[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

                              ----------                              


                         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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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).
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \6\ www.nccih.nih.gov/about/naccih-member-roster.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \8\ researchtraining.nih.gov/programs/career-development/k12.
---------------------------------------------------------------------------
  --Academic Research Enhancement Award (AREA) program.\9\
---------------------------------------------------------------------------
    \9\ grants.nih.gov/grants/funding/r15.htm.
---------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
                                 ______
                                 
            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.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    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\
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    \34\ gis.cancer.gov/ncicatchment/.
    \35\ ctep.cancer.gov/initiativesPrograms/etctn_catch-up2020.htm.
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    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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \75\ https://www.nia.nih.gov/research/ongoing-AD-trials.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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).
---------------------------------------------------------------------------
    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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    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).
---------------------------------------------------------------------------
    \99\ https://pubmed.ncbi.nlm.nih.gov/33497547/.
---------------------------------------------------------------------------
    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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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.]