question. What is being done to ensure that SBIR funding is 
addressing the critical translational gap for these neglected rare 
cancer patients?
    Answer. Consistent with the statutory mandate established by 
Congress, the NCI SBIR/STTR program is one of the largest sources of 
early stage technology financing in the United States. The program 
supports a diverse portfolio of research, from projects focused 
specifically on evaluating new treatments for rare cancers, to the 
development of cross-cutting technologies that enable research across 
cancer types. The NCI SBIR/STTR program does not direct funding based 
upon cancer type or research area. Funding is awarded through a 
rigorous and competitive peer review process, to identify the most 
promising research applications. NCI, including the SBIR/STTR program, 
recognize that there is a clear need to develop more effective 
treatments for many rare cancers and rare cancer subtypes that are 
refractory to currently available treatment options.
    Examples of current SBIR projects focusing on translational and 
clinical research for rare cancers include:
  --In 2018, NCI awarded a SBIR Phase IIB Bridge Award to Oncoceutics, 
        Inc., which seeks to develop a new cancer drug, ONC201, for 
        patients who have been diagnosed with recurrent glioblastoma 
        and high-grade glioma with limited treatment options and very 
        poor prognoses, including a pediatric high-grade glioma called 
        Diffuse Intrinsic Pontine Glioma (DIPG).\83\ Approximately 200-
        300 children are diagnosed with DIPG each year in the U.S., and 
        the median survival time from diagnosis is less than 1 year.
---------------------------------------------------------------------------
    \83\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9524880&icde=
44259659&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&pball=.
---------------------------------------------------------------------------
  --In 2018, NCI supported PEEL Therapeutics with an STTR award focused 
        on pre-clinical evaluation of a novel potential therapy for 
        osteosarcoma, a deadly pediatric bone tumor. The project is led 
        by Dr. Josh Schiffman, who is also a researcher at the Huntsman 
        Cancer Institute at the University of Utah.\84\
---------------------------------------------------------------------------
    \84\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9559358&icde=44276787.
---------------------------------------------------------------------------
  --In fiscal year 2018, NCI also funded a Phase I clinical trial of a 
        novel first-in-class drug combination of two agents (IV 
        fenretinide + IV safingol) through an SBIR Fast-Track Phase I/
        II award to CerRx, Inc. This trial, conducted at the South 
        Plains Oncology Consortium based at the Texas Tech University 
        Health Sciences Center, is testing for the treatment of 
        multiple relapsed rare cancer types including Non-Hodgkin's 
        Lymphoma, Peripheral T-Cell Lymphoma, and Esophageal 
        Adenocarcinoma. If successful, this novel biochemistry may 
        constitute a broad-based widely active treatment option for 
        both adult and pediatric malignancies.\85\
---------------------------------------------------------------------------
    \85\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9485913&icde=44283562.
---------------------------------------------------------------------------
    While these are all important examples of research underway to 
support development of new therapies for rare cancers, the SBIR 
Program's investment in cross-cutting technologies and tools is equally 
important to progress in this field. A notable example of this is NCI's 
support of Illumina, Inc. With support from NCI's SBIR program and its 
Innovative Molecular Analysis Technologies (IMAT) program,\86\ Illumina 
developed the base technology for the Infinium assay for genotyping, 
which is being used in the NIH All of Us Research Program, in other 
basic and clinical research, as well as by commercial companies like 
23andMe and Ancestry.com.\87\ In collaboration with NCI's SBIR/STTR 
program, the IMAT program is another opportunity for small businesses 
to pursue NCI support. IMAT aims to support the development and 
dissemination of novel and potentially transformative next-generation 
technologies, and uses a variety of investigator-initiated research 
project grant mechanisms to support cross-cutting, research-enabling 
disciplines.
---------------------------------------------------------------------------
    \86\ https://imat.cancer.gov/, https://imat.cancer.gov/about-imat/
outputs-and-achievements/individual-technologies-and-platforms/
sentrix%C2%AE-beadchip-and.
    \87\ https://www.cancer.gov/news-events/cancer-currents-blog/2019/
nci-sbir-working-with-small-business.
---------------------------------------------------------------------------
    These SBIR and IMAT examples, along with other NCI research efforts 
described in this response, represent important steps NCI is taking to 
support basic, translation, and clinical research to make progress for 
patients with rare cancers. NCI encourages small businesses interested 
in pursuing NCI funding to consider opportunities to apply for SBIR/
STTR \88\ and IMAT support,\89\ as well as support through the NExT 
program,\90\ also highlighted in this response.
---------------------------------------------------------------------------
    \88\ https://sbir.cancer.gov/funding.
    \89\ https://imat.cancer.gov/funding-opportunities.
    \90\ https://next.cancer.gov/entryToPipeline/default.htm.
---------------------------------------------------------------------------
    Question. What is being doing to ensure that all forms of cancer 
have significant dataset presence in publicly available data 
repositories?
    Answer. There are several data resources available from NCI that 
serve as data repositories for all forms of cancers, including rare 
cancers. Examples include the Genomic Data Commons (GDC) and the NCTN 
Navigator. The GDC \91\ is a data portal that serves as a centralized 
location to integrate and store the diverse datasets from NCI programs. 
The GDC includes cancer genomic data from over 32,000 cancer cases. All 
GDC data is available to qualified researchers free of charge and 
includes data from The Cancer Genomic Atlas (TCGA),\92\ where about 
one-third of cancer types within the TCGA resource are rare cancers; 
Therapeutically Applicable Research to Generate Effective Treatments 
(TARGET), where all of the cancers included in this pediatric genomics 
resource are considered rare; The Clinical Trials Sequencing Program 
(CTSP); and the Exceptional Responders Initiative. The GDC will also 
include data from future NCI Center for Cancer Genomics-sponsored 
cancer research programs.
---------------------------------------------------------------------------
    \91\ https://gdc.cancer.gov/.
    \92\ Rare cancer types within TCGA are: mesothelioma, adrenal gland 
tumors, testicular germ cell cancer, uveal melanoma, adrenocortical 
carcinoma, cholangiocarinoma, chromophobe kidney cancer, adult soft 
tissue sarcomas, thymomas, and uterine carcinosarcoma.
---------------------------------------------------------------------------
    Finally, the proposed fiscal year 2020 Childhood Cancer Data 
Initiative seeks to create a federated data system for pediatric cancer 
research to increase the number of cases represented, and all pediatric 
cancers are considered rare diseases. The data federation will include 
clinical records, genomic information, pathology and outcomes data and 
will build upon existing initiatives at NIH and NCI including the GDC 
and TARGET.
               cancer research and the deadliest cancers
    Question. While Congress has been providing the NIH, including the 
National Cancer Institute, with more funding each of the past 4 years, 
the odds of securing a grant from NCI have actually been getting more 
difficult.
    (A) What's driving this trend, what's its significance, and do you 
expect it to continue?
    (B) How much of the progress that you're seeing is occurring in NCI 
Cancer Centers and Translational Research centers, is it 
disproportionate, and what accounts for their success?
    (C) While the progress in cancer research is very encouraging, it 
remains elusive for those like cancers of the pancreas, esophagus, 
ovary and stomach, where progress remains elusive. What is NCI doing to 
address that?
    Please provide the number of grants and total grant funding devoted 
to research related to cancers of the pancreas, esophagus, ovary, 
liver, brain, lung and stomach for each year from fiscal year 2013 to 
fiscal year 2018.
    Answer. NIH appreciates the additional resources Congress provided 
NCI each of the past 6 years (Fiscal Years 2013-2018) to support cancer 
research. As members are fully aware, cancer continues to be a leading 
cause of death and disability for the Nation, and thus scientists 
around the country are motivated to find strategies for combatting the 
issue. The additional funding resulted in an approximately 24 percent 
increase to NCI's appropriation to support essential research into 
understanding and treating what we now recognize as a multitude of 
cancer subtypes. Over that same period, NCI received a nearly 50 
percent increase in the number of investigator-initiated grant 
applications (R01s) indicating that the field continues to attract 
researchers to propose novel scientific proposals. Specifically, during 
fiscal year 2013, NCI received 4,175 investigator-initiated R01 
applications. During fiscal year 2018 NCI received 6,113 R01 
investigator-initiated applications, and experienced year-to-year 
annual growth in the number of applications throughout the period. We 
have also observed that the increases represent a growing number of 
unique investigators applying for awards, and only a small portion 
(approximately 10 percent) of the increase in applications is driven by 
individual investigators submitting multiple applications As a result, 
even during an era of significant budget increases, this dramatic 
growth in applications had increased competition for NCI funding, and 
NCI is taking affirmative steps to improve the chances for applicants 
to be funded. Of note, in fiscal year 2019, NCI expects to increase the 
investigator-initiated research grant pool by $100 million, an amount 
that is greater than the increase NCI received to its fiscal year 2019 
base appropriation.
    (A) Regarding the increase in applications to NCI, we suspect that 
the public health burden in combination with the scientific opportunity 
is the likely source of a surging biomedical research workforce in this 
area. We are reaping the benefits of decades of investment in basic 
science and rapid advances in technology that have resulted in a record 
number of oncology drug approvals. This includes significant progress 
in the development of cancer immunotherapies and molecularly targeted 
therapies. At the same time, we are making gains in cancer prevention 
and survivorship. Taking these advances into consideration with the 
increasingly interdisciplinary nature of cancer research, that is the 
intersection of genomics, data science, biology, and more, this 
progress continues to attract more interest and talent to the cancer 
research enterprise.
    (B) The 70 NCI-designated Cancer Centers serve as anchors of the 
United States cancer research enterprise, convening concentrations of 
expertise that are vital to rapidly advance progress against cancer. 
NCI strives to provide opportunities to participate in cutting edge, 
NCI-supported research to every patient across the country, not just 
those with easy access to an NCI-designated Cancer Center and thus two 
additional pillars of the NCI research infrastructure are the National 
Clinical Trials Network (NCTN) and the NCI Community Oncology Research 
Program (NCORP), which seek to enroll diverse patient populations from 
across the Nation in NCI-sponsored research.
    The NCTN is a collection of organizations and clinicians that 
coordinates and supports cancer clinical trials at more than 3,000 
sites across the U.S. and Canada. The NCTN provides the infrastructure 
for NCI-funded treatment, screening, and diagnosis trials, centralizing 
many administrative efforts to rapidly facilitate easier enrollment of 
patients in clinical trials. For physicians and their patients, a 
variety of significant, innovative trials are widely available 
throughout the country, in large and small communities alike.\93\
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    \93\ https://www.cancer.gov/research/areas/clinical-trials/nctn.
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    NCORP, which works closely with the NCTN, expands NCI's reach even 
further. In addition to designing and conducting cancer prevention, 
supportive care and symptom management, screening, and surveillance 
clinical trials, NCORP sites recruit patients and participants to NCI-
supported treatment and imaging trials, most of which are conducted 
through the NCTN. NCORP is led by 7 research bases and 46 community 
sites, and there are over 900 NCORP component sites across the country. 
The sites represent collaborations between researchers, public 
hospitals, physician practices, academic medical centers, and other 
groups that provide healthcare services.\94\
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    \94\ https://ncorp.cancer.gov/about/.
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    Independent investigators fill out the robust research 
infrastructure supported by NCI. This includes principal investigators 
for NCI's Specialized Programs of Research Excellence (SPOREs),\95\ 
which represent collaborative translational research projects focusing 
on more than twenty organ sites, systems, and pathway-specific themes. 
While large programs like NCI-designated cancer centers, clinical 
trials networks, data commons, and biorepositories constitute the 
backbone of the cancer research enterprise, the majority of research 
proposals received and funded by NCI are investigator-initiated, 
meaning that the studies are developed by researchers themselves. This 
process allows for the scientific ingenuity and intellectual autonomy 
that is essential to advance biomedical research. In fiscal year 2018, 
NCI supported research at more than 700 institutions across the United 
States.
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    \95\ https://trp.cancer.gov/.
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    (C) NCI is committed to making progress against all cancers, 
including those that have proved most difficult to treat. Indeed, 
recognizing that the incentives that encourage private industry 
investment in therapies for more common cancers do not exist for 
cancers that occur less frequently, NCI has a responsibility to 
encourage and support research on these diseases, and does this through 
a variety of mechanisms, including support for disease-specific 
steering groups and the convening of scientific meetings and relevant 
cross-cutting research areas that seek to identify new scientific 
directions and opportunities.
    One way in which NCI encourages scientific collaboration and 
interdisciplinary research on these disease areas is through the SPOREs 
program, mentioned above. These programs include basic and clinical/
applied scientists working together to support projects that will 
result in new and diverse approaches to the prevent, detect, diagnose, 
and treat cancer. NCI currently supports SPOREs focused on pancreas, 
esophagus, ovary, liver, brain, lung and stomach cancers through the 
following awards:
  --Pancreatic SPOREs are located at the Mayo Clinic, University of 
        Nebraska Medical Center, and Washington University in St. 
        Louis.\96\
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    \96\ https://trp.cancer.gov/spores/pancreatic.htm.
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  --Gastrointestinal SPOREs, which include research on cancers of the 
        esophagus and stomach, are located at Case Western Reserve 
        University, Dana-Farber Harvard Cancer Institute, Johns Hopkins 
        University, and Vanderbilt University.\97\
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    \97\ https://trp.cancer.gov/spores/gi.htm.
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  --Ovarian SPOREs are located at Johns Hopkins University, the Mayo 
        Clinic, Roswell Park Cancer Institute, and University of TX/MD 
        Anderson.\98\
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    \98\ https://trp.cancer.gov/spores/ovarian.htm.
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  --A hepatobiliary (liver) cancer SPORE is located at the Mayo 
        Clinic.\99\
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    \99\ https://trp.cancer.gov/spores/hepatobiliary.htm.
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  --Brain SPOREs are located at Dana-Farber Harvard Cancer Institute, 
        Duke University Medical Center, Northwestern University at 
        Chicago, University of California, Los Angeles, University of 
        California, San Francisco, and University of Texas/MD 
        Anderson.\100\
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    \100\ https://trp.cancer.gov/spores/brain.htm.
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  --Lung SPOREs are located at the University of Colorado Cancer 
        Center, University of Texas/Southwestern Medicine, and Yale 
        University.\101\
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    \101\ https://trp.cancer.gov/spores/lung.htm.
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    Between June 2017 and May 2018, the FDA approved several therapies 
for cancers that are the focus of SPORE research, advances made 
possible through NCI or NIH-supported research.\102\ The approved 
treatments include: \103\
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    \102\ https://www.ncbi.nlm.nih.gov/pubmed/29440428.
    \103\ https://www.ascopost.com/issues/june-3-2018-narratives-
special-issue/fda-oncology-drug-
approvals-granted-between-june-2017-and-may-16-2018/.
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  --Rucaparib (Rubrical), a maintenance treatment for recurrent 
        ovarian, fallopian tube, or primary peritoneal cancers;
  --Lutetium Lu 177 Dotatate (Lutathera) for gastroenteropancreatic 
        neuroendocrine tumors;
  --Trastuzumab-DKST (Ogivri), a biosimilar, to treat patients with 
        certain types of metastatic stomach cancer and breast cancer;
  --Pembrolizumab (Keytruda) for patients with recurrent locally 
        advanced or metastatic, gastric or gastroesophageal junction 
        adenocarcinoma whose tumors express a certain biomarker;
  --Olaparib tablets (Lynparza) for maintenance treatment of patients 
        with recurrent ovarian, fallopian tube, or primary peritoneal 
        cancer who responded to certain chemotherapies; and
  --Several approvals to treat various subtypes of non-small cell lung 
        cancer (NSCLC):
    --Osimertinib (Tagrisso)
    --Durvalumab (Imfinzi)
    --Alectinib (Alecensa)
    --Dabrafenib (Tafinlar), in combination with Trametinib (Mekinist)
    As these approvals indicate, the scientific community recognizes 
that within each type of cancer, there are unique subtypes, and when 
possible, physicians should rely on genetic and molecular markers to 
guide treatment. NCI's investments in basic research--understanding the 
underlying mechanisms that give rise to cancer--enable rapid advances 
of precision medicine in cancer treatment. Investigators are continuing 
to identify disease subtypes, which often uncovers tumors with similar 
genetic profiles that occur in various sites throughout the body. Such 
advances led to the FDA approval of FoundationOne CDX Next Generation 
Sequencing, a genetic test to detect alterations in 324 genes and two 
genomic signatures in any solid tumor type.\104\ These developments 
benefit all cancer patients, including those with difficult to treat 
cancers.
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    \104\ https://www.ascopost.com/issues/june-3-2018-narratives-
special-issue/fda-oncology-drug-
approvals-granted-between-june-2017-and-may-16-2018/.
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    Precision medicine is the foundation for the NCI MATCH (Molecular 
Analysis for Therapy Choice) Trial, a precision medicine trial that is 
expected to provide new research ideas to advance treatments in all 
cancer types.\105\ This study is analyzing patients' tumors to 
determine whether they contain gene abnormalities for which a targeted 
drug exists, and with that information, the study assigns treatment 
based on the genetic abnormality. As of April 2019, 443 pancreatic 
cancer patients, 235 gastroesophageal cancer patients, 666 ovarian 
cancer patients, and 345 liver and hepatobiliary cancer patients, 131 
patients with brain and other central nervous system tumors, and 707 
patients with various types of lung cancers have been screened for this 
trial.
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    \105\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/nci-match.
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    Patients who are not assigned to an NCI MATCH treatment arm may be 
eligible for the NCI DART, or the Dual Anti-CTLA-4 & Anti-PD-1 blockade 
in Rare Tumors Trial. This study will also assess whether their tumors 
respond to two cutting-edge immunotherapy agents. DART is the first 
federally funded immunotherapy trial devoted entirely to rare 
cancers.\106\
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    \106\ https://www.swog.org/sites/default/files/docs/2017-11/
DARTrelease.pdf.
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    As this background demonstrates, NCI will continue to support 
research on cancers of the pancreas, esophagus, ovary, liver, brain, 
lung and stomach through multiple research mechanisms.
    Question. Please provide the number of grants and total grant 
funding devoted to research related to cancers of the pancreas, 
esophagus, ovary, liver, brain, lung and stomach for each year from 
fiscal year 2013 to fiscal year 2018.
    Answer. The information requested is provided in the tables below 
(Table 1--Fiscal Year 2018-2016 and Table 2--Fiscal Year 2015-2013). 
Brain cancer, liver cancer, lung cancer, ovarian cancer and pancreatic 
cancer are Research, Condition, and Disease Categories (RCDC) and the 
data provided include the total number of projects--grants (including 
subprojects and supplements), contracts, and intramural research--for 
the NIH for those cancer types. Total funding is broken out as total 
NIH and total NCI funding. The data are publicly available and can be 
found at: https://report.nih.gov/categorical_spending.aspx.
    Additionally, it is important to clarify that RCDC category 
listings are not budget line items. The category represents a list of 
projects selected for funding following the rigorous NIH peer review 
process. Each category list provides a look back at projects funded in 
a given fiscal year. NIH does not allocate funding prospectively by 
category, and the RCDC categories do not add up to the total NIH budget 
because projects can be applicable to more than one category, and 
categories are by their nature overlapping (e.g., neurosciences and 
brain cancer). RCDC is not intended to account for the entire NIH 
budget across thousands of research topics. More information is 
available on the RCDC FAQ page: https://report.nih.gov/rcdc/
faqs.aspx#q18.
    Esophageal cancer and stomach cancer are not currently RCDC 
categories. Therefore, the data provided for those sites are estimated 
based on NCI data for grants and intramural research projects. Although 
every attempt was made to provide data that is closely matched to the 
method used to assemble RCDC data for the other cancer sites. However, 
it is not comparable because there are no esophageal or stomach cancer 
RCDC categories.
    [The information follows:]

    
    
    
    
                 down syndrome and the include project
    Question. As a part of the INCLUDE Project, NIH has hosted 
scientific workshops to solicit input from the Down syndrome community 
on research between Alzheimer's disease and Down syndrome. What other 
topics does NIH plan to cover in future workshops and how will NIH plan 
to engage the Down syndrome community to ensure their robust 
participation in these workshops?
    Answer. The new, trans-NIH effort, Investigating Co-occurring 
conditions across the Lifespan to Understand Down syndrome, or INCLUDE, 
was launched in summer 2018. As a key component of the INCLUDE project, 
the NIA is supplementing an Alzheimer's clinical trials network to 
include adults with Down syndrome to learn more about the development 
of commonly co-occurring conditions in individuals with Down syndrome 
that are also seen in the general population, such as dementia and 
Alzheimer's disease. In addition, working through its established 
Pediatric Trials Network, in fiscal year 2019 (NICHD will create a new 
pediatric clinical trials infrastructure for Down syndrome. Such a 
resource will also ensure that new therapies can be brought to trial as 
they emerge in the future. To bolster these efforts, NIH is planning 
two major scientific workshops within the year to address the 
development of a cohort in Down syndrome, and how to include people 
with Down syndrome in clinical trials. These efforts can take advantage 
of the research registry for Down syndrome, DS-Connect,\107\ a Web-
based health registry that serves as a national health resource for 
people with Down syndrome and their families, researchers, and 
healthcare providers. Funded by NICHD since 2013, with over 4,400 
participants, the registry facilitates information sharing about 
research and upcoming trials for individuals with Down syndrome, their 
families, and researchers.
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    \107\ https://dsconnect.nih.gov/.
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    Question. How is NIH going to use the INCLUDE Project and other 
investments in Down syndrome research to support the pipeline of early 
investigators in this field?
    Answer. One of the immediate successes of INCLUDE was to attract 
new researchers and talent into the field. In fact, many of the 
recipients of awards in fiscal year 2018 were investigators who had not 
previously had a research focus on Down syndrome. Since the purpose of 
the INCLUDE project is to investigate conditions that affect both 
individuals with Down syndrome and the general population, researchers 
with subject matter expertise other than Down syndrome now have the 
opportunity to submit applications in response respond to one of 
INCLUDE's three major components: to conduct targeted, high-risk, high-
reward basic science studies on chromosome 21; assemble large study 
populations (cohorts) of individuals with Down syndrome; and include 
individuals with Down syndrome in new and existing clinical trials. 
These opportunities are widely disseminated across the Down syndrome 
community through the public-private Down Syndrome Consortium that 
includes the Trans-NIH Working Group, 16 national and international 
organizations whose missions focus on Down syndrome, and individuals 
with Down syndrome and family members. The consortium also works toward 
implementing the NIH Research Plan on Down Syndrome,\108\ which set 
research goals for Down syndrome.
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    \108\ https://www.nichd.nih.gov/publications/product/441.
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    In addition, NIH continues to fund from its baseline a wide range 
of research related to Down syndrome, across many of the NIH institutes 
and centers, nearly tripling its total funding for Down syndrome-
related research over the last few years. For example, NICHD is funding 
an early-stage investigator studying children with Down syndrome, to 
develop outcome measures for early childhood communication. In the 
future, we anticipate initiatives that will be focused on support for 
trainees to continue to build a pipeline of investigators studying Down 
syndrome.
    Question. People with Down syndrome have a unique disease spectrum 
that offers many opportunities for research. As the NIH works to set up 
a clinical trials network as a part of the INCLUDE Project, how do you 
plan to work with the Down syndrome community to encourage people with 
this condition to participate in clinical trials?
    Answer. Over the coming year, NICHD plans to work with NIA and 
other partners to coordinate building an infrastructure for a clinical 
trials network in Down syndrome across the lifespan. At the same time, 
full inclusion of individuals with Down syndrome into ongoing clinical 
studies that have been enrolling people without Down syndrome will 
ensure that they will reap the benefits of therapeutic agents already 
in development. Working through its established Pediatric Trials 
Network that has enrolled over 7,000 children, in fiscal year 2019 
NICHD will create a new pediatric clinical trials infrastructure for 
Down syndrome. This resource will also ensure that new therapies can be 
brought to trial quickly and efficiently as they emerge in the future. 
In parallel, NICHD will create and fund a training program, working 
with its pediatric trials experts, as well as specialists in Down 
syndrome, to help teach investigators how to recruit and work with 
individuals with Down syndrome and their families.
    Further, through the INCLUDE project, NIA is supplementing an 
Alzheimer's clinical trials network to include adults with Down 
syndrome to learn more about the development of dementia and 
Alzheimer's disease. To bolster these efforts, NIH is planning two 
major scientific workshops within the year to address the development 
of a cohort in Down syndrome, and how to include people with Down 
syndrome in clinical trials. These efforts will take advantage of the 
research registry for Down syndrome, DS-Connect,\109\ a Web-based 
health registry that serves as a national health resource for people 
with Down syndrome and their families, researchers, and healthcare 
providers. Funded by NICHD since 2013, the registry facilitates 
information sharing about research and upcoming studies for both 
individuals with Down syndrome and researchers.
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    \109\ https://dsconnect.nih.gov/.
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    Question. We are pleased to see so many NIH Institutes and Centers 
participating in the INCLUDE Project. What kind of feedback have you 
been getting from the Institutes on this project, particularly as it 
may offer lessons learned for other trans-NIH initiatives?
    Answer. INCLUDE involves research projects or programs funded by 14 
NIH Institutes and Centers. INCLUDE will investigate conditions that 
affect both individuals with Down syndrome and the general population, 
such as Alzheimer's disease/dementia, autism, cataracts, celiac 
disease, congenital heart disease, and diabetes. This approach is 
creating new synergies among the NIH institutes and centers that study 
these conditions. To give just two examples from the first round of 
awards, NICHD is funding a project that will sequence the genomes of 
children with Down syndrome who also have congenital heart defects or 
leukemia. The results will be publicly available, allowing researchers 
globally to test hypotheses and find new gene variants that are 
associated with both Down syndrome and these additional conditions. NIA 
is developing a Down syndrome module for its Alzheimer's disease 
research centers with the goal of learning more about the development 
of dementia that will lead to potential treatments.
    Question. I recently learned that people with Down syndrome rarely 
get solid tumor cancers. For example, women with Down syndrome most 
likely would not ever need to get a mammogram because they are highly 
unlikely to develop breast cancer. The connection between Down syndrome 
and cancer seems like a promising research opportunity. Can you tell us 
about some of the topics that NIH is prioritizing in the INCLUDE 
Project?
    Answer. NIH was grateful to have the opportunity to dedicate more 
resources in fiscal year 2018 toward research related to Down syndrome 
through the INCLUDE project. In its first year, over $22 million was 
spent on projects under this new initiative alone. This figure was in 
addition to the baseline funding of $37 million for Down syndrome for a 
total of approximately $60 million. Awards were made to a wide range of 
investigators across the country,\110\ covering all aspects of the 
INCLUDE project: research to improve the understanding of the biology 
of Down syndrome, research focused on connecting large study 
populations (or cohorts) of individuals with Down syndrome and 
enrolling new participants at different ages, and identifying existing 
clinical trials that seek to address conditions common in individuals 
with Down syndrome to bolster recruitment and inclusion in more 
clinical studies.
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    \110\ https://www.nih.gov/include-project/funding.
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    INCLUDE involves research projects or programs funded by 14 NIH 
Institutes and Centers, investigating conditions that affect both 
individuals with Down syndrome and the general population, such as 
Alzheimer's disease/dementia, autism, cataracts, celiac disease, 
congenital heart disease, and diabetes. This approach is creating new 
synergies among the NIH institutes and centers that study these 
conditions. To give just two examples from the first round of awards, 
NICHD is funding a project that will sequence the genomes of children 
with Down syndrome who also have congenital heart defects or leukemia. 
The results will be publicly available, allowing researchers globally 
to test hypotheses and find new gene variants that are associated with 
these conditions. NIA is developing a Down syndrome module for its 
Alzheimer's centers with the goal of learning more about the 
development of dementia and lead to potential treatments.
    Question. I was pleased to learn that one of the aims of the 
INCLUDE Project is to encourage scientists studying other topics like 
cancer, Alzheimer's, and autoimmune disease to add research on Down 
syndrome to their work. What kind of feedback have you gotten from the 
research community on these opportunities?
    Answer. One of its immediate successes of INCLUDE was to attract 
new researchers and talent into the field. In fact, many of the 
recipients of awards in fiscal year 2018 were investigators who had not 
previously had a research focus on Down syndrome. Since the purpose of 
the INCLUDE project is to investigate conditions that affect both 
individuals with DS and the general population, researchers with 
subject matter expertise other than Down syndrome now have the 
opportunity to submit applications. These opportunities are widely 
disseminated across the Down syndrome community through the public-
private Down Syndrome Consortium that includes the Trans-NIH Working 
Group, 16 national and international organizations whose missions focus 
on Down syndrome, and individuals with Down syndrome and family 
members. The response has been robust, demonstrating excitement among 
investigators who previously have not been involved in Down syndrome 
research.
                         antibiotic resistance
    Question. We have been hearing warnings for decades that overuse of 
antimicrobials is reducing their effectiveness, and that appears to be 
borne out by reports of a new superbug, Candida Auris.
    Where does NIH see the greatest opportunities for medical research 
to provide solutions to the threat posed by antimicrobial resistance?
    Answer. NIAID is the lead institute for antimicrobial resistance 
(AMR) research at NIH. NIAID supports a comprehensive portfolio of 
basic, translational, and applied research on AMR to better understand 
pathogenicity and the mechanisms by which resistant pathogens overcome 
antimicrobials, and to develop novel diagnostics, therapeutics, and 
vaccines. Recent advances in AMR research have created a number of 
scientific opportunities, particularly to: (1) accelerate the 
development of new antimicrobials with novel mechanisms of action; (2) 
identify ways to enhance or target the body's immune system to better 
fight infection; (3) manipulate microbial communities to prevent or 
treat colonization by harmful pathogens; and (4) develop state-of-the-
art antivirulence strategies and rapid diagnostics to help control the 
spread of AMR. NIAID is pursuing these opportunities for both bacterial 
and fungal pathogens.
    NIAID is supporting development of a number of novel antimicrobial 
agents, including a group of novel forms of a class of antibiotics 
(tetracyclines) that are not susceptible to existing resistance 
mechanisms in bacteria. One of these compounds, XERAVATM, recently 
received FDA approval to treat complicated intra-abdominal infections. 
NIAID funding also has led to the discovery of a new class of 
antibiotics, malacidins, that are being investigated for further 
therapeutic development. In addition, NIAID is providing CARB-X 
(Combating Antibiotic Resistant Bacteria-X), a public-private 
partnership led by BARDA within HHS with in kind and technical support. 
CARB-X is currently funding 35 innovative projects--including 13 that 
represent new classes of antibiotics.
    NIAID currently is exploring several alternatives to traditional 
antimicrobials that leverage advances in basic research on 
pathogenesis, drug resistance, immune system function, and the 
microbiome. NIAID-supported scientists are exploring the use of 
protective bacterial strains and fecal microbiota transplant to prevent 
and treat bacterial infections. NIAID grantees also are investigating 
ways to boost the ability of an individual's own immune system to fight 
infection. This includes the use of modified immune cells to control 
invasive fungal infections, and studies by NIAID investigators to boost 
the immune system's ability to fight the bacterial species Klebsiella 
pneumoniae infection using targeted antibodies. NIAID also is advancing 
the development of candidate vaccines against bacterial and fungal 
pathogens, including strains that exhibit drug resistance. One such 
experimental vaccine, NDV-3, exhibited protection in animal models 
against Staphylococcus and Candida species, including Candida auris (C. 
auris). NDV-3 also was shown to be safe and well-tolerated in a Phase 1 
clinical study. Vaccines that confer protection against bacterial and 
fungal pathogens have the added benefit of mitigating the use of 
antimicrobial drugs and potentially avoiding the development of AMR.
    NIAID also is supporting the development of novel diagnostic tools 
to help control the emergence and spread of drug-resistant pathogens. 
The NIAID Antibacterial Resistance Leadership Group (ARLG) oversees 
clinical research on antibiotic resistance, including antimicrobial 
stewardship, infection prevention, and improved diagnostics. ARLG 
efforts include the development of a master protocol for evaluating 
multiple diagnostic tests using samples from a single patient. NIAID 
support also has contributed to the development of several novel 
diagnostics capable of distinguishing between numerous infectious 
agents, including a sepsis diagnostic that simultaneously tests for 24 
bacterial and fungal species, and a pneumonia diagnostic that can 
detect a number of different bacterial and viral species as well as 
seven genetic markers of AMR. Both diagnostics have received FDA 
clearance. In addition, NIH, in partnership with BARDA, is supporting 
the AMR Diagnostic Challenge competition. The Diagnostics Challenge 
aims to accelerate the development of raid, point-of-need diagnostic 
tests that can help inform treatment and facilitate antibiotic 
stewardship. Submissions for Step 3 of the Challenge are due in January 
2020, and final results of the competition are anticipated in July 
2020.
    Question. There are already a number of superbugs like MRSA and C-
R-E that pose challenges in hospitals and other healthcare settings, 
what is significant about Candida Auris?
    Answer. Candida are fungi that can be found on the skin, mucous 
membranes, and in the intestinal tract. For people with certain risk 
factors, excessive growth of these fungi can cause invasive 
candidiasis--a serious infection that can affect the blood, heart, 
brain, eyes, bones and other parts of the body. C. auris is a newly 
emerging fungal species that is challenging to diagnose and is often 
resistant to multiple antifungal drugs. While most C. auris infections 
are treatable with existing antifungal drugs, the presence of C. auris 
infections resistant to three of the main classes of antifungal drugs 
is extremely concerning. In addition, C. auris is extremely difficult 
to eliminate from contaminated surfaces, and it can spread from person-
to-person. Drug development for fungal pathogens poses an especially 
challenging problem. Unlike antibacterial drugs, which mostly target 
bacterial pathways that are very different than those in humans, many 
fundamental biochemical and cellular processes are similar in fungi and 
humans. Thus, many fungal drug candidates may pose a safety risk to 
humans because they could also target the similar human pathways, with 
potentially toxic side effects.
    AMR research supported by NIAID is especially critical in light of 
the emergence of novel AMR pathogens such as C. auris, which exhibits a 
unique multidrug resistance that has not been seen in other species of 
Candida. A major component of NIAID-supported research on C. auris is 
focused on developing an improved understanding of resistance 
mechanisms to better inform therapeutic development efforts. This 
includes genomic analysis of C. auris--including isolates from two 
recent outbreaks--as well as efforts to better understand host-pathogen 
interactions and resistance mechanisms for particular antifungal drugs. 
NIAID also is screening antifungal compounds for in vitro effectiveness 
against C. auris. Of 15 compounds tested to date, 11 showed activity 
against C. auris. NIAID also supports studies of a broad-spectrum 
antifungal with activity against C. auris and other Candida species. In 
addition, NIAID scientists have developed animal models to study C. 
auris infection and to screen investigational therapeutics, three of 
which showed activity against C. auris. Two of these investigational 
therapeutics are currently in various stages of clinical development.
    Question. This is clearly a problem that goes far beyond the NIH or 
even the United States. How is NIH working its your other Federal and 
international partners?
    Answer. NIAID works closely with its Federal partners, including 
the Centers for Disease Control and Prevention (CDC), BARDA, and FDA to 
monitor the spread of drug-resistant pathogens and further the 
development of promising diagnostics, therapeutics, and vaccines for 
AMR pathogens. NIAID continues to support CARB-X, the BARDA-led public-
private partnership to incentivize the early development of 
antibiotics, vaccines, and diagnostics to combat resistance to 
antimicrobials that also is supported by the United Kingdom and 
Germany. NIAID also participates in the Transatlantic Task Force for 
Antimicrobial Resistance (TATFAR), which was established in 2009 with 
the goal of enhancing communication and cooperation in: 1) 
antimicrobial stewardship; 2) prevention and control of AMR; and 3) 
enhancement of the antimicrobial drug development pipeline. NIAID, 
through TATFAR, has aligned clinical trial networks with the European 
Union to expand access to patients in a clinical trial to optimize the 
antibacterial drug colistin for carbapenem-resistant Enterobacteriaceae 
(CRE) and in a clinical trial to evaluate an antibody for use against 
Pseudomonas. These collaborative efforts are helpful in gathering a 
sufficient number of patients to conduct critical AMR clinical studies. 
In addition, the NIAID-supported ARLG has established collaborations in 
19 countries and has recently established a collaboration with the 
Combatting Bacterial Resistance in Europe (COMBACTE) consortium to 
enable joint design and implementation of clinical research on 
antibiotic resistance. NIAID will continue to build on recent progress 
in AMR research, including studies on C. auris, and is committed to 
supporting partnerships with academia, industry, and Federal and 
international partners to develop novel strategies to combat the spread 
of AMR in bacterial and fungal pathogens.
                       new kinds of investigators
    Question. How have the BRAIN initiative and efforts around 
Alzheimer's disease helped recruit new investigators from various 
disciplines with diverse skill sets and backgrounds to work in these 
areas, and what have been the results? Is this something that could and 
should be replicated in other parts of NIH?
    Answer. The challenge, allure, and importance of understanding the 
brain and its disorders have always attracted scientists and clinicians 
with diverse skills and backgrounds. The Brain Research through 
Advancing Innovative NeuroTechnologies (BRAIN) Initiative, which is 
advancing the frontiers of technology and of brain science, has 
attracted an even wider breadth of skill and talent. The Initiative has 
engaged the full spectrum of neuroscientists and clinicians, including 
neurologists, neurosurgeons, and psychiatrists, and recruited experts 
from disciplines that include behavior, chemistry, cell biology, 
mathematics, nanoscience, optics, and physics, as well as computer 
science and informatics. More than a quarter of researchers at the 
BRAIN Initiative Annual Investigators meeting this April were 
engineers, which reflects the strong emphasis on technology 
development. About a quarter of principal investigators are also early 
stage investigators, receiving their first independent NIH funding, and 
many other project leaders and members of research teams are entirely 
new to neuroscience.
    To recruit this broad spectrum of investigators, the Initiative has 
emphasized the importance of diverse expertise since its inception. 
Funding opportunity announcements explicitly call for innovative and 
diverse approaches, with integration of technology developers and 
neuroscientists, and of theorists, computational biologists, and 
experimentalists. Peer review panels are attuned to this priority of 
the Initiative. Extensive outreach has reinforced this emphasis.
    NIH has also been particularly successful in encouraging early-
stage investigators as well as established investigators not previously 
focusing on Alzheimer's disease and related dementias (AD/ADRD) to 
apply for AD/ADRD-related research funding. An internal NIA analysis 
has shown that between 2015 and 2018, over a quarter of the Institute's 
Research Project Grant (R01) equivalent AD/ADRD awardees were either 
NIH-designated New Investigators (i.e., this was their first 
competitive NIH grant) or Early-Stage Investigators (not only was this 
their first competitive NIH grant, but they were also within 10 years 
of their terminal degree). Approximately one third of the R01 AD/ADRD 
awardees had not previously applied for AD/ADRD funding from NIH--just 
below half of whom were established investigators previously pursuing 
other lines of research. We anticipate that the success of these 
investigators in securing funding will ensure an active pipeline of 
energetic researchers looking at AD/ADRD from new perspectives for 
years to come.
    Recognizing the importance of bringing fresh perspectives, NIA also 
released a notice in 2018 inviting researchers holding non-AD/ADRD 
grants from other NIH Institutes and Offices to apply for supplemental 
funding for new research that was relevant to both AD/ADRD and the 
topic of their research grant. The response was robust. Over 300 
supplements were awarded to investigators representing some 25 NIH 
Institutes, Centers, and Offices, broadening the spectrum of research 
and inspiring investigators to think creatively about how their area of 
study could interface productively with research on AD/ADRD.
    Although each disease and field of medicine presents unique 
challenges, NIH is certainly learning from Alzheimer's disease research 
and the BRAIN Initiative on the value of bringing in diverse expertise 
and new investigators and the strategies to accomplish that. Just as 
the Human Genome Project stimulated many areas of science and medicine 
beyond genetics, we expect the knowledge, technology, and strategies 
stimulated by the BRAIN Initiative and the aggressive goals of 
Alzheimer's and related dementias research will have much broader 
implications. NIH will continue to track progress in multi-disciplinary 
collaborations to ensure best practices are promulgated.
                       methamphetamine treatment
    Question. Parts of the U.S. are seeing an alarming increase in 
methamphetamine overdoses over the past few years. As you know, there 
are currently no FDA-approved treatments for methamphetamine 
dependence. What can you tell me about NIDA's efforts to develop 
treatments methamphetamine addiction?
    Answer. NIH is committed to addressing the alarming increase in 
methamphetamine overdoses, which rose fivefold from 1999 to 2017. As 
mentioned, there are currently no FDA-approved treatments for 
methamphetamine dependence and the most effective treatments are 
behavioral therapies, such as cognitive behavioral therapy and 
contingency management. While drug targets exist for methamphetamine 
that are analogous to those used in treating opioid addiction, alcohol 
addiction, and nicotine addiction, targeting them has not been 
similarly successful, necessitating a novel drug development approach.
    NIH, primarily through NIDA, continues to invest in tackling 
methamphetamine addiction, investing roughly $49 million on 
methamphetamine research in fiscal year 2018. NIDA takes a multi-
pronged approach to this challenge, balancing its portfolio across 
basic research on the health effects of use, epidemiology of use and 
addiction, and efforts aimed at developing new treatments. This 
strategy allows researchers to test promising treatments and to 
leverage our increasing understanding of methamphetamine's mechanism of 
action to devise new ones. Importantly, as part of this portfolio, NIDA 
supports clinical trials using a wide range of potential approaches, 
from targeting signaling pathways involved in building tolerance to 
methamphetamine, to exploring immunotherapy and anti-inflammatory 
approaches, to testing effective pharmacotherapies for opioid use 
disorder that might have potential to help in methamphetamine use.
    Much of the research in this area to date has involved testing 
drugs that are already approved for other conditions, such as 
antidepressants and medications for opioid use disorder. While none of 
the drugs tested to date were sufficiently effective to warrant use in 
routine treatment, one potentially promising therapy uses antibodies 
that bind to methamphetamine and block it from reaching the brain, thus 
preventing both the euphoric effects and the brain changes that lead to 
addiction. NIDA is also supporting the study of behavioral 
interventions using mobile apps that might help individuals with 
methamphetamine addiction adhere to treatment and remain abstinent. 
While many of the trials are still in the fairly early stages, some 
have yielded preliminary analyses that may offer hope for patients 
suffering from methamphetamine dependence.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
                               new funding
    Question. Over the past 4 years, this Committee has provided NIH 
with more than $9 billion in increased funding, a 30 percent increase. 
Dr. Collins, what has this 30 percent increase meant to NIH? What new 
initiatives or projects have you been able to establish as a result of 
the new funding? How many new and promising grants have you been able 
to fund with the additional funding?
    Answer. These resources have supported a broad range of research 
conducted both through NIH's intramural research program and through 
the tens of thousands of extramural researchers in institutions across 
the country. This truly exciting, world class science is leading to 
breakthroughs in multiple areas.
    More than two-thirds of the NIH budget supports extramural research 
grants, and funding for these grants grew 33 percent over the last 4 
years, slightly faster than the 30 percent overall budget increase. 
Funding for research project grants (RPGs), which are the classic 
mechanism of support for investigator-led research into specific 
biomedical research questions, grew by 37 percent over this period. 
This funding increase allowed NIH to increase the number of RPG awards, 
while also compensating researchers for the effects of biomedical 
research inflation. The total number of RPG awards grew by 7,010, or 20 
percent, from fiscal year 2015 through fiscal year 2019. Meanwhile, the 
number of new and competing awards grew by 2,135, or 22 percent. This 
increase allowed the RPG success rate to rise from 18.3 percent in 
fiscal year 2015 to an estimated 20.3 percent in fiscal year 2019 in 
spite of an increase of more than 10 percent in the number of 
applications. Increased resources have allowed NIH to initiate or 
expand a number of critical research programs. The following list 
highlights just a few examples:\111\
---------------------------------------------------------------------------
    \111\ Estimates for Alzheimer's Disease and antimicrobial 
resistance are from NIH estimates of support for research, condition, 
and disease categories (RCDC), available on the NIH website at https://
report.nih.gov/. These estimates show research support for 288 
research, condition, and disease categories ranging alphabetically from 
Acquired Cognitive Impairment to Youth Violence Prevention, including 
project detail for completed years.
---------------------------------------------------------------------------
  --All of Us. Initiated in fiscal year 2016, the NIH All of Us 
        Research Program is a historic effort to gather data from one 
        million or more people living in the U.S. to accelerate 
        research and improve health. All of Us, funded in part with 
        amounts authorized by the 21st Century Cures Act, is a key 
        element of the Precision Medicine Initiative (PMI), which seeks 
        to take into account individual differences in lifestyle, 
        environment, and biology to enable prevention and treatment 
        strategies tailored to individuals. All of Us will serve as a 
        national research resource to support thousands of studies, 
        covering a wide variety of health conditions. As of early April 
        2019, more than 212,000 people had begun the enrollment 
        process, and more than 129,000 had completed all the steps in 
        the protocol.
  --Cancer Moonshot. Resources authorized by the Cures Act for the Beau 
        Biden Cancer Moonshot are catalyzing progress in a number of 
        areas to improve diagnosis and treatment of a broad range of 
        cancers. Investments in the rapidly advancing field of cancer 
        immunotherapy are particularly promising in harnessing the 
        body's own immune system to fight off the disease. Resources 
        are also being used to create a national ecosystem for sharing 
        and analyzing cancer data to facilitate efficient data 
        analysis, to overcome drug resistance of cancer cells, and to 
        minimize the debilitating side effects of some cancer 
        treatments.
  --Brain Research through Advancing Innovative Neurotechnologies 
        (BRAIN) Initiative. The BRAIN Initiative, which is also 
        supported in part with Cures Act funding, seeks to develop and 
        apply technologies that will revolutionize our understanding of 
        the human brain in health and disease. The initiative has 
        supported research identifying the gene expression patterns of 
        different subtypes of brain cells that can identify what makes 
        different types of cells unique, demonstrating the use of 
        neurotechnologies with clinical applications, such as deep 
        brain stimulation, and mapping functional circuits across the 
        brain, paving the way for an unprecedented level of 
        understanding of the human brain and improving human health.
  --Helping to End Addiction Long-Term (HEAL). The HEAL Initiative, 
        first funded in fiscal year 2018, aims to bring scientific 
        solutions to address the crisis of opioid addiction and to 
        provide safe and effective options for the more than 25 million 
        Americans who suffer from daily chronic pain. Through HEAL, NIH 
        is building on basic science discoveries to accelerate the 
        development of novel medications and devices to treat all 
        aspects of the opioid addiction cycle, including chronic use, 
        withdrawal symptoms, craving, relapse, and overdose. In 
        addition, studies on integrating prevention and treatment 
        approaches into practice, including the HEALing Communities 
        study, will inform understanding of how the implementation of 
        promising and evidence-based strategies and treatments can 
        decrease opioid use disorder and overdose deaths.
  --Alzheimer's Disease. Overall NIH funding for research into 
        Alzheimer's Disease and related dementias (AD/ADRD) has grown 
        almost threefold over the last 4 years, from $631 million in 
        fiscal year 2015 to $2,468 million in fiscal year 2019.1 
        Approximately 70 funding opportunity announcements (FOAs) 
        relating to AD/ADRD are currently active, including new 
        clinical and preclinical studies. A new NIH-supported clinical 
        trials consortium is expected to accelerate and expand studies 
        for therapies in Alzheimer's Disease and related dementias. The 
        Alzheimer's Clinical Trial Consortium (ACTC) will encompass 35 
        sites across the United States, and will address the timeframe, 
        complexity and expense of the recruitment process and site 
        activation for Alzheimer's trials to find new and effective 
        ways to treat or prevent these devastating disorders.
  --Combatting Antimicrobial Resistance. NIH-funded research to combat 
        the rising public health problem of drug-resistant bacteria has 
        nearly doubled since fiscal year 2015.1 Antibiotic resistant 
        bacteria cause at least 2 million infections and 23,000 deaths 
        each year in the United States, according to the CDC. These 
        efforts include the Antimicrobial Resistance Diagnostic 
        Challenge, a $20 million Federal prize competition seeking 
        innovative, rapid point-of-care laboratory diagnostic tests to 
        combat the development and spread of drug resistant bacteria. 
        Five finalists in the competition were announced in December of 
        2018.
    --The Challenge is a joint effort between the National Institutes 
            of Health and the HHS Office of the Assistant Secretary for 
            Preparedness and Response (ASPR) in support of the National 
            Action Plan for Combating Antibiotic Resistant Bacteria. 
            NIAID and ASPR's BARDA are each contributing $10 million to 
            the Challenge. The Challenge also was developed with 
            technical and regulatory expertise from the CDC, the FDA, 
            and NIH Office of the Director.
  --Universal Flu Vaccine. In fiscal year 2018, NIH unveiled a 
        strategic plan to guide future basic, translational, and 
        clinical research investments in areas essential to creating a 
        safe and effective universal influenza vaccine. Along this 
        path, NIH is funding basic research to understand the 
        transmission, natural history, and disease process of 
        influenza. Several universal flu vaccine strategies are already 
        being tested in NIH-supported clinical trials.
  --Down Syndrome. The INCLUDE (INvestigation of Co-occurring 
        conditions across the Lifespan to Understand Down syndromE) 
        project, launched in fiscal year 2018, is a new trans-NIH 
        research initiative on critical health and quality-of-life 
        needs for individuals with Down syndrome. INCLUDE will assemble 
        a large study population of individuals with Down syndrome and 
        include individuals with Down syndrome in existing clinical 
        trials. Individuals with Down syndrome are at higher risk for 
        certain diseases such as Alzheimer's Disease, but at lower risk 
        for others such as coronary artery disease and solid tumors, 
        raising the possibility that better understanding Down syndrome 
        will yield health benefits for the general population as well.
                              e-cigarettes
    Question. Big Tobacco says e-cigarettes are a ``safe'' alternative 
to cigarettes, a way to get people to stop smoking. They make this 
claim despite never having conducted a clinical trial in the U.S. to 
prove it. So, while we don't actually know if e-cigarettes help adults 
quit, we do know that they are causing kids to start vaping and 
smoking. In 2018, youth use of e-cigarettes increased by 78 percent 
among high school students, and 48 percent among middle-school 
students. Today, nearly 4 million children are using e-cigarettes. This 
dramatic uptick is due to products like JUUL and kid-friendly flavors--
fruit medley, fruity pebbles, choco milkshake, smurf, gummy bear. 81 
percent of kids vaping started with a flavored product. What is even 
more alarming is that there's evidence to suggest that e-cigarettes are 
actually causing kids to start smoking cigarettes! Dr. Collins, Dr. 
Lowy, and Dr. Volkow, are you alarmed by what you've seen with the 
massive increase in youth use of e-cigarettes? Just last week, the FDA 
reported that some people were having seizures as a result of e-
cigarette use. What do we know about the health effects of e-
cigarettes, especially for children?
    Answer. Any increase in nicotine use among adolescents is alarming. 
While youth cigarette smoking is at an all-time low, overall nicotine 
use through vaping is rising and reversing these gains. There is a 
perception that vaping is harmless because it does not involve the 
burning of tobacco--the source of carcinogenic tar in combustible 
cigarette smoke. While the long-term health impacts of e-cigarette use 
are unknown, emerging data from toxicological, animal, and human 
studies point to some concerning precursors to disease endpoints and 
health effects. For example:
  --Chemicals that are known carcinogens--for example, formaldehyde--
        have been found in e-cigarette aerosol and are found in 
        increasing amounts at higher heat levels.\112\
---------------------------------------------------------------------------
    \112\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954153/.
---------------------------------------------------------------------------
  --Primary exposure to e-cigarette aerosol may increase oxidative 
        stress and inflammation, important risk factors for cancer, 
        cardiovascular, and pulmonary health consequences.\113\ For 
        example, earlier this year, NCI-supported researchers published 
        findings that people who vaped were nearly twice as likely to 
        experience wheezing compared to people who didn't regularly use 
        tobacco products.\114\
---------------------------------------------------------------------------
    \113\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768608/.
    \114\ https://www.ncbi.nlm.nih.gov/pubmed/30760629.
---------------------------------------------------------------------------
  --E-cigarette use may cause lasting changes to gene expression. 
        Preliminary results from a study of nearly 100 e-cigarette 
        users led by NIEHS intramural investigators suggest that e-
        cigarette use may cause unique patterns of DNA modifications in 
        blood cells which could alter gene expression in these cells.
  --Nicotine exposure during adolescence can cause addiction and harm 
        the developing brain. NIDA, along with NCI, NIAAA, and other 
        NIH Institutes and Centers, is leading the Adolescent Brain and 
        Cognitive Development Study, which will examine the effects of 
        environmental factors, including nicotine use, on the 
        developing brains of adolescents.
    FDA recently reported on 35 cases of seizures among people who have 
used e-cigarettes, including youth and young adults, between 2010 and 
2019. Although seizure is a known potential consequence of nicotine 
poisoning, FDA cautioned that it does not know if there is a direct 
relationship between e-cigarette use and seizure risk, or how e-
cigarette use behavior, use of other substances, or underlying 
conditions may have contributed to these seizures.\115\ Despite those 
unknowns, NIH agrees with the FDA that it is important to share 
information on potential serious risks with the public as it becomes 
evident.
---------------------------------------------------------------------------
    \115\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm635157.htm.
---------------------------------------------------------------------------
    Several studies, some funded by an FDA-NIH partnership, demonstrate 
that e-cigarette use among never-smoking youth is a risk factor for 
future cigarette smoking.\116\ One found that non-smoking youth who try 
e-cigarettes are more likely to use combustible tobacco products in the 
future than never users of e-cigarettes.\117\ This is particularly 
worrisome considering that viewing e-cigarette advertising is 
associated with initiating e-cigarette use among youth,\118\ and 
exposure to e-cigarette ads on social media sites increases the 
likelihood of subsequent e-cigarette use among youth who had never used 
e-cigarettes.\119\
---------------------------------------------------------------------------
    \116\ https://jamanetwork.com/journals/jamapediatrics/fullarticle/
2634377;https://www.ncbi.
nlm.nih.gov/pubmed/26348249;https://www.ncbi.nlm.nih.gov/pubmed/
26811353;
https://www.ncbi.nlm.nih.gov/pubmed/27296866.
    \117\ https://jamanetwork.com/journals/jama/fullarticle/
2428954?resultClick=3,.
    \118\ https://www.ncbi.nlm.nih.gov/pubmed/29582078.
    \119\ https://www.ncbi.nlm.nih.gov/pubmed/29432916.
---------------------------------------------------------------------------
    Research regarding e-cigarettes and other electronic nicotine 
delivery systems (ENDS) (an umbrella term which includes JUUL), is of 
high interest to NIH. NIH recently developed and published two trans-
NIH Funding Opportunity Announcements--one calling for research on the 
population, applied, and clinical impacts of ENDS \120\ and the other 
on basic science studies of the health effects from ENDS.\121\ NHLBI 
also organized a two-day meeting of scientific experts in 2015 that led 
to two grant solicitations, one in 2017 and one in 2018. Twenty 
research projects have been awarded through these programs, including 
animal studies on the effect of e-cigarettes on young versus old 
hearts,\122\ the susceptibility of adolescent airways to e-cigarette 
exposure,\123\ and the cardiopulmonary health of individuals in 
households where family members smoke e-cigarettes.\124\ In addition, 
NIH is studying how prevention and cessation approaches developed for 
combustible cigarettes might be adapted for similar purposes in e-
cigarettes. By furthering our understanding of how they are used, how 
they affect the body, and how we can implement strategies to prevent 
and reduce their use, NIH aims to find ways to reverse this alarming 
trend and reduce the harms associated with it.
---------------------------------------------------------------------------
    \120\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-612.html.
    \121\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-476.html.
    \122\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9624711&icde=
44343194&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
    \123\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9567413&icde=
44343005&ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC&pball=.
    \124\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9564974&icde=44342386.
---------------------------------------------------------------------------
                            infant mortality
    Question. Too often in our country, new moms and infants--
especially women and babies of color--are dying from preventable health 
problems. The U.S. is one of only 13 countries where our maternal 
mortality rates are worse today than they were 25 years ago. 
Nationwide, more than 700 women die every year as a result of 
pregnancy--more than 70,000 others experience severe, near-fatal 
complications. In Illinois, 73 women die every year due to pregnancy-
related complications--70 percent of these deaths are deemed 
preventable. We are also losing babies. Annually, more than 23,000 
babies die in the U.S., many due to preventable factors. Education and 
income offer no protection--a black woman with an advanced degree is 
more likely to lose her baby than a white woman with less than an 
eighth-grade education. Dr. Collins, why is this happening in the year 
2019? What research is NIH doing with respect to infant and maternal 
mortality, especially for women and babies of color?
    Answer. NIH supports a large and diverse portfolio of research in 
maternal health, pregnancy and pregnancy outcomes, and infant 
mortality, including stillbirth and Sudden Infant Death Syndrome 
(SIDS). For example, in fiscal year 2018, NIH funded approximately $303 
million on research related to maternal health.\125\ The NICHD is 
holding a number of workshops aimed at looking at the high rate of 
maternal mortality in the U.S., with a focus on the factors that are 
contributing to maternal deaths in black women. The first, in April 
2019, was a forum for members of community-based and healthcare 
provider groups about community engagement strategies to improve 
maternal health. Participants learned how patient-provider interactions 
and the process for making clinical care decisions affect maternal 
healthcare experiences at the local level. The second workshop, to be 
held May 2019, will bring scientific experts together to discuss 
research needed to address maternal mortality in the U.S. Participants 
will examine data quality and trends, the populations 
disproportionately affected, social determinants of maternal mortality, 
and clinical causes of this serious public health issue. Among the 
issues to be discussed are potential causes of the disparities in 
maternal mortality, such as medical mistrust, neighborhood environment, 
and the cultural frameworks needed to improve maternal health outcomes. 
A third workshop, to be held in early 2020, will focus on research 
needed by the medical community to address maternal mortality due to 
co-morbid conditions such as obesity, hypertension and diabetes, 
conditions prevalent in black women. Finally, as requested by Congress, 
NICHD has also contracted with the National Academies of Sciences, 
Engineering, and Medicine to conduct a study on the choice of birth 
setting, including risk factors, social determinants that influence 
risk, and maternal health outcomes.
---------------------------------------------------------------------------
    \125\ https://report.nih.gov/
categorical_spending_project_listing.aspx?FY=2018&ARRA=
N&DCat=Maternal Health.
---------------------------------------------------------------------------
    In the meantime, NICHD continues to fund investigator-initiated 
prevention research on the factors that promote healthy pregnancy, 
e.g., weight gain in pregnancy, lifestyle interventions, and efforts to 
reduce exposure of pregnant women to risk factors. For example, a 
recent NICHD-funded study showed that health outcomes associated with 
short interpregnancy intervals vary by age. Compared to younger 
mothers, mothers over 35 are at higher risk of death and serious 
illness if they conceive 6 months or less after the birth of a previous 
child.
    NICHD also supports a range of research projects related to 
pregnancy loss and other adverse pregnancy outcomes, determinants 
(e.g., biomarkers) of healthy pregnancies, and disparities among racial 
and ethnic groups and geographic regions. Among NICHD's research 
priorities are the development of specific algorithms that include 
physiological, biochemical, and genetic markers to predict pregnant 
women at risk for pregnancy loss and/or stillbirth, improving the 
chances for intervention. One NICHD-supported study published in 2018 
found that, in an animal model, Zika virus infection caused early loss 
of one-quarter of the pregnancies. Unfortunately, many causes of 
pregnancy loss are still unknown and could result from chromosomal 
factors, problems with the placenta, fetal infection, and maternal 
disorders. Environmental exposures also may influence pregnancy loss. 
For example, population-based research conducted in NICHD's intramural 
division found that excessive exposure to high ozone levels during the 
last week of pregnancy, and exposures to extremes in temperature, 
increased the risk of stillbirths.
    NICHD has a longstanding program of research on newborn screening, 
part of the highly successful, nationwide newborn screening public 
health effort that allows infants with serious or even fatal conditions 
to be identified for early treatment. The research component, The 
Hunter Kelly Newborn Screening Research Program, was originally 
established as a provision of The Newborn Screening Saves Lives Act of 
2007. Research under the program, led by NICHD, focuses on identifying, 
developing, and testing new newborn screening technologies in order to 
improve existing tests and develop new tests, and developing and 
testing innovative interventions and treatments for conditions that can 
be detected through screening, but which are not yet treatable. In the 
past year, a NICHD-funded study developed a newborn screening tool to 
detect Niemann-Pick Disease, a rare but fatal disorder. Niemann-Pick 
disease type C (NPC) is a rare but fatal disorder that is caused by 
defects in how the body stores cholesterol. Because NPC symptoms vary 
widely, the disease often goes undetected, causing the brain and body 
to degenerate beyond the point of treatment. NICHD-supported 
researchers found that one bile acid is increased 101-fold in patients 
with NPC, and quickly developed a method to detect this bile acid in 
dried blood spots; the method helps to detect Niemann-Pick disease in 
patients after birth, allowing doctors to treat them as soon as 
possible.
    In the meantime, NICHD continues to fund research to uncover the 
causes of SIDS. Among the many research grants that NICHD recently 
funded are hippocampus and brain stem studies in SIDS infants, cardiac 
channel mutations, and respiratory and autonomic mechanisms potentially 
underlying SIDS. In addition, NICHD's leadership of the Safe to Sleep 
public education campaign, working with its many collaborators, allows 
us to translate scientific findings on Sudden Unexpected Infant Death 
and Sudden Infant Deaths Syndrome (SUID-SIDS) into audience-tailored 
actionable messages. These efforts provide training, education, and 
support for parents and families, healthcare providers, and other 
infant caregivers in applying safe infant sleep practices. We 
collaborate closely with our Federal HHS partners to ensure consistent 
public communication. NICHD also supports focused activities with 
health departments in areas with high SUID-SIDS rates to train service 
providers and community leaders on effective risk-reduction practices 
and outreach tactics. For instance, one currently funded grant is 
exploring ways of enhancing safe sleep practices of urban low-income 
mothers.
                               big pharma
    Question. All 210 drugs approved by the Food and Drug 
Administration (FDA) between 2010 and 2016 received NIH funding. But 
today, Americans are being hit twice by Big Pharma--we pay the highest 
prices in the world for many drugs, and we fund the development of them 
in the first place, mostly from NIH. On top of that, drug companies 
exploit another government-granted reward, the patent system. Two of 
the costliest cancer drugs are Rituxan and Revlimid. Both were 
developed with NIH funding, and both have received over 40 years of 
monopoly protection--because both of these medications has been issued 
more than 94 patents. The top 12 best-selling drugs in the United 
States each have an average of 71 patents, and their prices have 
increased by an average of 70 percent over the last 5 years. In fact, 
74 percent of all new drug patents are for drugs already on the 
market--extending monopolies well-past the 20-year patent term. In 
fiscal year 2017, the NIH executed 328 licensing agreements to transfer 
government- and taxpayer-funded intellectual property to industry to 
bring these inventions to market. Dr. Collins, do you believe drug 
companies are abusing the patent system? Do you believe that the 
practice of ``evergreening''--by which brand-name pharmaceutical 
companies obtain follow-on patents for often superficial or peripheral 
applications, such as a pill coating, to forestall generic 
competition--places a burden on the patient and societal benefits of 
innovative research?
    Answer. The mission of the NIH is to seek fundamental knowledge 
about the nature and behavior of living systems and the application of 
that knowledge to enhance health, lengthen life, and reduce illness and 
disability. Much of the research supported by the NIH is basic in 
nature, and the findings are published to inform the broader research 
community. The commercial sector may also use this information to 
inform their product discovery efforts. An analysis of 210 FDA approved 
drugs (2000-2016) and the published research associated with these 
drugs suggests that nearly 90 percent of the public sector funding 
underlying first-in-class drugs supported basic research of biological 
mechanisms, rather than drug-specific research (Cleary et al., PNAS, 
March 6, 2018). Every drug, whether first-in-class or a competing 
follow-on, was associated directly or indirectly with NIH-funded 
research. When the patent and regulatory exclusivity periods for these 
drugs end, they become generic.
    The NIH licenses technologies arising from the NIH intramural 
research program. Only 35 (11 percent) of the 328 license agreements 
executed by the NIH in fiscal year 2017 were exclusive licenses. In 
2018, NIH executed 329 license agreements, of which 26 (8 percent) were 
exclusive. The category of exclusive licenses often includes more than 
one exclusive license for a patented technology based on separate 
fields of use, e.g. a potential cancer therapy where one company 
develops it for blood cancers, another for solid tumors, and a third 
only in combination with its existing brand name drug. The category of 
non-exclusive license agreements includes commercial use of patented 
technologies and licenses for non-patented research materials such as 
cell lines, animal models and antibodies, which companies use in their 
research and development programs. NIH does not charge fees to transfer 
these non-patented research materials to non-profit researchers.
    Thus, NIH funding supports much basic research that is ultimately 
used by many for-profit researchers to develop new drugs for the 
prevention and treatment of disease conditions. Non-profit researchers 
make use of these published findings to further the understanding of 
biological processes and sometimes the development of new drugs. The 
innovative output of the US biomedical sector depends on this 
foundational government support. NIH manages the licensing of its own 
inventions in a manner that balances public health needs with 
incentives required by the private sector to bring new products to 
market. The NIH has no comment on the patent system because it is 
beyond the purview of NIH.
                    cost of specialty oncology drugs
    Question. The cost of specialty oncology drugs has increased more 
than 500 percent from 2006 to 2015, which is only expected to continue. 
Several studies and clinical trials, including those supported by NCI, 
have demonstrated significant cost savings from examination of de-
escalation in dose, schedule, or duration of oncology medications, or 
simply by taking medication with or without food. Such trials can be 
self-financing, in that the relative savings from the optimized doses 
could be put toward the trial operation. For example, the NCI recently 
supported an international randomized study comparing a 75 percent dose 
reduction (with food) to standard dosing for the prostate cancer drug, 
abiraterone, which demonstrated no decline in efficacy with the lower 
dose. Separately, the National Eye Institute funded a study in 2011 to 
examine optimal dosing for ranibizumab.
    Does NIH believe that there may be a potential clinical benefit for 
patients to the study of optimal drug dosing and frequency regimens, in 
particular for oncology medications?
    Answer. The NCI conducts and supports research to identify when 
patients will benefit from treatment, and when multiple therapies will 
not provide patient outcomes. Reducing the frequency and number of 
therapies a patient receives during cancer treatment not only reduces 
healthcare costs but often minimizes the risk of side effects, 
complications, and long-term (late) effects. Researchers are 
capitalizing on advances in molecular and genetic profiling of cancers 
to develop clinical studies that will help to identify when it is 
appropriate to de-escalate doses, adjust treatment schedules, or 
shorten the duration of oncology therapies.
    The mission of the NCI clinical trials programs includes an 
emphasis on filling gaps in the national cancer research effort and 
avoiding duplicating on-going private sector efforts. Research 
questions focused on de-escalation of standard therapies, or 
distributing less therapy, are not likely to be answered by industry-
sponsored trials--leaving a research gap that the NCI's clinical trials 
program seeks to fill. Removing or de-escalating well-accepted standard 
therapies in oncology requires significant care. Randomized trials are 
the gold standard, but require large numbers of patients and rigorous 
study design. NCI has supported several de-escalation studies through 
its National Clinical Trials Network, including recent trials in breast 
cancer and head and neck cancer.
    The Trial Assigning Individualized Options for Treatment (TAILORx) 
was a large phase 3 trial designed to evaluate the benefit of 
chemotherapy for patients with certain early stage breast cancers and 
an intermediate risk of recurrence based on the 21-gene breast cancer 
assay, Oncotype DX. Between 2006 and 2010, more than 10,000 patients 
were screened and more than 6,700 with a moderate risk of recurrence 
were randomized between hormonal therapy alone vs. hormonal therapy 
plus chemotherapy. The trial was designed to show that hormonal therapy 
alone is as effective at preventing recurrence, second cancers, or 
death as hormonal therapy plus chemotherapy. The trial results, 
published in the New England Journal of Medicine in July 2018, 
demonstrated that hormonal therapy alone and hormonal therapy with 
chemotherapy were similarly effective in this patient population, 
although some benefit of chemotherapy was found in some women over 50 
years old.\126\ This de-escalation trial demonstrated that chemotherapy 
could be safely dropped from therapy for this early stage breast cancer 
patient population--saving thousands of patients the burden and 
toxicity associated with chemotherapy treatment.
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    \126\ https://www.ncbi.nlm.nih.gov/pubmed/29860917.
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    Human papillomavirus (HPV)-driven head and neck (oropharyngeal) 
cancers have significantly better survival rates than tobacco and 
alcohol-induced head and neck cancers. HPV-positive (HPV+) patients are 
typically younger, healthier, and often likely to survive their 
disease. The goal of de-escalation trials for patients with HPV+ 
oropharyngeal cancers is to see if short and long-term toxicity can be 
reduced while maintaining high survival rates. The Phase 3 NRG/RTOG-
1016 trial was designed to see if the medication cetuximab therapy plus 
radiotherapy (RT) was as effective at controlling HPV+ oropharyngeal 
cancers as standard cisplatin therapy with RT, but with fewer side 
effects. The study opened in 2011 and closed in 2014, having screened 
987 patients for HPV+ tumors and randomizing 849 patients between the 
two therapeutic approaches. However, the trial's results, which were 
published in Lancet in January 2019, confirmed that cisplatin and 
radiation should remain the standard of care for HPV-related 
oropharyngeal cancers.\127\ This trial demonstrated the importance of 
testing such hypotheses to ensure that patients continue to receive the 
best care for their disease.
---------------------------------------------------------------------------
    \127\ https://www.ncbi.nlm.nih.gov/pubmed/30449625.
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    In addition to de-escalating, investigators also seek to identify 
the optimal dosing schedule for cancer therapies. For example, a recent 
collaboration between NCI intramural investigators in the Center for 
Cancer Research (CCR) and the University of Chicago Comprehensive 
Cancer Center seeks to identify when the interval between cancer 
therapy doses can be safely increased. This research uses 
pharmacological modeling, which predicts the effect of different doses 
and timing based on knowledge of disease processes and the rate at 
which drugs are cleared from the body. Initial results suggest that, 
following the initial treatments, the interval between later doses of 
two cancer therapeutics can be increased without sacrificing efficacy 
in most patients. The treatment schedule identified by this work would 
result in a potential 70 percent cost savings for treatment with the 
medications Pembrolizumab, which is used to treat a number of cancers 
including melanoma and non-small cell lung cancer, and Nivolumab, which 
is approved for treatment of non-small cell lung cancer.\128\ Advances 
in precision medicine, or choosing a therapy based on a cancer's 
particular genetic and molecular profile, may also ultimately help to 
contain healthcare costs. Recent work by several researchers in NCI's 
CCR have focused on classifying several types of cancer, including 
melanoma,\129\ diffuse B-cell lymphoma,\130\ and liver cancer \131\ 
into discrete subtypes based on gene expression patterns, as well as 
identifying molecular similarities between different tumor types. 
Identifying these different subtypes allows researchers and clinicians 
to better predict which treatments are likely to be effective for a 
patient and limit the use of expensive therapies with little hope of 
activity and potentially drive down costs.
---------------------------------------------------------------------------
    \128\ American Society for Clinical Oncology 2019 Annual Meeting, 
Poster #107, Abstract #3115: A modeling and simulation study of less 
frequent dosing of nivolumab 480 mg. Peer, Cody J.; Goldstein, Daniel 
A.; Figg, William D.; Ratain, Mark J.
    \129\ https://ccr.cancer.gov/news/milestones-2019/article/
predicting-immunotherapy-responses.
    \130\ https://ccr.cancer.gov/news/milestones-2019/article/sorting-
lymphoma-subtypes.
    \131\ https://ccr.cancer.gov/news/milestones-2018/article/
different-and-the-same.
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    As NCI leaders discussed in a recent article feature in the Journal 
of the American Medical Association (JAMA), the costs of conducting the 
clinical trials required for drug approvals contribute to the list 
prices of pharmaceutical products. The average per-patient costs have 
increased dramatically during the past two decades, an important factor 
in the total costs of drug discovery and development. Therefore, NCI is 
working to ensure that trials are appropriately sized to answer the 
scientific questions they pose, developing trials with fewer patients 
whenever possible. For example, in some trials of highly active agents, 
it may be possible to evaluate the drug without traditional control 
trials arms, instead relying on ``synthetic'' control groups created 
from data from previous trials. NCI is also considering the use of 
novel end points for clinical trials that are based on the agent's 
mechanisms of action and conducted through the aggregation of new and 
existing data.\132\
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    \132\ https://jamanetwork.com/journals/jama/fullarticle/2723062.
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    NCI will continue to work closely with the FDA and other Federal 
agencies and support research on the best therapeutic approaches for 
patients.
                            childhood trauma
    Question. So many children nationwide grow up in homes where they 
witness violence or drug misuse, or face abuse or neglect. I see this 
all over Chicago, but also in rural communities in my state. With the 
Adverse Childhood Experiences (ACEs) study, we now understand how this 
toxic stress from these situations can have serious, long-term impacts 
on the developing mind. Studies show that exposure to multiple ACEs or 
traumatic experiences increases the likelihood of chronic disease 
development, mental illness, drug use, poverty, and violence. 
Thankfully, there are interventions that can help children cope with 
this trauma, and process the experiences they have faced. This 
Subcommittee has included my language with Senator Capito each of the 
past 2 years to prioritize these trauma-informed best practices in more 
Federal grant programs. And Section 7132 of the SUPPORT for Patients 
and Communities Act established a Federal interagency task force to 
identify and disseminate such trauma-informed best practices. Dr. 
Collins, what research is NIH doing to study childhood trauma and its 
impact on long-term mental health and other outcomes, as well as 
interventions to mitigate the impact of such adversity? What more do we 
need to study?
    Answer. NIH, acting largely through NICHD, and NIMH, supports 
research on the mental and physical health effects of trauma, including 
funding investigator-initiated research related to improving our 
understanding of childhood trauma and its long-term impact and 
broadening the evidence-base needed to improve treatments, 
interventions, and mental health services for trauma survivors.
    The NICHD Pediatric Trauma and Critical Illness Branch was 
established in 2012 to coalesce the science in trauma, injury and 
critical illness across the Institute and to grow the field in these 
areas across the continuum of care.\133\ Of particular interest are 
studies that examine interactions between physical and psychological 
trauma, emergency medical services to children, injury prevention and 
the provision of critical care medicine to the most vulnerable 
children.\134\ The Branch's research portfolio on psychological trauma, 
traumatic stress, violence, and child maltreatment supports projects 
that examine the psychological processes that co-occur with physical 
trauma, which affect treatment, recovery, and well-being. To grow and 
maintain the pipeline of research experts in this area, NICHD also 
supports research training programs, such Career Development Awards, 
focused on training in child maltreatment research, and a national 
physician scientist training program for pediatric trauma surgeons and 
intensive care physicians.\135\
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    \133\ https://www.nichd.nih.gov/sites/default/files/publications/
pubs/Documents/Pediatric
Trauma_Action_Agenda.pdf.
    \134\ https://injuryprevention.bmj.com/content/injuryprev/21/6/
441.full.pdf.
    \135\ https://www.nichd.nih.gov/research/supported/pcctsdp.
---------------------------------------------------------------------------
    Recently, NICHD called for research resource-related projects on 
the epidemiology and prevention of injury, receiving an excellent 
response from the field. Among the projects funded is a study on the 
value of pediatric readiness in the emergency care of injured children. 
Its major goal is to construct a large, multi-State dataset to 
determine if pediatric readiness in emergency medicine will result in 
improved quality of care, patient health outcomes, and costs of care 
for injured children. This project will produce the largest population-
based, pediatric trauma database, a unique research resource that would 
fill important knowledge gaps in pediatric trauma care and help to 
identify a re-engineered, high-value emergency care system for injured 
children that optimizes quality, outcomes, and costs. A second project 
was funded to provide a research and treatment resource for the 
management of psychological distress in children who have been 
hospitalized for a physical trauma. The researchers are developing 
multi-media therapeutic modules to ameliorate post-traumatic stress 
symptoms and associated psychological impairment in children after an 
injury to improve health related quality of life.
    NICHD's hallmark program is the Capstone Centers for Child 
Maltreatment Research and Training. In 2018, funding was awarded to 
three new centers (for a total of four) to serve as national resources 
for research on the prevention, screening and treatment of child abuse 
and neglect.\136\ This program has already been productive; findings 
recently released from the first center showed that adverse childhood 
experiences, including being abused and having parents with mental 
health issues, are associated with higher out-of-pocket healthcare 
costs later in life.
---------------------------------------------------------------------------
    \136\ https://www.nichd.nih.gov/newsroom/news/100418-child-
maltreatment-research.
---------------------------------------------------------------------------
    NIMH recognizes that psychological trauma is an emotionally 
painful, shocking, stressful, and sometimes life-threatening 
experience. The cumulative nature of adverse childhood experiences can 
increase the risk for poor mental and physical health outcomes.\137\ To 
better understand trauma-related risk trajectories and how early life 
adversity shapes emotional, cognitive, and brain development, NIMH is 
supporting a landmark study on the developmental precursors of mental 
illnesses.\138\ Researchers are following mothers and their infants 
over the first 3 years of life to characterize development across 
multiple levels of analysis, from environmental risk to physiology to 
neural circuits to behavior. This research has the potential to define 
the contributions of modifiable factors (psychosocial adversity, 
inflammation, and early caregiver support) to the earliest indicators 
of risk for psychopathology, and may pave the way for innovative early 
interventions, and a greater understanding of childhood trauma.
---------------------------------------------------------------------------
    \137\ https://www.ncbi.nlm.nih.gov/pubmed/16311898.
    \138\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9518320.
---------------------------------------------------------------------------
    There remain many unanswered questions in the field of childhood 
trauma. Currently, NIMH supports over 120 human and animal research 
projects related to post-traumatic stress disorder (PTSD) across the 
lifespan. Through a robust traumatic stress research program that 
includes basic, translational, and services and intervention 
research,\139\ NIMH seeks to gain a deeper understanding of how 
exposure to traumatic stress affects individuals, and how to improve 
ways of identifying those at risk before adverse reactions develop. 
Current NIMH priorities also include testing preventive interventions 
to preempt PTSD, developing new treatments for PTSD, and making 
existing PTSD treatments more effective and accessible.
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    \139\ https://www.nimh.nih.gov/about/organization/dtr/traumatic-
stress-research-and-
dimensional-measurement-and-intervention-program/index.shtml.
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                                 ______
                                 
                Questions Submitted by Senator Jack Reed
                            childhood cancer
    Question. As you know, there is strong bipartisan support for the 
Childhood Cancer STAR Act, which was signed into law last year. For 
fiscal year 2019, we provided $30 million to fund this law, the largest 
piece of which we anticipated would be dedicated to developing a 
national childhood cancer biorepository. What progress have you made in 
this area, and how much of the $30 million provided by Congress do you 
anticipate investing in the biorepositories this year?
    Answer. NCI appreciates the strong bipartisan support for childhood 
cancer research demonstrated through passage of the Childhood Cancer 
STAR Act, and NIH is committed to implementing its provisions. At NCI, 
efforts are underway to implement the childhood cancer survivorship 
research and biospecimen and biorepository research provisions, as well 
as other provisions focused on enhancing pediatric expertise on NCI 
advisory boards, and continued reporting on childhood cancer research 
activities.
    NCI continues to make progress in expanding and enhancing 
biospecimen collection and related research. For many years, NCI has 
supported the Children's Oncology Group (COG) and the COG 
Biorepository, and these efforts serve as NCI's central effort to bank 
biospecimens from children and adolescents with cancer for future 
research use. The Institute is hosting a scientific meeting in May 2019 
to bring together representatives from across the COG, including those 
involved in the COG Biorepository, and subject matter experts from 
across the childhood cancer research community who focus on specimen 
collection for cancer subtypes that are most refractory to treatment. 
NCI has invited colleagues from the Centers for Disease Control and 
Prevention's National Program of Cancer Registries to this meeting, as 
well as members of the childhood cancer advocacy community.
    This meeting will provide an opportunity to discuss specimen 
collection and biobanking challenges, particularly those related to 
specimen sharing across institutions, standardization of specimen 
annotation, and specimen quality control. The meeting will also focus 
on opportunities to further enhance specimen collection and storage, to 
encourage greater collaboration across institutions, to collect 
additional high-priority specimens outside the context of clinical 
trials, and to ensure that any new specimen collection efforts are 
complementary to those underway, such as ongoing collection and 
analysis of specimens at relapse through the NCI-COG Pediatric MATCH 
trial.\140\
---------------------------------------------------------------------------
    \140\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/pediatric-match.
---------------------------------------------------------------------------
    We look forward to the valuable guidance and input this discussion 
will provide to the entire childhood cancer research community, which 
may inform any additional new biospecimen collection efforts or 
biorepository resource enhancements in fiscal year 2019, fiscal year 
2020, and beyond, to further implement these provisions of the STAR 
Act. While NCI is committed to making significant investments to 
advance this important work, we also recognize that the STAR Act 
authorization of $30 million per year covers all sections of the 
legislation, including aspects of the law that are directed at other 
entities within the Department of Health and Human Services.
    In fiscal year 2019, NCI is making several new investments to 
support biospecimen collection and analysis that align with STAR Act 
provisions. These include biospecimen analysis studies within NCI 
pediatric and the adolescent and young adult (AYA) clinical 
trials;\141\ the NCI Pediatric Oncology Branch MyPART (My Pediatric and 
Adult Rare Tumor) Network;\142\ and the Center for Pediatric Tumor Cell 
Atlas, part of the Cancer Moonshot Human Tumor Atlas Network. The 
Center, located at the Children's Hospital of Philadelphia, will focus 
on three high-risk cancer subtypes that combined, account for 50 
percent of all pediatric cancer deaths: high-grade glioma, high-risk 
neuroblastoma, and very high risk acute lymphoblastic B-cell precursor 
leukemia.\143\ NCI has also prioritized additional new funds in fiscal 
year 2019 for our National Clinical Trials Network Groups, including 
COG, to improve patient enrollment in clinical trials. Efforts are also 
underway through the Cancer Moonshot to perform retrospective analysis 
on pediatric biospecimens. The retrospective analysis involves 
additional sequencing of specimens from several completed COG trials, 
allowing for in-depth annotation of these specimens to support future 
research. These investments are all in addition to NCI's long-term 
commitment to supporting specimen collection through COG clinical 
trials, and specimen storage through the COG Biorepository.
---------------------------------------------------------------------------
    \141\ https://www.cancer.gov/about-nci/organization/ccct/funding/
biqsfp.
    \142\ https://www.cancer.gov/nci/pediatric-adult-rare-tumor.
    \143\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9627531&icde=0.
---------------------------------------------------------------------------
    There is a compelling need for the childhood cancer research and 
advocacy community to discuss opportunities specific to biospecimen 
collection and biorepository resources. Understanding these insights is 
best before we develop any new funding opportunity announcements to 
ensure that these rare and much needed research participant 
contributions are maximally impactful. With that principle in mind, NCI 
anticipates that fiscal year 2020 STAR Act implementation activities 
will expand emphasis on biorepositories, whereas fiscal year 2019 STAR 
Act implementation activities will include greater emphasis on 
survivorship research.
    Question. Can you provide additional details on the President's 
childhood cancer initiative and how it will coordinate with the STAR 
Act programs? Can you confirm that this $50 million request is in 
addition to the $30 million in funding that we secured in fiscal year 
2019 (and which we are seeking on a bipartisan basis to build on in 
fiscal year 2020)?
    Answer. There are approximately 16,000 children and adolescents 
diagnosed with cancer in the United States each year. The President's 
Budget proposes an additional $50 million in fiscal year 2020, to 
continue for 10 years and provide a total of $500 million to support 
the Childhood Cancer Data Initiative. This initiative focuses on the 
critical need to obtain and analyzing data to learn from children with 
cancer. This information, spanning the spectrum of tumor analysis to 
clinical care and outcomes of each child, will underpin our ability to 
develop new approaches to cure children with cancer.
    The additional resources of $50 million in fiscal year 2020 will 
allow the NCI to expand efforts to collect data, to make strides in 
federating existing sources of data, to ensure that data concerning 
childhood cancers are appropriately accessible and used, and to 
incentivize the cancer research community to develop new treatments for 
children with cancer. The initiative is a promising opportunity to 
enhance our ability to improve outcomes for children with cancer--first 
by learning from every one of these children in an intentional and 
organized manner and second by developing more efficient ways to share 
and use the information. We envision that it will aggregate the 
necessary information to foster essential research while also 
increasing available information about each child's illness. Such 
information will include extensive sequencing of tumors and additional 
clinical information regarding each child's response to treatment.
    NCI is hopeful that the Childhood Cancer Data Initiative will also 
serve as a force multiplier for efforts aligned with implementation of 
the Childhood Cancer STAR Act. NCI-supported biospecimen collection and 
associated data would all contribute to the aggregated data resources 
NCI plans to develop through the initiative. NCI would also aim to 
integrate data collected though new and continued childhood cancer 
survivorship research projects and ongoing longitudinal studies (e.g., 
Childhood Cancer Survivor Study, St. Jude Lifetime Study) through the 
initiative. New data linkages and resources may also enable the cancer 
research community to establish additional cohorts to complement the 
Childhood Cancer Survivor Study, allowing NCI to study the long-term 
effects of new immunotherapy and targeted chemotherapy treatments. NCI 
is also exploring opportunities to leverage data collected through NCI 
and CDC cancer registries programs, including data collected though 
CDC's early case capture efforts for pediatric and young adult cancer 
cases. This program is a central piece of CDC's STAR Act 
implementation, and the Childhood Cancer Data Initiative has the 
potential to further build upon that work.
    In summary, NCI will continue these important research efforts with 
whatever resources are available to us. If appropriated, the 
President's Budget request envisions the $50 million proposed for the 
Childhood Cancer Data Initiative as additional new resources. In the 
current fiscal year, NCI is supporting implementation of the STAR Act 
provisions that are directed toward the Institute. For example, in 
addition to continuing to conduct and support childhood, AYA cancer 
survivorship research, NCI is expanding support in this area for new 
research projects. Specifically, NCI issued a new request for 
applications in fiscal year 2019. We estimate that we will allocate 
approximately $4.8 million per year for 5 years, to this survivorship 
research priority, subject to receiving meritorious applications and 
future fiscal year funding, among other considerations. NCI is also 
working to enhance biospecimen collection, biobanking, and related 
resources for childhood and AYA cancers, with an emphasis on those 
cancer types and subtypes for which treatments are least effective, as 
specifically encouraged in the STAR Act.
                                suicide
    Question. CDC reported in June 2018 that the suicide rate has risen 
30 percent since 1999. Given this national crisis, can you discuss what 
research is being conducted on suicide prevention research at the NIMH 
and how does NIMH set research priorities specific to suicide and 
suicide prevention?
    Answer. Suicide prevention research continues to be a top priority 
for NIH.\144\ Over the past several years, NIH has steadily increased 
its support for suicide research. NIH spent approximately $46 million 
on suicide research in fiscal year 2015, $52 million in fiscal year 
2016, $68 million in fiscal year 2017, and $96 million in fiscal year 
2018.
---------------------------------------------------------------------------
    \144\ https://www.nimh.nih.gov/about/director/messages/suicide-
prevention.shtml.
---------------------------------------------------------------------------
    As the lead Federal agency for research on mental disorders, the 
National Institute of Mental Health (NIMH) within the NIH takes a 
central role in research aimed at identifying at-risk individuals and 
developing new treatments and interventions, ultimately to improve 
quality of life and prevent death. NIMH recognizes that comprehensive 
suicide prevention efforts require multiple approaches, with the 
following research projects exemplifying some of our most promising 
tools.
Identifying At-Risk Individuals:
  --Implementing Universal Screening: The Emergency Department Safety 
        Assessment and Follow-up Evaluation (ED-SAFE) study 
        demonstrated that a three-item screening tool improved 
        providers' ability to identify adults at risk for suicide.\145\ 
        This study showed that when screening was conducted for all 
        patients--regardless of the reason for their emergency 
        department (ED) visit--suicide risk detection increased nearly 
        twofold. If these findings remain true when scaled up, the 
        public health impact could be tremendous, because 
        identification of risk is the first and necessary step for 
        preventing suicide.
---------------------------------------------------------------------------
    \145\ https://www.ncbi.nlm.nih.gov/pubmed/26654691.
---------------------------------------------------------------------------
  --Maximizing Electronic Health Records: Building on the Army Study to 
        Assess Risk and Resilience in Servicemembers (Army 
        STARRS),\146\ the largest study of mental health risk and 
        resilience ever conducted among military personnel, researchers 
        from NIMH partnered with the Department of Veterans Affairs 
        (VA) and other collaborators to develop predictive models of 
        suicide risk among veterans receiving VA healthcare. This 
        research demonstrated the feasibility of developing algorithms 
        to identify patients within the VA system whose predicted 
        suicide risk was 20-30 times higher than average. Suicide 
        prevention coordinators at each VA facility work with these 
        patients and their clinicians on suicide-focused clinical 
        assessment and ways to enhance treatment. Other healthcare 
        systems are beginning to use data from electronic health 
        records in novel ways to help identify people with suicide 
        risk, including many of the 13 healthcare systems across the 
        United States that are part of NIMH's Mental Health Research 
        Network.\147\
---------------------------------------------------------------------------
    \146\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286426/.
    \147\ https://www.ncbi.nlm.nih.gov/pubmed/29792051.
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Developing New Treatments and Interventions:
  --Strengthening Mental Health Support: NIMH continues to support 
        research to identify effective interventions for individuals at 
        risk for suicide. One such intervention is Safety Planning 
        Intervention (SPI), in which a clinician collaborates with the 
        patient to identify specific strategies to decrease the risk of 
        suicidal behavior, such as ways to reduce the patients' access 
        to lethal means during a time of crisis, and to identify 
        personalized coping strategies. NIMH is supporting an 
        evaluation of the implementation of the Zero Suicide approach, 
        including SPI, in 145 community mental health clinics across 
        New York.\148\ In addition, NIMH's ED-SAFE study, which focused 
        on ED patients at risk for suicide, found that brief 
        interventions in the ED, plus follow-up phone calls to the 
        patient by a clinician, reduced suicide attempts by about 30 
        percent during a 12-month period.\149\
---------------------------------------------------------------------------
    \148\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9514242.
    \149\ https://www.ncbi.nlm.nih.gov/pubmed/28456130.
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  --Deploying Fast-Acting Pharmacologic Interventions: NIMH research 
        has also supported the study of fast-acting treatments for 
        individuals with acute suicide risk. Ketamine, an anesthetic 
        that has been around for decades, is emerging as a rapid onset 
        intervention. NIMH researchers showed that suicidal ideation 
        (in the context of major depressive disorder) was reduced 
        within 40 minutes of a ketamine infusion and remained improved 
        for up to four hours post-infusion.\150\ A subsequent meta-
        analysis reported that a single infusion of ketamine reduces 
        suicidal ideation for up to one week.\151\ In March 2019, the 
        FDA approved SpravatoTM, an esketamine nasal spray 
        (a form of ketamine), in conjunction with an oral 
        antidepressant, for treatment-resistant depression.\152\ This 
        treatment is only available at a trained doctor's office or 
        clinic to mitigate potential risks. The makers of 
        SpravatoTM are also conducting clinical trials of 
        intranasal esketamine in participants at imminent risk for 
        suicide.\153\
---------------------------------------------------------------------------
    \150\ https://www.ncbi.nlm.nih.gov/pubmed/20673547.
    \151\ https://www.ncbi.nlm.nih.gov/pubmed/28969441.
    \152\ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm632761.htm.
    \153\ https://www.ncbi.nlm.nih.gov/pubmed/29656663.
---------------------------------------------------------------------------
    NIMH's overall research priorities continue to be informed by 
strategic planning and include the input of stakeholders, advisory 
committees, and NIMH leadership. In developing these priorities, NIMH 
strives to balance public health needs and scientific opportunities, 
taking into consideration portfolio balance among other factors. For 
example, specific to suicide prevention, the stakeholder-informed 
Prioritized Research Agenda for Suicide Prevention is an available 
resource that can be used to help identify gaps in the NIMH suicide 
prevention portfolio.\154\ NIMH only funds research which is judged 
highly meritorious and follows a two-stage peer review process.
---------------------------------------------------------------------------
    \154\ https://theactionalliance.org/resource/prioritized-research-
agenda-suicide-prevention-action-plan-save-lives.
---------------------------------------------------------------------------
    Question. The recently released action plan from the National 
Action Alliance for Suicide Prevention outlines the need to develop a 
prioritized approach for allocating funds and monitoring future suicide 
research to ensure that available resources are directed towards 
research with the greatest likelihood of reducing suicide deaths. Has 
NIH reviewed these recommendations and, if so, what does NIH plan to do 
with the recommendations?
    Answer. NIMH is working with scientists and stakeholders to address 
the increasing incidence of suicide across the country, focusing on 
identifying research gaps, challenges, and opportunities to inform how 
to make change now and in the longer-term. Under the leadership of 
former NIMH Director Thomas Insel, M.D., the Research Prioritization 
Task Force (RPTF) aimed to advance the efforts of the National Action 
Alliance for Suicide Prevention (NAASP), a public-private partnership 
among Federal agencies, State governments, private companies, and 
national suicide prevention advisory and advocacy groups. As part of 
the RPTF, NIMH helped to develop the Prioritized Research Agenda for 
Suicide Prevention.\155\ The Agenda identifies research gaps, such as 
limitations in understanding of the etiology and course of suicidal 
ideation and behavior, the need for new interventions specifically 
targeting suicide, better matching of existing treatments to individual 
needs, and implementation of effective suicide prevention practices.
---------------------------------------------------------------------------
    \155\ https://theactionalliance.org/resource/prioritized-research-
agenda-suicide-prevention-action-plan-save-lives.
---------------------------------------------------------------------------
    NIMH has initiated research opportunities to address research gaps 
identified in the Agenda, such as studies to develop and test screening 
approaches for use in EDs to identify youth at risk for suicide, and 
develop methods to help assign youth who screen positive to appropriate 
interventions.\156\ NIMH also partnered with other NIH Institutes and 
Centers to support projects leveraging existing data sets to improve 
our understanding of risk trajectories and subgroups at risk for 
suicide, while addressing suicide research gaps in mortality 
outcomes.\157,158\ To further address gaps in the research workforce, 
NIMH issued a notice of special interest to expand the number of mental 
health researchers--both established scientists, as well as early 
career scientists--who engage in suicide research.\159\
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    \156\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
070.html.
    \157\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
400.html.
    \158\ https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-18-
410.html.
    \159\ https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-
026.html.
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    In addition, NIMH partners with NAASP to support their Zero Suicide 
initiative.\160\ Zero Suicide is a commitment, a goal, and a campaign 
to prevent suicide attempts and deaths among individuals receiving 
treatment within healthcare systems. NIMH is funding several projects 
aimed at Zero Suicide to create a stronger basis for dissemination and 
large-scale implementation of effective risk detection, intervention, 
and service delivery strategies for suicide prevention in real world 
settings.\161\ This effort is also consistent with the NIMH Strategic 
Plan for Research, Objective 4, improving public health through more 
practice-ready suicide prevention interventions.\162\
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    \160\ http://zerosuicide.sprc.org/.
    \161\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-
800.html.
    \162\ https://www.nimh.nih.gov/about/strategic-planning-reports/
strategic-objective-4.shtml.
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                                 ______
                                 
            Questions Submitted by Senator Patrick J. Leahy
                               migraines
    Question. Migraine is currently the second leading cause of all 
global disability. Unfortunately, due in part to limited research and 
treatment, inappropriate opioid prescriptions for migraine present 
Americans with ongoing risks of opioid use disorders and have worsened 
outcomes in patients. The NIH website on disease burden shows 
``migraine'' to have received by far the lowest level of research 
funding in 2015, among those diseases with the highest burden. In 2017, 
only 53 extramural investigators were funded for headache research, 
compared to 315 for epilepsy and 385 for schizophrenia, each of which 
has far lower burden than migraine. While migraine grant proposals are 
eligible for consideration under the HEAL RFAs recently issued for pain 
research, I am very concerned that these will fail to attract enough 
investigators to this historically under-funded research area.
    Does NIH have plans to issue specific RFA programs for headache 
disorders research, comparable in scope to the BACPAC group of RFAs for 
research on back pain?
    Answer. NIH recognizes the burden of headache disorders as 
prevalent and disabling conditions for patients around the country.
    NIH has identified priority areas of need unique to headache 
research, including fundamental mechanisms to guide new treatment 
development and advancing treatments through the clinical pipeline. 
Importantly, headache research is an area with trans-NIH interest for 
which funding has increased from $18 million in 2010 to $32 million in 
2018. NIH has supported important research that is providing exciting 
new therapies for headache. Basic research on potassium channels, delta 
or kappa opioid receptors, and TRP channels has fundamentally increased 
our understanding of trigeminal nociceptors and their involvement in 
initiating a migraine, giving us new targets for potential treatments. 
NIH investigators also provided the foundation for development of 
calcitonin gene receptor protein (CGRP) antibodies now used for 
migraine therapy. In addition, NIH sponsored research also led to 
efforts exploring the promising avenue of vagus nerve stimulation for 
headaches. Lastly, a pivotal trial on pediatric migraine is shifting 
clinical practice toward safer and more effective therapies. These 
exciting advances are all examples of NIH efforts toward relieving the 
burden of headache disorders.
    In addition, NIH's long-standing programs in these specific areas 
will be greatly enhanced by the recently launched HEAL (Helping to End 
Addiction Long-term) initiative and its efforts to advance the research 
agenda for pain and care across pain conditions. Through HEAL, NIH 
released many funding opportunity announcements for research on 
biomarker discovery, device and drug development, clinical trials on 
effectiveness of interventions and pragmatic trials for implementation 
of effective therapies for pain conditions. Headache research fits 
within the scope of all these initiatives and NIH has made strong 
efforts to network with and encourage the headache research community 
to submit applications to these solicitations. Furthermore, the 
infrastructure and resources being established through the HEAL 
initiative will be available to enhance pain research across all 
conditions which will greatly inform new areas of mechanisms for 
headache research.
    The HEAL BacPac Initiative was designed to fill a unique need for 
another highly prevalent pain condition for which much of the research 
framework is inadequate. Back pain is unique in that it lacks accurate 
diagnostic tools and assessments, a clear classification scheme based 
on causality, understating of the underlying mechanisms, and effective 
treatment approaches. Unlike the case for back pain, the diagnostics 
and classifications for headache disorders are better established and 
our understanding of the mechanisms of headaches is moving forward 
through existing programs and can be further advanced through HEAL with 
the participation of the headache research community.
                         cardiovascular disease
    Question. Over the past half-century, we have witnessed 
unprecedented progress in addressing cardiovascular disease, yet recent 
trends show that declines in heart disease and stroke mortality rates 
have slowed for all races and are increasing substantially among 
certain population groups such as rural, middle-aged white Americans. 
The American Heart Association recently announced new alarming data 
that shows that nearly half (48 percent) of U.S. adults have some form 
of cardiovascular disease.
    As our Nation's population ages, there is an urgent need for action 
to improve innovation in the treatment of cardiovascular disease. What 
is NIH doing to address the high rates of cardiovascular mortality, 
especially in rural areas like my home State of Vermont?
    Answer. The NIH is committed to ensuring that all Americans benefit 
from the life-saving advances made possible by federally funded 
research--regardless of their race, age, sex, income, or where they 
live. The National Heart, Lung, and Blood Institute (NHLBI) leads NIH's 
support for research on cardiovascular disease (CVD). Over the past 50 
years, research funded by the NHLBI has helped bring about a 71 percent 
decline in deaths from CVD nationwide. However, CVD remains the 
Nation's leading cause of death, with the highest mortality 
concentrated in certain groups, including African Americans, American 
Indian/Alaska Natives, and rural communities. We are supporting 
research to determine what causes these health disparities and how to 
correct them.
    High blood pressure is a leading risk factor for heart disease and 
stroke. Given that blood pressure medication dosing and adherence is a 
major challenge in rural and underserved communities, NHLBI is 
supporting innovative methods to help patients connect with 
pharmacists. For example, NHLBI's Collaboration Among Pharmacist and 
Physicians toto Improve Outcomes Now (CAPTION) study embedded 
pharmacists within 32 primary care physicians' offices in 15 states, 
serving high-risk socioeconomic and racial groups. After 9 months, 
patients treated through this physician-pharmacist team approach had 
sustained reductions in blood pressure, compared to patients who 
received usual care.\163\ Another recent NHLBI-funded study found that 
having blood pressure screenings and pharmacist consultations in 
barbershops helped men lower their blood pressure.\164\ Innovative 
programs like these could be adapted and used in rural settings to 
reduce hypertension and other cardiovascular risk factors.
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    \163\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063695.
    \164\ https://www.ncbi.nlm.nih.gov/pubmed/29527973.
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    A new NHLBI program launched in March 2019, Disparities Elimination 
through Coordinated Interventions to Prevent and Control Heart and Lung 
Disease Risk (DECIPHeR) will help bring evidence-based interventions 
like these to communities with a high burden of CVD. DECIPHeR 
researchers will form partnerships with local healthcare systems, 
government agencies, and community organizations so researchers and 
community members can work together to design, test, and sustain 
effective approaches to deliver proven treatments.\165\
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    \165\ https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-20-
003.html.
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    NHLBI also recently solicited proposals for new large cohort 
studies to address research on heart, lung, blood, and sleep disorders, 
with an emphasis on groups that are currently not well represented, 
including rural communities.\166\ We expect to fund three such cohorts 
later this year.
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    \166\ https://grants.nih.gov/grants/guide/pa-files/PAR-18-577.html.
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    NHLBI also supports research to address CVD through telehealth. 
This could include the use of audiovisual technology to deliver remote 
care for patients who live in remote areas or have other challenges 
accessing primary healthcare centers. For example, an ongoing NHLBI-
funded study is evaluating the effectiveness of traditional center-
based cardiac rehabilitation combined with telemedicine-guided 
rehabilitation at home.\167\ NHLBI is also funding a study to collect 
national data on the use of telemedicine in intensive care units to 
identify best practices.\168\
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    \167\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9588024.
    \168\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9061809.
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    Rural patients have traditionally been underrepresented in 
cardiovascular clinical trials, yet have a higher burden of CVD than 
patients from metropolitan areas. We are working to increase enrollment 
of rural patients in NHLBI's Cardiothoracic Surgical Trials Network, 
which has made significant contributions in advancing the evidence base 
for cardiothoracic surgery. Dartmouth-Hitchcock Medical Center in New 
Hampshire and Maine Medical Center were recently linked to the network 
to expand its reach into rural communities of Northern New 
England.\169\
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    \169\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9755050.
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                          nih pain consortium
    Question. Pain is a significant public health issue affecting an 
estimated 69.6 million Americans each year. According to the Institute 
of Medicine, the total incremental cost of healthcare due to pain 
management in the U.S. is estimated to range from $560 billion to $635 
billion, amounting to approximately 2.8 to 3.5 percent of our Nation's 
total GDP. This cost estimate combines the direct medical costs of pain 
management care as well as the economic costs related to lost 
productivity and disability programs. With little known about 
alternatives for treating and managing relief from pain, medical 
providers are often limited to prescribing highly addictive opioids or 
muscle relaxants to help patients mitigate symptoms from pain.
    Unfortunately, addiction to opioid painkillers has ravaged the 
Nation, and the number of opioid prescriptions has tripled in the past 
20 years alone. In 1996, the National Institutes of Health (NIH) 
established the NIH Pain Consortium to develop a strategy for research 
on pain. Since then, the NIH has worked to expand research in this 
area, while incorporating the work and expertise of stakeholders to 
find ways to better serve patients.
    Has the NIH Pain Consortium approached research on exploring opioid 
alternatives to treating and managing both acute and chronic pain? If 
so, please describe past, present, and ongoing projects in this area. 
If not, please describe if the NIH plans to develop more research 
focused on finding opioid alternatives to treating and managing acute 
and chronic pain.
    Answer. The NIH recognizes the significant public health crisis and 
individual burden of pain and supports research to better understand, 
manage and treat acute and chronic pain to relieve the burden of pain 
and reduce our reliance on prescription opioid medications.
    The NIH Pain Consortium is a collaboration of 27 Institutes, 
Centers, and Offices (ICOs) across the NIH charged with promoting and 
coordinating pain research across the agency. In 2018 the NIH Pain 
Consortium ICOs collectively spent $605 million on a wide range of 
research collectively aimed at understanding the mechanisms of pain, 
new targets for treatment, and more. NIH has existing programs to 
support development of novel and non-addictive treatments for acute and 
chronic pain, from early-stage drug target discovery of molecular 
pathways of pain signaling, exploration of receptors and channels as 
potential non-addictive analgesic targets, and testing of novel 
treatments in preclinical behavioral models. Through these programs, 
NIH researchers identified nerve growth factor receptor and pain-
related ion channel targets, which have led to industry-sponsored 
clinical trials for safe pain treatments for musculoskeletal pain and 
other pain disorders. NINDS supported early development of calcitonin 
gene receptor protein, the precursor to a compound recently approved to 
treat migraine. NIH programs for discovery of new formulations, 
combinations of medicines, and re-purposing molecules developed for 
other disorders are being expanded rapidly to find new pain 
medications. Through the NIH Blueprint Neurotherapeutics Program, which 
provides support for small molecule drug discovery and development, NIH 
currently is funding research to develop a non-addictive treatment for 
headache and non-opioid analgesics for diabetic nerve pain.\170\
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    \170\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9325694&icde=36528658
&ddparam=&ddvalue=&ddsub=&cr=3&csb=default&cs=ASC&pball=.
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    The NIH Pain Consortium worked with the Interagency Pain Research 
Coordinating Committee to develop the Federal Pain Research Strategy 
\171\ (FPRS), which outlines a long-term strategic plan to guide NIH 
and other Federal agencies in making their funding decisions to advance 
pain research. The development of safer opioids and new, non-opioid 
analgesics were considered high priority research areas in this 
strategy.
---------------------------------------------------------------------------
    \171\ Federal Pain Research Strategy: https://iprcc.nih.gov/sites/
default/files/iprcc/FPRS_
Research_Recommendations_Final_508C.pdf.
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    The NIH Pain Consortium, with the FPRS as a guide, has been 
involved in developing and implementing the recently released NIH HEAL 
(Helping to End Addiction Long-term) Initiative,\172\ which aims to 
enhance research to better treat addiction and opioid overdose and to 
improve pain care, thereby reducing our reliance on opioids. HEAL 
supported projects will increase our understanding of pain, expand and 
accelerate the development of non-addictive treatments, and rapidly 
advance new treatments to the clinic. Through HEAL, NIH supports 
biomarker discovery and validation to inform early phase clinical 
testing of potential non-addictive pain therapies. To improve success 
in bringing medications to the clinic, HEAL will facilitate the sharing 
of data on past and future drug development efforts across the 
biopharmaceutical industry and academia. To accelerate testing of novel 
pain treatments in humans, NIH is establishing the HEAL Early Phase 
Pain Clinical Network to test new, non-addictive pain treatments 
through clinical trials. The HEAL initiative also is establishing a 
pain management effectiveness research network to support large 
clinical trials to test the effectiveness of pharmacological and non-
pharmacological treatments across many pain conditions.
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    \172\ The NIH HEAL Initiative: https://www.nih.gov/research-
training/medical-research-initiatives/heal-initiative.
---------------------------------------------------------------------------
    NIH is working with Federal partners to provide the infrastructure 
through the NIH Health Care Systems Research Collaboratory for 
implementation of non-pharmacological treatments into healthcare 
systems, with the ultimate goal to embed evidence-based best pain 
management practices in clinics. These efforts represent unprecedented 
expansion of the NIH pain research portfolio.
                                 ______
                                 
               Questions Submitted to Douglas Lowy, M.D.
          Questions Submitted by Senator Shelley Moore Capito
                            childhood cancer
    Question. There is strong bipartisan support for childhood cancer 
here in Congress, as evidenced by the overwhelming support for the 
Childhood Cancer STAR Act that was signed into law last year. I was 
very pleased to see the President highlight the vital need to invest 
more in childhood cancer during his State of the Union and in his 
Budget Submission to Congress.
    How does the President's childhood cancer initiative coordinate 
with the STAR Act programs? Is your $50 million request for increased 
childhood cancer funding in addition to the $30 million we are working 
to provide for the STAR Act?
    Answer. There are approximately 16,000 children and adolescents 
diagnosed with cancer in the United States each year. The President's 
Budget proposes an additional $50 million in fiscal year 2020, to 
continue for 10 years and provide a total of $500 million to support 
the Childhood Cancer Data Initiative. This initiative focuses on the 
critical need to obtain and analyze data to learn from children with 
cancer. This information, spanning the spectrum of tumor analysis to 
clinical care and outcomes of each child, will underpin our ability to 
develop new approaches to cure children with cancer.
    The additional resources of $50 million in fiscal year 2020 will 
allow the NCI to expand efforts to collect data, to make strides in 
federating existing sources of data, to ensure that data concerning 
childhood cancers is appropriately accessible and used, and to 
incentivize the cancer research community to develop new treatments for 
children with cancer. The initiative is a promising opportunity to 
enhance our ability to improve outcomes for children with cancer--first 
by learning from every one of these children in an intentional and 
organized manner and second by developing more efficient ways to share 
and use the information. We envision that it will aggregate the 
necessary information to foster essential research while also 
increasing available information about each child's illness. Such 
information will include extensive sequencing of tumors and additional 
clinical information regarding each child's response to treatment.
    The Childhood Cancer Data Initiative should also serve as a force 
multiplier for efforts aligned with implementation of the Childhood 
Cancer STAR Act. NCI-supported biospecimen collection and associated 
data would all contribute to the aggregated data resources NCI plans to 
develop through the initiative. NCI would also aim to integrate data 
collected though new and continued childhood cancer survivorship 
research projects and ongoing longitudinal studies (e.g., Childhood 
Cancer Survivor Study, St. Jude Lifetime Study) through the initiative. 
New data linkages and resources may also enable the cancer research 
community to establish additional cohorts to complement the Childhood 
Cancer Survivor Study, allowing NCI to study the long-term effects of 
new immunotherapy and targeted chemotherapy treatments. NCI is also 
exploring opportunities to leverage data collected through NCI and CDC 
cancer registries programs, including data collected though CDC's early 
case capture efforts for pediatric and young adult cancer cases. This 
program is a central piece of CDC's STAR Act implementation, and the 
Childhood Cancer Data Initiative has the potential to further build 
upon that work.
    In summary, NCI will continue these important research efforts with 
whatever resources are available to us. If appropriated, the 
President's Budget request envisions the $50 million proposed for the 
Childhood Cancer Data Initiative as additional new resources. In the 
current fiscal year, NCI is supporting implementation of the STAR Act 
provisions that are directed toward the Institute. For example, in 
addition to continuing to conduct and support childhood, adolescent, 
and young adult (AYA) cancer survivorship research, NCI is expanding 
support in this area for new research projects. Specifically, NCI 
issued a new request for applications in fiscal year 2019. We estimate 
that we will allocate approximately $4.8 million per year for 5 years, 
to this survivorship research priority, subject to receiving 
meritorious applications, among other considerations. NCI is also 
working to enhance biospecimen collection, biobanking, and related 
resources for childhood and AYA cancers, with an emphasis on those 
cancer types and subtypes for which treatments are least effective, as 
specifically encouraged in the STAR Act.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
                              ethyl oxide
    Question. I'd like to ask about Ethylene Oxide--or EtO--a gas that 
is widely used for the sterilization of certain medical devices. EtO is 
a carcinogen. The National Cancer Institute acknowledges that exposure 
to this gas has been linked to certain types of cancer, including 
lymphoma, leukemia, and breast cancer. Illinois has three large 
facilities that currently use EtO, including Sterigenics in 
Willowbrook, Illinois, which was recently ordered to stop using EtO, 
after the Environmental Protection Agency measured alarmingly high 
levels of the gas in neighboring communities. Late last month, the 
Illinois Department of Public Health issued a report which showed 
higher rates of certain types of cancers around the Sterigenics 
facility--including Hodgkins lymphoma and breast cancer in women, and 
pediatric lymphoma in young girls. While we do not know yet if these 
cancers are definitively linked to the Sterigenics EtO emissions, they 
are certainly cause for concern. Dr. Lowy, what do we know about 
exposure to EtO? What do you make of reports like the one released by 
the Illinois Department of Public Health?
    Answer. The NCI supports a wide range of research to understand 
associations between exposures and cancer risk, including environmental 
exposures like ethylene oxide (EtO). NCI is committed to supporting 
research to increase our understanding of the complexity of cancer risk 
factors and working with other government agencies responsible for 
regulating such environmental exposures.
    NCI-supported research has contributed to the body of knowledge 
that has led to the classification of EtO as a carcinogen. EtO is used 
primarily to produce other chemicals, including antifreeze, and in 
smaller amounts, EtO is used as a pesticide and a sterilizing agent. 
The ability of EtO to damage DNA makes it an effective sterilizing 
agent but also accounts for its cancer-causing activity. Because EtO is 
highly explosive and reactive, the equipment used for its processing 
generally consists of tightly closed and highly automated systems, 
which decreases the risk of occupational exposure. Despite these 
precautions, workers and people who live near industrial facilities 
that produce or use EtO may be exposed to EtO through uncontrolled 
industrial emissions. The general population may also be exposed 
through tobacco smoke and the use of products that have been sterilized 
with EtO, such as medical products, cosmetics, and beekeeping 
equipment.\173\
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    \173\ https://www.cancer.gov/about-cancer/causes-prevention/risk/
substances/ethylene-oxide.
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    In 2000, the National Toxicology Program, part of the National 
Institute of Environmental Health Sciences, upgraded EtO from 
``reasonability anticipated carcinogen'' to a ``known human 
carcinogen.'' \174\ As an analysis conducted by the EPA reaffirmed last 
year, lymphoma and leukemia are the cancers most frequently reported to 
be associated with occupational exposure to ethylene oxide. Stomach and 
breast cancers may also be associated with ethylene oxide 
exposure.\175\
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    \174\ https://www.niehs.nih.gov/news/newsroom/releases/2000/may15/
index.cfm.
    \175\ https://www.tandfonline.com/doi/full/10.1080/
15376516.2017.1414343.
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    Because the evidence indicating the carcinogenicity of EtO is well-
established, NCI has a limited role in responses to suspected cases of 
EtO exposure. In these instances, NCI resources may provide data for 
investigators to determine whether EtO exposure may be contributing to 
high cancer rates. For example, those investigating such claims may use 
data collected by the NCI Surveillance, Epidemiology, and End Results 
(SEER) Program to inform conclusions about how EtO exposure has 
affected cancer incidence. The SEER Program collects information on 
cancer incidence, prevalence, and survival from specific geographic 
areas representing 34 percent of the U.S. population. The SEER research 
datasets, drawn primarily from State cancer registries, include SEER 
incidence and population data associated by age, sex, race, year of 
diagnosis, and geographic areas. SEER also provides analytical tools 
and methodological expertise in collecting, analyzing, interpreting, 
and disseminating population-based statistics.\176\ Another resource 
for those investigating instances of EtO exposure is the NCI Cancer 
Atlas, an exploratory tool that enables users to construct comparative 
maps, graphs, and charts of cancer statistics and risk factors. The NCI 
Cancer Atlas can help with the development of new methods of displaying 
geospatial data for clear communication to the public and for 
examination of complex multivariate data by researchers.\177\ Both the 
SEER Program and the NCI Atlas can act as resources to inform State and 
local health departments when assessing cancer incidence and 
surveillance.
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    \176\ https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf.
    \177\ https://gis.cancer.gov/gis-nci/gis_nci.html.
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    Federal agencies with the authority to research and monitor the 
effects of hazardous substances on human health are the U.S. 
Environmental Protection Agency (EPA), the CDC, and the Agency for 
Toxic Substances and Disease Registry (ATSDR). While the EPA identifies 
certain chemicals as hazardous air pollutants and regulates facilities 
with these emissions,\178\ the CDC is the lead Federal agency on 
addressing public health concerns about potential harmful exposures. 
ATSDR conducts research on the health impacts of specific sites and 
provides information and recommendations to Federal and State agencies, 
including CDC and EPA.\179\ The National Center for Environmental 
Health (NCEH), part of CDC, conducts research to investigate the 
effects of the environment on health by tracking and evaluating 
environment-related health problems through surveillance systems. NCEH 
partners with State, local, and tribal health State departments to 
conduct health surveillance, epidemiologic studies, communication and 
education, standard setting and guidelines, and technical support.\180\
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    \178\ https://www.epa.gov/haps.
    \179\ https://www.atsdr.cdc.gov/about/index.html.
    \180\ https://www.cdc.gov/nceh/information/about.htm.
---------------------------------------------------------------------------
    With technical assistance from CDC, State and local health 
departments determine whether a particular exposure is responsible for 
certain cancer cases. NCI assists CDC by supporting epidemiological 
research on cancer surveillance and studies of cancer incidence, 
including those programs mentioned above.
    NCI will continue to work with other Federal agencies to provide 
epidemiological data and other research findings to inform their 
investigation of EtO exposure.
                                 ______
                                 
               Questions Submitted to Anthony Fauci, M.D.
                Questions Submitted by Senator Roy Blunt
                antimicrobial and antibiotic resistance
    Question. Fauci, there was a New York Times article on April 7th 
describing the rise of drug-resistant germs. The article highlighted 
that just like bacteria, fungus is now becoming resistant to drugs 
developed to treat them. Over the past 4 years, the Labor/HHS bill has 
included specific funds to combat antibiotic resistance, most recently 
including $550 million in fiscal year 2019 for NIH, 50 percent more 
than you had in fiscal year 2016. Can you discuss the threat of 
antibiotic resistant germs and fungus and explain what research your 
Institute is focusing on in this area?
    Answer. The emergence of antimicrobial resistance (AMR) in a range 
of bacterial and fungal pathogens is a public health threat of great 
concern. Each year in the United States, there are more than 2 million 
infections with antibiotic-resistant bacteria and at least 23,000 
deaths as a direct result of these infections. Fungal infections also 
are a serious problem in healthcare settings, and infections with drug-
resistant fungi are more difficult to treat. A drug-resistant form of a 
fungal pathogen, Candida auris (C. auris), recently has emerged in the 
United States and elsewhere, and has led to severe illness in 
hospitalized patients. The National Institute of Allergy and Infectious 
Diseases (NIAID) is the lead Institute of the NIH for basic, 
translational, and clinical research confronting the critical issue of 
AMR in bacterial and fungal pathogens.
    Advances in AMR research have created opportunities to develop 
state-of-the-art diagnostics to detect and help limit the spread of 
AMR, accelerate the development of new antimicrobials, identify ways to 
use the immune system to eradicate bacterial or fungal pathogens, and 
manipulate microbial communities to prevent or treat infections. NIAID 
has used recent funding increases provided by Congress to expand its 
comprehensive AMR research portfolio and accelerate research in each of 
these areas of scientific opportunity.
    NIAID supports research to develop rapid point-of-need diagnostics 
to inform appropriate treatment and identify resistance to commonly 
used drugs. NIAID research has led to the development of several novel 
diagnostics capable of distinguishing between numerous infectious 
agents. These include two Food and Drug Administration (FDA)-cleared 
diagnostics: one that tests for 24 bacterial and fungal species that 
cause sepsis, and another that can detect a number of different 
bacterial and viral species that cause pneumonia along with seven 
genetic markers of AMR. In addition, the NIAID Antibacterial Resistance 
Leadership Group, which oversees clinical research on antibiotic 
resistance, is developing a master protocol to allow for the evaluation 
of multiple diagnostic tests using samples from a single patient. NIH 
also is partnering with the Biomedical Advanced Research and 
Development Authority (BARDA) to support the Antimicrobial Resistance 
Diagnostic Challenge competition to identify innovative and rapid 
point-of-need diagnostic tests that inform appropriate antibiotic 
treatment and facilitate antimicrobial stewardship. Submissions for 
Step 3 of the Challenge are due in January 2020, and final results of 
the competition are anticipated in July 2020.
    NIAID's investments in AMR research are advancing the development 
of promising new therapeutic candidates for drug-resistant infections. 
NIAID-supported researchers have developed a method to synthesize novel 
forms of a class of antibiotics (tetracyclines) that are not 
susceptible to existing bacterial resistance mechanisms. One of these 
compounds, XERAVATM, recently received FDA approval to treat 
complicated intra-abdominal infections. NIAID funding also has led to 
the discovery of a new class of antibiotics, malacidins, that are being 
investigated for further therapeutic development. In addition, NIAID 
provides in-kind and technical support for CARB-X (Combating Antibiotic 
Resistant Bacteria-X), a public-private partnership led by BARDA. CARB-
X is currently funding the development of 35 innovative projects, 
including 13 that represent new antibiotic classes.
    NIAID also supports the development of antifungal therapies, 
including those that may be effective against drug-resistant fungi. One 
fungal pathogen of particular concern is C. auris, which can cause 
serious infections that can affect the blood, heart, brain, eyes, 
bones, and other parts of the body. While most C. auris infections are 
treatable with existing antifungal drugs, the presence of C. auris 
infections resistant to the main classes of antifungal drugs is 
extremely concerning. NIAID is facilitating preclinical screening of 
candidate therapeutics for effectiveness against C. auris and has 
identified several lead candidates. NIAID also is supporting 
investigation of a broad-spectrum antifungal with activity against C. 
auris and other Candida species.
    NIAID-supported investigators are exploring approaches that 
leverage the immune system to combat drug-resistant infections. One 
novel approach uses antibodies to boost the ability of an infected 
individual's own immune system to fight infection. NIAID also is 
advancing the development of candidate vaccines against bacterial and 
fungal pathogens, including strains that exhibit drug resistance. This 
includes an experimental vaccine to protect against Staphylococcus and 
Candida species, including C. auris and Staphylococcus aureus (S. 
aureus). Vaccines against these bacterial and fungal pathogens could 
help prevent infections, thus avoiding the use of antibacterial or 
antifungal drugs and limiting the potential for development of AMR.
    NIAID also supports research investigating the use of beneficial 
bacteria to prevent or treat colonization with pathogenic AMR bacteria. 
NIAID funds studies on the use of fecal microbiota transplants to 
replenish beneficial gut microbiota and prevent and treat bacterial 
infections. This strategy may be particularly effective for difficult-
to-eradicate infections such as the bacterial species Clostridium 
difficile. In addition, NIAID scientists discovered that the use of 
probiotic digestive supplements containing Bacillus bacteria prevented 
S. aureus bacteria from growing in the gut and nose of healthy 
individuals.
    NIAID recognizes that a multi-pronged, multi-disciplinary approach 
is necessary to address the serious threat posed by drug-resistant 
microbes. NIAID will continue to support the development of improved 
tools and strategies to identify, prevent, and treat infections with 
AMR pathogens.
                         ending hiv initiative
    Question. The President's budget proposes to end HIV transmission 
in the United States in 10 years. Dr. Fauci, can you discuss what is 
necessary to reach this goal, how an HIV vaccine could help achieve it, 
and where you are in the development of a vaccine?
    Answer. The fiscal year 2020 President's Budget has proposed a new 
initiative of the Department of Health and Human Services (HHS) on 
Ending the HIV Epidemic to address the ongoing public health crisis of 
HIV in this country. The goals of the initiative are first reducing 
numbers of new HIV infections in the United States by 75 percent within 
5 years, and then by 90 percent within 10 years. The initiative will 
leverage critical scientific advances in HIV prevention, diagnosis, 
treatment, and care by coordinating the highly successful programs, 
resources, and infrastructure of the NIH, the Centers for Disease 
Control and Prevention, the Health Resources and Services 
Administration, and the Indian Health Service.
    The initiative is coordinated by the HHS Office of the Assistant 
Secretary of Health. During the initial phase of the initiative, the 
focus will be on geographic areas and demographic groups in 19 States, 
Washington, DC, and Puerto Rico, where the majority of new HIV cases 
are reported, as well as in 7 States with a disproportionate occurrence 
of HIV in rural areas. The initiative includes four pillars to help 
reduce HIV infections:
  --Diagnose all individuals with HIV as early as possible after 
        infection;
  --Treat HIV infection rapidly and effectively to achieve sustained 
        viral suppression;
  --Prevent at-risk individuals from acquiring HIV, including through 
        the use of pre-exposure prophylaxis (PrEP); and
  --Rapidly detect and respond to emerging local epidemics of HIV 
        infection to further reduce new infections.
    Advances in HIV treatment and prevention research suggest that, 
theoretically, the HIV epidemic in this country could be ended by 
expanding access to treatment to all persons with HIV and PrEP to all 
those at high risk. The Administration has developed a practical, 
achievable plan to focus on the places and populations in the United 
States that are most affected by HIV. Lessons learned and effective 
strategies emanating from this initiative would ultimately be applied 
to profoundly reduce HIV incidence nationwide through Federal, State, 
and local health departments and nongovernmental organizations. NIH-
supported research through the Centers for AIDS Research (CFARs) and 
AIDS Research Centers will play a critical role in developing best 
practices for the initiative by collecting and disseminating data on 
the effectiveness of approaches used to achieve the initiative's four 
pillars. The fiscal year 2020 President's Budget includes $6 million 
for NIH CFARs to support the HHS Ending the HIV Epidemic initiative.
    The development of a safe and effective HIV vaccine remains a key 
component to realizing an end to the HIV pandemic. If an HIV vaccine 
were to become available, it would add another key HIV prevention tool 
to complement the ongoing efforts on HIV diagnosis, treatment, and 
pharmaceutical-based prevention through this initiative. NIAID is the 
lead for HIV vaccine research at the NIH. Currently, NIAID-supported 
scientists around the world are following two complementary paths to 
accelerate the development of an HIV vaccine.
    The first approach to HIV vaccine development builds upon prior 
partial success of the RV144 vaccine regimen. In 2009, the findings of 
a large international clinical trial of the RV144 vaccine regimen 
showed for the first time that an HIV vaccine approach could confer 
modest protection against HIV. Today, NIH and our global partners are 
continuing to build upon the findings from the RV144 trial. Two large 
HIV vaccine efficacy clinical trials are now ongoing in southern 
Africa, one to evaluate an experimental vaccine regimen based on the 
one used in the RV144 trial, and another to assess an experimental 
``mosaic'' vaccine candidate designed to induce immune responses 
against a wide variety of global HIV strains. Results from these trials 
are expected in 2022 and 2021, respectively.
    NIAID scientists also are pursuing a second, theoretical path that 
involves studying the body's immune response to HIV infection and 
finding various ways to generate and enhance that response through 
vaccination. One theoretical approach involves designing vaccine 
strategies to generate cellular immune responses capable of protecting 
against HIV infection. Another promising strategy seeks to identify 
potential HIV vaccine targets by uncovering the molecular structure of 
the virus. An additional theoretical approach involves the design of a 
vaccine that elicits broadly neutralizing antibodies, or antibodies to 
HIV that can target multiple different HIV strains. Studies are 
underway to determine whether delivery of such antibodies could provide 
long-acting protection against HIV infection, similar to the way a 
traditional vaccine approach would work. Two large clinical trials with 
sites in the Americas, Europe, and Africa are currently evaluating 
VRC01, a broadly neutralizing antibody developed by the NIAID Vaccine 
Research Center. In addition, planning is underway for early phase 
clinical trials of a three-pronged antibody capable of binding to three 
different critical sites on the surface of HIV. NIAID scientists and 
public-private partners are developing this ``tri-specific'' antibody 
with the expectation that it could eventually be used for long-acting 
HIV prevention and treatment. NIAID scientists also are conducting a 
Phase 1 clinical trial of a therapeutic HIV vaccine regimen that uses 
an adjuvanted DNA vaccine ``prime'' followed by a viral vector 
``boost'' in participants with HIV. The goal of this vaccine strategy 
is to achieve prolonged undetectable levels of HIV, eliminating the 
need for lifelong anti-retroviral therapy.
    These scientific advances and ongoing investigations provide 
cautious optimism that the development of a safe and effective HIV 
vaccine is making headway. It is important to note that even a 
moderately effective HIV vaccine could substantially slow the HIV 
pandemic, if optimally implemented with current treatment and 
prevention modalities. NIAID is committed to the goal of developing a 
safe and effective HIV vaccine that would complement the HHS Ending the 
HIV Epidemic initiative and help end the HIV pandemic.
                                 ______
                                 
             Questions Submitted to Richard J. Hodes, M.D.
                Questions Submitted by Senator Roy Blunt
                          alzheimer's disease
    Question. Dr. Hodes, Dr. Randy Bateman, a researcher at Washington 
University in St. Louis, has developed a blood test that can detect the 
build-up of the Alzheimer's protein amyloid years before symptoms 
appear. This is a significant step toward predicting who will develop 
dementia. Further, another Washington University researcher, Dr. 
Gregory Van Stavern, has developed an eye scan that detects changes in 
the retina that may be able to predict Alzheimer's before dementia 
begins. These tools could ultimately save millions in healthcare costs 
because instead of paying thousands of dollars for a PET scan or a 
spinal tap, you will be able to detect the disease through only a blood 
test. Can you talk about the progress of this breakthrough as well as 
other potential ways to better detect Alzheimer's disease?
    Part of the issue with the recent drug failures is that may be 
targeting individuals too late in the disease progression process. Two 
years ago, you and I visited the Alzheimer's prevention trial in 
Medellin, Colombia that focuses on a family that is genetically 
predisposed to early-onset Alzheimer's disease. Can you discuss what 
research your Institute is supporting to prevent or delay Alzheimer's 
disease?
    Answer. Early detection of pathology consistent with Alzheimer's 
disease or a related form of dementia (AD/ADRD) opens a ``window of 
opportunity'' for us to target the disease before clinical symptoms 
appear. NIA supports studies exploring a variety of methods to detect 
AD/ADRD pathology prior to the appearance of symptoms, as well as to 
identify early, subtle signs of disease while cognitive abilities are 
still largely intact.
    The work of Dr. Bateman, who is affiliated with the NIA-supported 
Charles F. and Joanne Knight Alzheimer's Disease Research Center 
(Knight ADRC) at Washington University, uses subtypes of the amyloid 
beta protein in the blood to infer the presence of damaging amyloid 
buildup in the brain. Specifically, they have found that the ratio of 
two subtypes, amyloid beta 42 and 40, can indicate elevated brain 
amyloid. Multiple companies have now begun commercial development of 
diagnostic tests based on the amyloid beta 42/40 ratio.
    Other researchers are also working to identify blood-based 
biomarkers for early detection of AD/ADRD. For example, investigators 
with NIA's Intramural Research Program recently used advanced machine 
learning techniques to identify a panel of 26 blood and brain 
metabolites that were--when present in altered concentrations in 
blood--consistently associated with brain atrophy, cerebrospinal fluid 
measures of Alzheimer's pathology, cognitive performance, and disease 
risk before clinical symptoms appeared. Another team is using changes 
in autoantibodies--part of the body's immune response--as blood-based 
biomarkers to detect early AD/ADRD. Still another is testing special 
``indicator cells'' as a biosensor for AD pathology.
    Dr. Van Stavern, also affiliated with the Knight ADRC, used a 
noninvasive eye scanning technique, optical coherence tomography (OCT) 
angiography, to detect thinning in the retina as well as alterations in 
retinal blood flow among older people without clinical symptoms of AD/
ADRD. These findings correlated with elevated levels of amyloid and tau 
proteins as detected by PET scan and cerebrospinal fluid examination.
    Other ongoing, NIA-supported research using ocular biomarkers to 
detect early AD/ADRD includes a study correlating amyloid and tau 
levels in the fluid of the eye with OCT and cognitive testing for early 
detection of Alzheimer's disease. Elsewhere, NIA-supported 
investigators are using an innovative imaging method to detect 
Alzheimer's pathology, disease progression, and treatment response in 
people with Alzheimer's and in mouse models of the disease. In this 
study, individuals drink a solution made with curcumin, a component of 
the spice turmeric. The curcumin acts as a tracer, ``lighting up'' 
amyloid in the eye and enabling its detection with a custom-built high-
definition scanning instrument.
    In addition, NIA-supported investigators are exploring changes in 
smell, gait, personality, and even driving behaviors as early warning 
signs of incipient dementia. Ultimately, we hope to be able to 
intervene either with or prior to the earliest appearance of symptoms 
and thereby avoid progression to the later, devastating stages of 
disease.
    Research to prevent or delay AD/ADRD symptoms in at-risk and/or 
presymptomatic individuals remains a high priority at NIA. The 
Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's 
Disease Trial in Medellin, Colombia is one such study. Recruitment for 
this trial of the anti-amyloid agent Crenezumab among members of a 
family at very high genetic risk for developing the disease has been 
completed, and we anticipate reporting results in 2022. This study is 
one of several being conducted by the API, the goal of which is to 
identify pre-symptomatic interventions that will postpone, slow, or 
prevent the disease's progression.
    Another major initiative, the Dominantly Inherited Alzheimer's 
Network Trials Unit (DIAN-TU), is an international partnership 
dedicated to designing and managing clinical trials for individuals at 
high genetic risk of developing AD.
    The recently funded DIAN-TU Primary Prevention Trial is a 4-year 
study of two drugs, Solanezumab and Gantenerumab--antibodies that 
interact with different forms of amyloid--in 160 asymptomatic 
individuals at high genetic risk. Investigators will determine whether 
it is possible to prevent amyloid deposition in this population and if 
doing so will prevent the cascade of pathology associated with AD and, 
ultimately, dementia, in people who are otherwise certain to get the 
disease.
    In addition to these highly visible initiatives, NIA also supports 
studies of physical activity and exercise, diet, and cognitive training 
to prevent cognitive decline and dementia. Participants in many of 
these studies are at well-established risk of developing dementia but 
do not yet show evidence of cognitive decline.
    A new, NIA-funded Alzheimer's Clinical Trial Consortium (ACTC) will 
help investigators harness best practices and latest methods for both 
treatment and prevention trials. The ACTC includes 35 sites in the 
United States and will address the complexity, time, and expense of 
participant recruitment and site activation to find new and effective 
ways to treat or prevent these devastating disorders.
                                 ______
                                 
                Questions Submitted to Nora Volkow, M.D.
                Questions Submitted by Senator Roy Blunt
            opioid research and data collection from samhsa
    Question. Dr. Volkow, our Committee has invested significant 
resources into opioid treatment, prevention, education, and research. 
In particular, we now provide States with $1.5 billion in flexible 
State Opioid Response grants and require States to report to SAMHSA on 
how they are spending this funding. I believe it is incredibly 
important that we understand what opioid programs are working and how 
to replicate those programs across the country. Can you discuss (1) 
whether NIH researchers have access to this valuable State-by-State 
data; and (2) what research your Institute is undertaking to better 
understand what programs work and which do not in opioid prevention and 
treatment?
    Answer. (1) NIH researchers can gain access to data collected in 
conjunction with SAMHSA grants, such as the State Targeted Opioid 
Response and State Opioid Response (STR and SOR) grants, through State 
substance use agencies.
    (2) Determining which prevention and treatment approaches are most 
effective is central in addressing the opioid crisis, and this is 
precisely the goal of our HEALing Communities Study. Launched in 
partnership with SAMHSA on April 18, 2019, this multisite 
implementation research study tests the impact of an integrated set of 
evidence-based interventions across healthcare, behavioral health, 
justice, and other community-based settings. The ultimate goal is to 
generate the evidence needed to determine the most effective strategies 
for preventing and treating opioid misuse and opioid use disorder (OUD) 
within highly affected communities. This Study will examine the 
effectiveness of coordinated systems of care designed to reduce 
overdose fatalities and events; decrease the incidence of OUD; increase 
the number of individuals receiving medication to treat OUD, retained 
in treatment, and receiving recovery support services; and increase the 
distribution of naloxone.
    The HEALing Communities Study includes at least 15 communities in 
each of four participating States to measure the impact of these 
targeted strategies. The four institutions leading this research--
University of Kentucky, Boston Medical Center, Columbia University, and 
The Ohio State University--were required to demonstrate their 
partnership with State governments, and specifically how they plan to 
leverage SAMHSA funding (such as STR and SOR funding) to provide 
evidence-based prevention and treatment services. RTI International, 
based in North Carolina, will serve as the study's coordinating center, 
and will be responsible for data analysis, health economics research, 
and widespread dissemination of research findings over the course of 
the study, under provisions that safeguard the privacy and 
confidentiality of respondents. The data generated by this Study will 
inform best practices for other States looking to maximize the impact 
of their SAMHSA grant funds.
    Question. What barriers exist for NIH and SAMSHA to partner on data 
sharing and how can we help make sure this data is available to the 
research community?
    Answer. NIH has benefitted from a long-standing partnership with 
SAMHSA that facilitates the translation of sound research into 
effective practice and policy. SAMHSA and NIH are in regular contact 
regarding the need for data to be available to researchers. Currently, 
researchers access data compiled for monitoring SAMHSA grants through 
State substance use agencies. This is occurring in a number of recently 
awarded NIH-funded studies. For example, there are currently five 
studies underway to test approaches for expanding medications for OUD 
in the context of SAMHSA STR and SOR grants issued under RFA-DA-18-005 
(with another three studies underway with support from the Arnold 
Foundation). In addition, NIH's National Center for Complementary and 
Integrative Health recently funded five projects examining the impact 
of behavioral and complementary health interventions within the context 
of States' plans for using SAMHSA's STR and SOR grant funds.
    NIH continues to be committed to working with SAMHSA to find 
innovative ways to mutually share data and to ensure the data are 
available to the research community in order to maximize the impact of 
the research.

                          SUBCOMMITTEE RECESS

    Senator Blunt. The subcommittee stands in recess.
    [Whereupon, at 11:45 a.m., Thursday, April 11, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]