[Senate Hearing 117-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2023
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TUESDAY, MAY 17, 2022
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:02 a.m. in room SD-138, Dirksen
Senate Office Building, Hon. Patty Murray (chairwoman)
presiding.
Present: Senators Murray, Durbin, Reed, Baldwin, Blunt,
Moran, Kennedy, Braun, and Rubio.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF LAWRENCE TABAK, D.D.S., PH.D., ACTING
DIRECTOR
ACCOMPANIED BY:
ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
GARY GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
JOSHUA GORDON, M.D., PH.D., DIRECTOR, NATIONAL INSTITUTE OF
MENTAL HEALTH
RICHARD HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
NORA VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG ABUSE
opening statement of senator patty murray
Senator Murray. Good morning. The Senate Appropriations
Subcommittee on Labor, Health and Human Services, Education,
and Related Agencies, will please come to order.
Today, we are having a hearing on the Biden
Administration's fiscal year 2023 budget request for the
National Institutes of Health.
Senator Blunt and I will each have an opening statement.
Then I will introduce our witnesses. And after their testimony,
Senators will each have 5 minutes for a round of questions.
While we were unable to have this hearing fully open to the
public, or media for in-person attendance, live video is
available on our committee website. If you are in need of
accommodations, including closed captioning, you can reach out
to the Committee or the Office of Congressional Accessibility
Services.
Every day across my Home State of Washington, researchers
at the Fred Hutch Center, University of Washington, Washington
State University, Seattle Children's hospital, and so many
other world-class institutions are working around the clock and
making ground-breaking discoveries.
Discoveries that don't just drive innovation and economic
growth, but also bring families, cures, and treatments, and
hope for the future, discoveries that saves lives, discoveries
that don't just drive innovation and economic growth, but also
bring families cures, and treatments, and hope for the future.
I am pleased to say this budget request shows the
administration understands the tremendous importance of
supporting our Nation's biomedical research community, and
continuing our tradition of global leadership here, especially
as in the past few years, have been such a stark reminder of
how the investments we make in research today pay off down the
road.
The rapid development of safe, effective COVID vaccines was
made possible by research into mRNA vaccines we funded, in
response to Ebola and other viruses, and by a biomedical
research enterprise that has been built over decades.
And today, thanks to the vaccines and therapeutics that NIH
(National Institutes of Health) researched to help develop,
COVID deaths and hospitalizations are the lowest we have seen
in 2 years. However, we are not out of the woods yet when it
comes to this pandemic. There is still the threat of new, more
deadly variants, especially right now when caseloads are
inching up again, but our communities' resources have largely
been spent down.
We need to defend the hard-won progress we have made, and
that means passing emergency COVID funding, so our communities
have the tests, and treatments, and vaccines, and tools they
need to keep families safe.
This is really urgent. So I am going to keep fighting to
make sure we get it done. And in addition to providing our
communities the resources they need to fight this pandemic, I
hope we are able to come together this year, as we have so many
times in the past, to continue providing our researchers what
they need to help us to fight COVID-19, and so many other
challenges.
Challenges like: Developing better tests, making next-
generation vaccines that are effective against all COVID
variants, and understanding long COVID, and how we support the
millions of people who are living with it; and challenges like
the mental health crisis this pandemic has made so much worse,
especially for young people, or overdose deaths which have been
skyrocketing due to the rise of fentanyl.
Recently, our Nation lost a record 107,000 people to
overdose deaths in a single year, and in Washington State,
opioid deaths increased by two-thirds in 2021. This crisis is
tearing a hole in so many communities, so many families, it is
truly heartbreaking, and we have to pull out all the stops to
get this under control.
That is why I am working on bipartisan legislation to
strengthen programs that help our first responders, healthcare
professionals, and others on the front lines. And why I want to
make sure we continue investing in research here like this
budget proposes.
Of course the measure of success against any disease is not
how much we invest to fight it; it is how much we are helping
patients. For example, when it comes to Alzheimer's disease,
that is exactly what we need to be focused on, for patients
fighting this disease the stakes are intensely personal. They
are fighting to hold onto cherished memories with loved ones,
and a feeling of control over their daily lives, and the weight
of that fight falls on their family members, friends, and
caregivers.
With so much at stake in their lives, these families
deserve to know the research projects they are depending on are
being thoughtfully designed and prioritized for meaningful
outcomes and results. This is really important for me,
especially when we have increased funding for Alzheimer's
research six-fold since 2015; when the 2025 target date that is
established in the National Alzheimer Project Act is just
around the corner, and when there are so many other terrible
diseases families are desperate for NIH to put more resources
into as well.
Another important undertaking is the launch of the Advanced
Research Projects Authority for Health, which aims to break the
mold for how cutting-edge research is conducted, speed up the
discovery and development of medical treatments, and support
projects that have the potential to transform medicine.
I worked hard to provide resources to establish ARPA-H
(Advanced Research Projects Agency for Health) in our
bipartisan funding bill earlier this year, and I am working
hard right now to pass the Prevent Pandemics Act to set it up
for long-term success.
That requires striking a balance to ensure ARPA-H can
complement NIH's expertise while still operating independently
to nimbly seize opportunities to accelerate innovation and
breakthroughs.
I am focused on getting that balance right, so I will be
asking more about why so much of the NIH budget increase,
requested by the administration, goes towards ARPA-H when it is
yet to bring on a staff and what that means for the other NIH
institutes and centers.
Of course at the end of the day, innovation isn't just
driven by new programs and new investments, it is driven by
people, which is why, with as much as we invest in NIH each
year, and as important as this work is to our families, we
can't afford to have this agency's potential limited, or its
success threatened by bias, discrimination, or harassment in
the workplace.
We have to do more to address harassment in the biomedical
research community, as well as address the fact that the number
of researches of color is too low, and even clinical trials
often fail to be adequately representative.
These are real problems with real consequences for
research, and I have been pressing for progress on this for
years. So I have been glad to see NIH working to examine
barriers to diversity among its researchers, address how its
practices have reimbursed structural biases and discrimination,
and implementing a new policy, as secured in this committee
that requires those that receive NIH grants to notify the
agency when a Principal Investigator is removed, even
temporarily, for sexual harassment or bullying.
But more work remains to be done to remove racism,
discrimination, and harassment from research. And I will
continue to follow our progress here.
Finally, before I turn over to Senator Blunt, I just want
to take a moment to note that this will be the last NIH hearing
we have with him, and to say how grateful I am, Senator Blunt,
for all the work with you on this issue over the years.
It has been really great to have a partner across the aisle
who really understands why these investments are so important
to families, in Washington State, Missouri, across the country,
and who is really willing to sit down and work in a bipartisan
way to make sure we are delivering for folks back home.
So thank you so much, Senator Blunt. And I will turn it
over to you.
statement of senator roy blunt
Senator Blunt. Well, thank you, Chair. I appreciate the
work we have done together. As you said, this is in my, in all
likelihood, last NIH hearing. And as I have started to look
back on the time I have spent in the Senate, one of the things
I think will have the most long-term impact is what we have
done together for NIH research.
You have been a great partner in that effort. We have
worked closely with Chairman DeLauro, and Congressman Cole, in
the House, who chaired that subcommittee, and they both chaired
the committee during the 8 years we have been doing this work
together. The entire committee, of course, was involved, but I
would particularly like to mention Senator Durbin and former
Senator Alexander, who were right there at the beginning of
trying to see what we could do to change a trajectory that,
really, was not good.
And of course, Dr. Tabak, thank you for you, and the
directors being here with us today; and I think all of you
would remember when I became chairman nearly 8 years ago, NIH
funding was stagnant, and had been for about a decade, but over
the past 7 years, working together, we have increased that
funding by nearly 50 percent.
It was a period of time that, looking back, the NIH, not
only could count on sustained funding, but also having a
substantial increase every year. And I am hopeful and confident
that Senator Murray's continued partnership in that commitment
will let us do that again this year. And I hope we are able to,
successfully, work together and have a bill before the end of
the year.
I am disappointed that this budget request reduces funding
for 12 of the 27 institutes, including the National Cancer
Institute, and the National Institute of Allergy and Infectious
Diseases. The latter, of course, was demonstrated over and over
again how important it was during COVID. There are very few
increases, frankly, that are proposed in this request, the
increase in CURES is coincidental, and that this fiscal year
2023 year has that number already built in.
The only significant increase, as the Chair has pointed
out, at NIH this year, would be an increase of $4 billion for
ARPA-H. Now, I am a supporter of ARPA-H, I am a supporter of
the Secretary's decision to have it associated with NIH. But a
$4 billion increase for ARPA-H, and no increase for NIH would
really verify the worst concerns that people have had, about
ARPA-H as a competitor to our ongoing research, as opposed to
finding a way where the government can and should be willing to
take on more financial risks, to become a real partner in
targeted research outcomes, that have a specific short-term
goal in mind, and to help us reach that goal. That doesn't mean
we should jeopardize research challenges as big as cancer, and
Alzheimer's disease, or as small as hearing aids, as we look to
build, frankly, on the goal of doing more of what we were able
to do in the pandemic.
I was also surprised that the budget request failed to take
more of the lessons learned from the pandemic into
consideration, instead of embracing more high-risk, high-reward
science, and focusing on projects with instant impact which
proves so successful with programs like RADx (Rapid
Acceleration of Diagnostics), it appears that the budget got
bogged down with political priorities that don't quite fit the
agency's long-standing mission.
This is clearly illustrated with a request for a new Center
for Sexual Orientation and Gender Identity, yet virtually no
additional money for the Cancer Moonshot. NIH is clearly in a
period of transition. If there is one lesson to be learned from
the COVID-19 pandemic, it is that our Nation's success depends
on medical research infrastructure, across the country,
supported by NIH.
Now is not the time to abandon that goal, now is the time,
in fact, to make it even stronger. And I hope the original, or
the eventual budget that we propose to our colleagues in the
Senate, and to the whole Congress, will reflect that
determination, to make NIH stronger across the board rather,
than the way this budget proposal looks at NIH.
And Chair, thank you for your comments. And thank you for
the chance to speak, and for holding this hearing.
[The statement follows:]
Prepared Statement of Senator Roy Blunt
Good morning. Thank you, Dr. Tabek and the other Institute
Directors, for being here today.
This is my last NIH hearing. As I've started to look back on my
Senate career, one of my proudest accomplishments is realigning the
priorities within the Labor/HHS bill to focus on medical research.
When I became Chairman nearly 8 years ago, NIH funding was
stagnant. And it had been that way for nearly a decade. But over the
past 7 years, NIH funding has increased nearly 50 percent, and NIH
could count on sustained funding and a substantial increase each year.
I am hopeful, with Senator Murray's continued partnership and
commitment, we will continue this legacy in my last Labor/HHS bill this
year.
I am disappointed, however, that Dr. Tabek has to defend a budget
that is nearly indefensible. This is a budget request that reduces
funding for 12 of the 27 Institutes, including the National Cancer
Institute and the National Institute of Allergy and Infectious
Diseases, the latter of which demonstrated its importance during the
COVID pandemic. The very few and modest increases that are proposed in
the budget request were likely only accomplished because CURES funding
significantly increases in fiscal year 2023--a mere coincidence that
was not determined by the Administration.
The only significant increase NIH receives this year in the budget
request is an increase of $4 billion for ARPA-H. I am a supporter of
ARPA-H and particularly the Secretary's decision to house it within
NIH. ARPA-H has the ability to translate what we learned during COVID--
that the government can and should be willing to take more financial
risks to become a real partner in research outcomes--and expand that
model to other research challenges as big as cancer and Alzheimer's
disease to as small as hearing aids.
However, no matter how much I support the goal of ARPA-H, it cannot
be the sole focus of NIH's budget request. And it cannot displace other
scientific priorities or be funded at the expense of other critical
research efforts.
I am also surprised that the budget request failed to take more of
the lessons learned during the pandemic into consideration to move the
agency forward. Instead of embracing more high-risk, high-reward
science and focusing on projects with instant impact, which proved so
successful with programs like RADx, it appears that the budget got
bogged down with political priorities that don't quite fit the agency's
longstanding mission. This is clearly illustrated with a request for a
new Center for Sexual Orientation and Gender Identity, yet virtually no
additional funding for the Cancer Moonshot.
NIH is clearly in a period of transition. The long-time Director
has left and we are coming out of a pandemic that has been nearly the
sole focus of the agency for the past two-and-a-half years. I hope NIH
takes this opportunity to review its current mission and consider
whether it aligns with where you want it to be and where you want it to
go.
If there is one lesson learned from the COVID-19 pandemic, it is
that our nation's success depends on the medical research
infrastructure across this country supported by NIH. Now is not the
time to abandon it. Now is the time to make it even stronger.
Thank you.
Senator Murray. Thank you. I will now introduce our
witnesses. We have Dr. Lawrence Tabak, he is the Acting
Director of the National Institutes of Health; Dr. Anthony
Fauci is the Director of the National Institute of Allergy and
Infectious Diseases; Dr. Gary Gibbons is the Director of the
National Heart, Lung, and Blood Institute; Dr. Joshua Gordon is
the Director of the National Institute of Mental Health; and
Dr. Nora Volkow is the Director of the National Institute on
Drug Abuse.
Welcome to all of you, and thank you for being here today.
Acting Director Tabak, you may deliver your opening
remarks.
SUMMARY STATEMENT OF DR. LAWRENCE TABAK
Dr. Tabak. Thank you, Chair Murray, Ranking Member Blunt,
and distinguished subcommittee members. I am honored to be here
today with my colleagues representing the NIH. This is a time
for NIH and the entire biomedical research community to
reexamine all of our efforts. During the COVID-19 pandemic, we
were driven by the urgency of the moment.
NIH must learn from this experience, and seize the
opportunity to define a new normal. As acting director, I am
committed to new strategies, new voices, and a renewed focus on
the future.
Now is the time to reflect on what worked and did not work
to address COVID and to shape new strategies. Your sustained
investment in NIH research set the stage for the new mRNA
technology, and immunogen design that were key to the
development of safe and effective vaccines in an unprecedented
timeline. Since these vaccines became available, it is
estimated more than two million American lives were saved, and
more than 17 million hospitalizations were averted.
Now we need continued support for a wide range of
biomedical fields, including the behavioral and social
sciences, to identify and successfully implement better ways of
responding to the short- and long-term health effects of COVID-
19, to prepare for future pandemics, and to ensure equitable
protection of our diverse population.
And it is not just about vaccines. Our Rapid Acceleration
of Diagnostics, our RADx Initiative, fueled the development of
many new approaches for COVID-19 testing that are being used in
the communities.
To help ensure that such benefits were shared with of those
disproportionately affected by the pandemic, we initiated
efforts like RADx Underserved Populations, and the NIH
Community Engagement Alliance. These experiences, along with
other NIH-led efforts focus on COVID treatment development,
demonstrate the extraordinary value of public-private
partnerships.
The NIH can build upon the momentum of the COVID response,
and apply it to other challenges through the Advanced Research
Projects Agency for Health, ARPA-H. Thanks to your inclusion of
key authorities, and funding in the Omnibus, NIH is beginning
to frame the basic administrative infrastructure for ARPA-H.
This is a key first step in creating a permanent home for the
strategic partnerships that are so urgently needed to address
cancer, diabetes, Alzheimer's, and many other diseases.
But we can't stop there. In addition to new strategies,
biomedical research needs new voices. A growing body of
evidence demonstrates that inclusion of diverse perspectives
yields better outcomes. In the clinical setting medical teams
provide--diverse medical teams provide more accurate diagnoses
and improve health for patients while building trust.
We do better science when we have a diversity of
scientists, from different backgrounds and communities,
scientific fields in various career stages. NIH continues to
prioritize, fund and empower early-stage investigators so they
can succeed as independent researchers.
In 2021, we reached an all-time high of early-stage
investigators, funded 1,513. The passion and commitment of our
scientists is matched by the voices of people living with a
wide range of diseases and conditions. Conversations with
patients and their advocates are sometimes difficult, but those
are often the discussions that teach us the most.
From the AIDS (Acquired Immunodeficiency Syndrome) advocacy
groups of the 1980s, to today's groups for autism, ME/CFS
(Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), long
COVID, and many others, these voices have refused to be
ignored, and ultimately, all of us benefit.
This is a moment for renewed focus on the future. I spent a
lot of time encouraging early-stage scientists, but I also like
to think about the importance of engaging elementary school-
aged children, like those my wife has taught, for over 40
years.
During the pandemic, exposure to the importance of science
has become a big part of many of their lives. Past pandemics
have inspired young people to become scientists, but the images
they saw were usually of older men who looked pretty much like
me. Hopefully, today's kids are seeing more scientists who look
like them.
Still, we need to do better. Our Nation needs all the
bright minds we can find, and I hope you will continue to work
with the NIH to make this happen.
Thank you for your time. And my colleagues and I welcome
your questions.
[The statement follows:]
Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D.
Good morning, Chair Murray, Ranking Member Blunt, and distinguished
Members of the Subcommittee. I am Lawrence A. Tabak, D.D.S., Ph.D, the
Acting Director of the National Institutes of Health (NIH). It is an
honor to appear before you today.
I am grateful for the committee's long-standing support for NIH.
Whether it is cancer immunotherapy or sickle cell therapies or COVID-19
vaccines, NIH's successes would not have been possible without the
investment made by this committee.
The fiscal year 2023 President's Budget will support science that
helps tackle many critical national challenges: from initiatives to
address health disparities, fight the rising tide of addiction, and
transform nutrition science. The budget will also build upon the
initial investment in the new Advanced Research Projects Agency for
Health (ARPA-H).
advanced research projects agency for health
The President's Request proposes $5 billion to fully operationalize
ARPA-H \1\ in fiscal year 2023. This new agency will be a key component
to drive transformational innovation in health research and we are
grateful for your support. At the direction of the Secretary, we are
working to create an ARPA-H that is free to innovate and take risks, an
ARPA-H that leverages NIH infrastructure, and an ARPA-H that has
unfettered and frequent access to all of the brightest minds across all
research fields--from biomedicine to sociology to mathematics. In
alignment with the DARPA model, ARPA-H will recruit term limited,
visionary program managers who will use its catalytic platform to take
on critical challenges in conjunction with traditional and
nontraditional partners across academia, government, and industry.
ARPA-H will use directive approaches that will provide quick funding
decisions to support projects that are results- and use-driven and
time-limited, and identify emergent opportunities through advanced
systematic horizon scans of academic and industry efforts.
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\1\ 1 https://www.nih.gov/arpa-h.
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ARPA-H projects would be bounded in time, typically a few years
with longer periods allowed for efforts that are highly complex, and
with the understanding that a significant fraction of projects will not
reach their goals, a necessary outcome when conducting ambitious,
innovative research. To determine which bold questions should be
undertaken and to evaluate proposed programs and projects, ARPA-H would
adopt approaches similar to those utilized by DARPA, such as the
``Heilmeier Catechism,'' \2\ a set of principles that assesses the
challenge, approach, relevance, risk, duration, and metrics of success.
It will be critical for ARPA-H to engage with the broader biomedical
community, including patients and their caregivers, researchers,
industry, community groups, and others, to understand the full range of
problems and the practical considerations that need to be addressed for
all groups and populations.
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\2\ https://www.darpa.mil/work-with-us/heilmeier-catechism.
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cancer moonshot
The President's Cancer Moonshot\SM\ \3\ aims to accelerate progress
in cancer research and make additional therapies available to more
patients. Established in 2016, the Beau Biden Cancer Moonshot was a
bold action on behalf of cancer patients. The President's Budget
includes $216 million to the National Cancer Institute for Cancer
Moonshot.
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\3\ https://www.cancer.gov/research/key-initiatives/moonshot-
cancer-initiative.
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Prominent, ongoing Moonshot priorities include immunotherapy,
childhood cancer, cancer prevention and early detection, and cancer
implementation science. For example, several Moonshot initiatives focus
on rare pediatric cancers, including research on the fusion of genes
that yield novel ``fusion oncoproteins'' that drive some childhood
cancers. Additionally, Federal agencies, led by NIH, will develop a
focused program to expeditiously study and evaluate multicancer
detection tests, as we did for COVID-19 diagnostics, which could help
detect cancers early, when there may be other, more effective,
treatment options for patients. Finally, implementation science strives
to maximize the use of proven cancer prevention and early detection
strategies and to incorporate them into standards of care, which is an
urgent need among underserved, rural, and minority populations.
health disparities
A key area where NIH hopes to build upon investments made by this
committee in fiscal year 2022 is in the agency-wide effort to reduce
health disparities. In the wake of a pandemic that disproportionately
affected communities of color, this year's President's Budget will
enlist most of our Institutes and Centers (ICs) in developing and
testing interventions to reduce health disparities that have been
appropriately tailored to the breadth of clinical and community
services found in diverse settings and contexts.
Importantly, the health disparities research agenda will be aided
and informed by the NIH UNITE Initiative,\4\ composed of actively
engaged representatives from across all 27 NIH ICs and the Office of
the Director. This initiative was launched with the goal of identifying
and addressing structural racism within the NIH-supported and the
greater biomedical research community through development and
implementation of new policies, procedures, and practices. To gain a
better understanding of stakeholders' concerns, NIH issued a public
Request for Information in March 2021, which captured over 1,100
responses from researchers, external partners, and members of the
public. Responses will inform efforts to improve the culture and
advance structural change in biomedical research.
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\4\ https://www.nih.gov/ending-structural-racism/unite.
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NIH has recently launched several more initiatives to improve the
health of racial and ethnic minorities and other populations who
experience health disparities. One of the funding opportunities will
commit $60 million over the next 5 years to support transformative
research to address health disparities and advance health equity.\5\
NIH will also commit $30 million from 25 Institutes, Centers, and
offices to support observational research that will define the role of
structural racism and discrimination (SDR) in causing and sustaining
health disparities, and intervention research that will address SDR to
improve minority health or reduce health disparities.\6\ Finally, NIH
will provide approximately $24 million for the Transformative Research
to Address Health Disparities and Advance Health Equity at Minority
Serving Institutions initiative, which is designed to support research
projects with the strongest potential to have a profound effect on
health disparities research.\7\
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\5\ https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-21-
021.html;
https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-21-022.html.
\6\ https://grants.nih.gov/grants/guide/rfa-files/RFA-MD-21-
004.html.
\7\ https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-21-
022.html.
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mental health
With the fiscal year 2023 President's Budget Request, NIH intends
to direct increased attention towards mental health. Mental illnesses
are the fifth leading cause of disability in the United States,
accounting for 6.6 percent of all disability-adjusted life years in
2019. In addition, suicide rates for youth have risen over the past 2
decades in the United States; in 2019, an estimated 6,488 youth ages 10
to 24 died by suicide. Despite advances in the treatment of depression
and other serious mental illnesses, there remain few evidence-based
interventions that rapidly reduce suicide risk within healthcare
settings. NIH is supporting research projects that focus on testing the
safety, efficacy, and feasibility of several of the newest
antidepressant interventions--intravenous ketamine and intranasal
esketamine (medications known to rapidly reduce depressive symptoms in
hours or days) as well as transcranial magnetic stimulation (TMS; a
noninvasive treatment that uses magnets to activate specific parts of
the brain)--to rapidly reduce suicidal thoughts and behaviors in adults
and adolescents.\8,9\
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\8\ https://www.fda.gov/news-events/press-announcements/fda-
approves-new-nasal-spray-medication-treatment-resistant-depression-
available-only-certified.
\9\ https://www.nimh.nih.gov/news/research-highlights/2021/nimh-
addresses-critical-need-for-rapid-acting-interventions-for-severe-
suicide-risk.
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In response to the pandemic, which exacerbated mental illness
throughout the country, NIH launched a project to support research
focused on the social, behavioral, and economic impacts of COVID-19,
which supports research on the secondary effects of the pandemic, such
as financial hardship, reduced access to healthcare, and school
closures.\10\ The fiscal year 2023 President's Budget requests $2.2
billion for the National Institute of Mental Health (NIMH), that
includes targeted increases of $25 million to expand research on the
impact of the COVID-19 pandemic on mental health, $5 million to
undertake studies of the impact of social media on mental health, and
$5 million to inform mental health treatment approaches, service
delivery, and system transformation in support of the Administration's
mental health initiatives.
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\10\ https://covid19.nih.gov/news-and-stories/covid19-ripple-
effects.
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maternal morbidity and mortality
Even during a global pandemic, NIH has continued to focus on other
long-standing yet urgent public health needs. The Centers for Disease
Control and Prevention estimates 700 women die each year in the United
States of pregnancy-related deaths, 60 percent of which are
preventable, and over 50,000 experience severe pregnancy-related
morbidity each year.
To address this alarming trend, NIH established the Maternal
Morbidity and Mortality Task Force,\11\ an NIH-wide collaboration. The
Task Force coordinates the Implementing a Maternal health and Pregnancy
Outcomes Vision for Everyone (IMPROVE) Initiative,\12\ which invests in
studies to promote an integrated understanding of biological,
behavioral, sociocultural, and structural factors that contribute to
maternal morbidity and mortality and engages communities in the
development of solutions to address the needs of pregnant and
postpartum individuals. IMPROVE plans to launch a national network of
Maternal Health Research Centers of Excellence that will incorporate
local community needs and perspectives to expand and complement
existing research efforts by developing, implement and evaluating
community tailored interventions to address health disparities in
severe maternal morbidity (SMM) and maternal mortality (MM). Through
this strategy, IMPROVE will build an evidence-based approach to
reducing SMM/MM and its associated health disparities. To support this
key initiative, the fiscal year 2023 President's Budget requests $30
million for IMPROVE. In addition, the request also includes $3 million
for the Eunice Kennedy Shriver National Institute of Child Health and
Human Development to support research on mitigating the effects of
COVID-19 on pregnancies, lactation, and post-partum health with a focus
on individuals from racial and ethnic minority groups.
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\11\ https://www.nih.gov/research-training/medical-research-
initiatives/improve-initiative/trans-nih.
\12\ https://www.nih.gov/research-training/medical-research-
initiatives/improve-initiative.
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opioids and pain research
Since early in the pandemic, studies have found increases in the
use of many kinds of illicit drugs, including fentanyl, cocaine,
heroin, methamphetamine, and cannabis. The NIH Helping to End Addiction
Longterm (HEAL) Initiative,\13\ launched in 2018, is a cross-agency
program spanning basic, translational, and clinical research on opioid
and stimulant misuse and addiction, and pain. HEAL Initiative funds are
being used to accelerate the development and availability of longer-
acting formulations of existing opioid use disorder (OUD) therapies
(e.g., buporenorphine and methadone) and novel immunotherapies (e.g.,
vaccines) that could block the effect of opioids in the brain to help
people with OUD and decrease the incidence of overdose.
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\13\ https://heal.nih.gov/.
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The HEAL Initiative is building the Integrative Management of
chronic Pain and OUD for Whole Recovery (IMPOWR) network \14\ to
develop effective treatment interventions for people who experience
both chronic pain and OUD. The IMPOWR network consists of clinical
research centers that collaborate to develop effective interventions,
best models of care for delivery of services, and sustainable
implementation strategies for a variety of patients with co-occurring
chronic pain and OUD or opioid misuse, with an emphasis on highly
vulnerable groups.
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\14\ https://heal.nih.gov/research/clinical-research/integrative-
management-chronic-pain.
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In 2020, this committee directed NIH to expand HEAL to address
methamphetamine use and we are making progress toward this goal. For
example, NIH-funded research on immunotherapies for stimulant use
disorders led to the development of a monoclonal antibody called IXT-
m200 that targets methamphetamine.\15\ This treatment has received Fast
Track designation from the Food and Drug Administration and is now
being studied in emergency department settings in people with
methamphetamine overdose.\16\ It is the first novel, investigational
treatment for methamphetamine addiction ever to advance in the
medication development process to a Phase 2 clinical trial. In order to
continue to respond to these evolving challenges, the fiscal year 2023
President's Budget includes total funding of $2.6 billion in this
research area across NIH's ICs.
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\15\ https://nida.nih.gov/news-events/nida-notes/2020/02/part-2-
immunotherapies-new-tool-to-treat-methamphetamine-addiction.
\16\ http://intervexion.com/2016/01/intervexion-therapeutics-
announces-fast-track-designation-of-ixt-m200-for-treatment-of-
methamphetamine-addiction/.
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Importantly, NIH seeks to involve many more of our ICs in this
initiative, particularly with respect to research addressing pain. The
fiscal year 2023 President's Budget Request will expand research into
effective therapies that don't involve the brain or the central nervous
system by involving researchers from many Institutes and Centers like
the National Institute on Dental and Craniofacial Research (NIDCR),\17\
which I led for a decade prior to becoming the Principal Deputy
Director of NIH. As a dentist, I know that there is no group of
clinicians who have more to contribute or more to gain from identifying
better pain management approaches. For example, researchers have
identified clinical signs and symptoms that can help predict whether
temporomandibular disorder pain will linger and turn into chronic pain.
Research at the National Center on Complementary and Integrative Health
\18\ proposes to investigate the role of the brain in pain processing
and control, and how factors such as emotion, attention, environment,
and genetics affect pain perception.
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\17\ https://www.nidcr.nih.gov/.
\18\ https://www.nccih.nih.gov/.
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nutrition research
The complexity of human nutrition, combined with the impact of diet
on chronic diseases that were a contributing factor to the excess
deaths of the pandemic, demands that cutting-edge data science and
system science methods be employed to move nutrition science into the
21st century. To reflect the high priority NIH places on innovative,
multidisciplinary nutrition research, in 2021 the NIH Director moved
the Office of Nutrition Research (ONR) \19\ to the Office of the
Director. Dedicated funding is critical to ensure that the ONR can
operate effectively as a cross-cutting NIH entity and to accomplish the
goals of the plan. The fiscal year 2023 President's Budget requests
$97.2 million for the NIH Office of the Director to support ONR.\20\
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\19\ https://dpcpsi.nih.gov/onr.
\20\ https://officeofbudget.od.nih.gov/pdfs/fiscalyear23/ics/27%20-
OD%20FY%202023%20CJ%20
Chapter.pdf.
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Within this amount, one new collaborative project proposed is
Reducing Nutrition Health Disparities through Food Insecurity and
Neighborhood Food Environment Research. This research will use
precision regional implementation science and pragmatic research
approaches to test strategies to ensure food security and access to
healthy food, which are intended to prevent disparities in a variety of
diet-related diseases and conditions, such as cardiovascular disease,
obesity, diabetes, and cancer. Elucidating the role of these social
conditions on diet and nutritional status could help address and
prevent diet-related health disparities and promote health equity.
This kind of population and system science will be an important
complement to the Nutrition for Precision Health program \21\ (awarded
in January 2022 to recruit 10,000 diverse participants to study how a
person's nutritional status, metabolism, microbiome, genetics, and
environment affect health) and the $50 million Artificial Intelligence
for Chronic Disease initiative (first funded in fiscal year 2021, the
initiative leverages machine learning and data science tools to
untangle the complex underlying causes of chronic diseases and look for
early treatments).
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\21\ https://commonfund.nih.gov/
nutritionforprecisionhealth#: :text=The%20goal%20of%20the
%20NIH,prevention%20and%20treatment%20of%20disease.
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nih buildings and facilities
NIH strives to ensure that its facilities are safe and enable
scientists to discover new diagnostics, therapies, and cures. As part
of this effort, the President's Budget proposes $300 million for NIH's
Buildings and Facilities appropriation. These funds are meant to begin
addressing the backlog of life and safety repairs that totaled over $1
billion in the 2019 report by the National Academies of Science,
Engineering and Medicine on the condition of NIH's facilities on the
Bethesda Campus. A key aspect of NIH's strategy is to sustain the
condition of existing facilities to prevent premature deterioration and
the curtailment of research, including the physical plant, building
structures, utility systems, roads, and grounds at all NIH sites. These
projects will help to ensure the continued efficient and effective
performance of NIH's real property assets to meet ongoing and projected
research requirements and to offset the deterioration and obsolescence
caused by age and use.
The President's Budget request also proposes a modification to the
language governing repairs, which is intended to move NIH's property
stewardship beyond maintenance and repairs to more proactive efforts
like the modernization at NIH's research hospital, replacement of
obsolete, temporary, and fragmented research facilities, improvement of
facilities that advance computational and data science, and improvement
of the energy and water efficiency of buildings. To achieve this will
take time, so NIH looks to leverage prioritization processes currently
in place to focus on the projects that are of the most need to our
organization.
conclusion
A healthier nation is a more productive nation and a vibrant
research community is a pillar of an economically sound nation. With
your support, NIH looks forward in fiscal year 2023 to continue the
tradition of catalyzing major break throughs over decades, bettering
the human condition through rigorous and innovative science. My
colleagues and I look forward to answering your questions.
Senator Murray. Thank you very much. And I realized it as I
was going through the list of panelists in front of us, I
skipped Dr. Richard Hodes, is the Director of National
Institute on Aging. Welcome to you as well.
We will now begin a round of 5-minute questions of our
witnesses, and I ask my colleagues to please keep track of the
clock and stay within your 5 minutes.
DRUG OVERDOSE
Dr. Volkow, I want to start with you. As I mentioned in my
opening remarks, across the country overdose deaths continue to
rise dramatically. Last year they spiked in my home State of
Washington by 30 percent, and much like the rest of the
country, were really driven by fentanyl.
This is really a national crisis, so we have got to be
using every tool that we have to support our communities,
including fentanyl strips, which Secretary Becerra mentioned at
his hearing here a few weeks ago. The research I have seen
indicates that those strips which are used to detect fentanyl
in drugs, are an effective overdose prevention tool, but they
require several steps to use them, including chipping off some
of the pill to be able to test it.
Can you tell us what the research shows about the
effectiveness of those test strips? And really, are they easy
to use? Can you talk a little bit about that?
Dr. Volkow. Thanks very much for that question. And indeed
the fentanyl test strips have been tested for sensitivity and
specificity, and the data shows, actually, high sensitivity,
and there are only a few fentanyl analogs that are not
detected.
Having said that, the fentanyl test strips were developed
for testing drug use in urine, so for patients that are being
monitored; and so now this is a new application, and as a
result of that there can be problems on how it is implemented.
Overall, patients that have used the fentanyl test strips
report positive outcomes, and actually in terms of identifying
drugs that may put them at higher risk. The research is now
ongoing to try to determine what are the optimal guidelines on
how to use them, number one; but number two, if the results
were positive, what is it that an individual should do in case
that they still want to consume them.
As you know there are still multiple problems in terms of
making these fentanyl tests available throughout the United
States, and there is interest on actually determining and
getting approvals for some of these tests by the Food and Drug
Administration, so they can be utilized in healthcare settings,
which is not possible at this moment.
OVERDOSE PREVENTION
Senator Murray. Well, are there overdose prevention
strategies that you and HHS (Department of Health and Human
Services) hope to roll out in the coming months? Talk to me a
little bit about what we are doing in terms of prevention.
Dr. Volkow. Prevention strategies that have been shown to
be widely effective is perhaps one of the most important ones,
is widespread distribution of Naloxone, and that becomes
actually, in some instances, a challenge if the Naloxone is not
available for those that use them.
Another harm-reduction practice that has generated a lot of
attention, is the extent to which, because the drug supply is
so extremely dangerous these days, in which safe injection
sites could be viable for patients that otherwise may be at
high risk of overdosing. And while the data is still
preliminary in the United States, in other countries they have
shown that in certain settings they can be quite effective. So
there is interest on evaluating them.
There is also interest in the community to test other
products that may serve as harm reduction, for example, the use
of kratom, which is sold as tea, and that contains a drug--a
molecule that has the effects that are similar to those of
buporenorphine, but could be utilized also for decreasing
withdrawal or depression. So these are more novel, and we don't
have sufficient data, but those are things that are being
discussed.
ALZHEIMER'S DISEASE
Senator Murray. Okay. Thank you.
Dr. Hodes, it is said that science is a marathon, not a
sprint. However, Congress has really approached investing in
research to treat and cure Alzheimer's disease and related
dementias, with really a sense of urgency. We have poured
resources into this research, $17 billion since 2015 to really
supercharge the discovery process with a goal of finding a
treatment or cure by 2025.
And I am concerned that NIH isn't positioned to meet that
deadline. Given the sheer scale of Federal investment, what is
NIH doing to deliver meaningful and measurable outcomes that
assess its progress towards finding effective treatments?
Dr. Hodes. Thank you for that critical question. And let me
answer it very briefly in terms of process, and then with some
examples of meaningful accomplishments during this time. As you
know, we have counted on critical input from the national and
global research communities, advocates, et cetera, with our
annual summits, all of which feed into a careful identification
of milestones, that is the goals and targets which are
necessary to meet our most important needs.
I want to take a moment just to thank the staff of this
committee for the interactions we have had over the past year
to help us focusing these milestones into meaningful,
quantifiable outcomes, and making them transparent and
available.
To touch on just some of the examples of the important
advances, I would point starting with our clinical trials. So
for example, in pharmacological trials, there are currently
eight studies targeting amyloid, or not, which are Phase 3, in
their latest stages capable of identifying definitive, positive
outcomes, meaningful outcomes, clinically which are due over
the next years to reveal their answers.
There are some 62 early-phase clinical trials, and a
variety of targets, three-fourths of them not amyloid, and
these are the results of basic science, which has found more
and more potential targets. So the clinical trials, or
investment in them, are critically important, and you alluded
as well, to the burden on the families, and those living with
dementia, that is also an area of clinical research, clinical
trials, And we now are funding a large number of trials
studying interventions for care and care providing, which will
be producing their results.
The National Academy has identified two of those generated
with NIH funds that are ready for dissemination, being
disseminated with further evidence. Happy to elaborate as time
allows, but these are some of the examples of accomplishments,
and of our important process to continue being accountable to
ourselves, to you, and to the public for making the best use of
these very critical funds to accomplish the highest of the
priorities.
Senator Murray. Well, thank you. And I think transparency
is really important. The deadline is around the corner, and we
have put out a lot of money for this, and need to know, as
Congress, how those investments are going.
So I look forward to working with you. And Senator Blunt
will look forward to working with you on that as well.
Senator Blunt. Thank you, Chair.
UNDIAGNOSED DISEASE NETWORK
Dr. Tabak, during the time you were Deputy Director, the
seven hearings we had with Dr. Collins, who was the Director at
the time, I think every single time he talked about the
importance of NIH bringing hope to millions. I want to talk a
little bit about the proposed ending of funding for the
Undiagnosed Diseases Network.
We have one of those in St. Louis; Chair Murray has one in
Seattle. I had somebody reach out to me a couple of weeks ago,
Michele Herndon, from Affton, Missouri. She was concerned
because her son, Mitchell, who had suffered from a series of
health issues that doctors couldn't diagnose, had benefitted
from one of the centers.
In fact, by late-high school, he was in a wheelchair, his
hearing was gone, and his eyesight was gone. They were losing
hope, but after they sought treatment at the Undiagnosed
Disease Network in St. Louis, they found a neurological
condition so rare, that it didn't even have a name.
In fact, Mitchell lost his battle. The condition he had now
carries his name, the Mitchell syndrome. But Michele and her
family were comforted by the fact that they finally knew what
this long struggle had been about. This year's budget cuts the
Undiagnosed Diseases Network, and closes all l2 of its clinical
sites.
She was concerned about that. I am too. I think there is
some discussion where they may graduate in some way to where
they continue to exist. I think it would be a problem to walk
away from that. Not everybody can come to NIH in Bethesda. And
if you don't have the site within some reasonable distance of
where you are, you are unlikely to get this service. Do you
want to talk about why that decision was made to stop funding
these 12 sites?
Dr. Tabak. We certainly agree that the diagnostic services
provided by the Undiagnosed Diseases Network are extremely
valuable to patients and to their families. The challenge that
we face is there does come a point where the diagnoses become a
part of standard care, versus a research question, but finding
that right balance is something that we continue to work
through.
All the cases that are enrolled presently will continue to
undergo comprehensive evaluation. We will establish a Data
Management and Coordinating Center to draw upon the experience
of all of the centers that are participating in this program.
But really, we would like to work with you, going forward, to
come up, perhaps, with a better solution in the mid- and long-
term.
Senator Blunt. Good. Well, let us continue to work on that.
I mean, really you can't have standard care if you are still
discovering things that needs to be looked at as an option.
Mitchell syndrome is Mitchell syndrome only because he was the
first, and may be the only diagnosed person so far, that ever
had that. And that is going to fall outside of standard care
definition, I think. So let us continue to work on that.
RADX
Is Dr. Gordon available? Let me ask him, on RADx, Dr.
Gordon, in the mental health area, and in the RADx example of,
again, NIH itself, partnering directly with others to try to
find a rapid solution. Do you think that a Shark Tank RADx kind
of option would be a possibility, as you look for biomarkers in
mental health?
Dr. Gordon. I think that is a great idea, Senator Blunt. I
appreciate your support of that initiative, and NIMH (National
Institute of Mental Health) as well. We have funded a number of
small businesses, as well as a number of academics, who have
come up with really wonderful ideas for biomarkers that can
help guide clinical decisionmaking. Something that we
desperately need in psychiatry to help speed treatments and
make sure the people who need treatment, get the right
treatment from the get-go.
And one of the ideas for it, we have been thinking about is
using the RADx example where you had, essentially, a
competition between a number of different companies in RADx, it
was for tests for COVID. But the idea is to apply something
like that to the biomarker space for mental health.
And we think now is the right time to do that, and so we
are talking with our colleagues at NIBIB (National Institute of
Biomedical Imaging and Bioengineering), who ran the RADx
competition, and trying to figure out how we can do that for
biomarkers for mental health.
Senator Blunt. Very good. I would encourage that. I think
every single home test for COVID comes out of the RADx
experience, and again, if you have got people that have ideas
that can come to you, and see which of those you should partner
with; I think that would be a great step in the right
direction.
Thank you, Chair.
Senator Murray. Senator Reed.
Senator Reed. Thank you, Madam Chairman.
SUICIDE
Dr. Gordon, we are in the midst of a significant spike in
suicides, particularly among children, which is very
disturbing, and we know some of that is a result of the
pandemic, but I am just interested in what research at NIH is
pursuing this issue, to recognize warning signs. How is that
research being operationalized, and put out to practitioners,
particularly, and to families? And then the other point would
be, we have a new national hotline, 988, are you in any way,
sort of trying to coordinate, or work with that, or study that?
Dr. Gordon. The answer to both those questions is, yes, we
are deeply involved in making sure that our research informs
practitioners both in the clinic and at the State level when we
are talking about 988.
Let us talk about youth suicide first. NIMH has funded a
number of research programs in identifying individuals at risk,
particularly the young, and in getting to evidence-based care.
One quick example, the NIMH Intramural Program developed a
screening questionnaire called the ASQ (Ask Suicide-Screening
Questions) that has been disseminated to primary care
practices, and pediatric emergency rooms throughout the
country, and really it is being used nationwide.
We also have funded a number of research projects, looking
at school-based identification and prevention measures as well,
and we do our best to make sure that they are out there.
We also work with Federal partners, like the Substance
Abuse and Mental Health Services Administration, or SAMHSA, and
there we are working with them, especially around the 988,
looking, to try to make sure that States that are implementing
the follow-ups to 988, are aware of evidence-based approaches
to mental health crises.
For example, the proper utilization of mobile crisis teams
that are trained in responding to individuals in mental health
crises is one evidence-based approach that has been proven over
and over again to work. So yes, and we continue to work in both
of those areas. Thank you.
Senator Reed. All right. Thank you, Dr. Gordon.
LONG HAUL COVID
Dr. Fauci, the issue of long-haul COVID has been dominating
the news lately. Can you describe how NIH is tracking these
cases? Are there common elements to them? Are there treatments
showing any promise? Where are we in the process of tackling?
Dr. Fauci. Yes. Thank you very much for that question,
Senator. I will begin the answer, and then I will hand it over
to Dr. Gibbons, who is also very much involved in this.
Senator Reed. Thank you.
Dr. Fauci. As you well know, this is a real phenomenon, and
the epidemiology of it is still being worked out, I mean, the
range of people anywhere from 5 percent to up to 30 percent of
people have the persistence of symptoms that are not thoroughly
explainable by any pathogenic process that we have been able to
identify.
We put together large cohorts that are now being followed,
both to understand the actual prevalence, incidence, as well as
the pathogenesis.
With regards to treatment, Senator, it is very difficult to
do any treatment for it when you don't know exactly what the
pathogenic mechanisms are, and that is the reason why we are
putting so much effort into trying to find out just what is
going on. Is it immune activation? Is it persistence of virus?
Not necessarily replication competent virus, but maybe
particles of virus such as the nucleotides.
But let me hand it over to Dr. Gibbons who could also tell
you a bit about that.
Senator Reed. Thank you.
Dr. Gibbons. You know, I only add to Dr. Fauci's comments,
that we are indeed setting up the recovery--researching COVID
to enhance recovery effort. It is moving with a great sense of
urgency given the suffering of the patients with long COVID.
There are a number of elements that have launched effectively.
One is to create an electronic health record, a base set of
cohorts. They are derived from 60 million records of patients
across the country.
A diverse body of patients, of which, between four and five
million have COVID, and that provides an opportunity to track
those individuals electronically, and digitally, and
longitudinally, to see who develops long COVID, who does not,
that can inform, as Dr. Fauci mentioned, our understanding of
the prevalence, as well as the risk factors, as well as the
long-term effects, chronically.
It is already starting to show preliminary evidence that is
suggestive of--potentially the ability of vaccination to
prevent the development of long COVID. Similarly, they were
seeing signals that are telling us that the severity on the
acute COVID has bearing on your susceptibility to develop long
COVID.
Similarly, we are seeing trends towards, who is most
affected. And again it is identifying people of color, African-
Americans and Latinos as a high-prevalence group, developing
long COVID that really hasn't come to the fore as much; and so
we are learning as we go and develop this program. Thank you.
CHILDHOOD CANCER STAR ACT
Senator Reed. Thank you very much. Just a final point, if I
may. We have to reauthorize the STAR (Childhood Cancer
Survivorship, Treatment, Access, and Research) Act. It is the
best thing we have done in a long time, with respect to
childhood cancer.
And I think you would agree, Dr. Tabak? Just a nod of the
head is sufficient.
Dr. Tabak. Yes.
Senator Reed. Thank you. Thank you, Madam Chair.
Senator Murray. Senator Kennedy.
Senator Kennedy. Thank you, Madam Chair.
Dr. Tabak, what the National Institutes of Health has done,
and continues to do is nothing short of extraordinary, I mean,
it is really breathtaking. And I want to thank you and your
colleagues for doing that.
We have all been to pandemic school for the last several
years, and I want to use the few minutes I have to explore what
we have learned.
COVID RELATED SCHOOL CLOSURES
Dr. Fauci, whether you asked for it or not, you have sort
of been the government's face on the response to the pandemic.
Looking back, and I recognize that hindsight is crystal clear,
but looking back, do you think it was worth it, do you think
the benefits were greater than the costs of closing down our
elementary and secondary schools?
Dr. Fauci. I think it is difficult to give a definitive
answer to that. I know in the very beginning when we had really
no other protection prior to vaccinations that were available
to contain, somewhat, the spread of the virus. One of the
things that was felt to be important would be to protect
children as well as the rest of the population.
Right now we have felt, more than just recently, that it is
very important to keep the children in school for the simple
reason that we know of the deleterious effects, both
psychologically, mentally, and developmentally in children, to
keep them out of school. But you have to have a delicate
balance between protecting the children from getting infected,
and perhaps bringing the----
Senator Kennedy. Did we strike the proper balance?
Dr. Fauci. You know, I believe that we have. It is very
tough to tell. I think only time will tell whether that is the
case, because there is indication that has been deleterious
effects on children, but we believe from a public health
standpoint, that at the time it was the right decision.
Senator Kennedy. Well, can I ask you this Doctor. And I
realize, I am not asking--I am not saying, or offering judgment
of what was done at the time. I am asking what we have learned.
Let us suppose we have a substantial increase in prevalence of
the coronavirus next week, God forbid.
Dr. Fauci. Right.
Senator Kennedy. Would CDC (Centers for Disease Control and
Prevention) recommend shutting down the elementary and
secondary schools?
Dr. Fauci. It is very difficult for me to speak for the
CDC, but knowing the fact that we----
Senator Kennedy. Would you recommend it?
Dr. Fauci. Right now, I would do everything we can to keep
the children in school, and not shut down the school. And that
has always been my strong recommendation, to the extent
possible, not to keep the children out of school.
Senator Kennedy. But yet we did shut down.
Dr. Fauci. But to keep them safely in school, by getting
children that are available to be vaccinated, vaccinated.
Senator Kennedy. Right.
Dr. Fauci. To get the children who are eligible to be
boosted, vaccinated, and to surround the children with teachers
and personnel in the schools who are vaccinated. That is the
best way to protect the children while keeping them in school.
Senator Kennedy. Okay. Let me ask you this. In hindsight,
knowing what you know now, had you known it then, did we do the
right thing in shutting down society? Would we have been better
off saying: No, we are going to protect the vulnerable, the
elderly, the people who are immunocompromised, and we are going
to isolate them but have the rest of American society,
churches, businesses, universities, schools go on about their
business, while at the same time providing them guidance about
how to protect themselves?
Dr. Fauci. Well, it is a complicated question, I will try
and give as simple an answer as possible. I think there is a
misperception about who the vulnerable are. There are many,
many more vulnerables in society, and there is a misperception
that the only vulnerables----
Senator Kennedy. Yes. But I am about to run out of time.
Let us assume we can agree on a definition.
Dr. Fauci. I don't think you can. I think that society is
very heterogeneous, and it isn't a question of shutting down
completely, Senator, because we never shut down completely. If
you do shut down a society you do it for a purpose, and the
purpose is, at that period of time when you are protecting
people from interaction, that you get as many people vaccinated
as you possibly can.
Senator Kennedy. Let me stop you at that.
Dr. Fauci. To shut down----
Senator Kennedy. I am going to run out of time. Let me ask
you one last question.
Dr. Fauci. Sure.
Senator Kennedy. What would you do differently today?
Dr. Fauci. Right now I would hope that we would get many
more people vaccinated.
Senator Kennedy. No. But what would you do when you did it,
in hindsight, if you knew then what you know today?
Dr. Fauci. It depends on when we got the vaccine. Do you
mean before the availability of vaccine? Before the
availability of vaccine, when we had no other situation, I
would try to protect people by making sure that they masked,
and kept themselves separated from this congregate, indoor
settings, that is what I would do, in the absence of a vaccine.
But right now I think it is important, looking forward, we
still only have 66 percent of the total population vaccinated,
and less than half of those are boosted. I think we can
approach what we are likely going to be seeing, and are seeing
now, with an increase in surges, with the possibility of a
surge in the fall and winter.
One of the real things we can all do as a Nation, is pull
together and try to get our people vaccinated, and those who
are eligible to be boosted, boosted. That would solve a lot of
the problems that you are referring to.
Senator Kennedy. Okay. Thank you. Thank you all.
Senator Murray. Thank you. Senator Baldwin.
Senator Baldwin. Thank you, Madam Chair.
SUBSTANCE ABUSE EPIDEMIC
Welcome, Dr. Tabak. I am posing the first question to you
for an update on research efforts to better respond to the
substance-use epidemic, by way of context. As you well know,
the substance-use epidemic continues to ravage communities
across Wisconsin, and across the United States, and an
increasingly dangerous role is played by synthetic opioids,
such as fentanyl, as well as psychostimulants, like
methamphetamine.
So I believe it is vital that we invest in sustained
research into substance-use disorders to prevent deaths, treat
patients, and make our communities safer. If you could describe
recent research efforts, including what is happening with the
HEAL Initiative, the Helping to End Addiction Long-Term
Initiative, I would appreciate that.
Dr. Tabak. If I may, to turn to Dr. Volkow, who is our
expert in this field.
Senator Baldwin. Absolutely.
Dr. Volkow. Thanks very much for the question. And our
research is actually going from the basic to help develop
medications with new targets, to help develop formulations that
can be--actually lead to better outcomes. To epidemiology
research to understand the changing face of the overdose
crisis, which now, as you are mentioning, is no longer just
limited by our overdoses from prescription opioids, but
encompasses overdoses from fentanyl, methamphetamine, and
cocaine, to the implementation research that can help us
determine what are the optimal models of care that we can
deploy in community, and to take advantage of infrastructure.
So for example, research is ongoing to determine how the
health care system can be involved in the prevention and
treatment of substance-use disorders, and how can we bring
treatments to justice settings, like prisons, and jails, and
upon release, and maximize the possibility of these individuals
to get healthcare, to the involvement of community, so that we
can actually integrate the effort between healthcare, justice,
and communities.
Through the HEAL Initiative, we have been able to
accelerate significantly. Also, another area that has been
neglected, overall, which is the need to better treatments for
the management of severe pain, and if we do not address the
need of patients suffering from severe pain, we keep them as
very, very vulnerable, to seeking out much more dangerous
drugs, out in the illicit market.
And finally, we need to also ask ourselves: What is it in
the United States that is making Americans so vulnerable to the
use of these drugs? And that is relevant to prevention, because
if we do not understand it, then we cannot do interventions to
actually protect those that because of circumstances alien to
them, are actually at much higher risk to taking drugs, and
ultimately develop addiction or overdosing.
Senator Baldwin. I appreciate your response.
INVESTMENT IN RESEARCH
Dr. Fauci, the U.S. was able to bring a COVID-19 vaccine to
the public in really record time. And I am grateful for the
work of so many that made that possible; including several who
are in this room.
Unfortunately, the next pandemic, driven by an unknown
disease X will come. And I believe we can't wait. We should
invest in the development of novel antivirals, and vaccines,
and diagnostics for unknown threats from priority viral
families, now, so that we are better prepared in the future.
Can you explain how the investments we have made over time
at NIH and across the Federal Government, made the COVID-19
vaccines and medical countermeasures possible? And how would
sustained investments to develop responses to viral families of
concern make us better prepared?
Dr. Fauci. All right. Thank you very much for that
question, Senator. Yes, it is very, very clear that the
investment in basic and clinical biomedical research for at
least a few decades, and maybe more, prior to the realization
that we are dealing with a new, historic pandemic, allowed us
to do something that was completely unprecedented.
Two examples of that are the work that was done on what we
call vaccine platforms, the mRNA vaccine which was fundamental,
basic research, on how to get the mRNA molecule to actually
serve as a platform for vaccine.
Work at the NIH, in our own campus, as well as NIH-funded
investigators throughout the world, also worked on what is
called immunogen design to do work that led to the ability to
stabilize the optimal immunogen, in this case it was the spike
protein, which allowed us to go from the realization of a new
pathogen, on January 9-10, 2020, getting into Phase 1 trial, in
65 days and 11 months data, having a safe and effective
vaccine.
We did that because of the investment you are referring to.
Right now, looking forward, we have what is called a Prototype
Pandemic Preparedness Plan, which means you do just what I
believe you are alluding to. You develop a number of families.
There are about 20 families that are the high risk, of those
there are about 7 families of viruses that if you do the
fundamental work of looking at the commonalities among them,
and develop diagnostic tests, assays, immune correlates, and do
that now.
And if we don't get the resources now, Congress has been
very generous to us up to now, but if we don't get the
resources we need, we are not going to be able to do the kind
of preparedness, not only for vaccine, but also for targeted
development of antivirals, which we did so successfully with
HIV (human immunodeficiency virus), and did quite successfully
right now.
But we have programs that are not going to get off the
ground unless we get funding. So fundamental basic, and
clinical research are the core of everything that is going to
protect us in the future. Thank you.
Senator Murray. Senator Braun.
FUTURE COVID LOCKDOWNS
Senator Braun. Thank you, Madam Chair. So I am going to
have two questions, and I would like Dr. Tabak and Dr. Fauci to
answer each of the two questions. I am going to start with this
one.
So in navigating through the entirety of what we did to
fight COVID, clearly, the most expensive feature of the
navigation would have been lockdowns. We did that out of
uncertainty, we had no idea, you know, how that was going to
work.
Even in the business I ran, you had early dust ups, where
you would get a case and clear out a warehouse. And we quickly
understood you do not throw caution to the wind, and you take
the basic information that we all had to deal with, and you
took it seriously, you put protocols in.
Let us look at lockdowns. It costed us trillions of
dollars, and we are paying for that now, with super-high
inflation. You know, I think I am interested in, when Johns
Hopkins comes out with a study that said basically that didn't
have any impact on mortality, and I don't know that that study
addressed what mortality might have been impacted, in terms of
deferring other healthcare. Can we take lockdowns off the table
in terms of what we do in the future? Dr. Tabak, and then Dr.
Fauci.
Dr. Tabak. I can't say, because I don't know what that
future holds for us. If you have a pathogen that is very
virulent, very infectious----
Senator Braun. Let us assume it is in the same modality as
what we have been navigating through over the last couple 3
years.
Dr. Tabak. I think the initial presentation of the virus
was one that was devastating. It killed a lot of people.
Senator Braun. What about the study that Johns Hopkins did,
because we are always saying, pay attention to the science?
Dr. Tabak. I am not familiar with that study, sir.
Senator Braun. Dr. Fauci.
Dr. Fauci. Senator that is a very good question. If you are
going to lock down, you have got to use it temporarily for a
reason to prepare you to be able to un-lock down, and get the
public prepared for that.
Right now, looking forward, I don't see the need of
lockdown in the future unless something really, very, very
unusual happens. And the reason is, that what we really need to
do, is we need to get our population vaccinated, and we need to
get them boosted. That would completely obviate the need to
lock anything down.
So right now if you ask me the question, looking forward,
do I see, even if we do get a new variant, I think the
vaccinations that we have, have enough cross-reactivity and our
ability, with proper resources, to make variant-specific
boosts, I don't see lockdown in the future. Lockdown is a
temporary thing, to get you to be able to move quickly to save
lives.
Senator Braun. That is good to hear, because in that kind
of moment of uncertainty, I don't think we could afford to do
it again. I hope the Biden administration is listening to that.
VACCINE MANDATES
The other question; and I led the effort on it; is when we
took this and distilled it down to, you either get a vaccine or
you lose your job. And thank goodness, we did marshal
bipartisan support that said that didn't make sense, Supreme
Court used that as a cue, you know, in terms of what they did
to abrogate that.
So in the future, will we heed what the Supreme Court said,
and that you wouldn't calculate, even though don't disagree
that vaccines are an important tool, along with therapeutics,
and preventative? Would you push to do the same thing that we
almost did, that would have been the second calamity to occur?
In terms of what it would have cost the economy, and probably
not benefit from a result that would have been measurable?
Dr. Tabak, and then Dr. Fauci.
Dr. Tabak. As you know the vaccination is the single most
effective preventive measure, and so to the extent that the law
allows, you would want to continue to act----
Senator Braun. But would you recommend that we go down that
path again, down to 100 employees in a business, to where you
said, either get it, or lose your job.
Dr. Tabak. That is a policy call, sir. I don't make those
calls.
Senator Braun. Dr. Fauci.
Dr. Fauci. Again, it is a policy call. I would hope that we
would marshal everybody, you know, both sides of the aisle, to
get out there and encourage everybody to get vaccinated, and if
they did, we wouldn't even have to address that question. I
don't like mandating things. I don't like punishing people for
not doing something.
But I would hope that they would realize, if you look at
the data, and you just made an appropriate statement, Senator,
a moment ago, about following the science; if you look at the
data, of the differences in vaccinated versus unvaccinated
people, and hospitalizations, and death, it is striking what it
is.
So as a public health person, I would say why don't we all
pull together to get people vaccinated. We won't have to worry
about, essentially, putting what appears to be and is in fact a
penalty if you don't.
Senator Braun. And I think the key to that navigation is to
pay attention to the data, and the science, not the political
science.
Dr. Fauci. Right, exactly.
Senator Braun. Thank you.
Dr. Fauci. Thank you.
Senator Murray. Thank you. Senator Rubio.
Senator Rubio. Thank you. Thank you all, for being here.
GENDER TRANSFORMING CARE
Dr. Tabak, let me start with this question. You know, we
have recently seen that the--not just the Biden administration,
but the Biden administration, and others in the policy realm,
have been actively promoting and supporting the use of things
like, puberty blockers, and hormone therapy for young boys and
girls. I want to sort of limit my question to minors, for what
they have termed gender transforming care.
That is not an FDA-approved use of puberty blockers and
hormone therapy I don't believe in any people, but especially
in minors. So as the NIH is America's medical research agency,
what work have we done at NIH, what work has been done to
determine if this non-FDA-approved use of these medicines, this
off-label use of these medicines is appropriate for minors
seeking gender transforming care?
Dr. Tabak. So NIH funds a small number of observational
studies to gather the data on the effects of treatments that
transgender youth and their parents have chosen. And there are
also a small number of studies that describe the health issues
and risks, including HIV that are unique to these transgender
youth. But all of the research in this space is observational.
We do no interventional work.
Senator Rubio. I guess, my question is before--one thing is
a decision made by an adult, right, and especially given the
irreversible nature of some of these treatments, isn't there
some wisdom in the notion that before policymakers are out
there promoting the off-label use of medications that lead to
permanent changes, that there be some more research done on its
impact, you know, 5, 10, 15, 20 years from now?
Dr. Tabak. So as you know, transgender youth are more
vulnerable to depression, anxiety, engaging in self harm, and
so it is important that we examine and evaluate the potential
effects of these treatments.
Researchers are observing longer term psychological impact
of these protocols, and so by looking at individuals,
transgender youth, with and without histories of puberty
suppression, we will be able to better answer the types of
questions that you are posing.
Senator Rubio. Yes. I guess my--that is my point. My point
is, we don't know what its long-term implications are when we
weight the costs and the benefits. The FDA (Food and Drug
Administration) hasn't approved this, and yet we have
policymakers promoting it. And I think that is an important
point.
I mean, clearly, we don't want anybody harming themselves,
and things of this nature, but we don't know what--these policy
decisions are being made on the basis of observational
guidance, and by your own admission, without any sort of long-
term trajectory on its holistic impact.
COVID TRAVEL RESTRICTIONS
Dr. Fauci, I am running into something that is pretty
interesting. I believe the United States is the only major
Western country that now requires its citizens to test negative
for COVID before they can get on an airplane and reenter the
country. I believe that is accurate.
And on the other hand, we are hearing now that, for
example, Title 42, which is a COVID-era policy should be lifted
because we have reached the point now where COVID is
manageable, or at a level where we no longer need Title 42. And
we obviously know we have a problem in our southern border
where every day people are entering the country, illegally, and
many are not even being tested for COVID. And even if they are,
they are being allowed to stay, and most certainly would under
Title 42.
I don't understand. How do we tell American citizens, if
you test positive, even if it is a dead virus that has been in
your system for 10 days, because you can test positive days
after you are no longer infectious, and you can't enter your
own country? But people--if you arrive illegally, whether you
test positive or not, if you say the magic words for ``asylum''
you get to stay in the country.
And this is a real-life scenario. I know people that are
abroad, they test positive, they are not sick; maybe they were
sick a week ago. And they can't afford to continue to pay for
hotel rooms, and staying overseas until they can finally score
a negative test.
Has the time come for us to lift this, in your view; you
know, having been so integral in our COVID response? Are we at
a point now where American citizens should be allowed to return
to their country without testing negative?
Dr. Fauci. You know, I am not--thank you for the question.
It is an important question. I don't have the answer to that. I
mean, we work with our CDC colleagues to continue to examine
the feasibility of that, and the desirability of that. I think
the idea of having an immigration issue mixed with a public
health issue for the general population; I think those probably
should be separated.
Senator Rubio. Well, except they are interrelated, because
they both involve groups of people entering the United States.
One group is citizens of the country entering legally, the
other group, frankly, are people that are not entering legally.
The group that is not entering legally, even if they test
positive, if they are even tested, get to stay; the American
citizen can't reenter their own country until they produce a
negative test.
And my point is, if we have reached the point in COVID,
where we no longer need Title 42 as a COVID restriction for
illegal entry, why do we still need travel restrictions for
American citizens for legal entry into their own country? That
is the genesis of the question. That is where I think the link
is the--it sort of seems to be at odds with it.
Dr. Fauci. Yes.
Senator Rubio. All right. Thank you.
UNIVERSAL COVID VACCINE
Senator Murray. Thank you. Dr. Fauci, you talked a little
about this. But I wanted to go back through it again. I am
really pushing for Congress to pass additional emergency COVID
funding to make sure that our communities have the tests, and
the treatments, and vaccines they need to keep their families
safe.
And I understand your Institute is supporting research on
the development of these next-generation vaccines that could
protect against multiple variants. What can you tell us about
the progress of that research? And what does NIH need to see it
to completion?
Dr. Fauci. Well, thank you for that question. Well, the
progress has been substantial. To get what we call
``universal'', and that is probably too broad a term, is to get
a vaccine that works against multiple variants of SARS-CoV-2 is
the first step
And that would be something where you get a vaccine that
either is directed against the common component of all of the
variants, or has each of the components of the variants, for
example, in a nanoparticle with a mosaic or multiple components
to it.
We have studies that are, right now, gone from preclinical,
namely, in an animal model, into a human study, and the results
actually look very promising. The next step would be to get a
vaccine that not only is against all variants of SARS-CoV-2,
but against all of those group of variants, including, what we
call, sarbecoviruses, which overlap with the viruses that we
see in many bats, which almost certainly are the original
source of these viruses, that have jumped species and gone into
humans.
The work is going along very, very well. We are getting a
number of investigators, both people who have been established
in the field, and new investigators, but we can't continue it,
Madam Chair, without additional resources.
And that is really one of the things that is very, very
difficult for us, because the scientific opportunity is there,
and we really feel that we do have this, not only as an
aspirational goal, but we will be able to get to that goal of
getting a vaccine that would protect us against both known and
unknown variants. So we are excited about the science of it,
but we can't continue without additional resources.
INTERAGENCY WORK WITH BARDA
Senator Murray. To have resources, right. And how is your
Institute working with BARDA (Biomedical Advanced Research and
Development Authority) to accelerate innovation in the next-
generation vaccine development, particularly for COVID-19
vaccines?
Dr. Fauci. Well, we have had a long-standing collaboration
and cooperation with BARDA now for quite a long period of time.
And the way that works is that we do the fundamental, basic
research, and proof of concept, and very often get involved,
not only in the preclinical, but in the early trials, whereas,
BARDA partners with a pharmaceutical company to do the advanced
development of these concepts.
So it is a partnership that has really worked very, very
well, and hopefully we will be able to continue that, again
with the need for new resources.
Senator Murray. Okay. Thank you.
Dr. Gordon, I want to come back to you. You have had
several questions about mental illness, not surprising. It is a
huge issue for America today. And I know that despite the best
efforts of researchers, like yourself, in the past 30 years, we
have seen dramatic increases in mortality, morbidity, and
healthcare costs related to mental illness; and that is
actually before factoring in the effects of this pandemic, and
the opioid crisis.
MENTAL HEALTH DIAGNOSIS ISSUES
And on top of it all, diagnosis is really difficult. And
medications don't always work, and can have awful side effects.
So I know Senator Blunt asked you about using RADx, as one
possible approach, but what are the greatest barriers to
accurate diagnosis?
Dr. Gordon. Well, frankly, one of the greatest barriers to
accurate diagnosis, Senator, is that our diagnoses are not
terribly good, in terms of describing what is going on in the
brain. And so we need a better individualized approach, not
just to diagnosis, but really being able to make informed
clinical decisions in cooperation with our patients.
Well, the clinical issue really isn't, does this individual
have depression, or schizophrenia, or bipolar disorder,
although those diagnoses can be sometimes hard to differentiate
in the individual patients.
The bigger clinical question is: For this patient with
depression, are they going to benefit most from a medication,
or which type of medication? Or are they going to benefit most
from psychotherapy, or a brain stimulation treatment?
We have a number of different research projects that are
aimed at trying to make those kinds of clinical decisions with
the aid of technology, with the aid of increased attention to
details in the patients' behaviors, and cognitions. And that
approach I think is going to take advantage of things like big
data. So we need to collect lots and lots of information
about--well characterized patients.
And then we need to make careful experiments to try to
determine when that information helps us describe that patient
better. So it is really about precision medicine in psychiatry,
moving it forward in a number of different fronts, from grants,
to academic organizations. And as I mentioned also before,
small business grants that are really paying off. So we should
see some progress, hopefully in the future, near future.
Senator Murray. So I assume it is fair to assume that
solving this diagnosis puzzle, will really open doors for
better treatments?
Dr. Gordon. It would open doors to transforming how we
decide with our patients what treatments to use. It would
really change psychiatry. Right now, as a psychiatrist, if I
want to help someone with depression, our only discussion is
about which side effects they don't want. And so we try to
avoid one medication or another. As opposed to which
medication, or which treatment that I have to offer is going to
work better for them. So yeah, it would really transform
things.
Senator Murray. Okay. Thank you. Senator Blunt.
Senator Blunt. Thank you, Chair.
ADUHELM
Dr. Hodes, I have been watching the FDA decision on
Aduhelm, the Biogen drug, as well as the CMS (Centers for
Medicare & Medicaid Services) handling of that. I think that
decision is going to have some pretty long-term consequences,
particularly the CMS decision, and other companies will be
following. Biogen has already made some pretty dramatic
decisions, based on the CMS view that only the people in a
trial could benefit from the emergency approval, by FDA.
Would you talk a little bit about both of those things?
First the FDA approval process, what merit do you see in that
emergency approval process? And then, what concerns do you have
or not have about CMS then deciding that it would only be
available to a few people?
Dr. Hodes. Thank you for the question. Well, of course FDA
and CMS have their regulatory responsibilities, and we defer to
those. But we do work very closely particularly on the science
involved in these implications; so as many, or all of you may
know, the decision by FDA was what was called an accelerated
approval of Aducanumab, Aduhelm, based on its ability to clear
amyloid from the brain, and by brain scans.
Without compelling evidence of clinical effectiveness, and
that was the rub. And in fact, the FDA decision required that
the sponsors, Biogen, Eisai, then conduct a randomized,
controlled trial to look if--to determine if there was, in
fact, clinical outcome.
It was in that setting that CMS said that for widespread
coverage it would require randomized, controlled clinical
trial. It made the distinction, though, about the future of
such drugs. Any drug that received an approval based on
clinical outcome, based on FDA decision and judgment, would
have broader coverage without requirement for another
randomized clinical trial.
But any in which there was no demonstrated evidence of
effectiveness on clinical outcomes, would require that kind of
outcome before they went further. Again, those are regulatory
decisions.
Senator Blunt. So it sounds like, to me, the FDA decision
was really a CMS; or at least just the decision to continue the
trial. That may not have been what FDA thought it was doing,
but that is what CMS decided it was doing?
Dr. Hodes. No. FDA, again, by requiring that--for
maintenance even of the accelerated approval, that a clinical
trial, a randomized trial, be carried out, was also saying
there needed to be a continuation.
You asked, importantly I think, what the impact of this
will be on other studies, other agents. There are currently
three companies, Roche, Lilly, and Eisai--Biogen, which have
ongoing clinical trials of other antibodies to amyloid, they
have all received a breakthrough designation last year from the
FDA. They are all expected to produce their results in the next
few months. So above all, I think we all share hope and
optimism that will see effective clinical outcomes there.
For NIH, I think the implications are clear. We need to
support the most rigorous and continuing research toward
amyloid and other targets, the kind of research that will give
clear-cut, definitive answers about clinically important
outcomes. And that is certainly our part in this consortium.
VACCINE AND THERAPEUTIC DEVELOPMENT
Senator Blunt. Well, Dr. Fauci, while we are talking about
the accelerated approvals, or not, during COVID, obviously
NIAID (National Institute of Allergy and Infectious Diseases)
shepherded both successful vaccines and therapeutics, through
the approval process during the pandemic. I am concerned that
once the pandemic is officially behind us that both vaccine and
therapeutic research and development will be subjected to
normal development processes that, in what we have learned in
the last year-and-a-half may not be the structure that we
should use. Would you talk about that a little bit?
Dr. Fauci. Senator, are you referring to the fact that we
should not slow down the acceleration of approvals when we are
out of the pandemic phase?
Senator Blunt. I am asking that, or if there should be some
``new normal'' approval process, now that we have had, I think
two vaccines, and 20 treatments developed through those
partnerships?
Dr. Fauci. Yes. I am not sure I understand the question. It
is my fault. Are you saying that, should we continue the normal
standard of approval, which would take much longer than the
emergency-use authorization? Is that the question you are
asking?
Senator Blunt. That is the question.
Dr. Fauci. Yes. Yes, I think we should go through the
normal approvals, and if we are in an emergency situation
again, we absolutely should use the EUA (Emergency Use
Authorization) approach which has fared us very well. But when
we get behind us the outbreak, I think the normal approval
process, which is pretty much expedited pretty well by the FDA,
should continue.
Senator Blunt. All right. Thank you, Chairman.
Senator Murray. Senator Kennedy.
TITLE 42 RECISSION
Senator Kennedy. Thank you, Madam Chair. Did the Biden
administration ask any of you whether it was safe to rescind
Title 42?
Dr. Tabak. We have had no discussions about that, sir.
Senator Kennedy. You haven't done?
Dr. Tabak. I have not. No.
Senator Kennedy. How about you, Dr. Fauci?
Dr. Fauci. No. I have not.
Senator Kennedy. How about you, Dr. Gibbons?
Dr. Gibbons. No, No, sir.
Senator Kennedy. How about you, Dr. Gordon?
Dr. Gordon. No.
Senator Kennedy. Dr. Hodes?
Dr. Hodes. No, sir.
Senator Kennedy. Dr. Volkow?
Dr. Volkow. No.
Senator Kennedy. Well, the Biden administration says it is
safe, that under the science it is okay. Who did the
administration rely on, to suggest that rescinding Title 42 is
in the interest of public safety?
Dr. Fauci. That was a CDC decision. The Title 42 is a CDC
decision.
Senator Kennedy. Do you agree with it, Dr. Fauci?
Dr. Fauci. Well, I think that the immigration policy should
be separated from the public health----
Senator Kennedy. No. And I don't want to get you involved
in immigration policy; but people are people, physiology is
physiology.
Dr. Fauci. Right.
Senator Kennedy. And one is the susceptibility of the virus
has nothing to do with their country of origin or immigration
status.
Dr. Fauci. Right.
Senator Kennedy. And what I am asking you, purely from a
public safety standpoint.
Dr. Fauci. Right. Yes.
Senator Kennedy. Is it safe to rescind Title 42?
Dr. Fauci. I think given the level of infection at the
time, which is right now, that I think that the CDC decision
was a reasonable decision.
Senator Kennedy. Does anybody disagree with that? Do you
all agree with that? Let me get you, of record.
Dr. Gibbons?
Dr. Gibbons. Yes. I concur with Dr. Fauci on that.
Senator Kennedy. Dr. Gordon?
Dr. Gordon. I don't have the expertise to concur or not
concur.
Senator Kennedy. Okay. Dr. Hodes?
Dr. Hodes. I would also say I don't have the expertise to
weigh on this.
Senator Kennedy. Dr. Volkow?
Dr. Volkow. I don't have the expertise.
Senator Kennedy. Okay. All right; thank you very much.
Senator Murray. Senator Moran.
ARPA-H PRIORITIES
Senator Moran. Thank you, Chairman Murray. I don't have the
benefit of knowing what has been asked and answered. So I will
ask questions. Recently the ARPA-H proposal would initially
focus--this is for Dr. Tabak--would initially focus on three
diseases: cancer, Alzheimer's, and diabetes, and be housed
under NIH.
Congress and NIH already invest significantly into research
and development to these three diseases. How can NIH conduct
proper oversight to ensure NIH, through its current work, isn't
simply being replicated?
Dr. Tabak. I think those three diseases are meant to be
illustrative and not restrictive. In terms of the larger issues
that you raise, as you know, NIH does a rather extensive
portfolio analyses, and the expectation would be that there
will be a crosstalk between the new agency, and the NIH to
avoid, as you put, you know, the potential for duplication.
ALZHEIMER'S DISEASE TREATMENTS
Senator Moran. This is again for you, Dr. Tabak. In recent
National Coverage Determination, CMS indicated it would support
FDA and NIH, by covering drugs for Medicare beneficiaries,
participating in randomized, controlled trials. I would
interpret that to mean that there is a path to coverage through
NIH studies for participants qualifying trials, related in the
FDA-approved Alzheimer's disease treatments. Is that an
assessment that--and I am not--if that is an accurate
assessment? Or how would you elaborate?
Dr. Tabak. If I may turn to Dr. Hodes, who is the expert in
that space.
Senator Moran. Dr. Hodes.
Dr. Hodes. I think that is a very accurate statement. Thank
you.
Senator Moran. Good. And that is a good development, right?
Dr. Hodes shook his head, yes.
Dr. Hodes. Yes, sir.
NCI BUDGET REDUCTION
Senator Moran. Let me talk a moment, in the absence of Dr.
Sharpless, I will let you all direct who should answer my
question. The NIH 2023 budget request suggests $199 million cut
to the NCI (National Cancer Institute), a 2.9 percent cut from
the current fiscal year. I assume that that will be explained
as those dollars being picked up in ARPA-H. What is the
rationale for the significant funding pivot to ARPA-H at the
expense of NCI?
Dr. Tabak. So at the time the budget was prepared, the only
baseline that the administration had to work with was a
continuing resolution level. We are fortunate that the
Congress, in the Omnibus, provided us with substantially more
resources than were in the continuing resolution. And we
certainly look forward to working with you as the 2023
appropriations process works through.
Senator Moran. So there is room--there is no particular
insistence that that is the right ratio between the funding of
one ARPA-H, and the normal appropriations process for NCI?
Dr. Tabak. I think it is more than a reflection of using a
baseline that was available at the time.
Senator Moran. Well, the $16.9 billion increase for NCI in
fiscal year 2022, allowed the NCI to increase the funding
allocated toward competitive cancer grants. It is one of the
reasons we continue to advocate for higher NCI funding, is to
improve NCI's ability to award those competitive cancer grants.
In recent years NCI could only fund about one in eight
research grant applications. Dr. Sharpless indicated, in front
of the subcommittee, that that was a great concern to him, as
it is to me. If NCI funding is not boosted above the fiscal
year 2022 levels, can competitive grants be prioritized and
expanded?
Dr. Tabak. It would be very difficult to do that in the
absence of additional funding.
Senator Moran. Doctor, thank you, both of you. Thank you
all.
AUTOIMMUNE DISEASE RESEARCH
Senator Murray. Dr. Tabak, last week the National Academy
has issued its review of NIH's autoimmune research portfolio,
and the authors found that much of the work that that agency
does in this area is really extraordinary. But that NIH doesn't
do the best job coordinating, or setting priorities, or
focusing on innovation, or evaluating its autoimmune research
portfolio.
The authors' findings really echo an earlier 2010 National
Academy Study on women's health research, and to address these
problems, they recommended the creation of an Office of
Autoimmune Disease Research within the Office of the Director,
to facilitate collaboration and coordination.
Given the importance of this research for communities
across the country, it is critical that NIH does the best
possible job facilitating it. Do you have concerns with
establishing this office?
Dr. Tabak. Senator, the report, as you know, was released
last week, and we are still reviewing the specifics of it. In
reviewing the top line messages, among the things they suggest
that we do, develop an agency-wide strategic plan, make sure
that investments that we make align with those strategic plans,
coordinate both within and outside the agency, do evaluation,
do reports to the Congress.
At first glance, I think these are things that we could
probably do without the creation of a new office, but I
certainly, you know, would be willing to work with you, and
other members of the committee, going forward, as we sort
through the specifics of the report, and get a better
understanding of the rationale behind their specific
recommendation.
Senator Murray. Okay. I would like to work more with you on
that. I think this is extremely important. I want to make sure
we are addressing it in the correct way, and I want to talk to
you more about that.
Dr. Tabak. Thank you.
Senator Murray. Senator Blunt.
EARLY STAGE INVESTIGATORS
Senator Blunt. Thanks Chair. I think my last question today
will start with Dr. Tabak, but anybody that wants to talk about
it. One of the things we were most concerned about 8 years ago
was the fact that young researchers were leaving the field.
That the pool of money, not only wasn't increasing, but it was
about 22 percent less in the research buying power, than it had
been.
What are we doing right now to keep young researchers in
the field, and try to see that they get their first grant, and
that there is not an obstacle based on numbers of first grants
to getting that second grant?
Why don't you start, Dr. Tabak? And if anybody else wants
to talk about what you are doing to keep young researchers
engaged I would be pleased to hear that.
Dr. Tabak. We have prioritized the funding of early-stage
investigators; back in 2013 we only supported 600 such
individuals, last fiscal year, 1,513. That has come as a result
of the Institute and Center leadership prioritizing
applications from these individuals. We have also created
certain mechanisms that would incentivize and enable early-
stage investigators.
So for example, we have the so-called Katz Early Stage
Investigator Award, in which no preliminary data is accepted.
This is important, it basically liberates a new investigator
from his or her post-doctoral or graduate school experience,
and they are able to think, you know, as boldly as possible in
preparing an application.
We also have the NIH Director's New Innovator Award Program
which is attracting early-stage investigators from very broad
biomedical fields. And so when you take these things together,
I think we are making good progress in ensuring the entree into
the system of biomedical research.
But let me turn to my colleagues to see if anybody else
wishes to comment.
Dr. Gibbons. If I might add to Dr. Tabak's comments. There
are two areas for the NHLBI (National Heart, Lung, and Blood
Institute) that we are particularly focusing on. As evident in
these hearings, a critical element is the translation of basic
science understanding into clinical science and clinical
medicine, and clinician scientists are critical to making those
transitional leaps that are so important to public health.
And this is an area, quite frankly, where there is a
paucity of early-stage investigators, in a critical pipeline.
And so we have special awards for them to get their first RO1,
in particular, to launch their careers as early-stage clinical
investigators.
I would also add the diversity of that early-stage
investigator pool is critical, and recognizing the supportive
efforts to expand that diversity is, again, another high
priority which we have programs, specifically, designed to do
that, like our PRIDE Program. Over.
Senator Blunt. Anybody else?
Dr. Hodes. I had to reinforce the points made. And note
that we also try to track outcomes of our programs, including
training, career development. So for example, with the expanded
research around Alzheimer's and related dementia's research,
since 2015 through the present, fully a third of the
investigators awarded have been new and early-stage
investigators who have had no prior, major NIH research. And we
think this is an important reflection of our ability to
recruit. And now we will see about retaining them into the
research workforce.
Dr. Volkow. And I was just going to make a comment, because
Dr. Tabak alluded to it, and an area that is crucial is to
ensure that we get the brightest interested in science; so
going after younger kids, and teaching them, and giving the
opportunity to see what science is all about, is a way that you
can ensure that you will have the throughput then, to get
investigators.
Senator Blunt. Thank you, Chair.
Senator Murray. Thank you. Senator Moran.
Senator Moran. I will just take this moment, Chairman
Murray, to thank you and Senator Blunt, for your leadership,
and the success that we have had in numerous years, now in a
row, in the support for the National Institutes of Health.
I have been a ranking member of this committee with Senator
Harkin. You both have been ranking members, and chairmen and
woman of this committee during a period of time in which we
were capable, in a bipartisan way, of increasing the investment
in fighting the diseases and afflictions that Americans and
people around the globe suffer from.
And not knowing what our committee schedule is into the
future, this may be the last time we have Senator Blunt here
with the NIH crew. And I take this moment to thank him, in
particular, for his efforts that have been recognized around
the country, and certainly in our home States of Kansas and
Missouri, of making a tremendous difference in the efforts to
find the cures and the treatments to reduce the afflictions
that we face in the world, of our well-being, of our health.
And so to you, to Senator Blunt, particularly today, thank
you for that leadership. I am pleased that the world is in a
better position, and that Americans have a greater chance of
fighting these diseases, and there is a lot more hope than
there used to be.
Senator Murray. Thank you. Thank you for those comments. I
think we all agree.
That will end our hearing today. And I want to thank my
fellow committee members for a thoughtful conversation.
I want to thank Doctors Tabak, Fauci, Gibbons, Gordon,
Hodes, and Volkow. Thank you all for joining us today to share
your expertise.
ADDITIONAL COMMITTEE QUESTIONS
For any Senators who wish to ask additional questions,
questions for the record will be due May 27, at 5:00 p.m.; the
hearing record will remain open until then, for members who
wish to submit additional materials for the record.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted to Dr. Lawrence Tabak
Questions Submitted by Senator Patty Murray
Question. The budget request concentrates most of its proposed
spending increase in ARPA-H, even though that agency has yet to hire
anyone. If Congress funded ARPA-H at $5 billion as the budget proposes,
what impact would that have on N-I-H's 27 institutes and centers? While
Congress's work on the ARPA-H authorization continues, there's broad
agreement that it should not be based in Bethesda with the rest of NIH
and that its staff should be recruited from outside the agency. Given
the transformative role ARPA-H is supposed to play by supporting high-
risk, high-reward research, I believe NIH should rely on outside
expertise to recruit the right staff to stand up the agency.
Who is handling ARPA-H's hiring? Is it NIH or an outside firm?
When does NIH expect to have a permanent director on-board?
Answer. HHS is in the process of standing up ARPA-H and developing
plans for its operations and functions, including recruiting an
innovative group of people to help launch the important work of the
agency. HHS is bringing onboard staff in key support functions--
acquisitions, budget/finance, and strategic resources. Program managers
will be recruited after an inaugural director is on board. The
Secretary is also seeking to identify an interim leader prior to the
appointment of an inaugural Director. Ideally, this acting deputy
director would have considerable experience in government--specifically
familiarity with the ``ARPA'' model, broad technical and management
experience across several disciplines, and a proven record innovating
around experimental platforms and tools to facilitate discovery,
quantification, and validation of fundamental measures in science.
Meanwhile, the White House is currently looking for candidates for
President Biden to appoint as an ARPA-H Director who will be
responsible for administration and operation of ARPA-H and who will
report to Secretary Becerra. The ideal candidate would be an
extraordinary leader with a vision and proven track record for driving
transformative change in health and biomedicine, a strong private
sector background, and experience in academia or government, as well as
a proven ability to build partnerships.
Question. Congress provided significant funding for research into
long-COVID with the goal of understanding this complex condition and
developing potential treatments.
When does NIH expect to exhaust its existing balances of long-COVID
funding and what steps would it take if faced with a shortfall?
Answer. Funds for the Researching COVID to Enhance Recovery
(RECOVER) initiative are being used to implement the necessary in-depth
and national scale approach to understanding, preventing, and treating
the post-acute sequelae of SARS-CoV-2 infection (PASC), including Long
COVID. The National Institutes of Health (NIH) has either obligated or
has planned/outyear RECOVER activities for all of the $1.15 billion
funding provided by Congress. Working on an accelerated schedule, NIH
has obligated approximately $674.5 million as of May 17, 2022. The
balance will be utilized in planned obligations to cover fiscal year
2022 and outyear spending for RECOVER studies.
Our understanding of the complexity and broad range of conditions
encompassed in PASC has evolved substantially since the time of the
original appropriation, and it is clear that we need to further
accelerate and expand our existing efforts and capacity to test a wider
range of interventions and develop assays for the diagnosis and
monitoring of patients with PASC.
______
Questions Submitted by Senator Roy Blunt
ARPA-H
Question. I am a supporter of ARPA-H. At last year's NIH hearing I
spent the majority of my statement highlighting that ARPA-H is the
right idea at the right time because, as we learned so well during
COVID-19, NIH can take a larger, more involved role in public-private
partnerships without overstepping the bounds of the role private
industry should play. Since that time, Congress has passed an Omnibus
appropriations bill that included $1 billion to establish ARPA-H. In
addition, the HHS Secretary has established ARPA-H at NIH, but with
direct reporting to the Secretary's office. Dr. Tabak, can you explain
why it is important to have ARPA-H under the NIH umbrella, and
specifically how this will help get ARPA-H established and working on
research programs faster?
Answer. On April 15, 2022, Secretary Becerra transferred ARPA-H to
the NIH as notified in the Federal Register published April 20, 2022.
The Secretary indicated that, following presidential appointment, the
ARPA-H director will report directly to the Secretary and be delegated
all the necessary authorities to administer ARPA-H.
The Secretary's decision to transfer ARPA-H to NIH is critical to
accelerating ARPA-H's establishment and reducing the use of funding for
redundant functions using critical infrastructure provided by NIH.
Broadly, ARPA-H's mission aligns with NIH's, in that both agencies
strive to improve health through research. Through close collaboration
between ARPA-H and NIH, along with other Federal, and public or private
entities, ARPA-H will ensure it reaches all people with better health
solutions faster. ARPA-H benefits from drawing closely upon NIH's role
as a global leader in biomedical research, including its knowledge,
expertise, and ongoing activities. Setting up ARPA-H within NIH will
avoid unnecessary duplication of scientific and administrative effort.
As a part of NIH, ARPA-H is benefitting from and leveraging the use of
several electronic systems to quickly establish its functional areas,
provide for a more seamless start up, and avoid building functionality
from scratch that already exists
Question. ARPA-H is in the process of being stood up. Can you
provide the Committee with additional details on:
What qualifications you are looking for in a Director?
Answer. President Biden will appoint an inaugural Director with the
requisite experience to lead this new agency. An ideal candidate would
be an extraordinary leader with a proven track record and vision for
driving transformative change in health and biomedicine, a strong
private sector background, and experience in academia or government. In
addition, the candidate should have a proven ability to build
partnerships.
Question. When do you expect a Director to be in place?
Answer. The White House manages the search, nomination, and
announcement, of all presidential appointees.
Question. How many program managers are you looking to hire?
Answer. ARPA-H will recruit and hire program managers based on the
organization's priorities and the funding available. Decisions will be
made when the inaugural ARPA-H Director is appointed.
Question. What are the qualifications for the location for an ARPA-
H headquarters and when will that decision be announced?
Answer. HHS is in the process of standing up the new agency and is
developing plans for its operations and functions. Currently, no
commitments as to the physical location of ARPA-H have been made.
Question. Will there be an official location search similar to how
locations for other agencies outside of Washington, DC were chosen?
Like the recently relocated National Institute of Food and Agriculture?
Answer. Currently, no commitments as to the physical location of
ARPA-H have been made. We will continue to engage in a thoughtful
process.
Question. When do you expect scientific programs to begin?
Answer. Scientific programs are expected to begin after the
appointment of an inaugural director and the recruitment and hiring of
the first program managers.
Question. How will ARPA-H be structured to ensure that biomedical
researchers at universities have an opportunity to be program managers
when typical sabbaticals from research institutions last 2 years, which
is less than the typical three year program manager term?
Answer. Program managers are expected to be appointed for a single
three-year term with the possibility of a single renewal, but shorter
terms could be negotiated. In a circumstance where a program manager's
home institution recalled the researcher prior to the end of an
appointment, ARPA-H would anticipate working with the institution for a
mutually agreeable solution.
Question. Will ARPA-H encourage researchers to publish outcomes of
their ARPA-H research in medical publications? This is currently
atypical at DARPA.
Answer. DARPA and ARPA-H operate in two different ecosystems. DARPA
funds performers to benefit the Department of Defense in execution of
its mission. ARPA-H's goal is for new technologies, capabilities, and
platforms to benefit everyone and improve everyone's health potential.
Where appropriate, ARPA-H performers will be encouraged to publish
their findings or otherwise make them widely available.
Question. Will ARPA-H run clinical trials? If so, what will be the
process to test/approve treatments or vaccines with FDA?
Answer. Scientific programs are expected to begin after the
appointment of an inaugural director and the recruitment and hiring of
the first program managers. A potential area of focus is to improve
clinical trials to speed the generation of research results and recruit
more inclusive trial participants so that those results are more
representative of the patient population. ARPA-H will seek
opportunities to work closely with other Federal agencies and the
private sector on these issues.
Question. More specifically, how do you envision the partnership
between ARPA-H and FDA?
Answer. See Answer above.
Question. How do you ensure the FDA approval process does not
hinder the urgency ARPA-H will need?
Answer. Operating within the Federal Government, ARPA-H anticipates
the benefit of forming close relationships, collaborations, and
agreements with other Federal agencies, either formal or informal. In
either case, the intent remains the same--to work closely with other
Federal agencies to engage them early in the program development
process and collaborate to promote synergistic goals.
Question. Are you concerned that FDA will hinder the fast moving
nature of the agency because of their slow approval process?
Answer. ARPA-H anticipates partnering with the FDA through
collaborative integration and involvement of FDA staff, where
appropriate, in relevant programs from their inception. These
collaborations would be developed to be mutually beneficial from ARPA-
H's and FDA's perspective.
Question. Will ARPA-H have an advisory board? If so, who will
comprise it? If not, why not?
Answer. This would be decided by the inaugural Director.
Universal Flu Vaccine
Question. In response to the COVID-19 pandemic, the US was able to
work through public-private partnerships to develop several vaccines
within less than a year. While this was a much needed triumph, I
assume, Dr. Fauci, it also greatly increases expectations that we can
develop vaccines for other diseases using the mRNA model or the
processes used for developing a COVID vaccine. What did you learn from
COVID-19 vaccine research and development that can now be applied to
the development of other vaccines, particularly a universal flu
vaccine?
Answer. The development of vaccines for COVID-19 was greatly
accelerated by the development of vaccine platform technologies as well
as advances in structural biology that allowed for the stabilization of
the SARS-CoV-2 spike protein and its incorporation into the mRNA
vaccine platform. Research advances that have supported the development
of COVID-19 vaccines, including current efforts to develop the next
generation of COVID-19 vaccines, will support ongoing efforts to
develop universal influenza vaccines by further validating and
advancing the vaccine platforms and technologies on which they are
based. For example, advances in mRNA vaccine platforms, including the
successful development of mRNA-based COVID-19 vaccines, have shown the
utility of this vaccine platform, especially in situations where rapid
development of vaccines is crucial or where traditional vaccine
technologies have not yet proven successful. Several mRNA-based vaccine
candidates for seasonal influenza are currently undergoing clinical
testing. The National Institute of Allergy and Infectious Diseases
(NIAID) also is sponsoring clinical studies of three novel mRNA-based
HIV vaccines. Evaluation and development of the mRNA vaccine platform
across a number of diverse virus families will further aid our efforts
to develop tools and resources for responding to the next pandemic
threat.
NIAID also will build on the advances made for COVID-19 vaccines
using other vaccine platforms, many of which are already in use for the
development of universal influenza vaccines. NIAID Vaccine Research
Center investigators have created a nanoparticle-based pan-coronavirus
vaccine candidate designed to elicit antibodies targeted to the spike
protein of multiple different coronaviruses. This mosaic nanoparticle-
based approach--based on the universal influenza vaccine concept known
as FluMos--is currently undergoing preclinical testing in an animal
model. Separately, NIAID-supported scientists provided proof of
principle that self-assembling mosaic nanoparticles displaying receptor
binding domains of multiple coronaviruses in the Sarbecovirus subgroup
(including SARS-CoV-2) can induce protection in mice when challenged
with another Sarbecovirus. These advances in nanoparticle vaccine
technology will help inform similar strategies for development of a
universal influenza vaccine. In addition, NIAID intramural
investigators are evaluating inactivated whole virus vaccine candidates
for a broadly protective beta-coronavirus vaccine based on related
efforts to develop a universal influenza vaccine. Development and
testing of this approach for beta-coronaviruses will provide valuable
insights into the development of broadly protective inactivated whole
virus vaccines for influenza and other viral families. NIAID also is
supporting studies through its vaccine adjuvant program to compare
different classes of adjuvants and identify the most efficacious
vaccine formulations. The identification of vaccine adjuvants that
promote cross-protective and durable immunity in vulnerable populations
would complement ongoing efforts to develop universal influenza
vaccines as well as vaccines for other pandemic threats.
In late 2021, NIAID announced four awards to fund
multidisciplinary, collaborative teams to conduct research on pan-
coronavirus vaccine candidates and help accelerate pan-coronavirus
vaccine development. The teams will incorporate advances in coronavirus
biology and immunology; immunogen design; and innovative vaccine and
adjuvant technologies to discover, design, and develop vaccine
candidates to protect against multiple SARS-CoV-2 variants and other
coronaviruses. NIAID expects that these efforts not only will advance
the development of pan-coronavirus vaccines, but also will complement
similar activities undertaken by NIAID intra- and extramural
researchers, including at the Collaborative Influenza Vaccine
Innovation Centers (CIVICs) and the NIAID-supported Vaccine and
Treatment Evaluation Units (VTEUs) to develop universal influenza
vaccines. In addition, NIAID-supported research to better understand
the immune response to SARS-CoV-2 infection and vaccination, including
the role of antibodies and T cells, will further advance our
understanding of the human immune system and may provide valuable
insights into new strategies for developing and evaluating broadly
protective vaccines for other pandemic threats, including influenza.
Long COVID
Question. Dr. Tabak, there are a lot of unknowns about long COVID--
what the causes are, why it affects only some, even what the defined
set of symptoms are--and that opens up a lot of research avenues. But
there is also a sense of urgency that should not be lost and NIH must
stay focused on finding ways to help those who suffer, which could be
as many as 30 percent of the population that has had COVID-19.
At the end of 2020, Congress provided $1.15 billion for research on
long COVID. Using this funding, NIH started the RECOVER program, which
in the intervening months has received a lot of criticism. Concerns
have been raised about NIH's lack of urgency and whether it is focused
too much on open-ended research questions as opposed to testing
treatments and moving therapeutics to clinical trials. Can you address
these concerns and specifically highlight why NIH chose to create a
large observational study as opposed to focusing on testing
therapeutics and other possible treatments?
Answer. Researching COVID to Enhance Recovery (RECOVER) program's
national longitudinal observation study is enrolling thousands of
diverse participants including adult, pregnant, and pediatric
populations from over 200 sites across the country, to fully understand
the incidence, prevalence, clinical signs, and symptoms of the various
forms of post-acute sequelae of SARS-CoV-2 infection (PASC) and risk
factors for their development. Of note, RECOVER is particularly
attentive to ensuring inclusion of those typically underrepresented in
biomedical research and those from the populations disproportionately
affected by COVID-19. The clinical data and specimens from this study
are necessary to provide the robust evidence base for development of
diagnostics, clinical monitoring strategies, as well as therapeutics.
Moreover, the data collected through this study will inform an
understanding of and strategies to address ethnic and racial
disparities in PASC, impact on pre-existing conditions, and mental
health effects.
Key data and findings from RECOVER's observational study have
ensured that NIH is now better poised to test currently available
treatments and agents to address symptomatology while simultaneously
continuing efforts to fully understanding the full spectrum of
diagnosis for the pathobiology of PASC--efforts that have not occurred
in research of other post-viral conditions. For example, with knowledge
gained through the observational study and other elements of RECOVER,
potential clinical trial interventions could explore pathways to
determine if there are viral responses that might generate some sort of
reaction (e.g., pro-inflammatory) that can be treated or to determine
if there are other types of disorders producing metabolic aspects that
can be therapeutic targets.
Clinical trials to identify safe and effective treatments as well
as preventive strategies for PASC are a priority for NIH. NIH is
addressing symptoms/symptom clusters and underlying mechanisms of
pathobiology of PASC by establishing a dedicated Clinical Trials Data
Coordinating Center to implement and manage multiple interventions, as
well as issuing a solicitation for well-designed clinical trials
testing a range of interventions. Clinical trial development is being
informed through a consultative process with engagement of patient,
practitioner, and research communities regarding symptoms/symptom
clusters, outcome measures, and interventions. The first trials are
anticipated to be launched by Fall of 2022.
The RECOVER initiative is also leveraging real-world data derived
from the electronic health records (EHRs) of over 60 million adult and
pediatric patients accessible through the National COVID Cohort
Collaborative (N3C), the PEDSnet consortium, and the National Patient-
Centered Clinical Research Network (PCORnet).\1,2,3\ RECOVER electronic
health records (EHR) to better define PASC in all its forms, to
discover and understand factors that influence the likelihood of
developing PASC in adults and children, to understand PASC treatment
strategies as quickly as possible, and to identify high priority
approaches to address PASC in the populations most affected. While this
work is ongoing, the RECOVER EHR studies have recently completed their
initial set of analyses at national scale and are publishing results on
several key clinical and public health issues including: PASC cardiac
complications; \4\ development of new onset diabetes as part of PASC;
impact of COVID-19 vaccination and viral variants on PASC;
manifestations of PASC in children and adolescents; and racial, ethnic,
and socioeconomic disparities in PASC.
---------------------------------------------------------------------------
\1\ https://ncats.nih.gov/n3c.
\2\ https://pedsnet.org/.
\3\ https://pcornet.org/network/.
\4\ https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm.
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The RECOVER pathobiology studies being launched soon will identify
mechanisms underpinning clinical phenotypes and symptomatic
manifestations and understand the pathology in multiple organ/systems
that has led or will lead to clinically significant health problems.
Analyses of clinical data and biospecimens from the longitudinal
studies will contribute to our understanding of the cause(s) of PASC,
help identify biomarkers, enable risk stratification, contribute to the
development of new therapeutic targets, and will help inform the design
of PASC clinical trials.
A systematic and standardized autopsy study at scale is underway
now to comprehensively identify the effects of SARS-CoV-2 infection on
organs/tissues throughout the body for the purpose of understanding the
pathobiology of PASC and informing development of diagnostics, clinical
monitoring, and potential treatment and prevention strategies.
Osteopathic Medicine
Question. Dr. Tabak, Colleges of Osteopathic Medicine educate
nearly a quarter of U.S. physicians, but only compromise a small
portion of NIH grants and are underrepresented on NIH study sections
and advisory boards. How will NIH work with Colleges of Osteopathic
Medicine to increase their representation on NIH panels and through
funding opportunities?
Answer. The National Institutes of Health (NIH) is dedicated to
strengthening and diversifying the biomedical research workforce. This
includes fostering opportunities for physician-scientists with
osteopathic medical degrees, a group of researchers NIH recognizes as
being underrepresented in the biomedical workforce. As part of this
effort, NIH continues to address recommendations described in a 2014
report focused on the physician-scientist workforce from the NIH
Advisory Committee to the Director.\5\ As the report notes and NIH
agrees with, ``findings which lead to advances in practice are driven
largely by the work of investigators with a variety of degrees
[including D.O.s], of whom those with clinical training contribute
essential knowledge and skills.''
---------------------------------------------------------------------------
\5\ acd.od.nih.gov/documents/reports/PSW_Report_ACD_06042014.pdf.
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Physicians with a Doctor of Osteopathic Medicine (D.O.) degree
represent an important component of the medical community. They
straddle the complementary, integrative health, and allopathic medical
communities and have historically been connected to the National Center
for Complementary and Integrative Health (NCCIH), one of NIH's
Institutes and Centers (ICs), through the practice of osteopathic
manipulation. Osteopathic manipulation is a full-body system of hands-
on techniques to alleviate pain, restore function, and promote health
and wellbeing. This promising intervention is of interest to NCCIH, and
the Center makes every effort to ensure that D.O.s have representation
on its advisory council. NCCIH currently has two members with a D.O.
degree on its 18-member council.\6\
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\6\ www.nccih.nih.gov/about/naccih-member-roster.
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NCCIH along with other NIH ICs has specific opportunities for
clinician-scientists, which includes D.O.s, who conduct research across
a wide range of complementary and integrative health approaches.
Examples of such programs include, but are not limited to:
--Mentored Clinical Scientist Research Career Development Awards.\7\
---------------------------------------------------------------------------
\7\ researchtraining.nih.gov/programs/career-development/K08.
---------------------------------------------------------------------------
--K12 career development award program.\8\
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\8\ researchtraining.nih.gov/programs/career-development/k12.
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--Academic Research Enhancement Award (AREA) program.\9\
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\9\ grants.nih.gov/grants/funding/r15.htm.
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Act for ALS
Question. Last year, Congress passed a bill I cosponsored, ACT for
ALS, that establishes a grant program to address neurodegenerative
diseases, and specifically ALS. The fiscal year 2022 Omnibus passed in
March provided $25 million to establish the program. Dr. Tabak, I know
NIH had concerns about this bill when it was passed. Can you discuss
the concerns and the challenges to this research so we can address them
moving forward?
Answer. The National Institutes of Health (NIH) strongly supports
investing in the unique and specific research needs of the Amyotrophic
lateral sclerosis (ALS) community. ALS and other rare and fatal
neurodegenerative diseases inflict immense suffering on people living
with these diseases and their families, and there is an urgent need to
develop effective therapies and cures. NIH is enthusiastic about
partnering with others to catalyze new approaches capable of bringing
us closer to developing effective interventions to prevent, diagnose,
mitigate, treat, or cure ALS.
NIH is supportive of the ACT for ALS provisions that have the main
intent of broadly enhancing research and development for ALS and other
rare neurodegenerative diseases, including the HHS Public-Private
Partnership for Rare Neurodegenerative Diseases, and the U.S. Food and
Drug Administration (FDA) action plan and grant program for research on
ALS and other rare neurodegenerative diseases. NIH has major
capabilities in administering grant programs in ALS research. NIH's
primary concerns with the legislation have been with the grant program
for research utilizing data from expanded access to investigational
therapies for ALS authorized in section 2 of the legislation. NIH's
concerns continue to be that (1) the creation of the expanded access
grant program fails to place appropriate focus on the real and
pernicious challenges impeding the development of effective ALS
therapies, namely, the desperate need for a real understanding of
disease mechanisms to allow for the development of effective
treatments; (2) supplying investigational therapies, especially those
unproven to have tangible improvements for patients, is beyond the NIH
mission to advance our fundamental knowledge to improve health; (3)
programs supplying investigational drugs have the potential to drive
patients away from enrolling in placebo-controlled trials that are
desperately needed to actually produce new and effective treatments for
ALS patients; and (4) few small businesses would qualify for the
program as defined by the statute, thus limiting the diversity of the
investigational drugs that could be in the grant program. The final
amended legislation addressed some of NIH's concerns by requiring
entities to conduct research enrolling patients ineligible for other
ALS clinical trials. However, NIH's principal concerns still hold true,
and we strongly emphasize that investments in mechanistic disease
research and therapy development are critical for the breakthroughs
needed to develop transformative therapies for ALS.
Regarding the research component of the expanded access provision
in the ACT for ALS, we remain concerned that the expanded access data
obtained from persons with ALS on whom there is no research-grade data
preceding an intervention, and for whom there is not a matched control
group (gender, age, time from onset, rapid vs. slow course, etc.) with
which to compare is unlikely to yield valuable scientific information.
Even in instances where some reliable data would be gleaned, the
information is unlikely to be transformative or rapidly accelerate ALS
research. Except for an investigational drug that is so potent that it
stops progression, any other finding would be impossible to ascribe to
anything other than chance. As section 2 of the ACT for ALS Act
specifies that investigational drugs in the expanded access grant
program are confined to those in phase 3 clinical trials, a highly
potent therapy would be first identified in the randomized controlled
phase 3 trial. As of the date of the hearing, NIH has begun
implementing the expanded access grant program. A request for
applications was published on May 12, 2022.\10\
---------------------------------------------------------------------------
\10\ grants.nih.gov/grants/guide/rfa-files/RFA-NS-22-071.html.
---------------------------------------------------------------------------
NIH places a high priority on research that will lead to the
development of interventions for ALS and has increased funding for ALS
research from $52 million in fiscal year (FY) 2016 to $120 million in
fiscal year 2021. This increase is primarily due to the rise in
research on Alzheimer's disease and related dementias, which supports
research on those mechanisms and conditions that cause both dementia
and ALS, rather than reflecting an increase in research on ALS alone.
In addition to a broad array of research projects to understand the
genetic and environmental causes of ALS and to elucidate the cellular
and molecular mechanisms by which the disease progresses, in fall of
2021 NIH funded four exciting projects \11\ through the Accelerating
Leading-edge Science in ALS (ALS2) initiative, part of the NIH Common
Fund's Transformative Research Awards, which aims to dramatically
advance our understanding of what triggers ALS and what drives the
rapid progression of this disease. NIH is also supporting several large
natural history and biomarkers studies to improve our understanding of
the disease process and to identify biomarkers that will predict when
people at risk for ALS might get the disease, which would allow them to
begin treatment early, perhaps even before symptoms appear. NIH-
supported preclinical research projects are testing a range of
therapeutic targets and agents, including gene therapies and small
molecule drugs, in experimental models of ALS, including animals or
cells/tissues, to treat inherited and sporadic forms of ALS. Several
promising industry-funded clinical trials are based upon NIH-supported
basic and preclinical research findings.
---------------------------------------------------------------------------
\11\ www.ninds.nih.gov/news-events/directors-messages/all-
directors-messages/spurring-innovative-research-toward-als-cures-
through-accelerating-leading-edge-science-als-als2.
---------------------------------------------------------------------------
NIH is preparing for the future of ALS research by initiating a
strategic planning process to identify the highest priorities for
research that will lead to the discovery of effective interventions for
the diagnosis, treatment, management, prevention, or cure of ALS. The
process is engaging researchers, clinicians, advocates, people affected
by ALS, multiple NIH institutes, and other Federal agencies, and has
multiple opportunities for the general public to contribute to the
process. Draft priorities will be presented for public comment at a
public workshop on October 26-27, 2022.\12\
---------------------------------------------------------------------------
\12\ www.ninds.nih.gov/about-ninds/strategic-plans-evaluations/
strategic-plans/amyotrophic-lateral-sclerosis-als.
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______
Questions Submitted by Senator Richard C. Shelby
Question. Dr. Tabak, the fiscal year 2023 budget request does not
continue its support for the Undiagnosed Diseases Network as it
graduates from the Common Fund. The University of Alabama at Birmingham
runs the Undiagnosed Diseases Network in partnership with Harvard and
it has been a valuable resource to which to refer challenging cases and
also is a network of strong collaborators to help researchers tackle
those cases. More than that, it is a national resource for Americans
who have an undiagnosed disease or disorder with no other place to
turn.
Why is there not a plan in place to retain the Network and its
clinical sites around the country?
Answer. The Undiagnosed Disease Network (UDN) was always planned
for 10 years--the maximum period of support for Common Fund programs.
In Phase II of the program (starting in 2018), the UDN was tasked with
developing a framework to continue its mission after expiration of
Common Fund support, ensuring sustained clinical utility for decades to
come. For the final year of the program, the National Institutes of
Health (NIH) will provide supplements and extensions to the UDN
extramural clinical sites, Coordinating Center, and some Cores to
ensure that all participants accepted by the end of the ninth year are
evaluated as the program transitions to a larger, self-sustained
network. Some sites have committed to continue enrollment during this
period, and NIH is exploring means to enable other sites to continue to
enroll new patients as well. The intramural Undiagnosed Disease
Program, housed within the NIH Clinical Center and currently supported
as a UDN clinical site, will continue to receive support and oversight
from multiple NIH Institutes and Centers (ICs).
Multiple NIH ICs released a notice of intent to publish a funding
announcement to support a Data Management and Coordinating Center to
provide infrastructure and research support for a new network of
clinical sites. Clinical sites with the appropriate infrastructure,
expertise, and resources needed to conduct the clinical evaluation and
DNA sequencing of participants enrolled at their sites can apply for
designation as a Diagnostic Center of Excellence. Diagnostic Centers of
Excellence will have access to resources of the Data Management and
Coordinating Center.
NIH is committed to the successful transition of UDN and welcomes
the opportunity to work with Congress to identify the best path
forward. NIH's long-term vision is to see an expanded Network continue
to make important scientific discoveries while improving clinical
practice for undiagnosed patients--regardless of geographic location or
socioeconomic status.
______
Questions Submitted by Senator Shelley Moore Capito
Question. I am pleased to be the lead sponsor along with Senator
Reed of the Childhood Cancer STAR Act. As we know, cancer remains the
most common cause of death by disease among children in the United
States. By the age of 50, more than 99 percent of the children who
survived their initial cancer diagnosis will have had a chronic health
problem, and 96 percent have experienced a severe or life-threatening
condition caused by the toxicity of the treatment that initially saved
their life. Thanks to the STAR Act, the NCI has supported new research
into improving the quality of life of childhood cancer survivors.
Could you advise the Committee on how much of the $30 million
Congress has provided for the STAR Act each year has been invested in
this research and how many new research projects you have been able to
support with the STAR Act fund?
Answer. The National Cancer Institute (NCI) appreciates your and
Senator Reed's leadership, and the Subcommittee's continued support for
childhood cancer research, including support for the Childhood Cancer
STAR Act. Each year, the Subcommittee has appropriated $2 million of
the $30 million authorization to support the Centers for Disease
Control and Prevention (CDC) in their implementation of STAR Act
provisions focusing on enhancing CDC cancer registry efforts (Section
102 of the Act). NCI has used the remaining $28 million of STAR Act
funding to support new biobanking research efforts (Section 101) and to
continue to conduct and support survivorship research projects (Section
202), as well as evidence reviews focused on childhood cancer
survivorship (Section 203) in partnership with the Agency for
Healthcare Research and Quality (AHRQ). These initiatives are supported
through a variety of mechanisms, including but not limited to new
research grants. Efforts in each of NCI's three areas are summarized
below.
1. Biobanking Projects:
NCI is committed to making progress for children and adolescents
and young adults (AYAs) with cancer, survivors, and their families, and
biobanking efforts have long been a part of this mission. In accordance
with the goals of the STAR Act, NCI provided supplemental funding to
the Children's Oncology Group (COG) Biobank in 2019 to support
immediate enhancements. NCI subsequently funded six supplemental
projects, which are listed below, starting in 2020 to bolster and
expand the current programs. The supplements included projects to
increase collection of diagnostic, relapse, and autopsy specimens, as
well as specimens from childhood cancer survivors enrolled in NCI's
Childhood Cancer Survivor Study (CCSS). Pediatric cancers are
classified as rare cancers, and these efforts will increase sample
availability to researchers and clinicians in an effort to advance
research and improve patient outcomes, especially for children with the
rarest cancer subtypes.
--Rare Tumor Populations Biobanking (COG): For rare cancers for which
COG does not have open clinical trials, tumor tissue collection
options are limited. This program expanded in fiscal year (FY)
2021 and supports tumor tissue and blood collection for
specific groups of patients for which current tumor tissue
collection is lacking or inadequate, with priority for tumor
types with high risk of treatment failure. This initiative also
collaborates closely with the Childhood Cancer Data Initiative
(CCDI) to analyze tumor tissue to obtain a clinically relevant
molecular profiling through the CCDI Molecular Characterization
Protocol. The data helps this Protocol support characterization
of tumors for rare cancers, with an initial emphasis on Central
Nervous System (CNS) tumors as well as soft tissue sarcomas.
--Tumor Specimens from Patients at Relapse (COG): An important
impediment to understanding mechanisms of treatment failure for
childhood solid tumors is the limited numbers of paired
specimens from both diagnosis and relapse that are available
for researchers to study. Specimens at relapse are critical for
evaluating biological changes between diagnosis and relapse
that can lead to the identification of mechanisms of treatment
failure and to the development of strategies for circumventing
these mechanisms. One area of focus is the collection of
relapse specimens from children with rhabdomyosarcoma.
--Rapid Autopsy Specimen Collection (COG): NCI and COG continue to
work with patient organizations to support rapid autopsy
collection of tumor samples from children and AYAs who have
died of their disease. Foundations and families within the
pediatric brain tumor community have been leaders in such
programs, and we hope to learn from their experiences to expand
this model to other childhood cancers. We are incredibly
grateful to these parents and caregivers, who amidst
unimaginable grief and loss, contribute to future research to
help other families.
--Pediatric MATCH Diagnostic Specimen Collection (COG): This effort
collects diagnostic samples for children and AYAs who have
already submitted samples at relapse through NCI's Pediatric
MATCH Trial and enables molecular characterization to identify
the changes in gene mutations and gene expression that occur
between diagnosis and relapse. This in-depth characterization
aims to inform development of more relevant treatments.
--Biobanking I--Specimen Collection of Subsequent Cancers (CCSS): The
development of subsequent malignant neoplasms (SMN) is
associated with significant morbidity and mortality for
survivors of childhood cancer. The CCSS has prioritized
collection of SMN somatic tissue specimens (tissue blocks,
scrolls, slides) from survivors with confirmed cases of
subsequent malignancies. The results help design treatment
protocols and interventions that will result in an increase in
survival, while minimizing harmful late effects. This research
is also used to develop and expand programs for early detection
and prevention of late effects in children and adolescent
cancer survivors.
--Biobanking II--Specimen Collection to Study Chronic Health
Conditions (CCSS): This project will enhance the CCSS as a
resource for future biologic and genetic evaluations to better
understand the causes of chronic health conditions in survivors
of childhood cancer.
Many of the STAR Act supplement projects are still collecting
samples and have contributed to many new NCI research projects.
Childhood cancer researchers have requested and used biospecimens from
STAR Act funded supplement projects for 11 new research projects, with
10 of these projects supported by NCI (in addition to the STAR Act
investments described here) and one supported by the Cancer Prevention
and Research Institute of Texas. Biospecimens will continue to be
available for researchers in the coming years with continued support.
Along with increasing the number of greatly needed samples, these
projects also address other concerns and barriers to biobanking and
provide opportunities to mitigate these challenges. Through
implementation of the STAR Act biobanking provisions, NCI continues to
support progress towards better understanding pediatric cancers.
Additional details about each of these biobanking projects will be
provided to Senators Capito and Reed, and their colleagues, in the
biobanking report required in Section 101 of the STAR Act, which is
anticipated to be transmitted to Congress in June 2022.
2. Survivorship Research Grants:
NCI also continues to conduct and support childhood and AYA cancer
survivorship research that advances additional goals of the STAR Act.
NCI issued a new request for applications (RFA) in March 2020, titled
``Research to Reduce Morbidity and Improve Care for Pediatric, and
Adolescent and Young Adult (AYA) Cancer Survivors'' (RFA-CA-20-027/
028), which builds upon a previous RFA, ``Improving Outcomes for
Pediatric, Adolescent and Young Adult Cancer Survivors'' (RFA-CA-19-
033), to continue to address survivorship research areas emphasized in
the STAR Act.
NCI funded seven projects in response to RFA-CA-19-033 in fiscal
year 2020, and 10 projects in response to RFA-CA-20-027/028 in fiscal
year 2021. An additional final round of awards is expected to be
finalized in the coming weeks. Commitments for these 5-year awards will
extend to fiscal year 2026, pending availability of appropriations.
Projects supported through the first two rounds of awards in fiscal
year 2020 and fiscal year 2021 are described in more detail in the
tables below.
These efforts aim to improve care and health-related quality of
life for childhood and AYA cancer survivors, through mechanistic,
observational, and intervention research projects that focus on six key
domains: (1) disparities in survivor outcomes; (2) barriers to follow-
up care; (3) impact of familial, socioeconomic, and other environmental
factors on survivor outcomes; (4) indicators for long-term follow-up
needs related to risk for late effects, recurrence, and subsequent
cancers; (5) risk factors and predictors of late/long-term effects of
cancer treatment; and (6) development of targeted interventions to
reduce the burden of cancer for pediatric/AYA survivors.
rrrrrrrrrrrrrrrrrrrrrrrr
RFA-CA-19-033: Tumor Types Late/Long Term
Improving outcomes for Effect(s)
Pediatric, Adolescent,
and Young Adult Cancer
Survivors
rrrrrrrrrrrrrrrrrrrrrrrr
Project Title,
Principal
Investigator,
Institution, Grant
Type
Using Information All Disease and treatment-
Technology to Improve related symptoms
Outcomes for Children
Living with Cancer
\13\
PI: Dr. Jin-Shei Lai
(Northwestern
University at
Chicago), U01
rrrrrrrrrrrrrrrrrrrrrrrr
A Randomized Trial of a All Sedentary behavior
Mobile Health and
Social Media Physical
Activity Intervention
Among AYA Childhood
Cancer Survivors \14\
PI: Dr. Nina Kadan-
Lottick (Yale
University), U01
rrrrrrrrrrrrrrrrrrrrrrrr
Utility of Memantine in Primary brain tumors Cognitive dysfunction
Preventing Cognitive after cranial
Dysfunction in radiotherapy
Children Receiving
Cranial Radiotherapy
\15\
PI: Dr. Nadia Laack
(Mayo Clinic), U01
rrrrrrrrrrrrrrrrrrrrrrrr
A web-based patient- Breast cancer Symptoms, unmet needs,
reported symptom concerns
monitoring and self-
management portal for
AYA breast cancer
survivors \16\
PI: Dr. Ann Partridge
(Dana-Farber), U01
rrrrrrrrrrrrrrrrrrrrrrrr
Telehealth based All Reduced exercise
exercise intervention capacity, impaired
to improve functional physical dysfunction
capacity in survivors
of childhood cancer
with significantly
limited exercise
tolerance \17\
PI: Dr. Kirsten Ness
(St. Jude), U01
rrrrrrrrrrrrrrrrrrrrrrrr
An Interactive All Emotional distress;
Survivorship Program adherence
to Improve Healthcare
Resources [INSPIRE]
for Adolescent and
Young Adult (AYA)
Cancer Survivors \18\
PI: Dr. Karen Syrjala
(Fred Hutchinson), U01
rrrrrrrrrrrrrrrrrrrrrrrr
Implementation of a All Elevated risk of HPV-
Provider-Focused related complications
Intervention for and malignancies
Maximizing HPV Vaccine
Uptake in Young Cancer
Survivors receiving
Follow-Up Care in
Pediatric Oncology
Practices: A Cluster-
Randomized Trial \19\
PI: Dr. Wendy Landier
(University of
Alabama), U01
rrrrrrrrrrrrrrrrrrrrrrrr
RFA-CA-20-027/028: Target Population Topic Area
Research to Reduce
Morbidity and Improve
Care for Pediatric,
and Adolescent and
Young Adult (AYA)
Cancer Survivors
rrrrrrrrrrrrrrrrrrrrrrrr
Project Title,
Principal
Investigator,
Institution, Grant
Type
Predicting and African American, Cardiotoxicity
Preventing doxorubicin-treated
Chemotherapy-Induced childhood cancer
Cardiotoxicity in survivors \20\
African American
Children
PI: Drs. Paul W
Burridge and Yadav
Sapkota (Northwestern
University at
Chicago), R01
rrrrrrrrrrrrrrrrrrrrrrrr
Bridging Information Childhood cancer Follow-up care
Divides and Gaps to survivors and primary
Ensure Survivorship: care providers
The BRIDGES Randomized
Controlled Trial of a
Multilevel
Intervention to
Improve Adherence to
Childhood Cancer
Survivorship \21\
PI: Dr. Nina S Kadan-
Lottick (Yale
University), R01
rrrrrrrrrrrrrrrrrrrrrrrr
Social Genomic Non-Hodgkin's lymphoma Social determinants of
Mechanisms of Health and Hodgkin's lymphoma health
Disparities Among survivors
Adolescent and Young
Adult (AYA) Cancer
Survivors \22\
PI: Dr. Bradley Jay
Zebrack (University of
Michigan at Ann
Arbor), R01
rrrrrrrrrrrrrrrrrrrrrrrr
SALSA--Study of Active Childhood cancer Cardiovascular disease
Lifestyle Activation survivors
\23\
PI: Dr. Eric Jessen
Chow (Fred Hutchinson
Cancer Research
Center), R01
rrrrrrrrrrrrrrrrrrrrrrrr
Individual, Cultural, Asian and Asian Follow-up care
and Area-Based Factors American childhood
Associated with cancer survivors
Survivorship Care
Among Asian/Asian
American Childhood
Cancer Survivors \24\
PI: Drs. Kimberly Ann
Miller and Joel E
Milam (University of
Sothern California),
R01
rrrrrrrrrrrrrrrrrrrrrrrr
Optimization of a Childhood and AYA Quality of life
mHealth Physical cancer survivors
Activity Promotion
Intervention with
Mindful Awareness for
Adolescent and Young
Adult Cancer Survivors
\25\
PI: Drs. Siobhan Marie
Phillips and David
Victorson
(Northwestern
University at
Chicago), R01
rrrrrrrrrrrrrrrrrrrrrrrr
Pilot Test of an Rural AYA cancer Alcohol consumption
mHealth Intervention survivors
for Reducing Alcohol
Use Among Rural
Adolescent and Young
Adult Cancer Survivors
\26\
PI: Drs. Carolyn
Lauckner and Laurie
Mclouth (University of
Kentucky), R21
rrrrrrrrrrrrrrrrrrrrrrrr
Treatment-Specific Childhood cancer Risk for chronic
Genetic Risk Scores survivors conditions
for Late Effects
Prediction in
Childhood, Adolescent,
and Young Adult Cancer
Survivors \27\
PI: Drs. Cindy Im and
Yan Yuan (University
of Alberta), R21
rrrrrrrrrrrrrrrrrrrrrrrr
Remote Monitoring of Anthracycline-exposed, Cardiac dysfunction
Cardiac Function in long-term childhood
Childhood Cancer cancer survivors \28\
Survivors
PI: Dr. Saro Armenian
(Beckman Research
Institute/City of
Hope), R21
rrrrrrrrrrrrrrrrrrrrrrrr
Caregiving for Young Latino AYA cancer Caregiving
Adults with Cancer in survivors and their
Latino Families: families and providers
Understanding
Healthcare Engagement
and Family Wellbeing
\29\
PI: Dr. Michael A Hoyt
(University of
California-Irvine),
R21
------------------------
\13\ reporter.nih.gov/search/owLPDXpgCU-iBbBTXwB1Qg/project-details/
10247641
\14\ reporter.nih.gov/search/WCYrRYv2jUyxTU5KGqHtRA/project-details/
10464453.
\15\ reporter.nih.gov/search/hhFq_KIhjUK_3mrhwe8Izw/project-details/
10020353.
\16\ reporter.nih.gov/search/6iqMWmTbbk2QCUxdJKPfVw/project-details/
10079364.
\17\ reporter.nih.gov/search/vD2lwK9vOkCEXKq0gt1xlA/project-details/
10075046.
\18\ reporter.nih.gov/search/ouCqFYfadUaDvFDHKRpQvQ/project-details/
10080015.
\19\ reporter.nih.gov/search/JL5OOraCfUSRsLG_1qNHJg/project-details/
10076219.
\20\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10275329.
\21\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10274932.
\22\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10272690.
\23\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10285925.
\24\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10275095.
\25\ reporter.nih.gov/search/SzDDxi0b_UWciL8xp_2iEw/project-details/
10278744.
\26\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10273171.
\27\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10273416.
\28\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10274206.
\29\ reporter.nih.gov/search/tuBqAK_RUkKcGDcJFdrNqg/project-details/
10269806.
rrrrrrrrrrrrrrrrrrrrrrrr
3. Childhood Cancer Survivorship Evidence Reviews, with AHRQ:
NCI entered into an Inter-Agency Agreement with AHRQ to support its
work to implement Section 203 of the STAR Act, focused on identifying
best practices in survivorship care, through AHRQ Evidence Reviews on
Childhood Cancer Survivorship. A summary of the progress is provided
below.
4. Disparities and Barriers to Pediatric Cancer Survivorship Care: \30\
---------------------------------------------------------------------------
\30\ effectivehealthcare.ahrq.gov/products/pediatric-cancer-
survivorship/research.
---------------------------------------------------------------------------
This report was posted on the AHRQ website for public comment in
October 2020, with simultaneous peer review. The final report was
published in March 2021. The NCI used the findings of the report to
provide funding through administrative supplements for the ``NCI P30
Cancer Center Support Grants'' to support research to understand and
address organizational factors that contribute to disparities in
outcomes among childhood cancer survivors (supported by NCI in addition
to STAR Act investments). Additionally, this report has already begun
to inform the broader cancer survivorship research community and
survivorship care providers based on dissemination of the review
findings.
5. Models of Care That Include Primary Care for Adult Survivors of
Childhood Cancer: \31\
---------------------------------------------------------------------------
\31\ effectivehealthcare.ahrq.gov/products/childhood-cancer-
survivorship-care/research.
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This report was posted on the AHRQ website in June 2021 for public
comment, with simultaneous peer review. The report was published in
February 2022. NCI and AHRQ are widely disseminating this report to
raise awareness of the role that primary care providers play in the
care of adult survivors of childhood cancers. NCI also plans to use the
findings of this report to evaluate its current grant portfolio, to
identify and assess potential gaps and opportunities for additional
research on this topic.
6. Transitions of Care from Pediatric to Adult Services for Children
with Special Healthcare Needs: \32\
---------------------------------------------------------------------------
\32\ effectivehealthcare.ahrq.gov/products/transitions-care-
pediatric-adult/protocol.
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The systematic review is anticipated to be posted on AHRQ's website
in May of 2022. Similar to the other two reports, AHRQ and NCI expect
to widely disseminate this report to the research community and the
general public once it can be publicly posted to raise awareness of
challenges in transitioning care from pediatric to adult services for
children with special healthcare needs. This report is expected to
serve as a resource for those with interests related to a number of
serious healthcare diseases and conditions including cancer. The NCI
also plans to use the findings of this report to evaluate its current
grant portfolio, to identify and assess potential gaps and
opportunities for additional research on this topic.
______
Questions Submitted by Senator Patrick Leahy
Question. The COVID-19 pandemic has adversely affected clinical
cancer care and profoundly impeded progress in the provision of
essential clinical trials for cancer patients, with rural populations
particularly hard hit. Vermont is currently one of seven states
eligible for the NIH Institutional Development Award (IDeA) that does
not have an NCI-designated facility. Therefore, Vermont has faced
reduced access to cancer clinical trials relative to more urban areas.
Because access to clinical trials directly correlates with improved
quality of cancer care, this reduced access leads to poorer outcomes
for Vermonters diagnosed with or at risk for developing cancer. Many of
these IDeA states that lack NCI-designated centers have medical schools
that would be capable of conducting clinical trials.
How will the NIH better support cancer care and clinician
investigator training in predominately rural IDeA states that lack an
NCI-designated cancer center?
Answer. The National Cancer Institute (NCI) leads, conducts, and
supports cancer research across the nation and is committed to helping
all people live longer, healthier lives. Ensuring equitable access to
cancer care and clinical trials across the country is a top priority
for NCI. This objective was also recently reaffirmed as one of the
goals identified in the next phase of the Cancer MoonshotSM, which
includes NCI efforts to continue to support and enhance enrollment of
underrepresented populations to cancer clinical trials, as well as
cancer control research in persistent poverty areas.\33\ In addition,
NCI and the National Institute of General Medical Sciences (NIGMS) have
recently issued several funding opportunity announcements (FOAs),
discussed in more detail below, focused on promoting cancer research in
rural communities, including communities in Institutional Development
Award (IDeA) states and those that are not home to an NCI-designated
cancer center.
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\33\ www.whitehouse.gov/ostp/news-updates/2022/03/17/fact-sheet-
white-house-announces-initial-steps-for-reignited-cancer-moonshot/.
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NCI-designated cancer centers are a cornerstone of the NCI's cancer
research efforts across the country, and many centers have large
catchment areas that cross state lines. For example, the Dartmouth
Cancer Center includes the entire states of Vermont and New Hampshire
as part of its service area.\34\ Greatly extending the reach of the
NCI-designated cancer centers are several key extramural networks that
support the majority of NCI-supported clinical trials: the National
Clinical Trials Network (NCTN), the Experimental Therapeutics Clinical
Trials Network (ETCTN), and the NCI Community Oncology Research Program
(NCORP). The NCTN primarily conducts later-phase cancer treatment and
imaging trials, while ETCTN conducts early phase cancer treatment
trials. Research groups within these networks hold annual meeting
sessions on topics related to underrepresented populations, and each of
these groups has a patient advocate committee to provide input on
developing and conducting trials. The ETCTN also recently launched the
Create Access to Targeted Cancer Therapy for Underserved Populations
(CATCH-UP.2020) program to enhance access via clinical trials to
targeted cancer therapy for minority/underserved populations.\35\
---------------------------------------------------------------------------
\34\ gis.cancer.gov/ncicatchment/.
\35\ ctep.cancer.gov/initiativesPrograms/etctn_catch-up2020.htm.
---------------------------------------------------------------------------
The NCORP includes 25 states with large rural populations \36\ and
expands the reach of the NCTN, bringing cancer research to people in
their own communities. NCORP provides infrastructure for conducting
studies on cancer control and prevention, cancer care delivery
research, and screening, treatment, and quality of life evaluations
embedded in treatment trials. The NCORP includes seven research bases
and 46 community sites across the United States, including 14 minority/
underserved community sites, and this locally based infrastructure
includes approximately 1,000 component and subcomponent sites (e.g.,
hospitals, cancer centers, oncology clinics) through which patients can
enroll in NCTN and NCORP clinical trials.
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\36\ ncorp.cancer.gov/news/2019-08-19.html.
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Even in IDeA states without NCI-designated cancer centers or NCORP
grantees (such as Vermont, Rhode Island and West Virginia), NCI has
active trial sites reaching rural patients. These sites are not
required to have an NCORP grant or be associated with a designated
cancer center to become a ``member site'' for an NCTN/NCORP group. Many
academic sites are members even if they are not a designated cancer
center, and community sites are eligible to be full members. These full
member sites also have affiliated sites throughout the state or region
where patients can be enrolled. In Vermont, for example, there are
approximately 55 NCI-supported trials open to patients with a treatment
site within the state,\37\ and more than 230 Vermont patients enrolled
in either NCORP or NTCN trials over the past 5 years. The top
enrollment site was the University of Vermont Medical Center/College of
Medicine in Burlington.
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\37\ clinicaltrials.gov/ct2/
results?cond=cancer&term=&cntry=US&state=US%3AVT&city=&dist=
&Search=Search&recrs=a&type=Intr&fund=0.
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Clinicians from these NCTN/NCORP member sites can fully participate
in the NCTN/NCORP groups, contribute to scientific development, and
develop expertise in clinical investigations. Dozens of these
investigators enrolled patients to NCTN and NCORP trials over the past
5 years, including more than 30 investigators with enrollments in
Vermont and more than 60 investigators with enrollments in West
Virginia. Investigator involvement in these NCI-sponsored programs
provides critical opportunities for rural patients and produces
valuable research findings. For example, Dr. Robert Ward of Rhode
Island Hospital is a co-author on research showing that improved
screening methods for women with dense breasts are needed because of
their increased risk of breast cancer and of failed early diagnosis by
screening mammography,\38\ work that was funded by an NCORP breast
cancer screening study.
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\38\ doi.org/10.1001/jama.2020.0572.
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NIGMS-supported research is also benefitting cancer patients in
rural communities through IDeA Networks for Clinical and Translational
Research (IDeA-CTR),\39\ such as the Northern New England Clinical and
Translational Research (NNE-CTR) Network,\40\ which includes
participating and collaborating healthcare, educational and research
institutions in Maine, Vermont, and New Hampshire. The IDeA-CTR awards
support state-wide or multi-state regional networks of clinical and
translational research, which build research infrastructure, develop
investigators, and support research activities that address health
conditions prevalent in populations of IDeA states. Since cancer
affects individuals nationwide as well as in IDeA states, all 12 IDeA-
CTRs invest in cancer research by supporting pilot research projects.
These projects include mechanistic, translational, clinical, and
prevention studies.
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\39\ grants.nih.gov/grants/guide/pa-files/PAR-14-303.html.
\40\ reporter.nih.gov/project-details/10205083.
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Recognizing that more research is needed to identify the best
strategies for providing care to rural populations, NCI and NIGMS are
currently providing funding for projects selected through three
targeted FOAs:
1. Improving the Reach and Quality of Care in Rural Populations:
\41\ This funding opportunity focused on strategies for delivering and
improving the quality of cancer care in rural areas among low-income
and/or underserved populations. Over the two funding rounds, nine
research projects were funded, including research focusing on financial
toxicity and navigation, survivorship, telehealth, community-based
patient navigation for cancer screening, palliative care, and symptom
management.
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\41\ grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-064.html.
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2. Social and Behavioral Intervention Research to Address
Modifiable Risk Factors for Cancer in Rural Populations: \42\ This
funding opportunity focused on research to develop, adapt, and test
individual-, community- or multilevel interventions to address
modifiable risk factors for cancer in rural populations. Three research
projects have been funded after the first round, focusing on tobacco
control in rural American Indian households, increasing physical
activity, and utilizing telehealth options for treatment of obesity.
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\42\ grants.nih.gov/grants/guide/rfa-files/RFA-CA-20-051.html.
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3. IDeA Clinical Research Resource Center:\43\ Increasing the
number of clinical trials and complex observational studies in IDeA
states is a pressing need that requires continued efforts to strengthen
clinical research capacity and maximize the use of existing resources
through innovative approaches. The IDeA Clinical Research Resource
Center (I-CRRC) funding opportunity aims to 1) strengthen communication
and develop collaborations between health research institutions in IDeA
states and clinical trial sponsors; and 2) develop clinical research
coordinators with the knowledge and skills to manage clinical trials
and complex observational studies.
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\43\ grants.nih.gov/grants/guide/pa-files/PAR-22-150.html.
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NCI is committed to serving patients across the country, including
those in rural areas who face disparities in incidence and mortality
rates that can be attributed in part to barriers in accessing health
services. NCI will continue to fund research and support efforts to
improve access and better address the unique needs of these
communities.
______
Questions Submitted to Dr. Anthony Fauci
Questions Submitted by Senator Roy Blunt
Question. Dr. Fauci, there has been limited evidence that antiviral
therapies to treat COVID-19, like Paxlovid, may relieve symptoms from
long COVID. The theory is that long COVID may be caused by the virus
persisting in parts of the body for months. What are your thoughts on
this and what work is NIH doing in this space to determine if
therapeutic treatments may relieve or even cure long COVID?
Answer. While most people recover quickly and fully from infection
with SARS-CoV-2, some experience ongoing or new symptoms or other
health effects after the acute infection has resolved, referred to as
post-acute sequelae of SARS-CoV-2 infection (PASC). An understanding of
the underlying mechanisms of PASC will be crucial as we work to
identify and test therapeutics. The National Institutes of Health (NIH)
supports research to inform estimates of PASC prevalence as well as to
understand the pathogenic mechanisms underlying the wide range of
observed symptoms and the risk factors for developing PASC. This
includes the examination of whether particular symptoms associated with
PASC may be caused by the persistence of virus or viral particles in
parts of the body. NIH has launched the Researching COVID to Enhance
Recovery (RECOVER) Initiative,\44\ a trans-NIH effort that aims to
understand, prevent, and treat the post-acute sequelae of SARS-CoV-2
infection. The NIH RECOVER Initiative complements ongoing studies
supported by the National Institute of Allergy and Infectious Diseases
(NIAID) to better understand the various post-acute manifestations of
COVID-19 and will engage more than 100 researchers at more than 30
institutions to build a diverse national study population and support
large-scale studies in this critical area, as well as clinical trials
of potential treatments for PASC. The knowledge gained through these
collective efforts will help inform the identification of effective
treatments for PASC, including those evaluated through RECOVER.
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\44\ https://recovercovid.org/.
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Question. How many clinical trials are funded by NIH that are
testing treatments for long COVID?
Answer. The highly diverse symptomology of PASC observed in
patients across the lifespan strongly suggests that PASC, rather than
being a singular condition, is likely multiple clinical conditions that
vary across the lifespan and demographic groups. This has important
implications for the research approach to PASC--namely, multiple
diverse diagnostic, treatment, and prevention strategies will be needed
for the range of PASC conditions and patient populations. This will
require an appropriately diverse portfolio of sufficiently scaled and
powered clinical studies to generate high-quality data that can inform
clinical and public health practices.
Toward this end, the NIH RECOVER Initiative, described above, is
preparing to launch clinical trials to identify safe and effective
treatments to enhance recovery of patients with persistent symptoms and
identify interventions which, if initiated early, could prevent end-
organ and systems damage and other sequelae. RECOVER has established a
dedicated Clinical Trials Data Coordinating Center to implement and
manage multiple interventions addressing symptoms/symptom clusters and
underlying mechanisms of pathobiology of PASC. RECOVER also issued a
solicitation for clinical trial proposals testing a range of
interventions to address symptoms/symptom clusters and underlying
mechanisms of pathobiology. RECOVER will test a variety of therapeutic
strategies. The first trials are anticipated to be launched by the Fall
of 2022. As understanding of underlying mechanisms leading to post-
acute sequelae of SARS-CoV-2 infection improves through the RECOVER and
other research activities, additional candidate interventions will be
evaluated and selected for testing.
Question. How many of these trials are beyond a phase I trial?
Answer. The RECOVER Initiative plans to launch Phase IIb-III PASC
clinical trials that leverage fit-for-purpose design strategies to
maximize rigor, efficiency, and flexibility. Initial trials will likely
focus on interventions that have shown promise in other recovery
contexts and on current hypotheses regarding pathogenesis. As our
understanding of underlying mechanisms leading to PASC improves through
RECOVER and other research activities, additional candidate
interventions will be evaluated and selected for testing.
Question. There have been recent reports of individuals taking
Paxlovid, and then their symptoms return after their treatment is
complete. Do you know why that may happen?
Answer. NIH scientists, in collaboration with the Centers for
Disease Control and Prevention (CDC) and the U.S. Food and Drug
Administration (FDA), are looking into possible ways to better
understand the phenomenon of COVID-19 rebound after Paxlovid treatment.
NIH currently does not have studies underway, but the agency is
actively discussing potential studies to learn more about who this is
affecting, how often it is occurring, and if a longer regimen would be
more effective in certain cases. For additional information on what is
currently known about the case reports of patients developing symptoms
again after completing a course of Paxlovid, please refer to ``FDA
Updates on Paxlovid for Health Care Providers'' \45\ and the ``CDC
Health Alert Network Health Advisory on COVID-19 Rebound After Paxlovid
Treatment''.\46\
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\45\ http://www.fda.gov/drugs/news-events-human-drugs/fda-updates-
paxlovid-health-care-providers.
\46\ http://www.emergency.cdc.gov/han/2022/han00467.asp.
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Question. How much of the $1.15 billion appropriated has been
obligated?
How much of this funding has been obligated or committed for
clinical trials?
Answer. In December 2020, Congress provided $1.15 billion in NIH
funding, available for obligation over 4 years, to support research
into the long-term effects of SARS-CoV-2. With this funding, NIH
launched Researching COVID to Enhance Recovery (RECOVER) in February
2021. As of May 17, 2022, $674.5 million has been obligated. Of that
amount, $137 million has been obligated to the launch of clinical
trials, including the establishment of the Clinical Trials Data
Coordinating Center.
The remaining funding will be distributed during the final 2 years
of the RECOVER Initiative to support outyear activities of these
ongoing clinical research studies, including (but not limited to):
longitudinal clinical follow up of adult and pediatric patients
enrolled in the cohort studies, autopsy studies, central research
services, pathobiology research, mobile health platform, data
repositories, clinical biospecimen collection and repositories,
Electronic Health Record/Other Real World Data studies, as well as
support for NIH management of the RECOVER initiative through
specialized administrative and technical expertise.
Question. What work is NIH doing related to long COVID to address
the most burdensome of symptoms or the most severe cases?
Answer. The National Institutes of Health (NIH) has designed and
launched Researching COVID to Enhance Recovery (RECOVER),\47\ a major
research effort of national scale to improve understanding of Post-
Acute Sequelae of SARS-CoV-2 infection (PASC), including Long COVID,
and to inform the development of safe and effective diagnostic,
treatment, and preventive strategies. RECOVER includes a longitudinal
study designed to have inclusive and diverse participant enrollment
that is representative not only of the U.S. population generally, but
of the population of sub-groups most severely affected by coronavirus
disease 2019 (COVID-19). RECOVER also includes electronic health
records (EHR) studies of over 60 million patient records; a systematic
and standardized autopsy study at scale; a mobile health platform to
enable broader and deeper engagement of participants; pathobiology and
mechanistic studies and development of animal models; and clinical
trials. Importantly, RECOVER is patient-centered and engages patients
at every level of the Initiative, from local studies to protocol
development, to overall governance of the Initiative.
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\47\ recovercovid.org.
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NIH RECOVER is preparing to launch clinical trials to test
treatment and preventive strategies for Long COVID. This includes
creating a portfolio of prioritized interventions that:
--Address symptoms/symptom clusters of high priority to patients
--Will test a broad range of interventions
--Address current nascent hypotheses regarding the pathogenesis of
Long COVID
--Have sufficient scientific rationale, appropriate safety profiles,
technical merit, and feasibility
--Would be available/accessible to most patients
--Are ready to launch in the short term
To identify which Long COVID symptoms have the highest impact on
patients' quality of life, RECOVER is taking a broad consultative
approach with engagement of patient, practitioner, and research
communities. For example, both patient participants in the RECOVER
longitudinal cohort studies and a national sample (non-RECOVER) of
patients are periodically surveyed regarding their symptoms and the
burden posed by them; and interviews and focus groups with highly
affected communities and the RECOVER National Community Engagement
Group and patient representatives are periodically conducted for in-
depth insights into patient perceptions of the burden of Long COVID
symptoms. The input from these engagement activities is informing
RECOVER clinical trial design, including the selection of
interventions, to ensure that RECOVER clinical trials address the most
burdensome symptoms of Long COVID.
______
Questions Submitted to Dr. Gary Gibbons
Questions Submitted to Patty Murray
Question. Our country has lost over a million people to COVID-19
and countless more have been infected by this virus. And people of
color have faced the worst of this crisis. Studies show that people of
color are more likely to be hospitalized for COVID, and while some
recover quickly and completely, others have persistent symptoms that
linger for months. That's why, in December 2020, we appropriated more
than $1 billion in supplemental funding for NIH to study long-COVID.
What updates can you share about NIH's RECOVER Initiative and what
we have learned about long COVID and how it impacts different
communities?
What are the challenges you're facing in terms of recruitment for
RECOVER's clinical trials, and how is NIH ensuring that they have
diverse representation?
Answer. The National Institutes of Health (NIH) launched the
Researching COVID to Enhance Recovery (RECOVER) initiative to better
understand and ultimately to prevent and treat the broad array of post-
acute symptoms of SARS-CoV-2 (PASC), commonly called Long COVID. At the
center of RECOVER is a longitudinal observational study that is
currently recruiting adults and children from other ongoing studies of
COVID, Long COVID clinics, and other cohorts--many of which have a
history of including people from communities disproportionately
burdened by disease.
The RECOVER research initiative is meant to significantly expand
both our knowledge about the full clinical spectrum of symptoms, long
term outcomes, and underlying biology of Long COVID, as well as our
ability to develop safe and effective therapeutic interventions. It
funds multi-disciplinary biomedical, clinical, and epidemiological
studies, many focused on untangling the complex social and biological
factors that cause higher rates of hospitalization and Long COVID in
communities of color.
RECOVER studies highlight diverse participation and community
engagement, and include clinical trials, clinical studies that leverage
cohort data and specimens, a patient registry, pathobiology studies, a
mobile health platform, and electronic health record (EHR) studies.
Clinical cohort institutions were selected for RECOVER studies that
have a proven track record in reaching communities hardest hit by the
pandemic. For example, RECOVER includes the Institutional Development
Award (IDeA) clinical research network, which supports research in
states that historically have had low levels of NIH funding. Their
clinical coordinating center is one of the main hubs for the adult
cohort study. In addition, a Research Centers in Minority Institutions
(RCMI) program awardee is also serving as a hub for the study.
As of May 2022, NIH has enrolled more than 5,000 people and is
close to RECOVER's target recruitment of 6,000. Participants are
undergoing testing at 46 sites in 23 states, along with the District of
Columbia and Puerto Rico. Twenty-seven percent of enrollees live in
federally designated medically underserved areas. Thirty-six additional
sites will come online before the end of 2022. The completion dates for
reaching target enrollment are January 2023 for adults and May 2023 for
children.
Other research efforts are helping to increase understanding of
Long COVID. For example, a recent study published in The Lancet Digital
Health,\48\ describes how researchers used Artificial Intelligence (AI)
technology to comb through an EHR database of more than 13 million
people to identify characteristics of people with Long COVID and those
likely to develop it.
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\48\ www.thelancet.com/journals/landig/article/PIIS2589-
7500(22)00048-6/fulltext.
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While recruitment into the RECOVER longitudinal observational study
is progressing steadily, researchers are facing challenges. Strong
competition for people with biomedical research skills has hindered
core and site hiring and led to delays in opening local sites and study
implementation. The enrollment of study participants--including those
who are currently infected with COVID-19, those with Long COVID
symptoms, and those who were previously infected but show no Long COVID
symptoms (to act as control cases)--is still challenging. Participating
in studies, which may require taking time off from work, is an economic
barrier. The recent decline in the number of cases of acute SARS-CoV-2
infection, milder symptoms associated with Omicron variants that make
people less likely to seek medical attention, and the rapid expansion
of home testing makes it difficult to identify and recruit acute cases.
In addition, the extremely high transmissibility rates of recent
variants means that many people have been re-infected, which reduces
the ability to find people who have never been infected.
Increasing enrollment rates in communities disproportionately
affected by SARS-CoV-2 infection is a critical goal for RECOVER; NIH is
therefore monitoring the diversity of enrollment closely. One of the
challenges is limited awareness in some communities about Long COVID.
Another is establishing trust among people with a history of mistrust
in the biomedical research establishment and the Federal Government.
This impedes RECOVER's ability to establish sufficient enrollment in
clinical studies that produce enough high-quality data to provide the
evidence base necessary to guide clinical practice and public health
policy.
The NIH Community Engagement Alliance (CEAL) Against COVID-19
Disparities initiative was launched to establish a research approach to
ensure the participation of black and brown communities in vaccine
research trials that were then underway.\49\ CEAL now bolsters RECOVER
recruitment by working with research teams in 21 locations across the
country to address misinformation, foster trust in science and
research, and ensure inclusive participation in NIH research.
Strategies include local media and social media outreach, search engine
optimization (SEO) tactics, local community outreach and education, and
using SARS-CoV-2 testing programs and point-of-care settings as
recruitment platforms. Through trusted messengers in communities hit
hardest by the pandemic, CEAL and its community partners are helping
increase diversity in Long COVID research.
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\49\ covid19community.nih.gov/.
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Question. Many patients with long-COVID have been diagnosed with a
blood circulation disorder known as postural orthostatic tachycardia
syndrome, or POTS. Symptoms associated with POTS include
lightheadedness, fainting and an uncomfortable, rapid increase in
heartbeat.
Has NIH determined the rough proportion of long-COVID patients
whose symptoms include POTS?
Answer. Dysautonomia refers to a disorder of autonomic nervous
system function. The autonomic nervous system controls many of the
unconscious and involuntary bodily processes such as heart rate, blood
pressure, and breathing. Postural orthostatic tachycardia syndrome
(POTS) is a relatively common dysautonomia in which moving to an
upright position can trigger an excessive increase in heart rate
(tachycardia) and other symptoms such as light-headedness, shortness of
breath, chest pain, and palpitations. Other common symptoms not
necessarily linked to posture include headache, fatigue, exercise
intolerance, and impaired sleep, digestion, and concentration. While
the cause of POTS is unknown, low blood volume, dysregulation of the
autonomic nervous system, autoimmunity, and viral infection may all
play a role, each perhaps leading to distinct subtypes of POTS. It is
likely that POTS has multiple underlying mechanisms resulting in
subtypes of POTS that need to be identified and characterized.
Symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC)
may overlap with those experienced by persons suffering with POTS/
dysautonomia. Research on the biological causes of PASC and potential
treatments pose a unique opportunity to possibly discover the key
pathophysiology underlying several disorders suspected to be the
sequelae of a viral illness in a significant subset of those affected,
such as POTS/dysautonomia and myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS).
The Researching COVID to Enhance Recovery (RECOVER) \50\ Initiative
seeks to better understand, treat, and prevent PASC, including Long
COVID, and to understand how SARS-CoV-2 can lead to long-lasting and
widespread effects such as fatigue, decline in some cognitive
abilities, pain, sleep disorders, and dysautonomia, among others.
RECOVER is a patient-centered study of national scale with diverse
participation and community engagement. RECOVER has multiple scientific
aims, including to understand the clinical spectrum and the biology
underlying recovery over time, and to define distinct sub-phenotypes of
Long COVID. It includes multiple sub-studies: longitudinal
observational clinical cohort studies with thousands of diverse
participants across the lifespan, ancillary clinical studies leveraging
the cohort data and specimens, pathobiology studies, analyses of
electronic health records, and clinical trials. We expect RECOVER
studies will advance understanding of other conditions believed to be
triggered by infection, which will include COVID-19 related cases of
POTS/dysautonomia and ME/CFS. We also expect that RECOVER studies will
reveal the proportion of Long COVID patients that meet the criteria for
POTS/dysautonomia and ME/CFS. RECOVER study teams and oversight bodies
include experts in those conditions.
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\50\ recovercovid.org/.
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What work is NIH supporting to understand the underlying causes of
POTS?
Answer. The National Institutes of Health (NIH) has supported a
wide range of POTS-related grants and currently funds research
examining the autoimmune basis of POTS and the autonomic
pathophysiology of POTS. In addition, NIH intramural researchers are
investigating possible associations between PASC and POTS/dysautonomia
\51\ through comprehensive testing of the extended autonomic system in
patients experiencing PASC.
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\51\ https://reporter.nih.gov/project-details/10491027.
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At the direction of the Senate Appropriations Committee, the
National Institute of Neurological Disorders and Stroke (NINDS) and the
National Heart, Lung and Blood Institute (NHLB), with participation by
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), jointly convened a workshop in July 2019 to
discuss the state of the science and gaps in the current understanding
of POTS. NINDS and NHLBI prepared and submitted a Report to Congress
\52\ based on workshop discussions between leading experts in POTS
research and care, officials from the three sponsoring Institutes, and
patient advocates.\53\
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\52\ https://www.nhlbi.nih.gov/sites/default/files/media/docs/
NIH%20RTC%20on%20POTS_Final.signed.pdf.
\53\ chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://
www.nhlbi.nih.gov/sites/default/files/media/docs/
NIH%20RTC%20on%20POTS_Final.signed.pdf.
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In addition, in April 2021, NHLBI posted an article \54\ about
research in this field, and NINDS and NHLBI issued a Notice of Special
Interest,\55\ ``Stimulate Research on the Diagnosis, Treatment, and
Mechanistic Understanding of Postural Orthostatic Tachycardia Syndrome
(POTS),'' to encourage researchers to submit proposals designed to
answer fundamental questions about POTS.\56,57\ The grant applications
submitted in response to the Notice are currently under review. , which
evaluates the scientific and technical merit of research applications.
NIH peer review process, which evaluates the scientific and technical
merit of research applications.
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\54\ https://www.nhlbi.nih.gov/news/2021/decoding-mysteries-
postural-orthostatic-tachycardia-syndrome.
\55\ https://grants.nih.gov/grants/guide/notice-files/NOT-HL-21-
008.html.
\56\ https://www.nhlbi.nih.gov/news/2021/decoding-mysteries-
postural-orthostatic-tachycardia-syndrome.
\57\ https://grants.nih.gov/grants/guide/notice-files/NOT-HL-21-
008.html.
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In addition, NHLBI is leading an NIH-wide workshop on sex/gender-
specific COVID-19 outcomes on June 16-17, 2022. The workshop will
include a presentation and discussion of autonomic hemodynamic
disorders, including POTS, in PASC and the need for better
understanding of the underlying pathophysiology and development of
specific treatment approaches. NIH continues to encourage investigator-
initiated research grant applications on POTS.
______
Questions Submitted by Senator Shelley Moore Capito
Question. Dr. Gibbons, I have a question about pulmonary fibrosis,
or PF, a complex and deadly lung disease that affects over 250,000
people in the U.S. I am especially concerned about this disease because
we have a lot of coal miners in West Virginia, and workers who are
exposed to coal dust and silica are at higher risk of developing PF.
Diagnosing this disease is complex, and by many estimates often takes
over 2 years. In far too many cases, patients already have advanced PF
by the time they receive a diagnosis.
What research is the NHLBI currently funding to address the serious
problem of late diagnosis in PF?
Answer. Currently, Pulmonary Fibrosis (PF) has no cure, and for
some forms of PF, such as Idiopathic Pulmonary Fibrosis (IPF), median
survival is 3-5 years from diagnosis. Some studies show an association
between coal and silica dust and the development of PF.
Current efforts by the National Heart, Lung, and Blood Institute
(NHLBI) to address PF include the Institute's Prospective Treatment
Efficacy in IPF using genotype for N-acetylcysteine (NAC) Selection
(PRECISIONS) study, a five-year study aiming to enroll 200 IPF
patients. PRECISIONS will use genetic testing to identify patients
likely to respond to the antioxidant NAC. The first PRECISIONS clinical
trial will explore the effectiveness of precision medicine for IPF.
NHLBI recently funded a cohort of currently unaffected but at-risk
individuals who have more than two close family members with PF, which
could demonstrate how genetics and family exposure could affect risk
disease risk.
The Lung Health Cohort, in partnership with the American Lung
Association, follows 4,000 healthy millennials (aged 25-35) to identify
early risk factors (e.g., lifetime air pollution, potentially noxious
inhalation exposures) and signs of lung disease, including IPF, to
allow earlier and effective intervention. In 2021, NHLBI-funded
researchers identified gene expression signatures in the blood of PF
patients. This research may reveal new therapeutic targets and help
monitor and predict disease course.
NHLBI is supporting collaborative projects to establish a set of
model systems that reproduce essential IPF disease-defining features to
advance understanding of the IPF pathogen from onset through disease
progression. These projects will also provide a platform for
identifying and testing novel treatment therapies. By developing
several model systems in parallel, scientists could identify common
fibrosis pathways.
______
Questions Submitted to Dr. Joshua Gordon
Questions Submitted by Senator Patty Murray
Question. We understand NIMH is working to eliminate disparities in
youth mental health by the year 2030.
What specific areas of research are needed in order for NIMH to
meet this ambitious goal?
Answer. As detailed in the September 2021 National Institute of
Mental Health (NIMH) Report to Congress ``Addressing Youth Mental
Health Disparities,'' NIMH is prioritizing research to address and
reduce mental health disparities among underserved and underrepresented
youth by 2031. To meet this goal, NIMH will encourage a full and
diverse range of research--including basic science, translational
science, and services and implementation research--focused on
addressing the needs of youth across race, ethnicity, culture,
language, gender identity, sexual orientation, geography, and social
determinants of health (e.g., education, economic stability, quality of
housing, access to healthcare). These research efforts will aim to
identify ways to decrease risk, increase resilience and protective
factors, improve access to and utilization of high-quality evidence-
based care, and improve outcomes of treatment and services among
populations negatively impacted by mental health disparities.
NIMH previously published information about the research needs that
guide the activities of NIMH Divisions, Offices, and Teams that support
mental health disparities research across the lifespan.\58\
Additionally, in December 2021, NIMH, the National Institute on
Minority Health and Health Disparities, and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) hosted
an expert conference to further inform research efforts specifically on
youth mental health disparities. This conference included a diverse
group of expert panelists to assess the state of the science and the
short- and longer-term research priorities related to improving mental
health treatment, services, and outcomes for youth and adolescents from
communities that experience health and related disparities.\59\
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\58\ www.nimh.nih.gov/about/organization/od/odwd/nimhs-approach-to-
mental-health-disparities-research.
\59\ www.nimh.nih.gov/news/events/2021/2021-youth-mental-health-
disparities-conference-identifying-opportunities-and-priorities-in-
youth-mental-health-disparities-research-summary.
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Specific areas of research that NIMH aims to support include:
1. Understanding structural social determinants of mental health
(e.g., housing instability, family income, community resources,
neighborhood characteristics, work or school environments, and
structural racism), how they can be modified, and how they drive risk
of, resilience to, and protection from the development of mental
illnesses.
2. Identifying and understanding contextualizing factors, including
environmental and historical factors, their impact on biology, emotion,
cognition, and behavior, and how they mediate mental health
disparities.
3. Assessing how local, state, and Federal policies, laws, and
regulations impact social determinants of mental health, mental health
service delivery, and outcomes among youth from populations impacted by
mental health disparities.
4. Characterizing variation in biological and genomic processes
within and among diverse populations historically underrepresented in
genetics research.
5. Conducting longitudinal studies and other research focused on
understanding and measuring how childhood experiences confer resilience
to or risk for mental illnesses and suicidal thoughts and behaviors in
youth from populations impacted by mental health disparities.
6. Improving the specificity of biomarkers and the accuracy of
culturally appropriate diagnostic assessments (including risk
calculators) for youth from populations impacted by mental health
disparities.
7. Developing and validating culturally appropriate preventive
interventions, including systems-level approaches (e.g., in classrooms,
schools, communities) for youth and parents from populations impacted
by mental health disparities.
8. Optimizing existing evidence-based approaches to minimize bias
in diagnosis and treatment, and to improve continuity of care and
mental health outcomes for youth from populations impacted by mental
health disparities.
9. Addressing co-occurring mental illnesses in youth with
intellectual and developmental disabilities, including youth with
intersectionality with other high-risk groups.
10. Improving the implementation and availability of mental health
prevention and treatment interventions and services, as well as
programs to support youth and family functioning, within youth-serving
institutions (e.g., educational settings, community-based after-school
programs, faith-based programs, child welfare programs, juvenile
justice settings).
11. Using innovative assessment and analytic methods to examine
sub-populations and low base-rate behaviors (e.g., death by suicide)
and to address complex, multi-modal datasets.
12. Developing, testing, and implementing prevention and treatment
interventions that are relevant to communities impacted by health
disparities across a broad range of ages (e.g., infancy through young
adulthood).
13. Engaging collaborative teams that include community partners to
ensure that the outcomes and interpretation of research reflect the
priorities of the population participating in the research.
14. Developing targeted interventions by examining risk and
resilience within populations impacted by youth mental health
disparities.
______
Questions Submitted to Dr. Richard Hodes
Questions Submitted by Senator Roy Blunt
Aduhelm Decision
Question. Dr. Hodes, I've been watching with interest, as I suspect
you have as well, the decisions FDA and CMS have made regarding the new
Alzheimer's treatment, Aduhelm. What are your thoughts about CMS'
decision to require only patients in a clinical trial to receive the
first approved Alzheimer's drug in more than a decade? And how does
that decision affect other NIH Alzheimer's clinical trials?
Answer. The National Institutes of Health (NIH) notes that the
decisions issued by the U.S. Food and Drug Administration (FDA) and
Centers for Medicare and Medicaid Services (CMS) are regulatory
decisions, and NIH defers to these agencies on such matters. To date,
the impact of the aducanumab (the generic name for Aduhelm) coverage
determination on NIH clinical trials has been minimal. NIH will
continue to press forward with its robust and diverse research
portfolio in the area of therapy development, building on the
advancements we have achieved thus far. We will continue to evolve our
understanding about Alzheimer's and to develop more ways to detect,
treat, and prevent this disease.
Question. Perhaps what is most concerning about the decision CMS
made on Aduhelm is that it impacts not only this specific treatment,
but all other monoclonal antibody treatments coming down the pike. Can
you address what this CMS decision means for the future of NIH's
clinical trials process for new Alzheimer's treatments?
Answer. NIH notes that the decisions issued by FDA and CMS are
regulatory decisions, and NIH defers to these agencies on such matters.
These decisions underscore the need to further advance our knowledge
and support a broad range of therapies for Alzheimer's and related
dementias. In fact, nearly three-quarters of National Institute on
Aging (NIA)-funded Alzheimer's and related dementias drug trials in
early phases (phase I or phase II) are for targets other than amyloid
proteins. NIH will continue to advance its robust and diverse research
portfolio in therapy development, building further on the significant
achievements thus far to effectively prevent, detect, and treat these
devastating diseases.
Question. Dr. Hodes, I know you had initial concerns about how CMS'
decision may pull patients away from other NIH clinical trials and
toward an Aduhelm trial instead, simply so they could have access to
the new drug. Has that fear been realized and how have you worked to
combat it?
Answer. These concerns have not been realized. To date, the impact
of the aducanumab coverage determination on NIH clinical trials has
been minimal.
Overactive Bladder
Question. Dr. Hodes, overactive bladder affects more than 38
million Americans, and is more common with aging and in women. Recent
studies on anticholinergic medications, which are commonly prescribed
drugs to treat overactive bladder, have shown that these medications
have a negative impact on cognition and may lead to the development of
Alzheimer's disease and related dementia. Given the potential adverse
impact on the nation's elderly that will only increase as our
population ages, is NIA studying these medications or working
collaboratively with other Institutes to determine the safety and
efficacy of anticholinergic medications, and any association they may
have with cognitive decline and Alzheimer's disease and related
dementia?
Answer. Overactive bladder occurs when the bladder is triggered to
empty at the wrong time, leading to a sudden urge to urinate that a
person may have difficulty suppressing. The symptoms of overactive
bladder include urinary frequency, urinary urgency, and urge
incontinence.
The National Institute on Aging (NIA) supports studies on a range
of issues related to the causes, prevention, and treatment of
overactive bladder. This includes research on the safety of long-term
use of anticholinergic medications commonly prescribed to treat
overactive bladder and the associated risk of cognitive impairment and
dementia. For example, NIA is supporting a clinical trial testing
whether discontinuing use of anticholinergics improves cognition and
lowers the risk of Alzheimer's disease and related dementias.\60\ NIA
is also funding a clinical trial to test a mobile app that integrates a
personalized anticholinergic risk calculator, targeted multimedia such
as videos and blogs to educate users regarding anticholinergics, and a
conversation starter to help a patient self-initiate ending
anticholinergic prescriptions with a healthcare provider.\61\ This
trial will explore the impact of the app on prescription
anticholinergic exposure among older adults and on cognitive function
and quality of life. Other research studies currently funded by NIA
seek to assess severe adverse events associated with the interaction of
cholinesterase inhibitors used to treat Alzheimer's with
anticholinergic medications; \62\ test mechanisms of neurotoxicity from
anticholinergics; \63\ evaluate extended cognitive, urinary, and
functional trajectories in older incontinent women without pre-existing
dementia who use anticholinergic medication; \64\ utilize a novel model
to investigate anticholinergic drug induced dementia; \65\ improve how
older adults living with dementia, their caregivers, and clinicians
make decisions about using anticholinergic medicines; \66\ and test
electronic health record-based tools that engage caregivers to help
primary care providers reduce medication overload and deprescribe
medications that can worsen cognitive burden in patients with mild
cognitive impairment, Alzheimer's disease, and related dementias.\67\
In addition, a recent NIA-supported study found that exposure to strong
anticholinergics increased the risk of transitioning from normal
cognition to mild cognitive impairment.\68\ Another recent NIA-funded
study that evaluated adverse outcomes of anticholinergic medicines in
patients with dementia and overactive bladder \69\ found an increased
risk of mortality associated with non-selective antimuscarinic (a
subtype of anticholinergic drugs) medications in older adults with
dementia.\70\
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\60\ reporter.nih.gov/search/Shaj-qYerkm0U6DRn1S6tg/project-
details/10129872.
\61\ clinicaltrials.gov/ct2/show/NCT04121858.
\62\ reporter.nih.gov/search/pZSsBABfW0K-DPFCtVqRcQ/project-
details/10212709.
\63\ reporter.nih.gov/search/Ggd69UkxpkGGqF5IAEfYrg/project-
details/10168318.
\64\ reporter.nih.gov/search/0lm26jQsukuQXix5r_QvGw/project-
details/10343015.
\65\ reporter.nih.gov/search/0lm26jQsukuQXix5r_QvGw/project-
details/10258975.
\66\ reporter.nih.gov/search/Ggd69UkxpkGGqF5IAEfYrg/project-
details/9926791.
\67\ reporter.nih.gov/project-details/10370471.
\68\ www.ncbi.nlm.nih.gov/pmc/articles/PMC6036636/.
\69\ reporter.nih.gov/search/-xMveMuhZUWqFIMIntQeIw/project-
details/9377896.
\70\ pubmed.ncbi.nlm.nih.gov/32026255/.
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The National Institutes of Health (NIH) is committed to continuing
to fund research to improve the lives of people living with overactive
bladder and will continue to fund research towards prevention of
cognitive impairment in this, and other, areas.
______
Questions Submitted by Senator Shelley Moore Capito
Question. Alzheimer's disease has certainly been in the news
recently. While, there is plenty to discuss on Adulhelm and decisions
regarding its coverage, I am interested in the role it can play in
moving the science forward.
What is on the horizon to better understand Alzheimer's disease and
how we can prevent/slow its progression?
Answer. Thanks to the increased investment in Federal funding for
Alzheimer's and related dementias, the National Institutes of Health
(NIH) has been able to embark on an ambitious research agenda and
continues to make significant progress in discovering approaches that
may prevent, diagnose, and treat these complex diseases.
Understanding Alzheimer's and related dementias: Roughly 10 years
ago, we knew of just 10 genetic areas associated with Alzheimer's
disease, and 20 years ago, we knew of only 4. That number has grown to
more than 70 associated genetic areas today. These advances are already
informing new pathways for potential prevention and treatments. For
example, NIH-supported research involving a Colombian family with more
than 6,000 living members led to the identification of a gene variant
that may protect against the development of Alzheimer's.\71\ Studies to
understand how this gene and others may protect against Alzheimer's
suggest new possibilities for treatment options, which NIH is exploring
further.
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\71\ https://www.nia.nih.gov/news/unique-case-disease-resistance-
reveals-possible-alzheimers-treatment.
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In addition, NIH funds research beyond genetics to understand the
biological mechanisms associated with dementia. For example, National
Institute on Aging (NIA) intramural researchers have identified several
biological pathways linked to abnormal brain metabolism in people with
Alzheimer's disease and related dementias.\72\ These researchers also
identified 15 promising candidate drugs that have already been shown
safe and effective for other conditions and are screening these for
potential use in treating dementia. By studying drugs approved by the
Food and Drug Administration (FDA) for other conditions, researchers
may be able to accelerate the drug discovery process for Alzheimer's
and related dementias.
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\72\ https://www.nia.nih.gov/news/nia-study-identifies-fda-
approved-drugs-may-also-be-helpful-dementia.
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Diagnostics: In the early 2000s, researchers could only confirm an
Alzheimer's disease diagnosis via autopsy. NIH support has been
instrumental in developing ways to image and visualize aggregations of
specific proteins like amyloid and tau--the hallmarks of Alzheimer's--
in the brain, making a diagnosis possible in living persons. NIH
continues to advance new, less invasive ways of detecting these
proteins. For example, NIH small business innovation research funding
helped researchers at C2N Diagnostics validate the
PrecivityADTM test, a more affordable and less invasive
alternative to traditional Alzheimer's tests like brain scans.\73\ This
blood biomarker test is now available to some doctors who are sending
blood samples to C2N's lab to analyze blood for amyloid. In
May 2022, the FDA granted marketing authorization for the first test
for the early detection of amyloid plaques using cerebrospinal
fluid.\74\ The clinical study of this test utilized cerebrospinal fluid
samples made available by the Alzheimer's Disease Neuroimaging
Initiative, a key component of NIH-supported Alzheimer's research
infrastructure.
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\73\ https://www.nih.gov/news-events/news-releases/nih-small-
business-funding-boosts-alzheimers-science-advances.
\74\ https://www.fda.gov/news-events/press-announcements/fda-
permits-marketing-new-test-improve-diagnosis-alzheimers-disease.
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These tests are poised to transform Alzheimer's diagnostics and
clinical trial recruitment. For example, because they can be done
without the need for expensive PET scanners and radioactive diagnostic
agents, they can be used in a much broader range of clinical settings,
such as community health centers, thereby removing a potential barrier
to participation in clinical trials.
Clinical Trials: In 2015, NIH funded 38 clinical trials to treat
and prevent Alzheimer's and related dementias. In 2022, NIH is
supporting more than 400 trials, approximately half covering dementia
treatment and prevention, and the other half covering care
interventions for persons living with these diseases.\75\ The growth of
NIH's clinical trial portfolio, which includes a diverse range of
promising therapeutic approaches, is directly attributable to increased
appropriations. In fact, the number of therapeutic targets for drug
candidates in NIH-supported trials has more than doubled from 2015 to
2022. This is particularly evident in early phase (phase I or phase II)
trials, where more than three-quarters of the drug trials currently
supported by NIH are for targets other than amyloid proteins in the
brain.
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\75\ https://www.nia.nih.gov/research/ongoing-AD-trials.
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Some of these clinical trials will share results soon. The Exercise
in Adults With Mild Memory Problems (EXERT) trial,\76\ which tests the
effects of aerobic exercise on cognition in adults with Alzheimer's,
will report topline results in August 2022. In December 2022, the
PEACE-AD trial,\77\ which evaluates the drug Prazosin to treat severe
agitation in adults living with Alzheimer's who require full-time
caregiving, will share topline results. In addition, the DISCOVER
Study\78\ testing the drug Posiphen in adults diagnosed with
Alzheimer's is expected to report results late this year or in early
2023.
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\76\ https://clinicaltrials.gov/ct2/show/record/NCT02814526.
\77\ https://clinicaltrials.gov/ct2/show/NCT03710642.
\78\ https://www.clinicaltrials.gov/ct2/show/NCT02925650.
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Prevention: We now know there are several risk and resilience
factors that may play a role in the development of dementia. One
example is blood pressure control. Recent NIH-supported studies showed
that intensive high blood pressure control significantly reduces the
occurrence of mild cognitive impairment, a precursor to dementia in
some individuals. NIH has taken steps to share these findings with the
public through efforts like the Mind Your Risks campaign.\79\
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\79\ www.mindyourrisks.nih.gov/.
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In addition, a recent analysis of data from two NIA-funded
longitudinal study populations, the Chicago Health and Aging Project
(CHAP) \80\ and the Memory and Aging Project (MAP),\81\ found that
adhering to a combination of healthy behaviors was associated with a
lower risk of Alzheimer's, including in individuals with genetic risk
factors for the disease.\82\
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\80\ www.alzrisk.org/cohort.aspx?cohortid=15.
\81\ www.alzrisk.org/cohort.aspx?cohortid=60.
\82\ pubmed.ncbi.nlm.nih.gov/32554763/.
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The behaviors included engaging in regular physical activity,
avoiding smoking, practicing light-to-moderate alcohol consumption,
eating a high-quality diet, and engaging in cognitive activities.
Practicing four or all five of these behaviors was associated with up
to a 60 percent reduction in Alzheimer's risk.
The finding that behavioral choices appear to have an impact on the
development of Alzheimer's even in individuals with a higher genetic
risk is encouraging in terms of the promise of nondrug therapies in the
search for effective treatments. To this end, NIH continues to support
research to identify the best ways to help prevent dementia, including
more than 130 clinical trials on nondrug interventions like exercise,
diet, and sleep.\83\ NIH also supports research on how to help people
adopt and sustain these healthy behaviors over a lifetime.\84\
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\83\ www.nia.nih.gov/research/ongoing-AD-trials.
\84\ www.nia.nih.gov/research/blog/2021/12/tis-season-healthy-
habit-research.
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______
Questions Submitted to Dr. Nora Volkow
Questions Submitted by Senator Roy Blunt
Opioids Research
Question. Dr. Volkow, since fiscal year 2018, NIH has been provided
$500 million in dedicated funding annually for opioids and stimulant
research. However, according to data released last week by the CDC,
opioid overdoses continue to rise, with deaths up nearly 50 percent in
the past 2 years. What research has NIH produced to move the needle on
overdoses?
Answer. The National Institute on Drug Abuse (NIDA) shares your
concerns about rising rates of drug overdoses and mortality. In the
past few years, this crisis has been driven largely by increasing
availability of potent synthetic opioids such as fentanyl and increases
in combined opioid and stimulant use. NIDA supports robust multi-
pronged efforts to stem the overdose crisis, including research on drug
use and overdose prevention interventions, emerging patterns of
substance use, harm reduction approaches, development of medications
for opioid and stimulant use disorders, and the impact of coronavirus
disease 2019 (COVID-19) on substance misuse and comorbidities.
Adolescence and young adulthood are periods of particularly high
risk for drug initiation and the development of addiction. Through its
prevention research portfolio and through the HEAL Prevention
Initiative,\85\ NIDA is developing and testing strategies to prevent
drug use risk in youth overall and specifically to prevent opioid
initiation, misuse, and use disorder, in populations including American
Indian/Alaska Natives, youth with justice system involvement, and youth
experiencing homelessness. This research will also address the
sustainability and cost of these interventions. Through one project,
researchers have developed a patient education program to prevent
diversion of stimulants prescribed for attention-deficit/hyperactivity
disorder.\86\ Initial evidence showed reductions in patients'
disclosure of their prescription to friends, their intent to share, and
being approached to share.\87\
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\85\ heal.nih.gov/research/new-strategies/preventing-opioid-use-
disorder.
\86\ https://reporter.nih.gov/project-details/9980049.
\87\ Molina BSG., Kipp, HL., Joseph, HM., et al. Stimulant
diversion risk among college students treated for ADHD: Primary care
provider prevention training. Acad Pediatr. 2020; 20(1): 119--127.
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In 2020, NIDA expanded its National Drug Early Warning System
(NDEWS), which monitors patterns of drug use, morbidity, and mortality.
By analyzing counterfeit pills seized by law enforcement, NDEWS
established that such pills are a growing source of fentanyl.\88\ This
suggests that many fentanyl exposures are unplanned, and that overdose
risk could be reduced with simple tools like fentanyl test strips
(FTS). NIDA supports studies on FTS use and research to improve FTS
technology. NIDA's Small Business Innovation Research (SBIR) and Small
Business Technology Transfer (STTR) programs also support innovative
technologies to surveil drugs in community wastewater to monitor
changes in drug use as well as the emergence of new drugs. These tools
are valuable for assessing the impact of prevention and treatment
interventions and helping to tailor resource allocation.
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\88\ Palamar, JJ., Ciccarone, D., Rutherford, C., et al. Trends in
seizures of powders and pills containing illicit fentanyl in the United
States, 2018 through 2021. Drug Alcohol Depend. 2022;1:234.
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In alignment with the National Drug Control Strategy, one of NIDA's
priorities is to expand research on harm reduction, which focuses on
reducing the risk of overdose and other harms associated with drug use.
Through the NIH Helping to End Addicition Long-term (NIH HEAL
Initiative), NIDA is establishing a new network to develop, test, and
implement harm reduction strategies and assess the impact of state and
local harm reduction policies.\89\ NIDA research is also evaluating the
implementation of peer-based opioid overdose education, naloxone
distribution, and social support interventions and their impact in
African Americans \90\ and veterans.\91\
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\89\ RFA-DA-22-046: HEAL Initiative: Harm Reduction Policies,
Practices, and Modes of Delivery for Persons with Substance Use
Disorders (R01 Clinical Trial Optional).
\90\ https://reporter.nih.gov/search/pXhkeRP_10CxXi3NjmRQig/
project-details/10354090.
\91\ https://reporter.nih.gov/search/pXhkeRP_10CxXi3NjmRQig/
project-details/10298478.
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Through its Clinical Trials Network (CTN), NIDA has helped create
an arsenal of medications for opioid use disorder (MOUD) that are
effective in reducing overdose. NIDA supported development of naloxone,
and more recently, Kloxxado, a nasal spray containing high-dose
naloxone that was approved by the U.S. Food and Drug Administration
(FDA) in 2021.\92\ NIDA continues to fund research aimed at treating
opioid and stimulant use disorders and overdose with nearly 90
compounds at various stages along the drug development pipeline,
including longer-acting overdose reversal agents; and since 2019,
NIDA's Pharmacotherapies Development Program has ushered twenty-four
investigational new drug (IND) applications and eight IND exemptions
through the FDA's IND process. One of the most promising preclinical
projects underway is optimizing, characterizing, and testing the
efficacy of a novel compound for reversing opioid-induced respiratory
depression involving fentanyl and fentanyl analogs, alone and in
combination with methamphetamine.\93\ Researchers are also studying the
unique physiological and pharmacological effects of co-intoxication
with fentanyl and methamphetamine in animal models and testing the
ability of CS-1103 to normalize these effects.\94\ Unfortunately, NIDA-
funded research also shows that MOUD are underutilized.\95\
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\92\ https://reporter.nih.gov/search/pXhkeRP_10CxXi3NjmRQig/
project-details/10298478.
\93\ https://reporter.nih.gov/search/Zmse6nG00kKHYseah5M4qw/
project-details/10227069.
\94\ https://reporter.nih.gov/search/51gwUKe_70eDNuM13Y1IOQ/
project-details/10433799.
\95\ Xu, KY., Mintz, CM., Presnall, N., et al. Comparative
Effectiveness Associated With Buprenorphine and Naltrexone in Opioid
Use Disorder and Cooccurring Polysubstance Use. JAMA Netw Open. 2022
May 2;5(5).
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NIDA funds research to overcome barriers to MOUD use in diverse
settings, including prisons and jails. For example, one recent study
found that 6 months after Rhode Island implemented a comprehensive OUD
screening and treatment program at its corrections facilities, the
state saw a 12.3 percent reduction in fatal overdoses overall and a
60.5 percent reduction among the recently incarcerated.\96\ With
support from the NIH HEAL Initiative, the HEALing Communities Study
\97\ and the Justice Community Opioid Innovation Network (JCOIN) \98\
are expanding research efforts to increase MOUD use; test the
effectiveness and adoption of new prevention interventions and
medications; and together, use real-world evidence to address the needs
of vulnerable populations.
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\96\ Green TC., Clarke, J., Brinkley-Rubinstein, L., et al.
Postincarceration Fatal Overdoses After Implementing Medications for
Addiction Treatment in a Statewide Correctional System. JAMA
Psychiatry. 2018 Apr 1;75(4):405-407.
\97\ https://heal.nih.gov/research/research-to-practice/healing-
communities.
\98\ https://heal.nih.gov/research/research-to-practice/jcoin.
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Stimulant misuse and overdose, primarily involving methamphetamine,
have also continued to rise and often co-occur with opioid misuse.
Unlike the case for OUD, there are no clinically proven medications for
methamphetamine use disorder (MUD), but NIDA has supported progress on
this front. Recent findings from a clinical trial demonstrated that
treating MUD with naltrexone, a type of MOUD, in combination with
bupropion, an antidepressant with stimulant effects, for six weeks
helped patients reduce their meth use and improved other symptoms, such
as depression \99\ (Trivedi, et al. 2021).
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\99\ https://pubmed.ncbi.nlm.nih.gov/33497547/.
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NIDA-funded research also helped establish that contingency
management (CM) is effective for reducing misuse of opioids,
stimulants, and other substances; in CM, patients are given incentives
for reducing their drug use or engaging in treatment. NIDA funding led
to the first FDA-authorized mobile apps for intended to help increase
retention in outpatient treatment programs for SUD.\100\ These
cognitive behavioral therapy apps are intended to be used in
conjunction with CM and other tools and strategies to reduce drug
craving. Ongoing studies seek to improve these apps and apply them in
new ways, such as at-home initiation of MOUD (3R44DA042652).\101\
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\100\ https://peartherapeutics.com/products/reset-reset-o/.
\101\ https://reporter.nih.gov/project-details/10153370.
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While these advances are moving the needle, the COVID-19 pandemic
has exacerbated the overdose crisis. Nearly 15 percent of U.S. adults
initiated or increased substance use to cope with pandemic-related
stress,\102\ and drug overdose rates among adolescents doubled during
the pandemic, after a decade of stability.\103\ While Federal drug
regulatory and healthcare agencies implemented policy changes to expand
treatment access for people with SUD, pandemic restrictions still
caused disruptions in treatment.\104\ NIDA has supplemented many of its
studies and programs during the pandemic, including the Adolescent
Brain Cognitive Development SM Study (ABCD study), to better
understand the risks of pandemic-related substance misuse and identify
possible ways to intervene, and to evaluate the impact of pandemic-
related policy changes.
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\102\ Czeisler, ME., Lane, RI., Petrosky, E., et al. Mental Health,
Substance Use, and Suicidal Ideation During the COVID-19 Pandemic--
United States, June 24-30, 2020. MMWR Morb Mortal Wkly Rep.
2020;69(32):1049-1057.
\103\ Friedman, J., Godvin, M., Shover, CL., et al. Trends in Drug
Overdose Deaths Among US Adolescents, January 2010 to June 2021. JAMA.
2022;327(14):1398-1400.
\104\ Meadowcroft, D. and Davis W. Understanding the Effect of the
COVID-19 Pandemic on Substance Use Disorder Treatment Facility
Operations and Patient Success: Evidence From Mississippi. Subst Abuse.
2022;16:11782218221095872.
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Question. During the COVID-19 pandemic, NIH stepped up and embraced
the sense of urgency by creating programs like RADx, which was a Shark
Tank-style program to develop more COVID tests. How can we incorporate
that model into the urgent needs related to the opioid epidemic?
Answer. Addressing the addiction and overdose crisis requires
innovation, and often, those in a position to develop solutions are not
even aware of their potential to help. Therefore, NIDA uses the Federal
government's small business innovation research (SBIR) and small
business technology transfer (STTR) programs and novel, fit-for-
purpose, funding authorities to help biotech startups develop
innovative solutions that translate addiction science into healthcare
and consumer products.\105\
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\105\ https://nida.nih.gov/research/nida-research-programs-
activities/nida-challenges-program.
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Under the statutory authority of the America Creating Opportunities
to Meaningfully Promote Excellence in Technology, Education, and
Sciences (COMPETES) Reauthorization Act of 2010, NIDA's annual
``$100,000 for Start a Substance Use Disorders (SUD) Startup'' is a
Shark Tank-style challenge that supports research ideas that are
intended to be the foundation for the development of successful new
startups.\106\ Each year, this challenge provides ten winners with
$10,000 each and technical mentoring from NIDA biomedical
entrepreneurship experts. This enables the winners to test the premise
that their research idea can be fostered into a biotech startup that
will eventually contribute to the pool of innovative small businesses
that can successfully compete for NIDA's SBIR and STTR funding. Sound
Life Sciences and Prapela were discovered and selected through this
challenge. Sound Life Sciences used this award to build a startup
around a novel app that turns a user's smartphone into a portable
respiratory monitor capable of detecting changes in breathing
associated with an overdose. If an overdose is detected, it will sound
an alarm, provide instructions, and summon emergency services to the
user's location.\107\ Prapela developed a hospital bassinet pad that
delivers gentle, random vibrations to treat newborns who were exposed
to opioids before birth. The bassinet pad may help improve newborns'
breathing and heart rate and may also be useful in infants with
breathing issues due to premature birth.\108\
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\106\ https://nida.nih.gov/research/nida-research-programs-
activities/nida-challenges-program/2021-start-sud-startup.
\107\ https://www.soundlifesci.com/.
\108\ https://www.prapela.com/.
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Other innovative products grew out of the NIDA Market Fair, a Shark
Tank-style funding solicitation strategy. NIDA staff pitched ideas for
potential funding concepts to ``Sharks'' who were experts in product
development and policy from other NIH Institutes and other Federal
agencies. The best ideas were rapidly selected and developed into
funding opportunities for small business applications. The Shark Tank-
style selection of concepts for development assured that there was a
need and a market, which, in turn, attracted the companies best suited
to develop specific products. Biobot Analytics developed a wastewater
testing and analysis method to detect community exposure to opioids
that can inform local opioid response efforts; this company was also
able to pivot and provide critical data on the presence of SARS-CoV-2
in communities.\109\ AppliedVR developed RelieVRxTM, an FDA-
authorized virtual reality-based tool to treat people with chronic low
back pain by helping them learn how to better cope with pain.\110\
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\109\ https://biobot.io/.
\110\ https://www.relievrx.com/.
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The goal is to reduce the need for opioids for many different pain
indications and reduce the associated risk of developing an opioid use
disorder (OUD). Workit Health is an app that uses video chat and
messaging technology to bring trained experts directly to those with
SUDs via a phone or computer.\111\ The company is working to develop a
chat bot to improve patient engagement and is continually working to
expand its services to treat additional disorders and co-occurring
conditions. Woebot, developed by Woebot HealthTM, is a
smartphone-based mental health chatbot intended to use artificial
intelligence and language processing technology to deliver personalized
cognitive behavioral therapy for people with SUDs.\112\ Woebot is being
expanded for use in additional mental health indications. In addition,
We the Village provides online support for families or friends of
someone who is struggling with substance use or has a SUD.\113\ The
online support includes a course that aims to teach people
communication and support skills and an online Q&A to help people share
what they've learned, with the overall aim of helping loved ones reduce
substance use and get treatment. These and other innovative products
developed through NIDA support demonstrate that pairing sound science
with biotechnology entrepreneurship has great potential benefit for
those with addiction or at risk for overdose.
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\111\ https://www.workithealth.com/.
\112\ https://woebothealth.com/new-rct-shows-woebot-reduced-
problematic-substance-use-
occasions-by-one-third/
#: :text=In%20short%3A%20Woebot%20significantly%20reduced%20
substance%20use%20occasions,a%20total%20score%20of%20%3E%2F%3D2%20on%20t
he%20
CAGE-AID%29.
\113\ https://wethevillage.co/.
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______
Questions Submitted by Senator Shelley Moore Capito
Question. The release last week of the preliminary 2021 overdose
statistics was a grim reminder of how much work we still have to do.
Last Friday, I spoke with a mother who had recently lost her daughter
to fentanyl laced methamphetamine. She shared that while the first
responders had tried to use Narcan, since meth was the primary drug in
her system it was ineffective.
How is research progressing for an overdose reversal drug similar
to Narcan for meth/stimulant overdoses?
Answer. Unprecedented increases in drug overdose deaths in the last
8 years have been driven mainly by fentanyl, alone and in combination
with other drugs. Co-involvement of stimulants in fentanyl-involved
overdose deaths as well as increases in overdose deaths involving
stimulants without any opioids are particularly concerning the National
Institute on Drug Abuse (NIDA).\114\ The rate of methamphetamine-
involved overdose deaths increased by 810 percent from 2013 to 2021,
and the rate of cocaine-involved overdose deaths increased by 398
percent.\115\ There are currently no U.S. Food and Drug Administration
(FDA)-approved medications to treat stimulant use disorder or stimulant
overdose, but NIDA research is underway to better characterize
stimulant overdoses and to develop treatments for overdoses involving
stimulants, alone or in combination with opioids.
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\114\ https://nida.nih.gov/research-topics/trends-statistics/
overdose-death-rates.
\115\ cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm.
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Researchers have developed an antibody against methamphetamine
(IXT-m200) that binds the drug in blood and keeps it from entering the
brain in animal models and is safe for use in healthy humans. As a next
step, NIDA is funding a study in emergency department patients with
methamphetamine intoxication to test the efficacy of the antibody in
alleviating methamphetamine overdose symptoms.\116\ NIDA-funded
researchers have developed a small molecule (CS-1103) intended to act
like a sponge and clear drugs from the body; they are testing its
ability to clear either fentanyl \117\ or methamphetamine. \118\
Researchers are also studying the unique physiological and
pharmacological effects of co-intoxication with fentanyl and
methamphetamine in animal models and testing the ability of CS-1103 to
normalize these effects. \119\ Other research underway is a preclinical
project to optimize, characterize, and test the efficacy of a novel
compound for reversing opioid-induced respiratory depression involving
fentanyl and fentanyl analogs, alone and in combination with
methamphetamine. \120\
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\116\ https://reporter.nih.gov/search/Zmse6nG00kKHYseah5M4qw/
project-details/10269933 (5U01DA053043).
\117\ https://reporter.nih.gov/search/Lv70TeON70-p34mvyTTKXg/
project-details/10390959 (2R44
DA052957).
\118\ https://reporter.nih.gov/search/uwfTgufCYka3Auu_FIsAng/
project-details/10425422 (5U01DA053054).
\119\ https://reporter.nih.gov/search/51gwUKe_70eDNuM13Y1IOQ/
project-details/10433799 (3U01DA053054).
\120\ https://reporter.nih.gov/search/Zmse6nG00kKHYseah5M4qw/
project-details/10227069 (5U0
1DA051373).
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In addition to the studies described above, NIDA is currently
supporting research on nearly 90 compounds aimed at treating opioid and
stimulant use disorders and overdose at various stages along the drug
development pipeline. NIDA also issued funding opportunity
announcements to solicit additional research to develop new medications
to prevent and treat stimulant use disorders and overdose co-involving
opioids and stimulants, \121\ to develop pharmacotherapeutics and other
medical therapeutic and diagnostic devices for opioid use disorder and
stimulant use disorders, \122\ and to understand the mechanisms
underlying the toxic effects of using opioids and stimulants together.
\123\
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\121\ NOT-DA-22-049: Notice of Special interest (NOSI): Medications
Development for Stimulant Use Disorders.
\122\ RFA-DA-23-021: Developing Regulated Therapeutic and
Diagnostic Solutions for Patients Affected by Opioid and/or Stimulants
use Disorders (OUD/StUD) (R43/R44--Clinical Trial Optional).
\123\ NOT-DA-20-007: Notice of Special Interest (NOSI): Preclinical
and Clinical Studies of the Interactions of Opioids and Stimulants.
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SUBCOMMITTEE RECESS
Senator Murray. And this committee will next meet in
Dirksen 138, Tuesday, May 24, at 10 a.m., for a hearing on the
Biden Administration's Budget Request for the Department of
Education.
The committee is adjourned.
[Whereupon, at 11:29 a.m., Tuesday, May 17, the
subcommittee was recessed, to reconvene at 10 a.m., Tuesday,
May 24.]