[Senate Hearing 115-277]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2019
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THURSDAY, MAY 17, 2018
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:02 a.m. in room SD-124, Dirksen
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
Present: Senators Blunt, Alexander, Moran, Capito, Hyde-
Smith, Murray, Durbin, Reed, Shaheen, and Murphy.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
WALTER J. KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
NORMAN E. SHARPLESS, M.D., DIRECTOR NATIONAL CANCER INSTITUTE
NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE
opening statement of senator roy blunt
Senator Blunt. The Appropriations Subcommittee on Labor,
Health and Human Services, Education, and Related Agencies will
come to order.
We are glad to have our friends from NIH (National
Institutes of Health) here today: Dr. Collins and the Institute
Directors.
Recent support, I think, of medical research from our
subcommittee and the full committee and the Congress is clear.
During the 3 years that Senator Murray and I have worked
together on this committee, we have increased funding for the
National Institutes of Health by 23 percent, $7 billion above
where we were just 3 years ago. We have nearly tripled the
Alzheimer's research amount, started the Precision Medicine
Initiative, and targeted resources to such revolutionary
projects as the BRAIN Initiative, the universal flu vaccine,
and efforts to combat antibiotic resistance.
A renewed investment in NIH has provided and can provide
millions of Americans and their families with hope that they
would not otherwise have. NIH-funded research has raised life
expectancy, vastly improved the quality of life for all
Americans. And in addition, I am hopeful that we can see ways
to lower healthcare costs and to create economic growth by
supporting the jobs, the research and the innovation that are
such an important part of dealing with healthcare issues now.
Both this administration and the last one have proposed
cuts in NIH funding. There is rarely a straight line in
success, but so far, we have been able to maintain an upward
momentum in the opportunity that I think everybody on this
subcommittee certainly sees at the moment we are in.
In addition to that, things around the world like the West
Africa challenge 3 years ago with the devastating outbreak of
Ebola, the disease killed more than 11,000 people in Africa,
became a major public health threat in the United States, and
both NIH and CDC (Centers for Disease Control and Prevention)
were an important part of responding to that. We see now
another outbreak in the Democratic Republic of Congo. There was
more news on that topic even this morning, and we need to be
well prepared to continue to be able to do what we need to do
to respond to those kinds of challenges.
Earlier this month, the National Institutes of Health
launched enrollment in the All of Us study, which will collect
health information from 1 million Americans, an idea that Dr.
Collins mentioned, I think, 2 years ago for the first time as
an NIH goal. All of Us has the potential to unlock precision
medicine for the majority of diseases that we suffer from
today. This initiative has the potential to change our health
system from one-size-fits-all to really understanding more
about personalized medicine.
We are also at a point where we see some drug repurposing
happening. We are testing current drugs that we know are safe
to see what other uses we might find in those drugs. There is a
current clinical trial targeting the most common adult leukemia
with a drug first approved to test arthritis more than 25 years
ago. That particular work is being done at the University of
Kansas. Certainly Senator Moran has been a real advocate for
NIH research, and he and I hope to visit The University of
Kansas Medical Center before too long and look at that project,
along with others.
The National Academy of Sciences published a report in
February that shows that NIH funding contributed to every one
of the 210 new drugs approved by the Food and Drug
Administration from 2010 till 2016. That is quite a record, and
we appreciate the fact that that work continues.
We see increased grants among young researchers. Anything
you have to say about that would be welcome. But this has been
an effort that this committee has entered into together, and
Senator Murray has been a great partner in NIH, as we hope to
be appropriately involved in our oversight responsibilities as
well.
[The statement follows:]
Prepared Statement of Senator Roy Blunt
Good morning. Thank you, Dr. Collins and the Institute Directors,
for appearing before the Subcommittee today to discuss the National
Institutes of Health's fiscal year 2019 budget request.
My support for medical research is clear. During my time as
Chairman of this Subcommittee, I am proud to have increased funding for
the National Institutes of Health by 23 percent, or $7 billion, in the
last 3 years. This investment nearly tripled funding for Alzheimer's
research, started the Precision Medicine Initiative, and targeted
resources to such revolutionary projects as the BRAIN Initiative, a
universal flu vaccine, and efforts to combat antibiotic resistance.
I stand by an investment in NIH because it has provided millions of
Americans and their families with hope. NIH-funded research has raised
life expectancy and vastly improved the quality of life for all
Americans. In addition, it has lowered healthcare costs and spurred
economic growth by supporting jobs in research and generating
biomedical innovations.
However, I understand that it is difficult to always quantify
success in medical research. Both this Administration and the last one
has proposed cuts to NIH. There is rarely a straight line to success.
Not every grant funded will result in a breakthrough. However, this is
not the time to abandon our commitment to medical research. The
advances made in just the past 3 years is example enough to show why
funding for the NIH is so important.
Three years ago, West Africa faced one of the most devastating
infectious disease outbreaks of the last 50 years--Ebola. This disease
killed more than 11,000 people in Africa, and became a major public
health threat in the United States. Now, the Democratic Republic of
Congo faces another Ebola outbreak. In response, the World Health
Organization will deploy an Ebola vaccine that appears to provide
protection for 2 years. This has been made possible, in part, due to
the support of the National Institutes of Health.
Earlier this month, the NIH launched enrollment into the All of Us
study which will collect health information from one million Americans.
All of Us has the potential to unlock precision medicine for the
majority of diseases we suffer from today. This initiative will change
our health system from one-size-fits-all to personalized medicine.
It is also important to point out discoveries in the revolutionary
work of drug repurposing--testing current drugs we know are safe for
other uses. There is a current clinical trial targeting the most common
of adult leukemia with a drug first approved to treat arthritis more
than 25 years ago.
These are just a few examples of how investing in medical research
can save lives and shows that this is not the time to back away from
our support. As further evidence of the benefits of these investments,
the National Academy of Sciences published a report in February that
showed that NIH funding contributed to every one of the 210 new drugs
approved by the Food and Drug Administration (FDA) from 2010-2016. Let
me say that again. Every single drug approved by the FDA over a 6-year
period had some NIH research associated with it.
The increased funding over the past 3 years, has also allowed the
best researchers in the country to have their research funded to
discover the next breakthrough. I am proud to say that the number of
grants have increased 2,200 during this period. We finally are in a
pattern of long-term investment in medical research.
I have worked closely with Senator Murray and other Members of the
Subcommittee to prioritize our commitment to NIH. I know that we will
continue to do so this year.
Thank you for being here today.
Senator Blunt. But let me turn to Senator Murray for her
comments.
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Well, thank you very much, Mr. Chairman.
Dr. Collins, it is great to see you again too and all of
your amazing team. Thank you all for being here today. And I
just want to say it is a pleasure to see Ann Houser back there
as well. She has done a lot to support our subcommittee's work
for many years. She is a great credit to the agency, and I
wanted to recognize her back there as well.
President Trump's budget for fiscal year 2019 once again
seeks deep cuts across the spectrum of health activities,
including a reduction to the National Institutes of Health that
would cut its funding down to roughly $100 million below the
2017 enacted level. That request is out of step with the
sentiments of Congress and the country.
Less than 2 months ago, Congress passed and President Trump
signed into law a bipartisan bill that increased funding for
NIH by $3 billion, the second largest increase in the agency's
history. Those funds will be used to accelerate efforts to
discover cures to Alzheimer's, cancer, and other diseases,
tackle the opioid addiction crisis, and develop a universal flu
vaccine, and new antibiotics and more.
President Trump's request would undermine these efforts
slowing their progress.
By comparison in just the past 3 years, Congress has
provided NIH an overall increase of $7 billion boosting its
budget by almost a quarter. After adjusting for inflation, the
NIH budget still falls short of its peak in 2003 and grants
remain highly competitive, especially for our early stage
investigators, but the numbers are trending in the right
direction. I am hopeful in the bill our subcommittee will
shortly begin writing, we will be able to continue closing the
gap. I know that Chairman Blunt feels the same way, and I want
to thank him for his work on this.
These funding increases reflect a sustained commitment to
invest in medical research with the goal of achieving
breakthroughs that benefit all of us, including those who have
been historically under-represented in clinical research, and
preserve our Nation's leadership in biomedical research. We are
in a time of immense promise and challenge for the research
community, the promise of unprecedented new tools,
technologies, and computational power balanced by the challenge
of making the most of the staggering and ever-growing amount of
data that NIH produces, the BRAIN Initiative efforts to cure
Alzheimer's disease, the Cancer Moonshot, and the All of Us
initiative to advance precision medicine that are massive
undertakings that pose extraordinary challenges, how to manage
and make sense of it all, allow the research community to
leverage it as much as possible, and find that proverbial
needle in an immense haystack, while at the same time ensuring
each patient's data remains secure.
I believe that much of NIH and its grantees are up to this
task. I see the potential every time I visit the Allen
Institute for Brain Science in Seattle, but few organizations
have their level of sophistication.
2 years ago, the committee tasked NIH with developing a
strategic plan for outlining how it would manage and make the
most of the data it is producing. NIH released that plan
earlier this month on schedule, but the real work lies ahead. I
am concerned there still remains no senior member of the
leadership responsible for that portfolio. I see that NIH
recently posted an opening for a chief data strategist and
understand you are actively reaching out to those in the
private sector in the hope of attracting the right person to
public service. It is essential we find them quickly, bring
them on board, and make sure you properly support them to
implement your strategic plan. I look forward to hearing more
about NIH's plans in this area when we turn to the questions.
I am pleased the administration's fiscal year 2019 budget
abandoned its ill-conceived proposal to drastically cut grant
support funding that it proposed last year, but troubled that
it now seeks to arbitrarily slash researchers' salaries by 20
percent. The budget claims this proposal would stretch grant
dollars to fund more research, but like the previous proposal,
it is blindly destructive and short on details, a gimmick not
meant to be taken seriously.
I see the budget follows Congress' lead by preserving the
increase we provided to address opioid addiction and spur the
development of non-addictive pain treatments. These are
critical investments of great importance to the members of this
subcommittee, and I think I can speak for all of us in saying
we expect NIH to make the most of those resources entrusted to
address this crisis. We and those we represent are really
counting on you on this one.
Finally, few agencies enjoy greater trust than the National
Institutes of Health. So it was particularly troubling that
questions have been raised about the impartiality of a study to
assess the health benefits of moderate alcohol consumption. Dr.
Collins, I know you have been focused on determining the facts
with this and ensuring the integrity of NIH's research
practices, and hopefully you will provide us with an update on
that.
Thank you very much, Mr. Chairman.
Senator Blunt. Thank you, Senator Murray.
I am glad again to welcome Dr. Francis Collins, the
Director of the National Institutes of Health and the Institute
Directors that are here with him today. I think the new
Director of the National Cancer Institute, Dr. Ned Sharpless,
is here for his first appearance before the committee, and we
are glad you are part of this team and look forward to the
chance to visit with all of you later.
But, Dr. Collins, glad to have your testimony right now.
SUMMARY STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D.
Dr. Collins. Well, it is an honor to be here, Mr. Chairman.
Also with me here at the table: Dr. Nora Volkow, at my
left, your right, the Director of the National Institute on
Drug Abuse. You mentioned Dr. Sharpless, our newbie, to my
right. Walter Koroshetz, Director of the National Institute of
Neurological Disorders and Stroke; next to him, Dr. Richard
Hodes, Director of the National Institute on Aging; and over at
the far end, somebody you know pretty well who is in his 439th
hearing or something like that----
[Laughter.]
Dr. Collins [continuing]. Dr. Anthony Fauci, who is the
Director of the National Institute of Allergy and Infectious
Diseases.
I just want to say to all of you, Chairman Blunt, Ranking
Member Murray, and all the friends of NIH that are here today,
thank you. You have gone above and beyond in your support of
NIH research and the patients for whom it brings healing and
hope. In behalf of all of them, I am immensely grateful for
your consistent support, and the words you have just spoken
give me a great sense of confidence that we are on a very good
and strong path towards the future.
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Dr. Collins. I spend a lot of time with early stage
researchers. I will show you a few pictures. Wherever I go, I
set aside time to hear directly from them about their dreams,
their ideas, and yes, their concerns. I know you too have met
many of them, both in your home districts and sometimes in your
much appreciated visits to NIH.
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Dr. Collins. As we move forward with implementing the
fiscal year 2018 budget and you begin considering the fiscal
year 2019 request, it is a good time to think about those early
stage researchers to ask what are we doing to foster this next
generation of discovery and what can we do to help our Nation
remain the world leader in biomedical innovation.
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Dr. Collins. I believe the answers could be said to lie in
certain key areas, and I would call them the five keys to
success in science today. They are, first and foremost, a
stable trajectory of support, followed by a vibrant workforce,
computational power, new technologies and facilities, and
perhaps most important of all, scientific inspiration.
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Dr. Collins. The good news is that, thanks to you, early
stage researchers are now beginning to see a stable trajectory
of support. Your work over the last 3 years is helping us begin
to reverse a distressing decade-long decline in NIH's
purchasing power for research, which is carried out in every
State of the Nation. Strong, stable public support lies at the
heart of NIH science, and of course, that is absolutely vital
to our second key to success, a vibrant workforce. Clearly
success cannot lie simply in boosting the number of grants
made. It must also include increasing the number of creative
minds that are receiving those grants.
So I want to show you a new metric we are using to evaluate
success. This shows the trend in the number of individual
principal investigators supported by NIH over the past 15
years. As you can see, that number is once again growing
nicely. Note especially the surge that occurs around 2016, a
surge that reflects when you began to change the trajectory of
NIH support, and shows how that investment in NIH science is
starting to pay off.
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Dr. Collins. The third key to success, already mentioned by
Senator Murray, is computational power. Like so much else,
biomedical research has been transformed by the recent
explosion in computing power and all of the big data it is
generating. For example, the BRAIN Initiative, which you have
supported for the past 5 years, has created new imaging tools
that are churning out troves of amazing data, and there is also
data generated by structural biology and microbiome research
and the All of Us research program supported by your precision
medicine appropriation. Just 10 days ago in a major national
launch event, all of us began the full scale of enrolling 1
million Americans, building on their pilot phase that already
enrolled over 25,000, aiming to determine how individual
differences and lifestyle, environment, and biological makeup
can influence health and at an unprecedented scale.
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Dr. Collins. To realize the full potential of these and
other resources, we also must develop new technologies and
facilities. Quite often it is the technology itself driving the
need for equally innovative facilities. Take the case of the
new cell-based treatments, immunotherapy and gene therapy. Many
involve removing cells from the patient's body using technology
to re-engineer those cells and returning them to the patient.
The challenge is that many of our labs are not set up to handle
these highly individualized processes, so it is crucial that we
make upgrades to keep pace. The President's fiscal year 2019
proposal includes a much needed increase in buildings and
facilities to assist with that.
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Dr. Collins. But now on to my favorite of these topics,
scientific inspiration. I can assure you that NIH-funded
researchers come to work every day full of innovative ideas and
the wherewithal to see those ideas through. I could talk about
this all day, but mindful of the clock, let me just share one
example.
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Dr. Collins. More than a decade ago, NIH launched a special
project on spinal muscular atrophy, or SMA. This is a uniformly
fatal inherited disease. As you see here, in its severe form,
it leaves babies floppy, unable to hold their heads up, feed
well, and eventually even to breathe. Death by 15 months is the
tragic and almost universal result.
10 years ago there was no treatment for SMA, but
researchers had just discovered the DNA (deoxyribonucleic acid)
mutations that cause it. So NIH supported more research,
working closely with patient advocates and industry to move
promising leads into therapeutic development. One of the most
exciting comes from Jerry Mendell's team at Nationwide
Children's Hospital in Columbus, Ohio, which recently tested
gene therapy in 15 infants with severe SMA. They infused the
viral vector designed to deliver the normal gene to the spinal
cord and held their breath.
And over the next few months, something truly dramatic,
almost miraculous, happened. Like little Mateo Almeda, whom you
see in this video, 100 percent of the infants who got the
highest dose of the gene therapy were alive at 20 months and
nearly all could talk and eat on their own, and some like
Mateo, shown here at age 2 standing up on his tiptoes, were
able to walk--and this is truly astounding--even play on the
monkey bars with his dad. As a direct result of an NIH-inspired
effort, we are seeing the emergence of lifesaving gene therapy
for SMA.
So in closing, I am proud to lead NIH at this time of
unprecedented scientific opportunity and with such strong
congressional support. The resources you have entrusted to us
will be used to bring hope to untold numbers of patients and
their families.
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Dr. Collins. In that spirit, I would like to finish with a
favorite quote from the poet Peter Levi. ``Hope,'' he wrote,
``in every sphere of life is a privilege that attaches to
action. No action, no hope.'' At NIH our idea of action is to
support the best investigators to apply the best science to
find answers for those millions waiting for their hopes to be
realized.
Thank you, and I look forward to your questions.
[The statement follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good morning, Chairman Blunt, Ranking Member Murray, and
distinguished Members of the Subcommittee. I am Francis S. Collins,
M.D., Ph.D., and I have served as the Director of the National
Institutes of Health (NIH) since 2009. It is an honor to appear before
you today.
Before I discuss NIH's diverse investments in biomedical research
and some of the exciting scientific opportunities on the horizon, I
want to thank this Subcommittee for your sustained commitment to NIH to
ensure that our Nation remains the global leader in biomedical research
and advances in human health.
I want to personally express gratitude to this Subcommittee and its
leadership for its support in crafting and passing the fiscal year 2018
Consolidated Appropriations Bill. The fiscal year 2018 Omnibus provides
an incredible increase of $3 billion for NIH, including funding for
opioid- and pain-related research, Alzheimer's disease, antimicrobial
resistance, and development of a universal influenza vaccine. NIH has
immediately set to work to invest those additional resources into
groundbreaking research.
As the Nation's premier biomedical research agency, NIH's mission
is to seek fundamental knowledge about the nature and behavior of
living systems and to apply that knowledge to enhance human health,
lengthen life, and reduce illness and disability. As some of you have
witnessed first-hand on your visits to NIH, our leadership and
employees carry out our mission with passion and commitment. This
extends equally to the hundreds of thousands of individuals whose
research and training we support, located in every State of this great
country, and where 81 percent of our budget is distributed.
The fiscal year 2019 Budget provides $34.8 billion for NIH to fund
the highest priority scientific discoveries while also maintaining
fiscal stewardship of Federal resources. This Budget will consolidate
research functions across the Department, optimize available grant
dollars to fund research, invest in NIH's buildings and facilities, and
support NIH priority areas including combatting the opioid epidemic,
advancing Precision Medicine, and investing in translational research.
The fiscal year 2019 Budget consolidates HHS research programs into
three new institutes within the NIH. The Budget provides $380 million
for the activities of the Agency for Healthcare Research and Quality
(AHRQ), consolidated into the National Institute for Research on Safety
and Quality. The National Institute for Occupational Safety and Health
(NIOSH), including the Energy Employees Occupational Illness Program
(EEOCIPA), currently administered by the Centers for Disease Control
and Prevention, and the National Institute on Disability, Independent
Living, and Rehabilitation Research (NIDILRR), currently administered
by the Administration for Community Living, are also proposed for
consolidation into the NIH.
America's continuing leadership in conducting biomedical research
requires infrastructure and facilities that are safe, compliant with
all laws and regulations, and conducive to cutting edge research and
research support. NIH owns 281 facilities, including a research
hospital, laboratories, and offices. NIH's Backlog of Maintenance and
Repair exceeds $1.8 billion. NIH is currently working with the National
Academies of Sciences, Engineering and Medicine to identify NIH
facilities and infrastructure most in need of repair. We look forward
to providing that report to the Committee as soon as it is final.
The fiscal year 2019 Budget makes much needed investments in NIH's
facilities. The Budget proposes $200 million to support multiple
biomedical research infrastructure priorities. The fiscal year 2019
Budget will allow NIH to continue to repair and upgrade deteriorated
infrastructure. In a recent analysis requested by this Committee, the
condition of NIH laboratories ranks near the lowest in the Federal
Government due to the high likelihood of floods, power outages, and
mechanical failures. Items on the backlog list include: install steam
and chilled water distribution systems; conduct structural repairs to
older buildings; upgrade plumbing systems; repair elevators; upgrade
heating, ventilating, and air conditioning systems; replace
deteriorated electrical systems, and more. In addition, due to the age
and use of NIH facilities, NIH must invest funds in removing
contaminants and hazardous waste before construction or capital repairs
can begin in most of its buildings. The Budget will allow NIH to track
what contaminants are being cleared from each of our buildings, which
will ultimately help NIH do a better job of anticipating the cost and
time required to begin new projects in existing buildings.
Truly exciting, world class science is taking place. I would like
to provide just a few examples of the depth and breadth of the amazing
research the fiscal year 2019 Budget supports across the Institutes and
Centers of NIH.
Over the past 15 years, communities across our Nation have been
devastated by increasing prescription and illicit opioid misuse,
addiction, and overdose. This Committee made a historic investment of
$500 million in our work in fiscal year 2018, and the fiscal year 2019
Budget builds on that with an investment of $850 million to support a
range of activities to advance research on pain and addiction. NIH has
and will continue to support cutting-edge research on pain, opioid
misuse, addiction, and overdose. Drug addiction is a complex
neurological condition, driven by many biological, environmental,
social, and developmental factors. Continued research will be key to
understanding the crisis and informing future efforts. Pain is an
equally complex condition affecting millions of Americans. NIH will:
explore new formulations for overdose reversal medications capable of
combatting powerful synthetic opioids; search for new options for
treating addiction and maintaining sobriety; continue to research how
best to treat babies born in withdrawal through our ACT NOW trial;
develop biomarkers to objectively measure pain; build a clinical trial
network for pain research; and attempt to find non-addictive and non-
pharmacological approaches to chronic pain. Thanks to your support, all
hands are on deck at NIH for this public health crisis.
Another exciting area of continued investment in fiscal year 2019,
building on this Committee's long-standing support, is Precision
Medicine. On May 6th, NIH officially launched the national roll-out of
the All of Us Research Program. This program will partner with one
million or more people across the United States to provide the most
diverse biomedical data resource of its kind and gain unprecedented
insights into the biological, environmental and behavioral influences
of disease. The fiscal year 2019 Budget, including resources from the
21st Century Cures Act, supports the ramp up of the program. After
pilot testing system and forming partnerships with community
organizations across the country, national enrollment is about to
begin. All of Us will not focus on only one specific disease. Rather,
it will be a national data resource to inform many research studies on
a wide variety of health conditions. The data provided by one million
participants will provide opportunities for researchers--including
academics and citizen scientists--who want to understand how and why
different people experience certain diseases and conditions while
others do not, and why many people respond differently to treatments
and prevention methods that will help accelerate medical breakthroughs.
NIH is the largest funder of basic biomedical research in the
United States, providing a critical research foundation for both the
public and private sector. Building on that solid foundation of basic
research, NIH also supports translational research that turns
observations in the laboratory, clinic, and community into
interventions that improve the health of individuals and the public,
whether those interventions be diagnostics, therapeutics, medical
procedures, or behavioral changes. For example, Congress created the
Cures Acceleration Network (CAN) at the National Center for Advancing
Translational Sciences (NCATS) to advance the development of high-need
cures and to reduce significant barriers between research discovery and
clinical trials. For example, CAN currently supports NCATS' Tissue Chip
for Drug Screening program, which was designed to revolutionize the
process for predicting drug safety. Researchers developing miniaturized
platforms that could support miniature models of living organs--such as
the lung, liver, and heart--that could be integrated into connected
organ systems. New Tissue Chip initiatives were funded in fiscal year
2017 and this support will continue into fiscal year 2019.
CAN uses flexible research awards using the special authorization
called other transaction authority to attract non-traditional
government partners, and to expand, modify, and, if needed, discontinue
activities to meet program needs. The fiscal year 2019 Budget will
allow NCATS, through CAN, to continue to invest in high-risk, high
reward initiatives designed to address significant scientific and
technical challenges that hinder translational research.
One of my personal priorities is developing the next generation of
talented biomedical researchers. Last year, I shared with the Committee
NIH's plans to build on our support for early-stage investigators
through a new initiative known as the Next Generation Researchers
Initiative. The fiscal year 2019 Budget includes a dedicated fund of
$100 million in the Office of the Director to incentivize additional
Institute and Center support for these researchers. NIH remains
committed to the development, support, and retention of our next
generation of investigators.
We have never witnessed a time of greater promise for advances in
medicine than right now. Your support has been critical, and will
continue to be. Thank you again for inviting NIH to testify today. We
look forward to answering your questions.
Senator Blunt. Well, thank you, Dr. Collins.
We will have 5-minute rounds of questions. There will be
time for a second round if we are still in the hearing when we
have the vote at 11:15. I think it is one vote. And so we will
try to work around that and continue the hearing.
PUBLIC/PRIVATE PARTNERSHIPS
One of the things that we put in the appropriations bill
this year was an effort that, frankly, we were asked to put in
where there would be some partnership money from pharmaceutical
companies into opioid research, the idea being that like other
partnerships, for example, the AMP partnerships between NIH and
other biopharmaceutical companies, that we could deal with that
quicker. You have decided and frankly, without consultation
with the committee, not to do that. It might very well relate
to the alcohol study that Senator Murray brought up. I would
like you to respond to both of those topics, starting with why
you decided not to do what you had asked us to put in the
budget to allow you to do.
Dr. Collins. Senator, I will be glad to explain that, and I
know this is a topic that many people have been interested in
and have been wrestling with a bit, as we have.
We have been in deep conversations with industry partners
for a year about ways in which we might develop a partnership
to come up with better ways to treat addiction, to treat
overdose, and to come up with non-addictive treatments for
chronic pain, which are desperately needed. Working with 33
such companies over the course of many months, we have
identified a number of areas of opportunity which we could do
effectively in a public-private partnership with them in ways
that neither sector could do alone. And that includes such
things as sharing data, sharing assets, repurposing compounds
that might have been tried for something else or have been
abandoned and could turn out to be valuable for pain, and
running clinical trials together in that space.
The good news is that partnership is very much alive and
will, in fact, be going forward. I think we are pretty close to
having the full plan laid out, and I would expect in the next
few weeks to be able to say much more about exactly how we are
going to conduct this.
The controversy, Senator, was whether in fact, given the
circumstances around the opioid crisis and the fact that there
are lawsuits now filed against no less than five of these
companies claiming that they may have played some role in the
opioid crisis in the first place by marketing such drugs as
OxyContin, whether it is in fact a good idea or potentially
carries a reputational risk for NIH to receive funds from the
company.
And ultimately I convened an expert group of advisors from
outside who had lots of experience in both sectors and who were
very finely tuned to the questions of reputational risk and
ethics. And to my surprise, they made a strong recommendation
that we go forward with the partnership but not have actual
cash contributions from the companies involved. Their concern
was that that would create at least the impression, if not the
reality that the project going forward would be in some way a
conflict of interest, would be driven by something other than
the best needs of the public.
I had to accept that strong recommendation coming from
those groups. The Foundation for NIH, by the way, which is our
partner in all of these partnerships, also convened their board
and came up with the same recommendation.
And so with apologies for not having consulted, as I should
have, with you and other members of this subcommittee, we felt
we had to make the decision that we did.
Again, the good news is the partnership will go forward
very much as planned, but we are not asking the companies to
contribute money, but we are asking them to contribute
expertise and resources and data and assets and help with our
clinical trials network.
Yes, the alcohol issue was also in this particular
discussion because we are in the midst of another place that I
wish we were not where there is deep concerns about whether a
study, which has really just gotten launched in the last 2 or 3
months, which aims to look at whether there might be medical
benefit of modest doses of alcohol in humans. And this
particular study was set up in such a way that the funding is
largely coming from the beverage industry, and there is
evidence that NIH employees assisted in recruiting those funds
for this study in a way that would violate our usual policies.
We are in the midst of investigating that through the
Office Management Assessment and through a working group that I
have convened. There are sufficient concerns about that study
that I would like to tell you that 1 week ago, we decided to
suspend enrollment in that study of the moderate effects of
alcohol on cardiovascular health while we continue the
investigation and make a decision about whether the study is in
fact still worth pursuing.
So all of those are complicated issues and believe me, have
caused considerable pain and stress upon the people involved.
But again, for NIH, our reputation is so critical, and if we
are putting ourselves in a circumstance where that could be
called into question, I felt we had to look at that very
seriously and come up with another strategy.
Senator Blunt. Thank you.
I could probably ask another question quickly and get way
beyond my 5 minutes but I am not going to do that, and I hope
nobody else will either. If you want to stay for a second round
of questions, we are going to do that.
Senator Murray.
BIG DATA
Senator Murray. Thank you very much.
And I wanted to go back to the big data because one of the
greatest challenges facing science today is how to manage and
effectively use this massive amount of data that researchers
are now producing, and without the tools to efficiently manage
and manipulate data, the value of it is significantly reduced.
Likewise, we do not want scientists spending time recreating
data that already exists from other research projects. And as
you know, the committee directed NIH in the 2017 omnibus to
develop a strategic plan to address these issues, which you
released last week.
Now that you have the plan, can you tell us what the
timeline for implementation is?
Dr. Collins. The plan is very ambitious, Senator. And I am
glad you had a chance to look at it. It is the product of many
deliberations with experts both within NIH and outside and also
responding to a request for comments from more than 800
individuals and organizations who put forward a plan.
Basically it does lay out what we need to be doing in the
area of infrastructure, in the area of the data ecosystem, in
the area of software and tools, particularly in the area of the
workforce. We realize our bench is not as deep as it should be
for expertise in this space, and also just sustainability, how
do we put together something that is not here today and then in
trouble tomorrow. All of those are laid out in the strategic
plan in a broad and bold way.
The way in which we are going to implement this certainly
includes a number of things that are already underway because
we have really been working on this issue since 2012 when a
working group of my advisory committee made the first set of
recommendations. We are, for instance, moving some of our
largest datasets into the cloud in a fashion that protects the
security and privacy of the participants but makes that data
accessible to researchers from all over the place. And that is
a big step forward, and most of our big datasets will need to
be handled in that way going forward.
And as you mentioned in your opening comments, we are
actively recruiting for a chief data strategist, someone who we
would ideally hope to recruit from industry and maybe from
Silicon Valley with deep experience in how to handle big
datasets and machine learning and artificial intelligence.
BARRIERS IN DATA SHARING
Senator Murray. Are there barriers that are worrying you
like cases where researchers face challenges sharing their data
or delay releasing the data until they have published their
findings, things like that?
Dr. Collins. We are certainly attuned to the risks there of
people hording data. I am happy to say the 21st Century CURES
bill gave me as the NIH Director some authorities about
requiring data access and data release from our grantees, which
I used to have to do some cajoling, but now I have the
opportunity to have more clout and that has helped us in that
regard.
I think the general ethic of the scientific community has
shifted, though, much more in the direction of it is your
responsibility to make your data available as soon as someone
else might be able to use it. We have encouraged that a lot.
Senator Murray. Okay, good.
DATA SHARING IN ALZHEIMER'S DISEASE
And Dr. Hodes, I wanted to ask you. Given the scale of
investments that we are making in Alzheimer's disease, the data
we are generating may be used to accelerate some major
scientific breakthroughs. Has NIA (National Institute on Aging)
looked at its existing data sharing policies to determine how
they are working? Do we know what percentage of grant
recipients are fulfilling their data sharing obligations on
this project?
Dr. Hodes. Thank you very much for the question.
I would echo very much what Dr. Collins has just said about
NIH's role in general.
I think we have had a history in the Alzheimer's research
community of a strong willingness to share, and I think that
has increased over past years. I think we are at a stage when
we are dealing in part with technical feasibilities of making
data cross-interpretable, shareable, and compatible and are
working very hard in collaborations across Federal agencies and
with outside groups to make that sharing more effective. But I
think we have the culture, as well as the armamentarium to
enforce sharing, and I think we are on an excellent trajectory
in that regard.
Senator Murray. Thank you.
MODERATE DRINKING STUDY
Dr. Collins, just one more question on the moderate
drinking study. NIH is a huge enterprise, and if this was
happening in one institute, it could be happening in others.
Are you doing anything to make sure this has not compromised
studies elsewhere in NIH?
Dr. Collins. I am very concerned that this might be the tip
of a larger iceberg, and that is part of the reason that I
pulled together this very distinguished group of experts to
look at it. We will look closely to see if there are other
examples of this sort because that would be very much against
the principles that we stand for, which is separation of
funding sources from outside with decisions about science, and
also of course, our peer review process ought to be absolutely
above any reproach as far as conflicts.
I would be glad to report back to you after we have done a
bit more digging into this. But I think this is one of my roles
as the NIH Director. When we find something that has gone awry,
we do not just assume that it is a little thing that you could
put a band aid on. We make sure that it is not reflective of
some larger issues, and then we aim to fix those too.
Senator Murray. Thank you very much.
And thank you, Mr. Chairman.
Senator Blunt. Senator Alexander.
Senator Alexander. Thank you, Mr. Chairman.
First, let me say to Chairman Blunt and to Senator Murray,
Senator Durbin, all the members of the committee, how much I
appreciate their leadership and the increase in funding for the
National Institutes of Health. And I pledge my support to do
that for the future.
Second, it is good to see a piece of legislation that had
such broad bipartisan support. Senator McConnell said it was
the most important law of 2016. Actually it would be so useful
in its implementation. A part of that is because of the talent
of the team we see before us and others like Dr. Gottlieb who
know what they are doing and are leaning forward and taking
advantage of the new authority.
Third, we have developed quite a consensus on science and
research. As Senator Blunt said, a 23 percent increase in
biomedical innovation. I would add to that that in the Energy
and Water Appropriations Subcommittee, which Senator Feinstein
and I chair, we increase funding for the Office of Science this
year 16 percent. That was the third straight year of record
funding for the Office of Science that supports the national
laboratories. So when you get 3 straight years for the National
Institutes of Health, 3 straight years of record funding for
the Office of Science, and you add to that in the Obama
administration and in the first 2 years of this administration
we have funded supercomputing at impressive levels to keep us
first in the world in that, I think the only people not on
board with the President's America First comments are the
Office of Management and Budget.
So I am going to try to talk to the President and others at
the White House and say why do you not include this in your
America First agenda. I mean, why not buy medical innovation,
why not national laboratories, why not supercomputing? We need
to lead the world in that. Congress wants to do it, both
Republicans and Democrats. We need to get the OMB (Office of
Management and Budget) on board.
NON-ADDICTIVE PAIN STRATEGIES
Now, let me use the rest of my time to ask you about one
area, non-addictive pain strategies. We have 25 million
Americans who hurt badly, chronic pain, 100 million who hurt
some, and then non-addictive treatment for opioid abuse. 95
percent of the treatment for opioids is more opioids. It is
medicated assisted abuse. And sometimes they say you do not
ever get off opioids.
So my question is in 2 minutes and a half, what progress
are you making? Senator Murray and I have included in the
opioids bill the transactional authority that you asked for to
give you even more flexibility in funding. What progress are
you making on pain, new pain strategies, and why are 95 percent
of the treatments for opioids more opioids? Why do we not have
more treatments like Vivitrol or some other treatment that
helps people get away from opioids?
Dr. Collins. So I am fortunate to have at the table two
experts who can handle both parts of that question. Maybe we
will go first to Dr. Volkow to talk about the treatments for
addiction and what we might be working on in that space. And
then I will ask Dr. Koroshetz to respond about non-addictive
treatments for pain. We are deep into that as well.
Dr. Volkow. Thanks, Francis.
This is one of our priorities, how do we develop
alternative medications for the management of opioid addiction.
We currently only have three of them, and two of them are what
we call agonists, opioid agonists. And Vivitrol is an
antagonist.
Senator Alexander. And I am right that two are about 95
percent of the treatment. Right?
Dr. Volkow. Correct. That is correct. Those are the
numbers.
And part of the problem is not all of the patients respond
to the Vivitrol intervention, and part of the problem is it is
very difficult to induct someone that is addicted right away
into Vivitrol. And that is when we lose the patients. So we are
trying to expand the alternative medications that we can give
to patients and focusing also on strategies that are not
involved in the opioid system so that we can help those
individuals be able to recover and be at one point able to stay
without opioid medications.
Dr. Koroshetz. So I think that you are absolutely right
that one thing that could really help in the long term stemming
the opioid problem is developing non-addictive pain medicines
to replace opioids in the prescription box for patients.
Senator Alexander. And we funded $500 million in research
this past year--Senator Blunt and Murray did--and $500 million
more proposed by the budget for this coming year.
Dr. Koroshetz. That is right. And so we, working with our
industry partners, as Francis mentioned, have a plan to really
accelerate the development of new medications. From the basic
science point of view, we have a number of different targets
that look very promising to develop medicines that are not
interacting with the opioid pathway.
One that is in current testing now is what is called anti-
nerve growth factor therapy, which came from really very
important basic science years ago on the intersection of that
growth factor and the pain system. And companies are now
developing antagonists to nerve growth factor which look
promising in early results. So just one example, but we think
there are many more.
Senator Alexander. Thank you, Mr. Chairman.
Senator Blunt. Senator Reed.
Senator Reed. Thank you very much, Mr. Chairman.
Thank you all. I particularly want to thank Dr. Sharpless
for giving me an opportunity to look at the pediatric oncology
program and meeting all the tremendous women doctors and Ph.D.s
who lead that effort. So thank you.
STAR ACT
With the support of another tremendous woman, Senator
Capito, we were able to pass the STAR Act. And can you give us
an idea of how you will use this? It will pass, we hope, the
House very soon and become law.
Dr. Sharpless. Sure. I should not directly comment on
pending legislation, but--and first off, thank you for the
visit. I think it really means a lot to the pediatric
oncologists to have the Senate come up and express an interest
in work that they are doing and I think is really, really
wonderful. And thank you for your support and Senator Capito's
support of pediatric cancer research.
The STAR Act--the intent of it is very laudable to address
issues, some issues in pediatric oncology and childhood cancer
that are important. So one is the issue of survivorship. The
good news about pediatric cancer is we are curing more and more
kids, but the problem is--well, the two problems are we are not
curing everyone. We still have kids die of cancer. And then a
lot of the kids we cure are left with lifelong toxicity. So the
results from therapy can be quite debilitating, infertility,
disfiguring surgery, and cognitive dysfunction that last for
decades.
So survivorship has become a major issue. There are
probably half a million pediatric cancer survivors now in the
United States. And trying further research to understand the
basic science of survivorship and why these toxicities occur
and what we can do is a really important area of pediatric
oncology research.
Similarly, I think we had this issue of aggregated data in
pediatric cancer. One of the shortages of that are samples,
biospecimens that can be sequenced and analyzed and catalogued,
and then presented to the research community in an aggregated
format that is de-identified and secure but usable for
research.
And so I think those two addressing survivorship and
biospecimens are really important and something NCI (National
Cancer Institute) is behind.
TRANS-NIH PEDIATRIC RESEARCH CONSORTIUM
Senator Reed. Thank you very much.
And Dr. Collins, thank you again for your hospitality on my
visit.
You have recently announced the creation of a trans-NIH
pediatric research consortium. Can you give us an idea of what
you want to accomplish with that, Doctor?
Dr. Collins. I would be very happy to.
We have the National Institute of Child Health and Human
Development, which sounds like it is the place where pediatric
research gets done and a lot does get there. But it is actually
only about 18 percent of pediatric research across all of NIH.
Most of the institutes--you have just heard a great example
from the Cancer Institute--are also heavily invested in
pediatric research.
I have asked Diana Bianchi who is the new Director of the
Child Health Institute to convene a trans-NIH group at a high
level from all of the institutes that are players, which is
essentially all of them, to see whether we could come up with a
more coordinated strategic plan for defining where are the
greatest priorities in pediatric research and how can we work
together, whether it is cancer or whether it is autism, whether
it is birth defects, whether it is development, whether it is
behavioral issues. I believe with her leadership--and she is a
very strong leader, indeed--that we have the chance to put
forward a plan for pediatric research that will be quite
exciting. That has just gotten going, and I would be glad to
report back to you in the coming months about how this is
leading us in new directions.
FOGARTY INTERNATIONAL CENTER
Senator Reed. I would be remiss if I did not applaud the
Fogarty Center, named after my beloved predecessor in the
United States Congress, John Fogarty. But this is the
international arm, if you will, of NIH, and we celebrated the
50th anniversary. And it seems particularly important today, as
we talk about Ebola emerging in countries like this, that we
have this agency in very close rapport with CDC.
Can you just comment upon the next wonderful 50 years of
the Fogarty Center? And tell Peter Kilmarx I said hello.
Dr. Collins. Senator, I appreciated very much your being
there at that 50th anniversary celebration and speaking to the
group.
One of the things Fogarty has done that has been most
powerful, even though it is the smallest of all of our
institutes, is their training program for fellows.
I am just going to quickly ask Tony Fauci to tell you a
story or two about how those Fogarty fellows have played a
significant role in global health challenges like Ebola and
Zika.
Dr. Fauci. Thank you, Dr. Collins.
Yes, the Fogarty International Center really has been very
important and very much interdigitated with what we do as the
National Institute of Allergy and Infections Diseases (NIAID)
in the area of infectious diseases. You may recall that when we
had the Ebola outbreak in West Africa in 2014, 2015, and early
2016, there were cases that, as you might expect, traveled not
knowing they were infected with Ebola to other places such as
Mali and Nigeria. And those cases did not result in outbreaks
in those countries. Almost all the people taking care of those
individuals infected with Ebola virus who traveled to Mali and
Nigeria were trained as Fogarty fellows. So we had a pre-
existing network of people there who had been trained in
science and public health with support from the NIH. That was a
dramatic public health example of how the Fogarty Center was a
true partner, not only with regard Fogarty activities on our
NIH campus in Bethesda, MD but Fogarty activities in Bamako,
Mali and Lagos, Nigeria. It was really quite striking.
Senator Reed. With a speech like that, you could be elected
to Congress from the 2nd district. Thank you.
[Laughter.]
Senator Blunt. Senator Capito.
OPIOIDS PARTNERSHIP
Senator Capito. Thank you, Mr. Chairman and the ranking
member, and thank you all of you.
And Dr. Collins, it is great to see you again.
My first question is on opioids and what you are doing. And
we have talked numerous times about this. Obviously, I live in
an area that is highly affected here.
Two questions. You mentioned and you said that we had put a
$500 million historic investment into this. But you have
mentioned in your response to questions that you have private
partners. Could you elaborate on how the private partnership
works, and what kind of commitment dollar-wise that private
partnership is committing to add to the $500 million that we
are doing in the research?
Dr. Collins. Happy to.
We have worked intensively since your wonderful decision to
make $500 million available in fiscal year 2018 and to have
that in the base so that it will be there in 2019 and beyond.
Working with all of the institutes across NIH, we have put
forward an opportunity for new and bold ideas to come forward,
and we are in a place now, I think, of having a remarkable
portfolio that we are ready to launch.
You also graciously gave us that first year of support as
2-year money so that we could, in fact, carry over some of the
fiscal year 2018 funds into 2019 since it is late enough in the
year that starting brand new things is a little challenging.
But we have figured out how we are going to spend a significant
fraction of that $500 million right away.
It does include a wide variety of applications, including
some of the things that have already been discussed by Dr.
Volkow and Dr. Koroshetz, but also such things as what to do
about the neonatal abstinence syndrome, which is of such deep
concern to all of us in terms of how best to manage, what
happens to those babies, and what is their long-term future.
The public-private partnership, which you mentioned, is
actually a modest part of this broad portfolio but an important
one. Again, as we talked about earlier, the decision was made
by me based on strong recommendations that that partnership
should involve assets that are contributed by industry that
have value, data, compounds, scientific expertise, but not a
cash contribution. It is a little challenging right now to
attach a dollar value to what their in-kind contributions are
going to add up to, but it will be substantial.
Senator Capito. Good.
Dr. Collins. So putting that all together, we think we are
in a good place to move both the public-private partnership and
the rest of this broad portfolio together quite rapidly.
NEONATAL ABSTINENCE SYNDROME
Senator Capito. Good. Thank you.
Dr. Volkow, on the neonatal abstinence syndrome, obviously
we are the State most highly affected by that as well. And this
is an area of deep concern to everybody. We have got 1,000 more
kids in foster care. A lot of these babies probably will be the
repeat mothers. They have repeat exposure. I mean, they have
numerous exposures to numerous drugs not just particularly one.
And I believe you visited our Lily's Place down in Huntington
to see what kind of care they are getting there.
The research that you are doing and the ACT NOW trials--
are those being conducted across the Nation, or how do you find
the right place to conduct those kinds of--and where are you
doing that?
Dr. Volkow. Well, the ACT NOW is one of the programs that
will be funded through the new money that has come for the
opioid crisis and will allow us to actually maximize protocols
that will enable us, for example, to determine what are the
optimal interventions for the best outcomes on neonates. And
that includes protocols that may not require the administration
of medications to those neonates with abstinence.
We have other research studies also ongoing. And I was at
West Virginia last week and I was in Huntington. And I was
horrified to hear that one out of five newborns had opioids on
them. And one of the points that is highlighted is that we need
to address the needs of the neonate, but we need to address the
needs of the mother once the baby is born. So the outcome from
that infant and child is not addressed. So we are working with
research of new medications and new non-medication
interventions to improve the outcomes of those neonates.
And the other aspect that Francis mentioned is we are very
interested in understanding how the brain of these newborns is
going to have been influenced by getting exposed to opioids, as
well as other drugs, during fetal development when the brain is
very, very vulnerable.
Senator Capito. Right. I am anxious to hear how we progress
with that.
I guess one of the points of asking my question is there a
wealth of data all around the country with people who are hands
on in these scenarios dealing with this right now that I think
can feed not only good information but can help you conduct
trials on a local level. It sounds like that is what you are
already moving forward on.
Dr. Volkow. Correct.
CLINICAL TRIALS--ALZHEIMER'S
Senator Capito. I am really pleased to be on the STAR Act,
the childhood cancer act. I am glad to hear about the
survivorship. That is something of great importance to me. A
lot of this I am very interested in, as Dr. Collins knows, but
I do want to go over to Dr. Hodes because Alzheimer's on the
other end of the spectrum is something that I have personally
been touched with.
And I would like to know, Doctor, one of the things I have
heard is that it is hard to recruit patients for clinical
trials for Alzheimer's. Is that the case? What are you finding
there? I mean, I know it is hard by the time you start
exhibiting the symptoms, you are already in it. How are you
developing all those trials with different----
Dr. Hodes. Senator, it is an excellent question. And it is
a challenge to us for multiple reasons.
As you have commented upon, for individuals who are already
affected with symptoms, we carry out studies that are extremely
important. But there is also a sense that in order to be most
effective in preventing the appearance of symptoms that we need
to intervene earlier before irreparable damage is done.
This means that we need to recruit people who are not
coming through a normal process where they see a clinician who
suggests they participate in a clinical trial. These are people
who are at high risk but show no symptoms. So we need to
develop and are developing strategies for screening those at
high risk and then the charge of finding people who are
committed, dedicated to participate in studies to see if we can
make a difference through early intervention.
Studies such as All of Us present a unique opportunity for
this with a million people, for example, who have signed on for
their interest in participating in research. We can screen
those who, by a variety of metrics, may be at high risk for
developing symptoms years or decades later and take an
opportunity to intervene with those now. So we are in the midst
of a nationwide program which will be announced this summer to
look at multiple modalities for recruiting patients into
studies.
Senator Capito. Good. Thank you. We want to support that.
Thank you.
Senator Blunt. Senator Shaheen.
FENTANYL
Senator Shaheen. Thank you, Mr. Chairman.
And thank you to you and Senator Murray and Senator
Alexander for your commitment to research and funding for NIH.
And to you, Dr. Collins, and everyone there, thank you so
much for the work that you are doing. You give hope to so many
people across this country.
Dr. Volkow, thank you for coming to New Hampshire. I
especially appreciate the work that is being done to address
the opioid epidemic. Like my colleagues on this committee, we
have been very hard hit in New Hampshire, as you know, from
your visit to Catholic Medical Center and other places in the
State.
I was interested in your discussion about new drugs that
are in development. As you are looking at what the potential
is, are you separating out fentanyl as a particular opioid that
has very deadly properties and therefore requires a different
kind of response, or are you lumping that in with everything
else?
Dr. Volkow. We cannot lump it with everything else because
what we are hearing from the field and being reported in the
literature is that when people overdose with fentanyl, the
doses that were used of Narcan are not sufficient actually to
reverse the overdoses. The other concern is if you get exposed
to fentanyl, because of its potency, your risk of addiction is
much higher.
So as of now, we, for example, have not ever done a trial
of how do you treat someone that is addicted to fentanyl, and
that is one of the projects that we would like to implement as
soon as we get the approvals.
But also with respect to the medications, we are actually
funding researchers who are partnering with pharmaceuticals to
develop a stronger antagonist. So this is the nasal Narcan,
which we actually developed, but it is not sufficient for
fentanyl. So we are developing with companies longer lasting,
more potent or alternative medications that may not be based on
the same mechanism as naloxone. Because the other challenge is
not just fentanyl, but what we are observing is people are
overdosing with multiple medications, alcohol, benzodiazepines,
and fentanyl. So this is not sufficient.
CO-OCCURRING MENTAL HEALTH ISSUES AND SUBSTANCE ABUSE
Senator Shaheen. And we see so many people who have co-
occurring mental health issues along with their substance use
disorder. So often they are using substances to address their
mental health issues.
So are you doing any research that looks at the two
problems together that may give promise as we think about what
the future holds?
Dr. Volkow. We cannot do that because the comorbidity is
many times much more frequent, the isolation. And if you
address, for example, the depression of someone that is
addicted to opioids, you are not going to succeed.
Also a very important component followed by the overdose is
we really do not know which ones are intentional, therefore
suicide. So if you are reverting someone on an overdose that
has suicidal behavior and you do not intervene, you are not
going to succeed.
So we are prioritizing. We are recognizing that the reality
is comorbidity, comorbidity of addiction with mental illness,
and comorbidity of addiction with pain. And those are more
challenging than when they are in isolation.
Senator Shaheen. So did you want to add anything to that?
Dr. Collins. I think Dr. Volkow very accurately
characterizes the situation.
I think one of the things that we are most concerned about
in terms of this crisis, just if I can show you this graph, is
the way in which the epidemic, in terms of the overdose deaths,
has shifted from being prescription opioids to now fentanyl
just going straight off the chart as it gets into the heroin
supply. And as more individuals who have fallen into addiction
cannot find sufficient access to prescriptions, then they shift
over.
EBOLA
Senator Shaheen. Absolutely. That is what we are seeing in
New Hampshire where we have the highest rate of overdose deaths
from fentanyl.
Dr. Fauci, Senator Blunt mentioned the Ebola epidemic and
the news report this morning that said the first case had been
found in an urban area, a large city, in the Democratic
Republic of Congo. And given DRC's other challenges, how
worried are we that that epidemic is going to get out of
control again?
Dr. Fauci. Given our prior experience, we are on very high
alert about this Ebola outbreak. There are some factors that
mitigate against their having the same situation as we saw in
West Africa, but there are also factors that actually might
favor that. As you mentioned, the first cases that were
reported in very early May, the first week in May, were in a
place called Bikoro, which is on a remote area called Lake
Tumba. The bad news is that it is very difficult to get help
in. The good news is it is very difficult to get anybody out.
But what you heard this morning in the report is that there
are multiple different zones. Bikoro is one zone. Another zone
is Mbandaka, which is an area that has a city of 1.1 million
people. And even though there is only one case there, there is
a total now of 44 cases. Even though only two have been
confirmed, there are 20 that are probable and 20 that are
suspicious. So there are probably many more cases.
What we are doing now is shipping in with the WHO (World
Health Organization) helping, obviously, the kinds of things
that were the fruits of the work that we did with the support
of this committee and others to develop countermeasures. And I
will very briefly give you an example.
You heard probably on the media that the WHO has authorized
the shipping of the VSV vaccine that had its first phase one
trial right at the Clinical Center at the NIH, and then we did
it in Africa and that was the one that did the ring
vaccination.
We also have ZMapp, which is that triple combination of
antibodies that we published in the New England Journal of
Medicine from the intramural program at NIH that went over
there in Liberia. That is also being shipped.
And we have some experimental drugs, one we are partnering
with Gilead, and some monoclonal antibodies that have been
developed by the Vaccine Research Center.
So although in direct answer to your question, we are on
high alert. We are always concerned when there is Ebola. But we
right now have a number of countermeasures that we are able to
develop to go in and hopefully block that. So our hopes are--
our expectations are always cautious, but the hopes are that we
will not have the kind of outbreak that we saw in West Africa.
Senator Shaheen. Thank you,
Thank you, Mr. Chairman.
Senator Blunt. Senator Durbin.
Senator Durbin. Thanks, Mr. Chairman.
Let me say at the outset that in a world of frustration and
partisanship, what is happening in this room this morning is a
welcome exception. You will find more positive feelings, more
achievement I hope, and more bipartisanship than in almost any
other room on Capitol Hill. And I want to salute the chairman
of the subcommittee, Senator Blunt, his ranking member, Senator
Murray. I told her I was going to praise her before she left.
And certainly Senator Alexander in his work and Senator
Shaheen. This is a great assignment because with the help of
the folks sitting at this table, we actually feel like we are
taking steps forward.
And to Senator Blunt for his leadership on this, we have
established a standard I think and I hope it is one that we can
live by of sustainable, reliable increases in medical research
funding in the United States of America. Dr. Collins told me
several years ago that is what we need, and we are doing our
best to meet that need.
CRISPR
One of the areas that I have recently learned a little bit
about was in ``Foreign Affairs'' magazine of all places, and I
happened to be reading it. And this liberal arts lawyer came to
try to understand something called CRISPR, which is included in
your publication here of promising technologies.
And ironically--I talked to Dr. Collins about this
earlier--a family from Illinois came to see me last week, and
the mother, the wife, has myotonic dystrophy, and it is a
genetic disease which she has unwittingly passed on to her
children, a son and daughter, whose circumstances are even more
challenging than her own, and of course, their future is really
unknown. I mentioned CRISPR to them, and they lit up. They said
this is the one area where we feel like there is a chance.
Please, Dr. Collins or one of your colleagues here, give us
a moment about CRISPR and what we are doing.
Dr. Collins. I am happy to because I agree that this is one
of the most exciting things that has happened in a long time in
terms of providing tools both for basic science and for
therapeutic applications. It opens up entirely new vistas
particularly for individuals with genetic disorders where we
know there is a misspelling in the DNA. This provides an
opportunity to go and fix that in a very precise fashion.
So it is also a great story about basic science because
this particular enzyme called Cas9 was discovered in a very
obscure area of people trying to understand how bacteria can
fight off their own viruses. Bacteria have their own viruses
and somehow they manage to survive. And it is a very elegant
system where the bacteria have an enzyme that basically
recognizes a foreign DNA sequence and goes and snips it and
inactivates it. But it is programmable.
And so Jennifer Doudna and her colleagues and Feng Zhang
and his colleagues and a few other people who are arguing about
who gets the credit basically came up with a way to take that
bacterial system and make it work in all kinds of cells,
including human cells.
It is very precise. You program it. It can find in a 3
billion letter instruction book--that is our DNA genome-- the
one that you want to alter and zero in on it and very precisely
make a cut or make a substitution.
Now, of course, in the basic science lab, this is
fantastic. Every laboratory that is doing molecular biology is
using CRISPR Cas9, including mine, including all the people at
this table who have active laboratories. But therapeutically
the promise here is what I think has us particularly excited.
As I mentioned to you earlier, sickle cell disease may well
be the first success of this because for sickle cell disease,
the problem is in the bone marrow stem cells. You can take them
out. You can purify them. You can utilize this enzyme system to
fix the sickle mutation and then put them back. And that should
be not just a treatment but a cure for people with this
disease, 100,000 of them in the U.S. I think that is going to
happen in the next 5 years. The first clinical trials are
probably going to start this year.
VAPING
Senator Durbin. I hate to interrupt you because this is
important. I have one other topic I want to mention. And I hope
that this subcommittee can zero in on the CRISPR technology and
what is happening there. I think there is so much promise.
But I wanted to mention one other thing that is important
to most of us. 27 percent of the high school students in the
State of Illinois have something in common. 27 percent of them
are now using e-cigarettes and vaping. It used to be 28 percent
using tobacco cigarettes. Now they are into e-cigarettes and
vaping. And the people who are peddling these products that
they inhale with nicotine are putting them in candy flavors.
Here is one. The brand is Lung Candy and the flavoring is Cake
Batter. In this listing here--it is a long listing of flavors
for children to see opportunities for vaping. We see exactly
what is happening.
Can I get a comment from any of you about what you consider
to be the perils or danger of this type of addiction?
Dr. Collins. Dr. Volkow.
Dr. Volkow. Indeed, we are very concerned because one of
the issues why 50 percent of teenagers say that they are
starting to vape only with flavors, 30 percent of them are
starting to vape with nicotine and are becoming addicted to
nicotine.
And in studies that have been already published, it has
been shown that if you start to vape, you are much more likely
to then go into nicotine vaping, and then if you got into
nicotine vaping, then to go into smoking tobacco. So a major
concern is that we will be losing a lot of the advances that we
did on prevention of smoking among teenagers.
Another aspect that people do not really recognize is that
nicotine acts as a priming. So anything that you take when you
have nicotine on board becomes much more reinforcing. And as a
result of that, if you get exposed to drugs while you are
having nicotine on board, you are much more likely to become
addicted. So the concern is not only that these teenagers will
become cigarette smokers, as the data has already shown--the
risk goes up--but also by doing this, their brain becomes
primed to the addictiveness of other substances.
Senator Durbin. Thank you.
Thanks, Mr. Chairman.
ZIKA
Senator Blunt. Thank you, Senator Durbin.
Dr. Fauci, let me give you a couple minutes to talk about
two things. First, Zika. I was at St. Louis University during
the Zika crisis where they were working on Zika vaccine
research and felt like they were coming to conclusions. So are
we going to have something available next time? And second,
flu, specifically universal flu, or whatever you want to talk
about on your research on those two topics.
Dr. Fauci. Thank you, Mr. Chairman.
First, we will take Zika. As you know, as I reported to
this committee on more than one occasion, we have progressed in
our vaccine trial from the phase 1 trial that we originally did
at the NIH to now deploying a phase 2b trial, 2b being
relatively advanced to not only ask is it safe, but does it
induce the kind of response that you would predict would be
effective.
And I am pleased to report to you that today we have
ongoing a phase 2b trial in several countries in South America,
in Mexico, in the Caribbean, Puerto Rico, in Texas, and in
Florida to determine if the vaccine is safe and if it does
induce that response. It is scheduled to have between 2,400 and
5,000 people in the study. We are recruiting very rapidly. We
anticipate--and I am pretty cautiously optimistic about that--
that we will have it fully accrued by the end of 2018. And then
if in fact there is an outbreak, we could get an efficacy
signal.
And if there is not, then we are working very closely with
the FDA (Food and Drug Administration) if we can get enough of
what we call immunogenicity data--namely, it shows that it does
induce the kind of response that you want--and bridge that to
the animal data, which are very convincing that this is a
vaccine that can induce a good response--we are working with
the FDA to determine if in fact we can get an accelerated
approval. You never anticipate what their decision will be, but
they are being very cooperative.
UNIVERSAL FLU VACCINE
Next, universal flu vaccine. Again, we are very grateful to
the committee for supporting the addition of the $40 million in
the 2018 omnibus for a universal influenza vaccine. So let me
report where we are with that.
We had a meeting in Rockville in June of 2017 in which we
developed, in association with experts from all over the world
and in the United States in influenza, what we call a strategic
plan and a research agenda, which we published in the Journal
of Infectious Diseases in February of this year.
We are now implementing that plan both from a basic science
standpoint but also with candidates that are at various stages
of development, namely either preclinical in animal study or a
phase 1 or phase 2.
And I might just close by saying you may have read just a
couple of days ago an NIAID-sponsored phase 2 trial with the
universal flu vaccine candidate in association with the company
BiondVax has been initiated. And we started a few months ago
one of the trials from our vaccine Research Center.
So things are on track. Obviously, as I mentioned to this
committee, it is not going to be an overnight type of a thing,
but we are well on the road at various iterations of going
towards a universal flu vaccine.
Senator Blunt. And do you see a point, if we got there--I
am assuming what we are trying to get is for every year we
would not have to try to calculate what that year's flu was
like and, more often than not, be slightly off target.
Dr. Fauci. You are absolutely correct, Mr. Chairman.
The perfect--and that is going to be difficult to do. A
universal flu vaccine would be one that would cover all
versions of seasonal and any potential pandemic. But the road
we are taking now is to go step by step. I tend to refer to it
as universal flu vaccine 1.0, which means that we will not have
to worry about any H3. The H3N2 that we do each year and we
have to change it a little from season to season, which is the
reason why we need to get vaccinated every year, the first
version will cover all of the H3N2's. The next one will cover
very likely an H1N1. There are two major groups of influenza
viruses that have multiple viruses in each group. Getting one
that covers both groups is getting close to the perfect one.
So the answer is the end game is that you and I, but most
likely our children, will be able to get a vaccine early on in
life, a boost, and then maybe every 10 years or so and not have
to worry about each year guessing what the next iteration is
going to be. It is the guess that is the problem because
sometimes you do not get it right, and even when you do, it
changes enough that it evades the vaccine. And that is what we
are trying to avoid.
Senator Blunt. Well, I may have unlimited time here, and I
may exceed that. Who knows what may happen?
[Laughter.]
FUTURE OF CANCER RESEARCH
Senator Blunt. Dr. Sharpless, so I think in the United
States today there are 15.5 million cancer survivors. In 1971,
there were 3 million cancer survivors. An incredibly exciting
time. Immunotherapy, the BRAIN Initiative, and, that I assume
will have a significant cancer-looking element to it, CRISPR.
You and I have some time here. Could you take just a few
minutes, a couple of minutes maybe, and talk about your vision
of what you hope and believe can happen over the next handful
of years in the Cancer Institute based on what we see happening
already?
Dr. Sharpless. Sure. I think you are really right about
that. It is a very exciting time in cancer research. I recently
had a colleague email me. It is like I picked the perfect time
to lead the National Cancer Institute because there are all
these exciting things going on. In fact, today is the release
of the ASCO abstracts. It is sort of like Christmas in our
field where all the new advances come out and a number of
exciting advances in a variety of different cancers.
So I think there really are a lot of opportunities that
cash in on this observation that cancer is not only one disease
or 10 diseases but hundreds or thousands of diseases, and each
one of them needs its own specific treatment.
So the good news is there is a lot of excitement going on.
There are a lot of new technologies and new approaches, and a
lot of that research has been empowered by the funding from
this committee.
But I think the bad news about it is that problem is
somewhat different from what we used to imagine. So we used to
think of cancer is like one disease and we had the cardiology
paradigm where we put 800 people on one arm of the trial and
800 people on the other arm of the trial. That sort of clinical
trials framework no longer really works. So the modern approach
to cancer I think has to be somewhat different.
So the things I thought the NCI should focus on are
training the workforce so that we have the right kinds of
cancer researchers. So we need cancer biologists who really
understand basic immunology because it is excessive
immunotherapy, and we need cancer researchers who understand
big data because we are aggregating data at such a furious pace
to try and use that information to treat cancer patients.
We need to recommit to basic science. You know, it is not
enough to make progress against some cancers. We really have to
make progress against all cancers, and that requires a basic
biological understanding of all cancers.
We need to fix the problem of clinical trials. The
structure of clinical trials in cancer has led them to become
smaller and more fragmented and much more expensive. And so we
need to sort of rethink how we do clinical trials. A very
interesting development there is the NCI-MATCH Trial, which
will be presented this year at meetings about how we sequence
patients and identify the mutations in their tumor and then
allocate them to therapy based on the genetic driver, the
personalized event that makes their cancer relevant.
And then lastly, we really need to get serious in cancer
about organizing our data and aggregating it and linking it so
that we have the genomic data, the radiology data, the
histology data, the clinical information--we have that all
available in a way that is safe and secure, available to the
research community so we can understand what mutations cause
what patient to respond to this drug and why they lived that
long and really get a handle on these bins of rare cancers that
we have to treat.
GENETICS AND CANCER
Senator Blunt. I was out at FDA not too long ago. They have
put a cancer team together that I know you are aware of that is
looking at all they are doing. You know, the thought in that
discussion came up that within the foreseeable future, there
just may be something that each individual is prescribed that
amps up, if you will, whatever their unique fighting capacity
needs to be on their unique attack that is likely to happen to
them. That is one look.
The other look is--I am not sure how the genetic--the
CRISPR effort works there. But it is an incredibly exciting
time. Even with immunology, I would think that 5 years ago an
observation made in passing would not have been made at all.
This is what we are doing. And there I am sure you are going to
continue to work on why this does not work on some cancers and
what you need to find. It may not be possible ever, but right
now--Dr. Collins, do you want to talk about that?
Dr. Collins. I appreciate your raising this, why does it
not work when it does not work.
And we talked earlier about partnerships, and I wanted to
point to this as a very successful public-private partnership
called PACT, the Partnership for Advancing Cancer Therapies.
Now 12 biotechnology pharmaceutical companies have partnered
with NIH to ask that question. What are the biomarkers that
actually tell you that immunotherapy is going to work or it is
not? Because we have these dramatic success stories. Emily
Whitehead, this little girl that had failed to respond to the
traditional treatment for leukemia and who was very much near
the end, and who with CAR T-cell therapy was not just
successfully treated, she was cured. She is 5 years out now.
She looks great and wonderful.
But it does not work for solid tumors nearly as well. Why
does it not work for pancreatic cancer? Why does it not work
for prostate and breast and brain tumors? We need to figure
that out, and that is what this partnership aims to do. In this
case no concern about, I think, conflict of interest. It is all
pre-competitive. It is all out there in public. So in this case
pharma is contributing both expertise and resources but also
cash, and it is pretty exciting to see this taking shape under
the leadership of Dr. Sharpless and his colleagues.
Dr. Sharpless. Yes. I think that is one of the initiatives
to really sort of--you know, each of these therapies requires a
really detailed understanding of how they work to make them
work in everyone. But it is just leaps and bounds. Every day
now we are seeing some new area where we have a drug that used
to work and we are making it work better for a whole new class
of therapies. And so a lot of good stuff going on.
However, I think it is also important to note that we do
still have some cancers, some even reasonably common cancers,
where we have not made much progress. So glioma, for example,
glioblastoma, brain cancer, is still a real problem, and I
think that we really as the NCI have to not only focus on the
cancers where we are having successes but also perhaps even
more so on the ones that have been recalcitrant and refractory
to therapy to date. And so that is an important part of our
mission as well.
ALZHEIMER'S AND DEMENTIA
Senator Blunt. I think the area of greatest spending,
certainly the quickest growing spending of Federal health
dollars would be Alzheimer's and dementia. And Dr. Hodes, if
you and maybe Dr. Koroshetz both would talk about what we are
finding there. We have made big investments here. You have
probably eliminated a lot of things we know do not work. Now,
how are we doing on the other end of that and the dementia
impact, too, Dr. Koroshetz, when it comes to you on that? And
then when you are done, we will go to Senator Hyde-Smith as she
settles in here.
Dr. Hodes. Thank you.
I first want to thank the committee, Congress for the
increased appropriation of resources towards Alzheimer's
disease and related dementias. It has had an enormous impact.
For example, in 2015, we funded 152 awards supporting research
in this area. 2 years later in 2017, that had increased to 442.
And importantly, this is reflected with confidence and
excitement that we heard about across the research community
seeing the national commitment to sustained resources, a
renewed energy on the part of new and early stage
investigators. So of all these new awards we have seen, more
than a quarter, 27 percent, were to the categories of early
stage and new investigators who had not received any NIH major
support previously. An even larger number than that, more than
a third, 36 percent, had never had any support for Alzheimer's
and related dementias research. So we are bringing into the
community not just more dollars and opportunities but the
energy that comes with new people willing to commit their
careers and to bring new disciplines into the field.
This has included an expansion of the number of clinical
trials currently supported to over 140. And equally important,
using new techniques of looking at gene expression patterns,
proteomics, metabolomics, and an amazingly effective
consortium, AMP, Accelerating Medicines Partnership, around
Alzheimer's disease to bring public and private science,
clinical expertise, and financial support together to fund new
discoveries that have identified the so-called wall of targets
now--there had been a consensus to find new molecular targets
not appreciated before that might lead to entirely new
approaches much needed, in addition to the directions we
currently take for translation into clinical trials.
So it is an incredible excitement I think you can
appreciate. The numbers are only meant to illustrate the
intensity of excitement there is now. Sustained funding has now
convinced investigators this is an area in which we can make
progress, and the pace has increased exponentially.
Senator Blunt. I think at Washington University they are
feeling more and more positive about a blood test. Things like
that that would begin to early identify what was happening with
amyloids in the brain would be a big step in the right
direction. Hopefully, we can go out there together and look at
that sometime.
Dr. Hodes. Yes.
Senator Blunt. Dr. Koroshetz.
Dr. Koroshetz. Thanks to the wisdom of the Congress for
including what we call the Alzheimer Disease-related dementias
in this major effort to decrease the public health problem of
dementia in our country. Most patients who have dementia are
diagnosed with Alzheimer's disease. Especially in the elderly,
when one looks at the brain, one more often than not will find
multiple different things going on. And one of the two areas
that are most common is the finding of what we call Lewy body
disease in people who have dementia diagnosed as Alzheimer's.
They have Alzheimer's changes but also have the signature of
Parkinson disease, which is synuclein aggregates. So
understanding the contribution of these synuclein aggregates
not just to Alzheimer's dementia but also to the dementia that
occurs in Parkinson's patients who have it for a long time is a
focus that we have been able to really pursue much more
aggressively.
The other area, which is even more common, is the
combination of vascular disease in people who are diagnosed
with Alzheimer's disease. And this is, I think, incredibly
important to understand because we have made strong progress
over the last 70 years in decreasing the risk of stroke, which
is the most common consequence of vascular disease in the
brain, and also incredibly common in people who have dementia
diagnosed as Alzheimer's.
So we have been working with the National Institute on
Aging on projects to be able to track the health of the
cerebrovascular system in the brain and its contribution to
dementia with the hope that the things we already know about,
if we can be more aggressive about them, may actually prevent
people from going on to develop dementia because we can block
this contribution of the vascular component.
Senator Blunt. Exactly.
Senator Hyde-Smith.
Senator Hyde-Smith. Thank you, Chairman Blunt.
And thank you, Dr. Collins, for testifying today and all of
you for testifying today.
EXPANDING CLINICAL TRIALS TO UNDERSERVED AREAS
I have been involved as a volunteer with the American
Cancer Society for many, many years in Mississippi. So I have
seen firsthand how new treatments and therapies have
transformed the prognosis for so many different types of
cancers. And I am grateful for the role that you have played,
that NIH has played in so many of those discoveries. What you
are all doing is so important, and I truly see it changing and
saving lives. And I am grateful to you for that.
However, despite these recent innovations in cancer care,
my State of Mississippi continues to have one of the highest
cancer mortality rates of any State. For many Mississippians,
receiving the cutting-edge treatments and participating in a
clinical trial would mean traveling hundreds of miles from home
to a cancer center in another State, which is not possible for
so many of our patients.
But, Dr. Sharpless, how is the National Cancer Institute
working to ensure that patients in States like mine, which do
not have an NCI-designated cancer center, are able to
participate in clinical trials and benefit from the newest
discoveries?
Dr. Sharpless. Senator, thanks for the question.
I think you raise a really important issue, which is that
it is in some ways great news we are making all this progress
against cancer and having those new therapies and new
approaches, but if we then cannot disseminate them into the
broader community and implement those therapies in sort of the
real world, then are we helping people to the extent that we
could do so?
So the National Cancer Institute is very concerned about
how we assure that our advances translate beyond just the NCI-
designated cancer centers, which are a great program but there
are only 70 of them, and their range is limited.
One program we have to address this is called the National
Community Oncology Research Program, or NCORP, which is 50
NCORP sites that then have each several satellite sites. So
there are sort of 900 NCORP sites across the country. Between
the cancer centers and NCORP, we reach virtually the entire
country. And these sites, in addition to being able to do
clinical trials, also have catchment areas that have patients
that are more likely to be rural patients as opposed to urban
patients and more likely to be underserved minorities. So it is
a way that we can enroll a demographic that looks more like the
United States in general. So it is a great program. We have
just decided to expand its scope somewhat. It is successful and
we want to build on that.
And it is also important to note that we can do clinical
trials in the NCORP program. For example, the NCI MATCH trial
enrolled 6,000 patients at 1,100 sites. It was the fastest
accruing trial in the history of the National Cancer Institute,
and it allowed us to do accrual in the community, which is also
a real need in cancer research because 5 percent of adult
oncology patients go on clinical trials. That number needs to
be higher, and we need to take the trials to them through like
the NCORP program. So it is one way that we are working to
address this important issue.
ALL OF US PILOT TESTING
Senator Hyde-Smith. Wonderful, very good.
And also, I am proud that The University of Mississippi
Medical Center and the Jackson-Hinds Comprehensive Health
Center were both chosen as sites in the All of Us research
program in Mississippi. This program, which seeks to enroll 1
million American volunteers, will no doubt lead to important
discoveries that will help doctors identify treatments and
personalized to patients' lifestyles, individual's environments
and genetic biology. Jackson-Hinds was only one of only six
community health centers nationwide chosen to help pilot the
project beginning in 2016.
Dr. Collins, as the NIH rolls this program out nationwide
this year, how have you incorporated lessons learned through
the pilot at Jackson-Hinds that participated in this?
Dr. Collins. That is a great question. We did spend the
last year in a pilot phase of ramping up All of Us, recognizing
this is probably one of the most ambitious projects that NIH
has ever mounted, and we needed to have great attention paid to
the needs of the participants and particularly for their
security and privacy. And we also made a commitment that this
was going to be a project that was truly national and it would
include people who were traditionally not invited to take part.
People in community health centers oftentimes have not been so
engaged in research. We wanted to reach out. And Jackson-Hinds
was in a particularly powerful place to be one of the first
ones to try and see how this would go.
I think we have been very encouraged. In the pilot projects
for All of Us, we enrolled over 26,000 people. That makes it
one of the biggest studies NIH has done in a long time. And
that was just the pilot on the way to our million.
And from the community health centers like Jackson-Hinds,
we were gratified to hear a lot of interest on the part of
people who came there for their medical care in getting engaged
in this kind of research and being included. They wanted to be
counted too. They wanted the results of this study to be about
them and therefore, provide information that they could use.
So I think it has been a wonderful experience. It has been
a kind of outreach we have not necessarily tried at quite this
scale before. And now, as of May 6th, we have done the full
launch, and anybody in the United States can join up,
joinallofus.org. That is all you need to know.
Senator Hyde-Smith. Great. Well, we certainly appreciate
it. All of you.
Senator Blunt. Thank you, Senator Hyde-Smith.
Senator Shaheen.
TYPE 1 DIABETES
Senator Shaheen. Thank you, Mr. Chairman.
I came back because I did not want to go home and tell my
family that I had this whole panel from NIH in front of me and
I did not ask you about the prospects of research into a cure
for type 1 diabetes. I have a granddaughter who has type 1. I
also co-chair the Diabetes Caucus in the Senate with Senator
Collins and know how devastating the potential is in this
country if we do not figure out a cure for this disease. One in
three by 2050 will have diabetes, and it is one of the most
expensive, if not the most expensive, chronic diseases that we
have.
So can you give me an update on where we are with research?
Dr. Collins. Senator, I would be happy to and appreciate
your leadership in this.
This is another one of these very exciting areas where
things are now moving very quickly for both type 1 and for type
2. Much of the excitement surrounds the potential of developing
an artificial pancreas that would take care of the production
of insulin when the body has failed to do so at the level it
needs to. And you already have seen, of course, the FDA
approving the very first example of an artificial pancreas in
sort of a closed loop where there is a sensor of what the
levels of glucose are and then it administers insulin
accordingly. But this is just the beginning of what I think is
going to be a remarkable series of advances.
Ultimately the whole stem cell area is going to be critical
here as well. We have, after much hard work through the work of
people like Doug Melton at Harvard, figured out how you can
take a skin cell from somebody, convince it to become what you
would call pluripotent and then give it the appropriate set of
cocktails to convince it to go down the pathway to be a cell
that makes insulin. But it is your own cell. And so ultimately
in the view of many of us, that is where we are headed, the
opportunity to make an artificial pancreas that does not have
silicon in. It actually has your cells that have been
reprogrammed to make up for what the other cells that should
have been doing this were able to do.
On top of that, I think in terms of prevention particularly
of type 2 diabetes where we know that this is tightly connected
to obesity and insulin resistance, increasingly trying out the
efforts to reduce weight and increase exercise are looking very
promising over the long term to keep people who are tipping
over into diabetes from actually getting there.
A lot of research as well on gestational diabetes and what
kind of information we can learn when this seems to happen
during pregnancy. What should be the follow-up to that because
that clearly indicates a risk for future illness.
So it is a very exciting time. I could go on much longer,
but I wanted to reassure you that NIH is deeply in the middle
of all this and the progress is quite gratifying.
ARTIFICIAL PANCREAS
Senator Shaheen. Well, I appreciate that. And I am excited
about some of the new developments. I think we need to think
about how we can reverse the incentives in our healthcare
system to do more for prevention with type 2 where it really
makes a difference. And unfortunately, I think we are not
providing the resources that we need there, and in the long
term, it is going to cost us more money.
But I wanted to ask a follow-up because one of the things I
have heard from the diabetes community is their frustration
with how long it has taken the FDA to approve an artificial
pancreas and further developments on that. So we are seeing
people in the community who are doing what they call bootleg--
and that is probably not a good term--but are basically making
their own artificial pancreas and feel like that provides more
relief than they are getting currently, given the system that
we have and the dependence on insulin and the way that works.
So can you speak to that? Is that something that you have
heard about, and are you concerned about what the risk might be
from that?
Dr. Collins. I do think there are reasons to be very
careful about putting in place an artificial pancreas system
without being absolutely confident that it has the appropriate
safety mechanisms because we all know that an overdose of
insulin can put you into a coma and can ultimately lead to
death. So this needs to be a system that is really well worked
out. So I understand why the FDA, therefore, has to be pretty
rigorous in terms of their evaluation of such things.
I do think, though, that in Scott Gottlieb you have an FDA
Commissioner who really is dedicated to moving things along as
soon as the data makes it possible.
Senator Shaheen. Yes, he has said that. I appreciate that.
Dr. Collins. We work very closely with FDA under his
leadership. And some of the things that we can do in terms of
providing that data is a part of that partnership that we are
pushing pretty hard right now.
Senator Shaheen. Well, thank you. Thank you all very much
for the great work that you are doing.
SOCIAL MEDIA AND SOCIALIZATION
Senator Blunt. Dr. Koroshetz, do you have anybody looking
at the socialization challenges of the constant exposure to
social media or the screens as something--the impact that that
may have on adolescents and others?
Dr. Koroshetz. So certainly social media is taking over our
country, and the consequences, whether they are pros or cons,
are still yet to be determined.
I think at NIH there are a lot of grantees that are
actually using social media to advance health research. I think
it would probably be the National Institute of Mental Health,
which is looking at the effects on adolescents. But Dr. Volkow
can mention a really innovative project which will look at this
and other exposures on the development of children that she has
just recently--well, almost half finished I guess.
Senator Blunt. I had a 50-50 shot there I thought.
[Laughter.]
Senator Blunt. And I missed it.
Dr. Volkow. For us, it is important because drug taking and
experimentation appears in adolescents, and it is a very social
behavior. And many times it follows peer pressure. And one of
the things that we have actually tried to understand is how the
dramatic changes that have happened in the way that teenagers
are interacting with one another may be influencing their
behaviors, including drug taking.
But most importantly, our brains are very neuroplastic and
they are developing during childhood and adolescence to
maximize your ability to respond to your environment. So we are
interested to know if you as an adolescent or as a child get
exposed massively to the social communication as opposed to the
one-to-one, how does that influence the development of the
brain.
So in September of 2016, we started a study with many of
our partners at the NIH called the ABCD, Adolescent Brain
Cognitive Development, where we are aiming to recruit 10,000
children. We have already recruited 9,500, and we will be
finishing in September. But to monitor them on the next 10
years to actually do brain imaging, characterize them
cognitively, characterize them socially, and measure how
exposure to social media ultimately influences the development
of the brain. So this is probably the most notable study that
we have because it will allow us to understand how this very
dramatic change on how people are interacting with one another
may influence the brain.
We also have research to understand how social media is
used to actually change the perspectives of teenagers with
respect to getting exposed to drugs, the likelihood that they
will take a drug when they see it in social media. So the
vaping device and the electronic cigarettes, to what extent
they are being frequently mentioned in social media are
influencing the probability that a teenager will use them. And
the same thing with marijuana and the same thing with alcohol.
So this is a completely new world for all of us, and we do
not actually, as of now, have an understanding about how it is
going to influence the human brain and behavior.
Senator Blunt. Thank you.
Senator Moran.
Senator Moran. Chairman, thank you. I am glad the meeting
is still going. I do not know that you are pleased with my
arrival.
[Laughter.]
Senator Moran. But I am honored to be here. Thank you.
Senator Blunt. I am always pleased with your arrival.
Senator Moran. Thank you, Chairman.
BIOMARKERS AND ALZHEIMER'S DISEASE
Dr. Hodes, I am not exactly sure what has been asked and
answered, but I want to pursue a couple of concepts that are
now developing in regard to Alzheimer's.
We have talked about detection and the efforts to use
biomarkers to identify someone who is at risk or has
Alzheimer's before they begin showing symptoms. The National
Institute on Aging just coordinated to propose a biological
construct which looks at the use of measurable changes in the
brain to better understand the earliest biological signs that
lead to symptoms.
How will this new framework help to drive research forward?
Does it represent a new understanding of the beginning of the
disease?
Dr. Hodes. Thank you.
The importance of being able to identify the changes that
accompany Alzheimer's disease and related dementias early, as
you have emphasized, is critical where we think that the best
opportunity to intervene at an early point and be able to track
success or failure of interventions by measuring biomarkers is
going to be absolutely critical.
The definition that you refer to is a publication which
suggested that for the pathologic definition of Alzheimer's
disease, based on plaques, tangles, and neurodegeneration,
there is a set of biomarkers that have standardized, would
allow us to assess across studies both longitudinal studies and
clinical trials, and in doing so, rigorously harmonize the
results of multiple efforts, so more quickly understand which
biomarkers are best predictive of disease and importantly,
predictive of a response to intervention to treatment or not.
So the studies that Senator Blunt referred to at Wash U are
among those. Right now, the biomarkers that are most accessible
and most widely used are either imaging, which works extremely
well but is cumbersome and expensive, or cerebrospinal fluid
analyses which works. But the goal of many now is to establish
so-called fluid biomarkers that can take the advantage of blood
and serum and identify either a single molecule or a pattern of
molecules that will allow us to screen many people, more than
we currently can through longitudinal studies and through
interventions.
Senator Moran. Doctor, thank you.
RETURN ON INVESTMENT IN BIOMEDICAL RESEARCH
Let me address this question to Dr. Collins. With the
leadership of Senator Blunt and others, we have had success in
large part, I would say, because you all have made a case for
additional resources within each of your institutes in which
the public good is demonstrated and the advancements that are
being made are sufficient for American people to feel
comfortable that progress is happening and that we are on the
cusp of developments that will make a difference in their
lives.
In the last year since you were here, Dr. Collins, in this
setting, what can I tell my constituents that has transpired to
reassure them that their tax dollars are being wisely spent? I
sometimes head down the track in a town hall meeting explaining
that there are things that we should spend no money on, things
we should reduce spending on, and there are things we should
spend more money on. And by the time I say that sentence, I am
wondering what my constituents are thinking about a Senator
from their State who is interested in spending more money on
anything. Then I use NIH as the example.
And one of the things that we have been able to do in this
subcommittee and the Senate is to prioritize our spending. So
it is making decisions about where to spend more money, not
just always the thing that I think many Kansans might think
happens around here, just spending more money on everything.
So, Dr. Collins, give me the town hall description of how
successful our spending has been in the year since we last met.
Dr. Collins. I love to give that description. Thank you for
the opportunity.
One thing that I would say is maybe the most important
discovery that happened in the last year is one we do not know
about yet because it was a basic science discovery that sort of
seemed at the time interesting, but we did not realize until
maybe a year or 2 from now just how profound it might be. We
talked about CRISPR Cas earlier. When that was discovered,
nobody had it on their list of the big deal from that year.
Another big discovery that probably we could mention for
anybody across this table would be something that has just
happened in the more therapeutic applications. In my opening
statement, I told the story of a little boy who should not be
alive who is walking around and hanging on the monkey bars
after being diagnosed with spinal muscular atrophy, a fatal
disease, and which with gene therapy now appears to have had a
dramatic response.
I could say, well, let us talk about drug abuse. Just
yesterday, approval by the FDA of lofexidine, the first non-
opioid way to help people withdraw from opioids, which is an
effort that NIDA and their colleagues had put together with
industry.
With cancer, the advances in cancer immunotherapy, which
was already pretty good stuff a year ago--oh, my gosh, it has
gotten so much more exciting now with the additional advances,
as Ned could no doubt tell you.
In terms of neurological diseases and advances in aging,
some of the basic science of aging has also had some
interesting findings in the last year about the normal process,
not just when it goes awry.
And certainly Dr. Fauci would say, well, goodness, where
were we a year ago in terms of Zika and Ebola and where are we
now when it comes to such things as a vaccine for the flu, a
vaccine for HIV, and maybe also ways to deal with that
antimicrobial resistance problem, which have come a long way in
that last year.
So my town hall speech has already gone on too long, but I
think you get the sense there is a long list of things we could
point to in just this last year.
And in case anybody thinks, well, that is fine but is it
really worth the money, it is also the greatest return on
investment of anything that the government spends money on,
$8.38 of return in 5 years from every dollar that you all
allocate to NIH because of what happens in terms of its
economic impact.
Senator Moran. You do, Dr. Collins, what I do in my town
hall meetings in wrapping up and concluding and then I have
another few paragraphs as well.
Dr. Collins. Guilty.
Senator Moran. But you have a great story to tell and I
appreciate you reminding us of those successes. Thank you.
Senator Blunt. Thank you, Dr. Collins and the Institute
directors with you today.
ADDITIONAL COMMITTEE QUESTIONS
The record will stay open for 1 week for additional
questions.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted to Francis S. Collins, M.D., Ph.D.
Questions Submitted by Senator Roy Blunt
personalized medicine
Question. Dr. Collins, over the past 3 years, this Subcommittee has
provided $650 million in funding for personalized medicine initiatives,
including the recently launched ``All of Us'' program. At the same
time, the National Human Genome Research Institute has continued other
important genomics research efforts. As the NIH advances the ``All of
Us'' program, which is a large personalized medicine initiative, how
are you ensuring that you continue to leverage and support the genomics
expertise and facilities currently in place across the country?
Answer. The NIH thanks the Subcommittee for its support of
personalized medicine initiatives overall, and for its support of the
All of Us Research Program in particular. The field of precision
medicine is a major area of growth across the U.S., and the All of Us
Research Program will dramatically advance the fields of personalized
medicine and precision health through integrating a wide variety of
environmental, behavioral, and biological information at an
unprecedented scale. The program launched nationally on May 6, 2018,
after establishing a major consortium of academic researcher
institutions, healthcare provider organizations, technology experts,
community partners, and participants. The program leveraged the
expertise of the genomics community through the Genomics Working Group
of the All of Us Research Program Advisory Panel which issued a report
in December 2017.\1\ This Working Group included expertise from
academia, industry, and NIH, including the National Human Genome
Research Institute. The report provides information on the pros and
cons of different approaches and options for corresponding
implementation plans, and encompasses effective strategies to generate,
analyze, and manage genomic data at the scale of All of Us. The program
recently issued a funding announcement for Genome Centers to generate
genotype and whole genome sequence data from participants' biosamples.
The program anticipates funding up to two Genome Center awards in
fiscal year 2018, with analyses to begin this fall with a goal of
ramping up to 200,000 genotypes and whole genome sequences annually.
This is a scale only feasible because of the outstanding achievements
of the U.S. genomics research community. The program has been able to
make major advances in its genomics approach not only through the
world-class genomics expertise in its consortium and Advisory Panel,
but also through the on-going interactions of its senior leadership
with the broader community through frequent participation in events and
workshops held by organizations across the country, as well as its
strong relationships with Institutes and Centers across NIH, including
leveraging the expertise within the National Human Genome Research
Institute.
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\1\ Considerations Toward a Comprehensive Genomics Strategy.
Available at: https://allofus.nih.gov/sites/default/files/
gwg_final_report.pdf.
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opioids vaccine
Question. The fiscal year 2019 budget proposes a coordinated
strategy with two primary aims to combat the opioid epidemic in our
country. One of those aims is to accelerate the development of new,
non-addictive pain therapies with the goal of making a wide-range of
therapeutics accessible to those who need them as quickly as possible.
Can you describe what types of non-addictive pain therapies are
currently in the NIH research pipeline, and how quickly can these
therapies can be developed and distributed to the market?
Are there any vaccine candidates being considered?
Answer. NIH is particularly excited about the new Helping to End
Addiction Long-term (HEAL) Initiative. HEAL will bolster research
across NIH in an effort to improve the treatment of chronic pain by (1)
exploring biomarkers that predict the transition from acute to chronic
pain, (2) identifying new targets for treating chronic pain using
neurotechnologies developed through the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program,
and (3) building the evidence base on the effectiveness of nondrug and
integrated pain treatments. In addition, the Initiative will pursue
public-private partnerships to develop new non-addictive pain medicines
by sharing data on past and present research projects, and matching
researchers with a selection of potentially promising but abandoned
pharmaceutical industry compounds to explore their effectiveness for
the treatment of pain. Finally, NIH will develop a clinical trials
network for pain, allowing multiple new and repurposed compounds to be
tested for effectiveness simultaneously.
The Initiative will tap into the expertise of the NIH Pain
Consortium,\2\ a trans-NIH consortium made up of NIH institutes that
fund pain research. Funded projects are investigating the entire range
of therapeutics development- from preclinical safety and efficacy
testing and early phase human trials to health services research.
Currently, the consortium members are working on developing more
effective and less addictive treatments for chronic pain. For example,
a study using a molecular imaging technology called x-ray
crystallography has revealed the molecular structure of the receptors
that mediate drugs' effects; this information is already leading to the
development of safer medications to treat pain.
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\2\ https://www.painconsortium.nih.gov/About/Members.
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NIH-funded research is developing medications with properties that
affect opioid receptors to produce analgesia with reduced risk of
addiction and misuse. Some of these exhibit novel properties as a
result of their combined activity at different opioid receptors (mu,
delta, and kappa). Compounds with combined activity at the mu and delta
receptors or at all three receptors can induce strong analgesia without
producing tolerance or dependence in animal models. In addition, the
discovery of adjunct medications that can be combined with opioids to
reduce the needed dose has the potential to result in lower potential
for dependence and addiction. Innovative methods are being explored for
drug delivery to increase specificity and efficacy and to reduce
analgesic side effects, as well as modified formulations to enhance
delivery.
NIH supports an initiative called the Blueprint Neurotherapeutics
Program for small molecule drug discovery and development. For example,
NINDS funds studies through this program that aim to develop non-
addictive kappa opioid receptor antagonists for migraine and a safe,
non-opioid analgesic that can be taken orally to reduce diabetic nerve
pain.
NIDA continues to fund development of anti-opioid vaccines capable
of generating an immune response that would prevent opioids from
entering the brain, thereby blocking both their euphoric effects and
their dangerous respiratory depressant properties. Current projects
include:
--Optimization and preclinical testing of a practical heroin-HIV
vaccine \3\
---------------------------------------------------------------------------
\3\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9110917&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=20&csb=default&cs=ASC&pball=.
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--Preclinical development of vaccines against heroin, oxycodone,
hydrocodone, and fentanyl \4,5,6,7\
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\4\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9444613&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=11&csb=default&cs=ASC&pball=.
\5\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9330137&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=26&csb=default&cs=ASC&pball=.
\6\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9461410&icde=39707102.
\7\ Olson ME, Janda KD. Vaccines to combat the opioid crisis:
Vaccines that prevent opioids and other substances of abuse from
entering the brain could effectively treat addiction and abuse. EMBO
Rep. 2018 Jan;19(1):5-9.
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Results from preclinical models thus far have shown that these
vaccine candidates are capable of producing an immune response that
blocks opioid effects.32 While none have yet advanced to clinical
trials, the heroin vaccine candidate developed by the Walter Reed Army
Institute of Research in collaboration with NIDA has been in-licensed
by Opiant Pharmaceuticals for further development.\8\
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\8\ https://www.opiant.com/pipeline/heroin-vaccine/.
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______
Questions Submitted by Senator Lamar Alexander
fda enforcement actions
Question. In April 2018, at my request, the Federation of State
Medical Boards issued a report on regenerative and stem cell therapy
practices. The report included information on the regulatory history of
regenerative medicine and recommendations for state medical boards.
The report described how ``some clinics . . . are engaged in the
provision of treatment modalities that lack evidence . . . or use what
have been described as `tokens of scientific legitimacy' to lend
credence to treatments offered or the quality of a clinic and its
associated professionals.'' According to the report, these tokens
include ``patient or celebrity testimonials and endorsements, clinician
affiliations or memberships in academic or professional societies, and
registrations in clinical trials, among others.''
Last week, the Food & Drug Administration (FDA) filed two
complaints in Federal court seeking permanent injunctions to stop two
stem cell clinics from marketing products without FDA approval. The
National Institutes of Health runs clinicaltrials.gov and includes a
disclaimer that not all studies on the website have been evaluated by
the U.S. Federal Government.
What steps can NIH take to make sure patients visiting
clinicaltrials.gov are aware of any enforcement or regulatory actions
taken by FDA? Is there any other legislative action Congress can take
to help NIH address this issue?
Answer. Research participant safety is of utmost importance to NIH.
The ClinicalTrials.gov website currently includes information to help
potential participants learn more about the potential benefits and
risks of participating in a trial and always recommends talking with
trusted healthcare professional before starting a trial. NIH is taking
several steps to increase transparency and clarify information on
clinicaltrials.gov including:
--Adding more prominent disclaimers explaining that listing a study
does not mean it has been evaluated by the U.S. Federal
Government
--Adding a question about whether the product being tested is under
FDA oversight
--Continuing to evaluate and improve other resources to help
potential participants identify questions they may want to
consider when deciding whether to participate in research and
encouraging them to consult with their healthcare provider on
such decisions
NIH is committed to continuing to improve these resources to help
ensure people understand important issues to consider before
participating in a clinical trial and working closely with FDA to
determine best strategies for educating the public on FDA activities
and providing information on FDA oversight of clinical research.
NIH does not believe additional legislative action is needed at
this time. As noted, NIH is committed to working with FDA to identify
ways to improve communication about FDA actions, including enforcement
or regulatory actions that may be relevant to information on
ClinicalTrials.gov.
______
Questions Submitted by Senator James Lankford
stem cells
Question. As you know, despite years of research and use of tax
dollars, there is currently no validated, successful patient treatment
from embryonic stem cells. Additionally, alternatives to embryonic stem
cell research exist. In 2012, the Nobel Prize in Physiology or Medicine
was awarded to two researchers for their discovery of induced
pluripotent stem (iPS) cells, which mimic the qualities of embryonic
stem cells but do not use embryos in any way. Similarly, NIH has had
great success in treating and curing more than 70 diseases using adult
stems cells and iPS cells.
Despite that, in 2009, President Obama issued E.O. 13505, which
gave HHS and NIH authority to use human stem cells, including embryonic
stem cells, in research. E.O. 13505 revoked a previous EO from
President Bush that outlined ethical principles for stem cell research.
Because the research has yet to yield positive results, have you
considered a plan to stop embryonic stem cell research or limit such
research if the cell line is not already included on the NIH Human
Embryonic Stem Cell Registry?
Answer. NIH funds a range of stem cell research, using human and
non-human adult stem cells, induced pluripotent stem cells (iPSCs), and
since 2001, human embryonic stem cells (hESCs). NIH stem cell research
must be conducted in accordance with the NIH Guidelines for Human Stem
Cell Research, which detail stringent criteria for voluntary informed
consent by which the NIH Director determines the eligibility for use of
specific hESC lines in NIH-funded research. NIH-funded stem cell
research is exploring applications in regenerative medicine, drug
screening, and the study of the molecular pathways in biological
development and human disease. Projects studying how undifferentiated
stem cells become specialized cells with specific functions in the body
have produced knowledge that is essential for developing regenerative
medicine treatments. For example, NIH-supported researchers have
established protocols for development of specific cell type from hESCs:
e.g., pancreatic beta cells (which were effective in a mouse type 1
diabetes model), dopaminergic neurons (tested in a mouse Parkinson's
model), liver hepatocytes, and cardiomyocytes. NIH-supported
researchers are using hESCs to study cells with particular diseases,
such as neurons with a Niemann Pick type C1 mutation, which causes a
progressive neurological disease. NIH-supported researchers have also
used hESCs to develop organoids, including intestine, colon, and
kidney, to model organ-specific diseases.
Several investigational cell therapies developed from hESCs are
currently in FDA-regulated clinical trials for spinal cord injury,
macular degeneration, and type 1 diabetes. The first trial using an
investigational cell therapy from iPSCs is taking place in Japan for
macular degeneration; an NIH intramural investigator also plans to file
an IND this year for using a product from human iPSCs for macular
degeneration.
One can never be certain where the next cure or treatment will come
from, and maximizing researchers' access to diverse tools, methods, and
experimental systems is critical for enhancing the likelihood of
success in advancing the NIH mission. Therefore NIH will continue to
support highly meritorious research with NIH-approved hESCs.
______
Questions Submitted by Senator Patty Murray
big data
Question. The Committee directed NIH in the fiscal year 2017
omnibus to develop a strategic plan to address these issues, which was
recently released. Now that NIH has a plan, what's the timeline for its
implementation?
Answer. The NIH Strategic Plan for Data Science \9\ (subsequently
referred to as ``the Plan'') describes NIH's Overarching Goals,
Strategic Objectives, and Implementation Tactics for modernizing the
NIH-funded biomedical data-resource ecosystem. The Plan was developed
by the NIH Scientific Data Council, and reflects input from HHS,
scientists, policymakers, scientific and professional societies, the
general public, and leadership and staff from NIH and its constituent
Institutes and Centers.
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\9\ https://datascience.nih.gov/sites/default/files/
NIH_Strategic_Plan_for_Data_Science_ Final_508.pdf.
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NIH is mapping out the Plan's implementation and expects activities
will intensify over the next year. Implementation of key areas are
already underway, including the NIH Data Commons Pilot and NIH's cloud-
marketplace initiative. In addition, targeted training and career
development opportunities to enhance the biomedical data science
workforce are in preparation, such as data science fellowships. NIH
also is in the process of aligning data science-related funding
opportunity announcements to help ensure support for databases,
knowledgebases, and tools development are addressed in the most
efficient and cost-effective way. Other Plan goals, such as developing
data standards, are in early discussion and will require additional
research, planning, and interaction with the community to determine the
scope and context of future guidance.
As NIH moves forward, the Scientific Data Council, a sub-committee
of the NIH Steering Committee composed of Institute and Center
directors and deputy directors, as well as key NIH subject matter
experts, will have an active role in overseeing execution of the Plan.
The NIH Chief Data Strategist, currently being recruited, will
collaborate closely with the Scientific Data Council, Data Science
Policy Council, and other key NIH stakeholders to lead implementation
of the NIH Strategic Plan for Data Science. We anticipate that full
implementation plans will be in place within the next year, with a
majority of Implementation Tactics launched in the same timeframe.
Question. Given the scale of this undertaking, what does NIH see as
the biggest potential barriers to achieving the plan's vision?
Answer. During development of the Plan, a number of data science
challenges for NIH were characterized (see pages 4-5 of the Plan). Some
of the most pressing barriers to achieving the Plan's vision are
summarized below:
--The exponential expansion of data quantity and complexity is
increasing costs of data infrastructure, storage and
management, including data access, integrity, and privacy
considerations.
--The siloed nature of the current data ecosystem is a challenge for
data integration, standardization, and interoperability.
Implementation of FAIR (Findable, Accessible, Interoperable,
and Reusable) principles will enhance stewardship by improving
the sustainability of data resources supported through NIH
investments.
--The funding mechanisms currently used by NIH incentivize tool
development and primary analysis of data but are less
compatible with data resource maintenance and sharing. A key
objective of the Plan is to tailor the funding mechanisms to
the desired outcomes for NIH-supported data resources.
--Novel bridges between academic research institutions, NIH, and the
technology industry are needed to enhance development and
dissemination of efficient and effective data resources and
analytical tools. Flexible funding strategies, including
expanded use of Other Transaction Authority, would assist in
building these bridges.
--A new generation of trained biomedical data science experts will be
essential to bringing the vision elaborated in the Plan to
fruition. However, the discrepancy in pay scales between the
technology industry on the one hand and academics and
government on the other presents a challenge for recruiting and
retaining talent in data science for biomedical research.
As noted in the response to Question 1, NIH is working to overcome
these challenges and implementing new programs and initiatives to
address these barriers.
Question. Are there cases where researchers are reluctant or face
challenges sharing their data, or they delay releasing that data for
years until they've published their findings? What do you do in these
situations? Do you see an opportunity to revise policy to address this
issue?
Answer. The current culture of data sharing is moving towards
openness and transparency. Consistent with these efforts, the NIH
encourages and expects the sharing of data from supported research
through policies and practices. For example, under the NIH Genomic Data
Sharing \10\ (GDS) Policy, investigators seeking NIH funding for
genomics projects are expected to submit a Genomic Data Sharing Plan as
part of the application for funding, which includes the data submission
and release timeline. NIH recognizes that different types of genomic
data undergo different levels of processing, and the expectations for
data submission and data release are based on those levels. However, in
general, data are released to NIH-designated data repositories for
access by other investigators no later than 6 months after the initial
data submission begins, or at the time of acceptance of the first
publication, whichever occurs first, without restrictions on
publication or other dissemination.
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\10\ https://osp.od.nih.gov/wp-content/uploads/NIH_GDS_Policy.pdf.
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In some cases, restrictions or limitations on the data may exist
that prevent broadly sharing the data. For example, based on the
informed consent provided by the research participants, there may be
limits on who may use the data or for what purposes the data may be
used. Other restrictions may stem from legal issues or limitations
placed on downstream data use by the study populations who participated
in the research, for example tribal populations. In some cases, it may
not be appropriate for researchers to share genomic data. In such
cases, NIH may grant an exception to the typical data sharing
expectations and allow for an alternative genomic data sharing plan. An
example of an alternative data sharing plan might be the sharing of
summary-level information only. Summary-level information is study data
that has been aggregated across the study population (as opposed to
sharing data at the level of each individual study participant).
NIH recognizes that investigators often do not want to share their
data until they have had the opportunity to publish their own findings.
However, at the same time, NIH has a strong interest in increasing the
impact and rigor of research studies it funds. Therefore, the NIH
officially announced in March 2017 \11\ that researchers may cite their
interim research products and claim them as products of NIH funding in
order to increase the impact and rigor of a research study. Interim
research products can be cited anywhere other research products are
cited in the NIH grant application. An example of such a product is a
preprint publication, which is a complete and public draft of a
scientific document that typically has not yet undergone peer review.
NIH encourages investigators to use interim research products, such as
preprints, to speed dissemination and enhance the rigor of the
research.
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\11\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
050.html.
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NIH also has addressed specific data sharing challenges through
targeted policy development. For example, the NIH Policy on the
Dissemination of NIH-Funded Clinical Trial Information \12\ promotes
broad dissemination of summary-level results from NIH-funded clinical
trials by establishing the expectation that researchers will register
the trials in and submit the results information to ClinicalTrials.gov.
Under this Policy, NIH expects the results information to be submitted
no later than 1 year after the trial's primary completion date.
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\12\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-
149.html.
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Another example policy is the NIH 2003 Data Sharing Policy, which
expects that investigators submitting a research application requesting
$500,000 or more of direct costs in any single year include a plan for
sharing their final research data or state why they cannot. In this
Policy, NIH expects the timely release and sharing of data to be no
later than the acceptance for publication of the main findings from the
final dataset. The specific time will be influenced by the nature of
the data collected. However, despite guidance on implementation, there
is not a structured format for the plans, and policy compliance has
been inconsistent.
The NIH is evaluating its existing data sharing policies with an
eye on furthering the current culture of data sharing. From November
2016 to January 2017, NIH sought public comment on how scientific data
generated from NIH-funded research should be managed, and to the
fullest extent possible, made publicly available through a Request for
Information: Strategies for NIH Data Management, Sharing, and
Citation.\13\ This public comment solicitation also specifically asked
the public for the greatest barriers and challenges associated with
data sharing. Input \14\ from the public, which included universities,
associations, companies, and publishers, noted specific barriers to
data sharing, such as establishing a culture of sharing that would
appropriately incentivize and encourage data sharing, the need for
community-based standards for long-term preservation or sustainability
of data, data preparation and submission, and the costs and resources
associated with data management and sharing, e.g., data curation,
personnel, infrastructure. Suggestions to resolve some of these
barriers included providing incentives (e.g., citation of datasets and
attribution for sharing data) to help to change the culture of data
sharing. Respondents felt that the use of community-based standards, as
well as the ability to budget for data management and sharing in NIH
funding applications and proposals, would help mitigate some of the
resource barriers associated with data management and sharing.
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\13\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
015.html.
\14\ https://osp.od.nih.gov/wp-content/uploads/
Public_Comments_Data_Managment_
Sharing_ Citation.pdf.
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The NIH intends to continue ongoing outreach and community
engagement on existing policies and practices to refine the
implementation of existing policies and to develop new policies when
warranted to achieve the goal of encouraging a culture of data sharing.
Question. Given the scale of investments Congress is making in
Alzheimer's disease, the data we are generating may be used to
accelerate major scientific breakthroughs. Has NIA looked at its
existing data sharing policies to determine how they are working? Do we
know what percentage of grant recipients fulfil their data sharing
obligations at the end of their projects?
Answer. NIA does not currently keep an overall tally of compliance
with data-sharing plans. With that said, a number of NIA initiatives
related to Alzheimer's disease (AD) and related dementias have data-
sharing plans built in, and in those situations sharing of data is used
as a criterion for continued funding from year to year. Major programs
that operate under these terms include the Accelerating Medicines
Partnership for AD initiative (AMP-AD); the Model Organism Development
and Evaluation for Late-Onset AD (MODEL-AD) initiative; and the
Alzheimer's Disease Neuroimaging Initiative (ADNI). We are currently
exploring the feasibility of and possible mechanisms for tracking
compliance more globally across research project grants.
Question. The committee has prioritized a biomedical research
ecosystem that is amplified by sustainable, interoperable, accessible,
and usable research data, including Alzheimer's research data. How do
you ensure that data sharing is prioritized at the start of the NIH
grant process? Is there a process to make sure researchers are
preparing to share their data from the start? What are the most
frequent comments you hear from researchers about why they can't share
their data?
Answer. Effective data sharing relies upon appropriate
identification, adoption, and crediting of good data management and
sharing practices. Thus, NIH encourages data sharing consistent with
the FAIR (Findable, Accessible, Interoperable, Re-usable) data
principles. For example, in order to facilitate access by qualified
investigators to genomic data for the study of Alzheimer's disease, NIH
funded the creation of The National Institute on Aging Genetics of
Alzheimer's Disease Data Storage Site \15\ (NIAGADS), currently
maintained at the University of Pennsylvania. NIAGADS along with other
National Institute for Aging (NIA) approved sites make genomic data and
associated phenotypic data available to qualified investigators in the
scientific community for secondary analysis in accordance with
standards established by the NIA and the NIH Genomic Data Sharing (GDS)
Policy.
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\15\ https://www.niagads.org/.
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NIH policies on data sharing typically expect that a plan is
submitted with a funding application, indicating for example what data
will be shared, and how, when, and where it is expected to be shared.
These policy expectations suggest that researchers and institutions
should be thinking through these issues during the planning phases of
their applications.
For example, the implementation of the NIH GDS Policy sets the
expectation that applications for funding that propose the generation
of large-scale human or non-human genomic data include a Genomic Data
Sharing Plan in the Resource Sharing Plan section of the grant
application. Applicants are expected to describe the data type(s) and
repository for data deposition. Applicants proposing to generate human
data should also provide information addressing data submission and
release timelines, Institutional Review Board assurance of the genomic
data sharing plan, the appropriate uses of the data, and if
appropriate, a request for a data sharing exception, prior to award.
Those proposing to generate non-human data also need to address the
data submission and release timelines prior to award. The Genomic Data
Sharing Plan is approved by the funding NIH Institute or Center. In
addition, for the NIH Policy on the Dissemination of NIH-Funded
Clinical Trial Information, applicants proposing to conduct clinical
trials must submit a plan for the dissemination of the trial
information.
NIH continues to discuss, with public input, the value of data
sharing and what information is most helpful to include in a plan for
managing and sharing data that ensures shared data are findable,
accessible, interoperable, and reusable (the FAIR principles).\16\ NIH
and the National Science Foundation held a joint workshop on the Value
of Data Sharing in October 2017.\17\ Some consistent themes included in
plans for data management and sharing among various Federal funders
include describing the types of data to be shared; what tools may be
needed to analyze shared data; what standards apply to the collected
data; how, where, and for how long data will be available; and whether
any barriers to data sharing exist.
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\16\ https://www.force11.org/group/fairgroup/fairprinciples.
\17\ https://osp.od.nih.gov/2017/12/18/data-destiny-debrief-nih-
nsf-workshop/.
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Through responses to the Request for Information: Strategies for
NIH Data Management, Sharing, and Citation,\18\ the public indicated
that barriers to data sharing include the resources and repositories
needed to manage and share data, the need for data standards to ensure
that data is reusable and reproducible, and incentives. NIH continues
to gauge ways to address these barriers in the process of evaluating
its existing data sharing policies and practices.
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\18\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-
015.html.
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alzheimer's vaccine
Question. In 2000, the NIH set aside $50 million over 5 years to
support research on new ways to treat Alzheimer's disease with a
special emphasis on the development of a vaccine to prevent the
disease. While the first generation of Alzheimer's vaccines were
developed shortly thereafter, in 2008 these studies were halted due to
patient safety concerns. Can you describe what the NIH has done in
recent years--or plans to do in the future--to support development of a
vaccine to treat the more than 5 million Americans currently living
with Alzheimer's?
With the most recent omnibus funding bill bringing total 2018
funding to $1.8 billion, does the NIH plan to fund research for an
Alzheimer's vaccine in fiscal year 2019?
The Alzheimer's Association has made a commitment to prevent or
effectively treat Alzheimer's disease by 2025. We're less than 6 years
away from that target, and in spite of continued Congressional
increases to the NIH budget, safe and effective treatments are still
out of reach. Can you describe the current research being done, and if
you believe there are any gaps in research that could be addressed in
fiscal year 2019?
Vaccines have been one of the most effective and impactful
medicines in history. Is vaccine research a priority for NIH's
Alzheimer's research goals, and if not, why?
Answer. Vaccination is one of many treatment modalities currently
under study for both prevention and treatment of Alzheimer's disease
and related dementias (AD/ADRD). For example, the Alzheimer's
Prevention Initiative Autosomal Dominant Alzheimer's Disease (API-ADAD)
study is exploring ``preventive immunotherapy'' among members of an
extended Colombian family that carries a genetic mutation placing many
members at greatly increased risk of developing the disease. Another
study, the Dominantly Inherited Alzheimer's Network (DIAN) trial,
evaluates the safety, tolerability, and effectiveness of several drugs,
including two vaccines, and will determine if they can prevent, delay,
or even reverse Alzheimer's disease changes in the brain. NIA also
supports a large cooperative agreement to complete preclinical safety
and efficacy testing for AV-1959D, a cutting-edge DNA vaccine. DNA
vaccines use pieces of DNA from specific pathogenic proteins to
stimulate an immune response and offer potential technical and safety
advantages over conventional protein/adjuvant vaccines. All of these
studies remain important priorities within our AD/ADRD portfolio and
will remain active in fiscal year 2019.
With respect to current AD/ADRD research and gaps, NIA has
leveraged the extraordinary influx of funding directed at these
diseases to build a series of bold and innovative research programs,
infrastructure, and new partnerships that are enabling some of the
Nation's leading scientists to tackle the problem of AD/ADRD at an
unprecedented scale and pace. High-priority research and infrastructure
programs that are currently underway include:
--Alzheimer's Clinical Trial Consortium (ACTC), to accelerate and
expand trials of AD/ADRD therapies;
--Resilience-AD, a new program bringing together experts from
multiple disciplines to understand why some high-risk
individuals remain dementia free;
--Molecular Mechanisms of the Vascular Etiology of Alzheimer's
Disease (M\2\OVE-AD) Initiative, exploring how metabolic and
vascular risk factors such influence brain aging and AD
pathology and identifying blood-based markers of the disease;
--Alzheimer's Biomarker Consortium--Down Syndrome (ABC-DS), in which
researchers use biomarkers to track disease progression in
people with DS, a uniquely vulnerable population at high risk
for developing AD;
--The Model Organism Development and Evaluation for Late-onset AD
(MODEL-AD) project to develop better animal models of late-
onset AD;
--Approximately 140 active clinical trials of interventions to
prevent, treat, or manage symptoms of AD/ADRD and to enhance
caregiver well-being;
--Development of new therapeutics, including some that target
molecules other than beta-amyloid; and
--Harnessing the power of big data to identify existing drugs or
combinations currently used to treat other conditions that
could be effective for the treatment of AD/ADRD.
Gaps continue to exist around development of caregiver support
interventions; implementation of a national recruitment strategy that
ensures inclusion of diverse populations in AD/ADRD research;
understanding gene-environment interactions that increase risk or
confer resilience against AD/ADRD; infrastructure development,
including big data infrastructure; workforce training across the
spectrum of research; and harmonization and distribution of data from
large datasets. NIH considers each of these a priority area for fiscal
year 2019, and NIA has begun to implement strategies to fill these
gaps, with a number of relevant Funding Opportunity Announcements
issued or approved in concept by the National Advisory Council on
Aging.
next generation researchers
Question. Ensuring a strong pipeline of the best and brightest U.S.
scientists is of paramount importance. To this end, the Fred Hutchinson
Cancer Research Center in Seattle participates in the Coalition for
Next Generation Life Science, which seeks to increase transparency of
life science career prospects by providing new data and information to
help students make informed choices about their science careers. What
steps is the NIH taking to ensure young and mid-career investigators
remain engaged in academic research?
The National Academies of Sciences, Engineering, and Medicine
released a report in April on the next generation of biomedical and
behavioral researchers and recommended that NIH increase by five-fold
the number of individual research fellowship (F) awards and career
development (K) awards available to support postdoctoral researchers.
It also recommended that NIH create a Next Generation Researcher
Innovation Fund to support innovative pilot projects that seek to
improve and accelerate transitions into independent careers. Which of
these recommendations or others in the report, do you anticipate NIH
adopting or considering?
Answer. NIH is currently assessing the recommendations of the
National Academies Next Generation Researchers Initiative (NGRI)
committee, convened in early 2017, to study and recommend solutions to
any barriers that may extend periods of training, time to independence,
or impede sustained success in research. As you noted, a final report
titled, ``Next Generation of Biomedical and Behavioral Sciences
Researchers: Breaking Through'' was released in April 2018. As these
recommendations are being considered, NIH is also awaiting a related
report from a working group of the Advisory Committee to the Director
focused on the next generation of researchers, expected in June 2018.
NIH expects to incorporate guidance from both groups to prioritize
further actions to bolster the careers of early-stage investigators.
Within the NIH Office of the Director, the Office of Extramural
Research's Division of Biomedical Research Workforce conducts regular
evaluations of outcomes of NIH training and career development
programs. These activities help us assess strategies that are
successful in promoting continued engagement in academic research. NIH
has, and continues to grow, an evidence-base to support positive
impacts of individual postdoctoral fellowship (F) awards and individual
career development (K) awards on subsequent, sustained research
careers. NIH is currently considering how to optimize the benefits and
outcomes of these awards for early stage researchers.
NIH appreciates the recommendation to increase the number of F and
K awards. NIH will carefully consider the cost to benefit ratio of
increasing their numbers as well as other options, such as enhancing
stipends, salary, or research support offered with each award, to
maximize their impact on successful research careers.
In addition, as we consider the National Academies' and Advisory
Committee to the Director Working Group's recommendations, we will work
with the NIH Institutes and Centers to consider expansion of other
programs that have been particularly successful for early stage
investigators, including:
--NIH Director's New Innovator Award Program (DP2), which supports
early-stage investigators of exceptional creativity who propose
bold and highly innovative new research approaches with the
potential to have a major impact on broad, important problems
in biomedical and behavioral research.
--The Maximizing Investigators' Research Award (R35) supports early-
stage investigators to enhance their ability to take on
ambitious scientific projects, spend time on research, and
reduce the time spent writing grant applications.
--The NIH Pathway to Independence Award (K99/R00) program to
facilitate a timely transition of outstanding postdoctoral
researchers to independent, tenure-track, or equivalent faculty
positions and help researchers to launch competitive,
independent research careers.
--The Director's Early Independence award (DP5), as part of the NIH
Common Fund's high-risk high reward initiative, aims to support
more bold and innovative research activities with the
opportunity for rapid progress. Specifically, this program
accelerates the entry of exceptional junior scientists into an
independent research career by forgoing the traditional post-
doctoral training period. These select investigators have
established a record of scientific innovation and research
productivity as well as demonstrated unusual leadership, drive,
and maturity,
--The High Priority, Short-Term Project/Bridge Awards (R56) supports
early-stage investigators by providing limited, interim
research support to gather additional data for revised grant
applications.
salary cap
Question. The Administration's fiscal year 2019 budget request
proposes limiting the percentage of an investigator's salary that can
be paid with grant funds at 90 percent of total salary. Like the fiscal
year 2018 proposal to cap facilities and administrative costs, limiting
salary support is proposed under the guise of identifying
``efficiencies.'' Congress firmly rejected the proposal to cap F&A in
the final fiscal year 2018 omnibus because these infrastructure costs
are integral to conducting successful research. Perhaps to an even
greater degree, researchers who develop ideas, articulate research
questions, design studies, and conduct experiments and clinical trials
are essential to quality research and the pursuit of life-saving
treatments and cures. Would NIH agree that if Federal support for
principal investigators' salaries is cut, in addition to resources
being redirected from other activities to cover salaries, wouldn't this
send a message to those interested in entering academic research that
they may not be fully supported?
Answer. Because Federal research funds are limited, reductions in
the NIH contributions to the salary of researchers on NIH grants leaves
more funds for additional scientists along with the equipment and
resources they need to carry out their critically important work. This
may also provide funds that may be used to fund additional grants.
NIH is aware of varying degrees of salary support for its funded
scientists. In some institutions, scientists are expected to seek
external grant funds to support most of their salaries. Other
institutions provide most, if not all, of the salary support.
Based on a NIH enumeration study,\19\ the NIH supports
approximately 313,049 full-time and part-time positions, or the
equivalent of 121,465 full-time employed individuals each year. We
believe that approximately half of these full-time researchers are
affected by the salary cap. Institutions may choose to increase
tuition, utilize funds from their endowments, or solicit state level
support to absorb some of the costs engendered by the salary cap. Some
stakeholders have voiced concern that stringent salary caps may lead to
disincentives for certain highly-skilled clinician scientists who may
be well-positioned to conduct the kind of science solicited by NIH. The
selective pressures on such individuals may lead to a lower number of
them willing to engage in NIH-funded research. The NIH is cognizant of
these potential effects, but in no way intends for the policies
included in the President's Budget to hinder the critically important
biomedical research funded by NIH.
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\19\ Pool, Lindsay R., et al. ``Size and characteristics of the
biomedical research workforce associated with U.S. National Institutes
of Health extramural grants.'' The FASEB Journal30.3 (2015): 1023-1036.
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national academy of medicine
Question. According to the 2015 National Academy of Medicine report
Improving Diagnosis in Healthcare, eliminating diagnostic errors is a
``moral, professional, and public health imperative.'' Are there steps
that NIH can take to invest in basic research on improving diagnosis in
medicine, consistent with the findings of the National Academy of
Medicine report? Given NIH's disease-specific institute missions, are
there structural barriers, either administrative or legislative, that
would need to be addressed for successful advancement of basic research
by NIH in improving diagnosis in medicine?
Answer. NIH invests in basic research on improving diagnosis in
medicine, primarily through the National Library of Medicine (NLM). Of
the approximately $30 million NLM expects to spend on extramural
research projects in fiscal year 2018, about 1/3 supports investigator-
initiated research projects in clinical/healthcare informatics and
data. NLM-funded researchers have examined safety-related issues such
as the unintended consequences of physician order entry, data mining of
clinical data repositories, and tools for inpatient monitoring using
evidence from the electronic health record (EHR). Current NLM research
projects which are consistent with the recommendations of the National
Academies study are: ways to monitor clinical workflow to detect
adverse events, workflow capture to improve trauma resuscitation
outcomes, terminology services to make orders consistent and reduce
avoidable CT imaging, extraction of typical and atypical disease
progression patterns from multi-site EHRs, and patient medical history
representation, extraction and inference from EHRs. NLM's intramural
research program also emphasizes analysis of large health data sets to
enable discoveries that can inform diagnosis. In addition, the
intramural research program supports work on health information/data
standards and text processing that can improve the consistency of the
terminology used in EHRs to support large scale analysis and extract
meaning from narrative text, such as clinical notes, to support
research on diagnosis. NLM's expanding portfolio of data science
research will emphasize needs of precision medicine initiatives and
organizations like OHDSI (Observational Health Data Sciences and
Informatics) to characterize completeness, assure accuracy, and
mitigate bias in large heterogeneous data sets. One challenging area is
the need for large data sets of personal health data from individuals
for fundamental research. Restrictions and concerns about access,
confidentiality, permissions and bias in the data remain a challenge
and are important areas for future research.
______
Questions Submitted by Senator Jack Reed
bioethical issues
Question. Gene editing research such as the NIH's Somatic Cell
Genomic Editing program holds the potential for curing diseases and
significantly improving lives; however, we will need to contend with
serious bioethical concerns as we continue to make advances in this
research. Can you explain how NIH is staying ahead of bioethical issues
as the research continues to progress? How is NIH coordinating these
efforts with other Federal agencies, both within and outside of HHS?
Answer. Gene editing technologies are powerful tools that enable a
broad range of applications, including investigating gene function,
developing better animal models to study specific human diseases, and
developing new strategies to reduce the spread of malaria and other
infectious diseases by vectors such as mosquitoes (through an
application called a gene drive). Gene editing technologies are also
already being used in clinical trials to potentially treat genetic or
acquired diseases, ranging from infectious diseases to cancer.
The bioethical issues associated with gene editing depend on the
specific application of the technology, that is, how the gene editing
technology is being used and for what purpose. Applications such as
somatic gene therapy, human germline modification, and gene drives to
eradicate disease all have different bioethical considerations. In many
cases, the bioethical concerns raised by these technologies are similar
to those first raised at the advent of recombinant DNA technology and
human gene therapy and are well explored and integrated into current
oversight structures. For instance, NIH supports gene therapy research,
including gene editing approaches, in somatic cells in humans. Somatic
cells are not involved in reproduction, so changes in somatic cells are
not inherited by subsequent generations. The well-established oversight
frameworks and FDA regulatory authority over human gene therapy trials
would apply to clinical research involving gene editing. In fact, gene
editing applications have already been in the clinic for several years
in trials involving different types of technologies targeting such
diseases as HIV infection, cancer, and several genetic disorders such
as Hemophilia B.
The potential use of gene editing to modify the human germline such
that changes would not only affect an individual, but subsequent
generations, has been a subject of ethical debate. NIH has participated
in multiple activities of the National Academies of Sciences,
Engineering, and Medicine (NASEM) focused on issues related to gene
editing. The 2017 NASEM report, Human Genome Editing: Science, Ethics,
and Governance,\20\ supported basic research and gene therapy in
somatic cells but recommended a cautious approach to heritable gene
editing in clinical studies.\21\ Given the ongoing concerns in this
space, NIH will not fund any use of gene editing technologies in human
embryos (NIH Director's statement, April 28, 2015).\22\ There are also
legislative and regulatory prohibitions including the ``Dickey-Wicker''
amendment attached to the annual appropriations bill for the Department
of Health and Human Services, which prohibits the use of NIH funds for
``(1) the creation of a human embryo or embryos for research purposes;
or (2) research in which a human embryo or embryos are destroyed,
discarded, or knowingly subjected to risk of injury or death greater
than that allowed for research under applicable Federal regulations.''
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\20\ https://www.nap.edu/catalog/24623/human-genome-editing-
science-ethics-and-governance.
\21\ https://www.nap.edu/catalog/24623/human-genome-editing-
science-ethics-and-governance.
\22\ https://www.nih.gov/about-nih/who-we-are/nih-director/
statements/statement-nih-funding-
research-using-gene-editing-technologies-human-embryos.
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Potential bioethical issues exist for gene drive technology, which
allows for the spread of desired traits through populations of
organisms at a faster rate than what typically occurs in nature. This
approach could potentially provide a means to address environmental or
public health problems (e.g., control of invasive species or vector-
borne infectious diseases like malaria), but there are potential
ethical concerns, especially related to possible effects on the
environment. To engage in a robust conversation and to address ethical,
scientific, and safety issues, NIH funded in part a 2016 NASEM study
\23\ on responsible conduct of gene drive research. In a Director's
Statement (June 7, 2016), NIH accepted the report, which included
support for continuing basic and applied research in gene drives while
holding off on release of gene drive modified organisms into the
environment at this time.\24\
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\23\ http://nas-sites.org/gene-drives/.
\24\ https://www.nih.gov/about-nih/who-we-are/nih-director/
statements/statement-national-academy-sciences-report-gene-drives-non-
human-organisms.
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As new gene editing technologies come to fruition, NIH continues to
be prepared to investigate their ethical, legal, and social
implications (ELSI). For example, the National Human Genome Research
Institute (NHGRI), has a Congressionally-mandated, 5 percent set-aside
in its extramural budget to fund ELSI research. In anticipation of
myriad bioethical issues, NHGRI's ELSI portfolio covers research to
explore the downstream implications of emerging genomic technologies.
How is NIH coordinating these efforts with other Federal agencies,
both within and outside of HHS?
Answer. NIH has been closely engaged with other Federal agencies,
both inside and outside of HHS, on bioethical issues associated with
gene editing. NIH works closely with the Food and Drug Administration
(FDA) on issues related to gene editing through fora such as the NIH/
FDA Joint Leadership Council, in which there is a dedicated effort to
coordinate gene editing activities.
NIH continues to participate in many NASEM activities, including
the ongoing Human Genome Editing Initiative, which involves many
components across the U.S. Government and beyond.\25\ As noted above,
NIH also supported a NASEM study on gene drives, which involved other
funders including the Defense Advanced Research Projects Agency, the
Foundation for the National Institutes of Health, and the Bill &
Melinda Gates Foundation. NIH continues to coordinate with these
funders to promote the safe and ethical conduct of gene drives
research.
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\25\ http://nationalacademies.org/gene-editing/index.htm.
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NIH also engages in bioethics conversations in international fora,
including discussions of the ethics of gene editing at the fourth
``Unite to Cure Conference'' in April 2018, which was hosted at the
Vatican to discuss the bioethics of gene editing and other
biotechnologies with physicians, researchers, and religious thought
leaders from across the globe. NIH will continue to engage in such
discussions, both inside and outside the government, and both
domestically and internationally.
______
Questions Submitted by Senator Christopher Murphy
center for excellence in genomic sciences
Question. As you know, I represent a State that has two significant
academic medical research institutions--Yale University and the
University of Connecticut. The University of Connecticut, via a
collaboration with the Jackson Labs, has in recent years made
significant investments in genomics research, a field that Yale has
done work in as well. As the technology and tools to do genomics
research and screening have become more widespread, more universities
like UConn have aspired compete for Federal funding.
As you know, the largest of such awards at the National Human
Genome Research Institute is called the Center for Excellence in
Genomic Sciences (CEGS) program. Each 5-year CEGS grant supports a
multi-investigator, interdisciplinary team to develop innovative
genomic approaches to address a particular biomedical problem and is
funded at up to $1.75 million annually.
The CEGS program was launched back in 2001 with two awards.
Additional rounds of awards in subsequent years eventually expanded
that number to 10 centers. However, at present there are only 8 CEGS
awards active in the U.S. spread among only 7 research institutions.
Furthermore, only 20 institutions total have ever received one of these
awards in the past 17 years. I understand the importance of
institutional knowledge at these universities but am also concerned
that the same players may get these awards while other universities,
like UConn, are left with little chance to compete for these larger
awards.
Do you have any suggestions on how NIH might address this problem?
Answer. The Centers of Excellence in Genomic Science (CEGS) were
established in 2001. Three CEGS awards were made that year, including
one to Yale University. NHGRI generally makes one to two CEGS awards
per year, although in 3 years we made three or four awards. In the 18
years that the program has existed, NHGRI has issued 23 awards, to 20
institutions. The group of 20 institutions that has benefited from the
CEGS program is quite geographically and institutionally diverse.
The CEGS program generally makes awards for 5 years, and only eight
institutions have renewed for another 5 years. Awards currently in
their first 5 years of funding are located at Harvard Medical School,
Stanford University, the University of Washington/Altius Institute for
Biomedical Sciences, the University of Chicago, the University of
California Berkeley, and the University of Pennsylvania. Those in
renewals are located at Yale University, the University of Washington/
Arizona State University, Tempe, Stanford University, the University of
Southern California, Harvard Medical School, Johns Hopkins University,
and the Dana Farber Cancer Institute. NIH recognizes the importance of
allowing as many different institutions as possible to benefit from
such funding, and, as referenced below, institutions in Connecticut
have received various awards from NHGRI. As stated in the CEGS Funding
Announcement \26\ ``The total length of support for any Center under
this program will not exceed 10 years''. This limit was put in place to
encourage diversity of funding recipients.
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\26\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-436.html.
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Applications to renew enter the same competitive pool as
applications from institutions applying for CEGS funding for the first
time, and not all requests to renew are successful. NHGRI encourages
all eligible institutions to consider submitting CEGS applications.
NHGRI also strongly recommends that applicants contact program staff
early in the application development process, to increase their chances
of success.
Research institutions interested in receiving grant money for
genomics research are not limited to applying to the CEGS program; they
may also choose from a range of funding opportunities with varying
award sizes provided by NHGRI and other NIH institutes. Outside of the
CEGS program, NHGRI in recent years has issued awards comparable in
size to a CEGS award to genomics researchers from Yale University, the
University of Connecticut, and Jackson Laboratory for Genomic Medicine
in Farmington, Connecticut. The total NHGRI dollars going to Yale and
the University of Connecticut in each fiscal year 2017 and fiscal year
2018 are $7 million per fiscal year, and at least $5.6 million will be
awarded in fiscal year 2019. A few examples of awards to those
institutions are listed below. Several smaller awards have also been
awarded to Yale University and the University of Connecticut.
--In fiscal year 2018, Brenton Graveley at the University of
Connecticut School of Medicine was awarded $1,815,769
($8,624,902 total for fiscal year 2018-fiscal year 2021) for a
Genomic Community Resource Award to develop A Comprehensive
Functional Map of Human Protein-RNA Interactions.
--In fiscal year 2016, Richard Lifton at Yale University received a
renewal of a Center for Mendelian Genomics Award, which is part
of NHGRI's largest funding program, the Genome Sequencing
program. This award started in 2011; the current 4-year renewal
award is co-funded by NHGRI and the National Heart, Lung, and
Blood Institute (NHLBI). In fiscal year 2018, NHGRI is
contributing $1,947,043, and will contribute another $2,425,542
in fiscal year 2019.
--In fiscal year 2017, Charles Lee at the Jackson Laboratory for
Genomic Medicine in Farmington, CT, received $2,868,077 for
fiscal year 2017 and $1,986,604 for fiscal year 2018, for An
Integrative Analysis of Structural Variation for the 1000
Genomes Project, which NHGRI has funded since 2013.
Examples of other NHGRI programs (in order from largest to smallest
budgets) include the Genome Sequencing Program (GSP), the Genomic
Community Resources Program, the Electronic Medical Records and
Genomics (eMERGE) program, and general investigator-initiated (R01 and
R21) research grants. These programs include geographically diverse
grantees pursuing work on both the basic and clinical sides of the
research spectrum. Additionally, NHGRI is not the only, or even the
largest, funder of genomic research at NIH. The National Institute on
Aging (NIA), the National Cancer Institute (NCI), and the National
Institute of Mental Health (NIMH) are examples of other institutes that
provide funding for this type of research. Some other non-NHGRI
programs that offer funding for large scale genome sequencing are the
Gabriella Miller Kids First Pediatric Research Program (GMKF) (Common
Fund) and the Trans-Omics for Precision Medicine (TOPMed) program
(NHLBI). Interested parties may look to these and other institutes/
programs as possible sources of funding as well.
national institute on occupational health and safety
Question. As you mentioned in your testimony, the administration's
budget request proposes to move the National Institute on Occupational
Health and Safety (NIOSH), which is currently located in the Centers
for Disease Control and Prevention, into the National Institutes of
Health. The 2019 budget also proposes a significant reduction in
funding for NIOSH activities from $335 million to $200 million.
As you know, NIOSH currently has multiple responsibilities in the
areas of occupational health, including research, training of
occupational health professions and professionals, and implementing
research into practice with our Nation's businesses, manufacturers,
forestry, and agricultural sectors.
Could you provide a list of NIH's current research or training
activities in the field of occupational health and safety, and provide
the NIH's underlying statutory authorities that would enable NIH to
implement NIOSH's core mission and its activities?
Statutory authority for NIH activities is found in section 301 and
title IV of the Public Health Services Act
Answer. The fiscal year 2019 Budget proposes consolidating certain
HHS research programs into three new institutes within the NIH. The
Budget provides $380 million for the activities of the Agency for
Healthcare Research and Quality (AHRQ), which would be renamed the
National Institute for Research on Safety and Quality. The National
Institute for Occupational Safety and Health (NIOSH), including the
Energy Employees Occupational Illness Program (EEOCIPA), currently
administered by the Centers for Disease Control and Prevention, and the
National Institute on Disability, Independent Living, and
Rehabilitation Research (NIDILRR), currently administered by the
Administration for Community Living, are also proposed for
consolidation into the NIH.
NIH currently does not track its research or training activities in
the field of occupational health and safety but could do so in the
event of a consolidation. The Budget proposal assumes that existing
statutory authorities for NIOSH's core mission and activities would be
amended to make them available to NIH along with the necessary funding.
Consolidating targeted research programs from across HHS--AHRQ/
NIRSQ, NIOSH, NIDILRR--into NIH allows high priority research programs
to benefit from focused resources and NIH research infrastructure. NIH
will continue to implement strategies to increase operational
efficiencies and administrative reforms.
clinical trials definition
Question. NIH has expanded the definition of clinical trials
through a set of case studies to include both fundamental basic and
health-related research, which will have a significant impact on and
consequences for principal investigators and research projects.
Although there were a number of revisions in response to concerns from
research universities and associations, issues remain unresolved.
Congress included language in the fiscal year 2018 Omnibus to suspend
NIH's new definition of clinical trials and called on NIH to revamp the
policy with input from the scientific community. With that in mind,
could you answer the following questions:
What steps has NIH taken to satisfy the requirement in the fiscal
year 2018 Omnibus bill that directs NIH to consult with the basic
science research community about the implementation of the new clinical
trials definition?
Has NIH considered creating a new or alternative framework to
ClinicalTrials.gov for reporting basic science research involving human
subjects?
The new clinical trials definition will include small-scale
mechanistically driven clinical studies involving human subjects. These
studies cannot inform a change in clinical practice, and yet the new
definition will impose tremendous costs associated with registration,
training, continuing education, record keeping, and special reports
under the assumption that these are clinical trials. Is NIH concerned
that the new policy will provide a disincentive for this type of
research with human subjects?
Answer. As the largest public funder of clinical trials in the
United States, currently investing more than $3 billion each year, the
National Institutes of Health (NIH) takes its stewardship of the
nation's clinical trial enterprise very seriously. Therefore, NIH must
ensure that supported trials investigate a mission-relevant question
that is of high priority, do not needlessly duplicate previously
conducted trials (in contrast to providing needed replication), and
have the highest likelihood to advance knowledge and improve health. To
achieve this goal, several challenges in the design, efficiency, and
reporting of clinical trials need to be addressed. In combination,
these targeted reforms are intended to ensure stewardship and
transparency in the scientific enterprise. The NIH definition of a
clinical trial, is focused on fostering this stewardship and
transparency to assure the public that scientists will report the
results of research with human participants--in a timely manner--
regardless of how different scientists might classify them.
NIH recognizes the concerns expressed by the research community and
has spent the past few years continuing to solicit input and work with
the community to chart the best path forward for achieving the aims
outlined in NIH's stewardship reforms. Moreover, NIH has taken several
steps to satisfy the requirement in the fiscal year 2018 Omnibus bill
that directs NIH to consult with the basic science research community
regarding its policy on the Dissemination of NIH-Funded Clinical Trial
Information.\27\ For example, NIH leadership met with interested
stakeholders on May 2 to discuss their concerns, and NIH leadership met
with Senate and House staff to review those discussions and propose
plans, including:
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\27\ https://Federalregister.gov/d/2016-22379.
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--Issuing a Guide Notice stating that for basic science trials that
meet the October 2014 NIH definition of a clinical trial NIH
will delay enforcement of the NIH policy \28\ on registration
and reporting posted in the Federal Register on September 16,
2016.
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\28\ https://www.Federalregister.gov/documents/2016/09/21/2016-
22379/nih-policy-on-the-dissemination-of-nih-funded-clinical-trial-
information.
---------------------------------------------------------------------------
--Issuing a Guide Notice describing flexible, lenient implementation
of other clinical stewardship and transparency policies as they
apply to basic science studies that meet the October 2014 NIH
definition of a clinical trial.\29\
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\29\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-
015.html.
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--Issuing a basic science parent Funding Opportunity Announcement
(FOA) in early fiscal year 2019 for fundamental human studies
that meet the NIH definition of clinical trials. This enables
the agency to combine the transparency we all agree on with the
recognition that these types of studies often occur outside of
the clinic.
--Issuing a targeted Request for Information (RFI) to consult with
researchers and the public to determine the reporting standards
best suited to fundamental research with human participants.
NIH is also interested in soliciting comments to consider
alternative frameworks for reporting basic science research
involving human subjects.
As stated in the policy issued on September 16, 2016,\30\ NIH
recognizes that additional effort is required to register and report
the results of research studies. Nonetheless, reporting the results of
scientific work is integral to the scientific method. The benefits of
timely registration and reporting will, in the long run, accrue to the
investigators as well as to the public, patients, and the enterprise
because transparency will improve future research designs and maximize
the public's investment--and their trust--in research. Equally
important, it will help investigators fulfill the ethical obligation
they have to research participants, namely to ensure that the findings
from their participation contribute to generalizable knowledge and the
advancement of public health.
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\30\ https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-
149.html.
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pulmonary fibrosis
Question. Unfortunately, like many Americans, my family was touched
by pulmonary fibrosis years ago when my uncle passed away from this
devastating disease. Estimates are that about 200,000 people are
affected in the United States, there are 50,000 new cases each year,
and 40,000 people die from the disease each year.
In this era of precision medicine, is the NIH and the National
Heart, Lung and Blood Institute applying precision medicine approaches
to tackling this disease? How can patient registry's, such as the
registry created by the Pulmonary Fibrosis Foundation, play a role in
NIH precision medicine efforts relating to this group of diseases?
Answer. Pulmonary fibrosis, which causes progressive scarring of
lung tissue, can run in families, but the exact cause of the disease is
not well understood. The National Heart, Lung, and Blood Institute
(NHLBI) supports a vigorous research program on pulmonary fibrosis to
improve understanding of the disease and identify better treatments. In
2014, a NHLBI workshop report, ``Future Directions in Idiopathic
Pulmonary Fibrosis'' recommended continued support for precision
medicine efforts including genomic and molecular studies.\31\ Examples
of NHLBI efforts include:
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\31\ https://www.ncbi.nlm.nih.gov/pubmed/24160862.
---------------------------------------------------------------------------
--NHLBI-funded researchers have used whole-exome sequencing--scanning
all of the protein-coding genes in the genome--to better
understand genetic factors involved in idiopathic pulmonary
fibrosis (IPF). They analyzed data from >250 patients who had
pulmonary fibrosis with little or no family history, and found
that variation in three genes (TERT, RTEL1 and PARN) is
associated with a risk of IPF.\32\ All three genes had
previously been implicated in familial PF and are involved in
the maintenance of telomeres (a region at the end of
chromosomes that protects the ends chromosome from damage).
Shorter telomere length also has been associated with higher
mortality in three IPF patient cohorts.\33\
---------------------------------------------------------------------------
\32\ https://www.atsjournals.org/doi/abs/10.1164/rccm.201610-
2088OC.
\33\ https://www.ncbi.nlm.nih.gov/pubmed/24948432.
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--The NHLBI-funded IPF Clinical Research Network (IPFnet) conducted a
trial to investigate whether the antioxidant N-Acetylcysteine,
when used in combination or with immunosuppressant drugs, is
effective in patients with IPF. Analysis of the trial results,
combined with genetic data from the participants, showed that
N-acetylcysteine monotherapy improved clinical outcomes in
patients who carry a particular mutation in the Toll-
interacting protein (TOLLIP) gene.\34\
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\34\ https://www.ncbi.nlm.nih.gov/pubmed/26331942.
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--Genomic and molecular studies have revealed small bits of RNA,
called microRNAs, as a potential form of therapy. MicroRNA-29
appears to play a key role in preventing fibrosis in the lung.
Researchers at Yale are collaborating with industry to create a
similar--but more stable--version of microRNA-29 that can
potentially be used as a therapy for IPF. Their current efforts
to develop such a therapy have shown promise in mouse models.
The same researchers \35\ also have identified a 52-gene
signature \36\ in the blood that can be used to develop a risk
profile for recently diagnosed IPF patients, which may help
identify IPF patients who will benefit most from a given
therapy.
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\35\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9270067.
\36\ https://www.ncbi.nlm.nih.gov/pubmed/28942086.
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--In research funded through NHLBI's LungMAP \37\ and Lung Repair and
Regeneration Consortium, as well as a program project
grant,\38\ researchers performed the first single-cell RNA
sequencing analysis of epithelial cells in pulmonary
fibrosis.\39\ This revealed aberrant lung epithelial cells that
appear to be in an ``indeterminate'' state of differentiation
(cell fate) not seen in normal lung development. This work also
provides sequencing data that can be utilized by other
researchers conducting future IPF research.
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\37\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9062494.
\38\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9111936.
\39\ https://www.ncbi.nlm.nih.gov/pubmed/27942595.
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NHLBI encourages IPF investigators to utilize existing clinical
resources, including the Pulmonary Fibrosis Foundation's patient
registry and NHLBI's lung tissue repository,\40\ when submitting grant
applications. By leveraging these longitudinal patient data and
biosample repositories, alongside the collection of additional genetic
and genomic information, clinical researchers have a greater potential
to predict risk, disease progression, and response to therapy--
information that is necessary to develop precision medicine approaches
to treating IPF.
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\40\ https://www.nhlbi.nih.gov/science/lung-tissue-research-
consortium-ltrc.
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psychotic disorders
Question. Despite advancements for many diseases, I continue to
hear from constituents frustrated by the slow pace of development of
new medicines to treat psychotic disorders such as schizophrenia. The
absence of biomarkers and specific molecular targets, as well as the
complexity of the brain, create enormous challenges for drug discovery.
What steps can the National Institute of Mental Health (NIMH) be
taking to spur development of innovative therapies to treat these
devastating disorders? Is NIMH examining the viability of a public-
private partnership to advance discovery of new medicines?
Answer. NIMH supports innovative approaches aimed at improving
treatment for individuals living with schizophrenia and other psychotic
disorders through research on novel therapeutics, biomarkers to inform
therapeutics development and treatment, and services and interventions
to optimize existing evidence-based treatments.
NIMH supports early-stage therapeutic discovery and development for
the treatment of mental illnesses across the drug development pipeline,
including first-in-human and early efficacy trials.\41\ The NIMH Drug
Discovery and Clinical Therapeutics Program supports research to design
and develop novel therapeutics agents for the treatment of mental
illnesses and supports the NIH National Cooperative Drug/Discovery/
Development Groups (NCDDG) program for the Treatment of Mental
Disorders.\42\ The NCDDG encourages public-private partnerships to:
accelerate the discovery of pharmacological agents targeting novel
molecular processes implicated in the pathophysiology of mental
illnesses; facilitate the development and validation of predictive
assays for developing novel therapeutics for mental illnesses; support
early phase human clinical testing to rapidly assess the safety and
efficacy of promising drug candidates; and, facilitate the development
and validation of new clinical measures or biomarkers suitable for use
in human proof of concept trials of novel therapeutics. As an example,
the NIMH Psychoactive Drug Screening Program provides the research
community with access to broad screening capabilities in the form of
pharmacological and functional assays to stimulate innovative research
and development efforts including potential therapeutic agents for the
treatment of psychiatric disorders.\43\ In addition, NIMH supports
research on the development and testing of novel drug compounds for
their potential to improve cognition in people with schizophrenia.
These compounds modulate cholinergic signaling in the brain, which
plays an important role in arousal, attention, memory, and motivation.
Two of these compounds are at the stage of safety and tolerability
testing in human subjects.\44,45\ This line of research aims to
ameliorate neurocognitive dysfunction, which is a hallmark of
schizophrenia and a significant contributor to disability associated
with schizophrenia.
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\41\ https://www.nimh.nih.gov/research-priorities/therapeutics/
index.shtml.
\42\ https://www.nimh.nih.gov/about/organization/dnbbs/molecular-
cellular-and-genomic-neuroscience-research-branch/drug-discovery-and-
clinical-therapeutics-program.shtml.
\43\ https://www.nimh.nih.gov/funding/grant-writing-and-
application-process/concept-clearances/2017/the-nimh-psychoactive-drug-
screening-program-pdsp.shtml.
\44\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9339822&icde=32296266.
\45\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9140071&icde=32296291.
---------------------------------------------------------------------------
To inform novel therapeutics development, NIMH continues to fund
research aimed at identifying biomarkers and charting trajectories of
psychotic disorders. Through the NIH Neuroscience Blueprint, which uses
state-of-the-science brain imaging technologies to acquire and broadly
share data about the structural and functional connectivity of the
human brain, NIMH co-funds two NIH Human Connectome Projects (HCP)
focused on psychosis. One project examines brain anatomical and
functional connectivity in individuals with early psychosis.\46\ The
second project tests quantitative models of local and long-range neural
mechanisms to understand abnormal visual perception in psychosis.\47\
These projects aim to identify neural correlates of clinical symptoms
observed in psychosis and could pave the way for novel treatment
development. In addition, NIMH supports the North American Prodrome
Longitudinal Study (NAPLS), a nine-site consortium combining brain-
based biological and clinical markers to predict the onset of psychosis
in vulnerable populations and chart trajectories of mental illness. An
improved predictive algorithm and better understanding of biological
mechanisms underlying psychosis onset could inform patient
stratification for clinical trials of novel preventive treatments.\48\
NIMH also supports the Early Psychosis Intervention Network (EPINET) to
create a common database of information gathered during routine
clinical encounters to inform effective early psychosis care and
accelerate research into psychosis risk factors, biomarkers of
psychosis risk and onset, and pre-emptive interventions.\49\
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\46\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9108511&icde=32296915.
\47\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9109802&icde=32296932.
\48\ http://campuspress.yale.edu/napls/.
\49\ https://www.nimh.nih.gov/funding/grant-writing-and-
application-process/concept-clearances/2015/early-psychosis-
intervention-network-epinet-a-learning-healthcare-system-for-early-
serious-mental-illness.shtml.
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In addition to seeking pathways to novel interventions, NIMH is
also committed to improving implementation of current evidence-based
practices for the treatment of psychosis. Antipsychotic medications
provide substantial benefits to many patients, and consistent
medication use is associated with lower rates of relapse and re-
hospitalization. Through the Small Business Innovation Research and
Small Business Technology Transfer (SBIR/STTR) program, NIMH supports
research to help patients maintain treatment through efforts that
improve medication adherence, medication monitoring, and the use of
technologies to enhance interventions.\50,51,52,53,54\ In addition, the
Advanced Laboratories for Accelerating the Reach and Impact of
Treatments for Youth and Adults with Mental Illness (ALACRITY) Research
Centers aims to improve the effectiveness, delivery, and quality of
evidence-based services in diverse settings for individuals with
serious mental illness, including psychotic disorders.\55,56,57\
Through the Early Psychosis Prediction and Prevention (EP3) initiative,
NIMH supports several projects to develop and test interventions to
improve cognitive and social skills for persons at clinical high risk
for psychotic disorders.\58,59,60,61\ NIMH recently issued a funding
opportunity announcement to support a large-scale initiative focused on
testing the effectiveness of interventions that target early symptoms
associated with clinical high risk for psychosis (i.e., problems in
thinking, mood, and social functioning suggestive of a pre-psychosis
risk state).\62\
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\50\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9254370&icde=39687639.
\51\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9201433&icde=39687639.
\52\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9128708&icde=39687639.
\53\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9361111&icde=39687639.
\54\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9201713&icde=39687639.
\55\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9374695&icde=39592663.
\56\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9485776&icde=39592663.
\57\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9486324&icde=39592663.
\58\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9345577&icde=22682326.
\59\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9304884&icde=22682332.
\60\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9302540&icde=22682334.
\61\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9302539&icde=22682335.
\62\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-
211.html.
---------------------------------------------------------------------------
NIMH will continue to fund research on psychotic disorders to
identify and develop the breakthrough treatments of tomorrow, as well
as to optimize and implement the effective treatments of today. In
pursuit of its mission to transform and understand treatment of mental
illnesses, NIMH will continue public-private partnerships through the
NCDDG and consider other partnerships that support excellent science
and the NIMH mission.
neurological conditions
Question. As you may know, the 21st Century Cures Act authorized
the CDC to implement a national neurological conditions surveillance
system. I worked on this section with Sen. Isakson because despite the
fact that estimates indicate that one in six Americans lives with a
neurologic condition, many condition-specific figures are severely
outdated. For instance, the last national study of prevalence and
incidence of Multiple sclerosis was done in 1975 and data on the
prevalence of Parkinson's disease is based on a 1985 study.
How would a neurological disease registry help provide a foundation
for evaluating and understanding aspects of neurological conditions?
How could such a surveillance system accelerate neurological research?
Answer. For many neurological diseases, there are no recent,
reliable data on the incidence, prevalence, geographical distribution,
and demographics in the U.S. population, nor for changes over time.
Such information can be useful in several ways. These data are
essential to understand the societal burden of neurological disorders,
which is an important factor that NIH and the research community must
consider in setting research priorities, along with scientific
opportunity. Such data are also crucial for designing public health
programs. In some cases, these data may provide clues to risk factors
and potential environmental influences that more targeted studies may
follow up, such as reported differences in geographical distribution in
multiple sclerosis and the association of some cases of Parkinson's
disease with occupational exposure. Data on frequency of diseases also
can demonstrate the effectiveness of research on public health; for
example, in stroke, for which we do have good data, there has been a 70
percent decline in the age adjusted death rate, reflecting the
cumulative benefits of decades of research.
Although potentially useful, surveillance of neurological disorders
presents formidable challenges, especially in a healthcare system that
does not have a single central record system. There are hundreds of
diseases of the brain and nervous system, many of which are difficult
to diagnose correctly. Some disorders, like chronic pain, are among the
most common of all diseases, and the many rare genetic diseases
collectively have an enormous burden despite being individually rare.
Together, neurological diseases affect people of all ages, who may be
treated via family physicians, various medical specialties, hospitals,
nursing homes, or by self-care. All of this makes tracking very
difficult because the optimal strategy is different for different
diseases. The 21st Century Cures Act acknowledged the difficulty,
noting that the surveillance system may initially address a limited
number of neurological diseases.
______
Questions Submitted by Senator Joe Manchin, III
superfund site
Question. Dr. Collins, as you may know, Minden, West Virginia has
been listed as a Superfund site by the EPA since 1984 because the small
rural community was contaminated with PCBs by an industrial facility
related to coal mining.
I am gravely concerned about the reports stating that cancer rates
are significantly higher in Minden than the rest of Fayette County and
the rest of the State.
The National Toxicology Program ranks PCBs as ``reasonably
anticipated to be human carcinogens'' and the EPA has classified PCBs
as a probable human carcinogen. Both designations indicate that there
is substantial likelihood that extended exposure to PCB contaminated
sites could result in cancer.
Yet, the EPA has found that PCB exposure from the superfund site is
not responsible for these high cancer rates or for a cancer cluster in
this small, rural Appalachia town. That is why it is so critical that
we conduct additional research to fully understand the potential causal
connection between PCB exposure and cancer rates.
Dr. Collins, will you commit to directing the National Toxicology
Program at NIH to promptly prioritize further research on PCB exposure
and the link to cancer?
Further, will you work with me and the other members of this
Committee to ensure that the National Institute of Environmental Health
Sciences has the resources needed to conduct this critical research?
Answer. Thank you for your questions, and I appreciate your sharing
information about the situation with the Superfund site in Minden, West
Virginia. The National Institute of Environmental Health Sciences
(NIEHS) is home to the National Toxicology Program (NTP), which is
dedicated to testing and evaluating substances in the environment.
NIEHS and NTP have a long history of funding research into the health
effects associated with exposure to polychlorinated biphenyls (PCBs).
NTP has conducted extensive rodent studies with component PCBs to try
to understand how these components interact in the body to cause
cancer. Other NIEHS investments in this area cover relationships
between exposure to PCBs and risks of developmental disorders, immune
responses, obesity, metabolic disorders and diabetes, and neurological
problems. Given their current and past research activities, NIEHS and
NTP are well positioned to advise and share information with other
agencies involved in answering scientific questions about PCB exposure
levels in affected populations.
rural health
Question. In 2017, the America's Health Rankings Report ranked West
Virginia 46th in overall health. This low ranking is driven by high
obesity rates, high rates of smoking, and high rates of drug related
deaths. We're also 48th highest in cancer deaths and 49th highest in
the number of West Virginians with diabetes.
West Virginia has, in many ways, been left behind as medical
advances have saved lives in other places. In fact, I have heard from
West Virginians who want to participate in clinical trials, but are
forced to leave the state to do so.
Dr. Collins, what is NIH doing to bridge this gap in health
outcomes?
How do you ensure that the medical research that you do benefits
people in poor, rural communities?
How can we better expand access to research studies and then to
successful treatments to rural Americans, particularly in states like
mine where the disease burden is so high?
Answer. NIH recognizes the unique health disparities that rural
communities face, and as such, rural health is an important area of
research for the agency. Through diverse collaborations and
partnerships with communities, academic institutions, and state
agencies, NIH supports and conducts rural health research to improve
health outcomes and reduce rural health disparities with a special
emphasis on populations in poor, rural communities. NIH's rural health
research focuses on key areas of concern to you and rural residents and
are aimed at addressing health disparities that rural populations in
West Virginia and around the U.S. experience.
In fiscal year 2017, NIH supported more than 500 rural health-
related grants for approximately $259 million. NIH is committed to
ensuring that there are opportunities for poor rural Americans to
access the benefits of research and that research addresses the unique
strengths and challenges of rural communities. NIH supports several
programs focused on cancer, cardiovascular disease, and other chronic
diseases disproportionately affecting rural communities. For example,
Screen to Save \63\ is a colorectal cancer outreach and screening
initiative aimed at increasing cancer screening rates for individuals
in rural communities, particularly among racial and ethnic minority
populations. The Heart Truth Community Action Program \64\ initiative
engages and empowers women to learn about risk factors for heart
disease and steps they can take to live a heart-healthy life. The
Strong Hearts, Healthy Communities \65\ program works to reduce rural
disparities in cardiovascular disease through community-based
interventions (e.g., nutrition and physical activity classes) in ten
underserved, rural towns. NIH's Healthcare for Rural Populations
Research Initiative \66\ aims to enhance the resources and
infrastructure underlying healthcare access and quality for rural
populations, including methods for improving oral health in rural
school-based cavity prevention programs.
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\63\ https://www.cancer.gov/about-nci/organization/crchd/blog/2016/
screentosave-launch.
\64\ https://www.nhlbi.nih.gov/health/educational/hearttruth/
partners/grantees.htm.
\65\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9245732&icde=34114853.
\66\ https://www.nimhd.nih.gov/programs/extramural/resource-
related.html#healthcare-rural.
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Recognizing the unique needs of Appalachian communities, NIH
supports the Kids SIPsmartER \67\ project, a school-based, behavior and
health literacy curriculum aimed at improving sugar-sweetened beverages
(SSB) behaviors among middle school students in medically underserved
Appalachian counties in southwest Virginia. The program uses a two-way
short service message strategy to engage caregivers in SSB role
modeling and supporting home SSB environment changes. The primary aim
is to assess changes in SSB behaviors among 7th grade students at
schools receiving Kids SIPsmartER; evaluate changes in secondary
student outcomes such as BMI and quality of life; changes in caregiver
outcomes; and maintenance of outcomes. The overall goal is to establish
an effective, scalable, and sustainable multi-level strategy to improve
SSB behaviors and reduce SSB-related health inequities and chronic
conditions in rural Appalachia.
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\67\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9495908&icde=39783928.
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Several West Virginia institutions are also engaged in rural health
research, including the West Virginia State Department of Health and
Human Resources, West Virginia University, West Virginia School of
Osteopathic Medicine, CAMC Health Research Institute, and Marshall
University. In one West Virginia-based project for example, NIH
supports the West Virginia University Stroke Center of Biomedical
Research Excellence (WVU Stroke CoBRE),\68\ a part of the WVU Center
for Basic and Translational Stroke Research, which works to identify
and treat the known risk factors for stroke among Appalachian
populations. Research conducted by the WVU Stroke CoBRE focuses on
stroke prediction, causes, prevention, acute treatment and
rehabilitation. The Stroke CoBRE also has an intensive mentoring
program for junior investigators. The WVU Stroke CoBRE recently became
a formal part of the StrokeNet clinical trial consortium which will
allow the Center to conduct multi-centered clinical trials to enhance
its rapid translation of basic research into clinical trials and
studies.
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\68\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9313278&icde=39683671.
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The Rural West Virginia Responds to Opioid Injection Epidemics:
From Data to Action \69\ project seeks to eliminate the opioid epidemic
and associated infectious diseases in West Virginia through
collaborations with communities and public health agencies. The project
will create an evidence-based roadmap to coordinate and improve
screening, prevention, and treatment for HIV and other insular
injection drug use-associated diseases; develop and test a novel
strategy to rapidly identify the emergence of HIV in rural communities;
and deploy and evaluate an integrated service delivery model to enhance
delivery of evidence-based services, screening strategies, and
treatment.
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\69\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9412006&icde=39683671.
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Continued collaborations and partnerships with scientists and
organizations from rural communities, such as many in West Virginia,
will contribute to NIH's reach in rural communities and support our
work to combat rural health disparities.
institutional development award
Question. The Institutional Development Award (NIH IDeA) program
has been critical for West Virginia. It brings NIH funding to help
build the medical research programs in underserved states.
West Virginia currently only receives about $20 million in NIH
grant funding, but WVU estimates that the economic benefit of these
grants in West Virginia is $180 million and the IDeA program has been
critical for expanding access to medical research in my State.
The IDeA program received $350 million in the bipartisan fiscal
year 2018 Omnibus Appropriations bill, but the budget would cut funding
for the National Institute of General Medical Sciences--which houses
this program--by more than $935 million, and this program was not even
specifically listed.
I believe that we should continue to strongly support this program.
Dr. Collins, what impact the proposed cuts to NIH funding would
have on this important program?
Can you tell me why this program was not specifically listed in the
budget and what the recommended fiscal year 2019 funding level is?
Can you please speak to the importance of funding research at a
wide variety of institutions, particularly those in rural, underserved
states?
Answer. The Budget recognizes that importance of funding the
highest priority scientific discoveries while also maintaining fiscal
responsibility of Federal resources. The IDeA Program will continue to
fulfill its congressional mandate of broadening the geographic
distribution of NIH funding for biomedical research and enhancing the
competitiveness of investigators at institutions located at eligible
states and jurisdictions at the fiscal year 2019 funding level.
Consistent with other NIH Institutes, the fiscal year 2019 National
Institute of General Medical Sciences (NIGMS) Congressional
Justification only included the total program level. Individual NIGMS
program details were not provided, also consistent with other NIH
Institute Congressional Justifications.
Prior to the increase of the budget caps and the fiscal year 2018
enacted levels, the fiscal year 2019 President's Budget was built on
the fiscal year 2018 Annualized CR level which reduced the NIGMS budget
by 2.29 percent. Like the overall NIGMS Program level, the fiscal year
2019 President's Budget for the IDeA Program would be reduced by 2.29
percent from the fiscal year 2018 Annualized CR. When comparing fiscal
year 2019 President's Budget over the fiscal year 2018 enacted level,
the overall NIGMS total program level and the IDeA program would be
reduced by 7.6 percent.
The IDeA Program managed by NIGMS is a long-term interventional
capacity-building program targeting states and jurisdictions that have
consistently trailed in obtaining significant NIH support. The intent
of the program is to transform institutions with infrastructure, human
resource, and economic challenges to become more competitive biomedical
research enterprises through various distinct but complementary
initiatives. Some benefits of the IDeA Program in the eligible states
and jurisdictions include:
--Builds active biomedical research environments in IDeA states and
improves access to modern, state-of-the-art biomedical research
for students, researchers, and the general public.
--Ensures that states without medical schools have an opportunity to
develop research capacity for conducting basic, translational,
and clinical research.
--Provides opportunities to address health disparities in medically
underserved groups residing in IDeA states.
--Promotes SBIR/STTR programs, technology transfer, entrepreneurship,
and public-private partnerships that could lead to the
formation of bio-related industries, potentially benefitting
the local economy.
--Encourages collaborations and leveraging among IDeA research
resource centers to capitalize on each other's unique
capabilities to solve complex research questions and encourages
consolidation of research resources with complementary
technologies to improve efficiency and crate economies of
scale.
--Enhances the competitiveness of institutions by providing
opportunities for talented and highly motivated undergraduate
students to participate in research training and pursue
research careers in the biomedical sciences.
--Develops best practices, training tools, workflows, databases, and
analysis tools that assist clinical and translational
researchers to develop and perform clinical and translational
protocols to address important questions in multiple areas of
biomedical science quickly and efficiently.
Funding research at a wide variety of institutions is extremely
important to ensure that a rich diversity of scientific and
geographical perspectives is represented and that all available human
capital is deployed in the critical work of addressing vital biomedical
research questions and pressing health problems. Local investigators
are often the best equipped and experienced to conduct research on
local health concerns. Further, NIH strongly believes that scientific
discoveries can arise anywhere where there are well-trained and
determined investigators working in adequately resourced environments.
Ensuring that all jurisdictions and institutions across the United
States are afforded the opportunity to become active and significant
contributors to this country's research agenda increases the likelihood
of breakthroughs in science and medicine.
medical research can save money--alzheimer's
Question. I am someone who is very concerned about the Federal
debt, but I have always supported strong funding for NIH because it is
an investment that saves lives, preserves America's role as a global
innovator, and has the potential to save a lot more money in the future
if we're able to reduce the costs of treating expensive diseases.
Alzheimer's disease, for example, cost West Virginia's Medicaid
program $394 million in 2017 and this cost is expected to increase as
the number of people with the disease increases. The Alzheimer's
Association estimates that the cost of caring for people with
Alzheimer's and dementia will rise from $236 billion to $1.1 trillion
in 2050. In short, we can't afford to not invest in medical research.
That is why I share my colleagues concern about the President's
budget cuts of more than $2.2 billion to NIH overall and more than $1.1
billion to the National Institute on Aging in particular relative to
the funding that we included in the fiscal year 2018 Omnibus.
Dr. Hodes, as the Director of the National Institute on Aging, can
you please speak to the research that your agency is doing on
Alzheimer's disease?
Do you believe that investments in this research now is a fiscally
responsible choice given the astronomical costs that our country is
likely to face as our Nation ages?
Answer. NIA has leveraged the extraordinary influx of funding
directed at Alzheimer's disease and related forms of dementia (AD/ADRD)
to build a series of bold and innovative research programs,
infrastructure, and new partnerships that are enabling some of the
Nation's leading scientists to tackle the problem of AD/ADRD on an
unprecedented scale and pace. High-priority research and infrastructure
programs that are currently underway include:
--Alzheimer's Clinical Trial Consortium (ACTC), to accelerate and
expand trials of AD/ADRD therapies;
--Resilience-AD, a new program bringing together experts from
multiple disciplines to understand why some high-risk
individuals remain dementia free;
--Molecular Mechanisms of the Vascular Etiology of Alzheimer's
Disease (M\2\OVE-AD) Initiative, exploring how metabolic and
vascular risk factors such influence brain aging and AD
pathology and identifying blood-based markers of the disease;
--Alzheimer's Biomarker Consortium--Down Syndrome (ABC-DS), in which
researchers use biomarkers to track disease progression in
people with DS, a uniquely vulnerable population at high risk
for developing AD;
--The Model Organism Development and Evaluation for Late-onset AD
(MODEL-AD) project to develop better animal models of late-
onset AD;
--Approximately 140 active clinical trials of interventions to
prevent, treat, or manage symptoms of AD/ADRD and to enhance
caregiver well-being;
--Development of new therapeutics, including some that target
molecules other than beta-amyloid; and
--Harnessing the power of big data to identify existing drugs or
combinations currently used to treat other conditions that
could be effective for the treatment of AD/ADRD.
Other current priorities include development of caregiver support
interventions; implementation of a national recruitment strategy that
ensures inclusion of diverse populations in AD/ADRD research;
understanding gene-environment interactions that increase risk or
confer resilience against AD/ADRD; infrastructure development,
including big data infrastructure; workforce training across the
spectrum of research; and harmonization and distribution of data from
large datasets.
The financial costs associated with AD/ADRD to affected families
and to society are considerable. Data published by the Alzheimer's
Association estimate total payments in 2018 for all individuals with
AD/ADRD at $277 billion, much of which will be paid by Medicare and
Medicaid. NIH-funded researchers found that, in the last 5 years of
life, total health and long-term care spending for people with dementia
was more than $250,000 per person, greater than costs associated with
death from other major chronic diseases. Average out-of-pocket spending
for patients with dementia was 81 percent higher than for patients
without dementia. Caregiving costs, including loss of wage income due
to caregiving responsibilities, are also significant.
NIH-supported researchers estimate that delaying onset of AD for 5
years would result in 41 percent lower prevalence and 40 percent lower
cost of AD by 2050. Given these findings, research to ameliorate not
only the physical and mental burdens of these diseases but also the
economic burden is not only fiscally responsible, it is crucial to the
health of our economy.
______
Questions Submitted by Senator Patrick J. Leahy
Institutional Development Award (IDeA)
Question. The IDeA program, operated by the National Institute of
General Medical Sciences (NIGMS) at the National Institutes of Health
(NIH) has long been a fundamental source of support for institutions
that participate in biomedical research. With a focus on health-related
research, specifically in rural and medically underserved communities,
IDeA is critical in the goal of supporting researchers' work to uncover
lifesaving methods to combatting disease. In my home State of Vermont,
IDeA awards have contributed to advances in genetic research, new
medical technologies, and vaccine and drug developments.
With the help of IDeA awards, the University of Vermont, our
State's largest research institution, developed the Vermont Genetics
Network, the Vermont Center for Immunology and Infectious Diseases, the
Vermont Center for Neuroscience, and the Vermont Center on Behavior and
Health. IDeA grants have also expanded the employment of STEM
professionals in several other institutions of higher education across
the State. These institutes have contributed to some of the world's
most groundbreaking medical understanding on how to cure lung and heart
disease and on understanding the effect of brain disorders on learning
and development.
I am concerned that the administration's proposed cuts to NIH and
NIGMS will undoubtedly place pressure on the IDeA program by reducing
the amount of grant dollars awarded for institutional biomedical
research. This means less opportunities for our Nation's institutions
to develop lifesaving treatments to debilitating disease.
What are the benefits of the IDeA program in building capacity in
states that might not otherwise receive NIH funding, including a
description of not only how this program has benefited not just local
communities, but also helped advance the national dialogue on
biomedical and translational research?
Answer. The overarching mission of the Institutional Development
Award (IDeA) Program is inclusive Biomedical Research Capacity-
building--to develop and strengthen biomedical science research
programs in States/Jurisdictions of the country that are
underrepresented in the NIH portfolio, to enable increased engagement
and participation of these states in scientific areas that are
supported by NIH, and to promote biomedical research capacity and
capabilities in these states that are competitive and sustainable.
Benefits of the IDeA program in states/jurisdictions receiving IDeA
funding include the following:
--Through targeted professional development efforts, the IDeA Program
grows and nurtures the pool of next generation scientific
leaders and innovators.
--The IDeA program develops and enhances the research facilities and
resources in these states/jurisdictions, thereby enabling
investigators to expand their contributions to scientific
discovery, innovation, and learning.
--Inclusive and sustainable biomedical workforce development pathways
are established and formalized that equip local human resources
with the appropriate intellectual and technical scientific
skills. Biomedically skilled human capital, in turn, can serve
as the nidus or help attract the formation of bio-related
industries, potentially benefitting the local economy.
--Through meaningful engagement of the local community, both the
scientific research community and the community at-large form
important partnerships that begin to address vital and urgent
scientific questions and regional health priorities.
Within the past year, some of the important contributions made by
investigators and other highlights/impacts emanating from the IDeA
Program initiatives include the following:
--Vermont IDeA Network of Biomedical Research Excellence (INBRE) \70\
researchers characterized the processing of a protein in
neurons called progranulin, a mechanism that impacts the
neuropathology of frontotemporal dementia (FTD), a
neurodegenerative disorder characterized by progressive changes
in personality, behavior, and/or language. FTD is the second
most common cause of early-onset Alzheimer's disease. This
finding was published in the scientific journal Molecular
Neurodegeneration.
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\70\ The IDeA Network of Biomedical Research Excellence (INBRE)
initiative enhances, extends, and strengthens the research capabilities
of biomedical research faculty in IDeA states through a statewide
program that links a research-intensive institution with primarily
undergraduate institutions.
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--A New Mexico Centers of Biomedical Research Excellence (COBRE) \71\
team reported on a collaborative intervention to increase
awareness on risk of falls for Zuni Native American community.
The innovative collaborative approach can produce dramatic
improvements in clinical outcomes, health related quality of
life, and reductions in healthcare costs. The Zuni Health
Initiative (ZHI), an integrated model of community, family and
clinic-based education, life style modification and healthcare
will facilitate the translation of validated national
guidelines for screening and treatment of chronic disease and
reduce health disparities in this high-risk population of Zuni
American Indians.
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\71\ The Centers of Biomedical Research Excellence (COBRE)
initiative develops and strengthens institutional biomedical research
capabilities in IDeA states through three 5-year phases of
infrastructure and faculty development of multidisciplinary research
centers focused on a specific biomedical science theme.
---------------------------------------------------------------------------
--A report from Advances in Physiology Education reported on North
Dakota INBRE's impact on undergraduate research at rural
primarily undergraduate institutions (PUIs) over a 12-year
period. Participation of the PUIs in the ND INBRE generated a
more robust research culture at the undergraduate institutions.
The number of faculty participating in undergraduate research
increased two- to four-fold. The high level of student success
(550 participants) is supportive of the concept that
undergraduate research (350 posters presented) is a value-added
component of the INBRE initiative that will help prime the
pipeline for the next generation of health professionals in
research, service, and teaching.
--A COBRE team from Vermont carried out research on adverse effects
associated with using commercially available cigarettes and
explored the effects of reducing potential for addiction in
highly vulnerable populations (socioeconomically disadvantaged
smokers, individuals with psychiatric conditions). Three
manuscripts were published that reported the following: (1)
significant positive association between using commercially
available high nicotine yield cigarettes and risk of nicotine
dependence and continuing to smoke during pregnancy in a
nationally representative sample of U.S. women of reproductive
age (published in Preventive Medicine), (2) reducing the
nicotine content of cigarettes significantly reduces the
addiction potential of cigarette smoking in adults highly
vulnerable to tobacco addition (smokers with psychiatric
disorders or socioeconomic disadvantage) (published in JAMA
Psychiatry), and (3) dependence severity has no moderating
influence on the ability of reduced nicotine content cigarettes
to lower the addiction potential of smoking, and minimal
effects on relief from craving/withdrawal or smoking topography
(published in Preventive Medicine).
--INBRE researchers from Alaska reported on the ability of the arctic
ground squirrel, a seasonal hibernator, to resist brain damage.
Investigating how oxygen glucose deprivation induces tolerance
has very important translational implications in ischemic brain
injury in stroke patients (reported in Journal of
Neurochemistry).
--Investigators supported through the Kentucky INBRE elucidated the
role of a Zika capsid (membrane) protein in brain damage and
published their results in Nature.
--Shayna Bennett, an alumna of Johnson State College in Vermont, was
named an awardee of the 2018 National Science Foundation
Graduate Research Fellowship Program (GRFP). The program
supports graduate students with high potential to be leaders in
STEM research. The program supports NSF's goal of developing a
workforce that leads the world in advancing science and
engineering research. While Shayna was an undergraduate student
at Johnson State College, she was funded by the Vermont INBRE
to conduct biomedical research from 2014-2015. The experience
influenced her decision to pursue a graduate degree in a STEM
research field. She is currently a first-year doctoral student
in applied mathematics at the University of California Merced.
--A report at the Advances in Physiological Education demonstrated
how the Kansas INBRE annual symposium, a 10-institute
collaboration, improved undergraduate education. The 16-year
undertaking has supported 1,000 students. Survey results
indicate that students and mentors alike find the symposium to
be beneficial and enriching of the student experience, with
almost 80 percent of student respondents indicated that their
participation in the symposium fostered appreciation of
research. The KA-INBRE symposium provides a terrific
opportunity for students to gain experience in collecting,
preparing, and communicating research in a professional
environment.
--An Arkansas COBRE team published their findings on the effects of
radiation on normal tissues and certain age-related diseases
vis-a-vis aging stem cells and the ability of tissues to
regenerate and repair, drive inflammation, and oxidative
stress. The report focused on ABT-263, a molecule initially
developed as an anti-cancer therapy drug, which could
effectively deplete senescent (aging) cells. The depletion
appeared to reduce premature aging of the bone marrow due to
irradiation and rejuvenated the function of stem cells in
normally aged mice (reported in Nature Medicine).
--Investigators supported through the Louisiana IDeA-Clinical and
Translational Research (CTR) \72\ award found that Mycoplasma
genitalium is an etiologic agent of cervicitis in HIV-infected
women, providing a potential mechanism for enhanced HIV
transmission to an uninfected partner. M. genitalium is an
emerging sexually transmitted pathogen implicated in
inflammatory syndromes of the female reproductive tract
(reported in Journal of Infectious Disease).
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\72\ The IDeA Program Infrastructure for Clinical and Translational
Research (IDeA-CTR) initiative develops network infrastructure and
capacity in IDeA-eligible states to conduct clinical and translational
research focused on health concerns that affect medically underserved
populations and/or that are prevalent in IDeA states.
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--Montana IDeA researchers collaborated on a report on the
transmission of a pathogen from animals to humans (zoonotic
transmission). This work provides a foundation for
transdisciplinary investigation of spillover and synthetic
theory on zoonotic transmission (reported in Nature Reviews
Microbiology).
--A New Hampshire COBRE team reported on a plant-based nanotechnology
that could generate an antitumor immune response. The effect
was observed to be systemic and durable, resulting in immune-
memory and protection from recurrence (reported in Nature
Nanotechnology).
tick-borne diseases
Question. The spread of tick-borne diseases, such as Lyme disease
(Lyme), to humans have been increasing in Vermont and many other
northern states. While reports of Lyme in Vermont used to be rare in
the early 1990s, it is now common to see over 400 confirmed cases
reported in a year. This trend has proven to be true for other
northeastern and upper Midwestern States as well, as the number of
reported cases of Lyme has tripled and the number of high-risk counties
has increased by more than 300 percent since the late 1990s. Ticks, and
thus Lyme and other tick-borne diseases, have expanded their geographic
range and are now being found in places where there were not seen 20
years ago. It is estimated that 20 percent of the population that live
in areas where Lyme is common are unaware that they live in high-risk
areas for tick-borne diseases.
Given the ever-growing threat of tick-borne diseases, what efforts
are NIH pursuing to better detect or cure tick-borne diseases such as
Lyme?
Answer. The National Institute of Allergy and Infectious Diseases
(NIAID) maintains a diverse research portfolio on Lyme disease and
other tick-borne diseases and encourages development of diagnostics,
therapeutics, and vaccines to combat these infections. As part of this
effort, NIAID engages in important collaborations with Federal
partners, Lyme disease experts, patients, and others as a member of the
Department of Health and Human Services Tick-Borne Diseases Working
Group created by the 21st Century Cures Act.
NIAID supports basic research on how Borrelia species, including B.
burgdorferi and B. mayonii, infect the host, multiply, and ultimately
cause Lyme disease. Basic research also is underway for a variety of
tick-borne infections such as anaplasmosis, babesiosis, tick-borne
encephalitis, and others. Findings of these early-stage studies will
help to identify targets for additional diagnostic tests, treatments,
and vaccines for these infections. For example, NIAID grantees are
using real-time imaging to track the spread of bacteria that cause Lyme
disease and to monitor treatment effectiveness in infected mice. NIAID
scientists also have developed a novel tick infection model for
flaviviruses that could be used to evaluate tools to combat the deadly
Powassan and tick-borne encephalitis viruses.
NIAID is committed to discovering better ways to diagnose Lyme
disease that would enable more informed treatment decisions. In
collaboration with the Centers for Disease Control and Prevention and
others, NIAID is working to develop novel diagnostics including next
generation molecular tests. NIAID-supported scientists are working to
identify biomarkers that could allow for earlier and more rapid
diagnosis, accurate indication of disease stage and progression,
indications of successful treatment, and ability to distinguish between
Lyme and other tick-borne infections. NIAID scientists and extramural
researchers recently developed a novel tool, the TBD-Serochip, to help
differentiate several tick-borne infections. This test is designed to
discriminate between eight major tick-borne pathogens in the United
States, including species of Anaplasma, Babesia, and Borrelia.
NIAID also supports Lyme disease prevention research, including
efforts to develop effective vaccines. NIAID is funding research
exploring the adaptation of a successful canine Lyme disease vaccine
for potential use in humans. Other NIAID-supported studies are pursuing
vaccine strategies to limit Lyme disease transmission, including oral-
bait vaccines targeting wildlife reservoirs of B. burgdorferi and
efforts to target proteins in tick saliva that are critical for
effective transmission of Lyme bacteria.
NIAID is committed to supporting basic, translational, and applied
research on tick-borne diseases, including studies on the pathogens,
the ticks that transmit them, and their vertebrate hosts. Through
ongoing research support, as well as collaborations with Federal and
public partners, NIAID will continue to advance the development of
vaccines, therapeutics, and diagnostics for Lyme and other tick-borne
diseases.
______
Questions Submitted to Anthony Fauci, M.D.
Questions Submitted by Senator Patty Murray
combatting antibiotic resistant bacteria
Question. How has the threat posed by antibiotic resistant bacteria
changed since you helped write the National Action Plan a few years
back? Is the situation worse, better or unchanged?
Answer. The National Institutes of Health (NIH) continues to
prioritize research to address the public health threat of
antimicrobial resistance. The National Institute of Allergy and
Infectious Diseases (NIAID), part of the NIH, plays a lead role in
addressing the goals of the National Action Plan for Combating
Antibiotic-Resistant Bacteria (CARB), including the development of
diagnostics, therapeutics, and vaccines for drug-resistant bacteria.
The Progress Report: CARB Years 1 and 2 \73\ outlines NIAID-supported
efforts, along with those of Federal CARB partners, toward achieving
the goals of the National Action Plan for CARB. While our understanding
of antibiotic-resistant bacteria--and how to combat them--has improved
since the development of the National Action Plan for CARB, the
emergence and re-emergence of drug-resistant bacteria continue to pose
a threat to the public health. NIH and its CARB partners are committed
to sustaining our critical efforts to develop countermeasures and
strategies to address the ongoing challenge of antibiotic-resistant
pathogens.
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\73\ https://aspe.hhs.gov/system/files/pdf/258516/
ProgressYears1and2CARBNationalActionPlan.
pdf.
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Question. What is the status of efforts to fund clinical trials to
test new antibiotics and diagnostics to quickly identify bacterial
pathogens?
Answer. NIAID supports a comprehensive research portfolio on
antimicrobial resistance, including clinical trials to test new
diagnostics, treatments, and vaccines. NIAID is funding highly
meritorious research projects on antimicrobial resistance focused on
developing: (1) clinical diagnostics; (2) tools to facilitate discovery
of novel therapeutics; and (3) prevention strategies. These awards will
build on successes in NIH-supported CARB research, including prior
support for more than 35 clinical studies through the NIAID
Antibacterial Resistance Leadership Group (ARLG), which oversees
clinical research to reduce the public health threat of antibacterial
resistance. The ARLG has undertaken studies investigating diagnostic
devices, optimized treatment regimens, new drugs, and projects on
antimicrobial stewardship. NIAID also supports basic and preclinical
research to identify promising antibacterial products that may move
into clinical trials. NIAID continues to collaborate with the
Biomedical Advanced Research and Development Authority (BARDA) on CARB-
X, a unique public-private partnership dedicated to accelerating the
development of innovative antibacterial products from target/candidate
identification and characterization through Phase 1 clinical trials.
NIH also continues to partner with BARDA to support the CARB diagnostic
challenge seeking to identify innovative, rapid point-of-need
diagnostics to combat the development and spread of drug-resistant
bacteria, as well as increase antibiotic stewardship. These efforts are
critical to generating a robust pipeline of candidate antibiotics and
diagnostics to support clinical testing of promising products against
drug-resistant organisms.
Question. Does NIH expect these efforts to help reduce the number
of drug-resistant infections and deaths that occur each year, or is
that too much to expect?
Answer. The ultimate goals of NIAID-supported research on
antimicrobial resistance, ranging from basic research to identify
targets for antimicrobial products to applied research and clinical
trials to test new diagnostics, treatments, and prevention strategies,
are to help reduce the number of drug-resistant infections and deaths
and to increase antibiotic stewardship. As one example, NIAID
scientists have been using next generation sequencing to study the
evolution of community acquired methicillin-resistant Staphylococcus
aureus (MRSA) strains to help identify how these strains developed and
to understand why those strains have become more prevalent. This
research, which collected MRSA isolates from patients in many
geographic regions, may inform new strategies to limit community
acquired MRSA infections throughout the United States. NIAID also has
evaluated a new drug to treat Neisseria gonorrhoeae, a bacterium that
is increasingly resistant to currently used drugs, in clinical trials
through the Sexually Transmitted Infections Clinical Trials Group and
the Phase 1 Clinical Trial Units for Therapeutics. Based on these early
studies, which found the investigational gonorrhea therapeutic to be
well-tolerated and effective, the drug will advance to later-stage
clinical trials. NIH anticipates that its ongoing CARB research and
partnerships across government, as well as new activities enabled by
increases to CARB research funding in fiscal year 2018, will continue
to support progress against antibiotic-resistant bacterial infections.
universal flu vaccine
Question. NIH recently announced the phase 2 clinical trial of a
potential universal flu vaccine. How long is that trial expected to
last, and does NIAID have other vaccine candidates in the pipeline? If
so, when might we see trials for candidates begin?
Answer. The National Institutes of Health (NIH) is prioritizing the
development of universal influenza vaccines that would represent a
groundbreaking advance in influenza preparedness by allowing for
durable protection against multiple influenza strains. The National
Institute of Allergy and Infectious Diseases (NIAID), part of the NIH,
has outlined its research priorities for a universal influenza vaccine
in a strategic plan published online on February 28, 2018, by The
Journal of Infectious Diseases. As one example of research consistent
with the strategic plan, NIAID recently launched a Phase 2 clinical
trial of an experimental universal influenza vaccine called M-001. The
vaccine, which was developed and produced by BiondVax Pharmaceuticals,
is designed to stimulate an immune response against peptide sequences
shared among many different influenza strains. The clinical study will
be conducted at NIAID-funded Vaccine and Treatment Evaluation Units
(VTEUs) and is estimated to be completed in early 2019. The VTEUs also
are planning to initiate Phase 1 clinical studies to inform the
development of universal influenza vaccines, including a study to
evaluate whether the addition of a novel adjuvant to an existing pre-
pandemic H5N1 influenza vaccine can enhance the breadth of the immune
response to different influenza strains.
NIAID is studying additional strategies to create a universal
influenza vaccine, several of which have advanced to early-stage
clinical trials. For example, NIAID Vaccine Research Center scientists
have initiated Phase 1/2 studies of a universal influenza vaccine
approach that includes an investigational DNA-based vaccine followed by
a licensed seasonal influenza vaccine ``boost'' to improve the potency
and durability of seasonal influenza vaccines. NIAID also developed a
ferritin nanoparticle-based vaccine approach that showed promise in
animal testing and is being evaluated in early-stage clinical trials.
In another strategy, NIAID scientists developed a vaccine made from
non-infectious virus-like particles (VLPs). This VLP-based vaccine
candidate incorporates four subtypes of the viral hemagglutinin protein
into one vaccine. This candidate broadly protected against multiple
influenza virus subtypes in animal models and may advance to clinical
trials in the future. NIAID is supporting a number of preclinical
studies to evaluate additional universal influenza vaccine candidates.
In addition, NIAID funds basic research to better understand how the
immune system responds to influenza infection or vaccination, and
efforts to develop new assays and reagents to evaluate the efficacy of
novel influenza vaccines.
NIAID will continue to support the development of a robust pipeline
of candidate universal influenza vaccines that may advance to
evaluation in clinical trials. The availability of a universal
influenza vaccine would eliminate the need to update and administer the
seasonal influenza vaccine each year and could provide protection
against newly emerging influenza strains, including those with pandemic
potential. NIAID efforts to achieve this important goal will be
facilitated by the generous support of the Congress in providing $100
million dedicated to research on universal influenza vaccines in NIH's
fiscal year 2018 budget.
opioid epidemic
Question. What share of NIDA's roughly $1.4 billion budget for
fiscal year 2018 will be devoted to opioid-related efforts, be it
prevention, clinical trials or the development of new therapeutics?
Answer. We are unable to provide this information until fiscal year
2018 concludes, but we will provide the information when it becomes
available.
Question. When can we expect to see the agency's strategic plan for
the opioids initiative, and will it include specific targets and
milestones for what we're trying to achieve?
Answer. The research plan for the Helping to End Addiction Long-
term (HEAL) Initiative \74\ is available online. Setting specific
targets and milestones is difficult due to the unpredictable nature of
scientific inquiry, so at this time, specific targets are not included.
The overall goals of the HEAL Initiative are preventing addiction
through enhanced pain management and improving treatment for opioid use
disorder.
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\74\ https://www.nih.gov/research-training/medical-research-
initiatives/heal-initiative/heal-initiative-research-plan.
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Question. The fiscal year 2019 budget proposes a coordinated
strategy with two primary aims to combat the opioid epidemic in our
country. One of those aims is to accelerate the development of new,
non-addictive pain therapies with the goal of making a wide-range of
therapeutics accessible to those who need them as quickly as possible.
Can you describe what types of non-addictive pain therapies are
currently in the NIH research pipeline, and how quickly can these
therapies can be developed and distributed to the market?
Answer. NIH is particularly excited about the new Helping to End
Addiction Long-term (HEAL) Initiative. HEAL will bolster research
across NIH in an effort to improve the treatment of chronic pain by (1)
exploring biomarkers that predict the transition from acute to chronic
pain, (2) identifying new targets for treating chronic pain using
neurotechnologies developed through the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative and the
Stimulating Peripheral Activity to Relieve Conditions (SPARC) program,
and (3) building the evidence base on the effectiveness of nondrug and
integrated pain treatments. In addition, the Initiative will pursue
public-private partnerships to develop new non-addictive pain medicines
by sharing data on past and present research projects, and matching
researchers with a selection of potentially promising but abandoned
pharmaceutical industry compounds to explore their effectiveness for
the treatment of pain. Finally, NIH will develop a clinical trials
network for pain, allowing multiple new and repurposed compounds to be
tested for effectiveness simultaneously.
The Initiative will tap into the expertise of the NIH Pain
Consortium,\75\ a trans-NIH consortium made up of NIH institutes that
fund pain research. Funded projects are investigating the entire range
of therapeutics development- from preclinical safety and efficacy
testing and early phase human trials to health services research.
Currently, the consortium members are working on developing more
effective and less addictive treatments for chronic pain. For example,
a study using a molecular imaging technology called x-ray
crystallography has revealed the molecular structure of the receptors
that mediate drugs' effects; this information is already leading to the
development of safer medications to treat pain.
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\75\ https://www.painconsortium.nih.gov/About/Members.
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NIH-funded research is developing medications with properties that
affect opioid receptors to produce analgesia with reduced risk of
addiction and misuse. Some of these exhibit novel properties as a
result of their combined activity at different types of opioid
receptors (mu, delta, and kappa). Compounds with combined activity at
the mu and delta receptors or at all three receptors can induce strong
analgesia without producing tolerance or dependence in animal models.
In addition, the discovery of adjunct medications that can be combined
with opioids to reduce the needed dose has the potential to result in
lower potential for dependence and addiction. Innovative methods are
being explored for drug delivery to increase specificity and efficacy
and to reduce analgesic side effects, as well as modified formulations
to enhance delivery.
NIH supports an initiative called the Blueprint Neurotherapeutics
Program for small molecule drug discovery and development. For example,
NINDS funds studies through this program that aim to develop non-
addictive kappa opioid receptor antagonists for migraine and a safe,
non-opioid analgesic that can be taken orally to reduce diabetic nerve
pain.
It is difficult to estimate the time to market for these various
alternatives, but NIH is establishing a Clinical Trial Network to
accelerate the development of novel non-addictive chronic pain
medications and devices by optimizing analgesic trial design, targeting
appropriate patient populations for trials, and engaging research
expertise at existing clinical sites.
Question. Are there any vaccine candidates being considered?
Answer. NIDA continues to fund development of anti-opioid vaccines
capable of generating an immune response that would prevent opioids
from entering the brain, thereby blocking both their euphoric effects
and their dangerous respiratory depressant properties. Current projects
include:
--Optimization and preclinical testing of a practical heroin-HIV
vaccine \76\
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\76\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9110917&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=20&csb=default&cs=ASC&pball=.
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--Preclinical development of vaccines against heroin, oxycodone,
hydrocodone, and fentanyl \77,78,79\
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\77\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9444613&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=11&csb=default&cs=ASC&pball=.
\78\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9330137&icde=39707102
&ddparam=&ddvalue=&ddsub=&cr=26&csb=default&cs=ASC&pball=.
\79\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9461410&icde=39707102.
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Results from preclinical models thus far have shown that these
vaccine candidates are capable of producing an immune response that
blocks opioid effects.\80\ While none have yet advanced to clinical
trials, the heroin vaccine candidate developed by the Walter Reed Army
Institute of Research in collaboration with NIDA has been in-licensed
by Opiant Pharmaceuticals for further development.\81\
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\80\ Olson ME, Janda KD. Vaccines to combat the opioid crisis:
Vaccines that prevent opioids and other substances of abuse from
entering the brain could effectively treat addiction and abuse. EMBO
Rep. 2018 Jan;19(1):5-9.
\81\ https://www.opiant.com/pipeline/heroin-vaccine/.
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Question. The budget emphasizes that the NIH will work with the FDA
and pharmaceutical partners to build a public-private partnership to
accelerate the development of new non-addictive pain therapies. Can you
describe what these partnerships will look like, and how small
biopharmaceutical companies who may be working on novel approaches
might be able to participate?
Answer. As part of the NIH HEAL Initiative, NIH will pursue public-
private partnerships to accelerate the development of non-addictive
pain medicines by sharing data on past and present research projects,
as well as matching researchers with a selection of potentially
promising but abandoned pharmaceutical industry compounds to explore
their effectiveness for the treatment of pain. Companies of all sizes
can participate in this initiative.
______
Questions Submitted to Richard Hodes, M.D.
Questions Submitted by Senator Roy Blunt
alzheimer's vaccine
Question. Dr. Hodes, vaccines have been one of the most impactful
medicines in history. Is there the scientific possibility that a
vaccine would work in Alzheimer's?
What is the state of the research in this area?
Is NIA planning to fund any vaccination programs in fiscal year
2018?
Answer. Vaccination, a form of immunotherapy, using your body's own
immune system to help fight disease, is one of many treatment
modalities currently under study for both the prevention and treatment
of Alzheimer's disease (AD). While we have every reason to hope that we
will see positive results from these studies, our cautious optimism is
tempered by the acknowledgement that previous vaccine trials have been
largely unsuccessful. For example, in 2002 a trial of AN1792, the first
vaccine to target deposition of beta-amyloid, a pathological hallmark
of the disease, ended early because dangerous brain inflammation
occurred in some patients. More recently, industry-supported clinical
trials of passive immunization (i.e., direct transfer of antibodies
that attack beta-amyloid) with the monoclonal antibodies bapineuzumab
and solanezumab produced disappointing results.
However, these studies were initiated in individuals who were
already showing clinical symptoms of the disease, and more recent
vaccine studies are targeting at-risk individuals much earlier in the
disease course, before symptoms appear. For example, the Alzheimer's
Prevention Initiative Autosomal Dominant Alzheimer's Disease (API-ADAD)
study is exploring ``preventive immunotherapy'' among members of a
large extended family that carries a genetic mutation placing many
members at greatly increased risk of developing the disease. Another
study, the Dominantly Inherited Alzheimer's Network trial, evaluates
the safety, tolerability and effectiveness of several drugs, including
two vaccines, and will determine if they can prevent, delay, or even
reverse Alzheimer's disease changes in the brain. The Alzheimer's
Prevention Initiative APOE4 Trial (API APOE), or Generation 1 study, is
determining the safety and efficacy of two drugs targeting beta-
amyloid, including an active immunotherapy injection, in older adults
at genetic risk of the disease, while the Anti-Amyloid treatment in
Asymptomatic AD Trial (A4 Trial) is evaluating a passive vaccine in
clinically normal older adults with evidence of AD pathology on
screening positron emission tomography imaging who are at risk for
developing dementia.
NIA also supports a large cooperative agreement to complete
preclinical safety and efficacy testing for AV-1959D, a cutting edge
``DNA vaccine.'' DNA vaccines use pieces of DNA from specific
pathogenic proteins to stimulate an immune response and offer potential
technical and safety advantages over conventional protein/adjuvant
vaccines.
More broadly, NIA supports research on underlying mechanisms of the
immune system in the brain. For example, one study is exploring immune-
mediated mechanisms underlying clearance of beta-amyloid from the brain
and central nervous system, while others are investigating possible
immunotherapies targeting tau, another pathological hallmark of AD. All
of this important work will be active in fiscal year 2018 and 2019.
trans-angiogenesis
Question. In May 2013, the NIH hosted the NIH Trans-Angiogenesis
Workshop. In March 2016, the NIH released a meeting summary, which
included an outline of clear steps needed to bring angiogenesis
research forward. The resources needed included:
--Develop potential partnerships with pharmaceutical companies for
the development of new drugs that require investigations using
structural biology approaches and medicinal chemistry.
--Develop cross-disciplinary NIH resources to increase research on
the molecular understanding of angiogenesis across therapeutic
fields, such as cancer, diabetes, obesity, and cardiovascular
diseases.
--Develop a biomarker identification project that moves beyond
prognostic biomarkers to the development of validated
predictive biomarkers of clinical benefit (or lack of benefit)
and biomarkers of toxicity.
--Improve the translation of basic research angiogenesis focused
findings across disciplinary fields to clinical applications.
--Organize a cross-disciplinary meeting of basic science,
translational and clinical scientists and clinicians where NIH
grantees would be required to present their research.
--Create trans-NIH Program Project Grants and Specialized Centers of
Clinically Oriented Research for angiogenesis research.
Could you please provide the Subcommittee an update on the progress
on these issues?
Answer. Angiogenesis is the process of new blood vessel formation
and growth that is vital for normal embryonic development, new blood
vessel formation, and wound healing. Insufficient, excessive, or
aberrant angiogenesis may have significant clinical consequences in
diseases such as stroke, myocardial infarction, peripheral arterial
disease, cancer, chronic inflammation, and retinopathy.
Multiple NIH Institutes fund angiogenesis-related research aimed at
improving the understanding of normal and abnormal angiogenesis and
translating findings into therapeutic interventions.
Because angiogenesis research applies to many diseases, the trans-
NIH workshop was convened to provide leaders in angiogenesis research
an opportunity to examine the diverse nature of the sciences involved
across the field, to identify current gaps, and to explore potential
advantages in integrating basic, translational, and clinical research
in the prevention and treatment of angiogenesis-related diseases.\82\
NIH has continued to address research gaps and focus on priorities
identified by the workshop. Here are a few examples:
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\82\ https://prevention.cancer.gov/news-and-events/meetings-and-
events/trans-nih-angiogenesis-workshop/meeting-summary.
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basic and translational research
Research supported by the National Heart, Lung, and Blood Institute
(NHLBI) has contributed to a better understanding of angiogenesis
mechanisms at the molecular and cellular level.\83\ Signaling pathways
and regulation of angiogenesis have been better defined,\84\ as has the
role of inflammation and metabolism of cells that line the interior
surface of vessels in angiogenesis.\85\ For example, researchers found
that changes in endothelial cell glucose, fatty acid, and protein
metabolism may function as a ``metabolic switch'' for angiogenesis.
Further investigation of these pathways is ongoing to identify
biomarkers of endothelial cell health and disease and to discover
potential ways to alter defective angiogenesis.
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\83\ http://circres.ahajournals.org/content/120/11/1713/tab-
supplemental.
\84\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966612/.
\85\ https://www.ncbi.nlm.nih.gov/pubmed/29795441.
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Recognizing that cancers need a blood supply to grow and spread,
the National Cancer Institute (NCI) provides support for research on
elucidating the cellular mechanisms that give rise to the creation of
new blood vessels and the therapeutic potential of anti-angiogenesis
drugs. One area of particular interest is the action of vascular
endothelial growth factor (VEGF) and other signaling molecules that
stimulate angiogenesis. Since the discovery of VEGF almost 30 years
ago, these proteins have become a major target for therapy; drugs that
inhibit VEGF have become an intensively studied--and in some cases,
successful--approach to block abnormal angiogenesis.
Yet, some cancers are also resistant to these inhibitors.
Researchers are examining the basic mechanisms of resistance in
glioblastoma, with a focus on VEGF and stromal-cell derived factor 1
(SDF-1), a protein involved in tumor growth and metastasis.\86\ NCI
also supports basic research into tumor microenvironments, which may
help illuminate future therapeutic pathways. Examples include a project
examining the role of low oxygen, acidity, and depleted nutrient levels
in the tumor microenvironment, and the effects these factors may have
on glioblastoma angiogenesis,\87\ as well as a study on how immune
system activity promotes angiogenesis in melanoma tumor
microenvironments.\88\
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\86\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=8997986.
\87\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9274829.
\88\ https://projectreporter.nih.gov/
project_info_description.cfm?aid=9236367.
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Angiogenesis research is also relevant to stroke, as collateral
blood vessels around a blocked vessel can provide an alternative path
for blood flow to the brain. Researchers funded by the National
Institute on Neurological Disorders and Stroke (NINDS) are exploring
the molecular and genetic mechanisms that determine the number and size
of collateral vessels around major arteries, as well as the remodeling
of these vessels after a stroke. Researchers also are exploring the
role of angiogenic pathways in brain blood vessel stability and the
risk for hemorrhage, as well as in processes that support protection
and recovery of brain tissue following a stroke. Additionally, NINDS-
funded investigators are exploring avenues to improve the effectiveness
of angiogenesis inhibitors for treating brain cancers such as
glioblastoma. Ongoing work is investigating the molecular mechanisms
that lead to therapeutic resistance, and tumor recurrence and
progression.
Angiogenesis research is also important to eye health. Diabetes and
the most common type of age-related macular degeneration (AMD) can
cause vision loss due to abnormal blood vessels in the retina.
Researchers funded by the National Eye Institute (NEI) have
demonstrated that gene therapy can be used effectively to block
proteins in the VEGF pathway to reduce vision loss in animal
models.\89\ This proof of concept supports a novel treatment for
angiogenesis-related retinopathy.
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\89\ https://www.ncbi.nlm.nih.gov/pubmed/29730824.
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clinical research
The NCI hopes to expand the successes of angiogenesis inhibitors in
treating cancer and currently supports clinical trials of these agents
to treat glioblastoma, pancreatic cancer, metastatic breast cancer,
prostate cancer, ovarian cancer, colorectal cancer, lung cancer, liver
cancer and other solid tumors. Many of these trials involve the
therapeutic agent bevacizumab (Avastin), a monoclonal antibody directed
against VEGF.
The NHLBI also funds significant clinical research relating to
angiogenesis. This includes a planning grant for a clinical trial
testing an anti-angiogenesis drug to treat hereditary hemorrhagic
telangiectasia, a genetic disorder that involves abnormal blood vessel
formation and can result in hemorrhage and stroke.
NHLBI has also supported, research to develop pro-angiogenic
factors to treat ischemic diseases that restrict blood supply. Such
efforts have not yielded reproducible and sustained success in late-
stage clinical trials.\90\ While the use of pro-angiogenic stem cells
may offer more promise, its clinical application is still limited.\91\
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\90\ https://journals.lww.com/cardiovascularpharm/Abstract/2014/
08000/Identifying_and_
Overcoming_Obstacles_in_Angiogenic.1.aspx.
\91\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869986/.
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The Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD) supports a range of intramural and extramural
research projects on aspects of angiogenesis, specifically on
development of the utero-placental interface, placenta formation, and
early development of the vascular system. In addition to investigator-
initiated research, NICHD also supports clinical research aimed at
achieving healthier pregnancy outcomes through its Maternal Fetal
Medicine Units network. Recently, similarities in the pathology of
cardiovascular disease and preeclampsia, a dangerous spike in a
pregnant woman's blood pressure, prompted NICHD-supported researchers
to conduct a preliminary study of a commonly used cardiovascular drug
in high-risk pregnant women in their second trimester. While the risk
of preeclampsia was unchanged in women who received a placebo, women
who received this drug did not develop preeclampsia.\92\
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\92\ https://www.ncbi.nlm.nih.gov/pubmed/?term=26723196.
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A noninvasive retinal imaging approach called optical coherence
tomography (OCT) has emerged as an effective tool to view the layers of
the retina as well as any fluid leakage--a useful biomarker for AMD and
for responses to treatment.\93\ Over the past decade, the introduction
of anti-angiogenesis drugs, such as Avastin, Lucentis, and Eylea has
revolutionized treatment of AMD, slowing the disease and even reversing
vision loss in some cases. However, monthly treatment injections are
expensive and not always needed. OCT is also used for treatment
decisions for other angiogenesis-related causes of blindness, such as
diabetic retinopathy.
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\93\ https://www.ncbi.nlm.nih.gov/pubmed/29077605.
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trans-nih efforts
Question. Several NIH Institutes are involved in a Neuroscience
Blueprint initiative--Neurobiology of Small Blood and Lymphatic Vessels
in Health and Disease. This initiative will support the development of
innovative tools and technologies to explore heterogeneity of small
blood and lymphatic vessels in the central nervous system (CNS), as
well as human studies to identify targets, biomarkers, and mechanisms
specific to CNS small blood and lymphatic vessels. This initiative
emerged from a trans-NIH scientific workshop on the role of small
vessels in health and disease across different organ systems in the
body.\94\ While not specifically focused on angiogenesis research, it
may support angiogenesis projects.
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\94\ https://www.ncbi.nlm.nih.gov/pubmed/27815267.
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Because angiogenesis plays an essential role in health and is
implicated in a wide range of diseases and disorders, the NIH will
continue to support a full spectrum of research in this area, including
development of pro- and anti-angiogenic therapies.
______
Questions Submitted to Norman Sharpless, M.D.
Questions Submitted by Senator Roy Blunt
cancer research & treatment in rural communities
Question. The network of National Cancer Institute-designated
cancer centers and comprehensive cancer centers play an important role
in our national efforts to prevent, diagnose, and treat cancer. As
someone from a rural state who understands the difficulty in access to
cancer treatments in rural and remote areas, Dr. Sharpless, can you
describe how existing resources are used to help those Americans in
rural and underserved communities?
How do NCI-designated cancer centers ensure those in rural
communities can benefit from clinical trials and breakthrough cancer
treatments?
Answer. Rural communities face disadvantages compared with urban
areas, including higher poverty, lower educational attainment, and lack
of access to health services. These challenges contribute to higher
incidence of certain cancers and worse cancer-related outcomes in low-
income, underserved rural populations. New data has shown that--for the
first time--cancer death rates are higher in rural areas than in urban
areas. This shift has been demonstrated by two studies--one by NCI
researchers \95\ and one led by researchers from the Centers for
Disease Control and Prevention (CDC).\96\
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\95\ https://www.ncbi.nlm.nih.gov/pubmed/28600296.
\96\ https://www.cdc.gov/mmwr/volumes/66/ss/ss6614a1.htm.
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There are several areas where the National Cancer Institute (NCI)
plays a significant role in advancing rural cancer prevention and
control research. Key areas include working with NCI's Community
Oncology Research Program (NCORP) and NCI-Designated Cancer Centers to
build on their experience with community outreach and developing
partnerships with local organizations. To inform NCI's efforts to
better address cancer disparities in rural communities, NCI is also
convening researchers, community representatives, and providers to
discuss these important issues. In May 2018, NCI hosted a diverse group
of speakers from across these disciplines to discuss collaboration and
coordination for rural cancer control. The objectives of the meeting
were to (1) identify gaps in rural cancer research and practice; (2) to
build partnerships across the country to address challenges and
disseminate solutions; and (3) to highlight and identify methods to
address competing and common agendas of clinics/providers, researchers,
and community/patients.\97\
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\97\ https://cancercontrol.cancer.gov/research-emphasis/meetings/
arcc-meeting.html.
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NCI has a broad and growing range of research in this area and will
continue to work with the cancer community and others to refine and
reinvigorate our cancer control efforts in rural areas across the
country. NCORP is a crucial part of NCI's efforts to prevent, diagnose,
and treat cancer in rural populations.\98\ NCORP's mission is to bring
clinical trials and cancer care delivery research to people where they
live, with a special focus on rural communities. NCORP is comprised of
seven research bases; 46 community sites, 12 of which are designated as
minority/underserved; \99\ and more than 900 component sites across the
country.\100\ NCORP community and component sites, which are comprised
of public hospitals, physician practices, academic medical centers, and
other groups that provide healthcare services in community settings,
play an important role in accruing patients to NCI-supported research
studies and clinical trials, including the groundbreaking NCI Molecular
Analysis for Therapy Choice (NCI- MATCH) precision medicine cancer
treatment trial.
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\98\ https://ncorp.cancer.gov/.
\99\ NCORP minority/underserved sites have a patient population
that is of at least 30 percent racial/ethnic minorities or rural
residents.
\100\ https://ncorp.cancer.gov/findasite/map.html.
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NCI-Designated Cancer Centers also play an increasingly important
role in rural cancer control. There are currently 70 NCI-Designated
Cancer Centers located in 36 States and the District of Columbia. These
cancer centers develop and translate scientific knowledge from
promising laboratory discoveries into breakthrough treatments for
cancer patients. Each year, approximately 250,000 patients receive
their cancer diagnosis at an NCI-Designated Cancer Center, and an even
larger number of patients are treated for cancer and/or enrolled in a
clinical trial at these centers.\101\ Cancer centers applying for NCI-
designation are required to describe the geographic area they intend to
serve, and are encouraged to describe how the center plans to extend
its reach beyond this catchment area to bring the center's expertise to
bear on wider populations, including rural populations.\102\
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\101\ https://www.cancer.gov/research/nci-role/cancer-centers.
\102\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-095.html.
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To incentivize cancer center engagement in rural health, NCI has
provided supplemental funding to 15 cancer centers to collect
additional data concerning their catchment area population and align
local measures with national ones, enabling more direct comparisons
across centers and with national surveillance data. To extend this
commitment, in fiscal year 2018, NCI plans to support NCI-Designated
Cancer Centers in further developing their rural cancer control
research capacity.
In addition to the programs described above, NCI recently released
a standalone Funding Opportunity Announcement (FOA) inviting
applications for research aimed at improving the reach and quality of
cancer care in rural populations.\103\ Depending on receipt of
sufficiently meritorious applications, NCI intends to fund up to 10
awards in fiscal year 2018.
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\103\ https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-18-
026.html.
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pediatric cancer
Question. Dr. Sharpless, we hear a lot about the need for more
research on childhood cancer, often from families who have lost a child
to cancer. What is the National Cancer Institute doing to improve
outcomes for children with cancer, and to address the factors that make
childhood cancers unique?
Answer. Pediatric cancer research remains a top priority for the
National Cancer Institute (NCI), and each year the Institute identifies
the best research opportunities to build upon the foundation of basic
science, further develop the scientific understanding of genetic
drivers of childhood cancers, identify effective therapies, and enhance
the quality of life for pediatric cancer survivors.
NCI recognizes cancers that strike infants, children, teens and
even young adults are different from those that affect adults, and that
they require specific research. Additionally, even when long-term
survival is achieved, many survivors of childhood cancer experience
serious long-term adverse effects from the disease or its treatment.
Future discoveries made through additional research are needed so that
new, more effective, and less toxic treatments for cancers that affect
children and young adults can be developed.
Recognizing that childhood cancers are distinct from adult cancers,
NCI supports numerous targeted programs aimed at advancing research in
pediatric oncology. These efforts include:
--The Children's Oncology Group (COG),\104\ part of NCI's National
Clinical Trials Network (NCTN), develops and coordinates
pediatric clinical trials across more than 200 member
institutions. In addition to conducting late-phase clinical
trials, the COG receives NCI support for the Phase 1 and Pilot
Consortium,\105\ which conducts early-phase trials and pilot
studies to rapidly introduce new anticancer agents into
pediatric care.
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\104\ https://www.childrensoncologygroup.org/.
\105\ https://www.childrensoncologygroup.org/index.php/phase-1-
home.
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--The Pediatric Oncology Branch (POB) \106\ in NCI's Center for
Cancer Research, part of NCI's intramural research program,
conducts high-risk, high-impact basic, translational, and
clinical research.
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\106\ https://ccr.cancer.gov/Pediatric-Oncology-Branch.
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--The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)
Trial,\107\ launched in July 2017, tests molecularly targeted
therapies in children and adolescents with advanced cancers who
have few other treatment options. This nationwide trial is open
to children and adolescents from 1 to 21 years of age and
currently has eight treatment arms.
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\107\ https://www.cancer.gov/about-cancer/treatment/clinical-
trials/nci-supported/pediatric-match.
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--Other efforts include the Pediatric Preclinical Testing Consortium
(PPTC),\108\ the Therapeutically Applicable Research to
Generate Effective Treatments (TARGET) \109\ program, the NCI
Experimental Therapeutics (NExT) Program,\110\ the Childhood
Cancer Survivor Study (CCSS),\111\ the Pediatric Provocative
Questions (PQ) Program,\112\ the Pediatric Brain Tumor
Consortium (PBTC),\113\ the Pediatric Cancer Immunotherapy
Trials Network (CITN),\114\ and the New Approaches to
Neuroblastoma Therapy (NANT) \115\ Consortium.
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\108\ http://www.ncipptc.org/.
\109\ https://ocg.cancer.gov/programs/target.
\110\ https://next.cancer.gov/.
\111\ https://www.cancer.gov/types/childhood-cancers/ccss.
\112\ https://grants.nih.gov/grants/guide/pa-files/PAR-16-217.html.
\113\ https://www.pbtc.org/.
\114\ https://ctep.cancer.gov/MajorInitiatives/
cancer_immunotherapy_trials_network.htm.
\115\ http://www.nant.org/.
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In addition to these well-established programs, the Institute is
enthusiastic about the scientific opportunities provided by the Cancer
MoonshotSM to stimulate further investigation of pediatric cancers.
Current programs supported by the Cancer MoonshotSM include the Fusion
Oncoproteins in Childhood Cancers (FusOnC2) Consortium, which will seek
to develop models of, and therapeutic agents for, fusion-driven
childhood cancer; \116\ the Pediatric Immunotherapy Translational
Science Network, which will aim to identify targets for immunotherapy
treatments for pediatric patients; \117\ and the Rare Tumor Patient
Engagement Network,\118\ which aims to study rare tumors, including
pediatric tumors, and develop a network of clinical trials.
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\116\ https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-17-
049.html.
\117\ The foundation of this initiative began in 2017, with the
release of two FOAs to establish the Pediatric Immunotherapy Discovery
and Development Network (PI-DDN): https://grants.nih.gov/grants/guide/
rfa-files/RFA-CA-17-051.html; https://grants.nih.gov/grants/guide/rfa-
files/RFA-CA-17-050.html.
\118\ https://ccr.cancer.gov/research/cancer-moonshot.
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NCI is committed to addressing the unique scientific challenges and
opportunities that pediatric cancers pose in ways that lead to better
outcomes for children with cancer. NCI continues to demonstrate this
commitment through its ongoing support for childhood and adolescent
cancer research efforts, through a continued investment in basic
research and other crosscutting research efforts, and through its
collaborations with the childhood cancer community.
NCI also encourages you to visit the ``Childhood Cancers Research''
page on its website for additional information about current research,
including more comprehensive descriptions of some of the programs
mentioned above.\119\ Research on pediatric cancers will continue to be
a top priority.
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\119\ http://www.cancer.gov/researchandfunding/areas/childhood.
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indefinite delivery/indefinite quantity
Question. It is my understanding that NIH is using more Indefinite
Delivery/Indefinite Quantity (ID/IQ) awards, which can provide several
advantages: (1) greater competition in the procurement process; (2)
smaller well-defined program tasks; (3) tighter financial control on
each program task; and (4) incremental milestone driven funding.
However, many small, not-for-profit contractors have a difficult time
justifying the large commitment of time and resources when contracts
are small and delayed. Therefore, the return-on-investment for
contractors is becoming harder to justify. Can you discuss the issues
NIH faces with ID/IQ contracts and why they are not being more
regularly awarded?
Answer. NIH makes regular use of Indefinite Delivery/Indefinite
Quantity (ID/IQ) contracts and continues to look for more opportunities
to establish new or use existing ID/IQs. We carefully consider small
business opportunities when establishing or using the ID/IQs. The
advantages of establishing multiple award ID/IQs far outweigh the
challenges. However, one challenge is once the contracts are awarded,
new vendors tend to be unable to pursue NIH business for a period of
time because so much of the ordering is limited to the existing
contractors. Additionally, due to bid protests, NIH tends to award
contracts to a large number of contractors rather than limiting the
awardees to a smaller, more manageable pool. This tends to make the
competition at the task order level less efficient. Small companies
often feel the investment of time and energy expended when pursuing an
ID/IQ is potentially wasted when the competition for individual task
orders involves so many competitors and requires additional resources
to receive the order. One last issue is the inability to award flexible
orders when issuing task orders against multiple award ID/IQs. The firm
nature of the orders often cause the NIH program to consider other
arrangements such as a Blanket Purchase Agreement (BPA) against a GSA
Schedule contract.
______
Questions Submitted by Senator Patty Murray
functional genomics
Question. Fred Hutch researchers recently received NCI funds to
continue work on an approach termed functional genomics, in which they
focus directly on a patient's tumor cells. The approach can be applied
toward different types of cancer, to pinpoint which drugs work best for
an individual patient's tumor and identify drug resistance. With this
new infusion of funding, researchers will have the opportunity to
identify new drug targets in difficult to treat cancers and collaborate
with various partners to help oncologists deliver individually tailored
therapies to cancer patients. Can you tell me more about NCI's plans to
support this type of highly targeted treatment?
Answer. The National Cancer Institute (NCI) is supporting a wide
range of cancer genomic programs focused on understanding how cancer
develops, the molecular changes that drive cancer, and the vast tumor
heterogeneity within and across cancers. Precision oncology is rooted
in a deep understanding of the genetic and functional changes that
occur in cancer cells and the tumor microenvironment. NCI is committed
to supporting research in genomics and other disciplines to increase
our understanding of the complexity of cancer biology to advance
precision oncology.
The NCI Center for Cancer Genomics (CCG) unifies NCI's activities
in cancer genomics by aiming to synthesize research in different fields
of cancer genomics. CCG's programs and collaborations generate cancer
genomic and clinical data, and, importantly, make these data available
for widespread use by the research community. Using a collaborative
``team science'' approach, CCG engages in three complementary sub-
disciplines within cancer genomics: structural genomics, functional
genomics, and computational genomics. Structural genomics identifies
alterations in cancer that contribute to cancer growth, metastasis, and
recurrence. Functional genomics studies the role of cancer genes,
mutations, and pathways, and develops therapeutic strategies to target
them. Computational genomics uses statistical and computational
approaches to derive insight from big data on cancer. By testing
hypotheses derived from structural genomics research, and by generating
new ideas from experiments in cancer cells, functional genomics
research reveals patterns in cancer biology that can be translated into
novel therapies for precision cancer care.
To translate genomic insights to the clinic, the findings must be
tested in models of cancer to understand the functional impact of
insults to the genome. In addition to supporting investigator-initiated
grants and other extramural research in this area, NCI provides
resources to the extramural community to support their research on the
molecular changes that drive cancer. One example is The Cancer Genome
Atlas (TCGA),\120\ which contains the genomes of more than 30 types of
cancer and catalogues thousands of genetic alterations in cancer cells
that could be targets for existing or new therapies. Another example is
the Genomics Data Commons (GDC), a unified data system for sharing
genomic and clinical data launched in 2016. The GDC centralizes,
standardizes, and makes data from large-scale NCI programs more
accessible and useful to scientists and clinicians. One measure of the
importance of this resource is that non-profit and for-profit
organizations are now offering their data sets for sharing through the
GDC.
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\120\ Collaboration with the National Human Genome Research
Institute.
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One program geared towards bridging the knowledge gap between data
generated from large-scale genomic studies and the underlying etiology
of cancer development, progression, and/or metastasis is the Cancer
Target Discovery and Development (CTD) \96\ Network. The CTD \96\
Network is accelerating the use of molecular data to speed the
translation of basic science findings to clinical trials. Through
validation studies that rely on bioinformatics analysis of genomic
data, high-throughput screening of small molecules, and research that
involves cancer models or other tools, the CTD \96\ Network supports
research to capitalize on a growing volume of data to identify new
cancer vulnerabilities and treatments.
The initial phase of CTD \96\ Network generated 19 novel
bioinformatic tools which enable the identification of therapeutic
targets, gene and molecular networks, and driver mutations (genetic
changes that drive the development of cancers), and chemical
sensitivities. These tools are available to the scientific community
and can be accessed through the CTD \96\ analytical tools page.\121\
During the first phase, the Network has been highly successful and
published over 60 manuscripts with preclinical and clinical
relevance.\96\ The results from some studies have provided supporting
evidence for the initiation of several clinical trials.\122\ Highlights
of progress during this first phase include the discovering the
mechanism of action of a compound that selectively inhibits the growth
of breast cancer stem cells, and the discovery of novel, rare driver
mutations in pancreatic cancer and confirmation of their importance
through validation studies in model systems.
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\121\ https://ocg.cancer.gov/programs/ctd2/analytical-tools.
\122\ https://ocg.cancer.gov/programs/ctd2/publications.
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The second phase of the CTD \96\ Network (multi-year awards funded
in fiscal year 2017) is exploring cancer complexity in terms of various
types of heterogeneity, that is differences in genetic characteristics
within each patient (i.e., across tumor tissue, the tumor
microenvironment, and normal tissue), as well as genetic differences
within each tumor (i.e., different tumor cells may have different
genomic characteristics and molecular drivers). Projects seek to
understand the potential impacts of heterogeneity (i.e., acquired
resistance to chemo and immunotherapies) and develop efficient
strategies to overcome treatment resistance. Through active
collaboration and the sharing of data and resources with the cancer
research community, each of the twelve funded Centers within the CTD
\96\ Network will utilize functional and computational genomic
approaches to contribute to the understanding of mechanisms of cancer
and potentially accelerate the development of clinically useful
markers, targets, and therapeutics for precision oncology.
Complimenting these efforts, NCI is supporting development of the
Human Tumor Atlas Network (HTAN) as part of the Cancer Moonshot.\SM\
The HTAN is planned to be a 5-year pilot consortium focused on
generating comprehensive, multidimensional tumor atlases (detailed
mapping of molecular and cellular characteristics) describing key
transitions in the development of cancer that will inform future cancer
research and, ultimately, clinical decisionmaking. The HTAN efforts
build upon and extend the efforts of TCGA. The HTAN will draw upon the
lessons learned from TCGA, address its limitations, and use evolving
state-of-the-art information technology and other emerging technologies
to achieve its goal. Additional efforts supported by the Cancer
Moonshot,\SM\ such as those focused on cancer immunology and
immunotherapy, will increase our knowledge of genetic changes that
occur in cancer cells and the tumor microenvironment to enable use of
precision immunotherapy for both adult and pediatric cancer patients.
Currently ongoing Precision Oncology trials that utilize molecular
characterization to inform treatment choice include the NCI Molecular
Analysis for Therapy Choice (NCI-MATCH) Trial and the Pediatric MATCH
Trial. For these trials, rather than selecting therapies based on where
a tumor originated in the body, the focus is on evaluating the
effectiveness of treating cancer based on specific genetic changes. In
2017, the adult NCI-MATCH Trial achieved its enrollment goal, nearly 2
years ahead of schedule. The trial involves more than 6,000 patients
from all 50 States. NCI also successfully opened enrollment for the
Pediatric MATCH Trial in 2017. Other NCI precision medicine trials
include the Lung Cancer Master Protocol (Lung-MAP) Trial, the Adjuvant
Lung Cancer Enrichment Marker Identification and Sequencing Trials
(ALCHEMIST), and Molecular Profiling-Based Assignment of Cancer Therapy
(NCI-MPACT) Trial.
NCI's investment in cancer genomics programs such as the CTD \96\
and the HTAN will inform future precision medicine trials and build
upon the results of ongoing trials in this paradigm changing approach
to precision oncology for cancer patients.
nci-funded research
Question. Dr. Sharpless, cancer immunotherapy is one of the great
success stories of NCI-funded research. After decades of basic
research, patients today are receiving immunotherapy treatments for a
growing number of cancers, including melanoma, lung cancer, lymphoma,
leukemia, head-and-neck cancer, and more. Many of these patients
previously had few other treatment options. Some who had even very
advanced cancer are now doing extremely well. And, we are just getting
started. What is being done to educate healthcare providers about the
principles of immunotherapy and how to manage the toxicity? And what
efforts is NCI taking to retrain laboratory scientists to advance the
immunotherapy field?
Answer. Immunotherapy, a treatment that uses a patient's own immune
system to help fight diseases including cancer, is a major focus of
National Cancer Institute (NCI)-supported research that spans basic
science to clinical applications. NCI-supported researchers publish
their research results in peer-reviewed journals, and frequently
present their research at professional conferences, including the
annual meetings of the American Association of Cancer Research (AACR)
and the American Society of Clinical Oncology (ASCO). For example, at
the June 2018 meeting of ASCO, NCI-supported researchers participated
in a two-day seminar entitled ``Cancer Immunotherapy Today: Maximizing
Patient Outcomes,'' co-hosted by ASCO and the Society for Immunotherapy
of Cancer (SITC).\123\ This session provided continuing education to
clinical oncologists, nurses, pharmacists, and the entire medical team
on effectively providing the most up-to-date and comprehensive
immunotherapy options to their patients, and included guidance on
patient selection and managing toxicities.
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\123\ https://www.sitcancer.org/events/event-
description?CalendarEventKey=796e7e32-bba9-
4712-9491-daed98d7a3c8&Home=%2fevents%2fcalendar.
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NCI supports training for immunotherapy investigators across the
research spectrum, from basic to translational to clinical research.
NCI's Center for Cancer Research (CCR) supports an Immunotherapy
Fellowship for physicians who have completed a medical oncology
fellowship program and who seek specialized training in immunotherapy,
including the design and facilitation of clinical trials.\124\
Immunotherapy researchers are encouraged to apply for NCI-supported
training awards.\125\ Different awards are available to pre- and post-
doctoral researchers, clinical fellows, established investigators, and
non-tenured early-career stage faculty.
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\124\ https://www.cc.nih.gov/training/gme/programs/
immunotherapy.html.
\125\ https://www.cancer.gov/grants-training/training/funding.
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NCI's intramural Center of Excellence in Immunotherapy (CEI)
focuses on creating opportunities for immunologists in the intramural
and extramural communities to exchange information and to facilitate
collaborations. To that end, CEI sponsors an annual series of meetings
on cancer-related immunology research, with the next meeting entitled
``Frontiers in Basic Immunology'' \126\ planned for September 2018.
Prior meetings included the 2017 ``Cancer and Immunology and
Immunotherapy: From Conception to Delivery,'' meeting and the 2016
``Immunotherapy Biomarkers 2016: Overcoming the Barriers'' meeting.
Videos of the presentations and discussions are freely available
online.\127\
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\126\ https://ncif-staging.ncifcrf.gov/Events/Conferences/
Frontiers/.
\127\ https://ncif-staging.ncifcrf.gov/Events/Conferences/
Frontiers/PastConferences.aspx.
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In addition to these resources, NCI plans to support new training
and education efforts in fiscal year 2018 including supplemental
training awards for cancer immunotherapy, and additional funding to
support the development of a consortium. The consortium will engage
external partners that will develop standardized educational content
for oncology care providers and deliver the content nationwide.
NCI will continue to encourage the dissemination of research
advances and the career development of the immunotherapy research
community.
______
Questions Submitted to Nora Volkow, M.D.
Question Submitted by Senator Roy Blunt
chronic pain
Question. Dr. Volkow, unfortunately, much of the opioid crisis we
are experiencing today can be linked to opioid prescriptions to treat
chronic pain. Your Institute has studied the effectiveness and risks
associated with long-term opioid use for chronic pain, but what
research is currently ongoing related to new and alternative options to
treat chronic pain other than opioids?
Answer. In fiscal year 2017, NIH spent $516 million on pain
research ranging from cell and molecular mechanisms of acute and
chronic pain to safe, effective therapy development, to large scale
clinical trials. The portfolio includes many research projects that
address the pressing need to develop new non-opioid, non-addictive,
pain treatments. Research studies range from early-stage drug target
discovery focusing on molecular pathways of pain signaling, including
exploration of receptors and channels as potential non-addictive
analgesic targets to testing in behavioral models. A number of targets
identified through NIH basic science, such as nerve growth factor
receptor and pain-related ion channels, are now being pursued in
industry-sponsored clinical trials for non-addictive treatments. NIH
supported early development of calcitonin receptor gene protein, a
compound recently approved for migraine treatment.
A tissue--based tool for screening potential migraine drugs is
under development and a library of small molecules is being leveraged
to screen candidates for optimization as analgesics. Tissue engineering
and regeneration to create tissue scaffolding and microenvironments to
promote wound healing, joint cartilage, and intervertebral disc
replacements is being applied to relieve pain. Neural stimulation
technologies for chronic, intractable pain are being improved. For
example, wearable ultrasound devices and implantable micro-stimulators
are being tested on peripheral and central nervous system targets to
relieve pain.
Evaluation and dissemination of complementary and integrative
health approaches is a crucial component of quality pain management.
NIH-supported studies include mechanism-based clinical studies on
cognitive behavior therapy, exercise, yoga, acupuncture, massage,
fitness, and mindfulness practices are an important component of the
NIH Federal pain research portfolio.
______
Question Submitted by Senator Joe Manchin, III
research into alternative pain management
Question. Dr. Volkow, communities across the country are seeing an
alarming rise in substance abuse and addiction to prescription opioids.
Opioids killed more than 42,000 Americans in 2016. That's 115 people
every day. In West Virginia, we lost more than 909 people to a drug
overdose in 2017.
So many of these people who become addicted started taking these
drugs because their doctor prescribed them for pain even though--
according to the CDC--there is little evidence that opioids improve
chronic pain.
This is a public health crisis and we have to find a better way. I
am proud to have worked with my colleagues to dedicate an additional
$500 million to NIH for research on opioid addiction, the development
of opioid alternatives, pain management, and addiction treatment.
That is why I am so worried about the President's Budget Request to
cut more than $500 million from the National Institute on Drug Abuse.
Dr. Volkow, what research is being done to develop non-addictive
alternative pain management options for patients--particularly those
dealing with long-term, chronic pain who are currently being prescribed
opioids despite the lack of evidence of their effectiveness?
What impact would the proposed budget cuts have on NIDA's ability
to do continue to do this research?
Answer. Chronic pain is a complex neurological condition, driven by
many biological, environmental, social, and developmental factors. To
this end, NIH supports a range of activities to advance research on
understanding and treating pain.
Chronic pain is a disorder of brain circuits, and the
neurotechnologies emanating from the trans-NIH Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative enable
scientists to explore these circuits to advance diagnostics and
therapeutics. Similarly, the Stimulating Peripheral Activity to Relieve
Conditions (SPARC) program at the NIH Common Fund supports novel means
to alter peripheral nerve pathways to relieve pelvic pain and has
promise for application to other pain conditions.
Complementary and integrative health approaches address the
biopsychosocial nature of chronic pain and its treatment. NIH supports
numerous clinical studies on cognitive behavioral therapy (CBT),
exercise, yoga, acupuncture, massage, fitness, and mindfulness
practices. For example, trials showed that mindfulness-based stress
reduction with CBT and yoga improved function and reduced low back
pain.
The NIH Health Care Systems Research Collaboratory supports large-
scale, pragmatic clinical trials focused on the management of patients
with multiple chronic conditions, including pain. One study is
evaluating multidisciplinary approaches to pain management in the
primary care setting in patients who are currently on long-term
opioids. This large-scale trial aims to develop integrated pain care
approaches to reduce pain and opioid use in patients enrolled in a
large healthcare system. The NIH, Department of Defense and Department
of Veterans Affairs Pain Management Collaboratory's goal is to develop
the capacity to implement cost-effective large-scale clinical research
in military and veteran healthcare delivery organizations focusing on
non-pharmacological approaches to pain management and other comorbid
conditions.
To accelerate the development of novel non-addictive chronic pain
medications and devices, NIH is establishing a Clinical Trial Network
to optimize analgesic trial design, target appropriate patient
populations for trials, and engage research expertise at existing
clinical sites. A related initiative is to pursue, through the Network,
development and validation of biomarkers of pharmacodynamic response
and biomarkers for treatment response to optimize patient
stratification based on phenotyping and thus allow smaller sample size
and improve assay sensitivity for screening novel analgesics. These
efforts provide a valuable set of clinical research resources which
will allow researchers to identify effective pain medications more
quickly.
The NIH Common Fund is currently in the planning stages of a broad
scale clinical study to identify a set of objective biomarkers to
predict which patients will transition to chronic pain after an acute
pain event. This program, known as Acute to Chronic Pain Signatures
Program, will collect longitudinal data from two large patient groups
that have acute pain associated with a surgical procedure or an acute
musculoskeletal trauma such as a bone fracture. Neuroimaging, genetic
and molecular data, sensory testing, and psychosocial assessments from
patients will be collected for months after the acute pain event and
analyzed to explore transition or resilience characteristics to help
predict which patients will recover and which patients will develop
long-lasting pain. Identifying such markers will help to predict which
people might be at risk for developing chronic pain, reducing reliance
on opioids thereby, guide precision medicine approaches to prevent
chronic pain, and by doing so, reducing our reliance on opioids.
The current state of the science, emerging technologies, and
mobilization of the research community holds great promise for advances
in evidence-based, quality pain care.
SUBCOMMITTEE RECESS
Senator Blunt. The subcommittee stands in recess.
[Whereupon, at 11:38 a.m., Thursday, May 17, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]
MATERIAL SUBMITTED SUBSEQUENT TO THE HEARING
[Clerk's Note.--The following outside witness testimony was
received subsequent to the hearing for inclusion in the
record.]
Prepared Statement of Christopher P. Austin, M.D., Director, National
Center for Advancing Translational Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National Center
for Advancing Translational Sciences (NCATS) of the National Institutes
of Health.
NCATS is dedicated to understanding and transforming translation,
defined as the process of turning scientific, medical, and public
health observations in the laboratory, clinic, and community into
interventions that improve the health of individuals and the public. At
a time of unprecedented science discoveries, our collective ability to
translate research findings into health benefits often is too slow and
ineffective. Developing a new drug requires on average 10 to 15 years
and more than $2 billion given the high prevalence of failure along the
translational pipeline. We must deliver the promise of science to
patients in an accelerated and more efficient manner. NCATS studies and
supports translation on a system-wide level as a scientific and
operational problem, addressing roadblocks that impede or preclude
promising advances.
accelerating clinical translation
The largest portion of NCATS' budget is dedicated to its Clinical
and Translational Science Awards (CTSA) Program. Through this program,
NCATS supports a national network of medical research centers, called
hubs, that collaborate locally, regionally, and nationally to foster
innovation in clinical researcher training, patient engagement, and new
research tools and processes. There are multiple initiatives within
this program, including the Trial Innovation Network that is composed
of the hubs as well as Trial Innovation Centers and a Recruitment
Innovation Center. Through this network, researchers are identifying
and implementing ways to improve the clinical trial process, including
participant recruitment and other aspects of clinical trial conduct.
The process of obtaining ethics approval from multiple
institutional review boards (IRBs) to conduct a clinical research study
at multiple institutions is a longstanding challenge that can lead to
significant delays in study activation. To address this problem, NCATS
supported the development of a single IRB reliance platform for
multisite clinical studies, enabling study sites to rely on a single
IRB of record. The platform, known as the Streamlined, Multisite,
Accelerated Resources for Trials (SMART) IRB, includes resources such
as umbrella agreements, guidance documents, and consultation services
that investigators nationwide can access to harmonize and streamline
IRB review for their own multisite studies. SMART IRB is serving as a
roadmap to help implement the NIH policy released in June 2016 that
requires all NIH-funded multisite clinical studies to use a single IRB.
Providing the resources to train, cultivate, and sustain future
leaders of the biomedical research workforce is another key CTSA
Program emphasis. The program supports a coordinated, national effort
to help ensure a pipeline of trained translational investigators who
can move basic research findings into applications for improving health
outcomes as novel therapies, diagnostics, and preventives. Program
grantees have developed clinical and translational sciences training
resources, including educational core competencies, best practices for
training mentors, and curriculum materials. These tools are freely
available, and many institutions nationwide are using them.
Engaging patients at all stages of translation is crucial; their
perspectives as members of the research team provide insights, focus,
urgency and connectivity that can be instrumental in making the
development, testing and deployment of new interventions more
effective. NCATS supports the Rare Diseases Clinical Research Network
(RDCRN) and requires each consortia member to include patient groups as
full partners on their research teams, an approach that helps achieve
greater success. The RDCRN Coalition of Patient Advocacy Groups
develops and shares best practices, and the RDCRN website includes a
contact registry for patients who may be interested in participating in
RDCRN clinical studies. Rare diseases, which cumulatively affect
approximately one in 10 people in the U.S., are in crucial need of
innovative translational technologies, and are thus a crucial NCATS
focus.
Measurable outcomes can help determine whether a new translational
process is actually an improvement. NCATS' Discovering New Therapeutic
Uses for Existing Molecules program matches academic investigators with
pharmaceutical companies that have compounds that were found to be
ineffective in treating specific diseases. Repurposing these compounds
for potentially treating other diseases saves time in the drug
development process because significant foundational work already has
been completed. NCATS helps to further accelerate this process by
providing collaboration agreement templates that now are being used
broadly in the research community and by supporting researchers with
new ideas for how existing compounds can be repurposed.
finding new therapies for clinical study
NCATS also is dedicated to removing pre-clinical translational
science roadblocks. Through its Therapeutics for Rare and Neglected
Diseases (TRND) program, the Center works to ``de-risk'' potential
therapeutics so that private sector companies may be more inclined to
acquire them to finish their development.
Despite promising results in clinical trials outside of the U.S.,
work on further developing a gene therapy for the rare pediatric
disease aromatic L-amino acid decarboxylase (AADC) deficiency was
seemingly insurmountable. Through TRND, NCATS teamed with a private
sector partner, Agilis Biotherapeutics, to convert promise into
reality, jointly creating a manufacturing process for a therapy that
complies with FDA regulations, and obtaining the required pre-clinical
data. In addition to getting this potentially lifesaving therapy to
patients, this project established technological and regulatory models
that will accelerate development of other rare disease gene therapies.
The NCATS Cures Acceleration Network (CAN) supports high-risk,
innovative programs to advance the development of high-need cures and
reduce significant barriers between research discovery and clinical
trials. Through the CAN-funded Tissue Chip for Drug Screening program,
NCATS is working on new methods for predicting both safety and efficacy
of experimental drugs using engineered ``chips'' that contain human
cells and model human organs. Current methods such as animal and cell
models are not always reliably predictive and can result in wasted time
and effort. In addition to developing these chips for testing potential
drugs, NCATS soon will send tissue chips to the International Space
Station (ISS) for research on the effect of microgravity on these model
organs. Microgravity can accelerate aging and have other effects
relevant to diseases on Earth, making the ISS a unique and significant
research environment.
New drug development for currently untreatable diseases has been
greatly limited because known chemical structures affect only 10
percent of potential drug targets within the human body. With CAN
support, NCATS plans to launch its Automated Synthesis Platform for
Innovative Research and Execution (ASPIRE) program to bring together
chemistry, robotic engineering, biological activity testing, and
artificial intelligence. Tools developed through ASPIRE will minimize
the time chemists spend on tedious and repetitive tasks, freeing them
up for more complicated pursuits such as designing, synthesizing, and
testing compounds for diseases that currently have no treatment.
adaptability to tackle emerging public health needs
With its unique collection of programs, initiatives and resources,
NCATS has the capacity and capability to address public health crises.
For example, a team of researchers from NCATS and the Icahn School of
Medicine at Mount Sinai developed a miniaturized assay for high-
throughput screening to find compounds that block the ability of Ebola
virus-like particles (VLPs) to enter and infect cells. A screen using
2,816 compounds identified 53 drugs with entry-blocking activity
against Ebola VLPs.
In another example, investigators from Johns Hopkins University and
Florida State University collaborated with NCATS experts on drug
repurposing and high throughput screening to identify rapidly two
classes of existing compounds that potentially can be used to fight
Zika. These compounds were effective either in inhibiting the
replication of the Zika virus or in preventing the virus from killing
brain cells. All data have been made available through public
databases, allowing these compounds to be further studied by the
broader research community.
NCATS also is well-positioned to help combat the current national
epidemic of opioid abuse. The Center's high-throughput screening
facility could be used to test potential opioid abuse therapeutics, and
CTSA Program-supported researchers could help identify opioid patients
and rapidly enroll them in multisite clinical trials.
conclusion
Through its programs and initiatives described above, and others,
NCATS is improving health through smarter science in unprecedented
ways, with the ultimate goal of getting more treatments to more
patients--and to the public at large--more quickly.
______
Prepared Statement of Dr. James F. Battey, Jr., M.D., Ph.D., Director,
National Institutue on Deafness and Other Communication Disorders
Mr. Chairman and Members of the Subcommittee: I am pleased to
present the President's fiscal year 2019 budget request for the
National Institute on Deafness and Other Communication Disorders
(NIDCD) of the National Institutes of Health (NIH).
NIDCD conducts and supports research and research training in the
normal and disordered processes of hearing, balance, taste, smell,
voice, speech, and language. NIDCD focuses on disorders that affect the
quality of life of millions of Americans in their homes, workplaces,
and communities. The physical, emotional, and economic impact for
individuals living with these disorders is tremendous. NIDCD continues
to make investments to improve our understanding of the underlying
causes of communication disorders, as well as their treatment and
prevention. It is a time of extraordinary promise, and I am excited to
be able to share with you some of NIDCD's ongoing research and planned
activities on communication disorders.
preventing hearing loss caused by common cancer drug
NIDCD intramural researchers have discovered why cisplatin and
other popular and effective platinum-based chemotherapy drugs cause
ototoxicity--damage to the delicate cells in the inner ear which can
lead to hearing loss. In previous studies, researchers have focused on
why the inner ear is more vulnerable to cisplatin ototoxicity than
other areas in the body. The NIDCD research team, however, studied the
cause of cisplatin ototoxicity from a different perspective; they
explored if cisplatin remains in the inner ear continuing to cause
damage for a longer time than in other areas of the body. The
scientists found that, both in mice and humans, cisplatin remains in
the inner ear long after it is already eliminated from other areas of
the body. These results suggest that the inner ear readily takes up
cisplatin, but it has little ability to remove the drug.
In mouse and human tissues, the research team saw the highest
accumulation of cisplatin was in a part of the inner ear called the
stria vascularis, which is responsible for maintaining the positive
electrical charge in inner ear fluid that certain cells need to detect
sound. The research team determined that the accumulation of cisplatin
in the stria vascularis portion of the inner ear contributed to
cisplatin-related hearing loss.
This research suggests that if we can find ways to avoid cisplatin
from entering the stria vascularis during treatment with cisplatin, we
might be able to prevent the hearing loss that goes along with it. As
hearing loss is often associated with isolation, depression, and other
conditions, helping to preserve hearing in individuals who are required
to undergo cancer treatment with these chemotherapy drugs would greatly
contribute to maintaining the quality of their lives.
treating hereditary deafness with gene editing
Hearing problems in infants and children can delay the development
of voice, speech, and language skills. Approximately 80 percent of
hearing loss is due to genetic factors, and treatment options for
genetic deafness are limited. A research team, supported in part by
NIDCD, used a mouse model of human genetic deafness to design a
potential treatment approach.
Mutations in a particular gene, TMC1, are known to cause hereditary
deafness in both humans and mice. The mutation causes the death of
sensory hair cells in the cochlea of the inner ear. These hair cells
transform sound waves into electrical signals that the brain recognizes
as sound. To prevent hair cell death and the resulting progressive
hearing loss in mice with the TMC1 mutation, the scientists used the
CRISPR-Cas9 gene-editing system to remove the mutation and disable the
gene.
The researchers developed a novel approach to deliver the gene-
editing complex into the inner ears of newborn mice. They packaged the
gene-editing complexes in lipids (fats) that form structures called
liposomes. The liposome-packaged complexes move readily through cell
membranes into cells. Eight weeks later, substantially more hair cells
survived in ears of treated compared to untreated mice. The treatment
also significantly reduced progressive hearing loss. This novel
strategy may help scientists develop new therapies for hearing loss
caused by inherited genetic mutations.
taste, balance, and more--a proton channel with many roles
Our ability to taste helps us choose and enjoy nutritious foods and
avoid foods that have been spoiled by bacteria. On our tongue, sensory
taste cells respond to chemicals that are released from food and drink.
Taste cells respond to these chemicals via protein receptors and
channels that are specific to certain taste molecules. For instance, to
detect sourness in food, specialized channels let protons (Hydrogen
atoms) that are released from acidic sour-tasting foods enter proton-
sensitive, ``sour'' taste cells on the tongue.
The identity of this ``sour detector'' protein has been elusive.
Now, NIDCD-supported scientists have located a protein called OTOP1 and
determined that it forms a channel that allows protons to enter taste
cells on the tongue. They have also confirmed that human OTOP1 forms a
channel with properties similar to those of the mouse OTOP1 protein.
When OTOP1 gene was altered in mice, the scientists observed that taste
cells had significantly fewer protons going into them. This evidence,
together with other supporting studies on OTOP1, suggests that OTOP1 is
the long-sought after sour taste receptor. The next step to test this
theory will be to record whether mice that lack OTOP1 respond to sour
tastes. Studies like this one, that increase our understanding about
how we taste, may help scientists learn to restore a sense of taste to
those who have lost it due to disease or injury.
This study may help us understand far more than just how we detect
taste. OTOP1 is also required for the vestibular (balance) system in
the inner ear to detect gravity, so it is important for helping us keep
our balance. OTOP1 is also expressed in many other body tissues,
including fat, heart, uterus, breast, and the nervous system. Since we
know that OTOP1 functions as a proton-sensitive channel, what we learn
from this taste study may help us understand cell signaling in these
other tissues, too. When protons enter cells, they change the acid/base
(pH) concentration. So, a better understanding of OTOP1 could also help
us understand other body processes that involve changes in pH, such as
pain sensation, fat metabolism, and pH changes seen in cancer cells.
personalized voices for people with severely impaired speech
Approximately 2.5 million Americans and millions more people
worldwide have a severe speech impairment since birth or as a result of
a neurological disorder that occurred later in life, such as a stroke.
For these people, communicating is a daily challenge that relies upon
their use of a computer to generate their voice. While these devices go
a long way toward helping people with a voice disorder express
themselves, the synthetic voices produced are usually a poor
representation of a natural human voice. In addition, the lack of
diversity in available synthetic voices means that many people must use
the same generic voice.
Through a Small Business Innovation Research Program grant, NIDCD
voice scientists have moved research from the lab into real-world
application. Researchers are in the second phase of developing a
personalized text-to-speech augmentative and alternative communication
(AAC) device called VocaliD. This device involves blending the speech
of two individuals--a donor and the recipient. First, a recording is
made of whatever vocal sounds the recipient is still able to make. The
next step is accomplished with the help of a volunteer voice donor. For
the best results, the donor should match the recipient in terms of
gender, age, region of origin, and other characteristics. By
commercializing VocaliD, NIDCD scientists have refined the technology,
automating certain steps and making the entire process of creating
personalized, synthetic voices faster and more efficient. These
improvements will advance speech synthesis while humanizing machine-
mediated spoken interaction for AAC devices and beyond.
______
Prepared Statement of Diana W. Bianchi, M.D., Director, Eunice Kennedy
Shriver, National Institute of Child Health and Human Development
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD) of the National Institutes of Health (NIH).
achieving lifelong health
Understanding human development, both normative and atypical, is at
the core of NICHD's mission. As our name reflects, NICHD supports and
conducts a wide range of research, including but not limited to
pediatric research, on all phases of human development to maturity,
with the goal of achieving optimal health, cognitive, and physical
function.
Child Health.--The epidemic of opioid use disorder and its
consequences is among the most serious public health threats in this
country today. Among those exposed to opioid use are the thousands of
infants born to women with the disorder. Every 15 minutes, a baby is
born with Neonatal Opioid Withdrawal Syndrome (NOWS) in the United
States; to date, NOWS has cost about $2 billion in additional costs for
Medicaid-financed deliveries.\1\ Symptoms of NOWS, also known as
Neonatal Abstinence Syndrome (NAS), often do not begin until after
infants have been discharged from the hospital. Their needs are placing
huge stresses on the healthcare and foster care systems nationwide. To
address this problem, NIH launched a new study called the Advancing
Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) to
evaluate treatment options and improve clinical care of affected
infants. The study is a collaboration between NICHD's Neonatal Research
Network and the new IDeA States Pediatric Clinical Trials Network
(within the Office of the NIH Director's Environmental Influences on
Child Health Outcomes program), with sites located in rural and
medically underserved communities. This joint research effort will use
the reach of both networks to assess the prevalence of NOWS, understand
current approaches to managing these cases, and develop protocols for
conducting large scale studies to inform clinical care, so that these
babies may get a better start in life.
---------------------------------------------------------------------------
\1\ Winkelman, T.N., Villapiano, N., Kozhimannil, K.B., Davis,
M.M., Patrick, S.W., Incidence & Costs of Neonatal Abstinence Syndrome
among Infants with Medicaid: 2004-2014, Pediatrics published online:
March 23, 2018 (doi: 10.1542/peds.2017-3520).
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One of NICHD's longest standing research priorities is to improve
the lives and health of people with intellectual and developmental
disabilities, such as Down syndrome. NICHD leads the public-private
Down Syndrome Consortium, which includes 11 NIH Institutes and Centers,
13 national and international organizations whose missions focus on
Down syndrome, and individuals with Down syndrome and family members.
Consortium members provided valuable input to DS Directions: The NIH
Down Syndrome Research Plan. Among the plan's major objectives is the
call for research on the co-existing conditions commonly experienced by
people with Down syndrome. For example, studies show that virtually all
middle-aged adults with Down syndrome exhibit the neuropathological
hallmarks of Alzheimer's disease, 50 percent of whom will develop this
type of change to the brain by age 40. Funded jointly by NICHD and the
National Institute on Aging, a new project, the Alzheimer's Biomarker
Consortium--Down Syndrome (ABC-DS), seeks to identify biomarkers and
use brain imaging to help us understand the progression of the disease.
In addition, the research teams will make their data and samples freely
available to qualified researchers worldwide, with the goal of
accelerating the testing of potential interventions, which in turn may
have widespread implications for Alzheimer's and other conditions. In
fiscal year 2018, NICHD will lead a major new initiative to explore the
risk and resilience of people with Down syndrome to common, co-existing
conditions such as autism, cancer, and cardiovascular disease.
NICHD's research on child health explores basic biological
processes that control healthy or atypical development, translational
research, behavioral and social science, and clinical studies. Basic
research studies provide fundamental knowledge essential to
understanding causes of structural and functional birth defects. NICHD
has long provided the evidence base informing the panel of conditions
included in newborn screening tests to help diagnose and treat infants
early. Further, in collaboration with NHGRI, the Newborn Sequencing in
Genomic Medicine and Public Health (NSIGHT) is exploring the challenges
and opportunities associated with sequencing the entire genome of a
newborn infant to advance our understanding of undiagnosed disorders.
And, although it is widely recognized that children are not small
adults, only five of the 80 drugs most frequently used in newborns and
infants have been labeled for pediatric use to date. However, progress
is being made under The Best Pharmaceuticals for Children Act,
reauthorized by Congress for the fourth time in summer 2017, which
charged NIH/NICHD with leading a trans-NIH effort on pediatric
therapeutic needs. This year, through its Pediatric Trials Network,
NICHD tested a commonly used combined antibiotic (piperacillin-
tazobactam), finding the dose of this combination drug that is safe for
infants who acquire severe infections in the hospital. NICHD-supported
researchers also recently reported that children who are engaged during
shared reading experience a boost in the area of the brain that is
involved in language development, comprehension, memory, and problem
solving; understanding how reading shapes a child's brain can help
educators and parents develop and use effective early learning
strategies.
Maternal Health.--The World Health Organization defines maternal
mortality as the death of a woman while pregnant or within 42 days
after the pregnancy ends due to causes related to or aggravated by the
pregnancy. Between 1987 and 2013, maternal mortality in the United
States increased from 7.2 to 17.3 per 100,000 live births, the only
developed nation in which the rates have been rising since 2000. NICHD
supports a wide range of research efforts to counter this disturbing
trend. For example, NICHD-supported researchers studying placental
abruption (a dangerous condition that occurs when the placenta
separates from the uterus before birth) found that women who had a
placental abruption were about twice as likely to have abnormal levels
of specific proteins in their blood. These results may help identify
women at risk in the future.
NICHD is supporting two major projects to gather unprecedented
amounts of information about pregnancy. Its ongoing Human Placenta
Project, designed to provide insights into placental health
noninvasively and in real time, continues to yield new data to improve
maternal health and pregnancy outcomes. Another effort launched this
year, PregSource is a longitudinal, crowd-sourced, citizen science
registry that will expand our knowledge about women's typical
experiences during pregnancy and after birth, the effects of pregnancy
on women's lives, and special health challenges some women face. In
addition, many pregnant or breastfeeding women must either take
prescription medications to ensure their own health or are urged to
take medications to benefit the baby's health outcomes. As part of the
21st Century Cures Act legislation, NICHD was asked to lead the newly
mandated Federal Task Force on Research Specific to Pregnant Women and
Lactating Women. Although pregnant women in the United States take
between three and five prescription medications, usually for serious
health conditions, very few of these therapies have been tested during
pregnancy. Almost nothing is known about the transfer of medications
into breast milk, nor the risks and benefits of breastfeeding while on
medication. The Task Force's report and recommendations are due to the
Secretary of Health and Human Services and Congress by September 2018,
which will shed light on this understudied issue.
Rehabilitation.--About 5 percent of children aged 5 to 17 in the
United States live with disability. Conditions such as brain injury,
cerebral palsy, or spina bifida can impede children's education and
future potential to lead productive lives. The 2016 NIH Research Plan
on Rehabilitation, led by the National Center for Medical
Rehabilitation Research (NCMRR) at NICHD and the trans-NIH
Rehabilitation Working Group, set out priority areas for medical
rehabilitation research and assistive technologies to improve the lives
of people of all ages. Multiple funding opportunities have been
published to encourage scientists to submit applications on topics such
as sleep disorders during medical rehabilitation; grants recently have
been awarded on the biomechanics of movement and regenerative medicine.
Another priority is to support research that will improve function for
individuals with limb loss, yet the lack of data on the number of
individuals who experience limb loss and the types of procedures or
devices they receive to enable them to return to optimal function at
home, school and work, has presented a barrier to research in this
area. This year, NCMRR, in partnership with the Department of Defense,
will solicit applications for a nationwide Limb Loss Registry to enable
researchers the data they need to develop new devices and track health
and functional outcomes.
Helping Young Scientists.--To continue to foster groundbreaking
health research, NICHD's commitment to investing in the next generation
of researchers has been unwavering. For example, the Institute holds an
annual young investigators conference to facilitate the training of
physician scientists. The conference focuses on developing the skills
needed by young clinician investigators who are working in any of the
areas within NICHD's mission. We are also analyzing long-term success
as a function of different types of training awards so that training
resources can be directed to provide the maximum return on investment.
To help young investigators get started with testing hypotheses and
performing original research and to make maximum use of public
investment, NICHD makes data and other research resources available
through the Data and Specimen Hub (DASH), which offers de-identified
data from clinical research on pregnancy, infant care, child health,
HIV/AIDS, and other topics. Currently, the repository includes data
from 63 studies, and more than 12,000 users have visited the site,
including many young investigators who are exploring possible research
collaborations; future plans include linking hundreds of thousands of
residual biospecimens to the de-identified data.
conclusion
To capitalize on the many scientific areas within NICHD's mission,
and to determine scientific priorities, the Institute is engaging in a
new strategic planning process, with input from a wide array of
stakeholders, and in collaboration with NIH and scientific leadership.
As the new plan emerges, NICHD will continue its life-changing research
efforts to improve the lives of children and families.
______
Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T, A.T.S,
Director, National Institute of Environmental Health Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Environmental Health Sciences of the National Institutes
of Health (NIH).
team science for health solutions
Human beings are faced with an increasingly complex environment in
which we experience thousands of exposures--both healthy and
hazardous--on any given day over the course of our lifetimes. Although
advances in knowledge and technology enable individual scientists to
delve deeper than ever into how such exposures may impact our health,
the use of diverse, multidisciplinary teams of scientists to
investigate complex problems offer the promise of accelerated discovery
to prevent disease and improve health. A 2015 report by the National
Research Council concluded that ``Several strands of research and data
suggest that team science can rapidly advance scientific and
technological innovation by increasing research impact, novelty,
productivity, and reach.'' Such outcomes are directly in line with the
imperatives of Optimize NIH and ReImagine HHS to increase efficiency,
maximize talent, and accelerate innovation.
Team science, in the NIEHS context, is the collaborative effort of
researchers from diverse scientific disciplines, often in partnership
with communities that have relevant experience or perspectives, to
solve public health problems that arise from environmental exposures.
NIEHS continues to build on a long tradition of interdisciplinary
approaches that engage a range of scientific and community stakeholders
in creating the knowledge to inform public health decisionmaking. I
will describe some of the ways in which we implement team science
approaches as we work to fulfill the mission of the NIEHS--to discover
how the environment affects people in order to promote healthier lives.
centers, consortia, and collaborations
NIEHS both conducts team science intramurally and supports team
science through a variety of center, consortia, and interagency
collaborations. We use the centers framework to capitalize on the
diverse talent at universities and create a supportive environment for
multidisciplinary science and community engagement. NIEHS-supported
centers include those focusing on areas such as Environmental Health
Sciences, Breast Cancer and the Environment, Environmental Health
Disparities, Children's Environmental Health and Disease Prevention,
and Oceans and Human Health. These centers provide a centralized hub to
support research, training, and scientific exchange among investigators
across disciplines and often in partnership with patient advocacy or
other community organizations. Each center must also conduct research
translation, provide information and education, and engage with
interested patient groups and communities.
The centers are highly productive and last year generated numerous
significant discoveries, including how omega-3 fatty acids contained in
fish oil could be used to treat asthma patients; that dementia is
linked to a certain genetic variation combined with exposure to air
pollution, and an impaired sense of smell in such persons may serve as
an early warning sign; that children with asthma may be more likely
become obese later in childhood or adolescence; links between exposure
to seasonal harmful algal blooms and elevated risk of amyotrophic
lateral sclerosis (ALS); and potentially safer alternatives to
bisphenol A (BPA), to name just a few.
Consortia are another way that NIEHS supports team science that
extends beyond a single institution to create a network of linked
expertise to focus on a complex environmental health problem or set of
related issues. NIEHS led the Gulf Long-term Followup (GuLF) Study and
the 5-year, $25.2-million Deepwater Horizon Research Consortia, both of
which partnered researchers with communities to investigate health
effects stemming from the oil spill, including the long-term mental
health impacts of the spill on coastal residents, especially women and
children; the resilience of individuals and communities; and whether
seafood in the Gulf was safe for human consumption. These research
partnerships continue to yield new insights: a 2017 study linked a
range of health problems in workers who were exposed to dispersants
used to clean up the oil spill.
Research needs identified by the Deepwater Horizon consortia
provided further momentum for the creation of the NIH Disaster Research
Response (DR2) program, which comprises a national framework for
research on the medical and public health aspects of disasters and
public health emergencies. Led by the NIEHS and the National Library of
Medicine, DR2 has rapidly grown into a Federal interagency effort with
broad engagement in the goal of understanding how to be prepared for
disasters and how to limit any negative disaster-related health
effects. Examples of such research include human health studies to
assess effects of exposures on first responders, worker volunteers, and
community members; characterizing chemical hazards in floodwaters and
identifying post-flood molds; and assessing risks to vulnerable people
such as those with asthma from wildfire pollution. DR2 tools and
trainings were used last year to enable critical data collection and
analysis, and inform response to the devastating Hurricanes Harvey,
Irma, and Maria. In addition, NIEHS awarded time-sensitive research
grants specifically aimed at hurricane response research.
NIEHS is leading the Nation's coordinated science response to
another type of environmental threat--the potential for serious human
health impacts from exposure to PFAS, the collective name for per- and
polyfluoroalkyl substances, chemicals widely used over the past 50
years in food packaging, lubricants, water-resistant coating, and fire-
fighting foams, and other manufacturing. Although some have been phased
out, these endocrine-disrupting chemicals continue to be found in
drinking water supplies in multiple States, and NIEHS-funded research
suggests links to health effects on immune and thyroid function, fetal
growth and development, risk of cancer and obesity, and others. NIEHS
helped to organize a recent meeting of 16 Federal agencies that focused
on exchanging information on PFAS exposure science, health science, and
remediation and treatment of contaminated areas, and generated
opportunities for collaborative research. The National Toxicology
Program Laboratory Branch, one of the NIEHS research components of this
interagency program, is also responding to public demand for more and
faster information on the threat posed by PFAS through its Rapid
Evaluation and Assessment of Chemical Toxicity (REACT) program.
Outcomes of these collaborative efforts will help to target research
and inform decisionmaking by both government and communities.
Perhaps the most prominent environmental hazard demanding a team
science approach from across a broad spectrum of disciplines is lead
exposure. NIEHS-supported science established the knowledge base for
lead's major health impacts. But although we understand the primary
outcomes of lead poisoning, particularly neurodevelopmental damage in
children, the need continues for research to make clear exactly how
lead works in the body to cause damage so that successful interventions
can be developed. An NIEHS-funded study using lead in baby teeth as a
marker of exposure found associations between lead levels just before
and after birth with the risk for and severity of autism in later
childhood. Another study of children whose mothers took multivitamins
during pregnancy suggested they were 30 percent less likely to develop
autism. The concerns are not just for children however; a recent study
estimated that low-level lead exposure (<5mg/dL blood) is responsible
for more than 400,000 deaths each year in the United States, some
250,000 of which from cardiovascular disease in adults. Combined with
the estimated half million children still exposed beyond the CDC
reference level, the health, economic, and societal consequences of
lead exposure remain great. NIEHS and our grantees are continuing to
respond to this threat through research, training for workers involved
in lead cleanup and remediation, and engaging with our Federal partners
on the President's Task Force on Environmental Health Risks and Safety
Risks to Children to develop a Federal Lead Strategy.
connecting the data points
No matter what the environmental health issue is, it has become
increasingly clear that finding solutions demands a strong commitment
to team science--data science, sharing, and integration offer the
promise of incredible breakthroughs in preventing disease and promoting
health, but require unprecedented levels of engagement, coordination,
and standardization across a rapidly evolving scientific landscape.
NIEHS has been working to foster data collaborations through support of
training grants in the Big Data to Knowledge (BD2K) initiative,
partnership with the NIH Data Commons, development of an NIEHS Data
Commons, convening of National Academies workshops, establishment of an
Office of Cyberinfrastructure, and prioritization of data science and
integration goals across our developing Strategic Plan.
To conclude, environmental health problems present large, costly,
and complex issues for our society that demand the focused attention of
multidisciplinary teams of scientists. NIEHS will continue to provide
the critical support and leadership necessary for such teams to succeed
in discoveries that will prevent disease and promote the health of the
American people.
______
Prepared Statement of Patricia Flatley Brennan, Director, National
Library of Medicine
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Library of Medicine of the National Institutes of Health (NIH).
accelerating biomedical discovery & data-powered health
The National Library of Medicine (NLM) plays an essential role in
catalyzing basic biomedical science through its cutting-edge data
science and informatics research, comprehensive information systems,
and extensive research training programs. As the world's largest
biomedical library, NLM acquires, organizes, and delivers up-to-date
biomedical information across the United States and around the globe.
Millions of data scientists, health professionals, and members of the
public use NLM's electronic information sources every day to translate
research results into new treatments, products, and practices; provide
useful decision support for health professionals and patients; and
support disaster preparedness and response.
Leveraging its 180-year history of organizing and disseminating
biomedical literature, NLM is committed to the application of emerging
data science capabilities to challenges in biomedical research and
public health. It will do this by expanding its data and information
resources and providing leadership in both the acquisition and analysis
of data for discovery. It will expand its core biomedical literature
and genomic collections to include a broad array of health, clinical,
and biological data types and make these data findable, accessible,
interoperable, and reusable (FAIR) for research. NLM will enhance its
research programs to systematically characterize and curate data
describing complex health phenomena and to devise new methods to
uncover the knowledge held in data. It will restructure its biomedical
informatics training programs to address data science as they continue
to foster excellence and support a diverse workforce. NLM will develop
an efficient organizational structure to accommodate emerging
directions in research and services.
research in biomedical informatics and data science
NLM's research programs support pioneering research and development
to advance knowledge in biomedical informatics and data science. Its
research portfolio spans such areas as artificial intelligence,
computational biology, clinical decision support, public health
surveillance, visualization, and discovery mining in digital data sets.
This research encompasses areas of high importance to NIH and society
at large, and for audiences ranging from clinicians and scientists to
consumers and patients.
Research in data science produces novel analytical approaches and
visualization tools that help scientists accelerate discovery from data
and translate these findings to clinical solutions. It also aims to
solve problems consumers face in accessing, storing, using, and
understanding their own health data and to produce tools that make
precision medicine discoveries available and more understandable to
patients. Biomedical informatics research is yielding advanced
analytical methods and tools for use against large scale data generated
from clinical care, leading to fuller understanding of the effects of
medications and procedures as well as individual factors important in
the prevention and treatment of disease processes.
Recognized as a leader in clinical information analytics, NLM
conducts intramural research in areas such as medical language
processing, high-speed access to biomedical information, analysis and
use of high quality imaging data, advanced technology for emergency and
disaster management, health data standards; and analysis of large
databases of clinical and administrative data to predict patient
outcomes and validate findings from clinical research studies.
Leveraging extensive machine learning experience and field-based
projects, NLM is now advancing analytical tools and deep learning
techniques for application in image analysis research.
NLM's biomedical informatics research also addresses issues in
computational biology. Research creates new ways to represent and link
together genomic and biological data and biomedical literature and
produces analytic software tools for gaining insights in areas such as
genetic mutational patterns and factors in disease, molecular binding,
and protein structure and function.
biomedical information systems for research and health
NLM develops and operates a set of richly linked databases that
promote scientific breakthroughs and play an essential role in all
phases of research and innovation. Every day, NLM receives up to 12
terabytes of new data and information, enhances their quality and
consistency, and integrates them with other NLM information. It
responds to millions of inquiries per day from individuals and computer
systems, serving up some 100 terabytes of information, including
genomic, chemical, and clinical trial data, as well as citations to
more than 25 million journal articles in PubMed and more than 4.7
million full-text articles in PubMed Central.
NLM also offers sophisticated retrieval methods and analysis tools
to mine this wealth of data, many of which grow out NLM's research and
development programs. For example, NLM tools are used to mine journal
articles and electronic health records (EHRs) to discover adverse drug
reactions, analyze high throughput genomic data to identify promising
drug targets, and detect transplant rejection earlier so interventions
to help clinical research participants can begin more quickly. Data
analysis tools also support complex analyses of richly annotated
genomics data resources, yielding important molecular biology
discoveries and health advances for applications to clinical care. Such
applications demonstrate how the benefits of big data critically depend
upon the existence of algorithms that can transform such data into
information.
As a major force in health data standards for more than 30 years,
NLM's investments have led to major advances in the ways high volume
research and clinical data are collected, structured, standardized,
mined, and delivered. In close collaboration with other HHS agencies
and the Veterans Administration, NLM develops, funds, and disseminates
clinical terminologies designated as U.S. standards for meaningful use
of EHRs and health information exchange. The goal is to ensure that EHR
data created in one system can be transmitted, interpreted, and
aggregated appropriately in other systems to support healthcare, public
health, and research. NLM produces a range of tools to help EHR
developers and users implement these standards and makes them available
in multiple formats, including via application programming interfaces
(APIs).
engaging the public with health information
NLM uses multiple channels to reach the public with health
information, including development of consumer-friendly websites,
direct contact, and human networks that reach out to communities.
Direct-to-consumer information is made available in lay language
through MedlinePlus, which covers more than 1000 health topics. EHR
systems can connect directly with MedlinePlus to deliver information to
patients and healthcare providers at the point of need in healthcare
systems. In collaboration with NIH Institutes and Centers (ICs) and
other partners, NLM produces the print and online NIH MedlinePlus
magazine, and its Spanish counterpart, NIH Salud.
The National Network of Libraries of Medicine (NNLM) engages 6,500
academic health sciences libraries, hospital libraries, public
libraries, and community-based organizations as valued partners in
conducting outreach to ensure the availability of health information,
including from NLM services. The NNLM provides a community-level
resource for NIH's All of Us program, ensuring a point of presence in
almost every county in the US. NNLM partners with local, State, and
national disaster preparedness and response efforts to promote more
effective use of libraries and librarians and ensure access to health
information in disasters and emergencies. NNLM also plays an important
role in increasing the capacity of research libraries and librarians to
support data science and improve institutional capacity in management
and analysis of biomedical big data.
conclusion
To conclude, through its research, information systems and public
engagement, NLM supports discovery and the clinical application of
knowledge to improve health. Its programs provide important foundations
for the field of biomedical informatics and data science, bringing the
methods and concepts of computational, informational, quantitative,
social, behavioral, and engineering sciences to bear on problems
related to basic biomedical and behavioral research, healthcare, public
health, and consumer use of health-related information.
______
Prepared Statement of Anthony S. Fauci, M.D., Director, National
Institute of Allergy and Infectious Diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Allergy and Infectious Diseases (NIAID) of the National
Institutes of Health (NIH).
NIAID has a dual mandate to maintain and grow a robust basic and
clinical research portfolio in the areas of microbiology, infectious
diseases, immunology, and allergy as well as to launch a swift research
response when infectious diseases emerge and re-emerge. NIAID makes
vital contributions to developing diagnostics, therapeutics, and
vaccines by supporting medical countermeasures specific to single
pathogens as well as platform technologies that can be deployed to
target multiple pathogens. Also, NIAID research that has responded to
ongoing public health threats has been a key component of U.S.
biodefense preparedness.
research on infectious diseases
Influenza, Including Universal Influenza Vaccine Development. NIAID
supports basic, translational, and clinical research to address the
constant threat of seasonal and pandemic influenza. Concerns over the
efficacy of seasonal influenza vaccine, and the threat of pandemics
such as posed by H7N9 influenza, highlight the need for a new
generation of influenza vaccines. NIAID recently convened influenza
research experts from around the world at a workshop that led to the
development of a Strategic Plan for a Universal Influenza Vaccine.
NIAID's Strategic Plan outlines research priorities in three areas
important for understanding the formidable challenges posed by
influenza and advancing the development of universal influenza
vaccines. These research areas are: 1) transmission, natural history,
and pathogenesis of influenza infection; 2) influenza immunity and
factors correlated with immune protection; and 3) vaccine approaches to
elicit broad, protective immune responses.
NIAID is pursuing the research agenda outlined in the Strategic
Plan, including research on cohorts of infants to determine how
influenza vaccinations and natural influenza infections may affect
immunity to influenza infection or immunization later in life. These
cohort studies will provide vital information to facilitate the design
of broadly protective influenza vaccines. NIAID also is supporting the
development of several universal influenza vaccine candidates. One
strategy pursued by NIAID Vaccine Research Center scientists uses a
platform to display portions of an influenza surface protein--
hemagglutinin--that do not easily mutate and are relatively constant
among influenza strains. A separate NIAID-supported approach uses non-
infectious virus-like particles that display four types of influenza
hemagglutinin in one vaccine. Another NIAID-funded strategy employs
several influenza fragments recognized by the immune system that are
common to different influenza virus strains. Each of these vaccine
strategies aims to produce broad and durable immune responses that
would be effective against multiple influenza strains.
Zika. NIAID research has led to the rapid development of
diagnostics, candidate vaccines, and therapeutics to address the public
health threat of Zika virus disease, especially Zika virus-related
congenital abnormalities. NIAID scientists developed a DNA-based Zika
vaccine that is now being tested in a large-scale clinical trial in
Zika-endemic regions. NIAID is developing other candidate Zika
vaccines, including a live, attenuated vaccine that targets both Zika
virus and the related dengue virus. In addition, NIAID is partnering
with other NIH Institutes and the Fiocruz Institute in Brazil to
support the Zika in Infants and Pregnancy cohort study, which is
assessing the risks of Zika infection in expectant mothers and tracking
infant outcomes for at least 1 year.
Other Vector-borne Diseases. NIAID supports research to address
mosquito-borne diseases such as dengue, malaria, chikungunya, and
yellow fever, and tick-borne diseases such as Lyme disease. NIAID
scientists developed a candidate dengue vaccine, TV003, that targets
all four sub-types of dengue virus. TV003 currently is being tested in
a large-scale clinical trial in Brazil. An NIAID-supported malaria
vaccine, PfSPZ, contains a weakened form of the mosquito-borne malaria
parasite. Recent clinical trials showed PfSPZ protects people against
multiple malaria strains and prevents infection in a malaria-endemic
region. NIAID also is supporting a clinical trial of a vaccine designed
to trigger an immune response to mosquito saliva. This vaccine aims to
prevent multiple mosquito-borne diseases by blocking their transmission
from infected mosquitoes.
HIV/AIDS. NIAID research has led to powerful HIV treatment and
prevention tools that improve the lives of individuals living with HIV
and that have the potential to eventually end the HIV/AIDS pandemic.
NIAID is supporting new HIV vaccine studies, including the Imbokodo
trial in sub-Saharan Africa that is evaluating a vaccine candidate
designed to protect against multiple global HIV strains. NIAID also is
developing broadly neutralizing antibodies that can block most subtypes
of HIV found worldwide. VRC01 is one such antibody that is currently
being evaluated by passive infusion in two ongoing HIV prevention
trials in individuals at high risk of HIV infection. Another broadly
neutralizing antibody protected against infection in a monkey model of
HIV. Further study in this model showed that a mixture of two broadly
neutralizing antibodies could treat already infected animals. Enabled
by the HOPE Act, NIAID also is building on its pioneering clinical
trials of organ donation between HIV-infected individuals by launching
a multi-site clinical trial of kidney transplantation in this
population. NIAID continues to pursue additional methods to combat HIV,
including microbicide-based approaches such as a vaginal ring infused
with an anti-HIV drug, and long-acting injectable drugs to prevent and
treat HIV.
Tuberculosis. NIAID supports research to address tuberculosis (TB)
including the challenges of TB/HIV co-infection and increasing drug
resistance. NIAID also leads the research component of the National
Action Plan for Combating Multidrug-Resistant TB. NIAID scientists and
collaborators have developed a new diagnostic tool that detects
resistance to key antibiotics used to treat TB and may facilitate a
point-of-care diagnostic approach to guide TB therapy. In addition, an
NIAID clinical trial of HIV-infected individuals demonstrated that a 1
month course of preventive TB medication was as safe and effective as a
nine-month regimen. Patients were more likely to complete the short
regimen, suggesting it may be a preferred TB prevention strategy.
Antimicrobial Resistance. NIAID plays a critical role in research
components of the National Strategy for Combating Antibiotic-Resistant
Bacteria (CARB). NIAID is collaborating with the Biomedical Advanced
Research and Development Authority (BARDA) on the CARB
Biopharmaceutical Accelerator, or CARB-X, a global public-private
partnership to advance the preclinical and early clinical development
of promising antibacterial drugs and other products. In addition, NIAID
funds multiple clinical trials to evaluate novel antibiotics or
optimize the use of current antibiotics. One recent study found that
two common, inexpensive antibiotics can effectively treat methicillin-
resistant Staphylococcus aureus skin abscesses. NIAID also supports
clinical trials to develop zoliflodacin, a novel antibiotic for
gonorrhea, an increasingly drug-resistant infection.
research on immunology and immune-mediated disorders
NIAID research has led to transformational advances in our
understanding of the immune system and to new ways of treating and
preventing immune-mediated diseases. For example, NIAID research on
mechanisms of T-cell activation led to the development of ``checkpoint
inhibitors,'' a new class of immunotherapy drugs for cancer.
Food Allergy. NIAID research investments have led to important
advances in the prevention and treatment of food allergies. NIAID
convened an expert panel to build on the findings of pivotal food
allergy studies by developing new clinical guidelines to help prevent
peanut allergy in at-risk infants. NIAID-supported researchers also
have found that combining oral immunotherapy with the asthma drug
omalizumab may be an effective strategy to simultaneously desensitize
children with multiple food allergies.
Stem Cell Transplants for Treatment of Autoimmune Diseases. Two
recent NIAID-supported clinical trials found that intensive
immunosuppression followed by transplantation of a patient's own stem
cells was an effective treatment for progressive and life-threatening
autoimmune diseases. The Scleroderma: Cyclophosphamide or
Transplantation (SCOT) trial showed that stem cell transplantation
improves survival and quality of life for people with severe
scleroderma when compared with routine immunosuppression. The HALT-MS
trial demonstrated sustained remission in most people with relapsing-
remitting multiple sclerosis for 5 years following transplantation.
conclusion
NIAID research continues to drive rapid progress in the development
of vaccines, therapeutics, and diagnostics that improve human health
and enhance our ability to respond rapidly to emerging and re-emerging
infectious diseases. NIAID-supported science and innovation will
continue to pave the way to solutions for many of the formidable health
challenges facing the Nation and the world.
______
Prepared Statement of Gary H. Gibbons, M.D., Director, National Heart,
Lung, and Blood Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National Heart,
Lung, and Blood Institute (NHLBI) of the National Institutes of Health
(NIH).
This year, the NHLBI commemorates its 70th anniversary and a legacy
of achievements across the broad spectrum of research--including basic
science, epidemiology studies, implementation research, training, and
landmark clinical trials--that have helped people all over the world
live longer, healthier lives. Moving forward, the Institute remains
committed to leveraging scientific opportunities and working in
partnership with the public and private sector to prevent and treat
heart, lung, blood, and sleep disorders.
investing in basic research today for tomorrow's cures
The NHLBI's continued investments in fundamental discovery science
provide the foundation for tomorrow's medical breakthroughs. This
includes the NHLBI's support for research on the circadian rhythm (the
body's daily internal clock), how it is regulated, and its relationship
to the risk of chronic disease. Well known to cardiologists, blood
pressure rises and falls on a daily rhythm, reaching its peak in the
early morning--which is also when the risk for heart attacks and other
cardiovascular events is greatest. Moreover, disruption of circadian
rhythms has been shown to contribute to obesity, diabetes, and other
conditions that can increase the risk of heart, lung, blood, and sleep
disorders. Recent discoveries from basic research--including work on
fruit flies recognized with the 2017 Nobel Prize in Medicine--have
revealed new insights on the genetic and molecular pathways underlying
circadian rhythms that are opening new doors to prevention and
treatment.
To leverage these discoveries, the NHLBI has partnered with the
National Institute of Diabetes and Digestive and Kidney Diseases on a
program to better understand how circadian-dependent mechanisms
contribute to obesity and to the risk of heart and lung disorders
linked to obesity. Such research may help identify novel therapies that
act on the circadian rhythm to prevent or manage these disorders.\2\ As
researchers learn more about the basic pathways underlying circadian
function, they may also gain new insights into treating sleep disorders
such as sleep apnea.
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\2\ https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-17-
020.html.
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the power of data to personalize medicine
The goal of precision medicine is to give healthcare providers the
tools to better predict health and preempt chronic disease, and to
tailor treatment strategies to a patient's unique characteristics. To
accomplish this, the NHLBI's Trans-Omics for Precision Medicine
(TOPMed) program is integrating clinical, genomic, and other data from
diverse cohort studies, including the NHLBI's long-standing Framingham
Heart Study and Jackson Heart Study, which continue to help us
understand who is vulnerable to chronic diseases and why. To date,
TOPMed has generated whole-genome sequences from 120,000 individuals in
these studies, which we expect will identify new genetic risk factors
for disease and new molecular targets for therapy.
Data from TOPMed will be included in a pilot of the new NIH Data
Commons, a public-private partnership to bring research findings into a
cloud-computing environment to enhance data sharing. This effort will
give researchers access to data from hundreds of studies, creating new
opportunities for collaborative research, innovation, and discovery.
reducing health disparities
Despite declines in overall death rates from cardiovascular disease
(CVD), many populations in the United States, whether defined by race,
gender, geography, or other factors, continue to experience a high
burden of CVD and other chronic diseases. Increasingly, it is clear
that place matters. Where people live, work, and play affects their
susceptibility to disease and their health outcomes.
A 2017 study of more than 3,000 counties found a high burden of CVD
throughout the U.S. heartland, from Kentucky to Oklahoma, with
mortality rates in the highest-burden counties up to four times higher
than in the lowest-burden counties.\3\ New CDC data also shows that
rural Americans face a higher burden of chronic obstructive pulmonary
disease (COPD) than urban Americans and are dying from it at higher
rates.\4\ Many communities face economic, cultural, and geographic
barriers to disease awareness, prevention, and treatment, reflected in
a high burden of CVD risk factors such as high blood pressure, smoking,
low physical activity, and high-calorie diets.
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\3\ https://jamanetwork.com/journals/jama/fullarticle/2626571.
\4\ttps://www.cdc.gov/mmwr/volumes/67/wr/mm6707a1.htm.
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These data help inform efforts to reduce health disparities through
implementation research. For example, a recent NHLBI-funded study shows
the power of using non-traditional settings to adapt and implement
healthcare interventions for high-risk communities. In the study, blood
pressure screenings and pharmacist referrals at barbershops helped
reduce high blood pressure among African American men in the Los
Angeles area.\5\ In alignment with the comprehensive Federal COPD
National Action Plan, other research seeks to improve COPD care in
medically underserved areas. One recent study found that a set of
simple affordable diagnostic tools can help primary care providers
identify patients with COPD and follow up with appropriate
treatment.\6\
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\5\ https://www.ncbi.nlm.nih.gov/pubmed/29527973.
\6\ https://www.ncbi.nlm.nih.gov/pubmed/27783539.
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The NHLBI is expanding its implementation research programs. The
STIMULATE initiative seeks investigator-initiated proposals to overcome
barriers to implementation of proven interventions, and DECIPHeR will
create opportunities to integrate intervention trials into the NHLBI's
long-running observational studies of minority populations.
sickle cell disease: from better treatments to a cure
While the NHLBI supports implementation research programs in sickle
cell disease (SCD) that are helping develop and test approaches to
improve patient outcomes, fundamental discoveries in stem cell biology
and genomics are converging toward a cure. SCD is a genetic blood
disorder that affects 100,000 Americans and millions worldwide. It is
caused by a genetic mutation that causes the body's red blood cells to
take on a sickled shape and obstruct blood flow, leading to severe
frequent pain, organ damage, and other debilitating effects.
More than 50 percent of adults with SCD have significant pain more
than three days per week, and about 40 percent take opioid pain
medications daily. The NHLBI supports research to investigate
mechanisms of pain in SCD and the potential for non-opioid treatments.
This research will assist in addressing the Nation's devastating opioid
epidemic, by helping ensure that individuals with SCD and other types
of chronic pain can acquire effective relief without over-reliance on
opioids.
In addition to managing pain and other complications of SCD, it is
possible to cure SCD with a bone marrow transplant. However, this
procedure requires that the patient have a healthy, immunologically
matched marrow donor, which is not an option for most patients.
Advances in gene-editing technologies, such as CRISPR, are offering
new hope for a cure that works for all patients. By using the patient's
own bone marrow stem cells, researchers can replace the faulty SCD gene
or edit the misspelled gene and transplant the corrected cells back
into the patient, without the risk of immune rejection. NHLBI
intramural scientists are leading cutting-edge research and clinical
trials in this area.
Curing this disease within the decade is not something the NIH can
do alone. The NHLBI Cure Sickle Cell initiative is bringing together
patients, patient advocacy groups, healthcare providers, academic
researchers, and industry to accelerate development of a widely
available SCD cure.
conclusion
Medical breakthroughs and improvements in public health that once
seemed impossible are now within reach due in large part to the NHLBI's
seven decades of investing in excellent science. The Institute remains
committed to funding investigator-initiated discovery science, training
and building a talented diverse scientific workforce to help address an
array of research needs, forming new strategic partnerships, and
promoting the implementation of evidence-based care. Through these
multi-pronged efforts, the NHLBI will continue to stimulate the
scientific advances needed to further reduce suffering from heart,
lung, blood, and sleep disorders.
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Prepared Statement of Roger I. Glass, M.D., Director, Fogarty
International Center
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the Fogarty
International Center (FIC) of the National Institutes of Health (NIH).
introduction
The idea that the U.S. could benefit from international
collaborative research was central to the creation of the Fogarty
International Center in 1968. Fogarty's namesake, Rhode Island
Congressman John E. Fogarty, foresaw that U.S. citizens would reap the
benefits of international discoveries and that global health was a
smart investment for the U.S. and the world. Fifty years later,
Congressman Fogarty's vision remains a guiding force as Fogarty
continues to provide leadership in strengthening the research workforce
here and abroad to ensure that the best and brightest minds are
harnessed solve complex health challenges that affect us all.
Well-trained scientists have never been more critical to protecting
the health of Americans and populations around the world. Infectious
diseases like Ebola and Zika have traveled across borders, and diseases
formerly found only in other countries are now present in the U.S.
Therefore, it is imperative that we train scientists in developing
countries to detect pandemics at their point of origin, contain
outbreaks, and minimize their impact. In addition, the ability to
collaborate with scientists abroad can generate valuable knowledge
about diseases such as Alzheimer's Disease and cancer.
Fogarty supports research and research training programs for U.S.
and low- and middle-income country (LMIC) scientists. These programs
are built on long-standing partnerships between U.S. and LMIC academic
institutions. Fogarty programs also extend the reach and
competitiveness of U.S. universities, where there is high demand for
international research opportunities. Currently, Fogarty supports over
500 research and training programs involving 100 universities. Roughly
80 percent of Fogarty grants are awarded to U.S. institutions and all
Fogarty awards involve U.S. researchers.
strengthen and sustain the biomedical workforce
Global Health Security
Emerging epidemics such as Ebola demand a critical mass of in-
country scientists with relevant research expertise and skills. In
2016, Fogarty initiated the Emerging Epidemic Virus Research Training
for West African Countries with Widespread Transmission of Ebola
program. These grants fund collaborations between U.S. and African
research institutions in Guinea, Liberia, and/or Sierra Leone to plan
capacity building programs for Fogarty's Global Infectious Disease
Research Training Program, with a focus on emerging viral epidemics.
This support enables scientists on the front lines in these countries,
which were ground zero for Ebola, to design training programs that
increase expertise in Ebola, Lassa fever, and other emerging viral
diseases. For example, Yale University, in partnership with the
University of Liberia, will develop a training program focusing on
predictive transmission modeling and epidemiological research. Fogarty
has also awarded a grant to Tulane University, the Vanderbilt Institute
for Global Health, and the University of Sierra Leone. Together, these
institutions will advance research focused on efficacy studies of novel
and existing therapeutics for endemic viral hemorrhagic fevers like
Lassa fever, while simultaneously building capacity on how to conduct
higher-level clinical trial research during an epidemic like Ebola.
An in-house team of Fogarty-supported scientists develop and use
advanced computational models to study the emergence, evolution, and
transmission of pathogens to help predict future pandemics, provide
actionable information early in outbreaks, and protect the U.S.
population from these threats. For example, these researchers and their
collaborators recently modeled the global migration of Zika virus and
their potential for causing large outbreaks in the U.S. They have also
studied the transmission dynamics and evolution of influenza viruses in
humans, domestic animals, and migratory birds to help predict future
pandemics.
Combatting Common Disease Threats
Fogarty also supports training of scientists in LMICs, many of whom
have become leaders in academic institutions and ministries of health
in their home countries and serve as critical partners for U.S.
scientists. Notably, many health challenges facing Americans are most
effectively addressed through research conducted in a global context,
where diseases are often highly prevalent or where the study of unique
genetic predispositions can inform how we detect and prevent certain
diseases that affect U.S. citizens.
HIV/AIDS. Key scientific discoveries in HIV/AIDS treatment and
prevention have been made by Fogarty-supported trainees and former
trainees, including interventions to reduce mother-to-child
transmission of HIV, using HIV treatment to prevent new HIV infections,
and novel approaches to address HIV/TB coinfection. Fogarty-trained
scientists in South Africa are now studying broadly neutralizing
antibodies, which can kill multiple strains of the virus that causes
AIDS. Produced by only about 20 percent of people with HIV, these
antibodies show up too late to be able to stop disease progression in
the people who make them. However, scientists are exploring their
potential to prevent HIV in others--either through a vaccine that would
coax the body to generate similar types of antibodies or via passive
immunization in which an antibody product would be given directly.
Alzheimer's Disease. Columbia is home to the largest known family
with an inherited, early-onset form of Alzheimer's. Testing new
therapies on healthy individuals who are at a high risk for the
disease, like those in this family, is providing valuable clues for
understanding how to prevent it. Members of this family are now
participating in a trial to determine if a drug provided by a U.S.-
based company can stave off the decline in memory and brain function
associated with the disease. Fogarty-supported research training helped
to build a strong neuroscience research community in Colombia, which
set the stage for this potentially game-changing research.
research
Brain Disorders. Fogarty's Global Brain and Nervous Systems
Disorders Research across the Lifespan Program supports cutting-edge
research in LMICs on nervous system development, function, and
impairment throughout life. The program allows U.S. investigators to
gain experience working in LMICs, expanding the research workforce in
these settings by developing long-lasting international partnerships.
This research network spans over 45 countries and has contributed to
the creation of new interventions, new tools for clinical assessment,
and new laboratory methods.
Hydrocephalus--excessive accumulation of fluid in the brain--is one
of the most common birth defects in the U.S. The traditional treatment
for hydrocephalus is the surgical placement of a shunt, which often
involves complications like mechanical failure, obstruction, and
infection. Global Brain-supported researchers working in Uganda
developed a new treatment for infant hydrocephalus. They combined
endoscopic third ventriculostomy and choroid plexus cauterization (ETV/
CPC) into one treatment, where a small hole drains fluid from the brain
and heat is applied to brain tissue to reduce fluid production. Both
procedures have been practiced separately, but scarce resources in
Uganda inspired researchers to combine the two practices. This
combination treatment has helped to avoid shunt dependence in most
Ugandan infants treated for this condition. Notably, ETV/CPC is now
being practiced in the U.S.
Influenza. The Multinational Influenza Seasonal Mortality Study
(MISMS) is an international effort led by FIC to model the epidemiology
and evolutionary dynamics of influenza in human, swine and avian
populations. With funding from DHHS since 2007, MISMS has developed a
network of over three-hundred influenza experts in forty-five countries
and studied a broad range of topics, including: the global circulation
of influenza virus; cross-species transmission; pandemic preparedness;
control strategies; transmission dynamics; historical pandemics;
disease burden; and seasonality.
Mobile Health. Mobile technologies present exceptional
opportunities and new tools for improving health outcomes. A mobile
health tool conceived by a Fogarty grantee for HIV patient care in
Uganda is now being used to help patients use their phones to adhere to
strict medication regimen at a lower cost for conditions like opioid
addiction, tuberculosis, and hepatitis C. Fogarty-supported researchers
from the U.S. and Zambia are developing a simple diagnostic test for
malaria that uses a few drops of blood and tiny magnetic beads to
accurately detect the parasite that causes the disease. This new,
inexpensive test improves malaria detection and reduces drug resistance
by treating only those who have the disease.
conclusion
Fogarty investments are enabling researchers to take science to
where the problems are most acute, conduct research, and develop
solutions in the places where diseases are especially challenging. This
is the unique niche that Fogarty will continue to fill in fiscal year
2018 and beyond.
______
Prepared Statement of Joshua A. Gordon, M.D., Ph.D., Director, National
Institute of Mental Health
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Mental Health (NIMH) of the National Institutes of Health
(NIH). I am excited to discuss NIMH's efforts to accelerate scientific
progress that will improve our understanding of mental illnesses,
fueling transformative care for the greatest public health impact.
funding impactful science to alleviate burden
To help millions of Americans suffering from a mental illness, NIMH
continues to ardently pursue its mission to transform the understanding
and treatment of mental illnesses. In 2016, approximately 44.7 million
U.S. adults suffered from a mental illness; of these, an estimated 10.4
million U.S. adults experienced serious mental illnesses (SMI). To
balance the challenge of alleviating the burden of mental illnesses
now, while supporting research that will inform future treatments and
interventions, NIMH prioritizes excellent and impactful science and
strives for a diverse research portfolio of short-, medium-, and long-
term investments. For example, in the short term, efforts in suicide
prevention research, such as screening and predicting risk in emergency
departments, could result in significant decreases in suicide events.
In the medium term, research on techniques to manipulate neural
circuits could be applied to the treatment of mental illnesses in
humans. In the long term, computational and theoretical approaches to
psychiatry are needed to refine treatments.
early identification and intervention
Each year, thousands of adolescents and young adults in the United
States experience first episode psychosis. To explore methods for
establishing early intervention programs to help people with psychosis,
NIMH launched the Recovery After an Initial Schizophrenia Episode
(RAISE) project, which clearly demonstrated that when coordinated
specialty care was provided early in the disease, outcomes for
individuals were superior to usual care, including symptom reduction,
improvement in school and work functioning, and increased quality of
life. Based on these findings, the Centers for Medicaid & Medicare
Services extended Medicaid coverage for coordinated specialty care, and
the Substance Abuse and Mental Health Services Administration (SAMHSA)
set aside 10 percent of its Mental Health Block Grant allocation for
each State to support evidence-based programs that target first episode
psychosis. Today, over 200 CSC programs operate in 49 States.
Suicide is a potential consequence of mental illnesses and one of
the leading causes of mortality in the United States. Suicide rates
have increased since 1999, and nearly 45,000 Americans died from
suicide in 2016. Recent studies show that most individuals who die by
suicide have had recent contact with a healthcare provider, and that
early identification of those at risk for suicide is key to prevention.
To address this major public health concern, NIMH partners with the
National Action Alliance for Suicide Prevention and supports its Zero
Suicide initiative to support healthcare systems reduce suicide events.
Another example of NIMH-funded work in this area is the ED-SAFE
project, which demonstrated that universal screening for suicide risk
among adults in emergency departments (EDs) doubled the rate of
detection, and ED-initiated interventions for high-risk adults
decreased suicide attempts by as much as 30 percent.
In addition, researchers in the NIMH Division of Intramural
Research Programs developed a brief pediatric suicide risk screening
instrument; the four-item Ask Suicide Screening Questions (ASQ) is now
used in medical facilities around the world. Additional examples of
NIMH-funded research include the Emergency Department Screen for Teens
at Risk for Suicide (ED-STARS) study, which uses innovative approaches
to suicide screening and assessment for youth in EDs. NIMH also
supports collaborative research hubs, which aim to reduce the high
suicide rates among American Indian and Alaska Native youth.
Similarly, NIMH recognizes the importance of early identification
and intervention strategies for individuals with autism spectrum
disorder (ASD). NIH-funded research has identified ASD risk markers
within the first 12 months of age; early signs of behavioral
differences correspond with genetic and environmental risk for ASD that
appear to act before birth and alter the very early stages of brain
development. However, a critical gap exists in translating these
methods into practical screening tools that could be widely used to
identify ASD early in life. NIMH plans to launch an initiative aimed at
developing and validating new screening methods for ASD for use in
infants (0-12 months of age) which could lead to novel transformative
treatments that improve outcomes.
developing effective and transformative treatments of tomorrow
NIMH supports efforts to systematically and rapidly employ `lessons
learned' from research findings and clinical practice to improve
patient care. To help narrow the gap between research and practice, the
Mental Health Research Network (MHRN), a learning healthcare system
that includes large-scale practical trials and services research, uses
electronic health records large and diverse healthcare systems to
improve delivery of effective treatments. The NIMH Early Psychosis
Intervention Network (EPINET) is another learning healthcare system,
which will focus on early psychosis treatment clinics by linking
clinical sites. Like other learning healthcare models, the aim of
EPINET is to share and compare data that will narrow the time gap for
feedback and can help guide practice and ultimately improve mental
healthcare. In addition, NIMH-funded research on mobile health
(mHealth) technologies includes smartphone and texting approaches to
help treat and monitor patients with mental illnesses. These methods
are examples of how NIMH-funded research create opportunities for
continuous evaluation and improvement of care.
It is ever important that we continue to support research focused
on developing tools that can be used to study and treat mental
illnesses. For example, NIMH co-leads the cutting-edge NIH Brain
Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative. Maps of whole brains in action, the ability to identify
thousands of brain cells at a time, and innovative brain scanners are
just a few of the advances funded by this groundbreaking effort. In the
past 3 years, research under the Initiative has advanced so rapidly
that now many of the previously funded individual projects will receive
expanded support to achieve the ambitious goals of the BRAIN
Initiative.
Specifically, NIH recently announced funding for 110 new awards for
the BRAIN Initiative. The new round of awards includes the BRAIN
Initiative Cell Census Network (BICCN), aimed at providing researchers
with comprehensive references of diverse brain cell types to generate
the knowledge necessary for understanding brain disorders, including
mental illnesses. Additionally, new BRAIN Initiative research awards
aim to address neuroethical issues associated with human brain
research. Through the innovative studies supported by the BRAIN
Initiative, researchers will be able to produce a revolutionary,
dynamic picture of the brain that will lend to new ways to treat, cure,
and even prevent mental illness.
Finally, NIMH has supported successful efforts to map the genes
that predispose individuals to schizophrenia and other SMIs. Thanks to
these efforts, we now know of hundreds of locations in the genome
associated with risk for SMI. Each of these locations represents an
important clue into the neurobiology of SMIs and holds promise as a
potential therapeutic target. Current efforts, including the
PsychENCODE consortium, which studies the relationship between genetic
risk and protein expression in the brain, and an initiative that uses
convergent neuroscience approaches to elucidate how these risk factors
alter the function of neurons and circuits in the brain, are aimed at
translating these genetic discoveries into new knowledge and novel
treatments.
NIMH will continue to vigorously support research using novel
approaches to enhance biological understanding, translation of
evidence, services and intervention delivery, and therapeutics
development, all aimed at reducing the tremendous burden shouldered by
individuals and families living with mental illnesses.
______
Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN Director,
National Institute of Nursing Research
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 Budget request for the National
Institute of Nursing Research (NINR) of the National Institutes of
Health (NIH).
introduction
The mission of NINR is to promote and improve the health of
individuals, families, and communities. In pursuit of this mission,
NINR has set forth a bold, innovative scientific agenda in our
strategic plan, ``Advancing Science, Improving Lives.'' The plan, which
incorporates long-standing focus areas of nursing science and 21st
century solutions for improving the Nation's health, encompasses four
focus areas, including symptom science, wellness, self-management, and
end-of-life and palliative care; along with continued development of a
21st-century nurse scientist workforce, and finding ways in which
technology and innovation can contribute across all these areas. I
appreciate this opportunity to share some examples of NINR's research.
symptom science: promoting personalized health strategies
Through its focus on symptom science, NINR supports research to
develop new knowledge in biology and behavior to improve our
understanding of symptoms such as fatigue, pain, and sleep disturbance.
For example, NINR-supported investigators found a potential connection
between the use of opioids to treat pain and the rate of healing for
chronic wounds. They found that patients who had never received opioids
healed more rapidly, and that patients receiving higher opioid doses,
because they had a larger wound size or painful co-occurring
conditions, had slower wound healing in comparison with those receiving
lower doses or no opioids. Their findings raise important
considerations on potential connections between symptoms, biological
factors, and clinical management of pain and chronic wounds.
wellness: promoting health and preventing illness
In promoting wellness, NINR strives to build the science to
understand and prevent chronic conditions, reduce burden for patients
and caregivers, and eliminate health disparities. A recent NINR-
supported study found that family caregivers of persons with
Alzheimer's and related dementias (ADRD) reported an average of seven
new or worsening symptoms and signs in the care recipient, such as
confusion, decreased activity, and agitation, over a six-month period.
Understanding the range of symptoms that caregivers must respond to
when caring for loved ones with ADRD can guide the development of
future educational materials and interventions. Other NINR-supported
researchers are testing: a family-focused intervention to reduce the
risk of type 2 diabetes and cardiovascular disease in Hispanics; the
effectiveness of an intervention to reduce the rate of obesity in rural
Alaska Native children; and an intervention to increase physical
activity and reduce falls in older adults.
end-of-life and palliative care: the science of compassion
As the lead Institute for end-of-life research at NIH, NINR
supports research to inform high quality care for individuals and their
caregivers, improve management of pain and other advanced symptoms, and
facilitate decisionmaking at all stages of illness, including at the
end of life. With our support of the Palliative Care Research
Cooperative (PCRC) group, we continue to build the science of end-of-
life and palliative care by expanding this extensive network of over
400 multidisciplinary palliative care scientists to include over 160
clinical trial research sites across the U.S. NINR recently expanded
its Palliative Care: Conversations Matter initiative, which aims to
raise awareness of pediatric palliative care, by developing a new Web
feature profiling different members of the pediatric palliative care
team, including a chaplain, a child life specialist, a nurse, a nurse-
scientist, a pediatrician-researcher, and a social worker. This
resource gives families insight into the array of providers and
services available to support them and gives providers a glimpse into
how teams work together.
supporting a 21st century nursing science workforce
NINR has long-recognized the importance of supporting scientists at
all career levels, particularly those at an early career stage. NINR
supports a variety of training opportunities for scientists and
trainees. In addition to funding extramural trainees, NINR sponsors a
Symptom Methodologies Research Boot Camp, focused on precision health
methodologies and the latest advances in various `omics' such as
genomics and microbiomics. NINR's Summer Genetics Institute provides a
foundation in molecular genetics to improve research and clinical
practice for graduate students, faculty, and clinicians. NINR also
provides on-line video training resources on its website to support an
innovative workforce, from students to early- and mid-career
scientists.
conclusion
Thank you for this opportunity to share some of NINR's recent
accomplishments. We look forward to continuing to support nursing
research to advance science, improve lives, and envision new pathways
to improve health.
______
Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National
Human Genome Research Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National Human
Genome Research Institute (NHGRI) of the National Institutes of Health
(NIH).
the forefront of genomics
NHGRI is, and always has been, at the forefront of genomics
research. NHGRI led the U.S. contribution to the Human Genome Project,
which was completed in 2003, and has since embarked on evermore
ambitious endeavors, including the dissemination of genomic
technologies, knowledge, and expertise throughout the NIH, into the
private sector, and around the world. NHGRI accomplished this by
driving cutting-edge research, developing new methods and approaches,
and studying the impact of genomics on society with the goal of
improving the health of all humans through genomic advances. The
current pace of genomics is breathtaking, and we are approaching a
transitional time in which there will be rapid uptake of genomics in
medicine for prevention, diagnosis, and treatment of disease.
To prepare to lead the next phase of genomics, NHGRI officially
launched a new strategic planning process in early 2018. This 2-year
effort will generate a `2020 Vision for Genomics' and position the
Institute to lead genomics research and its applications to human
health into the next decade.
Our strong tradition of audacious thinking and effective strategic
planning has led to advances that today are enabling some of the most
high-profile initiatives in biomedical research. Examples include the
NIH All of Us Research Program, which seeks to build the largest, most
diverse dataset of its kind for health researchers, and the Cancer
Moonshot initiative, which aims to accelerate cancer research and to
improve our ability to detect, prevent, and treat cancer. The NHGRI-
funded Electronic Medical Records and Genomics (eMERGE) Network, now in
its third phase, has served as an invaluable pilot for precision
medicine research studies, like All of Us, by developing the tools and
approaches for using genomic information coupled with data in
electronic medical records to study human health and disease, including
prevention. The Cancer Genome Atlas (TCGA), equally funded by NHGRI and
the National Cancer Institute (NCI), generated comprehensive maps of
key genomic changes in 33 types of cancer and made all the generated
data publicly available to the research community; this program
provided a foundation upon which the molecular bases of cancer continue
to be defined, revealing new approaches for cancer treatments. In
addition, efforts like TCGA and the Cancer Moonshot heavily rely on the
dropping costs of genome sequencing, which has been greatly facilitated
by NHGRI's technology development research programs.
As noted earlier, the uptake of genomic medicine approaches will
increase rapidly in the coming years, and NHGRI is committed to laying
the groundwork for these changes. An example effort that will be
underway in fiscal year 2019, if funding allows, is the Clinical
Sequencing Evidence-Generating Research Program (CSER), which aims to
generate and analyze evidence for the use of genome sequencing in
clinical care and to address barriers to genomic medicine
implementation. This program has a targeted focus on recruiting
ancestrally diverse and underserved populations, recognizing that the
full benefit of genomic medicine will not be realized unless all of the
diverse populations in the United States benefit equitably from genomic
advances.
Compared to even a decade ago, genomics is now associated with a
much greater breadth and depth of research activities. Furthermore,
influenced by NHGRI's leadership, virtually every NIH Institute and
Center now funds genomics research to some extent, and a significant
amount of genomics research is funded beyond NIH. Recognizing that
going forward, a majority of genomics research will be funded by others
in the U.S. and internationally, NHGRI aims to identify, lead, and
support areas of genomics that are paradigm-setting, that enable novel
applications, and that expand the field--all with a focus on
applications to human health and disease. In doing so, NHGRI will
directly stimulate and achieve highly impactful and generalizable
progress in genomics that will benefit the efforts of others for years
to come.
research
Our foundational work in technology development, coupled with new
approaches for elucidating genome function, is fueling discoveries of
how genomic variation relates to human health and disease; in turn,
this knowledge is increasingly being applied to patient care through
pilot projects that study the implementation of genomic medicine.
In fiscal year 2019, if funding allows, NHGRI's longstanding Genome
Sequencing Program will continue its fundamental work to identify
genomic variants associated with disease and to provide resources for
the research and clinical communities to discover the genomic
underpinnings of disease. The Centers for Common Disease Genomics
(CCDGs) are conducting an in-depth genomics study of roughly 10 common
diseases, including cardiovascular disease and developmental disorders,
to identify genomic variants that either increase or decrease risk
associated with those diseases. Using the generated data, the sites
intend to develop improved and novel analysis methods and study designs
across the entire program. So far, the CCDG sites have generated over
50,000 whole-genome sequences and over 38,000 whole-exome sequences
(the protein-coding portions of the genome); the size of such studies
is needed to generate the statistical power that will allow reliable
conclusions about these diseases to be derived.
Many of NHGRI's principal accomplishments have centered on
unraveling the complexities of the genome and giving researchers open
access to valuable data. For example, the Encyclopedia of DNA Elements
(ENCODE) Project is creating a catalog of all the parts of the human
genome that are functional (i.e., that play an active biological role).
All of the generated ENCODE data are made freely available, providing
every scientist rapid access to this unique and valuable information
for their research. In fact, ENCODE's value in biomedicine can be
readily appreciated by the widespread use of these data: there are more
than 2,000 scientific publications from research groups that have used
ENCODE data for their published work.
Another treasure trove of data for the biomedical research
community was generated by the NHGRI-led Common Fund project GTEx
(genotype-tissue expression), which began in 2008 and aimed to
establish a database and accompanying tissue bank to allow scientists
to study the relationship between genomic variation and gene
expression. In October 2017, Nature published a collection of papers
highlighting discoveries from the program. The analyses include data
for thousands of tissue samples and demonstrated how gene regulation
differs across individuals and tissue types.
NHGRI has also been building its portfolio in genomic medicine,
piloting projects that seek to explore how to integrate genome
sequencing within clinical care and begin to build an evidence base
demonstrating its effectiveness. One example is the Newborn Sequencing
in Genomic Medicine and Public Health (NSIGHT) program, which began in
2013 to study the opportunities and challenges in the use of genome
sequencing for the care of newborns. NSIGHT has shown ways in which
newborn sequencing can be critical for saving lives by increasing the
speed of diagnosis. For example, one of our NSIGHT grantees, whose work
was recently featured in Time magazine, is using genome sequencing to
provide diagnoses and suggest treatment changes for critically ill
infants in the neonatal intensive care unit in a timeframe that can
make life-altering differences.\7\ Notably, this group recently set a
Guinness World Record for the fastest genomic diagnosis--19.5 hours.
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\7\ Park, A. (2017) Genetic Testing is Providing New Hope for
Babies Born with Mysterious Ailments. Time. http://time.com/4951200/
genetic-testing-providing-hope-babies-ailments/.
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conclusion
As is clear from our research portfolio, NHGRI does more than fund
the discovery of knowledge and create new technology--we have catalyzed
cultural changes across biomedical research. We have demonstrated an
unrelenting commitment to data sharing, our `team science' approach has
fostered a spirit of collaboration among scientists, and we have
provided researchers with access to shared tools and data to transform
genomic advances into health discoveries. As NHGRI delves into
strategic planning in fiscal year 2019 and beyond, we will collaborate
with experts in the field to identify the cutting-edge areas across our
diverse research domains that the Institute should champion and support
in the coming decade. We will also continue to tackle the
underrepresentation of minorities in genomics research to be sure that
the knowledge gained through the Federal investment in genomics
benefits all.
NHGRI believes that advances in genomics research are transforming
our understanding of human health and disease, and we are excited to
continue accelerating breakthroughs, improving patient care, and
advancing genomics in society.
______
Prepared Statement of Jill Heemskerk, Ph.D., Acting Director, National
Insitute of Biomedical Imaging and Bioengineering
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the
National Institutes of Health (NIH).
The mission of NIBIB is to improve human health by leading the
development of biomedical technologies and accelerating their
application. NIBIB supports research that integrates engineering with
the physical and life sciences to develop emerging technologies that
can be applied to a broad range of biomedical and healthcare problems.
Building partnerships with industry, academia, and other Federal
agencies is a high priority for the institute. A few examples from the
many exciting NIBIB-funded research efforts that are leading to better,
faster, and less costly ways to advance public health are shared in
this testimony.
on the spot food allergy testing
Eating out can be a challenge for people with allergies. Diners
must rely on knowing what ingredients contain the allergens they must
avoid, and on restaurants to serve dishes that exclude them.
Recognizing this widespread public health problem, researchers have
developed a system called integrated exogenous antigen testing (iEAT).
The purpose of the iEAT system is to give those who suffer from food
allergies a rapid, accurate device that allows them to personally test
foods in less than 10 minutes. The device is small enough to fit on a
keychain and can test for common allergens such as gluten, milk, or
nuts. The device contains a disposable testing chamber, so once a test
is completed the chamber can be replaced and the device used again.
After developing and testing a prototype of the device, the research
team granted a license to a local start-up company to make iEAT
commercially available. In the future the device could be adapted to
test for other allergens or substances.
cuff-less blood pressuring monitoring
A person's blood pressure is one of several key indicators of
health, but the inflatable cuff device used to measure blood pressure
is largely the same as it was 100 years ago. Measuring blood pressure
while in a doctor's office gives physicians a limited view since blood
pressure can vary throughout the day. Researchers are developing a new
``cuff-less'' method to accurately measure blood pressure more
frequently and without the need for special equipment. One group is
making progress using a modified smart phone case with built-in sensors
and an app to capture blood pressure by pressing a finger on the
phone's home button. The ability to monitor blood pressure on an
ongoing basis could help alert people to potential problems and more
consistently monitor their blood pressure if they are at risk or are
taking medications. This could help reduce the risk of cardiovascular
disease through improved management of blood pressure.
clearing out blood clots
Blood clots that form in the deep veins of the legs are called deep
vein thrombosis and can be quite painful, and even fatal if a clot
dislodges from the wall of the vein and travels to the heart or lungs.
Currently, intravascular treatments use devices inserted into the vein
to trap clots, but they have limitations including damage to the blood
vessel wall. In some patients, clot-thinning medication is required,
which can have a range of side effects. A new approach to overcome
these limitations uses a surgical tool that is inserted into a vein and
directs ultrasound waves directly at clots to break them up into tiny
pieces. It is targeted and therefore minimizes damage to blood vessels;
and because the broken pieces are tiny, patients do not need to use
blood thinning medication following the procedure. In addition to using
ultrasound, researchers are adding injectable microbubbles that vibrate
when exposed to the ultrasound waves. This helps to further break up
the clot. This tool is portable and is estimated to cut the declotting
procedure time by more than half, from 10 hours to four hours. So far,
the tool has only been tested in synthetic blood vessels, and more
study is needed to bring this treatment to patients.
nanovaccines weaponized to battle tumors
A new vaccine designed to stimulate a multi-pronged immune response
can stimulate the immune system to specifically attack a tumor, while
simultaneously inhibiting the suppression of the immune system, which
often occurs in people with cancer. The researchers also developed a
way to shrink the vaccine molecule so that it can more easily reach the
parts of the immune system to activate it. Using colon cancer that had
spread to the lungs as a test case for this approach, the nanovaccine
successfully blocked lung tumor growth in a mouse model. Further
testing revealed that mice receiving the nanovaccine had a significant
increase in a type of immune cell that can target cancerous cells.
Another potential benefit of this approach is that it mounts an anti-
tumor immune response that circulates through the system, and therefore
is particularly valuable for finding and inhibiting metastatic tumors
growing throughout the body.
solving a common heart disease with engineering
Ischemic cardiovascular disease is a result of impaired blood
circulation to tissues and organs and is the leading cause of death and
disability in the U.S. Damage to small blood vessels is difficult to
treat and can result in heart failure, stroke, or other arterial
diseases. To address this problem, researchers developed a way to grow
new blood vessels using 3D printed patches. The specially designed
patches are seeded with cells and implanted into damaged areas. Once
implanted, the patches induced the growth of new blood vessels. This
early stage, basic research is an example of interdisciplinary teams
including engineers, biologists, and clinicians combining their
expertise and collaborating to solve health problems.
advances from nibib laboratories
While the majority of NIBIB's budget supports research projects
throughout the U.S., NIBIB also supports a small, but robust program
within its Intramural Research Program (IRP). These investigators are
working to create optical imaging technologies that provide
unprecedented high resolution and speed to study living cells in real
time. Others create ``theranostic'' imaging probes--based on
nanomaterials--that combine therapeutic and diagnostic capabilities to
improve early diagnosis, monitor therapeutic responses, and guide drug
discovery and development.
In one example, researchers developed a new radiotracer to help
diagnose prostate cancer. Prostate cancer is the fifth leading cause of
death worldwide and is especially difficult to diagnose, particularly
early on. While prostate cancer is relatively easy to treat in its
initial stages, it is prone to metastasis and can quickly become
deadly. The research team developed a radiotracer that could identify
prostate cancer at all stages. This new tracer is one of the first
dual-receptor target tracers, which target more than one biomarker, to
be studied in humans. This new method improves on the current practice
that can lead to many false positive results and cause the patient to
undergo unnecessary treatments or painful biopsies. A successful Phase
I clinical trial with a small group of patients to establish safety and
identify any possible side effects was recently completed.
conclusion
Advances in technology are catalyzing the development of solutions
to previously intractable disorders and improved approaches to
biomedical research. As these examples illustrate, this type of
research requires many disciplines to work together. This integration
of disciplines is what defines NIBIB's approach. NIBIB is committed to
supporting such teams of researchers to solve major biomedical
challenges that will improve the health of all Americans.
______
Prepared Statement of Richard J. Hodes, M.D., Director, National
Institute on Aging
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute on Aging (NIA) of the National Institutes of Health (NIH).
aging: a universal risk factor
Each one of us is susceptible to the effects of aging, which
remains the most powerful driver of chronic diseases and disabilities
that affect older adults. As the number of Americans ages 65 and older
soars in the coming decades--from an estimated 46.2 million in 2014 to
82.3 million in just 26 years, according to projections from the U.S.
Census Bureau--it is increasingly urgent that we pursue a comprehensive
national effort to understand aging, to develop interventions that will
help older adults enjoy robust health and independence, and to support
American elders' active engagement with their families and communities.
At the NIH, the NIA leads this effort. We support genetic,
biological, clinical, behavioral, and social research related to the
aging process, healthy aging, and diseases and conditions that increase
with age. We also support training of the next generation of
researchers in geriatrics and related fields. In addition, we are the
lead Federal agency supporting research on Alzheimer's disease and
related forms of dementia (AD/ADRD).
research on alzheimer's disease and related dementias
In a recent analysis based on 2010 data, 5.5 million Americans were
projected to have Alzheimer's disease by 2018. It's true that several
studies, including the long-running Framingham Heart Study, have
identified declines in the incidence and prevalence of dementia since
the 1970s, possibly associated with increased educational attainment
among study populations. However, if current population trends
continue, these numbers will increase significantly as the number of
older Americans rises--unless we learn how to prevent or effectively
treat the disease.
Since passage of the National Alzheimer's Project Act in 2011, an
extraordinary influx of funding directed at AD/ADRD has made it
possible for NIH, led by NIA, to begin building a series of bold and
innovative research programs, infrastructure, and new partnerships
aimed at laying the foundation for precision medicine for AD/ADRD. NIA
and other NIH Institutes are harnessing the tremendous power of big
data to gain insight into the basic biology of AD/ADRD, as well as
factors that may confer resilience to these diseases; accelerating the
discovery of the next generation of new targets and biomarkers through
the open science research model of the Accelerating Medicines
Partnership for AD (AMP-AD); and establishing new translational
infrastructure programs to enable rapid sharing of data and research
models and enhancing research rigor and reproducibility.
NIA currently supports over 140 active clinical trials of
interventions to enhance cognitive health in older individuals and to
prevent, treat, or manage symptoms of AD/ADRD. These studies range from
studies of emerging therapeutics developed in academic centers and the
small business community, to studies of the cognitive effects of drugs
commonly used for other conditions, to clinical trials involving
lifestyle interventions such as exercise, dietary change, and cognitive
training. Investigators with AMP-AD have identified over 100 potential
new drug targets for AD/ADRD, and over 30 projects for development of
novel therapeutics against a variety of targets are under way in NIA's
Alzheimer's Disease Translational Research Program. NIH has also
established the Alzheimer's Clinical Trial Consortium (ACTC),
consisting of 35 sites across the United States, to support trials
across the full spectrum of AD/ADRD. The ACTC will also spur innovation
in trial design and recruitment, with a specific focus on inclusion of
communities underrepresented in AD research.
We have made important progress. For example, an NIA-supported
international research team used cryo-electron microscopy to visualize
the structure of individual tau fibrils (a pathological hallmark of
several forms of dementia) for the first time. The high-resolution,
exquisitely detailed images helped explain why tau-based therapies have
been difficult to develop--its components are so tightly bound together
as to be impermeable--but also suggested possible new avenues for
therapy. Other investigators analyzed Medicare data and noted an
association between use of cholesterol-lowering statin drugs and
reduced risk of AD. Intriguingly, the reduction in risk varied across
sex, race, and particular statin used, suggesting that the right statin
type for the right person at the right time may provide a relatively
inexpensive means to lessen the burden of AD.
Our continuing efforts have been informed by input from researchers
and advocates worldwide through key scientific conferences, including
periodic Summits on Alzheimer's Disease (most recent: March 2018) and
Alzheimer's Disease-Related Dementias (most recent: 2016, with the next
Summit planned for 2019). A Summit in October 2017 also brought
together experts to discuss dementia care and the unique needs of
caregivers of persons with AD/ADRD.
advancing aging research
Recognizing aging as the most powerful risk factor for diverse
diseases and frailties, NIA supports research into the underlying
biological mechanisms of aging. For example, the trans-NIH Geroscience
Interest Group, established by the NIA and joined by most NIH
Institutes, promotes research on the links between aging biology and
etiology of chronic diseases. NIA also supports research on diet and
healthy aging, as well as two multi-investigator interventions testing
programs to identify and validate compounds that extend life and
improve health in laboratory animals. Ongoing collaborations with the
National Institute of Allergy and Infectious Diseases and the National
Cancer Institute continue to expand our understanding of the aging
immune system and the role of aging in the etiology of cancer.
NIA's longtime flagship studies in aging remain vibrant with
opportunities to apply new technologies and thinking to their treasure
troves of data. The Baltimore Longitudinal Study on Aging, 60 years old
in 2018, continues to break new ground in identifying the longitudinal
physical and cognitive changes that define aging; elucidating the
factors that affect the rate of age-related change; and understanding
the relationship between advancing age and chronic disease. BLSA
investigators are particularly interested in ``exceptional agers''--
those rare individuals who live well into their eighties with few
health problems. This year the Health and Retirement Study (HRS) will
complete 25 years of data collection and will mark the occasion with
several enhancements, including deployment of an improved approach to
assessing cognitive impairment and dementia and expanded collection of
objective health measures, including blood-based assays capturing the
aging of the immune system and related molecular and cellular age-
related changes. This project and others are designed to reveal the
biological pathways through which differences among social and
demographic groups can affect health.
NIA-supported investigators are looking at better ways to translate
what we know into clinical practice that will help improve the health
and well-being of older Americans. For example, starting in fiscal year
2019, NIA will support demonstration projects leading to pragmatic
trials--clinical trials that are conducted under ``real-world''
conditions, as opposed to the tightly controlled conditions of a
traditional trial--for a variety of age-related diseases and
conditions, including care of persons with dementia in long-term
settings. The National Advisory Council on Aging has also recently
approved in concept a new initiative to explore ``deprescribing''
strategies for older adults with multiple chronic health conditions.
This research, which will begin in fiscal year 2019, will address
inappropriate prescribing of medication, which is estimated to affect
20 percent of older adults, one-third of individuals in long-term care
facilities and over half of the persons with advanced dementia in
nursing homes.
empowering the next generation of scientists
As the number of older Americans continues to grow, we must foster
the development of the next generation of scientists whose research
will lead to improved care and more effective treatment for older
patients with complex medical conditions. To encourage emerging
scientists, NIA supports an advantage in pay line for new and early-
stage investigators. The Paul Beeson Career Development Awards in Aging
Research program, sponsored by the NIA, the National Institute of
Neurological Disorders and Stroke, and private partners, continues to
produce leaders in the fields of aging and geriatrics research. A
recent Funding Opportunity Announcement led to awards for four new
training programs for joint MD-PhDs in the social sciences relevant to
aging. Finally, the Butler-Williams Scholars Program (formerly the NIA
Summer Institute) remains a vibrant and vital institution at NIA.
Thank you. I welcome your questions.
______
Prepared Statement Of Stephen I. Katz, M.D., Ph.D., Director, National
Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of
the National Institutes of Health (NIH).
niams research impacts everyone
NIAMS is the primary Federal agency for supporting medical research
on diseases of the bones, joints, muscles, and skin. As such, our work
touches the lives of nearly every American. A 2018 publication by the
Centers for Disease Control and Prevention notes that an estimated 23
percent (54 million) of Americans have been diagnosed with some form of
arthritis, including osteoarthritis, rheumatoid arthritis, gout, and
fibromyalgia; 24 million of whom have symptoms severe enough to hinder
activities they want or need to do. This problem is expected to grow as
our population ages; 78.4 million adults will have arthritis by 2040 if
current trends continue. When arthritis is combined with other bone and
joint conditions such as neck and low back pain, osteoporosis, and
musculoskeletal injuries, the total cost of medical care and lost wages
is estimated to be $874 billion annually. Diseases in the NIAMS
research portfolio also have a global impact. In 2015, low back and
neck pain was the leading cause of disability worldwide, while skin
diseases such as eczema and psoriasis ranked fifth.
NIAMS is enhancing health, lengthening life, and reducing illness
and disability by supporting basic and translational research and
clinical trials that will inform medical practice; training the next
generation of bone, joint, muscle, and skin scientists; and
disseminating health information and the findings from the studies it
supports to all Americans. For the remainder of my statement, I will
describe a few of the many recent research activities that are
benefiting people today and enabling future advances.
research advances funded by niams
My first two examples focus on the risks and benefits of steroids,
which an estimated 1 percent of the entire U.S. population takes as
chronic therapy. A team of researchers studying the effects of repeated
steroid injections for knee pain found that people who received shots
every twelve weeks for 2 years showed worsening joint damage and no
long-term reduction in pain compared with those who received saline
injections. While this study did not evaluate the benefits of steroid
injections into the knee for short-term pain relief, it does not
support their long-term use for treatment of symptomatic knee
osteoarthritis. Another group of investigators looked at the mechanisms
by which steroids preserve muscle function for boys who have Duchenne
muscular dystrophy. Using cells and a mouse model, the team determined
that a weekly dosing regimen increases the activity of two genes
involved in muscle cell repair, while daily dosing activates pathways
that cause muscle to shrink and weaken. Their discovery explains the
seemingly contradictory results of previous studies into the drugs'
effects. If these observations from cell cultures and mice also occur
in patients, this study could directly inform how steroids are
prescribed to maximize their therapeutic benefits while minimizing
their negative effects.
After decades of investigating Pompe disease, a rare, life-
threatening condition that cripples the muscles, NIAMS-funded
researchers have developed a gene-transfer approach that shows promise
in mice. While the study's main goal was to test whether the strategy
would prevent the animals from developing an immune response, it also
demonstrated that this gene therapy could potentially replace standard
care. These results directly contributed to an investigational new drug
approval by the Food and Drug Administration to move this approach into
clinical trials. Gene therapy also holds promise for people who have
the rare and life-threatening skin disease recessive dystrophic
epidermolysis bullosa, which causes fragile, blistering skin. In a
phase 1 clinical trial, investigators collected skin biopsies from four
patients and used a harmless virus to correct the gene for the
defective skin protein in the patients' cells. Next, they coaxed the
genetically modified cells to grow into sheets of skin about the size
of a deck of playing cards. Then, the new skin was grafted back onto
patients to speed healing of the open wounds that characterize the
disease. After 12 months, half of the two-dozen grafts were still
covering patients' wounds. Investigators will continue monitoring these
patients and are recruiting people for a phase 2 clinical trial.
NIAMS research is also developing techniques to help clinicians
identify which patients are likely to have more severe or rapidly
progressing disease. For example, researchers found that positron
emission tomography (PET), a technique that can visualize the body's
metabolic processes, could be used to distinguish between patients who
have large vessel vasculitis or other diseases with similar symptoms.
PET may also help clinicians predict which patients are at highest risk
of disease relapse. Another study examined children with juvenile
myositis, a disease where the muscles are attacked by antibodies in the
patients' blood. The investigators found that children with a certain
type of antibody experience worse muscle disease and more severe
weakness. This finding also explains why these children show less
benefit from existing therapies and opens a possibility for better
treatments. Other researchers discovered blood markers that may
distinguish the subset of people who have systemic sclerosis that are
at risk of developing interstitial lung disease (the leading cause of
death for these patients). This advance also may lead to new therapies.
Other studies of basic cellular processes hold promise for people
who suffer from skin diseases. Investigators determined that a
molecular pathway involving the protein JAK1 is involved in chronic
itch. They then tested whether an existing drug that blocks JAK
signaling could help people who do not respond to other treatments
(e.g., some cases of atopic dermatitis). Their results were promising
although further clinical studies are needed to confirm the findings.
Additional teams of researchers are examining how microbes on the skin
may influence a person's susceptibility to atopic dermatitis. A pair of
studies, focusing on the role of the bacterium Staphylococcus aureus in
driving the disorder, suggest that reducing S. aureus by increasing
beneficial skin bacteria could be an effective treatment.
NIAMS-funded research is also having an impact beyond arthritis and
musculoskeletal and skin diseases. For example, psoriasis has been
linked to an increased risk of developing type 2 diabetes. A new
finding that the risk of diabetes is highest for those with the most
severe psoriasis sheds light on the causes of both diseases and
provides compelling evidence that certain patients should receive
targeted diabetes prevention strategies. Other investigators are
showing that while early antiretroviral therapy saves HIV patients'
lives, it also damages their bones, emphasizing the importance of
developing bone-preserving strategies for this population. Weight loss
due to bariatric surgery, another life-saving intervention, also is
associated with bone loss, and researchers are beginning to understand
the role that glucose metabolism plays in bone health. This discovery
could lead to targeted prevention and treatment strategies for
osteoporosis, the skeletal complications of bariatric surgery, and
diabetic bone fragility. Still other research is explaining why muscle
breaks down in cancer patients (a process known as cachexia). A number
of molecular pathways and targets underlying the muscle wasting process
have been discovered recently, and investigators are beginning to
identify existing drugs or new targets to stop this from occurring.
looking to a promising future
The wide reach of NIAMS-funded research is allowing people affected
by diseases within our mission to benefit from large multi-agency
programs such as the Cancer Moonshot Program and the Regenerative
Medicine Innovation Project supported by the 21st Century Cures Act.
Moving forward, investigators will examine connections between
immunotherapies for cancer and autoimmune disease and will continue to
be encouraged to apply for funding for research on bone, joint, muscle,
and skin regeneration. NIAMS, along with the National Institute of
Allergy and Infectious Diseases, continues to lead the Accelerating
Medicines Partnership (AMP) in rheumatoid arthritis and lupus which is
working to identify and validate promising biological targets for those
diseases. With guidance from NIAMS, three other Institutes, and the NIH
Common Fund, the trans-NIH Molecular Transducers of Physical Activity
in Humans program continues to make progress developing a database that
researchers can use to elucidate changes that take place in our bodies
in response to exercise and how those changes relate to human health.
In fiscal year 2019, NIAMS plans to continue support for its
Research Innovations for Scientific Knowledge (RISK) funding
opportunities, which allow investigators from around the country to
submit cutting edge, unconventional, innovative research proposals for
up to 3 years of funding. To help bolster the next generation of
researchers, the Institute also continues to encourage early
established investigators who have successfully renewed their first
NIAMS research project grant to apply for a supplemental funding
program to aid the transition of their individual research project into
a broader, more robust and resilient research program.
______
Prepared Statement of George F. Koob, Ph.D., Director, National
Institute on Alcohol Abuse and Alcoholism
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute on Alcohol Abuse and Alcoholism of the National Institutes of
Health (NIH).
burden of alcohol misuse in the united states
Alcohol misuse has profound effects on the health and well-being of
individuals, families, and communities. Approximately 15 million people
in the United States have alcohol use disorder (AUD), a chronic
relapsing brain disease related to alcohol misuse. 88,000 lives are
lost to alcohol-related causes annually, making alcohol the third
leading preventable cause of death in the United States. Alcohol misuse
cost the U.S. almost $250 billion in 2010. Guided by its 2017-2021
strategic plan, the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) supports research and initiatives to generate and disseminate
fundamental knowledge about the effects of alcohol on health and well-
being, and apply that knowledge to improve the diagnosis, prevention,
and treatment of alcohol-related problems, including AUD, across the
lifespan.
advancing translational and clinical research
For nearly five decades, NIAAA has supported cutting-edge research
to reduce the toll that alcohol misuse takes on human health and well-
being. The Institute's vast portfolio of translational and clinical
research has led to more effective interventions to prevent and treat
alcohol misuse and related conditions, provided support for integrating
prevention and treatment services into mainstream healthcare, and paved
the way for the development of novel strategies to address medical
conditions associated with alcohol misuse.
Alcohol Treatment Navigator\SM\
In any given year, less than 10 percent of individuals diagnosed
with AUD receive treatment. Although effective behavioral interventions
and medication-assisted treatment are available, in addition to mutual
help groups, people often do not know the full extent of their options
or where to turn for help. In October 2017, NIAAA launched the Alcohol
Treatment Navigator\SM\ (alcoholtreatment.niaaa.nih.gov), a
comprehensive online resource to help people search for professionally-
led, evidence-based alcohol treatment. The Navigator educates consumers
about AUD and treatment options, provides 10 recommended questions to
ask a potential provider, and suggests five signs of higher quality
treatment to recognize. It also provides instructions for searching
several existing online directories of licensed professional
therapists, accredited alcohol treatment programs, and board-certified
addiction medicine physicians. With the Navigator, adults searching for
AUD treatment will be better able to find care that meets their unique
needs, friends and family members will feel empowered to help an adult
loved one struggling with AUD, and healthcare providers can feel more
confident in screening their patients for AUD knowing there is a tool
to share with those who need a referral to treatment. Given that
treatments for AUD work better for some people than others, NIAAA will
continue to support research on the neurobiological mechanisms that
underlie AUD to identify novel medication targets that could ultimately
expand the number of effective treatment options.
Addiction Medicine in Routine Healthcare
Many individuals with AUD often seek primary care for a health
problem related to alcohol misuse rather than for the misuse itself,
indicating a need for addiction medicine approaches in routine medical
practice. NIAAA provides primary care and other healthcare providers
with tools to help them become more proficient in conducting alcohol
screening and evidence-based interventions, including medication-
assisted treatment. The Institute is also partnering with the National
Institute on Drug Abuse, the Substance Abuse and Mental Health Services
Administration, and others to improve physician training in the
diagnosis, prevention, and treatment of alcohol and other substance
misuse and to expand the range of healthcare providers appropriately
trained in identifying and addressing these problems.
Alcohol-Associated Liver Diseases
In the United States, about half of liver disease deaths are
attributable to alcohol misuse. NIAAA will continue to invest in
clinical and translational research to develop treatments for alcohol-
associated liver diseases such as alcoholic hepatitis, a deadly form of
liver disease for which there are no treatments approved by the Food
and Drug Administration (FDA). The Institute aims to strengthen its
research programs in alcoholic hepatitis through the establishment of a
clinical and translational network to streamline the design,
initiation, and conduct of clinical trials, reduce administrative
redundancy, and optimize the use of scientific innovations. NIAAA is
collaborating with the FDA to identify appropriate clinical trial
endpoints for studies investigating novel treatments for alcohol-
associated liver diseases as well as safe, effective therapies for AUD
in liver disease patients.
Fetal Alcohol Spectrum Disorders
Prenatal alcohol exposure is a leading preventable cause of
developmental abnormalities that contribute to a broad range of
lifelong physical, cognitive, and behavioral challenges known as Fetal
Alcohol Spectrum Disorders (FASD). Among NIAAA's extensive portfolio in
FASD research are studies to establish more accurate FASD prevalence
estimates. A new NIAAA-supported study of more than 6,000 first-graders
across four U.S. communities (Midwest, Rocky Mountain, Southeast and
Pacific Southwest) has found that as many as 1-5 percent of first-grade
children have FASD. This finding provides further evidence that FASD is
a significant public health problem in the U.S. and strategies to
expand screening, diagnosis, prevention, and treatment in communities
are needed to address it.
emerging public health issues
Changing patterns in alcohol consumption, shifts in the burden of
alcohol-related disease, and shifts in the demographic composition of
the U.S. pose new challenges for alcohol prevention and treatment.
Identifying and addressing emerging public health issues early can
lessen the societal burden and associated costs.
Increases in Alcohol-Related Emergency Department Visits
A new study found that the rate of alcohol-related emergency
department visits in the U.S. increased by nearly 50 percent between
2006-2014, especially among women and older adults. About 15 percent of
the visits involved substances in addition to alcohol. Alcohol
interacts with a variety of prescription and illicit drugs, including
opioid pain relievers, which dramatically increase the risk of overdose
deaths and may partially explain the increased prevalence of emergency
department visits also observed for alcohol and medication
interactions. The relationship between alcohol and pain is another area
of interest including how chronic alcohol misuse increases sensitivity
to pain, and how pain drives alcohol misuse. NIAAA is supporting
epidemiological studies to determine the associations between alcohol
and opioid misuse as well as basic research to elucidate the
neurobiological mechanisms through which alcohol, opioids, and pain
interact.
Extreme Binge Drinking
A recent NIAAA study based on 2012-2013 data found that that nearly
32 million adults in the U.S. (13 percent of the population aged 18 and
older) engaged in extreme binge drinking, i.e., consuming alcohol at
levels two or more times the binge thresholds, in the past year.
Extreme binge drinking was associated with an elevated likelihood of
emergency department visits and other adverse consequences. NIAAA is
forming a working group of external experts to better understand the
social and cultural determinants of extreme binge drinking to inform
the development of improved interventions.
Alcohol Misuse Among Women
A growing body of evidence indicates that women who drink are at
increased susceptibility to short- and long-term alcohol-related
consequences, and alcohol use and misuse are increasing more
significantly among women than men. NIAAA encourages basic, clinical,
and translational research on the biological bases of sex differences
in the development of AUD and associated consequences, factors that
increase risks for AUD and co-occurring disorders, and improved
diagnosis and evidence-based interventions that consider the unique
needs of women.
Alcohol Misuse Among Older Adults
As people age, they tend to be more sensitive to alcohol's effects,
and are more likely to experience health conditions exacerbated by
alcohol misuse as well as alcohol-medication interactions. An analysis
of data from 1997-2014 showed an increase in drinking and binge
drinking among adults aged 60 and older, particularly among women.
NIAAA-supported studies are focused on identifying and reducing
unhealthy alcohol use among older adults as well as elucidating how
alcohol contributes to age-related changes in the brain. For example, a
recent study of older adults with AUD has shown accelerated declines in
various brain regions and circuits, including in the frontal cortex
which may lead to accelerated impairments in cognitive function.
conclusion
Advances in alcohol research have expanded our knowledge of the
effects of alcohol on health and resulted in numerous evidence-based
preventive and treatment interventions. Still, more work needs to be
done to reduce the burden of alcohol misuse in our Nation. With its
fiscal year 2019 budget, NIAAA will continue to invest in basic,
clinical, and translational research to address existing and emerging
public health concerns and cultivate the biomedical research workforce
to harness the contributions and perspectives of the broadest range of
investigators.
______
Prepared Statement of Walter J. Koroshetz, M.D., Director, National
Institute of Neurologcial Disorders and Stroke
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Neurological Disorders and Stroke (NINDS) of the National
Institutes of Health (NIH). NINDS research improves the diagnosis,
treatment, and prevention of brain diseases and other nervous system
disorders, and the Institute is the world's largest supporter of basic
research to understand the normal brain, which drives progress against
disease throughout the public and private sectors.
the challenge of neurological disorders
According to the Centers for Disease Control and Prevention, in the
United States: traumatic brain injury (TBI) is the leading cause of
death and disability in children and young adults and a major problem
for the elderly (falls), about 795,000 strokes occur each year,
epilepsy affects 3 million adults plus nearly half a million children,
dementia is a growing public health challenge, and chronic pain is
perhaps the most common of all medical problems, and a major factor in
the opioid crisis. Parkinson's disease, multiple sclerosis, amyotrophic
lateral sclerosis, cerebral palsy, and hundreds of other disorders,
common and rare, also affect the brain, spinal cord, and nerves of the
body. Because of the multiplicity of brain disorders and the
extraordinary complexity of the brain, neurological disorders present
the most daunting challenges in all of medicine. For most of these
diseases, treatments are still far from adequate.
progress against neurological disorders
Historically, progress against neurological disorders has been
slow, but the pace appears to be accelerating, with encouraging
advances against several neurological disorders in recent years. As NIH
has driven medical progress in general, NINDS basic research has
provided the foundation for these recent advances against neurological
diseases, and the Institute's translational and clinical research have
also made major contributions. A few recent examples illustrate:
--Stroke.--Two decades ago, NINDS-supported research showed that tPA
therapy can restore blood flow to the brain following a stroke.
For the first time, stroke became a treatable emergency, and
the care system organized to take advantage. Building on NINDS
funded research, clinical trials in 2015 showed that timely
intervention with intravascular devices can directly clear a
blocked brain artery in severe strokes when tPA does not
restore blood flow, with striking clinical benefit. In 2018 the
NINDS DEFUSE 3 clinical trial reported that a brain imaging
method can identify people who may respond well beyond the
current restricted time window for this intervention, now up to
16 hours, so many more people with strokes may benefit.\8\
These recent results again transform emergency stroke
treatment, and stroke care systems are now making these
catheter-based treatments available in both urban and rural
communities.
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\8\ N Engl J Med. 378:708-718 2018.
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--TBI.--The 2018 FDA marketing authorization of the first blood test
to help in the diagnosis of concussion exemplifies the
extensive NIH and DoD cooperation on TBI. NINDS funded the
foundational basic science and clinical studies to the
successful research team, and DoD supported the subsequent
development and testing. The test could reduce the cost and
radiation exposure from thousands of unnecessary CT scans.
--New Drugs.--Pioneering NIH-supported basic and translational
research, and subsequent private sector development, led to FDA
approval of the first disease-modifying drugs for two rare
pediatric diseases, spinal muscular atrophy (SMA) and Batten
disease. The FDA also approved the first drugs for primary
progressive multiple sclerosis, for movement problems
associated with Huntington's disease, and a drug for
amyotrophic lateral sclerosis (ALS). And researchers reported
promising results for migraine, adrenoleukodystrophy, Niemann-
Pick disease, and several other disorders.
--Dementia.--A long-term NIH study with more than 15,000 people found
that middle aged Americans who have vascular risk factors,
including diabetes, high blood pressure and smoking, are more
likely to suffer from dementia later in life.\9\ The findings
add to a growing body of evidence linking cardiovascular health
to brain health. The hope is that managing vascular risk
factors in middle age may slow or prevent the development of
dementia, and there are hints that may be happening.\10\
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\9\ JAMA Neurology 74:1246-54 2017.
\10\ New England Journal of Medicine 374:523-32, 2016.
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driving future progress
NINDS will continue to emphasize investigator-initiated research
with rigorous peer review because of its proven track record.
Complementing this core strategy, the Institute calls for research
proposals to address unmet public health needs or exceptional
scientific opportunities. Among the notable activities for the coming
year:
--The Opioid Crisis.--Through a series of workshops and discussions
in 2017, Federal agencies, the scientific community, and
industry forged a partnership to accelerate the development of
safe and effective, non-addictive treatments for pain. NINDS
leads two key priorities of the plan-- development of
biomarkers (objective indicators) of pain and of a clinical
trials network to use biomarkers for the development of non-
addictive pain treatments. Together with the NIH Pain
Consortium and the NIH Director's Common Fund, NINDS is also
targeting the key question of why acute pain leads to chronic
pain for some people, well after the original cause of pain has
been resolved.
--ADRDs.--Through the National Alzheimer's Project Act (NAPA),
Congress recognized the impact of not just Alzheimer's, but
also Alzheimer's disease-related dementias (ADRDs).
Frontotemporal dementia (FTD) is the most common dementia in
people younger than 60, and Lewy body and Parkinson's dementias
also have a major impact. The most common ADRD, Vascular
Cognitive Impairment and Dementia (VCID), like stroke, affects
brain blood vessels. VCID is so intertwined with Alzheimer's
disease that most elderly people with dementia have a
combination of the two. NINDS leads several new and ongoing
initiatives to understand and develop treatments for the ADRDS,
working closely with the National Institute of Aging (NIA),
which provides funding to a suite of these NINDS-led programs.
NINDS also leads the ADRD summits that occur every third year,
as mandated by NAPA.
--AMP PD.--NINDS, Celgene, Verily, Pfizer, GlaxoSmithKline, Sanofi,
the Michael J. Fox Foundation (MJFF), and the Foundation for
NIH are launching the Accelerating Medicines Partnership for
Parkinson's Disease (AMP-PD). This new addition to the NIH AMP
program will identify and validate biomarkers and new
therapeutic targets for Parkinson's disease, leveraging a
treasure trove of data and resources supported over the past
several years by NINDS, MJFF, and others.
--Pediatric Concussion.--An NINDS initiative will develop biological
measures of persistent symptoms following pediatric concussion,
which addresses the highest research priority identified by a
2016 NIH scientific workshop on pediatric concussion.
--Biomarkers.--The lack of reliable biomarkers for most neurological
disorders heightens the challenges of developing treatments and
dissuades private sector investment. An NINDS initiative will
support the advanced development and validation necessary to
bring potential biomarkers to clinical practice, complementing
the extensive early phase biomarkers discovery research that is
already underway.
--BRAIN Initiative.--NINDS is an enthusiastic leader of the Brain
Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative. The Initiative is developing and applying new
technologies to understand how circuits of interconnected nerve
cells in the brain enable us to perceive, act, think, and
learn, and what goes wrong in brain disorders. Remarkable new
tools now enable researchers to identify all of the individual
brain cell types, monitor activity of thousands of cells in a
circuit at once in real time, precisely manipulate cells'
activity, and non-invasively monitor and stimulate the human
brain with increasing precision. As the Initiative continues,
engaging these new opportunities to enhance research on pain
and addiction is a high priority.
Finally, NINDS continues its longstanding emphasis on investigator-
initiated basic research, which is yielding remarkable advances on many
fronts in addition to circuits. Among the many findings this year, for
example, research discovered unexpected links between bacteria and
brain blood vessels, new roles of non-nerve cells in the brain,
insights about how genes orchestrate brain development, the role of
undetected seizure-like activity in Alzheimer's disease, how the gut
conveys information to the nervous system, mechanisms of memory, and
novel ways that nerve cells respond to stress. Which findings from
basic research will launch the next advances against disease is not yet
apparent. However, NIH basic research will surely continue to be the
wellspring of progress for both the public and private sector.
______
Prepared Statement of Jon R. Lorsch, Ph.D. Director, National Institute
of General Medical Sciences
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of General Medical Sciences (NIGMS), a component of the
National Institutes of Health (NIH).
The NIGMS focuses on promoting and supporting fundamental or
``basic'' biomedical research that increases scientific knowledge about
how living systems work, from individual molecules to cells, organs,
whole organisms, and populations. The Institute's priority is to
support investigator-initiated research, based on the principle that
the best scientific ideas, directions, and approaches stem from
scientists themselves. Thus, NIGMS aims to enable creative, innovative,
and ambitious research conducted by individuals and teams of
investigators to promote scientific discovery and medical advancement.
One indication of the success of the Institutes' strategy is the
number of Nobel Prizes awarded to NIGMS grantees. Of the 153 Nobels
given for NIH-funded research, over half--87--have been for work
supported by NIGMS. This year, the Nobel Prizes in both chemistry and
in physiology or medicine were awarded to multiple NIGMS grantees. The
2017 Nobel Prize in chemistry was awarded to a NIGMS grantee and two
others for the development of cryo-electron microscopy (cryo-EM), a
technique that simplifies and improves the imaging of biomolecules.
Similarly, the 2017 Nobel Prize in physiology or medicine was awarded
to three NIGMS grantees for their work on molecular mechanisms
controlling circadian rhythms, more commonly known as ``biological
clocks.'' Biological clocks influence a variety of physiological
responses such as alertness, hunger, metabolism, fertility, and mood;
clock dysfunction is associated with various disorders, including
insomnia, diabetes, and depression. These awards serve as yet another
testament to how investing in the study of fundamental biological
processes can yield important insights into the principles that
underlie human biology, health, and disease.
Because scientific breakthroughs generally cannot be predicted in
advance and often originate from unexpected or disparate strands of
knowledge, a cornerstone of NIGMS' strategic plan is to support a broad
and diverse portfolio of fundamental research. This strategy builds the
strongest possible foundation on which breakthroughs can arise.
nigms strategic priority: new funding approaches to accelerate
scientific progress and discovery
In order to enhance the efficiency and productivity of fundamental
biomedical research, the NIGMS has developed a new mechanism to fund
scientists. The Maximizing Investigators' Research Award (MIRA) seeks
to transform how fundamental biomedical research is supported by
providing individual investigators with a heightened level of both
scientific stability and flexibility.\11\ These awards allow
investigators to follow new research directions and insights in real-
time, while simultaneously providing an extra year of support as part
of a more coordinated scientific program (versus single project) focus.
In addition, the peer review process for MIRA applicants reviews early
stage investigators (ESIs) independently from established investigators
(EIs), thus allowing each group of applicants to be examined relative
to their own peer group. Since the creation of the program, the NIGMS
has awarded 231 MIRAs to EIs and 192 MIRAs to ESIs. The MIRA program is
especially beneficial for ESIs, as evidenced by the increase in the
number of ESI applications from 393 in 2015 (prior to MIRA) to 649 in
2017. The number of ESIs funded by the Institute per year has nearly
doubled in the same time period. The NIGMS will continue to monitor the
progress and outcomes of the MIRA program as it evolves.
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\11\ https://www.nigms.nih.gov/research/mechanisms/MIRA/pages/
default.aspx.
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Because some areas of biomedical investigation require groups of
investigators to synergistically work together to solve complex
problems, the NIGMS recently developed and implemented a new team-
science support mechanism known as the Collaborative Program Grant for
Multidisciplinary Teams.\12\ This investigator-initiated funding
opportunity supports multidisciplinary teams of researchers to work
toward a shared goal that has the potential to have a major impact on
one or more fields of biomedical research. Because this program only
funds highly integrated research teams working toward a common
objective, it will promote and enable a type of collaborative science
that can't easily be supported through other kinds of research grants.
Further, these new awards possess an optional component that allows for
support of pilot projects by early-stage investigators to develop
research in the team's area(s) of expertise with a goal of helping the
junior researchers obtain independent funding.
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\12\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-340.html.
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nigms strategic priority: develop and sustain a highly skilled,
diverse, and productive biomedical research workforce
The NIGMS plays a leading role in supporting the career development
and training of the next generation of scientists, including the
development of institutional research capacities in regions across the
country in which the levels of NIH support have been historically low.
Given the rapidly evolving landscape of science and medicine, the
Institute is working to catalyze the modernization of graduate
education. Recently, the NIGMS issued a new funding opportunity
announcement (FOA) for its pre-doctoral T32 training grants \13\ that
focuses on addressing several key issues such as: shifting the emphasis
from simply teaching scientific ``facts'' to teaching both scientific
and professional skills; developing the acumen needed to become
rigorous and responsible scientists; supporting a safe, inclusive and
diverse training environment; promoting the use of evidence-based
teaching and mentoring practices; and enhancing student career
development. Over the next several years, the NIGMS will work to
implement this revised T32 program and will carefully evaluate its
outcomes. In addition, the NIGMS is also working to ensure that
emerging issues can be quickly incorporated and addressed in the
training process, as appropriate. For example, the Institute has
recently supported the development of open-access curricular training
modules in areas related to improving the rigor and reproducibility of
biomedical research. These modules are available on the NIGMS
website,\14\ with more modules due to be added this year. The goal is
to generate useful resources for graduate training programs.
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\13\ https://grants.nih.gov/grants/guide/pa-files/PAR-17-341.html.
\14\ https://www.nigms.nih.gov/training/pages/clearinghouse-for-
training-modules-to-enhance-data-reproducibility.aspx.
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Through its Institutional Development Award (IDeA) program, the
NIGMS provides targeted support to help broaden the geographic
distribution of biomedical research funding by enhancing the
competitiveness of investigators located at academic institutions in
States having a historically low level of NIH support. The IDeA Centers
of Biomedical Research Excellence (COBRE), for instance, support
thematic, multidisciplinary centers that expand and develop faculty
research capabilities and research infrastructure, in part through the
development of core technology facilities needed to carry out modern
multidisciplinary collaborative research. Another important aspect of
the IDeA program is its support of medical research for rural and
underserved communities. The IDeA Clinical and Translational Research
Network (CTR), for instance, provides support for clinical and
translational research that addresses conditions that have been
traditionally higher among certain regions, populations or communities,
including (but not restricted to) cancer, cardiovascular disease, and
substance abuse disorders.
Because developing a well-trained research workforce begins with
early outreach and education, the NIGMS was proud to welcome the NIH
Science Education Partnership Awards (SEPA) to the Institute in
2017.\15\ SEPA supports diversity in the workforce by providing
opportunities for students (specifically at the pre-kindergarten to
grade 12 levels) from underserved communities to learn about careers in
basic or clinical research. Ten of the fourteen SEPAs in IDeA States
are currently in partnerships with IDeA COBREs or IDeA Networks of
Biomedical Research Excellence (INBREs). An Institute goal is to fund
at least one SEPA in every State.
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\15\ https://www.nigms.nih.gov/Research/DRCB/SEPA/Pages/
default.aspx.
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nigms strategic priority: create and share cutting-edge tools and
resources
Given that technology plays a critical role in biomedical research,
the NIGMS continues to place a high level of significance on supporting
the development and dissemination of innovative, new technologies that
have the potential to transform research. To this end, the NIGMS
supports a multi-phased funding strategy that consists of support for
an initial proof-of-concept phase for a given technology followed by
potential support for a second prototype refinement phase. These phases
can then lead to the adoption and expansion of the technology via
commercialization through small business innovation research or small
business technology transfer (SBIR/STTR) grants. Technologies can also
be applied toward answering specific scientific questions through their
incorporation into regular research project grants or, once
sufficiently mature, through their incorporation into resources
supported by the Institute's Biomedical Technology Research Resources
(BTRR) program.\16\ Programs such as the BTRR form an important part of
the NIGMS' portfolio as the Institute seeks to ensure broad access
across the research community to cutting-edge technological resources.
For example, synchrotron-based technologies, an extremely powerful
source of X-rays, are critical for structural biology research; more
than 90 percent of all three-dimensional structures of biological
molecules in the Protein Data Bank \17\ were determined using data from
synchrotrons. The NIGMS recently shifted its support for these
important resources from research grants to a mechanism focused on
user-access, utility and efficiency of operations. A similar model will
be used to support the new national cryo-electron microscopy centers.
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\16\ https://publications.nigms.nih.gov/btrrs/searchresults.asp.
\17\ https://www.rcsb.org/.
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conclusion
Mr. Chairman, in this statement, I have tried to highlight just a
few examples of how NIGMS' programs maximize the scientific returns on
the taxpayers' investments in fundamental biomedical research. As the
scientific enterprise and national clinical landscape continue to
evolve, the NIGMS looks forward to continuing to meet and address both
the challenges and opportunities associated with this dynamic
environment, and in so doing, to the many more advances that will
emerge from institutions, laboratories, research teams, and individual
investigators across the Nation. We thank you for your continued
support and for this opportunity to describe some of the new
initiatives at NIGMS.
______
Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P., Director,
National Institute of Diabetes and Digestive and Kidney Diseases
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the
National Institutes of Health (NIH).
combating chronic disease to improve human health
NIDDK supports research on diseases and conditions affecting the
health and well-being of millions of Americans. Its mission spans
diabetes and other endocrine and metabolic diseases; digestive and
liver diseases; kidney and urologic diseases; blood diseases; obesity;
and nutrition disorders. Though diverse in nature, most of these
diseases and conditions are chronic, consequential, and costly. For
example, diabetes, kidney disease, and digestive diseases alone run
into hundreds of billions of dollars yearly for medical care,
disability, loss of work or productivity, and other costs. Obesity is
at high prevalence among U.S. adults and youth and is a risk factor for
many of these chronic and sometimes deadly health problems. The
challenges are vast, and the needs urgent. Through research and related
activities, NIDDK continues to seek out ways to prevent, treat, and
cure chronic diseases and conditions to improve human health and
quality of life.
research
To foster discovery important to combating chronic disease, NIDDK
supports a multi-faceted scientific portfolio spanning basic to
translational to clinical studies, while also creating and leveraging
partnerships that can fortify and accelerate research. For example, in
basic research, scientists have used a specialized microscopy technique
to develop a three-dimensional picture of a cellular protein that is a
target for certain diabetes drugs. Because this protein is also a
member of a protein ``family'' targeted by about 40 percent of
pharmaceutical drugs on the market today, the intricate knowledge
gained from this work is not only important for diabetes but will
inform the search for new drug treatments and refinement of current
ones for other diseases. New findings in mice may also open up new
therapeutic avenues important to prevention of obesity and type 2
diabetes: One research group has identified a group of brain cells
that, upon activation, induces rapid binge eating and weight gain,
while another has found that bones secrete a hormone that both
suppresses appetite and regulates blood sugar levels. Studies in mice
have also revealed a more complex view of the kidney's role in salt and
water balance and blood pressure regulation and suggest new areas of
investigation for human hypertension. NIDDK-supported scientists have
also been able to produce human intestinal ``organoids''--small bundles
of cells that model various aspects of the small intestine and its
functioning, facilitating study of certain digestive system diseases
and disorders and creating potential for tissue replacement therapy.
In fiscal year 2019, NIDDK will build upon research accomplishments
such as these and upon other research avenues and continue its support
for basic studies of both normal and disrupted biological functions and
systems. For example, the ReBuilding a Kidney (RBK) consortium will
continue efforts to enable tissue repair or replacement in kidney
disease; already, RBK scientists have found that selecting the proper
substrate for growth and structural support is critical to creating
blood supply in a ``kidney on a chip.'' Recent studies have shed light
on the multiple levels of complex interactions that contribute to how
human gut microbes affect health, from molecules produced by the
microbes themselves to differences in human diet; a 2017 workshop on
best practices for studies of diet and gut microbiome will help inform
rigor and reproducibility in future efforts in this aspect of research
on the gut microbiome, which is rapidly emerging as an important
contributor to digestive diseases, obesity, nutrition, and many other
chronic diseases and conditions.
Similarly, NIDDK-supported translational and clinical studies have
yielded fruit. For example, in the translation of genetic discovery to
treatment, NIDDK-supported scientists developed a personalized
treatment plan for a child suffering from a severe anemia after
discovering that the cause was a rare mutation affecting a protein
already available in a therapeutic form. New findings about the impact
of being diagnosed with diabetes before age 20 include that youth with
type 2 diabetes are more than twice as likely as peers with type 1
diabetes to have or be at high risk of a diabetes health complication
by age 21. The Multidisciplinary Approach to the Study of Chronic
Pelvic Pain (MAPP) Research Network has yielded important new insights
into the nature and course of the urologic chronic pelvic pain
syndromes interstitial cystitis/bladder pain syndrome (IC/BPS) and
chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), such as new
knowledge about the prediction of and bodily patterns of pain. NIDDK-
supported scientists have also developed the first method for
calculating the average rate of blood filtration by the individual
functional units in the human kidney, an important measure of kidney
health. Discoveries such as these can now be harnessed into new
research toward interventions or into other actions to improve health.
NIDDK will continue its support of research that, in partnership
with human volunteers, can elucidate causes of and treatments and cures
for chronic diseases and conditions and ways to implement those
findings. For example, the third phase of the Diabetes Prevention
Program Outcomes Study, spearheaded by NIDDK with several NIH partners,
will study outcomes that are of increasing concern in an aging
population with a high burden of pre-diabetes and diabetes. These
include evaluating the potential benefit of the diabetes drug metformin
on the development of cardiovascular disease and cancer. Gestational
diabetes has long-term health impacts for affected mothers and
children, and NIDDK will continue to capitalize on new findings and
efforts to better understand this condition and identify ways to
improve outcomes. Efforts will continue in development and testing of
artificial pancreas systems for treatment of type 1 diabetes. NIDDK
will also continue support for many clinical research efforts to
address overweight and obesity, including major ongoing studies to
assess the health risks and benefits of weight-loss surgery in
extremely obese adolescents. The new Kidney Precision Medicine Project
will pursue innovative efforts to elucidate the heterogeneity of kidney
disease in human study participants, which could lead to novel and
tailored treatments for both acute and chronic kidney disease. NIDDK
will sustain its long-term investment in the Drug-Induced Liver Injury
Network (DILIN) so that it may continue its highly productive and
informative efforts to characterize liver injury from herbal and
dietary supplements and prescription and over the counter drugs.
To help tackle complex challenges and move discovery forward, NIDDK
continues to forge effective partnerships with other NIH ICs and
Offices, other Federal agencies, and private organizations. For
example, the NIH Nutrition Research Task Force chaired by NIDDK and co-
chaired by the National Heart, Lung, and Blood Institute (NHLBI),
National Cancer Institute (NCI), and Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) has sought
input from across NIH and external stakeholders and is developing the
first NIH-wide strategic plan on nutrition. The public-private
Accelerating Medicines Partnership-Type 2 Diabetes (AMP-T2D) project,
spearheaded by NIDDK with partners from industry and nonprofit
organizations, continues to exceed expectations in terms of progress
and will continue augmenting content and access to genetic and clinical
data on diabetes and related traits made available through its
Knowledge Portal.
other
Indivisible from research are the minds and hands that generate new
ideas and bring forth results. NIDDK will continue to foster and grow a
diverse biomedical research workforce that can meet, with innovation
and creativity, the challenges posed by chronic diseases and
conditions. NIDDK supports several special training opportunities
spanning high school to medical school to attract students, including
those underrepresented in science and medicine, to NIDDK research
areas. Mentorship opportunities offered by NIDDK's Network of Minority
Health Research Investigators, which celebrated its 15th anniversary in
2017, focus on junior investigators and will continue to promote a
diverse research pipeline. NIDDK will also continue efforts to help the
new generation of biomedical researchers realize their potential, such
as priority funding strategies for those early in their careers. NIDDK
is also pursuing multiple efforts to enhance rigor and reproducibility
in research. Simultaneously, NIDDK will continue disseminating health
and scientific information through multiple venues to educate and
inform the public, healthcare providers, and researchers about new
developments germane to chronic diseases and conditions.
conclusion
In closing, NIDDK has a robust and vigorous commitment to research
and related activities to combat chronic diseases and conditions. This
is reflected in its five guiding principles: maintain a vigorous
investigator-initiated research portfolio, support pivotal clinical
studies and trials, preserve a stable pool of new investigators, foster
research training and mentoring, and disseminate science-based
knowledge through education and outreach programs. Through research,
NIDDK hopes to advance progress toward new and improved prevention,
treatment, and curative strategies.
______
Prepared Statement of Norman E. Sharpless, M.D., Director, National
Cancer Institute
Mr. Chairman and Members of the Committee, I am pleased to present
the President's fiscal year 2019 budget request for the National Cancer
Institute (NCI) of the National Institutes of Health (NIH). With the
resources that this subcommittee provides, NCI supports a broad array
of biomedical research to advance scientific discovery, reduce the
burden of cancer, and help all people live longer, healthier lives.
NCI Progress under the 21st Century Cures Act
In the Cures Act, Congress authorized $1.8 billion across seven
fiscal years for the Cancer Moonshot. The fiscal year 2018 Consolidated
Appropriations Act provided the second Cures Act installment of $300
million. Guided by the recommendations of a Blue Ribbon Panel convened
to identify research priorities, NCI awarded fiscal year 2017 funding
in ten promising areas of cancer research targeted for rapid
translation into new treatment and prevention. NCI will fund all
remaining Blue Ribbon priorities during fiscal year 2018.
One example of NCI's commitment to the progress envisioned in the
Cures Act is the promising area of immunotherapy--activating a
patient's immune system to attack cancer cells. To accelerate the
development of immunotherapy strategies for cancer patients, in the
fall of 2017, NCI launched a public-private partnership with NIH and
pharmaceutical companies, known as the Partnership for Accelerating
Cancer Therapies, or PACT. The Foundation for the National Institutes
of Health will manage and coordinate PACT, and the Food and Drug
Administration will play an essential advisory role. Twelve
pharmaceutical companies are now members of PACT.
A centerpiece of PACT is NCI's $54 million investment of Cures Act
funds across 5 fiscal years to establish four Cancer Immune Monitoring
and Analysis Centers and a Cancer Immunologic Data Commons. Together,
the centers and data commons will operate as a network to identify
mechanisms of response and resistance to cancer therapy and to support
adult and pediatric immunotherapy trials.
NCI created the immunotherapy network to speed discovery of
molecular signatures associated with immune response and to predict
whether immunotherapy will benefit individual patients. The network
will identify biological markers of disease and response to treatment
that researchers and clinicians can use to design optimum treatment
strategies for cancer patients. The entire cancer research community
can access data from analysis conducted by the four centers and use
this resource to further their research on cancer cures. Other
priorities of the NCI immunotherapy network and the 12 PACT partners
include establishing a set of standardized biomarkers for testing in
research studies, harmonizing assays to strengthen data
reproducibility, fostering data comparability across clinical trials,
and reducing duplication of effort, thereby allowing researchers to
conduct more high-quality clinical trials for children and adults with
cancer.
In addition to support for PACT, NCI also awarded Cures Act funding
to other promising research on harnessing the immune system to attack
cancer. The goal of this research is to expand the initial successes in
immunotherapy to a much wider range of cancers, to a broader range of
patients experiencing the same form of cancer, and to cancers that have
been most resistant to cure.
Appropriations for Other Cancer Research Priorities
While the 21st Century Cures Act deserves prominence in any
discussion of NCI's current cancer research priorities, as a component
of our total budget, fiscal year 2017 Cures Act funding represented
about 5 percent of NCI's total cancer research appropriation. It is
therefore important to emphasize the breadth of other research that
NCI's appropriation conducts.
As the detailed narrative accompanying NCI's budget request
demonstrates, sustained progress that will benefit cancer patients
relies on many forms of research, including:
--basic research, such as genetics, cell biology, immunology, and
structural biology
--translational and clinical sciences to prevent, screen, and
diagnose cancer, and to develop and test drugs, biomarkers,
imaging technologies, diagnostics, and radiotherapies
--population sciences, including epidemiological, environmental, and
behavioral studies.
These areas constitute the bedrock of NCI cancer research.
Continued funding across all these disciplines is essential to
understanding the causes and mechanisms of cancer, preventing cancer,
strengthening cancer screening, developing and refining cancer
therapies, and improving cancer survivorship. Many of these disciplines
will experience profound changes based on the new understanding of
cancer that is driving precision oncology and to tailor treatments to
individuals. Others will continue to depend on more traditional
approaches to research.
The research resources that NCI makes available to the cancer
research community is another mechanism of growing importance to cancer
science. Examples of NCI research resources include:
--The Biopharmaceutical Development Program (BDP) produces novel
antibodies and proteins when they cannot be manufactured
elsewhere. For example, researchers turned to the BDP to
manufacture a monoclonal antibody (ch14.18) necessary for a
clinical trial to proceed. The antibody is now the standard of
care for children with certain types of neuroblastoma.
During fiscal year 2018, NCI will use the capability of the BDP to
expand production of CAR T-cells for use in immunotherapy
trials. The BDP will help meet the growing demand for
experimental therapies to serve adult and pediatric patients in
intramural and extramural clinical trials. CAR T-cell therapy
is an immunotherapy treatment in which a patient's T-cells (a
type of immune cell) are modified in the laboratory so they
bind to cancer cells. Millions of CAR T-cells are grown in the
laboratory and then given to the patient by infusion, where
they bind to an antigen on cancer cells and kill them.
--NCI's Experimental Therapeutics (NExT) program advances
breakthroughs in new cancer therapies by shortening the
timeline for drug discovery, development, and approval.
Researchers with promising cancer drug development projects can
apply to NExT for assistance to overcome the challenges they
face along the path to drug approval.
Vanderbilt University's recent progress developing therapies to
inhibit a protein known as Mcl-1 is an example of the
breakthroughs that NExT helps to foster. After engaging NExT
scientists to resolve therapeutic development challenges,
Vanderbilt is now collaborating with Boehringer Ingelheim to
develop drugs to treat a range of cancers known to overexpress
the Mcl-1 protein.
--NCI's RAS Initiative supports the development of therapies for
tumors that contain mutations in the RAS family of oncogenes.
One-third of all cancers involve RAS gene mutations. Through
the RAS Initiative, NCI generates standardized reagents,
assays, and datasets and provides them to scientists worldwide
to support research on RAS oncogenes.
--The Cancer Genome Atlas (TCGA)--a collaboration between NCI and the
National Human Genome Research Institute--is a resource of
comprehensive, multi-dimensional maps of key genomic changes in
33 types of cancer. The publicly-available TCGA dataset--
containing 2.5 petabytes of data--has contributed to more than
a thousand cancer studies. An NCI priority for fiscal year 2018
is to update TCGA data with new details on patient therapeutic
response, outcome, and survival, and to support additional
clinical research based on the new data.
--Launched in June of 2016, NCI's Genomic Data Commons (GDC) is a
unified data system for sharing genomic and clinical data. The
GDC centralizes and standardizes data from large-scale NCI
programs, and makes it more accessible and useful to scientists
and clinicians. One measure of the importance of this resource
is that non-profit and for-profit organizations are now
offering their data sets for sharing through the GDC.
I also want to highlight our progress with the NCI Molecular
Analysis for Therapy Choice (NCI-MATCH) Trial and the Pediatric MATCH
Trial, two cornerstones of NCI's Precision Medicine Initiative. Rather
than selecting therapies based on where a tumor originated in the body,
these trials test the effectiveness of therapies that target specific
genetic changes. In 2017, the adult NCI-MATCH Trial achieved its
enrollment goal nearly 2 years ahead of schedule. The trial involves
more than 6,000 patients from all 50 States at more than 1,000
institutions.
NCI opened enrollment for the Pediatric MATCH Trial during fiscal
year 2017. This is a phase 2 clinical trial for children and
adolescents with certain advanced solid tumors that have not responded
to treatment or have progressed on standard therapy. The study is led
jointly by NCI and the Children's Oncology Group, a clinical trials
group including more than 9,000 childhood cancer experts across 3
continents that is part of the NCI-sponsored National Clinical Trials
Network. The Pediatric MATCH trial is taking place at 200 participating
children's hospitals, university medical centers, and cancer centers
across the United States.
Thanks to support from Congress over many years, NCI research in
these and other areas has yielded important results that have
contributed to steady decreases in cancer mortality. Sustained
Congressional support for NCI and the national cancer program has led
to new diagnostics, treatments, and prevention strategies, improved our
ability to manage the symptoms of cancer and the side effects of cancer
treatments, and allowed us to more effectively monitor the prevalence
of cancers and the factors associated with cancer risk.
NCI-led cancer research on prevention and treatment is paying off:
translating into a more than 25 percent reduction in cancer death rates
since 1991. Yet despite steady progress, too many Americans face a
cancer diagnosis, and far too many still die from the disease. There
will be more than 1.6 million new cases of cancer in the United States
in the coming year and more than 600,000 will likely die from cancer.
Thus, much work remains to meet the needs of those suffering from
cancer, those at risk of cancer, and the growing population of cancer
survivors. The resources proposed in this fiscal year 2019 budget will
allow NCI to continue to conduct our cancer research mission in ways
that deliver important results for the patients we serve.
______
Prepared Statement of David Shurtleff, Ph.D., Acting Director, National
Center for Complementary and Integrative Health
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National Center
for Complementary and Integrative Health (NCCIH) of the National
Institutes of Health (NIH).
The mission of NCCIH is to define, through rigorous scientific
investigation, the safety and effectiveness of complementary and
integrative health approaches, which are a group of practices and
products that originate outside of conventional medicine. This diverse
group of health practices includes natural products such as dietary
supplements, plant-based products, and probiotics, as well as mind-body
approaches such as yoga, massage therapy, meditation, mindfulness-based
stress reduction, spinal manipulation, and acupuncture. According to a
2012 National Health Interview Survey (NHIS), Americans are spending
approximately $30.2 billion a year on complementary approaches to
improve their overall health, manage symptoms of chronic diseases, and/
or counter the side effects of conventional medicine. However, the
scientific research base surrounding the safety and efficacy of these
practices is limited. Therefore, NCCIH is committed to providing the
American public with valuable information about these practices, while
also investigating how specific complementary approaches can be
integrated into conventional medical care.
exploring nonpharmacologic approaches for pain management
NCCIH is devoting significant resources to understand the basis of
pain and how complementary and integrative health approaches can be
utilized in pain management. Pain is a major public health problem and
is the most common reason Americans turn to complementary and
integrative health practices. Data from the 2012 NHIS found that an
estimated 25.3 million adults in the U.S. (11.2 percent) experience
daily pain with nearly 40 million adults (17.6 percent) experiencing
severe levels of pain. The use of highly addictive opioids as a primary
pain management strategy in the U.S. is helping to fuel the growing
opioid misuse epidemic. Improved strategies for pain management may
lead to a decreased reliance on opioids for patients suffering from
pain. NCCIH supports research to better understand the biologic
mechanisms of pain and to identify effective nonpharmacologic
approaches to reduce the duration and intensity of pain.
Research supported at NCCIH is focused on understanding the role of
the brain in perceiving, modifying, and managing pain, with the long-
term goal of improving clinical management of chronic pain through the
integration of pharmacologic and nonpharmacologic approaches. Recently,
scientists discovered a new class of sensory nerve cells that respond
to high-threshold (intense) mechanical stimuli, such as hair pulling.
This work provides insights into how our bodies encode and transmit
pain sensations. Another study mapped the regions of the brain
activated during pain to establish a ``pain signature'' and found that
specific regions of the brain respond to pain intensity, while other
regions mediate the psychological effect, and yet another region showed
increased activity related to pain relief. This work not only provides
insights into how pain is interpreted but could lead to the development
of new methods to detect, quantify, or target pain.
NCCIH-supported research is also advancing understanding of the
mechanisms of action of mind and body interventions and determining
their effectiveness for treating pain. One study investigated the
effect of acupuncture on carpal tunnel syndrome and found that it
affected activity within brain pain centers, decreased associated pain
symptoms, and improved overall wrist function. Mindfulness meditation
is another promising area of research. Numerous studies have shown that
mindfulness meditation helps relieve pain, but the mechanism through
which meditation exerts this effect is not well known. New study
results demonstrate that mindfulness meditation activates the same
region of the brain as opioids; however, it reduces pain independently
of opioid neurotransmitter mechanisms. These results suggest that
greater pain control could be achieved through the combination of
mindfulness meditation and opioid-signaling-induced pharmacologic
approaches. NCCIH-supported research has also shown that mindfulness-
based stress reduction and cognitive behavioral therapy can improve
functioning and reduce chronic low back pain in young and middle-aged
adults and may provide patients with skills for long-term management of
pain. Studies have demonstrated that these approaches resulted in
substantial cost savings over usual care.
Based on these and other promising results, NCCIH is leading a new
multi-agency partnership between the NIH, Department of Defense (DoD)
and Department of Veterans Affairs (VA). This initiative, called the
NIH-DoD-VA Pain Management Collaboratory (PMC), addresses the need to
focus on ``advancing better practices for pain management,'' which is
outlined in HHS's five-point strategy to combat the opioid crisis. The
PMC will focus on developing, implementing, and testing cost-effective,
large-scale, real-world research on nondrug approaches for pain
management and related conditions in military and veteran healthcare
delivery organizations. The PMC launched in fiscal year 2017 and the
agencies plan to fund 11 two-year UG3 (Planning Phase) awards, and up
to 10 four-year subsequent UH3 (Implementation Phase) Demonstration
Projects, contingent upon successful completion of the short-term pilot
and feasibility studies In addition, a PMC Coordinating Center has been
established at Yale University and the Veteran's Administration
Hospital in Connecticut to provide leadership and serve as a resource
for the projects by providing innovative tools and best practices.
Types of approaches being studied include mindfulness/meditative
interventions, movement interventions (e.g., structured exercise, tai
chi, yoga), manual therapies (e.g., spinal manipulation, massage,
acupuncture), psychological and behavioral interventions (e.g.,
cognitive behavioral therapy), integrative approaches that involve more
than one intervention, and integrated models of multi-modal care. The
results of these studies may inform new pain management practices
within the DoD and VA and support the use of nondrug approaches for
pain management in the general population
advancing research on natural products
According to the 2012 NHIS, nearly one in five U.S. adults use
botanical supplements and other non-vitamin, non-mineral dietary
supplements, such as fish oil/omega-3 fatty acids and probiotics.
Adverse events related to dietary supplements are estimated to
contribute to 23,000 emergency department visits in the U.S. each year.
To better inform consumers and their healthcare providers, NCCIH
supports rigorous research on the biological mechanisms of the benefits
and potential harmful effects of natural products with the goal of
improving the body of knowledge available to healthcare providers and
patients.
NCCIH is supporting a Center of Excellence to determine how best to
study potential adverse interactions between natural products and
conventional medications. The goal is to develop a definitive approach
to determine the clinical relevance of supplement-drug interactions to
inform design of future research and, ultimately, decisionmaking about
using natural products and medications together.
In fiscal year 2015, NCCIH partnered with NIH's Office of Dietary
Supplements (ODS) to establish the Centers for Advancing Research on
Botanical and Other Natural Products (CARBON) Program. Through this
program, researchers recently identified two chemicals found in grapes
that could significantly reduce depression-like behaviors in mice. The
systems targeted by these compounds are not the same as current
pharmaceutical antidepressants and may provide novel insights into the
biology of depression and could lead to new therapeutic agents. The
program is also developing new methods for chemical characterization of
natural product mixtures, biological profiling assays, and creating new
informatic tools to rigorously analyze and share data.
NCCIH is also supporting research on cytisine, a natural product
for smoking cessation. Despite promising results from clinical trials
conducted outside the U.S., cytisine has not yet been approved for use
in the U.S. NCCIH supported a series of pre-clinical studies on
cytisine through a strategic collaboration with Achieve Life Sciences,
Inc., OncoGenex Pharmaceutical, Inc., other NIH ICs, and private
research organizations. Phase 2 clinical studies will further assess
cytisine as a smoking cessation treatment. This continuing public-
private partnership may lead to the wide availability of a new option
to address the major public health issues associated with tobacco use.
conclusion
As a responsible steward of resources, NCCIH supports
scientifically meritorious basic, mechanistic, clinical, and
translational research. The Center focuses on areas with the greatest
potential impact by prioritizing research topics that show scientific
promise and are amenable to rigorous scientific inquiry. We leverage
strategic partnerships to build the scientific evidence needed on the
safety and efficacy of complementary health approaches and disseminate
evidence-based information to the American public.
______
Prepared Statement of Dr. Paul Sieving, Director, National Eye
Institute
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National Eye
Institute (NEI) of the National Institutes of Health.
fifty years of vision research
It may have been a hot day on August 16, 1968, when President
Johnson signed Public Law 489 to create the National Eye Institute, but
on March 21, 2018, the biggest blizzard of the season threatened a
reception hosted by Congressman Pete Sessions to celebrate NEI's 50th
anniversary. However, snow didn't deter over 100 vision research
stakeholders, National Institutes of Health scientists, patients, and
members of Congress from coming out to recognize the vision-saving
progress made in the past half century. While my statement usually
covers the latest advances, I want to start by reflecting on some of
our remarkable research progress, which has advanced clinical vision
care.
Over the past 50 years, NEI has funded research of nine Nobel Prize
winning scientists, including discovery of the molecular mechanisms by
which specialized neurons in the retina detect photons of light
entering the eye and initiate biochemical and electrical signals to the
brain that convey vision. The key light-detecting protein, rhodopsin,
became the first cell membrane-bound protein studied by x-ray
crystallography and imaged to reveal the protein structure in three
dimensions. This paved the way for the study of other molecules in
diseases in and beyond the eye. NEI-funded Nobel laureates also made
landmark neuroscience discoveries of how brain circuits form and self-
organize in the visual cortex. This has revolutionized treatment for
amblyopia, a disorder in which the brain favors visual information
coming from one eye over the other. The first use of antiviral
chemotherapy was developed for the eye to treat herpes outbreaks on the
cornea. In ground-breaking work, NEI scientists discovered the first
tumor suppressor gene, retinoblastoma, which transformed all of cancer
biology. Conversely, in the past decade, the ocular adaptation of a
cancer drug that blocks growth of abnormal blood vessels treats two of
the leading causes of blindness: age-related macular degeneration (AMD)
and diabetic retinopathy, stopping disease progression, and in many
cases, reversing vision loss for medical benefit to thousands of
patients.
In its early years, NEI pioneered new methodology for conducting
placebo-controlled, multi-center clinical trials, which led to vision-
saving laser surgery to treat diabetic retinopathy, AMD, and glaucoma.
Large trials identified dietary supplements demonstrated to slow
progression to end-stage AMD. Trials compared effectiveness of
different therapies for AMD, diabetic retinopathy, and an inflammatory
eye condition called uveitis, to inform patients and their doctors of
options for personalized treatment. Elevated fluid pressure in the eye,
called ocular hypertension, is a precursor for glaucoma, especially in
African Americans who have a disproportionate burden of this disease.
1,500 patients participated in the Ocular Hypertension Treatment Study,
including 400 African American participants, which led to new treatment
guidelines that can reduce incidence in African Americans by 50
percent. A 20-year follow-up study is currently underway to assess the
long-term impact. More recently, the first application of genomics
methods led NEI scientists to uncover new genetic components for AMD,
opening the door to new treatments. Before NEI was established, a major
cause of lifelong blindness was retinopathy-of-prematurity (ROP), a
disease caused by abnormal development of retinal blood vessels in low
birth weight babies born very prematurely. Technology to identify and
treat ROP has improved dramatically over the years and a recent NEI
trial demonstrated that premature infants can be screened for ROP
remotely via telemedicine, expanding access to specialists in rural and
underserved communities.
recent progress in vision research
NEI-supported vision research remains on the forefront of medicine,
from regenerative medicine to replace neural tissue lost due to retinal
degeneration; to advancing retinal prosthetics, including the Argus II
artificial retina which was approved by FDA through the Humanitarian
Device Exemption pathway; and pioneering the application of gene
therapy to correct blinding disease-causing mutations. One landmark
occurred in December 2017, when the FDA approved the first ever gene
therapy in the U.S. to correct a retinal degeneration, Leber Congenital
Amaurosis, which causes blindness in infants and children. The genetic
mutation had earlier been discovered by an NEI scientist in 1993, but
researchers had to invent the tools to turn that discovery into a gene
therapy. Having set this precedence for all of medicine, the path from
gene discovery to clinical trial is now being expedited with vision
loss mutations in a dozen genes currently being addressed in pre-
clinical and clinical studies.
Also in December, FDA approved two new drugs for glaucoma, the
first new medications for this disorder in 18 years. This new class of
drugs lowers pressure in the eye through novel targets that are
different from existing medications. An ongoing clinical trial is
testing a combination therapy of the newer and older drugs used
together, which may prove more effective than either drug alone. This
research represents the culmination of over 25 years of NEI basic
research on molecules that control the contractile machinery of cells,
which regulate the flow of fluid out of the eye.
Idiopathic intracranial hypertension (IIH), which primarily affects
obese young women, causes the buildup of pressure on the optic nerve,
leading to vision loss in nearly 10 percent of patients. The recently
completed IIH Treatment Trial of 165 patients showed that for mild
vision loss, intervention with acetazolamide plus diet was superior to
diet alone for reducing vision loss and improving quality of life.
However, neither intervention was effective for patients with moderate
to severe vision loss. NEI is funding a new three-arm trial testing
different surgical interventions to relieve pressure and protect the
optic nerve in 180 IIH patients with more severe vision loss.
seeing into the future
The NEI Audacious Goals Initiative (AGI) seeks to restore vision
through neuroregeneration in the eye and visual system. This
fundamental regenerative medicine approach was initiated in 2013 and is
advancing rapidly. NEI has established two collaborative consortia of
research teams working on different facets of the challenge: one on
functional imaging, and a second for discovery science to identify new
regeneration factors by looking in model systems. For example, unlike
adult mammals, zebrafish can regenerate their retina after injury,
which led NEI researchers to identify a key regeneration factor,
present in newborn mice, and through manipulating this factor, they
caused new neurons to form in adult mice. Scientists also found that
exosomes secreted from stem cells protect a type of retinal cells, the
ganglion cells, which are damaged by glaucoma. Exosomes are now being
examined for potential therapeutic effect. Exosome-treated rats lost
only a third of their retinal ganglion cells following optic nerve
injury, compared with 90 percent loss in untreated rats. NEI is now
reviewing proposals for a third AGI consortium, to develop animal model
systems to facilitate translation of discovery research into the
clinic.
NEI just launched new stem cell trials for retinal vein occlusion
(RVO)--the second leading retinal vascular cause of vision loss after
diabetic retinopathy, and for limbal stem cell deficiency (LSCD). In
RVO, the vessels draining blood from retinal tissue become clotted,
leading to leaking and bleeding and ultimately starving the neurons of
oxygen. The trial will test the safety, feasibility and efficacy of
injecting stem cells derived from the patient's own bone marrow into
their eyes. Corneal limbal cells, are responsible for renewing the
front layer of the transparent cornea. In thousands of patients with
LSCD, loss of these cells causes visual impairment from chronic
inflammation, abnormal blood vessel growth, and opaque corneas. The
21st Century Cures Act Regenerative Medicine Program is supporting an
NEI project to treat LSCD. Researchers identified a limbal cell marker,
ABCB5, which has allowed them to isolate, purify and expand limbal stem
cells in the lab in sufficient quantities for transplantation. This
summer, NEI scientists are about to launch the first clinical trial
using induced pluripotent stem cells-derived retinal tissue to treat
the dry form of AMD. Skin cells taken from AMD patients will be
manipulated in the lab for about 3 months, then transplanted back into
the same patients, thereby minimizing rejection of foreign tissue that
affects many types of transplant therapies.
In 2017, NEI launched a 3D Retina Organoid Challenge Competition
(3D-ROC), with the goal of developing functioning ``mini-retinas'' in a
culture dish from human adult stem cells. In September, NEI awarded the
$90,000 prize for the Phase I Ideation Stage, to a team that developed
the concept of building a retina by screen-printing adult neural
progenitor-derived retinal cells in layers that mimic the structure of
the human retina. The system is designed to be scalable, efficient, and
reproducible, enabling high throughput screening for drug testing. In
February 2018, NEI launched Phase II, which soon will award up to $1
million in prizes for developing this work to the critical stage of
functional prototypes of human retinas.
In January, NEI announced the launch of a new strategic planning
process, under the auspices of the National Eye Advisory Council. The
5-year plan will be developed with significant community input,
centered around scientific program working groups. It will also align
with the NIH Strategic Plan and requirements laid out in the 21st
Century Cures Act, including research to address health disparities.
______
Prepared Statement of Martha J. Somerman, DDS, Ph.D., Director,
National Institute of Dental and Craniofacial Research
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute of Dental and Craniofacial Research (NIDCR) of the National
Institutes of Health (NIH).
The mission of NIDCR is to improve dental, oral, and craniofacial
health through research, research training, and the dissemination of
health information. A recent study looking at personal healthcare
spending in the United States by condition estimates that Americans
spend $66.4 billion annually on the treatment of oral disorders and
another $48.7 billion for general dental care and preventive services.
Together, the total surpasses the costs of treatment related to a
common condition among Americans--diabetes--by more than $13
billion.\18\ NIDCR leads the effort to reduce this burden by supporting
basic, translational, and clinical research and research training to
improve dental, oral, and craniofacial health. By promoting the timely
translation of those findings into practice NIDCR helps advance
treatment and prevention strategies for all Americans.
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\18\ Dieleman J. US Spending on Personal Health Care and Public
Health, 1996-2013. JAMA. 2016; 316(24):2627-2646.
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To prioritize emerging areas of scientific inquiry that are ripe
for significant advances over the next decade, we launched a long-term
strategic initiative called NIDCR 2030. As part of this bold, forward-
looking plan, NIDCR will support research that integrates oral health
into overall health and uncovers the common risk factors and underlying
biological mechanisms of health and disease throughout the body. This
knowledge will inform the development of new preventative and
therapeutic interventions to improve dental, oral, and craniofacial
health--as well as the health of the whole body.
pioneering a gene therapy to treat chronic dry mouth
For most people who survive head and neck cancers, successful
treatment with radiation therapy comes at a high price--significant
loss of salivary gland function, leading to chronic dry mouth and its
adverse health effects. Radiation therapy works by killing malignant
tumor cells, but it does not discriminate among cell types. It also
kills saliva-producing cells, which causes saliva production to shut
down. This can lead to problems chewing, tasting, talking, and
swallowing food, and significantly increases the risks for dental
decay, tooth loss, and oral infections. NIDCR supports research to
unravel the complex molecular and cellular processes involved in
salivary gland function and fluid secretion. These investments have
inspired the development of a gene therapy to treat chronic dry mouth
caused by radiation treatment. The therapy delivers specific DNA
sequences into the surviving salivary gland cells, resulting in the
production of specialized tube-shaped proteins called aquaporins, which
allow water to flow out of the salivary gland cells. Studies in mouse
models showed that the gene therapy generated enough aquaporin proteins
to restore salivary flow. This research led to a clinical trial
conducted on the NIH campus that is currently recruiting patients to
test the gene therapy treatment in people whose salivary glands have
been damaged by radiation therapy for head and neck cancer. Results
from the first phase of the study are encouraging and suggest that this
approach could be a promising treatment. Building on these studies,
another clinical trial is being planned to see if the therapy can also
be used to restore salivary function in individuals whose chronic dry
mouth is caused by Sjogren's syndrome, an autoimmune disorder that
damages salivary glands.
developing innovative techniques to advance regenerative medicine
A major priority for NIDCR is advancing regenerative medicine
research to improve the lives of those with dental, oral, and
craniofacial conditions or diseases. A significant challenge in
regenerating load-bearing tissues such as joint cartilage is
engineering and growing tissues that are as strong and flexible as the
body's natural ones. The cartilage that makes up joints, such as the
temporomandibular joint in the jaw, must be extremely resilient to
withstand a lifetime of repetitive movement and mechanical stress. To
overcome this obstacle, NIDCR-supported scientists are developing
techniques to generate functional tissues in the laboratory for
regenerative medicine therapies. These scientists developed a device
that physically pulls on single layers of cartilage cells while they
are being grown on a flat, supportive matrix, resulting in tissues with
strength and elasticity that more closely resembles natural cartilage.
Using this technique results in engineered cartilage that is more
resilient to wear and tear, making it especially useful as a potential
replacement for damaged cartilage in highly mobile joints. Future uses
could include the development of better treatment options for
temporomandibular joint and muscle disorders (TMD) and joints damaged
by osteoarthritis. Further development of this novel cartilage growth
technique, and its expansion to other cell types could open the door to
exciting possibilities for the engineering and generation of more
durable and flexible tissues for use throughout the body.
finding pain relief in unexpected places
Chronic pain is a major health problem that affects almost one-
quarter of the U.S. population.\19\ Opioids are often prescribed to
alleviate chronic pain, although they carry a strong risk for
addiction. Identifying new effective and non-addictive pain treatments
remains a priority for NIDCR, especially in regard to TMD, a group of
conditions that can cause severe and chronic pain in the jaw and
muscles of the head and neck. In 2005, NIDCR launched OPPERA (Orofacial
Pain, Prospective Evaluation and Risk Assessment)--a multi-site
population-based study--to identify the biopsychosocial and genetic
risk factors that cause TMD. Early OPPERA studies found an association
between the gene for epidermal growth factor (EGFR) and the development
of chronic pain in patients with TMD. Drugs that block the activity of
EGFR are currently being used to inhibit tumor growth in some types of
cancer. Strikingly, there have been case reports of cancer patients
reporting a significant reduction in pain when treated with EGFR-
blocking drugs. Taking these observations into the laboratory, NIDCR-
funded investigators used a mouse model to show that EGFR-blocking
drugs alleviate inflammatory and neuropathic pain. These drugs function
by blocking the activity of EGFR in neurons that receive and interpret
sensory stimuli--such as pain--in the body. This intriguing finding
could lead to the development of more effective treatments for chronic
pain that also reduce the risks for addiction.
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\19\ Gereau RW, et al. A pain research agenda for the 21st century.
J Pain. 2014; 15(12):1203--1214.
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advancing treatments for hpv-positive and hpv-negative oropharyngeal
cancers
Oropharyngeal cancers form in the middle part of the throat,
including the back of the mouth, base of the tongue, and the tonsils,
and are often caused by HPV (human papilloma virus), the same virus
that causes cervical cancer. These cancers are known as HPV-positive
(HPV+) oropharyngeal cancers. Experts estimate that 60 to 70 percent of
newly diagnosed oropharyngeal cancers in the United States are likely
to be HPV+, especially among young men and women. Although people
exposed to the HPV virus are more likely to develop oropharyngeal
cancer, paradoxically, HPV+ cancers respond much more successfully to
chemotherapy than HPV-negative (HPV-) cancers. A collaboration of
clinicians and basic science researchers funded by NIDCR are studying
the biomolecular reasons for this difference in treatment outcomes to
see if there is a way to separate out the HPV+ beneficial response to
treatment and then apply it to HPV-negative (HPV-) oropharyngeal
cancers. To do this they looked closely at the activities of
cisplatin--the most commonly used chemotherapy for many cancers--which
is better at killing HPV+ cancer cells than HPV-cancer cells. The team
discovered an HPV protein called E7 that enhances the effectiveness of
cisplatin treatment, and then developed a small protein fragment
(peptide) called E2F5 that mimics the HPV protein E7 without the HPV
infection. Combining this novel peptide with cisplatin treatment in
HPV-negative patients led to improved outcomes, similar to those of
HPV+ patients. Next steps will be to clear the FDA requirements for
producing the E2F5 peptide and establishing treatment protocols for
clinical trials.
______
Prepared Statement of Eliseo J. Perez-Stable, M.D., Director, National
Institute on Minority Health and Health Disparities
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute on Minority Health and Health Minorities of the National
Institutes of Health (NIH).
advancing the science of minority health and health disparities
research
Today, revolutionary advances in biomedical science, such as the
emergence of genomics, precision medicine, and health information
technology hold greater promise to improve our Nation's health than has
ever before been possible. We are on the cusp of major scientific
advances that will change how we think about minority health and health
disparities. The mission of the National Institute on Minority Health
and Health Disparities (NIMHD) is to lead scientific research to
improve minority health and reduce health disparities. To accomplish
this, NIMHD plans, coordinates, reviews, and evaluates NIH minority
health and health disparities research and activities; conducts and
supports research in minority health and health disparities; promotes
and supports the training of a diverse research workforce; translates
and disseminates research information; and fosters innovative
collaborations and partnerships. As part of its charge to improve
minority health and reduce health disparities, NIMHD is currently
developing the 2018-2022 Trans-NIH Minority Health and Health
Disparities Strategic Plan in collaboration with the other NIH
Institutes and Centers and with input from community partners and key
stakeholders. Once completed, this strategic plan will provide a
blueprint to advance the direction and goals of minority health and
health disparities research.
As the science of minority health and health disparities research
evolves, a critical multidisciplinary approach is needed to focus on
research studies that facilitate scientific advances to improve
minority health and to reduce health disparities. Minority health
research is the scientific investigation of distinctive health
characteristics and attributes of minority racial and/or ethnic groups
who are underrepresented in biomedical research in order to understand
population health outcomes. Health disparities research is a field of
study devoted to gaining greater scientific knowledge about the
influence of health determinants, understanding the role of different
pathways leading to disparities, and determining how findings
translates into interventions to reduce health disparities. In order to
ensure that all populations have an equal opportunity to live healthy
and productive lives, NIMHD leads advancement in minority health and
health disparities research and promotes a diverse scientific workforce
reflective of the population.
research
Advancing the science of minority health and health disparities
requires scientific vision; that means building and developing
evidence-based information that takes into account the social
determinants of health and the places where we live, learn, work, and
play. To meet the demands of keeping up with biomedical advances, NIMHD
is strengthening research in minority health and health disparities;
increasing opportunities for investigator-initiated research;
strengthening the evaluation and reporting of minority health and
health disparities research; and supporting the expansion of workforce
diversity.
NIMHD promoted the fields of minority health and health disparities
by developing and posting NIMHD's Research Framework, a transformative
scientific agenda which addresses the complex influences on health and
health disparities. Specifically, the Research Framework reflects an
evolving conceptualization of factors relevant to the understanding and
promotion of minority health and to the understanding and reduction of
health disparities. The framework focuses on how these influences
affect individuals, families, communities and society at large. It
serves as a vehicle for encouraging NIMHD- and NIH-supported research
that addresses the complex and multi-faceted nature of minority health
and health disparities and guides researchers on where on the
scientific spectrum their research fits.
NIMHD's increased emphasis on the science of minority health and
health disparities has evolved into the three focused areas of clinical
and health services research, integrative biological and behavioral
research, and community health and population sciences. The Clinical
and Health Services Research area generates new knowledge to improve
health outcomes and quality of healthcare for minority and underserved
populations within the context of everyday clinical practice. It
examines the development of preventive, diagnostic and therapeutic
healthcare interventions that can contribute to reducing health
disparities and how precision patient-clinician communication may
reduce health disparities. Moreover, it supports clinical research that
generates new knowledge to improve health outcomes and quality of
healthcare. For example, researchers found that childhood cancer
survivors who reported greater well-being rated religion and
spirituality of high importance, accessed specialized cancer services
more regularly, and expressed a greater level of healthcare self-
efficacy.
The Integrative Biological and Behavioral Research area examines
research on how biological and behavioral mechanisms and pathways
influence resilience and susceptibility to adverse health conditions
that disproportionately affect racial and ethnic minority populations,
persons of less privileged socioeconomic status, and other health
disparity populations. Research examples in this area include genomic
and epigenomic risk and protective factors; human microbiome
contributions to health and disease; and mechanisms through which
behavioral risk and protective factors influence the development of
adverse health conditions by triggering adverse biological pathways.
For example, research found that changes in DNA, as a consequence of
environmental factors, can be used to accurately estimate gestational
age. This novel measure of gestational age may be a useful tool in
addressing persistent higher rates of low birth weights for some
minority populations.
The Community Health and Population Sciences research area focuses
on community engaged research and large studies of populations in a
defined geographic area that reflect overall health of minority and
underserved population groups. Community engagement refers to the
active participation of community members in contributing to the
research process in a partnership with investigators. Studies within
this area examine causes, prevention, screening, early detection, and
management of disease such as epidemiologic studies that identify and
describe disease burden and risk factors in disparity populations;
behavioral, sociocultural, and environmental influences on disease
risks and outcomes; and research integrating the multiple determinants
of health at the biologic, behavioral, and contextual levels and their
interactions. In a study examining the perspective of older breast
cancer survivors toward physical activity, researchers found that
physical activity programs should focus on cancer treatment related
concerns and include strength training.
Innovative partnerships and collaborations are instrumental and
essential to improve minority health and reduce health disparities.
NIMHD supports research partnerships across NIH and the Federal
Government with a goal to create synergistic research approaches to
improve public health for health disparity populations. Partnerships
conducted and supported by the NIMHD have created innovative studies
into how to promote screening for breast, prostate, and pancreatic
cancers; examine how children's experiences affect brain development;
investigate the effects of environmental exposures--including physical,
chemical, biological, social, behavioral, natural and built
environments--on child health and development; understand the sources
of persistent health disparities in overall longevity, cardiovascular
disease, and cerebrovascular disease; and to eventually eliminate
health disparities in dental care and oral/pharyngeal cancer.
building a diverse biomedical workforce
At the core of NIMHD's transformative scientific agenda is its
commitment to building institutional research capacity and a diverse
cadre of minority health and health disparities researchers. The
Centers of Excellence program creates collaborative hubs for minority
health and health disparities research among research institutions and
local communities, which support early-career scientists as well as
established investigators. The Research Centers in Minority
Institutions program builds research capacity, supports a new
generation of researchers from underrepresented populations through
pilot funding, and funds established scientists to conduct cutting edge
science in basic, behavioral or clinical research topics. The Research
Endowment program provides funds to low resource academic institutions
with a diverse student body and faculty to support endowments that will
help to support a training or research capacity program to promote
minority health and health disparities research.
NIMHD is committed to supporting and developing a diverse
biomedical workforce. We support training grants across the spectrum of
experience from pre-doctoral awards through mid-career awards.
Moreover, NIMHD has enhanced opportunities for early-stage
investigators by: expanding awards to help senior postdoctoral fellows
and junior faculty-level candidates to become competitive for major
grant support; providing fellowships to help less experienced
researchers to become productive, independent investigators; and
restructuring the NIMHD Health Disparities Research Institute to
support career development for promising early-career minority health
and health disparities research scientists.
conclusion
NIMHD continues to advance the science of minority health and
health disparities by building upon evidence-based research; developing
researchers from underrepresented populations and retaining their
diverse insights; and enhancing programs that create research
infrastructure and train a diverse scientific workforce. Through this
scientific research agenda, NIMHD's mission and vision will lead to
discoveries that will promote health equity and ultimately improve
minority health and reduce health disparities.
______
Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal
Deputy Director, Office of the Director
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the Office of the
Director (OD) of the National Institutes of Health (NIH).
The OD promotes and fosters NIH research and research training
efforts in the prevention and treatment of disease through the policy
oversight of both the extramural grant and contract award functions,
the Intramural Research program, and through the coordinating efforts
of several cross-cutting program offices responsible for stimulating
specific areas of research throughout NIH to complement the ongoing
efforts of the Institutes and Centers. The OD also develops policies in
response to emerging scientific opportunities employing ethical and
legal considerations; coordinates the communication of health
information to the public and scientific communities; provides
oversight and management of peer review policies; and coordinates
information technology across NIH. The OD also provides the core
administrative and management services, such as budget, human
resources, property management, procurement services, ethics oversight,
committee management, and the administration of equal employment
policies and practices.
The fiscal year 2019 budget request will also support activities
managed by the OD's operational offices. The OD Operations is comprised
of several OD Offices that provide advice to the NIH Director, policy
direction and oversight to the NIH research community, and administer
centralized support services essential to the NIH mission. In addition
to the Common Fund (CF) administered by the Division of Program
Coordination, Planning, and Strategic Initiatives, two additional
research programs, Environmental Influences on Child Health Outcomes
(ECHO) and the All of Us Research Program, are coordinated within the
OD. The functions and initiatives of the OD's research offices and
programs are described in detail as follows:
division of program coordination, planning, and strategic initiatives
DPCPSI (Division of Program Coordination, Planning, and Strategic
Initiatives) provides leadership for identifying, reporting, and
funding trans-NIH research that represents important areas of emerging
scientific opportunities, rising public health challenges, or knowledge
gaps that merit further research and would benefit from collaboration
between two or more ICs, or from strategic coordination and planning.
DPCPSI includes major programmatic offices that coordinate, and
support research and activities related to HIV/AIDS, women's health,
behavioral and social sciences, disease prevention, dietary
supplements, and research infrastructure. DPCPSI serves as a resource
for the ICs and OD for portfolio analysis by developing, using, and
disseminating data-driven approaches and computational tools. DPCPSI
serves as the focal point for coordinating research to advance the
health and wellbeing of sexual and gender minorities and for American
Indians and Alaska Natives, and coordinating tribal consultation
activities for the NIH.
The Office of Research Infrastructure Program (ORIP) provides
support for research into model systems of human diseases and a variety
of research infrastructure needs. ORIP supports a number of
repositories of animal models, biological materials, genetic stocks,
and human biospecimens. ORIP also makes grant awards to fund the
purchase of expensive state-of-the-art scientific instruments and to
update animal research facilities. ORIP supports training and career
development for veterinarian-scientists engaged in biomedical research
and contributing to interdisciplinary research teams addressing topics
at the intersection of human/animal populations and the environment.
The Office of Aids Research (OAR) plays a unique role at NIH by
serving as a model of trans-NIH planning and management, vested with
primary responsibility for overseeing all HIV/AIDS-related research
supported by the NIH. OAR coordinates the scientific, budgetary,
legislative, and policy elements of the NIH HIV/AIDS research program.
OAR's response to the HIV/AIDS epidemic requires a unique and complex
multi-institute, multi-disciplinary, global research program. This
diverse research portfolio demands an exceptional level of scientific
coordination and management of research funds to identify the highest-
priority areas of scientific opportunity, enhance collaboration,
minimize duplication, and ensure that precious research dollars are
invested effectively and efficiently.
The Office of Behavioral and Social Sciences Research (OBSSR)
furthers the mission of the NIH by emphasizing the critical role that
behavioral and social factors play in health, healthcare and well-
being. OBSSR serves as a liaison between NIH and the extramural
research communities, other Federal agencies, academic and scientific
societies, national voluntary health agencies, the media, and the
general public on matters pertaining to behavioral and social sciences
research. OBSSR's vision is to bring together the biomedical,
behavioral, and social science communities to work more collaboratively
to solve the pressing health challenges facing our Nation. OBSSR also
coordinates and helps support the NIH Basic Behavioral and Social
Science Opportunity Network, a trans-NIH initiative to expand the
agency's funding of basic behavioral and social sciences research.
The Office of Research on Women's Health (ORWH) has worked to
ensure the inclusion of women in NIH clinical research, to advance and
expand women's health research, and to promote advancement of women in
biomedical careers. ORWH is the focal point for NIH women's health
research and works in partnership with the NIH ICs to incorporate a
women's health and sex differences research perspective into the NIH
scientific framework. ORWH activities are guided by the NIH Strategic
Plan for Women's Health Research. This strategic plan outlines six
goals to maximize impact of NIH research effort. The NIH strategic plan
for women's health and sex differences research serves as a framework
for interdisciplinary scientific approaches.
The Office of Disease Prevention (ODP) is responsible for
assessing, facilitating, and stimulating research in disease prevention
and health promotion, and disseminating the results of this research to
improve public health. In fiscal year 2019, ODP will release a new
strategic plan which outlines the priorities that the Office will focus
on over the next 5 years and highlights ODP's role in advancing
prevention research at the NIH. The Office of Dietary Supplements (ODS)
is within the ODP organizational structure. The mission of ODS is to
strengthen knowledge and understanding of dietary supplements by
evaluating scientific information, stimulating and supporting research,
disseminating research results, and educating the public to foster an
enhanced quality of life and health for the U.S. population.
The Office of Strategic Coordination (OSC) and the Common Fund
(CF)- OSC manages the Common Fund (CF), which functions as a ``venture
capital'' space where high-risk, innovative endeavors with the
potential for extraordinary impact can be supported. CF supports
approximately 30 programs that focus on areas of emerging scientific
opportunities, rising public health challenges, and knowledge gaps that
deserve special emphasis; that would benefit from strategic
coordination and planning across NIH Institutes and Centers (ICs); and
that are designed to address specific, high-impact goals and milestones
within a 5- to 10-year timeframe. Collectively, these programs
represent strategic investments aimed at solving problems or building
resources to affect research throughout the entire biomedical research
enterprise. Most CF programs consist of a series of integrated
initiatives that collectively address a set of goals aiming to
transform the way research is conducted, the way that health and
disease are understood, and/or the way that diseases are diagnosed or
treated.
environmental influences on child health outcomes
Launched in fiscal year 2016, the Environmental Influences on Child
Health Outcomes (ECHO) program supports multiple synergistic,
longitudinal studies by leveraging, harmonizing, and combining existing
and new data from 83 maternal/pediatric cohorts to create one ECHO-wide
Cohort with 50,000 participants. Researchers will investigate the
effects of a broad range of early life environmental exposures (e.g.,
physical/chemical, societal, psychosocial, behavioral, biological) on
five key pediatric outcomes with high public health impact: pre-, peri-
, and postnatal outcomes; upper and lower airway conditions; obesity;
neurodevelopment and positive health.
The intervention component of ECHO is the IDeA States Pediatric
Clinical Trials Network, with a goal to provide access for rural and
medically underserved children to participate in state-of-the-art
clinical trials. This network builds institutional capacity, provides
professional development to researcher and their teams, and leverages
partnerships with outside academic institutions. In fiscal year 2019,
having built its infrastructure, ECHO Cohorts will disseminate research
findings, and the IDeA States Pediatric Network will continue to
conduct one or more clinical trials.
all of us research program
The All of Us Research Program, launched in fiscal year 2016, is an
ambitious effort to gather data on the biological, environmental, and
behavioral influences on health and disease over many years from one
million or more people living in the United States. All of Us will
serve as a national research resource to inform thousands of studies,
covering a wide variety of health conditions and enabling
individualized prevention and treatment options for patients.
Since July 2016, All of Us achieved several key implementation
milestones, including initial study protocol approval, establishment of
a state-of-the-art biobank to process and store biological samples from
patients, and construction of a big data IT system to store data for
research purposes. Working together with a consortium of Federal,
academic, and industry partners, All of Us began participant enrollment
for its beta testing phase in May 2017, and, as of March 25, 2018, more
than 35,000 participants are currently enrolled, of whom over 20,000
have completed the full protocol.
The program will begin full-scale, nationwide participant
enrollment in the spring of 2018.
______
Prepared Statement of Dr. Nora Volkow, Director, National Institute on
Drug Abuse
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2019 budget request for the National
Institute on Drug Abuse (NIDA) of the National Institutes of Health
(NIH).
drug use and addiction research priorities
As a part of NIH, the Nation's premier biomedical research agency,
NIDA's mission is to advance the science on the causes and consequences
of drug use and addiction and to apply that knowledge to improve
individual and public health. NIDA-supported research has transformed
our understanding of how biological, social, and environmental factors
contribute to substance use disorders (SUD), generating new knowledge
that fosters the development of smarter means for preventing and
treating SUDs.
Substance use and SUDs represent a constant and dynamic threat to
the health and well-being of our Nation. Their combined toll is more
than $740 billion a year in healthcare, crime, and lost productivity;
but dollars barely capture the devastating human cost of addiction to
individuals, families, and communities. In 2016 alone, over 63,000
Americans died because of an unintentional drug overdose. Over 42,000
of these deaths are attributable to opioids, due in large part to the
spread of powerful synthetic opioids such as fentanyl and its
analogues. Other challenges include the disconcerting rise in
fatalities associated with cocaine and methamphetamine use, as well as
the rise of new synthetic drugs and delivery systems, such as e-
cigarettes, that are changing how people perceive and use drugs.
Despite these complex challenges, this is a time of great
opportunities. In the last few years we have seen huge technological
advances and new research applications, from deep sequencing to precise
gene editing tools, and from more powerful brain imaging technologies
to mobile health platforms and electronic health records.
NIDA's commitment to leveraging these advances through synergistic
collaborations with Federal, community, and industry partners has been
codified in the 2016-2020 Strategic Plan, which charts our path forward
according to four broadly defined goals designed to:
--Understand the complex multilevel interactions influencing drug use
trajectories.
--Accelerate the development of treatments for SUDs.
--Address real-world complexities including comorbidities and poly-
drug use.
--Advance bi-directional translation from basic to clinical and
applied research.
research highlights
I'd like to highlight several high priority research areas that
NIDA is pursuing, the most prominent of which is addressing the opioid
crisis with medications development and implementation research efforts
as well as assessing the impact of adolescent drug use on brain
development and behavior that will build the evidence for personalized
prevention.
opioid crisis
Millions of Americans are suffering from an opioid use disorder
(OUD). The urgency and scale of this crisis calls for innovative
solutions:
Medications Development.--The Division of Therapeutics and Medical
Consequences supports synthesis and preclinical evaluation of potential
therapeutics, clinical trial design and execution, and preparing
regulatory submissions of medications. While there are current
treatments available to reverse opioid overdose and treat opioid use
disorder, the continued epidemic underscores the need for improved
treatment options. In addition to current projects, new projects on
reformulating drugs are underway and supported by NIDA grants and
contracts. For example, NIDA support is accelerating the development of
extended release formulations of existing medications used to treat OUD
(methadone, buprenorphine, and naltrexone), as well as new medications
to prevent and reverse overdoses from synthetic opioids or from drug
combination (alcohol and heroin).
Criminal Justice.--Juvenile Justice Translational Research on
Interventions for Adolescents in the Legal System (JJ-TRIALS) is guided
by the philosophy that all juvenile offenders can benefit from
evidence-based drug use and HIV-related prevention, screening, and
treatment interventions. JJ-TRIALS builds on the strong foundation of
our past work with criminal justice populations and includes three
interrelated research efforts: (1) a national survey of existing
practices within the juvenile justice system, (2) a large-scale, multi-
site randomized study of data-driven strategies to improve justice
systems' capacity to identify unmet substance use service needs, and
(3) a pilot study examining the capacity to form partnerships with
public health providers to address HIV and sexually transmitted
infection risk behaviors.
Rural Communities.--In rural areas, a lack of treatment
infrastructure and poor access to care hamper efforts to stem the tide
of opioid addiction. Together with SAMHSA, CDC, and the Appalachian
Regional Commission (ARC), NIDA is funding research to reduce the
adverse outcomes of injection opioid use in rural communities. Initial
projects focused on epidemiology, infrastructure, and policy issues to
lay foundation for future research and planning efforts throughout
Appalachia, while subsequent projects are testing the effectiveness of
community response models and best practices in responding to opioid
injection epidemics that can be implemented in similar rural
communities across the US.
Developing Alternative Pain Treatments With Reduced Abuse
Potential.--In addition to these strategies to reverse the opioid
overdose epidemic, we must develop more effective and less addictive
treatments for chronic pain; NIDA is working with the NIH Pain
Consortium to promote research in this key area. Funded grants span the
entire range of the therapeutics development spectrum from preclinical
safety and efficacy testing and early phase human trials, to health
services research. Worth highlighting in this context are new molecular
imaging technologies like x-ray crystallography that revealed the
molecular structure of the receptors that mediate drugs' effects,
information that is already leading to the development of safer
medications to treat pain including the potential for developing an
opioid pain medication devoid of addictive effects.
adolescent drug use and brain development
A deeper understanding of how biological, environmental, social,
and developmental factors interact and contribute to SUD risk is
critical for developing better prevention and treatment strategies.
This is particularly true when trying to understand how early onset
drug use impacts developmental processes. To address this high priority
need, NIDA has launched, jointly with other NIH institutes, centers,
and offices the Adolescent Brain and Cognitive Development (ABCD)
study, the largest long-term study of brain development and child
health in the United States. Approximately 10,000 children ages 9-10
will be studied at 21 research centers across the country; they will be
followed into early adulthood with brain-imaging, genetic,
neuropsychological, behavioral, and other health assessments. The
results will expand our understanding of how drugs can disrupt a young
person's life trajectory. As of March 2018, more than 8,300
participants were enrolled in the study and close to 30 terabytes of
data--about three times the size of the Library of Congress
collection--had been obtained from the first 4,500 participants.
prevention and treatment
Substance use disorders present a fascinating phenomenon: they are
wholly preventable but when they strike, they can be utterly
catastrophic. Hence, it is important to reassess our stance vis a vis
prevention and treatment as often as possible and in response to new
developments including the need for prevention strategies to protect
against opioid initiation that is rising among young adults (early
twenties).
Prevention and Treatment.--NIDA supports integrated approaches to
understanding and developing strategies to addressing the interactions
between individuals and environments that contribute to substance use
by fielding the annual Monitoring the Future survey of adolescent
students. NIDA also supports the National Drug Early Warning System
(NDEWS) network to survey emerging trends related to illicit drug use.
The Division also supports research on integrating prevention and
treatment services into healthcare and community systems to reduce the
burden of drug problems across the lifespan. Ongoing research is
exploring SUD treatment in the criminal justice system, including
studies on implementation of medication-assisted treatment (MAT) and
seek, test, treat, and retain (STTR) strategies for people with SUDs
who are also at risk for HIV. NIDA also funds research into the
efficacy of screening, brief intervention, and referral to treatment
(SBIRT) in primary care settings for reducing drug use including opioid
use disorders. Our research also examines the implementation of
evidence-based universal as well as tailored prevention interventions
and treatment services in real-world settings. For instance, NIDA is
funding researchers to partner with States as they use the State
Targeted Response funding from the 21st Century Cures Act to test
approaches for expanding access to MAT for opioid use disorder and
naloxone for the reversal of opioid overdoses.
The NIDA Clinical Trials Network (CTN) is a collaborative
partnership with clinicians, researchers, and participating patients
that cooperatively develops, tests, and delivers new treatment options
to patients with SUD including opioid addiction. The CTN studies
behavioral, pharmacological, and integrated treatment interventions in
rigorous, multisite clinical trials across a network of community-based
treatment settings. Current CTN-funded trials include studies on how to
implement buprenorphine in emergency departments and by primary care
physicians, engagement of pharmacists for prescribing and monitoring
buprenorphine to patients with an OUD and the effectiveness of a
combination pharmacotherapy regimen to treat methamphetamine use
disorder, among others.
Our efforts to develop effective addiction treatments respond to
urgent needs while facing significant challenges. For example, despite
remarkable advances in recent years, our menu of effective addiction
treatments still presents critical gaps. Most notably, there continues
to be a dire need for therapies to help treat addiction to stimulant
drugs, like cocaine and methamphetamines or to help treat addiction to
marijuana. As a result, NIDA is committed to evaluating the potential
of emerging new therapies for SUDs, including pharmacological and non-
pharmacological (e.g. psychosocial, biofeedback, brain stimulation
technologies). For example, NIDA's IRP is collaborating with partners
in the pharmaceutical industry to study a potential medication to
decrease methamphetamine craving and collaborating with Italian
researchers to test the efficacy of transcranial Magnetic Stimulation
(TMS) for treatment of cocaine use disorders. The IRP is also exploring
interventions to reverse the impact of prefrontal cortex deficits
caused by cocaine or heroin use and to develop clinically useful
indicators (biomarkers) of addiction severity or treatment efficacy
that will support the development of more effective treatments.
conclusion
Substance use and its attending disorders are complex conditions.
The fiscal year 2019 budget request will allow NIDA to support cutting-
edge research that leverages the most powerful technologies and latest
emerging opportunities to expand our understanding of drug use and
addiction in order to enhance prevention and treatment, help address
public health emergencies, and improve the health of the public.