[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 2022

                              ----------                              


                        WEDNESDAY, MAY 26, 2021

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:01 a.m., in room SD-562, Dirksen 
Senate Office Building, Hon. Patty Murray (chairwoman) 
presiding.
    Present: Senators Murray, Reed, Shaheen, Schatz, Baldwin, 
Murphy, Manchin, Blunt, Shelby, Graham, Moran, Kennedy, Hyde-
Smith, Braun, and Rubio.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR
ACCOMPANIED BY:
        DIANA BIANCHI, M.D., DIRECTOR, EUNICE KENNEDY SHRIVER NATIONAL 
            INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
        ANTHONY FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        GARY GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND BLOOD 
            INSTITUTE
        ELISEO PEREZ-STABLE, M.D., DIRECTOR, NATIONAL INSTITUTE ON 
            MINORITY HEALTH AND HEALTH DISPARITIES
        NED SHARPLESS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
        BRUCE TROMBERG, PH.D., DIRECTOR, NATIONAL INSTITUTE OF 
            BIOMEDICAL IMAGING AND BIOENGINEERING


               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 2022 Budget Request for the 
National Institutes of Health. Senator Blunt and I will each 
have an opening statement, and then I will introduce our 
witnesses. And after the witness testimony, Senators will each 
have 5 minutes for a round of questions.
    Before we begin, I do want to walk through the COVID-19 
safety protocols that are in place today. And again, I really 
want to thank all of our clerks and everyone who has really 
worked hard to get this set up and help us all stay safe and 
healthy. So, thank you to them.
    For today, we are going to be conducting this hearing 
following similar COVID protocols to what we have used in the 
past. Committee members are seated at least 6 feet apart. Some 
Senators are participating by videoconference. However, I do 
expect that this will be our final hybrid hearing, and we will 
be able to return to regular, in-person hearings at our next 
hearing.
    Consistent with CDC guidance, those who are fully 
vaccinated do not need to wear a mask, though they may still 
choose to do so. And while we are unable to have the hearing 
fully open to the public or media for in-person attendance, 
live video is available on our committee website. And if you 
are in need of accommodations, including closed captioning, you 
can reach out to the committee or the Office of Congressional 
Accessibility Services.
    As of today, almost half of U.S. adults are fully 
vaccinated. And while we have a lot of work left yet to do to 
reach communities who still cannot get vaccines and reassure 
people who still have many questions about them, we can see the 
light at the end of the tunnel. And, I really want to thank all 
of our witnesses, especially Dr. Collins and Dr. Fauci, for 
putting in long hours and putting science first.
    Where we are at today is a testament to the tireless work 
scientists at NIH have been doing to study this disease and how 
we can best fight it, and oversee clinical trials for vaccines 
and therapeutics and more, to ensure they are safe and 
effective. And, of course, as our witnesses know, our 
historically fast progress in fighting COVID-19 and developing 
safe and effective vaccines was actually years in the making.
    The pace of discovery we have seen this past year was made 
possible by research into mRNA vaccines we funded in response 
to Ebola and other viruses, and biomedical research enterprise 
that has been built over decades to become one of the most 
cutting edge in the world.
    This should be an important reminder when it comes to 
biomedical research. You can never fully predict how the 
discoveries of today will prepare you for the challenges of 
tomorrow. That is why you have to build the robust research 
enterprise and recruit diverse, world class talent, and make 
sure scientists can do their work free from political 
interference.
    And President Biden's budget, which proposes over $40 
billion for NIH (National Institutes of Health), the largest 
increase in the agency's history, will go a long ways towards 
making sure we can continue to prioritize this. This budget 
will reinforce our work to fight COVID-19, along with many 
other diseases and disorders that threaten families in my home 
State of Washington, or Missouri, or across the Country.
    It includes funding to improve treatments for addiction and 
substance use disorders, and funding to aid the fight against 
cancer, Alzheimer's disease, and rare diseases families across 
the Country are grappling with.
    President Biden's budget request will also fund research to 
help us study the health effects of climate change, which may 
be increasing the number of infectious disease outbreaks; 
identify solutions to gun violence, which continues to claim 
tens of thousands of lives each year in this Country; and root 
out the health inequities in our Country, which are undermining 
the health of people of color, people with disabilities, rural 
communities, those paid low incomes, and more.
    The President has also proposed $6.5 billion for a new 
initiative--the Advanced Research Projects Agency for Health. 
Like the defense initiative it is inspired by, ARPA-H is 
envisioned as breaking the mold for how cutting-edge research 
is conducted, speeding up the development of medical treatments 
by funding innovative projects. I am interested to hear more 
about how it can add to NIH's work and operate as something 
truly distinct from its other traditional, biomedical research 
programs.
    Of course, at the end of the day, innovation is not 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 its work to its families, our 
families, we cannot afford to have this agency's potential 
limited or its success threatened by bias, discrimination, 
harassment, or assault in the workplace.
    Unfortunately, we know that in the biomedical research 
community, the prevalence of researchers of color is too low, 
and the prevalence of sexual harassment is too high. These are 
real problems with real consequences for biomedical research 
and the people who do the lifesaving work we are all 
benefitting from today.
    I commend NIH for the efforts it has taken on both of these 
fronts so far. NIH has done work to examine barriers to 
diversity among its researcher ranks and how its own practices 
have reinforced structural biases that allow discrimination to 
persist. But, more work remains to tear down barriers and 
create lasting change.
    And when it comes to sexual assault, Director Collins, I am 
glad you have taken some forceful action to address the problem 
among the NIH workforce, but NIH must do more to use its 
enormous influence with the research community to enforce 
change in the Nation's universities and research institutions. 
I expect NIH to continue building on its efforts so far to 
remove racism, discrimination, and harassment from research, 
and I will continue to follow up on that progress.
    Finally, as proud as we all are of our Nation's biomedical 
research institutions, we do not invest billions of dollars in 
biomedical research out of pride, nor do we invest in them to 
help pharmaceutical companies make astronomical profits. We do 
it to bring new treatments, cures, and hope to people across 
the Country and across the world. It is important that we never 
lose sight of this because even the most brilliant miracle cure 
can only save people if they can actually get it.
    Just as I hope to work with my colleagues on both sides of 
the aisle to make lifesaving investments in biomedical research 
like those proposed in the President's budget, I also hope we 
can work together to bring down the cost of healthcare, 
especially for prescription drugs; keep working towards 
universal health coverage; and bring the cures we are investing 
in to the families who need them.
    With that, I will turn it over to Senator Blunt for his 
remarks.


                     statement of senator roy blunt


    Senator Blunt. Well, thank you, Chair Murray. I appreciate 
having this hearing today and appreciate being able, again, to 
start this process with you as we did last week on our first 
hearing.
    I am certainly glad that Dr. Collins and the Institute 
directors are here with us today. I think two of the directors 
are testifying before the committee for the first time, and, 
so, welcome to the two of you. And this is a helpful 
relationship for us, and hopefully for you.
    Certainly, the challenges we have faced over the past year 
have been unanticipated and significant. I think the global 
pandemic reinforced the importance of the National Institutes 
of Health. In less than a year, NIH was able to take this novel 
coronavirus and help develop two FDA (Food and Drug 
Administration)-authorized vaccines, two FDA-authorized 
therapeutics, and 16 rapid diagnostic tests, including the 
first FDA-authorized point-of-care diagnostic test for COVID-19 
to combat its spread and its effects.
    A year ago, when we would have had a similar discussion, 
one of the big topics would be, why can't we get enough tests? 
NIH stepped up and really played a big role in seeing that we 
had enough tests. We have not heard that discussion for a long 
time. And that does not mean that millions of tests are not 
being taken every day. It just means we figured out at this 
committee and NIH to be part of meeting that need.
    It was revolutionary to watch NIH work, but it did not just 
happen. In a time of crisis, during shutdowns, during social 
distancing, dealing with a disease that has never been seen 
before, the system and its nationwide grantees were able to use 
their expertise and infrastructure to, again, develop tests, 
treatments, and vaccines. Our research infrastructure was 
tested like never before and, in my opinion, it succeeded in 
remarkable ways.
    I believe there are really three reasons for that. First, 
in the past 6 years, this committee and the Congress, in a 
bicameral, bipartisan way have prioritized and invested in NIH. 
Within that 6-year timeframe, funding for medical research 
increased by almost $13 billion, or nearly 43 percent over that 
6 years after a decade at virtually level funding. This 
investment encouraged young scientists, young researchers, and 
mid-career researchers that were leaving the field before that 
to stay in the field. And, with your insistence, Dr. Collins, 
some of that money every time was set aside to be sure that it 
was going to first-time grantees.
    We were able to shore up the research infrastructure across 
the Country and provide research into mRNA, an idea that had 
never produced a vaccine before and, of course, became the 
foundation for the two principal vaccines that were developed 
very much with the involvement of NIH.
    Our ability to pivot so quickly and so successfully to 
fighting COVID-19 could not have been accomplished had we 
stayed at the funding levels we were at 7 years ago. The buying 
power was not where it needed to be. Young researchers were 
leaving the field. Tough budgetary decisions meant that people 
were not only getting their applications rejected at 
significant levels; they just, frankly, stopped making a lot of 
applications. That is not your problem, by the way, today.
    Second, at the height of the pandemic, Congress gave the 
Department of Health and Human Services significant funding and 
flexibility to create Operation Warp Speed. It was successful 
in developing two FDA-authorized COVID-19 vaccines and 
commercializing another with the help of NIH because we united 
in our effort to make that happen.
    One of the things we did was to really invest in vaccines 
that we did not think were certain to work, but thought were 
likely to work, and that meant that vaccines were available 
when they got FDA authorization rather than months after they 
got FDA approval. Because of that, fully half of all adults 
have been vaccinated now in the United States as we work toward 
a bigger number than that.
    We pushed private industry and worked with private industry 
in ways we had not before. I have said at the time, one way to 
win the horse race is to bet on all the horses. And I think to 
a great extent we did in the vaccine effort, bet on all the 
horses we thought had a chance to finish the race, and it made 
a difference.
    Finally, one of the most important lessons learned from the 
pandemic is the value of having the Federal Government, on 
occasion, as a more active partner in research and development 
instead of just a sponsor. The ambitious speed and goals that 
pushed private companies to research, develop, and manufacture 
a COVID-19 vaccine, along with what we did in testing, really 
created the kind of breakthroughs we needed.
    RADx and Warp Speed, I think put us in a different place 
than we would have been 2 years ago in thinking about how we 
can look at some of our research efforts in another way. That 
is why I want to work with the Administration to support the 
ARPA-H initiative. This will be a new institute, or is proposed 
to be a new institute, and I think that is what should be the 
case. They will have the flexibility and tools necessary to 
both nimbly and innovatively respond to both the next pandemic 
and also some of the big health issues we face today.
    This is a critical moment in a rapidly changing healthcare 
world. Finding those things that the kind of Warp Speed, Shark 
Tank, RADx relationship could enhance in cancer, in 
Alzheimer's, in every disease where there is an opportunity; 
where we see that moment and know that this is something that 
does not necessarily call for a 5-year research grant, but some 
sort of partnership different than that that moves toward a 
real conclusion sooner than we might otherwise be able to do 
that.
    ARPA-H should not do what the other institutes do, but it 
should do what the other institutes cannot do in a crosscutting 
way that goes throughout the institutes, looking for 
opportunities, frankly, in the other institutes where there is 
a breakthrough moment that we could look at differently. I 
think we can help fill gaps here that otherwise would not be 
filled and look forward to that discussion.
    Now, also, as someone working with Senator Murray for the 
last 6 years to increase the funding and the focus in what NIH 
has been doing, we clearly want to be sure that this somehow 
does not take away from the solid research that proves so 
effective in getting us ready for what we just saw.
    So, Dr. Collins, I look forward to working with you and 
Chair Murray and the Administration in making ARPA-H a reality. 
I think the moment is ready for that. I think because of what 
has happened in the last 2 years, NIH is ready for that, and 
look forward to the discussion today.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Thank you, Chair Murray. I appreciate Dr. Collins and the other 
Institute Directors for being here today.
    The challenges we have faced over the past year in a global 
pandemic reinforced the importance of the National Institutes of 
Health.
    In less than a year, NIH was able to take this novel coronavirus 
and develop two FDA-authorized vaccines, two FDA-authorized 
therapeutics, and 16 rapid diagnostic tests, including the first FDA-
authorized point-of-care diagnostic test for COVID-19, to combat its 
spread and effects.
    This was revolutionary, and it didn't happen without decades of 
preparation.
    In a time of crisis, during shutdowns and social distancing, for a 
disease never seen before, the NIH and their nationwide system of 
grantees were able to use their expertise and infrastructure to develop 
tests, treatments, and vaccines for COVID-19. Our research 
infrastructure was tested like never before, and it succeeded. And I 
believe there were three key reasons behind this success.
    First, for the past six years, this Committee and Congress have 
prioritized and invested in NIH. Within this timeframe, funding for 
medical research increased by $12.85 billion, or nearly 43 percent, 
after having spent the previous decade at virtually level funding.
    This investment encouraged young and mid-career scientists in the 
field, who often have the most novel and innovative research ideas, 
shored-up the research infrastructure across the country, and provided 
research into mRNA, which is the foundation for two of the COVID-19 
vaccines.
    Our ability to pivot so quickly and so successfully to fighting 
COVID-19 could not have been accomplished had this Committee let NIH 
funding stagnate for another decade, dragging down its buying power, 
and letting young researchers leave the field. Making the tough 
budgetary decisions necessary to prioritize the NIH paid off.
    Second, at the height of the pandemic, Congress gave the Department 
of Health and Human Services significant funding and flexibility to 
create Operation Warp Speed. It was successful in developing two FDA-
authorized COVID-19 vaccines and commercializing another, with the help 
of NIH, because it united the federal government, private companies, 
and researchers around a common goal.
    The reason that we have been able to fully vaccinate half of all US 
adults is because there was a deliberate strategy in the last 
Administration to focus and provide funding for any COVID-19 vaccine or 
therapeutic that had the likelihood to work. We took financial risks to 
manufacture vaccines as the development process was still underway.
    We pushed private industry to innovate their own approaches. And we 
forever changed the drug approval process. As I have said before, the 
way to win a horse race is to bet on all the horses. That is what this 
Committee and the previous Administration did.
    Finally, one of the most important lessons learned from the 
pandemic is the value of having the Federal Government become a more 
active partner in research and development, instead of just a sponsor.
    The ambitious speed and goals that pushed private companies to 
research, develop, and manufacture a COVID-19 vaccine through Operation 
Warp Speed demonstrated that active collaboration in public-private 
partnerships, in conjunction with significant funding, are game 
changers in creating scientific breakthroughs.
    Now we must learn from these lessons. There is an opportunity to 
build upon Operation Warp Speed and NIH's RADx diagnostic testing 
program to leverage public-private partnerships to dramatically 
accelerate the development and approval of new treatments and 
technologies. What two years ago would have been termed risky and 
financially unpalatable now is possible.
    And that is why I want to work with this Administration to support 
the ARPA-H initiative. This will be a new Institute that will have 
flexibility and tools necessary to nimbly and innovatively respond to 
both the next pandemic and also to some of the biggest health issues 
Americans face today, like cancer and Alzheimer's disease.
    ARPA-H should do what other NIH Institutes cannot. It needs to be 
cross-cutting throughout all the NIH Institutes and collaborative both 
internally with NIH and HHS and externally with partners. It needs to 
be innovative. And it should help fill the gaps we clearly saw during 
the pandemic between basic science and commercialization of COVID-19 
vaccines and therapeutics.
    Simply put, there are aspects of NIH research that could move much 
faster outside the traditional NIH grant cycle. The NIH peer review 
process is the gold standard, but we also need to recognize that it 
doesn't work for all research at all times.
    I look forward to working with you, Dr. Collins, and you, Chair 
Murray, on making ARPA-H a reality.
    It will take collaboration between the Administration, NIH, and 
Congress. But as we work toward a new Institute to accelerate the 
application and implementation of health discoveries, we must make sure 
that basic science is not abandoned. ARPA-H should not be the shiny new 
toy we all focus on, especially not to the detriment of the NIH 
research community as a whole.
    If there is one lesson we must take from this pandemic, it is that 
our nation's success depends on the medical research infrastructure 
across this country supported by the NIH. Now is not the time to 
abandon it. Now is the time to make it even stronger.
    Thank you.

    Senator Murray. Thank you very much, Senator Blunt.
    I will now introduce our witnesses.
    Dr. Francis Collins is the director for the National 
Institutes of Health.
    Dr. Diana Bianchi is the director of the Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development.
    Dr. Anthony Fauci is the director of the National Institute 
of Allergy and Infectious Diseases.
    Joining us virtually is Dr. Gary Gibbons. He is the 
director of the National Heart, Lung and Blood Institute.
    Dr. Eliseo Perez-Stable is the director of the National 
Institute on Minority Health and Health Disparities.
    Dr. Ned Sharpless is the director of the National Cancer 
Institute.
    And, finally, Dr. Bruce Tromberg is the director of the 
National Institute of Biomedical Imaging and Bioengineering.
    So, Dr. Collins, we will turn to you for your opening 
remarks.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Thank you, Chair Murray and Ranking Member 
Blunt and distinguished members of the subcommittee. I am 
honored to be here today with my colleagues representing the 
National Institutes of Health, the NIH.
    I could spend hours describing the exciting work the 
President's budget is proposing for NIH, including major 
investments to address impacts of the COVID-19 pandemic, reduce 
health disparities in maternal mortality, improve mental 
health, broaden approaches to pain and opioid addiction, and 
establish a bold, new agency within NIH called ARPA-H.
    But, in our brief time together, it is also important to 
emphasize how steady funding increases that you have provided 
to NIH, starting well before the pandemic, made it possible for 
NIH to meet the challenges of the pandemic and to prepare for 
what comes next.
    Often at these hearings, I share a story of a patient whose 
life has been saved by NIH research, but in this uniquely 
challenging year, it is hard to single out any one person. In 
fact, all of the more than 160 million Americans who have 
received COVID-19 vaccines as of today are success stories made 
possible by the sustained investment that this committee made 
years ago to basic biomedical research.
    The road to these mRNA vaccines actually started back in 
the 1960s when the function of messenger RNA was first 
understood. These messengers carry instructions from the cell's 
DNA manual to produce the proteins that do the work. Now, for 
vaccines, we knew that certain proteins, like the spike 
proteins on the coronavirus, could spur an immune response. 
But, might it be safer and just as effective to use the RNA, 
the codes for those spike proteins, to instruct the patient's 
body to produce them? And it took a lot of obstacles to 
surmount to get there over more than 20 years, but we are blown 
away by how well it works.
    In parallel, other NIH-supported scientists, including some 
at our own Vaccine Research Center, learned that locking those 
spike proteins into the right configuration could make an even 
better vaccine. So, when COVID hit, we knew exactly what to do, 
but we needed the help of the American people enrolling in 
clinical trials to finish the job. To facilitate that, NIH 
opened a dialogue with communities disproportionately affected 
by COVID to ensure that they had access to the vaccine trials.
    The Community Engagement Alliance, or CEAL, c-e-a-l, 
Initiative built on some existing, long-term partnerships with 
trusted leaders in underserved communities to engage directly 
on trial enrollment, and later with hesitant individuals on 
issues related to vaccine safety and efficacy.
    We were able to use the enrollment techniques we learned in 
the large, longitudinal studies, such as All of Us, that you 
have championed. The result is that all Americans can look at 
the major vaccine trials and see that people like them were 
included.
    While the vaccines were in early trials, the world was 
clambering for rapid diagnostics to understand and manage our 
risks. Members of this committee, most notably Senator Blunt, 
asked what NIH could do to ramp up innovation. And thanks to 
your support, and using a novel Shark Tank approach, NIH took 
on a new role as a venture capitalist through the Rapid 
Acceleration of Diagnostics, or RADx program.
    Today, there are 33 novel testing platforms helping perform 
just today, millions of tests daily, due to RADx. This program 
demonstrated the remarkable innovations that are possible when 
NIH brings together experts in engineering, business, and 
manufacturing to fund big ideas.
    Now, the President's budget proposes a major investment to 
build on this momentum the Advanced Research Projects Agency 
for Health, or ARPA-H. This new agency within NIH will catalyze 
novel strategies to speed transformational and innovative 
ideas, ideas such as simple blood tests to detect free-floating 
DNA or protein markers that signal a cancer is growing 
somewhere in the body; a micro needle patch that delivers a 
vaccine to hard-to-reach communities in the mail; using an 
innovation funnel to recruit, test, and scale up new 
technologies for ambulatory blood pressure measurement with the 
potential to transform the management of hypertension.
    These are just a few of the bold ideas that ARPA-H could 
tackle, but they are not science fiction. With standard 
approaches, well, they might happen in a decade or two. With 
ARPA-H, we believe it could take half that time.
    The President believes that with your help, we can learn 
from the lessons of pandemic and transfer this scientific 
momentum into big improvements in the health of all Americans. 
I do, too.
    My colleagues and I would be pleased to answer your 
questions.
    [The statement follows:]
    Prepared Statement of Francis S. Collins, M.D., Ph.D., Diana W. 
Bianchi, M.D., Anthony S. Fauci, M.D., Gary H. Gibbons, M.D., Eliseo J. 
 Perez-Stable, M.D., Norman E. Sharpless, M.D., and Bruce J. Tromberg, 
                                 Ph.D.
    Good morning, Chairwoman Murray, Ranking Member Blunt, and 
distinguished Members of the Subcommittee. I am Francis S. Collins, 
M.D., Ph.D., and I have served as the Director of the National 
Institutes of Health (NIH) since 2009. It is an honor to appear before 
you today.
    First, I want to thank this Subcommittee for your commitment to 
NIH, which allowed the biomedical research enterprise to respond 
quickly to the greatest public health crisis in our generation over the 
past year. We mounted vigorous research efforts to understand the viral 
biology and pathogenesis of the coronavirus disease 2019 (COVID-19), 
develop vaccines in record time, support and commercialize diagnostics 
at the point of care, and test therapeutics for both outpatient and 
inpatient settings. This work is far from finished.
    The President's Discretionary Request proposes budget authority of 
$51 billion for NIH in fiscal year (FY) 2022. The Biden Administration 
places great emphasis on research and development in general. At NIH in 
particular, the Request proposes to build on the successes of pandemic 
era research and to put the research enterprise to work on some of our 
Nation's most persistent and perplexing health challenges, including 
cancer, Alzheimer's disease, opioid use disorder, health disparities, 
maternal mortality, HIV/AIDS, gun violence, climate change, and other 
areas with major implications for our Nation's health.
    First and foremost, the President's Request proposes $6.5 billion 
to establish the Advanced Research Projects Agency for Health--ARPA-H 
to drive transformational innovation in health research and speed 
application and implementation of health breakthroughs. ARPA-H will 
tackle bold challenges requiring large scale, cross-sector 
coordination, employing a non-traditional and nimble approach to high 
risk research, modeled after DARPA in the Department of Defense. To 
achieve this, ARPA-H will invest in emergent opportunities by 
conducting advanced systematic horizon scans of academic and industry 
efforts, leveraging novel public-private partnerships, recruiting 
visionary program managers, and using directive approaches that provide 
quick funding decisions to support projects that are results-driven and 
time-limited. Potential areas of transformative research driven by 
ARPA-H include: the use of the mRNA vaccines to teach the immune system 
to recognize any of the 50 common genetic mutations that drive cancer; 
development of a universal vaccine that protects against the 10 most 
common infectious diseases in a single shot; development of wearable 
sensors to measure blood pressure accurately 24/7; and leveraging of 
artificial intelligence technology to advance care for individual 
patients and improve detection of early predictors of disease.
    ARPA-H represents the kind of transformative idea for biomedical 
research that only comes along once in a long while. Our confidence 
that NIH is ready has been greatly advanced by our experience in 
addressing the COVID-19 pandemic--developing vaccines in record time, 
establishing an unprecedented public-private partnership on 
therapeutics that has made it possible to test more than a dozen 
possible therapeutics in rigorous trials, and building a venture 
capital model for assessing SARS-CoV-2 diagnostic technologies that has 
yielded millions of daily tests in just months.
    But while we begin to imagine a life after COVID-19, we must 
acknowledge that there are COVID-related impacts that we have yet to 
understand and address, including the full impact of the pandemic on 
children. Children were largely spared from COVID-19 but for some 
children, exposure to the COVID-19 virus led to Multisystem 
Inflammatory Syndrome in Children (MIS-C), a severe and sometimes fatal 
inflammation of organs and tissues. The Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD) is leading a 
multi-institute initiative known as the Collaboration to Assess Risk 
and Identify loNG-term outcomes for Children with COVID (CARING for 
Children with COVID), which will assess both short-term and long-term 
effects of MIS-C and other severe illness related to COVID-19 in 
children, including cardiovascular and neurodevelopmental 
complications.
    For many Americans, this pandemic and its related socioeconomic 
effects have had an overwhelming impact on their mental health. Prior 
research on disasters and epidemics has shown that in the immediate 
wake of a traumatic experience, large numbers of affected people report 
distress, including new or worsening symptoms of depression, anxiety, 
and insomnia. To aid in mental health recovery from the COVID-19 
pandemic, NIH will continue to focus on research in this area. This 
will be done, in part, by utilizing participants in existing cohort 
studies, who will be surveyed on the effect of the pandemic and various 
mitigation measures on their physical and mental health.
    The COVID-19 pandemic has brought into sharp focus the dramatic 
health disparities that exist across the American population. In 
addition, the Nation has been shaken by the killing of George Floyd and 
other attacks on people of color, forcing a recognition that our 
country is still suffering the consequences of centuries of racism. NIH 
will continue to address these disparities, specifically through 
research managed by the National Institute on Minority Health and 
Health Disparities (NIMHD), the National Heart, Lung, and Blood 
Institute (NHLBI), the National Institute of Nursing Research (NINR) 
and the Fogarty International Center (Fogarty).
    NIMHD looks to better understand the human biological and 
behavioral mechanisms and pathways that affect disparity populations, 
better understand the long-term effects of disasters on health care 
systems caring for populations with health disparities and research 
focusing on the societal-level mechanisms and pathways that influence 
disease risk, resilience, morbidity and mortality. NINR and Fogarty 
both look to better understand and reduce rural health disparities in 
low-income counties in the southern United States, support nursing 
science focused on racial, ethnic, and socioeconomic health 
disparities, with the goal of closing the gap in health inequities and 
increase health disparity research in low and middle income countries.
    In addition to the core health disparities research, the 
President's Request puts an additional specific focus on maternal 
morbidity and mortality (MMM), which disproportionately affect specific 
racial and ethnic minority populations. Black and American Indian/
Alaska Native individuals are two to four times more likely to die from 
pregnancy-related or pregnancy-associated causes compared to white 
individuals. Furthermore, Black, Hispanic and Latina Americans, Asian, 
Pacific Islander, and American Indian/Alaska Native individuals all 
have higher incidence of severe maternal morbidity (SMM) compared to 
white individuals. The Implementing a Maternal Health and Pregnancy 
Outcomes Vision for Everyone (IMPROVE) initiative supports research on 
how to mitigate preventable MMM, decrease SMM, and promote health 
equity in maternal health in the United States.
    As the climate continues to change, the risks to human health will 
grow, exacerbating existing health threats and creating new public 
health challenges. Major scientific assessments document a wide range 
of human health outcomes associated with climate change. While all 
Americans will be affected by climate change, underserved populations 
are disproportionately vulnerable. These populations of concern include 
children, the elderly, outdoor workers, and those living in 
disadvantaged communities. NIH is poised to lead new research efforts 
to investigate the impact of climate on human health, with the goal to 
understand all aspects of health-related climate vulnerability. 
Therefore, the President's Request includes a $100 million increase for 
research on the human health impacts of climate change.
    The FY 2022 President's Discretionary Request makes a major 
additional investment to address the opioid crisis. The crisis of 
opioid misuse, addiction, and overdose in the United States is a 
rapidly evolving and urgent public health emergency that has been 
exacerbated by the coronavirus pandemic. Since the declaration of a 
public health emergency for COVID, illicit fentanyl use and heroin use 
have increased, and overdoses in May 2020 were 42 percent higher than 
in May 2019.
    The use of opioids together with stimulants, such as 
methamphetamine, is increasing; and deaths attributed to using these 
combinations are likewise increasing. Taking note of these trends, FY 
2021 appropriation language expanded allowable use of Helping to End 
Addiction Long-term (HEAL) funds to include research related to 
stimulant misuse and addiction. Identifying how opioids and stimulants 
interact in combination to produce increased toxicity will enhance our 
ability to develop medications to prevent and treat comorbid opioid and 
stimulant use disorders and overdoses associated with this combination 
of drugs.
    Finally, I'd like to take a moment to thank this Subcommittee for 
its recognition over the last two years that America's continuing 
leadership in biomedical research requires infrastructure and 
facilities that are conducive to cutting-edge research. With your 
support, we will break ground in the near future on a new Surgical, 
Radiological, and Laboratory Medicine division of our Clinical Center, 
which will replace severely outdated and deteriorating operating suites 
and lab space with state-of-the-art facilities. NIH continuously works 
to ensure that the buildings and infrastructure on its campuses are 
safe and reliable and that these real property assets evolve in support 
of science--but NIH's backlog of maintenance and repair is now nearly 
$2.5 billion. The President's FY 2022 Discretionary Request includes 
$250 million to make progress on reducing this backlog and requests 
flexibility for Institutes and Centers to fund construction, repair, 
and improvement projects.
    COVID-19 compelled us to perform a stress test on biomedical 
research enterprise. The enterprise performed nobly. We found what 
worked, and also identified barriers we hadn't fully appreciated 
before, and invented new ways around them. The President's FY 2022 
Discretionary Request is a roadmap for how to build on the successes of 
research, address our gaps, and apply our insights to the most 
important problems we face as a nation. With your support, the future 
is filled with opportunity. My colleagues and I look forward to 
answering your questions.

    Senator Murray. Thank you very much, Director Collins. I 
have to say, I have always loved your success stories. They are 
usually really beautiful. But, I will say, I think many of us 
in this room are grateful to be your success story this time. 
So, thank you.
    We will now begin our 5-minute rounds of questions, and Dr. 
Collins, I will start with you.
    As you just talked about, the President's budget includes 
$6.5 billion to create the ARPA-H within NIH that is modeled 
after DARPA. DARPA is a small, $3.5 billion agency that is 
composed mostly of program managers and empowered to push the 
limits of their disciplines and shape some milestone-driven 
breakthrough technologies in short 3- to 5-year stints.
    Given that the nature of NIH's work is different, relying 
on a peer review system or multi-year grants that is 
traditionally risk-adverse, where progress is often measured in 
decades, how do you envision ARPA-H fitting into the NIH 
ecosystem?

                            ARPA-H STRUCTURE

    Dr. Collins. Senator, it is a great question. I think you 
are right that much of what NIH does requires this kind of 
careful, deliberative, investigator-initiated, hypothesis-
driven research, and that is going to be the mainstay of what 
we do going forward. That has been the success story of NIH for 
many decades.
    But, there are opportunities, as we have seen happen during 
COVID, such as the need to develop diagnostics in a hurry, to 
develop vaccines in a hurry, that are not really amenable to 
that approach, where you need to have program managers that are 
empowered to move things swiftly and have the flexibility and 
the resources to do so. And that is the DARPA model. We have 
studied that closely, and we do think that there are projects 
in biomedicine now that would be greatly advantaged by that. 
That is not the typical peer review process that may take a 
year from the idea to the first award. With RADx, we made those 
first awards 5 days after the Congress gave us the budget for 
it, and that played out really well.
    So, we want to incorporate that mindset, and we want to 
bring on perhaps a hundred of these program managers, give them 
the opportunity to build the kind of collaborative ventures 
that include such organizations as small businesses that might 
otherwise not be likely to write an NIH grant.
    Ride herd over these things carefully so that if they are 
not doing well, they get basically stopped immediately. We 
expect there will be failures--this is high risk--but identify 
the areas of greatest opportunity. And every Institute at NIH 
is now coming forward saying, I have at least five ideas of 
what I would like to do with ARPA-H that I cannot do right now.
    So, this should not be seen as competing with the 
Institutes. It is going to be a synergistic relationship that 
will allow us to do things otherwise that would take a very 
long time.
    Senator Murray. Okay. Well, you have said that it should be 
within the office of the director. In that structure, how would 
decisions be made about what projects to fund?
    Dr. Collins. So, we will need to hire a director for ARPA-
H, who will need to be a visionary person, and the idea is to 
bring on somebody who is not probably going to be doing this as 
their long-term career, but maybe for one term, 5 years, with 
one possible renewal.
    That person will be very much engaged then in bringing 
onboard these very creative program managers who have to make a 
pitch about what kind of projects they think are worth 
investing in and convince the director that that is the case. 
And, then, they are given the flexibilities to go out and find 
the right partners and see what can happen. But, that is all 
going to be done in a way that is quite nimble. It is not going 
to involve our traditional peer review process.
    Senator Murray. Okay.

                  STRUCTURAL RACISM AND HEALTH EQUITY

    Dr. Perez-Stable, your career has really focused on 
improving the health of communities of color and underserved 
populations. And NIH recently released a $30 million funding 
opportunity to study the impact of structural racism and 
discrimination in order to promote health equity and eliminate 
health disparities. Can you talk to us a little bit about what 
more can NIH, and particularly NIMHD (National Institute on 
Minority Health and Health Disparities), be doing to address 
those issues, and what would be the benefit of making 
additional investments?
    Dr. Perez-Stable. Thank you, Senator Murray, for that 
question. So, first of all, we had to recognize that structural 
racism could be operationalized as a research construct and not 
just an organizational construct, and we went through a 
workshop and scientific reflection on this. I think the moment 
earlier this year for all of the NIH Institutes and Centers 
agreed that this was an area that we needed to move on and 
advance more quickly in the research side. And, so, we had a 
commitment from all the institutes that do this, although NIMHD 
was leading it from the beginning.
    We believe that two areas are susceptible for improvement. 
One would be the healthcare setting, where I think through 
interventions at the structural, as well as the clinician and 
the patient level will help. And, also, in promoting healthy 
communities so that we can have easier access to green space, 
to healthy food, accessible healthcare in community health 
centers.
    These are two areas that we believe are susceptible for 
improvement, although we will depend on our scientific 
community to promote and submit ideas that will be reviewed and 
hopefully funded within fiscal year 2022.
    Senator Murray. Okay. Thank you very much. I look forward 
to working with you and hearing more about that.
    Senator Blunt.
    Senator Blunt. Thank you, Chairman.

                          ARPA-H FUNDING LEVEL

    Dr. Collins, on the ARPA-H budget request, $6.5 billion, 
one part of the question will be, how do you think that number 
was arrived at, and is that a realistic number to commit in 
year one?
    And two, our concern would also be that we do not get in a 
position that--we have already given NIH $6.5 billion and level 
fund everything else. I do like the President's $2.5 billion. I 
am sure you could figure out how to spend more than that in the 
other institutes. That is pretty close to the average of the 
last 6 years from our committee. I would certainly like to stay 
at least at that level.
    But, how do you think those two numbers compete with each 
other? And how do you feel about actually being able to commit 
$6.5 billion in that first fiscal year of ARPA-H?
    Dr. Collins. That is a great question, Senator, and we have 
thought a lot about it. I am pleased the President's budget 
proposes that this would be 3-year money because, obviously, 
you are going to start from a standing start whenever the 
budget actually gets approved for fiscal year 2022. We hope 
that will be September 30th, right? Well, it might not be. So, 
at any rate, we would then really be benefitted by being able 
in that first year to stretch those dollars over a little bit.
    I do think we could, with a hundred program managers, 
readily come up with a number of projects that would fit within 
that envelope on an annual basis. But, I hear what you are 
saying about a concern because I have heard it also that this 
might in some way compromise the interest of the Institutes. I 
guess I would look at it a different way, though.
    As I said earlier, every one of the Institutes is coming 
forward with great ideas about how they would like to use ARPA-
H. They think of this as an augmentation of their capabilities, 
not a subtraction. And, so, they will be feeding ideas into 
this and have a lot to do about how those are chosen. So, even 
though the base number that is being proposed, $2.5 billion for 
the ICs (NIH Institutes and Centers), may sound like a sort of 
average one, in terms of the science they can do, ARPA-H is 
going to add to that.
    Senator Blunt. All right. Thank you.

                       ARPA-H AND CANCER RESEARCH

    Well, Dr. Sharpless, one of the things the President, of 
course, talks about in this issue, in this topic, is more 
rapidly moving toward ending cancer. Obviously, we want to do 
that. We also want to make the point that that is not the only 
thing that ARPA-H would be focused on, nor would it just be 
cancer or Alzheimer's. But, on that topic, how do you envision 
the ARPA-H role in cancer research and what might you be able 
to do with ARPA-H that you are not able to do in the 
traditional restraints of the National Cancer Institute?
    Dr. Sharpless. Thank you for the question, Senator Blunt. 
It is great to be testifying in front of this committee again. 
Good to see you virtually, at least, today.
    Yes, as the President has said, ending cancer as we know it 
is a top domestic priority for this Administration. We are 
obviously, the cancer research community, is galvanized by this 
notion and very excited.
    I think, as you know, the National Cancer Institute does 
some things really well. You know, we fund basic foundational 
science very well. We can do clinical trials quite well. But, 
there are some areas where we are challenged, where we have 
struggles, and I think the scale and nimbleness and ability to 
interact with industry is very appealing about ARPA-H for 
certain kinds of cancer projects.
    I think a good example of that is this blood-based cancer 
detector technology that Dr. Collins mentioned in his opening 
statement where you can, you know, find cancers at a very early 
stage in otherwise asymptomatic, healthy people, and that could 
have a profound effect on cancer mortality.
    So, you know, getting up a huge trial of that technology as 
quickly as possible is the kind of thing that I think would be 
a good fit for ARPA-H.
    Senator Blunt. Okay. Thank you, Dr. Sharpless.

                           RADX PARTNERSHIPS

    Dr. Tromberg, let me see if I can get one more question in. 
I think what you were part of at RADx is one of the reasons 
that gives me real optimism about new kinds of relationships 
that we might develop at ARPA-H. But, would you talk just a 
little bit about RADx and how that partnership continued right 
through the entire process of these companies that you were 
choosing to invest money with, going ahead and making the first 
home-based test, and I think producing well over two million 
tests every day now, in addition to the tests that would have 
come through the regular process?
    Dr. Tromberg. Yes. Thank you so much, Senator Blunt, and 
thank you for your question and for your generous support of 
the RADx program.
    The bioengineering-technology community has formed 
partnerships all across the government. That has included 
working with BARDA, FDA, DOD (Department of Defense), CDC 
(Centers for Disease Control and Prevention), HHS (Department 
of Health and Human Services), and the White House Testing 
Board. More than 900 scientists are working across government, 
academia, and the private sector in a very unique way to make 
this work.
    And, as you have mentioned, if we fast-forward to now, 
about 1 year later, we now have 33 RADx-supported companies 
that have increased the Nation's testing capacity by more than 
300 million new tests, and there have been 23 new FDA 
authorizations. And we have really changed the dialogue from 
laboratory testing of symptomatic folks to over-the-counter, 
widely available tests, point-of-care tests that are accessible 
to all. Greater choice and greater capabilities. And this has 
really happened because of all of these partnerships that we 
formed, the accelerated innovation.
    We have brought out new technologies. About 20 percent of 
our portfolio actually--not many people know about--has been 
based in nanoscience and nanotechnology.
    Senator Blunt. Good.
    Dr. Tromberg. So it has been a tremendous surge for 
innovation.
    Senator Blunt. Thank you, Doctor.
    Thank you, Chairman.
    Senator Murray. Yes. Senator Reed.
    Senator Reed. Thank you very much.
    I want to welcome all the panelists and thank them for 
their distinguished service to the Nation, particularly during 
this difficult and challenging COVID pandemic.
    Dr. Collins, one of the things that is becoming 
unfortunately and painfully obvious is the increase in 
suicides, and this is very disturbing. And we are concerned, 
also, about the impact of COVID-19 on accelerating, perhaps, 
that phenomenon.

                           SUICIDE PREVENTION

    So, the question I would have is, what research is NIH 
doing on suicide prevention so that we can recognize the 
warning signs, better communicate with friends and family, and 
also give healthcare providers more insight? I am told that 
many suicide victims visit emergency rooms frequently before 
their suicide and those signs are not picked up. So, your 
comments would be appreciated.
    Dr. Collins. Well, I appreciate the question, Senator, and 
it is a source of great concern and obviously great heartache 
for the way in which this is taking a toll amongst people 
across our Nation, and certainly at a time where mental health 
issues have been even further heightened by all the stresses of 
COVID-19. One can see this also becoming even more of a threat 
to people who have lost hope.
    NIH is deeply engaged in trying to understand ways to 
prevent this terrible outcome, and the National Institute of 
Mental Health has in fact invested in a number of new 
initiatives as a result of that concern.
    One that I would point to that has turned out to be a 
pretty encouraging development is the recognition that the drug 
Ketamine, which is used in anesthesia and sometimes used as a 
party drug, unfortunately. It also turns out to have benefits 
for people with serious depression, including people with 
suicidal ideation. Now approved by FDA, and the drug 
Esketamine, this is now available and it is being used in those 
acute situations of acute suicidal threat.
    You also mentioned that many people who are on the brink do 
end up visiting healthcare facilities. We have worked hard to 
try to make sure that this idea of having a screening tool that 
was used in emergency rooms for individuals who are there, even 
if they do not appear to be there for psychiatric reasons, gets 
used to identify, particularly with adolescents, whether they 
might be in a situation of contemplating self-harm.
    On top of that, certainly NIMH is investigating other means 
of treating depression, and also thinking hard about other 
interventions that might be beneficial here in terms of 
cognitive behavioral therapy combined with pharmacotherapy to 
try to assist those individuals who are in this difficult 
place. But, it is a terribly difficult problem.
    I will say, it is interesting, but it is not necessarily 
that encouraging, the actual suicide rate, as best we know, in 
the course of the last year has not gone up. It has actually 
gone down slightly, and that has tended to be the case in 
national crises before. But, what I worry about is what happens 
when we seem to be getting past the crisis, is there a pent up 
backup there that might in fact result in an even greater risk 
in the coming months.
    I would be glad to give you more information. I am sure Dr. 
Gordon would, as well, in terms of all the things that we are 
doing.
    Senator Reed. Thank you very much.

                               LONG COVID

    Very quick question to both--to Dr. Fauci. The long haul 
COVID-19 is beginning to trouble a lot of people. They never 
seem to be able to recover from it and recurrences. What 
attention are we paying to that issue?
    Dr. Fauci. Thank you for that question, Senator. We are 
paying a considerable amount of attention to it. In fact, we 
have a program to the tune of $1.15 billion, looking at 
developing cohorts of individuals so that we can study them for 
the incidence, the prevalence, underlying pathogenesis, and, if 
possible, if we can find this out, anything that we can do from 
an intervention. So, the NIH is taking this very seriously. 
Thank you.
    Senator Reed. Thank you very much.
    I have to commend Dr. Sharpless for his efforts on 
childhood cancer. I was teamed up with Senator Capito. We 
passed the Childhood Cancer STAR Act. We have been funding it, 
thanks to the Chairwoman, at $30 million a year, and I want to 
commend NIH on its renewed emphasis on childhood cancer, not 
only treatments, but also gathering data about these victims as 
they age so that we can see if there is any interventions that 
we can use later on. So, thank you, Dr. Sharpless, and thank 
you, panelists. Thank you very much.
    Senator Murray. Thank you. Senator Graham.
    Senator Graham. Thank you, Madam Chairman.

                          VACCINE DEVELOPMENT

    The vaccine, developing the vaccine as fast as we did, what 
is your biggest takeaway, Dr. Collins? How did we do that? And 
how can we do it again if we have to?
    Dr. Collins. It is really important to look and see that 
this was built upon decades of research in basic science that 
many people might have said would not probably end up being as 
relevant as it turned out to be.
    Senator Graham. So, all of our money in the past paid off 
here, right?
    Dr. Collins. Absolutely. This committee, and then the 
Congress, especially over the course of the last 6 years where 
you have increased the NIH support by 40 percent, has made it 
possible for us to do a lot of things that otherwise we would 
still not have been able to start. So, yes, it is all built 
upon that foundation.
    Senator Graham. Do you feel like the budget request being 
made is enough to continue to build on what we have done?
    Dr. Collins. I am very supportive of the President's budget 
request, as you might expect I would be. And I am particularly 
excited about this new proposal of ARPA-H, a new component of 
NIH that would give us kind of a DARPA attitude that we could 
bring to projects that are waiting for that kind of 
opportunity.
    Senator Graham. Well, I just hope we can memorialize what 
we did to get the vaccine out so quickly.

                      GLOBAL VACCINE DISTRIBUTION

    The developing world--Dr. Fauci, one thing I worry about is 
getting the vaccine out into the developing world, particularly 
Africa. What can we do better in that regard? And why should 
we?
    Dr. Fauci. Well, first of all, the answer to your second 
question, which is very relevant, Senator, is why should we? 
And the reason we should is that a global pandemic requires a 
global response. And even though, as you well know from the 
numbers, we are doing extremely well in this Country--we now 
have over 60 percent of adults having at least one dose, and 
about almost 50 percent of the adult population in this Country 
fully vaccinated.
    However, even if we get this pandemic under control, which 
I believe we will within a period of a few months, there is 
always the danger, when you have viral dynamics in other parts 
of the world, for the generation of variants that might 
actually undermine the protectiveness of the vaccines that we 
have.
    Senator Graham. So, it is in America's interest to get the 
vaccine out to as many people as possible?
    Dr. Fauci. It is absolutely to our interest. I believe--not 
only do I think it is a humanitarian, moral responsibility, but 
it is in what I call enlightened self-interest for us to do 
that.

                           ORIGIN OF COVID-19

    Senator Graham. So, let's talk about our enlightened self-
interest for a moment. Has there ever been a pandemic that we 
know of that started in a laboratory somewhere?
    Dr. Fauci. To our knowledge, no.
    Senator Graham. Okay. If this were in fact a breach of 
protocols in China, if it did come out of a lab, that would be 
a first for the world; is that right?
    Dr. Fauci. I believe so. There was a situation with an 
influenza where there was a suspicion that it might have 
escaped from a laboratory in Russia.
    Senator Graham. But this----
    Dr. Fauci. But that has never been validated or confirmed.
    Senator Graham. So, have we found any animals that carry 
COVID-19 that could have been the source of the transmission to 
humans thus far?
    Dr. Fauci. Thus far, not. I mean, if what you are referring 
to, Senator, is an intermediate host----
    Senator Graham. Right.
    Dr. Fauci [continuing]. We know clearly, for example, with 
SARS-CoV-1 that a bat virus went into a civet cat, which then 
transmitted it into the human population. With MERS, it was a 
bat to a camel to human.
    The intermediate host, if there is one, has not yet been 
found.
    Senator Graham. And we have been looking for that 
intermediate host; is that fair to say?
    Dr. Fauci. That is fair to say, sir.
    Senator Graham. At what point in time would it become more 
likely it came from the lab if we do not find an intermediate 
animal host? How much longer?
    Dr. Fauci. I do not think we can give a time element on 
that, Senator, for the simple reason we still have not yet 
confirmed what the host is from Ebola. We know that Ebola jumps 
from an animal reservoir to human, and it has been many years 
now since the original Ebola outbreaks, and we have not yet 
nailed that down.
    Senator Graham. But we believe that Ebola did not come from 
a lab?
    Dr. Fauci. Yes.
    Senator Graham. Okay.
    Dr. Fauci. Yes.
    Senator Graham. So, I guess my point is, who should look, 
what should we be doing to make sure we find out how it 
started?
    Dr. Fauci. Right.
    Senator Graham. And finally, what should be the 
consequences to any country, China included that allowed this 
to happen? What should the world expect of a country if they in 
fact allowed this virus to come from one of their labs through 
negligence?
    Dr. Fauci. Well, first of all, when you said, who should, 
you know, the WHO (World Health Organization) did what they are 
referring to now as phase one of an investigation, which they 
felt was not completely adequate, as you know. You have heard 
me and Dr. Collins and others in the Administration calling for 
a continuation of the investigation.
    I do not think I can comment on your second question. It 
would have to be the circumstances under which something like 
that happened, if indeed it happened.
    Senator Graham. Well, just very briefly--I know my time is 
out--I think we should send a clear signal to China--seems to 
be a source of a lot of pandemics--that if this did occur in 
the lab, expect something to happen because if we do not, we 
are just going to reinforce this in the future. And what that 
something is, I am open-minded to, but I am closed-minded to 
the idea of doing nothing.
    Senator Murray. Thank you. Senator Shaheen.
    Senator Shaheen. Thank you, Madam Chairman, and thank you 
to you, Dr. Collins, and everyone at NIH for all of your hard 
work over the last very difficult year and for everything else 
you are doing.

                          ARPA-H AND DIABETES

    As you are aware, diabetes is one of the most expensive and 
pervasive of our chronic diseases, and I was pleased that in 
the authorization at the end--re-authorization at the end of 
the year, we funded the Special Diabetes Program for 3 years 
and the work that is being done to advance treatment for Type 
1.
    But, can you talk about this new ARPA-H agency and to what 
extent it might be looking at ways to help address diabetes?
    Dr. Collins. I would love to, and thank you for the 
question, Senator. This is the hundredth anniversary year of 
the discovery of insulin, so we have come a long way in those 
hundred years, but we are not where we really need to be to say 
we have conquered this one.
    ARPA-H, because of its ability to tackle problems in a 
team-oriented, nimble way, offers us some new opportunities 
here. Certainly, one of the ones that the Diabetes Institute 
has been promoting to me of late, sending me ideas, is to 
transform the way that we actually develop and test 
therapeutics, shouldn't we at this point be able to come up 
with therapeutics for diabetes that do not require injections. 
A totally new approach to how we would treat this disease.
    Another one that I am excited about, and I know you have 
done a lot of encouragement about this, is the artificial 
pancreas.
    Senator Shaheen. Right.
    Dr. Collins. And we have made real progress there, Senator. 
But, I think we could go a lot faster if we had this 
coordinated, ARPA X kind of attitude brought to this, both for 
artificial pancreases that are built on engineering and sort of 
a feedback loop that gives insulin when it needs to, but maybe 
even more so the ones that built upon the patient's own stem 
cells that can be converted into that.
    Senator Shaheen. And how do we make sure that diabetes is 
one of those diseases that ARPA-H addresses?
    Dr. Collins. Well, fortunately, because I think we do have 
a pretty good budget being proposed here, and diabetes is 
already mentioned by the President as one of the three areas of 
interest, I think diabetes is extremely likely to be on the 
list.
    Senator Shaheen. Good. Thank you. I am glad to hear that.

                     COVID-19 VACCINE BOOSTER SHOTS

    Dr. Fauci, the question that everybody is asking is, are we 
going to need a booster shot to complement our COVID 
vaccination? Do you have any sense of that and what the timing 
might be for that?
    Dr. Fauci. Two parts to that question, and they are 
separate but important. I do not anticipate that the durability 
of the vaccine protection is going to be infinite. It is just 
not.
    Senator Shaheen. Right.
    Dr. Fauci. So, I would imagine we will need at some time a 
booster. What we are figuring out right now is what that 
interval is going to be. We know from studies following people 
from the original clinical trials that the protection goes out 
at least 6 months, and likely a year. But, we do not know right 
now how long that will be.
    So, what we are doing is we are following those cohorts 
because there is a level of protection that is called a 
correlate of immunity, and we know that if you are above that 
level, you are in quite good shape to be protected.
    The vaccine itself gives you a level up here. So, how long 
it takes to start coming back down, we are following it, and 
two ways of understanding that. One, does, from a lab 
standpoint, it get below a certain level; or, do we start 
seeing a lot more breakthrough infections. Either of those 
would be a trigger. But, we are following that very carefully.
    So, in answer to your first part of your question, I 
believe we will need a booster. I am not exactly sure when.
    Senator Shaheen. Thank you.

          SUBSTANCE USE DISORDER AND METHAMPHETAMINE RESEARCH

    And, Dr. Collins, you may remember that New Hampshire is 
one of the hardest hit States by the substance use disorder 
epidemic. And we have seen a decline over the last year because 
of the pandemic, but we have also seen a replacement of many of 
those opioids by meth. I think there is a belief among some 
people who use substances that meth cannot kill you in the same 
way that an opioid can. And, yet, as I talk to providers, they 
tell me there are very few treatments that they have available 
to them to deal with meth.
    So, can you tell me what the National Institute on Drug 
Abuse is doing to try and address the meth piece of substance 
misuse?
    Dr. Collins. Absolutely. This is an area of intense 
interest and concern because what was primarily an opioid 
crisis is now very much becoming a mixed crisis of opioids and 
stimulants, and particularly methamphetamine.
    I was pleased to see that NIDA (National Institute on Drug 
Abuse) ran a trial, a phase three trial, on treatment for 
methamphetamine addiction, which is a combination of injectable 
Naltrexone and oral Bupropion, and showed benefit. We have not 
previously had anything to offer to help people who are 
addicted to meth. That is one step forward.
    We also now are running this effort to vaccinate people 
against methamphetamine. I know that sounds odd, but you could 
immunize against that compound in a way that it would no longer 
provide anybody much of a benefit if they decided to use it 
anyway. We are doing that for heroin and Fentanyl, and we are 
doing it for meth. But it is very helpful.
    Senator Shaheen. Excuse me for interrupting. Does that work 
if people have already been users?
    Dr. Collins. It will. So, basically, getting your immune 
system to make an antibody so that in the future, if you 
encounter that drug, it cannot get to your brain because the 
antibodies grab onto it.
    Senator Shaheen. I will have to learn more about that. 
Thank you. My time is up.
    Thank you, Madam Chair.
    Senator Murray. That is very interesting. Thank you.
    Senator Kennedy.
    Senator Kennedy. Thank you, Madam Chairman, Chairwoman.

                   GAIN-OF-FUNCTION RESEARCH IN CHINA

    Dr. Fauci, I believe you have testified that you did not 
give any money to the Wuhan lab to conduct gain-of-function 
research. Is that right?
    Dr. Fauci. That is correct.
    Senator Kennedy. How do you know they did not lie to you?
    Dr. Fauci. Excuse me, sir?
    Senator Kennedy. How do you know they did not lie to you 
and use the money for gain-of-function research anyway?
    Dr. Fauci. Well, we have seen the results of the 
experiments that were done and that were published and that the 
viruses that they studied are on public databases now. So, none 
of that was gain-of-function, so----
    Senator Kennedy. How do you know they did not do the 
research and not put it on their website?
    Dr. Fauci. There is no way of guaranteeing that, but in our 
experience with grantees, including Chinese grantees, which we 
have had interactions with for a very long period of time, they 
are very competent, trustworthy scientists. I am not talking 
about anything else in China. I am talking about the 
scientists. That you would expect that they would abide by the 
conditions of the grant, which they have done for the years 
that we have had interactions.
    Senator Kennedy. So you do not think the Chinese would lie 
to you?
    Dr. Fauci. Well, when you say the Chinese, the Chinese are 
a rather broad group. I know the scientists that we have dealt 
with have been trustworthy.
    Senator Kennedy. You think all the scientists have told the 
truth in terms of the origin of the Wuhan virus and not been 
influenced by the communist party of China, do you?
    Dr. Fauci. I do not have enough insight into the communist 
party in China to know the interactions----
    Senator Kennedy. Right.
    Dr. Fauci [continuing]. Between them and the scientists, 
sir.
    Senator Kennedy. Right. Why are we giving them money in the 
first place?
    Dr. Fauci. Well, that is a very good question, and thank 
you for giving me the opportunity to----
    Senator Kennedy. You are welcome.
    Dr. Fauci [continuing]. Answer it. Well, SARS-CoV-1 started 
in China in Guangdong Province, and it went from a bat to a 
civet cat to a human.
    Senator Kennedy. Yes, and excuse me, Doc, for interrupting 
you, but our time is so limited.
    Dr. Fauci. No, no. I am going to be real quick.
    Senator Kennedy. Our time is so limited. Why are we giving 
money to the labs in China to study virology?
    Dr. Fauci. Well, I am going to give you a rather succinct 
answer to that, sir.
    Senator Kennedy. I would appreciate that.
    Dr. Fauci. And that is why I was saying the SARS-CoV-1, 
clearly the bats that have the viruses that are the 
coronaviruses are in China. As I said a couple of times, it is 
not in Fairfax County, Virginia or is it in New York. It is in 
China. So, if you want to show and study importantly the 
animal-human interface, the viral----
    Senator Kennedy. Because that is where the bats are?
    Dr. Fauci. Yes, the bats.
    Senator Kennedy. Okay. I got it.
    Dr. Fauci. That is where the bats are.
    Senator Kennedy. I want to be sure I understand your 
testimony. You did not give money to the Wuhan lab to do gain-
of-function research?
    Dr. Fauci. That is correct.
    Senator Kennedy. And you believe they did not do gain-of-
function research because they told you they did not?
    Dr. Fauci. We have seen the results of the studies that 
they conducted and they were not gain-of-function.
    Senator Kennedy. Including any private studies?
    Dr. Fauci. Excuse me? Including?
    Senator Kennedy. Any private studies.
    Dr. Fauci. I am not sure what you are getting at, sir.
    Senator Kennedy. Here is what I am getting at. You gave 
them money and you said, don't do gain-of-function research.
    Dr. Fauci. Correct.
    Senator Kennedy. And they said, we won't?
    Dr. Fauci. Correct.
    Senator Kennedy. And you have no way of knowing whether 
they did or not except you trust them; is that right?
    Dr. Fauci. Well, we generally always trust the grantee to 
do what they say, and you look at the results----
    Senator Kennedy. Have you ever had a grantee lie to you?
    Dr. Fauci. I cannot guarantee that a grantee has not lied 
to us because you never know.
    Senator Kennedy. Yes. Can we agree that if you took 
President Xi Jinping and turned him upside down and shook him, 
the World Health Organization would fall out of his pocket?
    Dr. Fauci. I do not think I can answer that question, sir. 
I am sorry.
    Senator Kennedy. Well, do you think President Xi Jinping 
has undue influence over the World Health Organization, do you?
    Dr. Fauci. I have no way of knowing the influence of the 
president of China over the WHO.
    Senator Kennedy. Okay. So you think the WHO is a completely 
independent body and level playing field, call-it-like-you-see-
it, and they really want to get to the bottom of the origin of 
the virus? Do you believe that?
    Dr. Fauci. My interaction with the WHO and for Dr. Tedros, 
the Director General, has been one----
    Senator Kennedy. Okay.
    Dr. Fauci [continuing]. That I do believe he is a person of 
high degree of integrity.

                 INVESTIGATION INTO ORIGIN OF COVID-19

    Senator Kennedy. I got it. I want to ask one last question. 
Why did you guys spike--not guys, and ladies. Why did you all 
spike the prior administration's investigation into the origins 
of the coronavirus and whether it could have come out of the 
Wuhan lab?
    Dr. Fauci. Sir, I--we did not spike anything in the prior 
administration. I am not sure what you mean by spike. But, we 
have no influence----
    Senator Kennedy. The State Department spiked the prior 
administration's study.
    Dr. Fauci. But that has nothing to do with the National 
Institutes of Health.
    Senator Kennedy. So they did not consult with you all?
    Dr. Fauci. They did not.
    Senator Kennedy. Did they consult with you, Dr. Collins?
    Dr. Collins. I read about it in the press this morning.
    Senator Kennedy. Doc.
    Dr. Bianchi. No.
    Senator Kennedy. They just spiked it without talking to 
their experts?
    You do not want to answer that one, do you?
    Dr. Collins. I just read about it.
    Senator Kennedy. Thank you, Madam Chair.
    Senator Murray. Senator Murphy.
    Senator Murphy. Thank you very much, Madam Chair.
    Listen, the World Health Organization is the most 
influential global public health institution in the world, 
whether my friends like it or not. They have more people and 
more influence on the ground across the world than anybody 
else, including the United States.
    And, so, if the complaint is that any country, including 
China, has too much influence, the answer is not for the United 
States to walk away. The answer is for the United States to 
double down and make sure that any grievances we have are 
addressed. Otherwise, the problem for which you are identifying 
is exacerbated by the United States not being at the table with 
the WHO.
    And while the major donors to that organization certainly 
have lots of influence, as is the case with every international 
organization, it is an oversimplification to suggest that they 
are in the pocket of the Chinese government. China has 
influence. The United States has influence, as well, so long as 
we are at the table.

                           FIREARMS RESEARCH

    I have two areas to cover, and the first I wanted to raise 
with you, Dr. Collins, and that is around the budget request to 
double the firearm injury and mortality prevention research 
account. Let me place myself solidly behind that request. Thank 
you for making it, and I was hoping you might--I apologize if 
you have gotten a question on this already. I have been 
listening but in and out a bit.
    I am hoping that you might be able to talk a little bit 
about how you might prioritize that additional funding, 
especially as it might relate to research on community-based 
interventions and what works and what does not. And, then, you 
know, how to make sure that all that information gets out to 
community partners, folks who are boots on the ground, maybe 
not the exact set of players that NIH is used to disseminating 
information to.
    Dr. Collins. Well, I appreciate the question, and we are 
enthusiastic about expanding our approach and the amount of 
funds we can put into research on firearm violence. After all, 
some 40,000 deaths happen each year from firearms. About 60 
percent of those are suicides, which is another topic that came 
up earlier and is also part of our suicide prevention, is to 
think about availability of guns.
    I think you are right, though, that community approaches 
are very much ripe for this kind of approach, where you might 
not just try to change one thing in the community, but see if 
by coordinating the efforts across multiple different ways in 
terms of making sure that firearms are not accessible to those 
people who might misuse them; in terms of particularly 
adolescent and youth risks of violence and how to intervene.
    Maybe we could take an approach that would be more holistic 
as opposed to trying to fix one thing at a time. With a larger 
amount of funding here and a community focus, I think we might 
be able to do that.
    Senator Murphy. The President has proposed, I think, $5 
billion to support these community-based interventions. Maybe 
some of that will be used for assessment and study. But, given 
the fact that I think we probably can get bipartisan agreement 
about supporting these investments in prevention, it really 
would be helpful to use some of this increased funding to 
assess which ones work and which ones do not.

                     SOCIAL DETERMINANTS OF HEALTH

    Second broad topic, and maybe I will address this both to 
Dr. Collins and I think, via video, Dr. Perez-Stable, is on the 
topic of social determinants of health. And I am just 
interested to hear a little bit about how we have adjusted 
research based upon our growing understanding that people's 
health is dictated by where they live and how much money they 
make and how close they are to pollution sources.
    My sense is that, you know, this is not an easy sort of 
thing to incorporate into a research community that is sort of 
used to working in labs and not always used to thinking about 
how factors outside the body impact health. What have we 
learned? How has that changed the way that we fund research and 
encourage applications to come to NIH that might support social 
determinant research?
    Dr. Collins. I am going to ask Dr. Perez-Stable to respond.
    Dr. Perez-Stable: Thank you, Dr. Collins, and thank you, 
Senator Murphy, for that important question.
    At the National Institute on Minority Health and Health 
Disparities, and throughout NIH, the topics of social 
determinants of health have always been present. We consider 
self-identified race and ethnicity and socioeconomic status 
standard measures to be fundamental factors that influence 
health in ways that we do not really understand, and that is 
why we believe that all research with human beings should 
measure these routinely and follow them.
    In addition to these two, though, there are other 
demographic and individual social determinants of health, of 
which many are issues related to age and gender, sexual 
orientation, but then structural social determinants of health 
that you refer to. Where one lives, plays, and prays, relate to 
both transportation, housing, and issues around green space 
and, of course, Internet access, which has become incredibly 
important, as we know, in the last year. So, we have these 
fundamentally incorporated into our standard research, and 
community engagement is really part of everything that we do at 
NIMHD, and increasingly across the Agency.
    Senator Murphy. Well, thank you for that. I appreciate the 
new focus you are putting on this. Again, this is an area of 
potential bipartisan agreement. Senator Sullivan and I have 
legislation in this space and look forward to working with you 
on it.
    Thank you, Madam Chair.
    Senator Murray. Thank you. Senator Shelby, are you ready? 
You want me to----
    Senator Shelby. Yes, I am ready.
    Senator Murray. Okay.
    Senator Shelby. I just got here. Thank you. I have been at 
another hearing, and this question may have been asked.
    Dr. Collins, always good to see you.
    Dr. Collins. Likewise.
    Senator Shelby. I agree with a lot of people on this 
committee that the money we put in to biomedical research 
benefits mankind, period. Not just our people, but the world, 
what it has taught.

                   AUTOIMMUNE RESEARCH BREAKTHROUGHS

    Two or three promising areas, biomedical research in the 
area of autoimmune--that is a big, big topic. You know it 
better than anybody. What are we--what are the breakthroughs 
there, the hopes, in two or three of those top areas?
    Dr. Collins. Well, thank you, Senator. It is good to see 
you, and I know you are running from one place to another. I am 
glad you are here.
    I just had a wonderful experience yesterday afternoon 
listening to presentations from a consortium of researchers 
that we have funded jointly with industry. So, this is called 
the Accelerating Medicines Partnership, and it is focused on 
rheumatoid arthritis and lupus.
    What they have done is to take this field, which was 
looking at immunology in a way that was pretty cutting edge 5 
years ago, and now completely transformed it by looking at 
individual immune cells in the synovium of people with 
rheumatoid arthritis--the lining of the joint--and say, what 
are you doing there, immune cells, and how does that teach us 
what the real pathogenesis about----
    And for lupus, they are looking at kidney biopsies, 
because, of course, lupus affects the kidney and that is one of 
its serious consequences. Same thing, looking at individual 
cells.
    It has completely revamped our understanding of these 
diseases. We have learned, for instance, that the pericyte, 
which was just sort of a cell that we thought was hanging out 
watching in the kidney of somebody with lupus, might be the 
driver of what is really happening there as far as the immune 
response. This is not p-a-r-a. This is p-e-r-i, cyte, in case 
that is not clear. For rheumatoid arthritis, it is the 
fibroblasts.
    And we are so excited about this. We are now planning to 
expand that same approach to other autoimmune diseases, to 
psoriasis, to psoriatic arthritis, to Sjogren's Syndrome, and 
maybe others, as well.
    So, you hit me at a great moment. I was so jazzed yesterday 
to see what has been possible.
    Senator Shelby. All based on bacteria, is it?
    Dr. Collins. It is all based on this ability to look at 
single cells, one at a time. We have not really been able to do 
that until about 5 years ago. We would have to look at 
thousands of cells and try to infer what was there, and now you 
can ask each one. And the cell is, after all, the basic unit of 
all life, and it has been outside of our reach, but not 
anymore.
    Senator Shelby. What could that do for the autoimmune area?
    Dr. Collins. I think it can have a huge impact because we 
now have new targets coming out of this recognition that I 
think in the next 4 or 5 years, we are going to see a whole new 
generation of drugs for autoimmune diseases based upon that 
insight that is just now emerging.

                        CYSTIC FIBROSIS RESEARCH

    Senator Shelby. I brought this up many a time, but in the 
area of cystic fibrosis, there have been so many breakthroughs 
in that area, extending children's lives, adults' lives, and 
everything. Where are we going there? We have come a long way, 
but we are not there yet.
    Dr. Collins. We are not completely there, but, oh, boy, 
have we come a long way, especially in the last 2 years now 
with this 30-year effort, and I have been deeply engaged in 
this having had a role in----
    Senator Shelby. I know.
    Dr. Collins [continuing]. Discovering the gene back in 
1989. And, now, we have this triple drug therapy, which for 90 
percent of patients with cystic fibrosis is dramatically 
beneficial. I get messages almost every week from somebody who 
was really in tough shape, and now they are back at work; or 
somebody who was on a transplant list, and now they were taken 
off of it because their lungs are doing so much better.
    But, there is still that 10 percent. This is where I think 
the gene-editing approach, where you actually figure out how to 
fix that misspelling of the cystic fibrosis gene in the lungs 
of somebody who is affected, might be the way to get to 100 
percent, and there is a lot of work going on that.

                             LUPUS RESEARCH

    Senator Shelby. What promises are out there that you have 
talked about before dealing in lupus, which is an autoimmune 
disease?
    Dr. Collins. Well, as I mentioned, we have this ability now 
to be able to see individual immune cells, what are they up to 
in lupus, both in the kidney and in other areas, as well. I 
think that is teaching us some new things about what the real 
fundamental cause is. And it will tell us that some of the 
treatments we have been giving, like steroids, are kind of a 
little bit too much of a sledgehammer, and what we need now is 
something much more subtle to go after the fundamental problem. 
We have a better chance at that now.

                       PANCREATIC CANCER RESEARCH

    Senator Shelby. What about the area of pancreatic cancer? 
That is a fast-moving thing, I know.
    Dr. Collins. It is, indeed. And if Dr. Sharpless is 
listening, maybe he would like to quickly give a response since 
that is his area at the Cancer Institute. Ned, are you there?
    Dr. Sharpless. Sure. Yes. Thank you, Francis.
    Pancreatic cancer is an area where we have not seen the 
success that we have seen in other cancers, but it is not for 
lack of good ideas. So, there are a number of----
    One of the realizations is that pancreatic cancer comes in 
lots of flavors, and each one needs its own treatment. So, now 
we are working on the subset approach to pancreatic cancer. I 
think there is also a real opportunity to detect pancreatic 
cancer earlier at a more curable stage.
    So, I think those are the exciting areas of pancreatic 
cancer research.
    Senator Shelby. Thank you. I would like to get in--I know 
my time is moving on. The chairperson has been very kind.

                              CTSA PROGRAM

    Dr. Collins, in the area of the CTSA Program, the Clinical 
and Translational Science Award Program. The CTSA hubs and 
their partners, I think, have done a lot of good work in that 
area, and valuable work, especially during the COVID-19 thing. 
It is my understanding that the NIH, National Institutes of 
Health that you head, is considering significant changes to 
that program that would discourage hubs, like UAB, for example, 
in Birmingham, from forming partnerships with certain non-
clinical universities in research questions.
    Is this true, and why is that?
    Dr. Collins. That is not a correct assumption. I know there 
are some rumors flying around about that, and there will be a 
public announcement about this.
    Basically, just, without trying to get too far ahead of 
what has not been revealed publicly, I think we are trying to 
simplify the application process to make it easier for those 
hubs, and we intend to keep them going in vigorous ways; to 
apply when they are up for renewal in a way that does not 
require an application of 2,000 pages, which is what it has 
been. But, we would not want to do anything to discourage these 
collaborations that you are mentioning. Take that from me.
    Senator Shelby. Thank you. Madam Chair, thank you.
    Senator Murray. Thank you. Senator Manchin.
    Senator Manchin. Thank you, Madam Chairman, and thank all 
of our presenters. I appreciate very much them being here.

                       DOMESTIC DRUG SUPPLY CHAIN

    My first question will go to Dr. Fauci. The Food and Drug 
Administration reports that nearly 40 percent of finished drugs 
and roughly 80 percent of active pharmaceutical ingredients are 
manufactured abroad. During the COVID-19 pandemic, we saw 
factories shut down in order to prevent the spread of virus, 
drug supply chains disrupted, and drug shortages increase. As a 
result, America's access to essential medicines was really put 
into jeopardy.
    As a preeminent infectious disease doctor, you know better 
than anyone how important it is to have access to essential 
medicines. So, my question will be, Doctor, can you comment on 
the importance of a strong domestic supply chain for essential 
medicines? And how can we ensure we do not experience future 
drug shortages when the global supply chains are disrupted?
    Dr. Fauci. Thank you very much for the question, Senator 
Manchin. I think it is absolutely critical that we have the 
capability, independent of supplies from foreign countries, to 
be able to supply the necessary medicines that we need in the 
United States. I have been of that opinion for a very long 
period of time.
    The solution to the problem is to be doing much less of the 
outsourcing to foreign countries for the important ingredients 
of many of our medications. So, right now, we are not in that 
good position, and I believe, particularly since the 
disruptions of the supply chain that have occurred with the 
COVID-19 pandemic, that this might be a good lesson for us for 
the future to make sure we have much more dependency on what we 
can do domestically as opposed to in foreign nations.
    Senator Manchin. Doctor, have you all looked at why? Why 
has most of the manufacturing left the United States and why 
are we not able to manufacture? Are we at a disadvantage in the 
United States for other reasons, cost wise, or basically 
different types of things, that we make people jump through 
hoops and everything else as far as permitting and all that? 
What would be the cause?
    Dr. Fauci. You know, Senator, to be honest with you, I do 
not know why that has happened. I think it was because it was 
felt it would be much less expensive to get this done outside, 
but I do not really know the answer to your question of why we 
have so much of a dependency of important materials outside of 
the Country. But, certainly, whatever the reason, I believe it 
needs to be corrected.
    Senator Manchin. Well, I need to work with you on that, 
Doctor, if I can, basically, in making sure this 
Administration--I think they understand the urgency we need to 
start basically manufacturing again, not only just our drugs, 
but so many things in our Country. So, I look forward to your 
support on that.

                         RURAL HEALTH OUTCOMES

    Dr. Collins, West Virginia is constantly ranked last in the 
Nation for health outcomes. In 2020, the America's Health 
Rankings reported my State of West Virginia 50th for premature 
deaths, frequent mental distress, and multiple chronic 
conditions. We also ranked last in life expectancy.
    What is the NIH doing to bridge this gap in health 
outcomes? And how do you ensure that the medical research that 
you do benefits people in poor, rural communities?
    Dr. Collins. Well, it is very troubling to see the fact 
that you have just cited that health outcomes are not what we 
would all want them to be. And, of course, there are many 
factors that play into that, Senator, and we are deeply engaged 
in research in trying to identify the ones that are 
addressable.
    Certainly, one of the things I might point to is the 
increasing focus we have on disease prevention. If we simply 
are limiting ourselves to trying to help people who have 
already developed a serious disease, we have kind of missed the 
opportunity. Unfortunately, our healthcare system does not do a 
great job in that situation of providing support for disease 
prevention, and it seems happier to pay for things once people 
are already quite ill, so there is additional work that needs 
to be done there.
    One of the things that I think I would point to is a series 
of large-scale efforts to really understand what are the 
factors that play out in people staying healthy or getting a 
chronic disease or how you manage that.
    The All of Us Program, which this Congress has supported, 
on the way to enrolling a million participants, including in 
West Virginia, is a way in which we can collect that kind of 
evidence, including their electronic health records and lots of 
information about their environmental exposures, and try to 
figure out in a holistic way, how can we take that information 
and bring forward a better chance for people to live not just a 
good lifespan, but a good health span. So, we are----
    Senator Manchin. Thank you, Doctor.
    Dr. Collins [continuing]. Deeply engaged.
    Senator Manchin. Thank you, sir.
    Dr. Fauci, finally, you know, my home State of West 
Virginia is battling an epidemic during the middle of a 
pandemic. We have been devastated by the drug epidemic, COVID-
19, and now--we now lead the Nation in new HIV infection rates. 
You spent much of your career focused on prevention, diagnosis, 
and treatment of HIV/AIDS, and your research has been 
instrumental in saving countless lives in the United States and 
around the world.

                INFECTIOUS DISEASE SURVEILLANCE EFFORTS

    So, Doctor, what is being done to replicate testing and 
surveillance efforts we saw put into place for COVID-19 for 
other infectious disease, like HIV/AIDS? And what public health 
infrastructure would be required to bring better infectious 
disease testing and surveillance to fruition?
    Dr. Fauci. Thank you for that question, Senator. The HIV 
testing situation, unfortunately, has been somewhat interrupted 
by the COVID-19 pandemic because of the interruption of 
multiple services.
    But, as you know, we have a 10-year plan to end HIV as an 
epidemic in the United States, and that is going to require 
access to testing for those who are not infected to put them 
on, if they are at risk, to pre-exposure prophylaxis; and those 
who are infected to immediately put them on antiretroviral 
therapy. Because, as we know, when you bring the level of virus 
to below detectable, not only do you save the life of the 
individual, but you make it essentially impossible for that 
individual to infect someone else.
    So, testing is really at the fundamental basis of how you 
address the epidemic and, for that reason, it is going to be 
extremely important to get our testing capabilities back up to 
snuff once we get the Country back on a degree of normality 
following control of the COVID-19 pandemic.
    Senator Manchin. Thank you. Thank you, Madam Chairman.
    Senator Murray. Thank you. Senator Braun.
    Senator Braun. Thank you, Madam Chair.
    Dr. Fauci, I was listening with interest in Senator 
Kennedy's line of questioning, which probably was asking you to 
maybe answer some things based upon what the WHO should do or 
not.

                 INVESTIGATION INTO ORIGIN OF COVID-19

    I would like to discuss something that is probably a little 
simpler to answer in terms of transparency in general. From the 
time I have known you and Dr. Collins, it has generally been in 
this seat, and we have been talking about something related to 
COVID. Would you agree that in the whole process of--now that 
there are second thoughts on how this thing derived, that it 
may have come from a lab, that we should emphasize as much 
transparency as possible in pursuit of getting the answer?
    Dr. Fauci. Without a doubt, Senator. No doubt.
    Senator Braun. And the next logical question would be that 
we do not know what we are going to get from the communist 
regime or the WHO, but we do know that through our Director of 
National Intelligence and probably DHS (Department of Homeland 
Security), from Haines and Mayorkas, that they have probably 
got information there. And, so, since you believe in 
transparency, wouldn't you think that we should declassify all 
the information that we own so that you, Americans, independent 
researchers, can see what we have got to sort through how this 
thing started?
    Dr. Fauci. Well, Senator, I have said publicly and most 
recently that I believe that there should be transparency, and 
open, fair, and independent, continue to look. As I have said, 
I still believe that the most likely scenario is that this was 
a natural occurrence, but no one knows that 100 percent for 
sure. And since there is a lot of concern, a lot of 
speculation, and since no one absolutely knows that, I believe 
we do need the kind of investigation where there is open 
transparency and all the information that is available to be 
made available to scrutinize.
    Senator Braun. So, since you have been the point person on 
just a variety of topics through the COVID saga, does that mean 
then that you will ask President Biden to declassify that 
information?
    Dr. Fauci. I do not think I can promise you----
    Senator Braun. But, I mean, would you ask him since you 
believe in transparency? Wouldn't it make sense that we get the 
information that we have? And I think if it does not come from 
you, Dr. Collins, someone that has been in the mix from the 
get-go, that we will not see it. And we owe it to the American 
people with what we have been through to at least look at the 
information that we have.
    Dr. Fauci. Yes. I am not sure the information we have, 
but--I am not sure if it is my place to tell the President of 
the United States to declassify----
    Senator Braun. But you have been very engaging on a wide 
range----
    Dr. Fauci. Right.
    Senator Braun [continuing]. Of topics, and I think he would 
respect your opinion as much as anyone.
    Dr. Collins, where are you at on that subject of giving the 
American people the information that we house?
    Dr. Collins. Well, I am very much where Dr. Fauci is with 
the desire to be as transparent as possible in this situation 
and really try to find out what happened. I agree with him that 
it is most likely that this is a virus that arose naturally, 
but we cannot exclude the possibility of some kind of a lab 
accident. That is why we have advocated very strongly that WHO 
needs to go back and try again after the first phase of their 
investigation really satisfied nobody, and this time we need a 
really expert-driven, no-holds-barred collection of 
information, which is how we are mostly really going to find 
out what happened.
    I am just not in a position to know what might be in the 
classified documents and what else might be there that would 
not be relevant to this and might actually be harmful to 
national security. I get--I take your point. But, I know the 
President is very interested, also, in seeing truth come out 
here, so it may not require Tony or me to tell him that this 
would be good, to make this as visible as possible.
    Senator Braun. Well, I think for the American public, if we 
are relying on the WHO to do it again, even though it seems 
like they have had somewhat of an epiphany that we need to dig 
deeper. I think if it does not come from the two of you to ask 
for simply the release of information, of course, keeping 
hidden anything that would be something that could not be 
exposed. But, I am guessing there is a good bulk of that that 
would be benign in terms of just the information we have about 
the origin of the disease.
    So, I think for many of us, many Americans, with what we 
have gone through, we ought to at least be willing to look at 
the information that we have to get people satisfied that we 
are getting to the bottom of it. So, I would ask each one of 
you to think about that and see if it makes sense, have our 
President declassify it so we can see it.
    Dr. Collins. Thank you.
    Senator Braun. Thank you.
    Senator Murray. Thank you. Senator Moran.
    Senator Moran. Chairman, thank you.
    Dr. Collins--well, Doctors, welcome. Good to be here with 
you, and I appreciate your presence and your work.
    Let me talk about clinical and translational science, if I 
could. Under Dr. Austin's prior leadership, the National Center 
for Advancing Translational Science at NIH has been essential 
in facilitating clinical and translational research, and I have 
seen it in Kansas. In fact, I have seen it with the director of 
that directorate.

                              CTSA PROGRAM

    In Kansas, NCATS' Clinical and Translational Science Award 
Program has served for a catalyst to bring lots of 
organizations in the research community and community partners 
together to advance research.
    I have concerns with potential changes that are under 
consideration for the CTSA Program. In particular, changes that 
would lower hub awards and limit CTSA partners.
    Moving forward, will there continue to be consideration for 
ensuring that CTSA centers are located in regions in the U.S. 
which do not already have those hubs? There is already a 
limited number in the Mid-West, and I would be concerned if any 
new changes to the program that would make it more difficult 
for these hubs to compete.
    And, then, I would ask the question about partners. At the 
University of Kansas, for example, they partner with Children's 
Mercy, Kansas City University of Medicine and Biosciences, 
Kansas State University, St. Luke's Health, University of 
Kansas Health System, KU Office of Research, KU School of 
Medicine in Wichita, and University of Missouri in Kansas City. 
Since the CTSA Program is focused on partnerships between 
regional research hubs and community partners, why would NCATS 
limit the ability of the program, in my view, to accomplish its 
goal?
    Dr. Collins. Well, Senator, thank you for the question. I 
am a big fan of the CTSA Program and enjoyed my opportunity to 
travel to Kansas with you and see some of the things they were 
doing a few years ago.
    And this is, I think, one of those circumstances where 
there seems to be some anxiety in the CTSA community about 
something that has not actually been announced yet, and I would 
like to be reassuring about this. The real intention of the 
change that is being proposed is to de-complicate the renewal 
process, which currently requires an application of about 2,000 
pages that I do not think anybody enjoys putting together, and 
to try to make this more straightforward.
    There is no intention to reduce the number of hubs. 
Certainly, every hub has to compete to show that they are 
actually using the funds wisely, and we will continue that 
process. And this notion that somehow the new process will 
discourage collaborations with other institutions I find a 
little hard to understand because I have no knowledge that that 
is at all intended to be the case, and I would personally 
oppose that.
    Senator Moran. Thank you for your reassurance. My question 
was more complicated than I wanted it to be, but your answer 
was very comforting.
    Let me ask just a couple of specific questions.

                      NCATS RARE DISEASE RESEARCH

    What can this committee do to support NCATS' efforts to 
enable and facilitate advanced important research in rare 
diseases for patients living particularly in rural communities?
    Dr. Collins. Well, the NCATS is deeply engaged in rare 
diseases. Our former director, Chris Austin, not only was a 
personal promoter of that; he was the head of the international 
committee for rare diseases, and that tradition will continue 
under Acting Director, Dr. Rutter.
    Certainly, the support that this committee has provided to 
NCATS to make it possible for that kind of investment to happen 
in rare diseases, for which companies probably are not going to 
make an investment because the market is too small, is one of 
the reasons that we have now made really significant progress 
in dozens of these rare diseases.
    We are also engaged right now in a serious conversation 
with industry about whether there is a way, with gene therapy 
emerging as an even more attractive opportunity for rare 
diseases, to make sure that we move that forward at all due 
speed and not have it held up by such things as a limitation in 
manufacturing of viral vectors.
    So, they are right in the middle of that, and the support 
that you all have provided has made that possible, particularly 
through the Cures Acceleration Network, which is part of NCATS.

                      ALZHEIMER'S DISEASE RESEARCH

    Senator Moran. Can one of the directors talk about the 
improved science this additional investment in Alzheimer's 
research will help fund, including a better understanding of 
risks and protective factors in individuals, again perhaps with 
a focus on rural populations?
    Dr. Collins. That is probably me because Dr. Hodes is not 
here. So, yes, this committee, this Congress, has increased 
funding for Alzheimer's research by five-fold over the course 
of the last 7 or 8 years, and that has made possible all kinds 
of bold approaches we otherwise would not have had.
    We now have dozens of new drug targets that have emerged 
from the very careful analysis of who gets Alzheimer's and who 
does not. Of course, we are all waiting to see what happens 
maybe next month when FDA makes a review decision about the 
monoclonal antibody from Biogen, Aducanumab, and that will make 
a big difference if they decide there is something there. But, 
we are not depending on that.
    So, yes, I might add, this ARPA-H proposal, which is part 
of the President's budget, specifically calls out Alzheimer's 
as an area of great opportunity to do some of these very bold, 
aggressive, and nimble approaches that would probably not 
happen so easily by our standard grant mechanism.
    Senator Moran. Dr. Collins, I was confused by what I 
thought was all the directors were appearing, although just not 
all of them in person. But, thank you. You can pinch-hit for 
each and every one of them and you did it----
    Dr. Collins. I will try.
    Senator Moran [continuing]. This morning. I am going to see 
if I can get Dr. Sharpless to come to Kansas and join us again 
on a visit.
    Dr. Collins. Well, he is listening, so he heard you.
    Dr. Sharpless. Oh, I look forward to that.
    Senator Moran. All right. Consider yourself invited, and I 
consider you just accepted.
    [Laughter]:
    Senator Murray. Thank you. Senator Schatz.
    Senator Schatz. Thank you, Chair Murray and Ranking Member.

                       PSYCHEDELIC DRUG THERAPIES

    Dr. Collins, in 2019, I wrote to you and the then-FDA 
commissioner requesting an update on efforts by NIH and FDA to 
research psychedelic drugs to treat mental health illnesses. 
Since then, there have been a number of potentially promising, 
peer-reviewed clinical research on this topic. Can you give me 
an update on what the next steps may be?
    Dr. Collins. I appreciate the question. Yes, there has been 
a resurgence, I think, of interest in psychedelic drugs, which 
for a while were sort of considered like not an area that 
researchers legitimately ought to go after. And I think as we 
have learned more about how the brain works, we have begun to 
realize that these are potential tools for research purposes 
and might be clinically beneficial.
    I will just mention one, which is Psilocybin, which has now 
been tried in no less than three randomized, controlled trials 
for depression, and is showing a signal there of potential 
interest, and that could be quite exciting because we are 
looking for new approaches to that.
    But, there are other trials going on with MDMA, even with 
Psilocybin--with LSD. I think at the moment, it is the 
Psilocybin that has gotten the greatest attention.
    Senator Schatz. And what are your next steps?
    Dr. Collins. I have been talking with the Drug Abuse 
Institute--and I am sorry they are not here--and the Mental 
Health Institute--and they are not here, so I am pinch-hitting 
for them, as well--about whether it is a good moment to 
consider having perhaps a workshop to say, okay, what have we 
learned so far, and what more might we want to do as far as 
designing the next generation of clinical trials, to see where 
these provide benefit going beyond depression to such things as 
PTSD (Post-Traumatic Stress Disorder).
    So, I think over the course of the next year, we are going 
to want to have a hard look at this.

                           MARIJUANA RESEARCH

    Senator Schatz. Thank you. In 2019, you wrote to me that 
the NIH is committed to advancing research on the risks and 
potential benefits of marijuana for therapeutic uses. In that 
letter, you cited a number of barriers to advancing this type 
of research. Are we making any progress?
    Dr. Collins. We are making some progress. You may know 
that, in the past, researchers who wanted to do a clinical 
study on marijuana had all kinds of limitations. It took 
generally at least a year to get through the process of 
paperwork to be allowed to utilize marijuana because it is a 
Schedule 1 agent.
    But, it was also an issue that there was only one source, 
which was our marijuana farm in Mississippi. When I became NIH 
director, I was told, hey, you are running a marijuana farm. 
Who knew? And that, of course, is an issue because it is a 
limited opportunity for access. DEA (Drug Enforcement 
Administration) has now given permission to expand the number 
of suppliers. That will help.
    But, frankly, what we really need is to moderate the 
Schedule 1 limitation. Dr. Volkow and I have been proposing for 
a while something called Schedule 1-R, which would be basically 
a different pathway if you are going to use this material for 
research.
    Senator Schatz. So, I have a bill with Senators Feinstein 
and Grassley, which passed the Senate, did not pass the House, 
to address some of these barriers. Do I have your commitment to 
work with my office on this legislation?
    Dr. Collins. I would be glad to.

                NON-OPIOID ALTERNATIVES TO CHRONIC PAIN

    Senator Schatz. Thank you. I want to talk to you finally 
about chronic pain and non-opioid alternatives. I passed a 
couple of laws in this area to enable research. And I think 
when people think about alternatives to opioids, they move 
right to--in their mind, they move right into alternative 
medicine. And, what I am talking about is a non-opioid, 
pharmaceutical solution to chronic pain, and I am wondering 
whether we are making progress in that space.
    Because, certainly, if people find other ways to alleviate 
their pain--physical therapy, yoga, whatever, mindfulness--I am 
for all of it. But, there is still a space here for a pill that 
you can take to alleviate chronic pain without getting you 
hooked on an opioid. Where are we with this?
    Dr. Collins. That is a critical issue, and this Congress 
has supported NIH in something we call the HEAL Initiative, 
which is--stands for Helping End Addiction Long Term. Part of 
that is about how to better treat people who are addicted to 
opioids, but a big part of it is coming up with alternatives 
for chronic pain management that are not addictive, that are 
not opioids.
    As a result of that, we have partnered up with industry to 
basically identify promising therapeutics that attack different 
targets in the pain mechanism that might, therefore, be 
beneficial. Such things as a sodium channel, for instance, 
called Nav1.7, that is involved in the pain transmission. But, 
if you block that, it should not give you any risk of 
addiction. We are making real progress there.
    We have something called EPPIC-Net, which is bringing 
onboard promising compounds, getting them into Phase 2 trials 
as part of the HEAL Initiative. I could give you a lot more 
information about that if you would like.
    Senator Schatz. Thank you. And I will just submit this one 
that you can consider for the record.
    The U.S. has the same Federal trust responsibility for 
native Hawaiians as it applies to Alaska natives and American 
Indians, and I am hoping that you will consider expanding the 
scope of the Tribal Health Research Office to include native 
Hawaiians. I will get you a more full question for the record 
and look forward to your response. Thank you.
    Dr. Collins. Glad to look at that.
    Senator Murray. Thank you. Senator Hyde-Smith.
    Senator Hyde-Smith. Thank you, Madam Chairman. Thank you 
for holding the hearing, and thanks to all the witnesses who 
are participating today, and I certainly appreciate your 
willingness to serve. That is not lost here, for sure, with the 
past year that we have had.

                FIREARMS RESEARCH AND FIREARM REGISTRIES

    Dr. Collins, I wrote to you last November to express my 
concerns that projects recently funded by NIH disregard the 
spirit, long-established policies against creation of a Federal 
firearms registry. And particularly, an NIH grant to Northwell 
Health of New York provided Federal funds for the hospital to 
ask the questions about lawful gun ownership of every patient 
seeking healthcare for any reason whatsoever at the hospital's 
emergency department.
    Even more concerning, every member of the advisory 
committee overseeing the grant has been a very outspoken 
advocate for expansive gun control, including bans on large 
classes of common and popular firearms.
    I have long been concerned about how firearm registries can 
undermine the ability of law-abiding citizens to exercise their 
Second Amendment rights. Several provisions of Federal law 
already prohibit data collection related to lawful gun 
ownership, and I have introduced legislation to strengthen 
these provisions even further.
    Dr. Collins, given that President Biden is seeking 
increased funding for grants like the one awarded to Northwell, 
how are you making sure that such projects do not infringe on 
Americans' constitutional gun rights or violate Federal 
statutory prohibitions on gun registries as they stand right 
now?
    Dr. Collins. Senator, I recall your letter, and we looked 
closely at that particular grant from Northwell and what they 
were proposing to do.
    First of all, I think we can all agree that gun violence, 
which takes about 40,000 lives every year, is something that 
does deserve close attention and scrutiny as far as the 
research that we might be able to do to understand what are the 
causes and how to save those lives if it is possible to do so. 
So, we will actually be glad to pursue those opportunities.
    But, we are mindful of the prohibition that Congress has 
put forward many years ago about not advocating for gun 
control, and we have been pretty careful about that. I think in 
that instance, the particular grant, while you are right that 
they were asking for this information, it fell somewhat short 
of what most people would have called a broad concept of a gun 
registry. And I think that is, if I remember, what we said in 
the letter in response to you.
    But, I want to promise you, we are going to be very 
sensitive to those issues, as we now, with the President's 
budget, seek to see if we can do more to try to identify 
reasons that gun violence is so prominent and what research 
might teach us about how to save lives.
    Senator Hyde-Smith. Thank you. I appreciate your 
consciousness of that.

                           ORIGIN OF COVID-19

    And this question may have been asked before. I have been 
in another hearing. I hope I am not being redundant. But, like 
many of my colleagues, I firmly believe we need to get to the 
bottom of the origin of COVID-19, and this seems even more 
important after this week's Wall Street Journal report that 
three researchers from China's Wuhan Institute of Virology 
sought hospital care in November 2019--for symptoms consistent 
with COVID-19.
    First, I want to go down the line for all of our witnesses 
of how strongly do you believe that it is possible that the 
origin of the COVID-19 pandemic resulted from a leak of the 
virus from the Chinese lab?
    And second, Dr. Fauci, I would like to ask you 
specifically, how is your institute working to get to the 
bottom of the origins of COVID-19, including exploring the 
laboratory leak theory?
    So, I am going to start with the entire panel for the first 
question of, how strongly do you believe that this is possible?
    Dr. Collins. Well, I will start, and then others can 
respond. Again, I will say, I think the most likely reason, 
mechanism, by which SARS-CoV-2 arose was a natural process of 
transfer from an animal to humans, but it is certainly possible 
that other options might have occurred, including a possible 
lab leak. We just do not have evidence to be able to say what 
that likelihood is.
    Dr. Bianchi.
    Dr. Bianchi. Yes. So, I would agree with Dr. Collins. We 
have no personal knowledge of anything that might have happened 
in China at the National Institute of Child Health and Human 
Development, but we fully support a full investigation of 
getting at the facts.
    Dr. Collins. Dr. Gibbons. Dr. Gibbons, are you there?
    Dr. Gibbons. Yes. I concur with my colleagues in terms of 
transparency is a critical part of this.
    Dr. Collins. Dr. Sharpless, I think I saw you on the 
screen.
    Dr. Sharpless. Sure. Yes, Senator Hyde-Smith, I saw the 
same report and I found that concerning. I think lab accidents 
happen and we need to investigate the possibility. Although I 
think many of us feel zoonotic transfer is perhaps more likely, 
I think we should investigate all possible explanations.
    Dr. Collins. Dr. Perez-Stable.
    Dr. Perez-Stable. I concur with my colleagues. I think of 
concern, but certainly we need evidence.
    Dr. Collins. And Dr. Tromberg.
    Dr. Tromberg. Yes, I agree with my colleagues, as well, and 
would like to see more investigation.
    Dr. Collins. Dr. Fauci.
    Dr. Fauci. Yes. As I have said many times, I feel the 
likelihood is still high that this is a natural occurrence. 
But, since we cannot know 100 percent whether it is or is not, 
other possibilities exist and, for that reason, I and my 
colleagues have been saying that we are very much in favor of a 
further investigation to the next phase from the WHO, who has 
already done a phase one. And, we are strongly in support of 
continuing that to a phase two investigation.
    Senator Hyde-Smith. Thank you----
    Senator Murray. Thank you.
    Senator Hyde-Smith [continuing]. Very much, and I yield my 
time.
    Senator Murray. Thank you so much. Senator Baldwin.
    Senator Baldwin. Thank you, Madam Chair.
    Last week, I had the privilege of joining some of my 
colleagues on a visit to the National Institutes of Health. 
While much of our discussion was centered on the response to 
the COVID-19 pandemic, I was struck by the broad applications 
of the innovation that we have seen during this time.

          ADVANCES IN VACCINE AND THERAPEUTIC DELIVERY SYSTEMS
                             (RADX PROGRAM)

    And, I have often spoken about the Wisconsin-based company, 
FluGen, which is working to make vaccines that can be 
administered as a nasal spray. I also believe that this type of 
innovation is key in terms of how we think about our ability to 
respond to future pandemics.
    Dr. Tromberg, it was great to see you on that trip to NIH. 
I wonder if you could describe how engineering advancements 
have contributed to our response to COVID-19. And, how are you 
thinking about the future of delivery and administration of 
vaccines and therapeutics? And, how will these advancements 
help us prepare for the future?
    Dr. Tromberg. Thank you, Senator Baldwin, for the question, 
and it was great to meet you last week, or I guess it was 2 
weeks ago when you came to visit.
    So, for COVID, we have supported a wide range of 
technologic advances in medical imaging and artificial 
intelligence, digital health platforms, PPE (Personal 
Protective Equipment), ventilators, new therapeutic approaches. 
Of course, the biggest probably and most impactful has been the 
RADx testing program, which has delivered, as you have seen, 
more than 300 million tests, including over-the-counter tests 
with very advanced technologies from nanoscience.
    In terms of vaccines, this is a very exciting area. Another 
one that we have had in our portfolio, one of the strategies 
that we have been supporting, are micro needle patches. So, 
imagine a dime-sized micro needle patch that has got--the 
needles are entirely soluble in water, and as soon as you put 
them into your skin, they start to deliver the vaccine. After 
the delivery, the needles are all gone, and you throw the patch 
away. You get a new one in the mail. So, this has moved into 
Phase 1 clinical trials. Efficacy has been shown.
    I might, if you have a moment, toss it over to Dr. Fauci 
because we have collaborated with his institute in the 
development of these new delivery approaches and they may have 
some other approaches, as well.
    Senator Baldwin. Please. Dr. Fauci.
    Dr. Fauci. Thank you, Bruce. Yes. We have an active 
collaboration with Dr. Tromberg's Institute and we are looking 
towards the future about how we can make it much easier to get 
people vaccinated. This is of particular relevance right now 
because, with COVID-19, even though we are doing really very 
well with vaccination, we still have a group of individuals who 
were really difficult to get to. And hopefully, when we have a 
much easier way to administer the way Dr. Tromberg has 
mentioned, that will make it easier for us.
    Senator Baldwin. Excellent. In April, the University of 
Wisconsin launched the Center for Health Disparities Research 
Center, which has a leadership team comprised entirely of 
women, will focus on how physical environment and social 
conditions intersect to influence an individual's health.
    Their first initiative, funded by the NIH, will use data 
from 22 Alzheimer's disease research centers throughout the 
U.S. to examine how social determinants of health throughout a 
person's lifetime impact their brain health.
    The pandemic has made it clear that we need to do more 
research like this to better understand and respond to health 
inequities, and I applaud the work of Dr. Amy Kind and the 
University of Wisconsin. It is imperative that we maintain our 
commitment to this into the future.

                    COVID-19 AND HEALTH DISPARITIES

    So, Dr. Perez-Stable, how has the impact of the COVID-19 
pandemic on communities of color informed how NIH thinks about 
studying health disparities going forward? And what additional 
investments are needed to fill these gaps?
    Dr. Perez-Stable. Thank you, Senator Baldwin, for that 
question. I think a year ago, when we understood the dimension 
of the dramatic, disproportionate burden by race, ethnicity, 
and socioeconomic status on the population, there was sort of 
an aha moment for all of NIH to say, this problem has been with 
us for a long time. We have made limited progress. It is time 
we put our innovation, our efforts, to address this.
    Out of this effort, we created the Community Engagement 
Alliance Against COVID-19. Dr. Gibbons and I are co-chairing 
that. Dr. Collins mentioned it in his opening statement. And I 
think to heighten the importance of community engagement, so 
talk to the people that are affected, bring them in as full 
partners, identify the problems, and then mobilize all sectors 
that we can mobilize. Not just the researchers and the 
healthcare clinicians, but also the housing, transportation, 
zoning, all the different sectors of society, to see how we can 
begin to make a difference in this setting.
    And I applaud the effort of Dr. Kind. She was a grantee of 
ours, as well as others, and also applaud the effort of looking 
at existing data with standardized measures to address problems 
of this kind, like Alzheimer's disease.
    Senator Baldwin. Yes. Thank you so much.
    Madam Chair, I yield back.
    Senator Murray. Thank you. Senator Rubio.
    Senator Rubio. Thanks, all of you, for being here.
    I think I will direct this to Dr. Fauci, but I welcome 
everybody's answer. I just want to go through, so, what we do 
know. We have heard a lot about what we do not know.
    So, here are the things that we do know, okay?

                           ORIGIN OF COVID-19

    So, SARS-1, we identified the host animal within 4 months.
    MERS, I believe, we identified the host animal within 9 
months.
    It has now been 15 and a half, 16 months, we have still not 
seen and China has not produced any evidence of the host animal 
that transmitted COVID-19 to a human.
    We know that China has a history of lab accidents. I think, 
Dr. Fauci, you answered Senator Graham's question. I think he 
phrased it as, has there ever been a pandemic that came out of 
a laboratory, and the answer was no.
    But, we know of outbreaks that came out of a laboratory. I 
believe back in 2004, two researchers in Beijing were infected 
doing research on SARS and it led to an outbreak. China has a 
history of lab accidents.
    This outbreak happened in a city that happened to be the 
home, coincidentally, of a lab which we know is involved in 
extensive research. And, what they do is they take this 
naturally-occurring virus and they manipulate it and they 
change it to make it infectious to humans. We know that they do 
that there. They have published about it.
    And, it also happened in a city in a lab where a Rutgers 
biosecurity expert raised concerns about its safety, and our 
diplomats in 2018 were cabling back to Washington expressing 
concern about the safety.
    So, I take all those facts together, right?
    SARS, we knew the host in 4 months.
    MERS we knew the host in 9.
    We still do not know the host in--for COVID, even though--
and China is not being transparent about it even though they 
have a vested interest in producing the host so they can put 
all this down.
    In a lab that we know is involved in changing viruses 
synthetically so that they become infectious for humans.
    In a lab that diplomats have told us is unsafe.
    In a country that had history of lab leaks.
    And, by the way, in a virus that we know can be 
synthetically-created because the Swiss did it. The Swiss 
created an exact replica of this virus in the lab for purposes 
of answering it.
    All of these facts were available to us last May, last 
April. Why--I will start with Dr. Fauci. Why did you dismiss 
the lab leak theory as credible?
    Dr. Fauci. I have always said that the high likelihood is 
that this is a natural occurrence. I did not dismiss anything. 
I just said it is a high likelihood that this is a natural 
occurrence from the environment of an animal reservoir that we 
have not yet identified, and I still maintain that.
    But, as I just mentioned in response to other questions, 
that since you do not know 100 percent about that, because no 
one knows, including me, 100 percent what the origin is, is the 
reason why we are in favor of further investigation.
    Senator Rubio. Well, given everything I have just cited--
and if anything I just cited is incorrect, I hope I will be 
corrected. I am relying--obviously, not my field of study, so I 
am relying on what other experts have published. What is the 
basis for this high likely--what is the basis for the 
conclusion that it is likelier to have been naturally occurring 
than a lab accident?
    I asked a specific question to the Director of National 
Intelligence, and how I posed it is, is it not true that it is 
the assessment that they are equally likely, based on our 
information that we have.
    So, as I outline all of these things here, is she wrong 
when she answered me yes? And, based on everything I have just 
cited, why the--what is it that we are basing the higher 
likelihood of naturally occurring? Is it simply because that is 
all we have ever seen in the past?
    Dr. Fauci. Well, we have historical experience that 
happened with SARS-CoV-1. It happened with MERS. It happened 
with HIV. It happened with virtually all the influenza 
pandemics. So, the historical basis for pandemics evolving 
naturally from an animal reservoir is extremely strong, and it 
is for that reason that we felt that something similar like 
this has a much higher likelihood.
    But, again, getting back to what I said--and let me repeat 
so there is no lack of clarity in that. No one knows, not even 
I, 100 percent at this point, which is the reason why we are in 
favor of further investigation.
    Senator Rubio. But, going back to precedent, precedents 
require them to be similar. The difference between this one and 
that one is--as I said, 4 months we knew the host for SARS, at 
9 months we knew the host for MERS. China has all the incentive 
in the world to produce this host and has not done so. And, 
then, you add up all these other things, I mean, is it just a 
coincidence it happened in the city that is doing this kind of 
research, which, by the way, is controversial? I know you and 
others have been supportive of it, but it is controversial. It 
is not widely accepted as good.
    My whole point is there are people out there who had 
Facebook posts taken down. They are called kooks, conspiracy 
theorists, for saying publically a year ago what we now say may 
be possible. I think those people deserve an apology, at a 
minimum.
    Thank you.
    Senator Murray. Thank you.

                           COVID-19 AND MIS-C

    Dr. Bianchi, thank you. NICHD (National Institute of Child 
Health and Human Development) is trying to develop ways to 
identify children at high risk for multi-system inflammatory 
syndrome in children. It is a rare and life-threatening after 
effect of COVID-19. Now, while most children who become 
infected, I know, have mild or no symptoms, some do go on to 
develop this severe and sometimes fatal condition. I know your 
research is still in the early stages, but could you describe 
the NICHD's efforts to develop clinical, predictive models 
using machine learning to identify children at risk and how 
physicians are using this testing device and data?
    Dr. Bianchi. Thank you very much for your question, Senator 
Murray. As you know, there are almost four million children who 
have been infected with SARS-CoV-2, but the key is to figure 
out which is the one-in-a-thousand child who is going to get 
very sick with this MIS-C, and that child could get critically 
ill, although most do recover. So, as a parent, you would want 
to know if my child tests positive, what is going to happen.
    And, so, as part of the RADx RAD program--NIH is supporting 
this. It is four different programs CARING for Children with 
COVID, but the predictive one that is using artificial 
intelligence and machine learning is called the PreVAIL Kids 
Program. And what that is, is it is eight different programs 
around the Country, with some international partners, that are 
using existing cohorts, as well as prospectively enrolled 
cohorts, to collect biospecimens and use artificial 
intelligence in conjunction with the electronic health records.
    The program started within the past few months, so we do 
not have evidence yet. But, the enrollments are on target, and 
we are expecting to enroll about 12,000--actually, we have 
already enrolled about 12,000 children out of 16,000 that are 
expected.

                       A.I. DETECTION OF CANCERS

    Senator Murray. Okay. And Dr. Sharpless, artificial 
intelligence has been shown to help improve the detection of 
breast cancer in mammograms, and lung cancer in CT scans. And 
suggesting that AI appears well suited for imaging, are you 
looking at the potential for AI to help early detection of 
other cancers?
    Dr. Sharpless. Oh, yes. This is a very important topic. I 
think artificial intelligence has really the ability to 
transform cancer research and cancer clinical care in dramatic 
ways.
    We have a very lively set of collaborations going on with 
the Department of Energy that has extensive expertise in this 
topic. To use, you know, AI to try and identify drug targets 
for medicinal chemistry, or to use AI to read 600,000 pathology 
reports that we get for the SEER database every year, or to use 
artificial intelligence for image analysis, both pathology 
images and radiology images.
    So, I think this is a tremendously exciting technology that 
has real opportunities to advance cancer research and cancer 
care in many important ways.
    I think we were also worried about the ethical issues of 
AI, and we want to make sure that we use practices that will 
not reinforce biases that are latent in some of our data sets.
    But, overall, I think the promise of AI is very exciting 
for cancer research.
    Senator Murray. Interesting. Okay.

                       CLIMATE CHANGE AND HEALTH

    Dr. Gibbons, the request, budget request, includes $110 
million to study the impact climate change is having on health. 
Talk to us about what kind of serious effects have we been 
seeing from climate change, and what kinds of research do you 
expect NHLBI (National Heart, Lung, and Blood Institute) to 
support with this kind of funding?
    Dr. Gibbons. Yes. Thank you for that question. As we know, 
climate change often involves these changes in our air, in our 
air quality, particularly it is likely to promote more air 
pollution. Certainly, the constituents on the West Coast are 
familiar with the impact of wild fires on air quality.
    And although air is all around us, air pollution tends to 
concentrate and have its greatest impact on certain 
communities, particularly communities in which those 
neighborhoods are closer to sources of air pollution, and 
therefore, the impact is also inequitable in terms of the 
health consequences of air pollution, and that is falling on 
the most vulnerable.
    We know that it exacerbates certain chronic conditions, 
certainly cardiopulmonary ones like chronic obstructive 
pulmonary disease, asthma, heart failure. Heart attacks are 
increased in the context of higher air pollution promoted by 
climate change.
    And, we anticipate that there will be a need to not only 
mitigate the impact of climate change, but also to enhance 
resilience to the effects of air pollution on health, and we 
anticipate that that will involve enhancing healthy communities 
that are disproportionately affected by the consequences of air 
pollution derived from climate change. And our programs that 
are community-engaged research with that health equity lens 
should be promising in that regard.
    Senator Murray. Okay. I think this is really important, and 
I think we all should recognize that this is an area we need to 
look at, so I appreciate your work on this and we will be 
following it closely.
    I will turn to----

                        SEXUAL HARASSMENT AT NIH

    Okay. I have one additional question and that is for Dr. 
Collins. In 2018, the National Academies, as you know, released 
a report that found that nearly 60 percent of women in academia 
have experienced--60 percent--have experienced sexual 
harassment on the job and recommended that Federal research 
agencies require institutions to notify them when individuals 
on grants have violated harassment policies or put on 
administrative leave due to harassment allegation. And other 
science agencies, like National Science Foundation, have 
implemented these changes.
    Tell me, what is NIH doing to require its research 
institutes to do the same?
    Dr. Collins. Senator, I share the sense that this is an 
extremely important issue. The National Academy report that you 
mentioned I think really got everybody to recognize how 
pervasive sexual harassment is and what a significant negative 
it has been for far too long for women in our scientific 
workforce.
    We conducted our own working group in the Advisory 
Committee to the Director that reported to me in December of 
2019 and made a series of very significant recommendations 
about how we might change our approach to this. We have been 
working through those and have already implemented a 
significant fraction of them. There are some that still require 
some additional legal authority that is hard for us to be able 
to do at the present time.
    In terms of what you are particularly pointing to, we have 
had now more than 300 allegations that have been brought to us 
about sexual harassment in our grantee institutions; others 
within our own intramural program. Of those 300, about 30 
percent of them have turned out to be actually entirely 
validated. That has resulted in a hundred different changes in 
grants that--particularly, removal of principal investigators 
and replacement of those with other individuals.
    One hundred and twenty-five individuals have been taken out 
of our pool of peer reviewers because of this kind of concern 
about the bias that they bring to that experience.
    And we have made it very clear to our institutions that we 
expect them to report any circumstance----
    Senator Murray. Well, expecting them does not require them 
to.
    Dr. Collins. And, Senator, you and I are in an interesting 
discussion here that I agree--I wish we were able to simply say 
require. At the present time, legally, we are told we do not 
have that authority. We would have to go through a 2-year 
rulemaking effort, or we would need statutory assistance.
    Senator Murray. Well, okay. This is really important, and 
whatever we need to do, I do not--you know, I know you have 
worked on it, I know you have focused on it, but I know of 
women who have left our scientific research institutes because 
of this. We cannot afford to have that happen for a thousand 
reasons. So, whatever it is we need to do here, we need to know 
what it is so we can do it.
    Dr. Collins. I am so with you. And if there is another 
iteration we can take at this to try to figure out--I will say 
that what we have said in terms of the expecting response from 
our institutions has gotten their attention in a pretty 
remarkable way. Even without requiring it, we are seeing 
reporting coming through.
    Senator Murray. Well, to every one of them that is 
listening, I am not done with this.
    Dr. Collins. Okay.
    Senator Murray. Senator Blunt.
    Senator Blunt. Thank you, Chair.
    I have three or four questions. Let me eliminate a couple 
of other topics by just making a couple of comments on some 
things that have already been said, one, and one thing that has 
not been, I do not believe, brought up today.
    One is on the CTSA awards. None of the people talking to us 
that are current recipients think that this simplifying the 
process makes it more likely that they will get the research 
bench-to-bedside result that they think you want and they think 
is the key to this award.
    And, you have heard a number of schools mentioned, and 
University of Washington would be one of them that Senator 
Murray would be very familiar with. Washington University in 
St. Louis collaborates through this program with Saint Louis 
University and the University of Missouri to get to more rural 
hospital settings and do things. So, I suspect you have heard a 
number of concerns about that today.
    I have not heard brought up one of my concerns, which I am 
just going to mention. I do not think you need to respond to 
it. I do think that waiving the intellectual property rights on 
COVID-19 vaccines is a problem. I think it is a problem because 
I do not think it actually would increase the number of 
vaccines, the capacity to produce a vaccine that has efficacy, 
in the timeframe we need to make it. It probably is not 
benefitted much by waiving the rights to the research. The WTO 
(World Trade Organization) has to unanimously agree, which I do 
not think they do. But, if they do, we give our research to 
everybody.
    And third, when this comes up again, companies would have 
less willingness, I think, to step forward. At least one of the 
companies, Dr. Collins that we dealt with in Warp Speed, there 
was no agreement at all that if they were not successful--we 
had a contract. We would buy 100,000 doses, but only if they 
were FDA authorized. So, they were out there totally on their 
own, as these companies you would expect to be.
    I do not think this is likely to happen because of the WTO, 
but I have some concerns that I suspect are shared by others at 
NIH.

          IMPACT OF COVID-19 PANDEMIC ON CHILDHOOD DEVELOPMENT

    Dr. Bianchi, just the title--let's just take the title of 
your Institute and look at COVID. What do you think the impact 
on child health and development of COVID and the COVID 
environment, the pandemic environment, the quarantine 
environment, has been? And how are we going to be looking at 
what the long-term ramifications of that might be and what 
advice we may be able to give to schools and moms and dads and 
behavioral health and other health providers as it relates to 
child development impacted by this?
    Dr. Bianchi. Thank you so much for that question, Senator 
Blunt, because children, you know, have not--I think they are 
so important in terms of our Nation's future, first of all. 
But, the fact that children have been home from school has 
affected the entire family, has affected the workforce, et 
cetera.
    But, because children in general have been asymptomatic or 
mildly symptomatic, they have not gotten as much attention, and 
yet being at home, being away from in-person schooling, I think 
may have significant impact for years to come. And, for that 
reason, we are trying to get the kids back to school as soon as 
possible.
    And as part of the RADx Underserved Population program, we 
are also leading an initiative to really develop, evaluate, and 
implement testing, along with mitigation, of, you know, hand 
washing, social distancing, et cetera, to get evidence to 
reassure people to get kids back to school. Two of the sites 
are actually in Missouri, and one is in Washington State. There 
is a program in Yakima, and there is a special program in 
Missouri that is looking at how you deal with kids who have 
intellectual disabilities and cannot mitigate in the same way.
    So, to answer your question, I think there will be long-
term effects. I think the answer is to get kids back to school 
safely, with evidence. And, this program is based on a funded 
project that was very successful in North Carolina that showed 
with all the mitigation, with the work with the superintendents 
of schools, that the secondary infection rate in schools was 
extremely low compared to the community.
    Senator Blunt. Yes. I would think here that some of the 
developmental issues, and they will be different with 4 and 5 
year olds and kindergarten and first grade than they will 
people in seventh grade, and those may be different than 
people----
    Dr. Bianchi. Absolutely.
    Senator Blunt [continuing]. In the eleventh and twelfth 
grade and how--you know, I think we are going to have to watch 
this carefully and try to get data and then share that data.

                       FUTURE OF MRNA TECHNOLOGY

    On vaccines--actually, on--maybe more on mRNA than 
vaccines, what do we think the impact may be as it relates to 
cancer, to HIV? We will start, Dr. Fauci, with you. Can we look 
at the flu shot in a different way? And what do we think the 
mRNA impact, now that we know this different use for it, may 
have on other healthcare settings? And Dr. Sharpless, I am 
going to come to you second on this.
    Dr. Fauci. It is going to--I believe, and many of my 
colleagues believe, that the mRNA technology, as it has been so 
spectacularly successful with SARS-CoV-2 to develop a vaccine 
against COVID-19, is already being pursued for other 
infections, including HIV and including influenza. So, there 
are a couple of things that are going on now. Even as we see 
the successes with COVID-19 in using the mRNA technology for 
the development, for example, of universal flu vaccines, as 
well as now having HIV vaccine researchers now looking at the 
possibility of an mRNA platform technology to use for HIV. So, 
it is already happening.
    Senator Blunt. Dr. Sharpless, on mRNA, I mean, we know the 
impact in just the last half dozen years of immunotherapy on 
cancer treatment. What about this mRNA intervention and how it 
might impact the way we look at fighting cancer?
    Dr. Sharpless. Yes, this is a very exciting topic. You 
know, people interested in this space have been working on 
this, you know, long before the pandemic. So, using mRNA for 
cancer therapy has many potential applications because you can 
really get the body to make a protein, and that protein could 
have a desirable effect against cancer, for cancer therapy, in 
a lot of ways.
    The furthest advance, as you mentioned, is the use of mRNA 
vaccines, you know, cancer vaccines. And clearly, they tend to 
be highly personalized, the ideas that you can sequence 
someone's own tumor and then make the vaccine to their very own 
tumor in a way that will not cause them autoimmune side 
effects, and this is an idea to augment other kinds of 
autoimmune cancer--or anti-immune cancer therapies.
    So, it is a very promising area. It is in clinical trials, 
and we just need to see how this develops.
    Senator Blunt. Thank you. My last question, Chair.

        IMPACT OF COVID-19 PANDEMIC ON RESEARCH AND RESEARCHERS

    Dr. Collins, in the pandemic, particularly with lab 
closings, we obviously lost some time, and lost research that 
is going to take a long time to recreate. Are the lab 
reopenings happening in the way they need to? And, do you have 
the flexibility to extend a grant to overcome the disruption? 
And probably just not this disruption of the time closed, but 
the research lost by closing, as well.
    Dr. Collins. I am glad you are asking because this is yet 
another of the terrible casualties of this terrible pandemic. 
It has been very hard on researchers, especially those who need 
a laboratory to do their work or who were running a clinical 
trial that was very hard to enroll participants. And, yes, we 
did have to have many of those folks staying away from the 
workplace for their own safety.
    They are coming back. Our own program at NIH, our 
intramural program, now is up to about 50 percent occupancy, 
but it is not anywhere near where it was pre-pandemic. We have 
done everything we can with our flexibilities to try to make 
sure, particularly, that trainees and early-stage investigators 
do not get further injured by this by extending the periods of 
their training; or by allowing grants if they are able to put 
forward a special request to be extended for an extra year, 
either without extra funds, or with, if the case is strong.
    And yes, I also think we need to be cognizant of the way in 
which this is affecting people in other ways. We have now come 
up with a way to provide childcare support for our trainees who 
otherwise have not had that, and that has been one additional 
burden on their shoulders.
    Our estimates are that it is about a $16 billion loss that 
has occurred because of the way in which this has affected 
research in our extramural institutions; that they are in a 
tough place to try to make up. So, I appreciate your asking the 
question.
    We are going to have a really big challenge getting 
ourselves back into the place that we were before this 
happened.
    Senator Blunt. Well, let us know what we need to be 
thinking about as we think about the rest of this bill on that 
topic. And thank you, Chair.
    Senator Murray. Thank you very much. And I want to thank 
all of our witnesses today for their really--for a really 
productive hearing. I think we all learned a lot. So, thank you 
very much.

                     ADDITIONAL COMMITTEE QUESTIONS

    For any Senators who wish to ask additional questions, 
questions for the record will be due one week after the 
President's budget is delivered at 5 p.m. The hearing record 
will also 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. Francis Collins
              Questions Submitted by Senator Patty Murray
    Question. The President's fiscal year 2022 skinny budget proposed a 
major new biomedical research effort by establishing ARPA-H. While the 
skinny budget was light on details regarding the structure of the 
program, the Administration's statement indicated that the initial 
focus of ARPA-H would be `on cancer and other diseases such as diabetes 
and Alzheimer's.'
    Assuming Congress and the Administration work together to establish 
ARPA-H, how would you envision ARPA-H setting priorities for research 
into additional diseases?
    Answer. Over the long term, the proposed structure for the Advanced 
Research Projects Agency for Health (ARPA-H) is intended to empower the 
ARPA-H leadership and staff to set and execute on research priorities 
for a variety of high-risk, high-reward, milestone-driven projects that 
can lead to novel capabilities, platforms, and resources that are 
applicable to a range of diseases.
    For the initial direction, the Administration is working to set up 
multiple pathways, both within the government and the broader 
stakeholder community, for priority setting and for exploring new areas 
ripe for research at ARPA-H. At the time of this hearing, the White 
House Office of Science and Technology Policy (OSTP) and the National 
Institutes of Health (NIH) are in the planning phases of convening 
multiple listening sessions with key stakeholder groups including 
patient organizations, industry, venture capitalists and 
philanthropists, and others from the academic and research communities. 
During these sessions, stakeholders will be asked to offer their 
perspective on what they see as the greatest research challenges and 
opportunities that could be addressed using the ARPA-H model. This 
input will help refine the scope and provide a wealth of ideas for the 
first ARPA-H director to consider as they develop the agency's vision.
    In mid-July, the Administration established a Joint Fast Track 
Action Committee (FTAC) to help steer the creation of ARPA-H and lay 
the groundwork for strong interagency coordination. OSTP and NIH serve 
as co-chairs of this committee that includes representatives from 
Department of Agriculture, DARPA, Office of the Under Secretary of 
Defense for Research & Engineering, ARPA-E, BARDA, CDC, CMS, FDA, VA, 
EPA, NSF, and the Smithsonian Institution, among others.
    Question. Some of the greatest advances in medical innovation in 
the last decade have been brought on through genetic analyses and use 
of sophisticated computer programs that can shorten the time taking 
drug candidates through clinical studies. In fact, the development of 
COVID-19 vaccines benefited from the use of 21st century technology 
like cloud computing and AI to help stop the virus' spread and save 
lives.
    How will the President's budget build on the use of modern tools 
like cloud computing, AI, and genetic analyses to further accelerate 
the delivery of cures to patients?
    Answer. Over the last decade, pharmacogenetics has advanced the 
frontier of personalized medicine such that drug therapeutics are 
developed based on the genetic aberrations of disease. This approach is 
most notably applied for cancer treatments and also other diseases. 
Cancers of various types are treated by first knowing the genetic 
mutations and/or deletion of genes. Then drug candidates are screened 
and developed by computer modeling of the target sites along with 
potential drug candidates. Such modeling requires various large 
datasets and analytics that, if stored in the cloud and interoperable, 
can be mined to find the best drug candidates that bind to the target 
sites for treatment. Storing large datasets in the cloud is only the 
first requirement for cloud computing. Such computation requires new 
tools, and support for tool development is essential to realize the 
opportunities for cloud computing.
    Artificial intelligence (AI) has advanced the pace of drug 
discovery and development via predictive models of drug/target 
interactions and also facilitates clinical trial design based on 
algorithms for go/no go decisions during the trials.
    The President's Budget Request supports the application of AI to 
improve diagnostics for diseases as diverse as coronavirus disease 2019 
(COVID-19) and cancer. In each case, information-rich data sources that 
are stored, aggregated together, and analyzed in the cloud are used to 
rapidly train and test these new capabilities. New programs like the 
Artificial Intelligence/Machine Learning Consortium to Advance Health 
Equity and Researcher Diversity program, or AIM-AHEAD, and Bridge2AI 
will harness AI for health by generating AI-ready datasets and best 
practices for machine learning. This will allow researchers to 
accelerate data-driven discovery for grand challenges in biomedicine 
using AI-based technologies. Additionally, NIH's partnership with cloud 
services providers--Google, AWS and now Microsoft Azure--further 
enhances researchers' abilities to leverage industry technologies and 
utilize AI-ready data for drug discoveries and therapeutic treatments.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
    Question. I have worked with the Subcommittee Chair and Ranking 
Member for years on sustained, predictable increases to the NIH 
budget--with the goal of providing at least 5 percent real growth year-
over-year. We have had success, leading to a 42 percent increase over 
the past 6 years, along with supplemental funding in COVID-19 relief 
packages. The President's fiscal year 22 budget calls for a 19 percent 
increase to the NIH overall budget. The vast majority of that comes 
from the proposed creation of a new advanced research effort, called 
ARPA-H. When I toured the NIH campus recently with many members of this 
Subcommittee, you discussed how innovative efforts during the 
pandemic--such as with the RADx testing program or Warp Speed vaccine 
development--align with the ARPA-H proposal, incorporation closer 
partnerships with industry and coordination at different stages in the 
research and development of promising breakthroughs. Your testimony 
discusses application of this nimble ARPA-H proposal for cancer, 
infectious diseases, and autoimmune diseases.
    As we evaluate this proposal, what are the core aspects of this 
ARPA-H policy that you want us to keep in mind?
    Answer. We envision that the Advanced Research Projects Agency for 
Health (ARPA-H) will be able to tackle large-scale challenges using a 
proven high-risk, high-reward approach that embraces nimbleness and 
flexibility with the broader goal of delivering rapid breakthroughs 
that serve all patients. Being successful in this endeavor requires 
close communication and collaboration across government and with key 
stakeholders in the external biomedical community. This could include 
undertaking projects with Federal agencies, private companies, 
independent research institutes, medical centers, as well as academic 
institutions--all collaborating to advance innovative health research. 
NIH deployed similar approaches in response to the COVID-19 pandemic 
(Accelerating COVID-19 Therapeutic Interventions and Vaccines, or ACTIV 
and Rapid Acceleration of Diagnostics, or RADx)--which yielded life-
saving results for Americans, and also served as a learning opportunity 
to appreciate further the value of employing a DARPA--like model to 
support research. With Congressional support, we believe we can 
leverage these models in other areas of health research to drive 
transformative change and impact.
    Question. We have spoken in the past about two seemingly divergent 
issues. On one hand, we talk about the need to invest in medical 
research to find breakthroughs and cures for patients, so we rightfully 
appropriate billions into NIH-funded research--sign me up for that. But 
then these drugs come to market--the vast majority of them benefitting 
from NIH research (e.g. a study finding that all 210 drugs approved by 
FDA between 2010 and 2016 benefitted from NIH-funded research in some 
form)--and too many of them with exorbitant price tags. Recent studies 
show that high costs contribute to poor medication adherence, including 
with one-quarter of cancer patients choosing not to fill a prescription 
due to cost. I know Dr. Sharpless has talked about the ``financial 
toxicity'' for cancer patients. Americans pay the highest prices for 
medications in the world, with a recent GAO report finding that the 
U.S. pays two- to four-times more for certain medications than other 
developed countries. It is counterintuitive and an outrage that 
taxpayers fund cutting-edge research, which leads to drugs, that we 
often cannot afford once they hit the market. I understand NIH does not 
set drug prices and does not want to limit the handoff or development 
of its research to stakeholders that commercialize the discoveries. But 
the current system does not maximize the benefits for patients.
    Given the role of NIH research in contributing to FDA-approved 
medications, many of which come with extremely high price tags, what 
specific steps can NIH take to ensure that patients are able to afford 
the incredible discoveries made at NIH?
    The NIH has received several petitions to exercise march-in rights 
(35 U.S.C. Sec. 203), but has never done so.
  --Under what circumstances would NIH consider doing so?
  --Under that statutory authority, how does NIH define and evaluate 
        the term ``practical application'' for the purposes of how a 
        contractor or assignee makes a subject invention funded by NIH 
        available to the public on reasonable terms?
  --What are the factors used in such definition and evaluation?
  --Can you provide an example of the analysis undertaken in evaluation 
        of a previously filed march-in-petition?
    Answer. The National Institutes of Health (NIH) shares your concern 
about the high price of drugs and the impact on public health. The 
article you reference shows that all of the 210 drugs approved by U.S. 
Food and Drug Administration from 2010 to 2016 were based on at least 
one scientific publication reporting on research funded by the NIH.\1\ 
The researchers reported that 96 percent of the NIH funded projects 
were identified based on a search for the ``target'' rather than the 
drug itself. Identifying a drug target, meaning a protein in a cell 
that has a function in a disease process, opens the door for any 
researcher in industry or academia to screen for drugs that bind to the 
target to slow or arrest disease processes. This research is key to a 
vibrant drug discovery process in the United States and does not limit 
discovery to one drug for each target. The development of multiple 
drugs for a particular disease allows the patient and physician to 
choose the best one for them and can lead to price competition in the 
market. Drug pricing is a complex problem that involves various 
segments of the market, much of which NIH has no control over. A 
smaller number of important drugs utilize patented inventions funded by 
the NIH. When NIH has been asked to consider march-in under the Bayh-
Dole Act based on the price of such drugs, NIH has stated that the 
issue of drug pricing is one that should be address by Congress, as it 
considers these matters in a larger context.\2\
---------------------------------------------------------------------------
    \1\ Cleary et al., 2018, www.ncbi.nlm.nih.gov/pmc/articles/
PMC5878010/.
    \2\ NIH march-in responses from 1997-2013 at ott.nih.gov/policy/
policies-reports under ``NIH March-In Response''.
---------------------------------------------------------------------------
    The Bayh-Dole march-in provision (See 35 U.S.C. 203) allows a 
government funding agency to require a grantee to grant a license to a 
patent of an invention made under that agency's awarded grants or 
contracts and allows other ``responsible applicants'' to obtain the 
license if one of four circumstances are met:
    1. the contractor or assignee has not taken, or is not expected to 
take within a reasonable time, effective steps to achieve practical 
application of the subject invention in such field of use
    2. to alleviate health or safety needs which are not reasonably 
satisfied by the contractor, assignee, or their licensees
    3. to meet requirements for public use specified by Federal 
regulations and such requirements are not reasonably satisfied by the 
contractor, assignee, or licensees
    4. the agreement required by section 204 [a requirement that 
patented products be manufactured substantially in the United States 
unless a waiver is granted]
    The first two criteria are typically cited in petitions to consider 
a march-in by the National Institutes of Health (NIH). For example, if 
a company has rights to a government funded patent for a drug candidate 
but is not making reasonable efforts to bring it to market, the company 
may be failing to meet the requirements to achieve practical 
application of the invention. These criteria are considered on a case-
by-case basis by the agency in view of the facts presented in each 
case.
    If NIH were to march-in, the grantee could appeal that decision 
through the Federal courts. Only after the company had lost all legal 
appeals could NIH grant a license to a second company, should there be 
one interested in developing a new version. Additionally, the drug 
could be covered by other patents that cover certain aspects of the 
drug, such as methods of making and administering it. In such 
instances, the march-in could be ineffective, because the original 
company could stop a new company from making the generic until the 
other patents expire.
    After the court appeals and expiration of any other patents, a 
company would typically have to conduct clinical trials or otherwise 
establish equivalency with the brand drug to obtain U.S. Food and Drug 
Administration approval. The entire process, including administrative 
hearings, court appeals and new clinical trials, could take years 
before the new product reached the market. In the meantime, alternative 
therapies may have become available or the patent subject to march-in 
may have expired.
    NIH has considered march-in on several occasions and was either 
able to work with parties to reach an agreement to address the issues 
raised, such as the case with CellPro and Fabrazyme, or decided that 
the march-in legal requirements were not met to march-in to address the 
public health and safety issues raised, such as was the case with 
Norvir.\3\
---------------------------------------------------------------------------
    \3\ See ott.nih.gov/policy/policies-reports under NIH March-In 
Response.
---------------------------------------------------------------------------
    Question. The COVID-19 pandemic has impacted every major sector of 
the economy of the United States, including our nation's biomedical 
research. I have heard from countless universities across the state of 
Illinois about the impact that this pandemic has had on the medical 
research pipeline. From shuttered labs, to interrupted or delayed 
clinical trials, to unforeseen pandemic-related costs, they have 
estimated that this pandemic has caused over $10 billion in lost 
research. Last year, Senator Moran and I sent a bipartisan letter to 
Senate leadership, requesting at least $10 billion in additional 
funding to help make-up for the unforeseen disruptions and costs to 
medical research nationwide.
    Dr. Collins, I am wondering if you can speak to the toll that the 
pandemic has taken on medical research nationwide and what Congress 
might be able to do to help.
    Answer. The National Institutes of Health (NIH) remains deeply 
concerned and mindful about how the spread of coronavirus disease 2019 
(COVID-19) has negatively affected the biomedical research 
enterprise.\4\ Last summer, the NIH estimated it would cost at least 
$10 billion to restart labs which were forced to rapidly close. That 
original estimate proved overly optimistic as the pandemic subsequently 
continued, and as such, the NIH now estimates the financial impacts to 
be approximately $16 billion on the biomedical and behavioral research 
enterprise.
---------------------------------------------------------------------------
    \4\ https://nexus.od.nih.gov/all/2020/11/04/continued-impact-of-
covid-19-on-biomedical-research/.
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    The estimates considered many factors:
  --Key resources, such as animal colonies, cell lines and expired 
        reagents that need to be re-established.
  --Access to core facilities that was limited due to a backlog of 
        requests.
  --Delicate and complicated equipment that required recalibration and 
        quality control testing prior to returning to routine use.
  --Requirements for social distancing to protect staff and clinical 
        trial participants coupled with anticipated reluctance by 
        participants to travel, which slowed the rate of clinical trial 
        accrual and progress and increased the cost of conducting 
        trials.
    In addition to the financial estimates, the NIH fielded two online 
surveys to objectively document COVID-19's impact on the extramural 
research workforce.\5\ The main finding from the surveys was that the 
majority of respondents noted concerns about research functions, 
research productivity, and financial status.\6\ Well into the pandemic, 
many NIH-supported research labs enforced social distancing, inherently 
restricting access and severely limiting the ability to generate 
research results and preliminary data at a crucial time in career 
development of early stage investigators and trainees. Junior faculty, 
often with only a single NIH award and unable to access their labs to 
generate additional data, are at risk of losing all funding and may 
have insufficient data to write papers while working from home. Some 
investigators, especially women with dependent care responsibilities, 
are more negatively affected. Investigators supported by training or 
career development awards are experiencing hiring freezes and job 
revocations, jeopardizing the ability of early-stage career 
investigators to transition to independence, particularly as they come 
to the end of their current funding. Clinical investigators have been 
diverted from their research labs to meet the clinical demands of 
COVID-19 patient care.
---------------------------------------------------------------------------
    \5\ https://nexus.od.nih.gov/all/2020/10/05/encouraging-
participation-in-upcoming-nih-surveys-to-identify-impacts- of-covid-19-
on-extramural-research/.
    \6\ https://nexus.od.nih.gov/all/2021/03/25/the-impact-of-the-
covid-19-pandemic-on-the-extramural-scientific-workforce-outcomes-from-
an-nih-led-survey/.
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    Considering these effects, the NIH is concerned about potential 
pandemic-related losses of scientists exiting the biomedical research 
workforce and abandoning scientific careers to seek alternative 
employment. In an effort to address the unanticipated impacts of the 
pandemic on the career trajectories of early career scientists, the NIH 
has provided several policy flexibilities, including grant award 
extensions (both funded and un-funded), opportunities for investigators 
to extend the timeline for early career status, provided administrative 
supplements, and more.
                                 ______
                                 
              Questions Submitted by Senator Brian Schatz
    Question. At the hearing, we discussed psychedelic drug research 
and the potential of these drugs to treat mental health illness. You 
stated that the NIH would consider having a workshop on this subject.
    What is the current status of NIH-funded clinical trials involving 
human subjects on the potential benefits of psychedelics combined with 
psychotherapy?
    Are there statutory or regulatory barriers to NIH pursuing or 
funding human subject research on psychedelic drugs?
    When does NIH plan to convene a workshop on psychedelic drug 
research?
    Answer. The National Institutes of Health (NIH) supports research 
on the development and testing of pharmacological interventions--
including the use of hallucinogens such as ketamine, and psychedelic 
drugs such as psilocybin--for the treatment of illnesses. In 
particular, the National Institute of Mental Health (NIMH) requires an 
experimental therapeutic approach for the development and testing of 
therapeutic interventions for mental illnesses, in which the studies 
not only evaluate the clinical effect of an intervention, but also 
generate information about the mechanisms underlying a disorder or an 
intervention response. Research on psychedelic drugs holds promise for 
uncovering mechanisms of mental illnesses and possible interventions, 
ultimately leading to novel treatments with fewer side effects and 
lower abuse potential. Further research is needed to examine the 
efficacy and long-term safety of psychedelic drugs, including with 
repeated exposure and potential interactions with existing treatments.
    The dissociative anesthetic ketamine has recently emerged as an 
effective fast-acting antidepressant.\7\ The NIMH Director's Message, 
``New Hope for Treatment-Resistant Depression: Guessing Right on 
Ketamine,'' describes the role of NIMH and other researchers in the 
development of esketamine, a U.S. Food and Drug Administration-
approved, rapid-acting medication that targets treatment-resistant 
depression.\8\ Within the NIMH Intramural Research Program, Dr. Carlos 
Zarate is now conducting clinical trials to better understand how 
ketamine rapidly reduces depressive symptoms in people with treatment-
resistant depression or bipolar depression.\9,10\
---------------------------------------------------------------------------
    \7\ pubmed.ncbi.nlm.nih.gov/27839782/.
    \8\ www.nimh.nih.gov/about/director/messages/2019/new-hope-for-
treatment-resistant-depression-guessing-right-on- ketamine.
    \9\ clinicaltrials.gov/ct2/show/NCT03065335.
    \10\ clinicaltrials.gov/ct2/show/NCT03973268.
---------------------------------------------------------------------------
    The National Institute on Drug Abuse (NIDA) currently supports a 
clinical trial which aims to assess the efficacy of ketamine, in 
combination with behavioral therapy, in the treatment of cocaine use 
disorders.\11\
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    \11\ clinicaltrials.gov/ct2/show/NCT03344419.
---------------------------------------------------------------------------
    Additionally, a privately funded clinical trial is assessing the 
potential efficacy of the psychedelic drug psilocybin for the treatment 
of obsessive-compulsive disorder.\12\ While the NIH is not directly 
funding this trial, NIMH does support the trial's principal 
investigator through a Mentored Patient-Oriented Career Development 
Award.\13\
---------------------------------------------------------------------------
    \12\ clinicaltrials.gov/ct2/show/NCT03356483.
    \13\ reporter.nih.gov/project-details/10127338.
---------------------------------------------------------------------------
    Further, a number of NIH-funded researchers are conducting basic 
and preclinical research to investigate the use of psychedelic drugs as 
potential therapeutic interventions for mental illnesses. For example, 
NIMH-funded researchers are examining the mechanisms underlying the 
antidepressant effects of psychedelic drugs in an effort to develop 
novel, non-hallucinogenic treatment strategies that are both safer and 
more effective than existing treatment options.\14\
---------------------------------------------------------------------------
    \14\ reporter.nih.gov/project-details/10003396.
---------------------------------------------------------------------------
    As with all human subjects research, clinical research on 
psychedelic drugs is governed by several statutes, regulations, and 
policies intended to protect the rights and welfare of research 
participants. For example, NIH has specific requirements for research 
staff and policies regarding research conduct, safety monitoring, and 
reporting of information about research progress.\15\ In accepting an 
award that supports human subjects research, the recipient institution 
assumes responsibility for all research conducted under the award, 
including protection of human subjects at all participating and 
consortium sites.\16\ All human subjects research must also be 
reviewed, approved, and monitored by an Institutional Review Board.\17\
---------------------------------------------------------------------------
    \15\ grants.nih.gov/policy/humansubjects/policies-and-
regulations.htm.
    \16\ grants.nih.gov/grants/policy/nihgps/html5/section_4/
4.1.15_human_subjects_
protections.htm.
    \17\ www.fda.gov/regulatory-information/search-fda-guidance-
documents/institutional-review-boards-frequently-asked-questions.
---------------------------------------------------------------------------
    Because psychedelic drugs are controlled substances, clinical 
research using psychedelic drugs must also follow Drug Enforcement 
Administration requirements, including registration, inspection, and 
certification of the drugs.\18\
---------------------------------------------------------------------------
    \18\ grants.nih.gov/grants/policy/nihgps/html5/section_4/
4.1.5_controlled_substances.htm.
---------------------------------------------------------------------------
    From April through June 2021, the Trans-NIH Integrative Medicine 
Course Organizing Committee hosted a series of research talks on 
psychedelic drugs.\19\ Building on these research talks, NIMH and NIDA 
are now working together to convene a scientific workshop in winter 
2021. This workshop will bring together leading researchers to examine 
the state of the evidence for the use of psychedelics in the treatment 
of mental illnesses.
---------------------------------------------------------------------------
    \19\ events.cancer.gov/nci/psilocybinresearch/agenda.
---------------------------------------------------------------------------
    Question. The United States shares a unique political relationship 
with the Native Hawaiian community. Different Federal agencies within 
HHS are responsible for the administration of Native healthcare 
programs, but the same Federal trust responsibility requires the 
provision of comprehensive, quality healthcare to Native Hawaiians, 
Alaska Natives and American Indians. In 2015, NIH established the 
Tribal Health Research Office within the Office of the Director to 
coordinate tribal health research activities across NIH. However, no 
such research office exists for Native Hawaiians.
    Would you consider expanding the scope of the Tribal Health 
Research Office to include Native Hawaiians? Would this help to 
increase the number of Native Hawaiian researchers and the amount of 
Native Hawaiian research being conducted across the country?
    Has NIH set any goals for the Tribal Health Research Office, and 
how will you measure its success and impact across NIH's Institutes and 
Centers?
    Some funding opportunities at NIH, such as the Native American 
Research Centers for Health program, do not permit entities serving 
Native Hawaiian communities to apply. Why are these entities excluded, 
and would NIH consider including these entities in the eligibility for 
these grant opportunities?
    Answer. The National Institutes of Health (NIH) Tribal Health 
Research Office (THRO) does not conduct disparity research on Native 
American populations. THRO ensures that the NIH fulfills its 
obligations to Indian Tribes as federally recognized sovereign nations, 
conducts government to government interactions appropriately, and holds 
formal Consultations with Tribal governments on policy, regulatory, and 
legislative issues that have a significant direct impact on Indian 
Tribes.
    The National Institutes of Health (NIH) published the NIH Strategic 
Plan for Tribal Health Research with input from American Indian/Alaska 
Native (AI/AN) Communities and the NIH Tribal Advisory Committee (TAC). 
The plan includes four agency-wide strategic goals: enhancing 
communication and collaboration; building research capacity for AI/AN 
communities; expanding research; and enhancing cultural competency and 
community engagement. The Tribal Health Research Office (THRO), along 
with the NIH Institutes and Centers (ICs), developed processes and 
metrics for evaluating progress on the strategic objectives and their 
supporting action items to achieve these goals. THRO regularly collects 
data on AI/AN health research activities from all ICs through an 
automated process to analyze the NIH research portfolio, assess 
progress towards the strategic goals, and measure impact across NIH.
    The National Institute of General Medical Sciences in conjunction 
with multiple NIH Institutes, Centers, and Offices (ICOs) partner with 
Indian Health Service (IHS) to support the Native American Research 
Centers for Health (NARCH). NARCH grant applications are submitted by 
and awarded to a tribe or tribal organization, who are sovereign 
nations with distinct governing bodies. Awarding the grant directly to 
the tribe or tribal organization allows for the community to dictate 
and oversee research priorities, while drawing upon necessary expertise 
from the research community to accomplish its scientific goals.
                                 ______
                                 
            Questions Submitted by Senator Joe Manchin, III
    Question. West Virginia is consistently ranked last in the nation 
for health outcomes. In 2020, the America's Health Rankings Report 
ranked West Virginia 50th for premature deaths, frequent mental 
distress, and multiple chronic conditions. We also rank last in life 
expectancy. West Virginia has, in many ways, been left behind as 
medical advances have saved lives in other places.
    What is NIH doing to bridge this gap in health outcomes?
    How do you ensure that the medical research that you do benefits 
people in poor, rural communities?
    How can we better expand the access rural Americans have to 
successful medical treatments, particularly in states like mine where 
the disease burden is so high?
    Answer. The National Institutes of Health (NIH) recognizes the 
unique health disparities that rural communities face, and as such, 
rural health is an important area of research for the agency.
    Through diverse collaborations and partnerships with communities, 
academic institutions, and state agencies, NIH supports and conducts 
rural health research to improve health outcomes and reduce rural 
health disparities with a special emphasis on the poor in rural 
communities. In fiscal year 2020, NIH supported more than 1,000 rural 
health-related grants for approximately $728 million. In 2020, West 
Virginia received approximately $45.7 million in funding from NIH, of 
which about $6.4 million supported research and research capacity-
building activities related to rural health.
    In 2019, NIH held the Inaugural NIH Rural Health Seminar, a 
collaboration of several NIH Institutes and Centers to explore topics 
in rural health and opportunities for research collaborations to 
improve rural health outcomes. In 2020, NIH hosted a virtual rural 
health conference entitled, NIH Rural Health Seminar: Challenges in the 
Era of COVID-19. In October 2021, NIH will host the Pathways to 
Prevention Workshop: Improving Rural Health Through Telehealth-Guided 
Provider-to-Provider Communication, a virtual event to identify 
research gaps, explore barriers, and facilitate successful, sustainable 
implementation of provider-to-provider telehealth in rural settings.
    NIH's rural health research focuses on key areas aimed at 
addressing health disparities that rural populations in West Virginia 
and around the United States experience. In fiscal year 2020, in 
response to the disproportionate impact of coronavirus disease 2019 
(COVID-19) on racial and ethnic minority, and other vulnerable 
communities including rural populations, NIH established the Rapid 
Acceleration of Diagnostics for Underserved Populations (RADx-UP) 
initiative. The overreaching goal of the RADx-UP initiative is to 
understand the factors associated with disparities in COVID-19 
morbidity and mortality and to lay the foundation to reduce disparities 
for those underserved and vulnerable populations more impacted by 
COVID-19. One example of a RADx-UP project in your state, is the 
Developing Novel Strategies to Increase COVID-19 Testing among 
Underserved and Vulnerable Populations in West Virginia through 
Community and State Partnerships. This project will implement 
collaborative strategies to increase availability and uptake of severe 
acute respiratory syndrome coronavirus 2 (SARS CoV-2) testing among the 
medically underserved, rural West Virginia population that includes 
multiple vulnerable groups at risk for severe COVID-19 and death. This 
initiative will test whether those implemented strategies, including 
home test kit and mobile unit mechanisms, successfully increase 
testing, and if not, determine why the interventions did not work to 
inform future sustainable testing policy.
    In addition, NIH supports the West Virginia University Health 
Sciences TME CoBRE project, which focuses on the microenvironment of 
different tumor types, including cancers initiating in the bone marrow, 
head and neck, breast, and brain. This project will increase 
understanding of the constant interaction between the tumor and its 
environment, provide diverse training opportunities and mentoring 
strategies for junior faculty, and develop critical infrastructure and 
recruit additional tumor microenvironment focused scientists to West 
Virginia. Another project, the West Virginia Clinical and Translational 
Science Institute: Improving Health through Partnerships and 
Transformative Research (WVCTSI), leads statewide collaborations and 
innovation in clinical and translational research. This project will 
build sustainable research infrastructure, recruit clinician scientists 
and translational researchers that excel in team science, and actively 
engage with multiple stakeholders that include communities, medical 
providers, and policy makers to improve the health of West Virginians.
    NIH is committed to ensuring that there are opportunities for poor 
rural Americans to access the benefits of research and that research 
addresses the unique strengths and challenges of rural communities by 
supporting several initiatives focused on human immunodeficiency virus 
(HIV), cardiovascular disease, cancer, drug addiction, and other 
chronic diseases disproportionately affecting rural communities. First 
announced in April 2018, the NIH Helping to End Addiction Longterm\SM\ 
Initiative, or NIH HEAL\SM\ Initiative, is an expansive agency-wide 
effort. It spans basic, translational, clinical, and implementation 
science and promotes collaborations of all types of research to address 
the crises of opioid misuse, addiction, and overdose in the United 
States. Launched in fiscal year 2020, Strategies to Improve Health 
Outcomes and Reduce Disparities in Rural Populations supports research 
to promote a greater understanding of the challenges faced by rural 
populations in developing or adapting evidence-based interventions that 
can reduce health risks faced by rural Americans. A total of eight 
awards were funded including: Harnessing the Power of Peer Navigation 
and mHealth to Reduce Health Disparities in Appalachia which is using a 
community-based approach to integrate peer navigation and mobile health 
strategies to develop a culturally congruent, bilingual intervention to 
increase the use of HIV, sexually transmitted infection, and Hepatitis 
C prevention and care services among individuals with health 
disparities living in rural Appalachia. Another study, Heart of the 
Family: A Cardiovascular Disease and Type 2 Diabetes Risk Reduction 
Intervention in High-Risk Rural Families is examining the effects of a 
family focused, lifestyle intervention that is culturally tailored for 
use with rural Hispanic or Latino and non-Hispanic or Latino adults. In 
2020, the National Institute on Minority Health and Health Disparities 
(NIMHD) funded four rural Resource Hubs to focus on rural health 
research. These hubs will involve coalitions of researchers and 
community partners to build research capacity in an identified rural 
catchment area and offer opportunities to share resources and data 
across collaborators.
    NIH continues to support the Accelerating Colorectal Cancer 
Screening and Follow-Up Through Implementation Science (ACCSIS) 
Program, a Cancer Moonshot? Initiative, designed to reduce cancer 
screening disparities. The aim is to identify evidence-based 
interventions and identify promising approaches for bringing these 
interventions to unscreened populations. Researchers test interventions 
such as mailing programs for home testing, provider education, and 
clinic-based patient navigation among Medicaid, rural, and racial and 
ethnic minority groups. In fiscal year 2020, NIH reissued and released 
the Pragmatic Research in Healthcare Settings to Improve Diabetes and 
Obesity Prevention and Care funding opportunity announcement. This 
initiative aims to improve diabetes and obesity prevention and/or 
treatment that are adapted for implementation in healthcare settings 
where individuals receive routine medical care. One of the funded 
grants, Telemedicine for Reach, Education, Access, Treatment and 
Ongoing Support (TREAT-ON), is a diabetes educator-driven, primary 
care-based telemedicine model that redesigns primary care practice to 
provide access to real-time ongoing support and help high risk 
participants in an underserved rural community to achieve and sustain 
improvements in clinical, psychosocial and behavioral outcomes. The NIH 
Minority Health and Health Disparities Strategic Plan 2021-2025 aims to 
test best practices for dissemination and implementation of minority 
health and health disparities research in diverse diseases and 
conditions into rural communities.
    Continued collaborations and partnerships with scientists and 
organizations from rural communities, such as West Virginia, will 
contribute to NIH's reach in rural communities and support our work to 
combat rural health disparities.
    Question. The NIH funds the WV Clinical and Translational Science 
Institute at West Virginia University through a 5-year $20 million 
grant. The Institute provides critical health research across West 
Virginia and has successfully mentored early career investigators, 
established pilot project funding, and created a research network 
across 27 primary care sites. Their research has focused on important 
health issues in my state including lung disease in coal miners, opioid 
addiction, and the hepatitis C epidemic, as well as cancer, heart 
disease, and stroke. Most recently, the Institute has been on the front 
line of COVID-19 research, having received a $1.5 million NIH Grant to 
lead an 8-state effort so that data from COVID-19 patients could be 
analyzed to develop the most impactful COVID-19 research. They're also 
responsible for utilizing the NIH RADx grant to scale up COVID-19 
testing in WV Communities.
    Can you comment on the importance of continued collaboration 
between the NIH and research institutions like the WV Clinical and 
Translational Science Institute at West Virginia University?
    What more can we be doing to support young researchers, such as 
those mentored through this Institute?
    Answer. One of the core programs supported by the National 
Institute of General Medical Sciences (NIGMS) Institutional Development 
Award (IDeA) is the IDeA Networks for Clinical and Translational 
Research (IDeA-CTRs), which includes the West Virginia Clinical and 
Translational Science Institute (WV CTSI). The IDeA-CTR network aims 
to:
  --Support the development and/or enhancement of infrastructure and 
        human resources required to address clinical and translational 
        research needs in IDeA-eligible states and jurisdictions;
  --Strengthen clinical and translational research that addresses the 
        broad spectrum of health challenges faced by populations in 
        IDeA-eligible regions; and
  --Foster and coordinate collaboration in clinical and translational 
        research within an IDeA-CTR network and with other 
        institutions.
    Strengthening and expanding the capacity for clinical and 
translational research in IDeA-eligible states is a pressing need, 
since health conditions such as obesity, diabetes, cardiovascular 
diseases, cancer, infectious diseases, chronic obstructive pulmonary 
disease, maternal health issues, and substance use disorders are 
disproportionally present in and borne by communities in these states. 
The IDeA-CTR networks support health research professionals who have 
first-hand knowledge of these challenges in order to understand and 
improve the health outcomes of residents in affected jurisdictions. 
Having the WV CTSI in place during the coronavirus disease 2019 (COVID-
19) pandemic, for instance, has allowed it to act as a springboard for 
West-Virginia-based research aimed at studying and addressing the 
virus. The $1.5 million supplemental award referenced in this question 
facilitated the development of an eight-state consortium that created 
an IDeA State COVID-19 Patient Registry. Through the collaboration 
between the NIH and WVU, the Registry has become a key component of the 
National COVID Cohort Collaborative, making important contributions in 
addressing the unique challenges brought by COVID-19 to traditionally 
underserved groups such as rural populations. Another supplement to the 
WV CTSI supports a network for conducting COVID-19 testing in West 
Virginia that includes the state health department, the national guard, 
and rural clinics. This collaborative effort is playing a major role in 
facilitating the state's testing efforts. Finally, the WV CTSI is also 
a key participant of an NIH-sponsored multi-site Post-Acute Sequelae of 
SARS-CoV-2 (PASC) study of ``Long COVID'' patients who continue to 
experience symptoms long after initial infection.
    Both NIGMS and NIH remain committed to supporting IDeA-CTR networks 
like the WV CTSI, given the very important role that such networks play 
in developing research infrastructure and improving health outcomes 
within IDeA states.
    The National Institutes of Health (NIH) believes that supporting 
early career researchers is crucial to maintaining a productive, 
innovative, and diverse biomedical research workforce that can continue 
to advance the vitality of the scientific research enterprise. NIH's 
Next Generation Researchers Initiative (NGRI) is developing and 
implementing strategies to identify, support and retain investigators 
across early career stages.
    As part of the NGRI, NIGMS has prioritized and included several 
strategies for supporting trainees and early-stage investigators (ESIs) 
within its 2021-2025 Strategic Plan, along with targets for 
implementing those strategies that provide accountability and the 
ability to measure progress. Career development initiatives such as the 
recently launched Maximizing Opportunities for Scientific and Academic 
Independent Careers (MOSAIC) program focus on retaining and supporting 
postdoctoral scholars from diverse backgrounds through the critical 
point of transitioning them into independent faculty careers. 
Cooperative agreements with professional organizations support 
educational activities that equip MOSAIC scholars with professional 
skills, mentoring, and career networks. At the individual level, grants 
such as NIGMS' Maximizing Investigators' Research Award (MIRA) offer 
support to early-stage investigators (ESIs) by providing them both the 
opportunity to perform creative and ambitious research as well as the 
flexibility to follow important new research directions and scientific 
insights. Since launching this award mechanism in 2015, MIRA has 
supported 628 early-stage investigators (ESIs), at least two of whom 
were in West Virginia. In fiscal year 2020 alone, NIGMS funded 200 ESIs 
through MIRA. As these examples illustrate, both the NIGMS and NIH 
remain committed to supporting promising early career investigators in 
every state in the nation.
                                 ______
                                 
                Questions Submitted by Senator Roy Blunt
    Question. Dr. Collins, I am a big supporter of the Clinical and 
Translational Science Award (CTSA) program. I believe we should look 
for ways to strengthen the CTSA program and reinforce the hubs around 
the country. That is why I am troubled to hear about a possible CTSA 
reorganization that will be announced in June. This reorganization 
comes with limited discussion and consultation with the CTSA directors. 
I am concerned, specifically, with the proposal to break up hub awards 
into smaller pieces, requiring CTSAs to write several grant 
applications instead of just one. Dr. Collins, I have two questions. 
First, as you know, this Committee pays a lot of attention to CTSAs and 
has been concerned in the past about communication between NCATS and 
the CTSA community. For example, NCATS emailed relevant stakeholders to 
combat the rumors about changes to the CTSAs, but did not provide any 
relevant data to explain what they want to do and why they want to do 
it. That did nothing but add to the concerns and speculation in the 
community.
    Why haven't these specific changes been discussed broadly within 
the CTSA community? I believe if there was open dialogue and a stronger 
partnership between NCATS and CTSAs, there would likely be more buy-in 
from the community.
    Two, how does cutting the hub award and requiring CTSAs to compete 
for multiple awards strengthen the program? It appears to me that this 
change would bring uncertainty to the program and jeopardize the 
stability of the hubs.
    Answer. The Clinical and Translational Sciences Award (CTSA) 
program is indeed a very valuable and important program for the 
National Center for Advancing Translational Sciences (NCATS), NIH, and 
the nation. NCATS understands that there are often concerns when there 
are planned updates to a program, particularly one as large and 
impactful as the CTSA Program. The planned updates are part of the 
regular NIH business process for reissuing Funding Opportunity 
Announcements (FOAs), which is required because FOAs expire after 3-4 
years. The planned updates will maintain the structure of the program 
and reflect the public input received--much of which was provided by 
the CTSA hub institutions and investigators. The planned updates are 
designed to strengthen the program, by prioritizing hub strengths, 
streamlining the overall application process, emphasizing clinical 
partnerships which are critical to achieving the objectives of this 
national program, and stabilizing the funding provided to the hub 
institutions by allowing up to 7 years of funding (rather than the 
typical five-year award period for NIH awards).
    How NCATS Engages with the CTSA Community: NCATS agrees that a 
strong partnership is extremely important and works closely with the 
CTSA community on a regular basis.
  --Regular Meetings: A CTSA Steering Committee \20\ including 
        leadership from NCATS and the CTSA Principal Investigator 
        community, meets monthly. A monthly webinar for all CTSA 
        Program investigators also shares information about the 
        program. NCATS CTSA leadership and program officers also 
        routinely engage with investigators and institutional 
        leadership across the CTSA Program as part of their regular 
        duties for implementing a program of this size and complexity. 
        In addition, there are yearly multi-day conferences where the 
        CTSA investigators and NCATS staff engage deeply on important 
        issues related to the CTSA program.
---------------------------------------------------------------------------
    \20\ clic-ctsa.org/groups/steering-committee.
---------------------------------------------------------------------------
  --Engaging the Community on Updates to the Planned FOA: To maintain 
        fair and open competition for funding opportunities, NCATS 
        cannot discuss specific details about a draft FOA with select 
        groups of the public, particularly those who already have 
        funding and would be re-competing for the funds. The level of 
        engagement must be framed to ensure that all investigators and 
        institutions, not only the current awardees, have an equal 
        opportunity to compete for the program funds and that NCATS 
        officials act impartially and not give preferential treatment 
        to any organization or individual.\21\ In following these NIH 
        policies, NCATS provided multiple opportunities to ask for and 
        receive input from the broader public, including the CTSA 
        community, on how to improve the CTSA Program.
---------------------------------------------------------------------------
    \21\ ethics.od.nih.gov/principles-ethical-conduct-government-
officers-and-employees.
---------------------------------------------------------------------------
    --A key approach for input was a Request for Information (RFI) 
            released in the Fall of 2019. The comments received, many 
            from the CTSA community, significantly influenced the 
            updates to the CTSA Program that NCATS is planning. (RFI; 
            NOT-TR-19-027 \22\)
---------------------------------------------------------------------------
    \22\ grants.nih.gov/grants/guide/notice-files/NOT-TR-19-027.html; 
(see this video,www.youtube.
com/watch?v=LDBJSl-_QbQ, for an overview presentation of feedback 
received).
---------------------------------------------------------------------------
    --General feedback was sought from CTSA application peer reviewers 
            over multiple study sections; many of whom are also CTSA 
            investigators.
    --Informal discussions occurred with CTSA Program consortium 
            members, individually and in small group settings, over the 
            course of typical program oversight and interactions.
    --Often the first public discussion about a future FOA occurs when 
            NCATS, like other NIH Institutes and Centers, seeks concept 
            approval from its Advisory Council during a session open to 
            the public. This occurs on June 11, 2021. Of note, the 
            NCATS Advisory Council includes three members that are 
            Principal Investigators from the CTSA Program.
    --In addition, NCATS has built in additional time after the release 
            of the new FOA--6 months, instead of 2-4 months, prior to 
            the first application receipt date--to familiarize all 
            potential applicants with the new FOA, including hosting of 
            webinars to provide technical assistance to the applicant 
            community.
    --NCATS widely shared a communication to address inaccuracies and 
            rumors about changes to the CTSA Program FOA. The letter 
            did not discuss planned changes to the CTSA Program nor 
            provide data, as sharing details about the FOA in a non-
            public manner prior to its posting is not permissible.
    --Summary of Stakeholder Feedback: From the input received through 
            the multiple approaches described above, stakeholder 
            feedback centered around four distinct areas: (1) 
            decreasing application administrative burden, (2) 
            increasing Hub flexibility and Hub specialization 
            opportunities, (3) expanding Hub funding options, and (4) 
            preserving partnerships and collaborations. Three 
            additional areas were identified by NCATS for improvement: 
            (1) ensuring the CTSA Program's sustainability (in terms of 
            avoiding the need to reduce the number of hubs or cut 
            budgets), which requires updates to budget formulas and 
            calculations; (2) increased emphasis towards addressing 
            health disparities; and (3) strengthening clinical research 
            capabilities, which have been critical to the national 
            responses to the opioid epidemic and the coronavirus 
            disease 2019 (COVID-19) pandemic.
    Hub Budgeting: NCATS takes the proper stewardship of taxpayer funds 
very seriously. NCATS does not intend to change the number of hubs or 
the amount of funding dedicated to the hub core awards. Future award 
amounts will be based on the amount requested by each applicant and 
will follow a revised formula for classifying the size of awards from 
what is currently used. In addition to incorporating feedback from 
different stakeholders, one of NCATS' objectives is to ensure the long-
term sustainability of the program while avoiding a reduction in the 
number of hubs or reducing hub budgets to stay within the appropriated 
budget for the program. Requested budgets for CTSA awardees have been 
increasing to the highest award size under the CTSA graduated award 
structure, which is not sustainable under current funding for the 
program, so a restructured award calculation is needed. The total award 
size of future hubs is anticipated to be similar to the current awards 
for the vast majority of awardees.
    Structure of the Program Applications: NCATS considered extensive 
public feedback, outlined above, in updating the CTSA Program FOA, 
including how these updates could contribute to stabilization for the 
awardees and to sustainability of the program. To date, the application 
process for institutions applying for CTSA hub awards has been 
complicated and burdensome, linking up to three separate activities 
together into one package, the U54 application. Linking the Hub, Career 
Development, and Training activities together for application 
submission and peer review is primarily for the benefit of NIH in being 
able to track these activities. However, based on feedback, it places 
substantial burden on the applying institution in the form of 
developing large, complex applications, often containing several areas 
of duplicate information. The review of three separate activities in 
one application risks pulling an institution out of funding range, due 
to one of the activities not faring well in peer review. Applicants 
that do not successfully compete face a prolonged period of uncertainty 
for funding, while having to address, revise, and resubmit the entire 
U54 application package for a subsequent review cycle. These factors 
combined with the duration of the awards--five years --raises the 
stakes of each application and contributes to an environment where 
applying and awarded institutions are in a constant state of 
application preparation.
    Stakeholder concerns about the complexity of the current 
application are an important and consistent piece of feedback NCATS 
received. Separating the applications will streamline the submission 
process for each component, will reduce duplication of information in 
an application, will result in less reliance on the success of one part 
of the application, will avoid the risk of significant delays in 
awarding a hub if the Training or Career Development components are not 
strong, and may allow better alignment of Training and Career 
Development awards with the clinical training calendar. Separating the 
Hub application from the training and career development applications 
will also allow the Hub application, which is the key institutional 
award, to be awarded for up to 7 years, more than the standard 5 years. 
With this strategy, NCATS intends to provide further stability to an 
institution's funding by extending the Hub award. Combining all 
applications together does not allow for that seven-year Hub award 
option, as NIH limits training and career development awards to 5 
years. Separating the applications and providing the additional planned 
funding opportunities will also give the institutions more control over 
where they place their priorities based on their own strengths, another 
key piece of feedback received through stakeholder input.
    In closing, we hope that these responses have addressed your 
concerns. If not, NCATS is happy to provide additional information. 
NCATS recognizes the significance of the CTSA Program. The pandemic has 
further served to highlight the importance of this program in 
responding to emerging clinical and translational needs at local, 
regional, and national levels. NCATS' intent with the proposed updates 
to the CTSA FOA is to strengthen the program, provide additional 
funding stability, and continue to incorporate research to tackle 
health disparities through this program. NCATS also wants to address 
important concerns raised by the CTSA community to streamline 
application and award preparation processes, continue to emphasize the 
importance of partnerships, and allow institutions more flexibility to 
leverage their strengths in contributing to this important national 
resource.
    Question. Dr. Collins, the impact of COVID-19 has been 
significant--both to Americans physical health, but also to their 
mental health. The fiscal year 2022 budget includes $25 million for 
focused research on the impact of the pandemic on mental health.
    Can you discuss what research areas this funding will be focused on 
and how the All of Us research initiative will play a role in 
understanding the full impact of the pandemic?
    Answer. The All of Us Research Program's participants come from 
diverse communities across the United States and generously donate 
their data and time to drive a wide range of biomedical discoveries, 
which are vital for informing public health strategies and 
preparedness. Due to the diverse nature of the program, the All of Us 
Research Program will play a vital role in understanding the mental and 
physical impact of the pandemic across the United States and within 
some of the hardest-hit communities. All of Us began to address the 
challenge of the coronavirus disease 2019 (COVID-19) pandemic in May 
2020 by leveraging its significant and diverse participant base to seek 
new insights into COVID-19 and its impact through an online COVID-19 
Participant Experience (COPE) survey.\23,24\ The COPE surveys focused 
on understanding the mental and physical impacts of the COVID-19 
pandemic on participants and included questions on symptoms, stress, 
social distancing, social determinants of health, and economic impacts. 
Participants were invited to take the survey in May, June, July, 
November, and December 2020, and February 2021. This multi-pronged 
assessment will enable researchers to study the effects of COVID-19 
over time and better understand how COVID-19 affects people's mental 
and physical health differently. To date, over 10,000 participants 
completed all six COPE surveys and over 100,000 completed at least one 
COPE survey during the pandemic, with 70 percent of those participants 
coming from a community that is historically underrepresented in 
biomedical research.
---------------------------------------------------------------------------
    \23\ allofus.nih.gov/news-events-and-media/announcements/all-us-
research-program-launches-covid-19-research- initiatives.
    \24\ www.nlm.nih.gov/dr2/
COPE_Survey_NIH_All_of_Us_Clean_4.27.20.pdf.
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    In addition to COPE, All of Us tested blood samples from over 
24,000 participants collected between January 2 and March 18, 2020, for 
the presence of SARS-CoV-2 antibodies, which provided evidence of 
infection in five states prior to initial reports. The program 
anticipates making the full results of this study available in June 
2021.\25\ Additionally, All of Us is collecting relevant electronic 
health record (EHR) information from more than 246,000 participants, 
some of whom have been diagnosed with COVID-19 or sought healthcare for 
related symptoms, to help researchers look for patterns and learn more 
about the physical and mental health impacts of COVID-19 and the 
effects of different medicines and treatment. As data are made 
available from all of these efforts, researchers will look for new 
leads that may bring greater precision to the diagnosis, treatment, and 
prevention of COVID-19, including those communities that have been hit 
the hardest. The program will make data gathered through these 
activities broadly accessible to approved researchers on a rolling 
basis, in future releases of its secure data platform, the Researcher 
Workbench.\26\ The program will continue to explore additional ways it 
can leverage its unique and diverse dataset to answer critical research 
questions to enhance our understanding about the full impact of the 
pandemic, especially with a focus on mental health.
---------------------------------------------------------------------------
    \25\ The results of this study were announced on June 15, 2021; 
complete details at: allofus.nih.gov/news-events-and-media/
announcements/nih-study-offers-new-evidence-early-sars-cov-2-
infections-us.
    \26\ www.researchallofus.org/.
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    Question. Dr. Collins, the COVID-19 pandemic highlighted the need 
to use non-human primates (NSP) in research. The budget requests $30 
million for NSP infrastructure.
    Can you provide further details to the Committee on the need for 
this funding and details on how this funding would be allocated and to 
whom?
    What types of research would be at jeopardy if NSPs were not 
replaced or expanded?
    Answer. The National Institutes of Health (NIH) remains committed 
to protecting animal welfare while, at the same time, advancing 
biomedical research and human health. The budget request for $30 
million for nonhuman primate infrastructure would cover facilities used 
to house nonhuman primates which require continual updates and 
maintenance to ensure responsible stewardship over these invaluable 
resources. The funds in the budget request would be distributed by 
soliciting applications from NIH grantees to improve existing 
facilities, not to establish new nonhuman primate facilities. Several 
nonhuman primate facilities have existed for over 60 years and housing 
enclosures require frequent repair and replacement. New construction 
for research facilities would include animal holding rooms, necessary 
equipment such as surgical tables, centrifuge, ultrasound, clinical 
analyzer, procedure, and veterinary clinical support in order to meet 
or exceed the current high-level care of the nonhuman primates. 
Additionally, the COVID-19 pandemic highlighted the need for new 
construction to expand animal biosafety level 3 areas in order to have 
biocontainment facilities associated with nonhuman primate facilities. 
In addition to ethically appropriate housing, nonhuman primates require 
a proper diet, clinical/veterinary care as well as psychological and 
environmental enrichment, which necessitates skilled staff and 
additional resources including supplemental produce, various enrichment 
devices such as foraging devices for food, various toys, and puzzles.
    NIH would support expansion at existing NIH-supported facilities to 
leverage the investment. The NIH Office of Research Infrastructure and 
Programs (ORIP) supports a well-coordinated national consortium of 
seven National Primate Research Centers (NPRCs) and other breeding 
colonies that collectively address research needs and trends, best 
husbandry practices, maintenance of genetic diversity, standardization 
of models, ethics, rigor, and reproducibility. NPRCs are national 
resources serving not only NIH-funded investigators but other federally 
funded investigators, foundations, and industry, including many SARS-
CoV-2 projects in the last year.
    Research with animal species, including nonhuman primates, remains 
critical for modeling human physiology and is essential for developing 
new prevention strategies, treatments, and cures for disease beyond the 
need for responding to emerging infectious diseases. Nonhuman primates 
have been essential for understanding human biology and developing 
treatments for diseases, mostly because of our shared anatomy, 
physiology, and behavior. Importantly, the genetic sequence 
similarities between nonhuman primates and humans can reach up to 98.77 
percent, which has made nonhuman primates models critical for studying 
neurobiology, transplant tolerance and rejection, infectious diseases, 
reproductive biology, and regenerative medicine. More recent 
applications have been in regenerative medicine and gene therapy and 
editing. There is a rapidly emerging need for marmosets in the 
neurosciences where recent National Academies of Sciences, Engineering, 
and Medicine (NASEM) reports and the Brain Research Through Advancing 
Innovative Neurotechnologies (BRAIN) Initiative community have pointed 
out that demand far exceeds supply.\27\ Another critical area of 
intense need and research development is nonhuman primate models of 
Alzheimer's disease to develop therapies. Nonhuman primate models are 
commonly used for studies of visual systems, auditory systems, 
cognitive function, and brain connectivity. The single largest 
application of nonhuman primates continues to be in developing vaccines 
and therapies for HIV/AIDS.
---------------------------------------------------------------------------
    \27\ www.nap.edu/read/25356/chapter/7.
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    Research using animal models, including nonhuman primate models, 
has led to tremendous advances critical for saving countless lives and 
extending human life expectancy around the world. Until suitable non-
animal models are developed, the complexity of human systems, both in 
health and in disease, can only be truly understood through 
complementary model systems with sufficient complexity, and nonhuman 
primates remain invaluable for this effort. When animal models are 
required, NIH will only conduct and support research in accordance with 
the highest scientific and ethical principles. To uphold these 
principles, the NIH budget includes investments in nonhuman primate 
facilities, resources, and enrichment.
    Question. Dr. Collins, how much funding, broken down by Institute 
or Center, has NIH repurposed for COVID-19 related lab reopenings or 
lost research activities?
    Answer. To support our recipients affected by the pandemic, the 
National Institutes of Health (NIH) provided extensions, both funded 
and unfunded, as well as administrative supplements, to address the 
unanticipated impacts of the pandemic. The NIH has also issued multiple 
funding opportunities for current recipients to repurpose existing 
awards and expand the scope of ongoing research to include coronavirus 
disease 2019 (COVID-19) research activities.\28\ Continued support for 
these projects is contingent on satisfactory progress, the availability 
of funds, and NIH Institute and Center (IC) funding priorities, which 
continue to change as the pandemic, and research on COVID-19 
progresses.
---------------------------------------------------------------------------
    \28\ grants.nih.gov/grants/guide/COVID-Related.cfm.
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    Decisions related to individual awards are made by the funding NIH 
IC on a case-by-case basis, taking into account those critical factors. 
All requests to change the scope of an NIH grant award require prior 
approval from the awarding NIH IC, as stipulated in the NIH Grants 
Policy Statement, section 8.1.2.5.\29\
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    \29\ grants.nih.gov/grants/policy/nihgps/HTML5/section_8/
8.1.2_prior_approval_
requirements.htm#Change4.
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    The NIH continues to analyze the data on the impact of COVID-19 on 
the biomedical research community, and its potential impact on NIH 
budget and grant activities.
    Question. It is my understanding that one of the main issues NIH 
faced related to COVID-19 expenses was for post-doctoral candidates 
finishing their training, research, or fellowship.
    How has this issue been addressed and do you expect to see a 
funding issue related to the extension of some of these grant awards 
into fiscal year 2022?
    Answer. The coronavirus disease 2019 (COVID-19) pandemic, along 
with extensive mitigation measures, has adversely affected progress in 
many biomedical research settings. Evidence from multiple sources, 
including results from a survey during the fall of 2020, indicates 
legitimate concerns about career trajectory for early career 
scientists.\30\ Hearing these concerns, the National Institutes of 
Health (NIH) issued a Guide Notice detailing our approach to support 
early career scientists whose career trajectories may have been 
significantly affected by the pandemic.\31\ Specifically, NIH is 
providing an opportunity for recipients in their last year of NIH 
Fellowship (F) and NIH Career Development (K) awards who have been 
impacted by COVID-19 to request extensions.\32\ Such extensions will be 
considered on a case-by-case basis, within the existing availability of 
funds.
---------------------------------------------------------------------------
    \30\ nexus.od.nih.gov/all/2021/03/25/the-impact-of-the-covid-19-
pandemic-on-the-extramural-scientific-workforce-outcomes-from-an-nih-
led-survey/.
    \31\ grants.nih.gov/grants/guide/notice-files/NOT-OD-21-052.html.
    \32\ https://nexus.od.nih.gov/all/2021/02/08/extensions-for-early-
career-scientists-whose-career-trajectories-have-been-significantly-
impacted-by-covid-19/.
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    Generally speaking, the NIH typically makes between 500 to 600 F 
and K extensions per year, the vast majority (more than 95 percent) of 
which are no-cost extensions. Only seven funded extensions were awarded 
in fiscal year 2019. In fiscal year 2020, the NIH awarded 548 
extensions, with 75 (14 percent) of these being funded extensions. Thus 
far in fiscal year 2021, 15 funded extensions are linked to NOT-OD-21-
052, but we will have a much better sense of uptake as the fiscal year 
concludes. Though there appears to be a relative increase in the number 
of funded extensions commensurate with the pandemic, the absolute 
numbers remain low.
                                 ______
                                 
            Questions Submitted by Senator Cindy Hyde-Smith
    Question. What is the fully intended scope of ARPA-H? Will it 
address diseases beyond cancer, diabetes, and Alzheimer's, such as ones 
with more challenging markets? Do you have examples?
    Answer. The scope of the Advanced Research Projects Agency for 
Health (ARPA-H) is intended to be broad and, indeed, stretch beyond the 
areas initially identified by the President. There are a number of 
areas with substantial unmet needs--some examples include emerging 
infectious disease, rare and ultra-rare disease, and antimicrobial 
resistance--and, with targeted investments over time, breakthrough 
progress could be made. In addition to specific disease areas, ARPA-H 
intends to build capabilities and explore various platform 
technological approaches which may have broad applicability across a 
range of diseases and conditions. A recent commentary in Science \33\ 
outlined some exciting concepts such as developing mRNA vaccines to 
prevent most cancers; creating molecular ``zip codes'' to more 
precisely target tissues and cell types while minimizing side effects; 
deploying holistic interventions that identify those at high-risk and 
leverage new telehealth approaches to eliminate racial disparities in 
maternal morbidity and mortality rates and premature births; and 
developing small, highly accurate, inexpensive, non-intrusive, wearable 
24/7 monitors for blood pressure and blood sugar. While these examples 
are meant to illustrate the breadth of potential projects that ARPA-H 
could support, we believe it is projects like these that can have a 
significant impact for patients who are relying on biomedical research 
and innovation to live longer, healthier lives.
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    \33\ science.sciencemag.org/content/373/6551/165.
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    Question. Additionally, how will ARPA-H fit into the larger health 
focused R&D structure? How will its role be defined as unique among the 
various funding programs, and will there be coordination with other 
entities such as BARDA to ensure cooperation and avoid duplication?
    Answer. The Advanced Research Projects Agency for Health (ARPA-H) 
is meant to become an integral component of the constellation of 
agencies focused on promoting health and research and development--both 
within and beyond NIH and HHS. As described in a recently published 
commentary in Science,\34\ ARPA-H should be housed as a new entity 
within NIH. The rationale for this organizing principle is two-fold. 
First, the goals of ARPA-H fall squarely within the mission of the NIH, 
which is ``to seek fundamental knowledge about the nature and behavior 
of living systems and the application of that knowledge to enhance 
health, lengthen life, and reduce illness and disability.'' Second, the 
NIH offers a rich source of fundamental health research that will be 
foundational for a constructive, collaborative, and productive 
relationship with ARPA-H. We envision robust collaborations on 
synergistic topics with the existing NIH Institutes and Centers, along 
with organizations both outside and within the government. The added 
benefit of housing ARPA-H within NIH is that it will create 
administrative efficiencies so that more resources can be directed 
toward the mission and help avert duplication of effort.
---------------------------------------------------------------------------
    \34\ science.sciencemag.org/content/373/6551/165.
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    In mid-July, the Administration launched a Federal Joint Fast Track 
Action Committee (FTAC) intended to help steer the creation of ARPA-H 
and lay the groundwork for strong interagency coordination. OSTP and 
NIH serve as co-chairs of this committee that includes representatives 
from the Department of Agriculture, DARPA, Office of the Under 
Secretary of Defense for Research & Engineering, ARPA-E, BARDA, CDC, 
CMS, FDA, VA, EPA, NSF, and the Smithsonian Institution, among others. 
Bringing these entities together at an early stage will help ensure 
strong collaboration and coordination among the various research-
focused organizations throughout the Federal Government. The agency 
personnel who sit on the FTAC will also be a valuable source of insight 
and advice as ARPA-H is launched.
                                 ______
                                 
            Questions Submitted by Senator Patrick J. Leahy
    Question. I strongly support the Administration's renewed approach 
to innovation in medical research through the establishment of the 
Advanced Research Projects Agency for Health (ARPA-H). COVID-19 has 
shown that a commitment to breakthrough innovation, directed allocation 
of resources, and collaborative approaches can accelerate how 
scientific breakthroughs can be transitioned to treatments and cures. 
The administration has proposed that the agency will focus on 
innovative treatments in cancer, Alzheimer's disease, and opioid 
disorders. Several institutions in Vermont are national leaders in 
these stated research fields despite their smaller and more rural 
nature. While I strongly support any efforts to accelerate innovation, 
I am concerned that valuable collaborators could be left out or lose 
out on Federal funding, particularly if there is no traditional grant 
application process.
    What role will smaller and more rural research institutes play in 
ARPA-H? If projects are funded outside a grant application process, 
will there be established guidelines to include collaborators from 
rural or traditionally underrepresented areas?
    Answer. Over the long term, the proposed structure for the Advanced 
Research Projects Agency for Health (ARPA-H) is intended to empower the 
ARPA-H leadership and staff to set and execute on research priorities 
for a variety of high-risk, high-reward, milestone-driven projects that 
can lead to novel capabilities, platforms, and resources that are 
applicable to a range of diseases. These priorities include the 
opportunity to fund smaller and more rural research institutes.
    For the initial direction, the Administration is working to set up 
multiple pathways, both within the government and the broader 
stakeholder community, for priority setting and for exploring new areas 
ripe for research at ARPA-H. At the time of this hearing, the White 
House Office of Science and Technology Policy (OSTP) and the National 
Institutes of Health (NIH) are in the planning phases of convening 
multiple listening sessions with key stakeholder groups including 
patient organizations, industry, venture capitalists and 
philanthropists, and others from the academic and research communities. 
During these sessions, stakeholders will be asked to offer their 
perspective on what they see as the greatest research challenges and 
opportunities that could be addressed using the ARPA-H model. This 
input will help refine the scope and provide a wealth of ideas for the 
first ARPA-H director to consider as they develop the agency's vision.
    In mid-July, the Administration established a Joint Fast Track 
Action Committee (FTAC) to help steer the creation of ARPA-H and lay 
the groundwork for strong interagency coordination. OSTP and NIH serve 
as co-chairs of this committee that includes representatives from 
Department of Agriculture, DARPA, Office of the Under Secretary of 
Defense for Research & Engineering, ARPA-E, BARDA, CDC, CMS, FDA, VA, 
EPA, NSF, and the Smithsonian Institution, among others.
    Soliciting a diversity of perspectives and approaches will be a key 
tenet of the Advanced Research Projects Agency for Health (ARPA-H). 
Much like DARPA and ARPA-E, it will do so by supporting the best 
strategies to solve an identified challenge and by pursuing multiple 
approaches. Program managers will also have the authority to combine 
proposals from different institutions to assemble the boldest, most 
innovative portfolio, allowing each team to build on their strengths 
while benefiting from the knowledge, expertise, and resources from 
other institutions. ARPA-H will also provide awards that range in size 
and mechanism--from smaller, pilot projects to develop a prototype, to 
complex multi-site trials, to prizes that stimulate healthy competition 
and ingenuity. Further, ARPA-H will support a Small Business Innovation 
Research (SBIR) and Small Business Technology Transfer (STTR) program 
with business development, commercialization, and other resources to 
provide small businesses with the tools they need to be successful. 
These approaches are examples of mechanisms that ARPA-H will utilize to 
support a range of organizations across the country which may include 
small and/or rural institutions, and its portfolio will be regularly 
evaluated to ensure there is diversity of perspective. Because ARPA-H 
will be a nimble, dynamic organization, it will be able to readily 
pivot to experiment with new approaches.
    Question. Chronic pain is a significant public health issue 
affecting an estimated 50.2 million Americans each year. Based on data 
from the National Health Interview Survey (NHIS), the total value of 
lost productivity due to chronic pain is estimated to be nearly $300 
billion annually. With little known about alternatives for treating and 
managing relief from pain, medical providers are often limited to 
prescribing highly addictive opioids or muscle relaxants to help 
patients mitigate symptoms from pain. Scientific research suggests that 
long term use of such medications can result in the body's reduction of 
its own ability to fight pain. Even for patients who do not experience 
direct abuse or addiction with long term use, scientists have found 
that withdrawal symptoms are present when patients stop taking these 
medications. Unfortunately, research into addiction and alternatives to 
treatment has historically lagged at NIH. Enhanced research on chronic 
pain management and treatment, other than through the use of highly 
addictive opioid painkillers, has the potential to reduce substance 
abuse and promote better methods for addressing pain.
    I strongly support the NIH Heal Initiative to find solutions to 
curb the national opioid public health crisis by understanding, 
managing, and treating pain. Please describe any progress made by the 
HEAL Initiative on medication development to alleviate pain and to 
treat addiction. What remains the biggest barrier to research to 
investigate new and alternative options to treat chronic pain?
    Answer. The National Institutes of Health (NIH) recognizes the need 
to improve pain management without risk of addiction and other serious 
side effects. NIH is taking a multi-pronged approach to develop safe 
and effective therapies to reduce our reliance on opioids and treat 
addiction. The NIH Helping to End Addiction Long-term (HEAL) Initiative 
launched in 2018 has awarded over $1.5 billion for research to discover 
and accelerate development of non-addictive pharmacological and non-
pharmacological pain treatments, as well as treatments for opioid use 
disorder (OUD) and overdose.
    Through the HEAL Initiative, NIH supports over 70 targeted studies 
to accelerate the development of treatments for OUD, including novel 
medications and biologic agents, as well as novel formulations of 
approved medications to treat OUD and prevent opioid overdose. To date, 
16 Investigational New Drug Applications were filed with the U.S. Food 
and Drug Administration and authorized to proceed for human studies. 
These studies focus on a variety of drug targets, as well as vaccines 
that could prevent opioids from entering the brain. HEAL currently 
funds nine opioid vaccine projects including vaccine candidates 
targeting oxycodone,\35\ fentanyl \36\ and heroin.\37\ This strategy 
could offer more accessible, manageable treatment through longer-
lasting vaccines to reduce the risk of relapse.
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    \35\ reporter.nih.gov/search/Pcd2IghkPU6lnJkOT7FlFQ/project-
details/9778811.
    \36\ reporter.nih.gov/search/Wp_sHzUhIUuYqDimSa90iw/project-
details/9737173.
    \37\ reporter.nih.gov/search/GNnJWbYvQUeIlbwhgFofXA/project-
details/9734921.
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    HEAL-supported work also includes studies to identify, optimize and 
test promising molecules, biologics, and devices for treating pain that 
target non-opioid pathways in the nervous system. Biomarker studies to 
enhance clinical trials and improve best practices are moving forward. 
In addition, non-pharmacological approaches to manage many different 
pain conditions are being evaluated through effectiveness and 
implementation research approaches.
    In these ways, HEAL is providing much needed resources to advance 
research on new and safe alternatives to opioids for chronic pain. The 
complexity and diverse nature of chronic pain itself along with a high 
prevalence of other co-occurring chronic conditions such as diabetes, 
depression, and autoimmune disorders create an enormous challenge for 
advancing research.
    Mechanisms for the causes of different pain conditions vary, 
biomarkers for patient response to treatment and likelihood for 
progression of disease also are characteristic of the disease 
condition. In addition, treatments for co-morbidities require careful 
balancing and often long- term multidisciplinary care. These and other 
factors require an expanded breadth and scope of pain research to 
better provide personalized care for those with chronic pain. The 
Federal Pain Research Strategy \38\ describes research priorities to 
relieve the burden of pain. The NIH HEAL initiative provided support to 
move many of the report's recommendations forward.
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    \38\ www.iprcc.nih.gov/federal-pain-research-strategy-overview.
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    Specifically, the NIH HEAL initiative established essential pain 
research infrastructure to accelerate development of new medications 
and devices to treat pain. An analgesic screening platform uses animal 
and human cell-based models such as neural tissue chips for rapid 
screening of molecules or devices for analgesic-relevant biological and 
pain behavioral activity. HEAL, with input from academic and industry 
partners, established an Early Phase Pain Investigation Clinical 
research network (phase 2 studies) to test safety and efficacy of novel 
therapeutics and a later stage pain management Effectiveness Research 
Network (ERN) to compare effectiveness of pharmacological and non-
pharmacological approaches in many different pain conditions. The 
Pragmatic and Implementation Studies for the Management of Pain to 
Reduce Opioid Prescribing (PRISM) network focuses on clinical trials of 
non- pharmacologic pain therapies in healthcare systems. The Phase 2 
network will launch trials on two new analgesics in late 2021. The ERN 
is supporting eight large trials for various pain management 
strategies. PRISM is supporting six large trials in healthcare systems. 
In addition, HEAL established an analgesic development pipeline to 
accelerate the development and testing of novel drugs and devices. This 
comprehensive program uses team-based science coupled with a 
comprehensive set of research resources to bring new therapeutics 
rapidly to the clinic. To advance the discovery and validation of new 
drug targets, HEAL has funded over 30 projects to discover and verify a 
diverse set of drug target types across multiple pain conditions, six 
drug optimization studies on new safe and effective pain treatments, 
and 11 projects to test the effectiveness of implanted devices and 
noninvasive stimulation of nerves in the brain or throughout the body 
to reduce perception of pain. In addition, to improve the efficacy of 
clinical trials for pain treatments, and to increase the chance that 
new therapeutics will advance along the regulatory path to approval, 
HEAL tests the development of biomarkers to objectively measure pain, 
including pain associated with sickle cell disease, musculoskeletal 
disease, nerve pain and headache. Promising biomarkers identified 
through this program may advance to clinical validation through the 
Early Phase Pain Investigation Clinical Network (EPPIC-Net). Findings 
from these studies could improve quality of life for millions of people 
in the United States who experience pain daily. Recent HEAL 
accomplishments toward new therapeutics include two patent filings for 
small molecule modulators of pain receptors involved in chronic pain 
and migraine.
    New directions for HEAL will also continue to pursue goals laid out 
in the Federal Pain Research Strategy,\39\ including demonstration 
projects to aid in the development of a coordinated approach to pain 
management in healthcare systems. This effort would assess multi-
disciplinary and multimodal approaches to pain management embedded in 
healthcare systems. Research within systems of pain care would allow 
for effective interventions to be adopted into the healthcare system 
and improve access for patients. Focused discussion with select 
healthcare program leadership would identify pain conditions of 
greatest opportunity, with an emphasis on effectiveness research, 
quality management and team-based care. This effort would seek to 
leverage existing infrastructure through ongoing collaborative and 
interagency efforts.
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    \39\ www.iprcc.nih.gov/federal-pain-research-strategy-overview.
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    Another specific effort in development aims to advance health 
equity to address the wide disparities in care and treatment for pain 
and addiction, known to result in both the undertreatment and 
overtreatment with opioids, increased risk of addiction and overdose, 
lack of access to effective non-pharmacological options for pain 
treatment, and lack of access to evidence-based addiction care. 
Disparities in pain management exist across multiple levels: pain 
assessment, treatment, and management at the patient, provider, 
community, and healthcare system levels. Planned expansion to HEAL 
includes the development and implementation of culturally appropriate 
interventions for the prevention and management of pain and addiction 
in diverse populations, with a focus on sustainable and scalable 
interventions that can be rapidly implemented by healthcare systems.
    In addition, recent discoveries in human genetics and molecular 
biology will be incorporated into the development of a novel team-based 
platform to rapidly test targets and candidate therapeutics for diverse 
human pain conditions and share findings with the wider pain research 
community. This research will address pain systems and allow for a 
variety of research questions including conditions of chronic analgesic 
use, other drug use, substance use disorders (SUDs) and other co-morbid 
conditions, and will enable and accelerate human gene- and cell- based 
validation of pain therapeutic targets through the HEAL initiative and 
other pipelines. This will build on existing HEAL research on 
preclinical and translational research in pain, and ongoing efforts to 
accelerate the development of novel treatments for pain. Through these 
and other efforts at HEAL and across the NIH, we aim to continue to 
improve our understanding of pain and develop non-addictive, effective 
therapies.
    Question. Migraine is currently the second leading cause of all 
global disability. Unfortunately, due in part to limited research and 
treatment, inappropriate opioid prescriptions for migraine present 
Americans with ongoing risks of opioid use disorders and have worsened 
outcomes in patients. Overall, 6 million Americans living with 
migraines are active opioid users. I strongly support the NIH Heal 
Initiative to find solutions to curb the national opioid public health 
crisis by understanding, managing, and treating pain. While migraine 
grant proposals are eligible for consideration under the HEAL request 
for applications (RFAs) issued for pain research, less than 1 percent 
of HEAL Initiative appropriations have funded headache disorders 
research--the least funded NIH area among all the nation's burdensome 
diseases. I am very concerned about the failure to attract enough 
investigators to this historically under-funded research area.
    Does NIH have plans to issue specific RFA programs for headache 
disorders research, comparable in scope to the Back Pain Consortium 
(BACPAC) group of RFAs for research on back pain?
    Answer. The National Institutes of Health (NIH) recognizes the 
burden of pain at the individual and population levels and that 
headache disorders are prevalent and disabling conditions which affect 
millions of Americans. The NIH launched the HEAL Initiative (Helping to 
End Addiction Long-term) to improve pain care and better prevent and 
treat opioid use disorder. Priorities of the HEAL initiative, developed 
with our stakeholders with expertise in pain research and care, include 
enhanced understanding of pain, discovery and validation of novel pain 
therapeutic targets, testing therapies in clinical settings, and 
accelerating the process to bring new therapies to patients. The 
initiatives are, or were, open to all pain conditions. The HEAL 
initiative also established much needed research infrastructure to 
support innovative science. Headache research fits within the scope of 
all these initiatives and will benefit from the enhanced 
infrastructure.
    HEAL funding solicitations call for proposals across all pain 
conditions. NIH staff recognizes the low submission rate of headache 
applications and broadly disseminates information on HEAL and other 
funding announcements to the research community to encourage 
submissions. Most funding announcements specifically cite headache as 
an area of interest and others are inclusive of headache. Low back pain 
is an exception among pain conditions in that it has unique research 
gaps such as lack of diagnostic tools and technologies, no accepted 
common data elements, poor diagnostic criteria, complex etiology, and 
lack of an adequate evidence base for effective practice guidelines. 
The HEAL Back Pain Consortium (BACPAC) initiative was launched to fill 
these extensive gaps to improve pain care across the spectrum of low 
back pain.
    Migraine and other headache disorders have good classification 
schemas, a range of effective treatment therapies whose development was 
supported by NIH research, and evidence-based diagnostic categories and 
treatment protocols (International Headache Society). Our understanding 
of migraine etiology is more advanced than that for back pain. NIH has 
supported transformative basic research that advanced our knowledge of 
migraine mechanisms, causes, and predictors, biomarker identification, 
and new therapy development. For example, NIH supported investigators 
provided the foundation for development of CGRP antibodies now used 
widely for migraine therapy. NIH sponsored research also contributed to 
understanding how migraine auras activate nociceptors and initiate a 
migraine, and the mechanism of action for new migraine therapies such 
as vagus nerve stimulation. Basic research on potassium channels, 
delta, or kappa opioid receptors, and TRP channels fundamentally 
increased our understanding of trigeminal nociceptors and their 
involvement in initiating a migraine, giving us new targets for 
potential treatments. An NIH sponsored pivotal pediatric migraine 
clinical trial changed clinical practice for children with chronic 
daily headaches.
    NIH and HEAL leadership recognize that far too many headache 
sufferers are prescribed opioids despite clear clinical practice 
guidelines that call for non-opioid effective alternatives rather than 
opioids. This practice reflects the sparsity of headache specialists 
and the lack of and education of our primary care providers who are 
often the first to treat those with disabling migraines. NIH also 
recognizes the need to expand the headache research workforce. The HEAL 
initiative recently released funding announcements to support training 
and mentorship of early and mid- career researchers in the field of 
basic, translational, and clinical pain research. We encourage those 
interested in headache research to benefit from these opportunities.
                                 ______
                                 
                Questions Submitted to Dr. Anthony Fauci
            Questions Submitted by Senator Richard J. Durbin
    Question. I have received a lot of questions from Illinois 
families, who are hoping for more clarity on the CDC's most recent mask 
guidelines. Many vaccinated parents--with unvaccinated children at 
home--are wondering if they should be wearing masks when out in public.
    What advice would you give to vaccinated parents who have 
unvaccinated children at home?
    When do you think we will have a COVID vaccine approved for 
children younger than 12 years of age?
    Answer. Currently authorized coronavirus disease 2019 (COVID-19) 
vaccines meet the U.S. Food and Drug Administration's (FDA's) rigorous 
standards for safety and effectiveness, and current data suggest that 
fully vaccinated people are less likely to transmit severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) to others. According to 
the Centers for Disease Control and Prevention (CDC), fully vaccinated 
people--including those living with unvaccinated children or 
adolescents--can resume activities without wearing masks or physically 
distancing, except where required by Federal, state, local, tribal, or 
territorial laws, rules, and regulations. Individuals ages 2 and older 
who are unvaccinated, however, should continue to wear masks in public 
and when around people who do not live in their household, except when 
eating or sleeping. CDC will continue to evaluate and update public 
health recommendations for fully vaccinated people as more information, 
including on Delta and other new variants, becomes available.
    Efforts to evaluate COVID-19 vaccines in children under age 12 
currently are underway, and a COVID-19 vaccine may be available for 
this age group by the end of 2021. On March 16, 2021, Moderna, in 
collaboration with the National Institute of Allergy and Infectious 
Diseases (NIAID) and the Biomedical Advanced Research and Development 
Authority (BARDA), launched KidCOVE, a Phase 2/3 study to evaluate the 
safety and efficacy of the Moderna COVID-19 vaccine in children ages 6 
months to less than 12 years. Pfizer also is conducting a Phase 1/2/3 
trial to evaluate its COVID-19 vaccine in this age group. In addition, 
other vaccine developers are planning to begin trials to test their 
vaccine candidates in children. Until a COVID-19 vaccine is available 
for children under age 12, it will be important for all individuals, 
especially children and other unvaccinated individuals, to continue to 
follow all public health measures for COVID-19 advised by the CDC, 
including frequent hand washing and the use of masks and social 
distancing in certain settings.
                                 ______
                                 
            Questions Submitted by Senator Joe Manchin, III
    Question. My home state of West Virginia is battling an epidemic 
during the middle of a pandemic. My state has been devastated by the 
drug epidemic, COVID-19, and we now lead the nation in new HIV 
infection rates. You have spent much of your career focused on the 
prevention, diagnosis, and treatment of HIV/AIDS. Your research has 
been instrumental in saving countless lives in the United States and 
around the world. The National Institute of Allergy and Infectious 
Diseases supports initiatives focused on diagnosing, treating, 
preventing and responding to the HIV epidemic in the United States. 
These efforts represent steps in the right direction, but will not 
alone end West Virginia's increasing numbers of new HIV infections and 
other opioid-related infectious diseases.
    What is being done to replicate testing and surveillance efforts we 
saw put into place for COVID-19 for other infectious diseases, like 
HIV/AIDS?
    What public health infrastructure would be required to bring better 
infectious disease testing and surveillance to fruition?
    Answer. The Federal response to coronavirus disease 2019 (COVID-19) 
relied heavily on the utilization and expansion of existing resources 
for human immunodeficiency virus (HIV) and other infectious diseases. 
By leveraging available resources, we have been able to accelerate the 
development of diagnostic tests and other medical countermeasures, as 
well as surveillance and community engagement efforts. In turn, 
knowledge gained from the COVID-19 response may inform strategies to 
address other infectious diseases such as HIV. This includes efforts 
undertaken by the U.S. Department of Health and Human Services (HHS) to 
end HIV in the United States by 2030 through the Ending the HIV 
Epidemic in the U.S. (EHE) initiative. EHE is coordinating across HHS 
agencies and with patient, community, academic, and other partners to 
plan, design, and deliver local HIV prevention and care services. This 
``whole-of-society'' approach is a model for ending both the HIV 
epidemic as well as the COVID-19 pandemic. Proper diagnosis and 
treatment of HIV are key components of this initiative, and efforts to 
improve testing and surveillance for HIV are ongoing.
    An important aspect of the response to the COVID-19 pandemic as 
well as the HIV epidemic is community engagement. The National 
Institute of Allergy and Infectious Diseases (NIAID), in cooperation 
with the Department of Defense, established the COVID-19 Prevention 
Network (CoVPN) by leveraging existing NIAID-funded clinical trials 
networks, including networks focused on HIV treatment and prevention. 
The CoVPN built on existing community relationships to enhance trust 
and meaningful engagement in key racial and ethnic minority communities 
throughout the United States to promote diverse participation in 
clinical trials for COVID-19. The community relationships enhanced by 
the CoVPN may be further leveraged to advance efforts, including 
testing and surveillance, for HIV and other infectious diseases.
    The National Institutes of Health (NIH) also anticipates that the 
rapid establishment of COVID-19 testing and surveillance may help to 
address HIV and other infectious diseases. NIH launched the Rapid 
Acceleration of Diagnostics (RADx) initiative to speed innovation in 
technologies to test for severe acute respiratory syndrome coronavirus 
2 (SARS-CoV-2), in partnership with the Biomedical Advanced Research 
and Development Agency (BARDA), the Centers for Disease Control and 
Prevention (CDC), the U.S. Food and Drug Administration (FDA), and the 
Defense Advanced Research Projects Agency (DARPA). As part of RADx, NIH 
and CDC are evaluating whether frequent self-administered, at-home 
SARS-CoV-2 testing helps reduce community transmission of SARS-CoV-2. 
Efforts to develop and deploy rapid, point-of- need diagnostics for 
SARS-CoV-2--including at-home testing kits--may inform community-based 
testing and surveillance strategies for other infectious diseases, 
including HIV.
    NIH and NIAID will continue to build on investments in improved 
diagnostic tests for SARS- CoV-2 to support the development of novel 
diagnostic tests for other infectious diseases such as HIV. In 
addition, lessons learned on the best way to integrate and expand on 
existing research efforts and infrastructure will be invaluable as we 
continue to prepare for--and respond to-- other existing and emerging 
infectious disease threats.
    As discussed in response to part a of this question, the Federal 
response to the COVID-19 pandemic has strengthened existing 
partnerships and coordination mechanisms, as well as established new 
partnerships that will inform the response to future infectious disease 
pandemics and existing epidemics, such as the HIV/AIDS epidemic in the 
United States. The coordinated efforts through RADx and the CoVPN 
allowed us to leverage the intrinsic strengths from public and private 
sector partners to achieve an unprecedented level of scientific 
achievement and community engagement. When the COVID-19 pandemic ends, 
lessons learned from our experiences with RADx and the CoVPN will 
continue to help inform efforts to address other infectious disease 
threats.
    NIH and NIAID will continue to work with HHS Operating Divisions 
and other Federal agencies to identify the actions that were most 
effective in responding to the COVID-19 pandemic. This information may 
result in new initiatives, strategic plans, and/or formal assessments 
of pandemic preparedness.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby
    Question. As America begins to assist the world to vaccinate all 
who want it, the current vaccine options can be problematic for 
countries without the infrastructure to store vials in a cooled or 
frozen environment.
    How beneficial could an effective, intranasal vaccine option be for 
developing countries that cannot store the current vaccines at frigid 
temperatures or produce the healthcare workers to give the shot?
    Do you see this option benefitting Americans who may be hesitant to 
receive the current vaccine dosage in a shot?
    Answer. Global access to safe, effective vaccines will be critical 
to address the coronavirus disease 2019 (COVID-19) pandemic. Limiting 
the spread of the severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) virus in foreign countries helps to control the pandemic 
in those countries while also limiting the development and spread of 
variants that could eventually be introduced into the United States. To 
enhance vaccine availability in foreign countries, the Biden 
Administration has supported and contributed to COVAX, a global 
mechanism for equitable access to COVID-19 vaccines. COVAX has 
delivered COVID-19 vaccines to more than 100 countries, the majority of 
which have lower-income economies. The United States also has made 
millions of doses of COVID-19 vaccines available to other countries to 
support vaccination campaigns around the world.
    Existing COVID-19 vaccines are being successfully administered 
globally, and several COVID-19 vaccines authorized for emergency use or 
in clinical testing in the United States can be shipped and stored at 
refrigerator temperatures (2-8 degrees Celsius). Still, the development 
of vaccines that can be administered with less skill and/or stored at 
warmer temperatures have the potential to expand vaccination efforts 
both in the United States and abroad. The National Institute of Allergy 
and Infectious Diseases (NIAID) is supporting the development of 
vaccine candidates and platforms that may be more accessible and 
convenient than currently available COVID-19 vaccines, including a 
single-dose intranasal SARS-CoV-2 vaccine candidate called ChAd-SARS-
CoV-2-S. NIAID scientists and collaborators recently showed that the 
intranasal ChAd-SARS-CoV-2-S vaccine candidate limited infection in 
non-human primates. Novel vaccines with alternative administration 
strategies, such as intranasal vaccines, may reduce barriers to 
transporting and administering vaccines in developing countries. It is 
important to note, however, that these vaccines may still need to be 
kept at low temperatures or may require administration by a healthcare 
provider with specialized training to ensure accurate dosing and 
administration. For example, FluMist Quadrivalent--a U.S. Food and Drug 
Administration-approved intranasal vaccine against influenza--must be 
administered by a healthcare provider in the United States.
    In addition, National Institutes of Health (NIH) scientists and 
NIH-supported researchers are studying additional vaccine delivery 
technologies, including vaccines that can be orally administered or 
that utilize microneedles in patches placed on the skin to deliver the 
vaccine. For example, NIH scientists have begun preclinical evaluation 
of a virus-like-particle-based vaccine candidate for SARS-CoV-2 that 
can be administered orally, and NIH-supported researchers are 
evaluating a patch-based vaccine for SARS-CoV-2. An NIH-supported Phase 
I trial of a patch-based vaccine candidate for influenza showed that 
individuals that received the vaccine had a similar immune response to 
those receiving the influenza vaccine via intramuscular injection. NIH 
also is supporting the development of another promising patch-based 
vaccine candidate for influenza that uses biodegradable microneedles 
originally developed through NIH-supported research to stabilize 
vaccines and antibiotics outside of the cold chain. Although additional 
testing will be necessary, orally administered and patch-based vaccines 
may prove to be an invaluable tool in resource-limited settings as they 
may require little to no refrigeration, as well as less training to 
administer correctly.
    As we work to address the COVID-19 pandemic, as well as other 
infectious disease threats, recent innovations in vaccine technology 
will help make it easier to get vaccines to areas that can be difficult 
to serve with traditional vaccines. NIH continues to support research 
on intranasal, oral, and patch-based vaccine platforms, all of which 
could be highly adaptable for use against a number of infectious 
pathogens.
    Vaccines that can be administered intranasally may be considered 
less invasive than those that require an injection. Such an option may 
encourage individuals who are hesitant to receive the COVID-19 vaccines 
currently authorized for emergency use in the United States, which are 
all administered via intramuscular injection, to become vaccinated. 
Additional vaccine delivery technologies, such as oral or patch-based 
vaccines may also provide additional flexibilities when trying to reach 
individuals in resource-limited areas or who are vaccine hesitant or 
needle adverse. As noted in the response to part a of this question, 
NIAID is supporting and will continue to support the development of 
vaccine candidates with different delivery technologies to reduce 
vaccine hesitancy as well as barriers to vaccine access.
                                 ______
                                 
  Questions Submitted to Dr. Diana Bianchi and Dr. Eliseo Perez-Stable
            Questions Submitted by Senator Richard J. Durbin
    Question. Our nation continues to struggle with racial disparities, 
especially in maternal health. The U.S. is one of only 13 countries 
where our nation's maternal mortality rates are worse now than they 
were 25 years ago. Every year, 700 women in the U.S. die as a result of 
their pregnancy--and more than 60 percent of these deaths are 
preventable. Tragically, African American and Hispanic women are three 
times as likely as White women to die from pregnancy-related issues. 
For years, I have introduced the MOMMA's Act with Rep. Robin Kelly, and 
I'm so pleased that a major component of our bill was recently signed 
into law as part of the American Rescue Plan. Now states can follow in 
Illinois' footsteps by allowing new moms to keep their Medicaid 
coverage for a full year, versus just 60 days.
    What research NIH is doing in this space?
    How is NIH working to actually improve maternal and infant 
healthcare?
    Answer. Maternal health is a priority for the National Institutes 
of Health (NIH) and multiple NIH institutes have heavily invested in 
research to prevent maternal morbidity and mortality (MMM) and improve 
health for women, before, during, and after pregnancy. In fiscal year 
2020 NIH supported $407 million in research on maternal health and $224 
million in research on MMM.
    In a year that was dominated by both the coronavirus disease 2019 
(COVID-19) pandemic and renewed calls to combat health disparities and 
inequities, NIH ensured these challenges were integrated into efforts 
to reduce MMM. In March 2020, researchers in the Eunice Kennedy Shriver 
National Institute of Child Health and Human Development's (NICHD) 
Maternal-Fetal Medicine Units Network designed the Gestational Research 
Assessments for COVID-19 (GRAVID) study, which evaluated data from more 
than 1,200 pregnant women at 33 hospitals across the country and found 
that pregnant COVID-19 patients with severe disease are at higher risk 
for cesarean delivery, postpartum hemorrhage, hypertensive disorders of 
pregnancy, and preterm birth. Data from the study is being shared with 
a larger registry to inform future studies of COVID-19's effects on 
pregnancy and maternal health.
    Tackling the challenge of reducing maternal MMM requires strong 
partnerships with and among local communities and resources, 
particularly with racial and ethnic minority populations that 
experience stark health disparities. To that end, several NIH 
Institutes, Centers, and Offices (ICOs) held community engagement 
activities to hear first-hand how patient communities can inform future 
research and what engagement strategies might enhance local efforts to 
improve maternal health. A common refrain was that research conducted 
in a community should be developed with and vetted by the community to 
ensure success and improved outcomes. These engagement activities 
informed the development of the IMPROVE (Implementing a Maternal health 
and PRegnancy Outcomes Vision for Everyone) Initiative, which aims to 
build an evidence base that will improve maternal care and outcomes 
from pregnancy through 1 year postpartum. IMPROVE is co-led by NICHD 
and the NIH Office of Research on Women's Health and engages over 30 
ICOs to research the leading causes of maternal mortality in the United 
States--cardiovascular disease, infection, and immunity--as well as 
contributing health conditions or social factors, such as mental health 
disorders, diabetes, obesity, substance use disorders, and structural 
and healthcare system issues that disproportionately affect Black 
pregnant and postpartum women. IMPROVE prioritizes comprehensive, 
interdisciplinary research that engages communities with high rates of 
maternal deaths and complications. This work will help create tailored, 
evidence-based solutions for pregnant and postpartum women.
    NIH research on MMM generates evidence that improves outcomes and 
clinical care, and several NIH Institutes have strong investments in 
this space. For example, an NICHD-funded study demonstrated that when 
hospitals implemented evidence-based recommendations for clinical 
practice there was a reduction in the risk of severe maternal morbidity 
from obstetric hemorrhage, a common complication of childbirth. The 
reduction was more dramatic for Black women more than for White women, 
reducing disparities and improving outcomes. NICHD is also supporting a 
machine learning framework to predict severe maternal morbidity. 
Researchers aim to analyze population-based data from Maryland state 
databases and hospital surveys to develop techniques that can predict 
maternal risks early. Identifying key predictors of severe maternal 
morbidity can help ascertain health disparities, strengths and 
weaknesses in obstetric care, and prevent adverse maternal and neonatal 
outcomes.
    In fiscal year 2020, the National Institute on Minority Health and 
Health Disparities (NIMHD) started an initiative entitled Addressing 
Racial Disparities in Maternal Mortality. This initiative supports 
multidisciplinary research projects that examine the clinical, social, 
behavioral, and healthcare system interventions to address racial 
disparities in MMM in the United States. Additionally, NIMHD funded the 
Maternal and Developmental Risks from Environmental and Social 
Stressors (MADRES) project in collaboration with the National Institute 
on Environmental Health Sciences, to examine prenatal environmental 
exposures and social stressors in relation to depression and 
cardiovascular risk factors postpartum.
    The National Heart, Lung, and Blood Institute (NHLBI) is weaving 
together a network of community-engaged researchers who will not only 
work to improve women's heart health and reduce maternal mortality, but 
will also address other health disparities. For example, NHLBI's new 
Maternal Health Community Implementation Program, will fund three or 
four regional coalitions to pilot test community-based strategies in 
areas where maternal death rates are high, particularly in the 
southeast. Additionally, NHLBI's Early Intervention to Promote 
Cardiovascular Health of Mothers and Children (ENRICH) will tap into 
existing Federal home health/wellness programs that serve at-risk 
families to determine if adding a cardiovascular intervention will 
enhance maternal and early childhood outcomes. Approximately 3,000 
mother- child pairs across various sites will be reached as part of 
this effort.
    These are just a few examples of how NIH's broad investment in 
addressing MMM is improving maternal and infant care.
                                 ______
                                 
             Questions Submitted by Senator Jeanne Shaheen
    Question. I am hopeful that our continued investment in the Special 
Diabetes Program, and diabetes research at NIH as a whole, can help 
spur a new wave of breakthroughs, and maybe one day a cure for 
diabetes.
    Now that Congress has secured longer-term funding for the Special 
Diabetes Program, can you please provide information on NIH's priority 
areas for Special Diabetes Program research in the years to come?
    Answer. The National Institutes of Health (NIH) appreciates the 
recent extension of the Special Diabetes Program, which will allow us 
to continue critical ongoing research programs and to support new 
research to improve the health and quality of life of people with or at 
risk for type 1 diabetes and its complications. For example, the recent 
extension will allow the National Institute of Diabetes and Digestive 
and Kidney Diseases (NIDDK) to continue the Human Islet Research 
Network, which is working to better understand how insulin-producing 
cells are lost in type 1 diabetes and to find strategies to replace or 
protect them in people, toward curing the disease. NIDDK plans to begin 
new clinical trials through the Type 1 Diabetes TrialNet network, 
testing agents to prevent onset of clinical type 1 diabetes. Such 
research will build on the landmark success of previous TrialNet 
research demonstrating for the first time ever that early preventive 
treatment can delay onset of clinical type 1 diabetes in high-risk 
individuals. NIDDK also plans to support research building on the 
tremendous recent progress in developing transformative diabetes 
management technologies, such as artificial pancreas devices. For 
example, future research is needed to improve components of artificial 
pancreas devices (e.g., glucose sensors, hormone formulations), develop 
simpler and more user-friendly devices, and test devices in 
understudied populations (e.g., older adults, pregnant women, people 
with poorly controlled blood glucose levels). This type of research 
will move us closer to our goal of developing multiple different 
artificial pancreas technologies for people of all ages so that they 
can choose the technology best suited to their clinical needs. NIDDK 
also plans to support new research to identify novel ways to detect and 
monitor type 1 diabetes onset and progression, such as by determining 
whether ``extracellular vesicles'' that originate from pancreatic 
tissue may be useful to detect earlier stages of type 1 diabetes than 
currently possible. NIDDK is collaborating with the National Heart, 
Lung, and Blood Institute on new research toward reducing 
cardiovascular disease in people with type 1 diabetes, as very little 
is known about how best to prevent and treat this life-threatening 
complication. To inform other future research directions, NIDDK is 
spearheading a planning meeting in spring 2022 under the auspices of 
the statutory Diabetes Mellitus Interagency Coordinating Committee to 
obtain input from external scientific and lay experts on critical new 
and emerging research opportunities that could be supported by the 
Special Diabetes Program.
    Question. New Hampshire continues to be one of the hardest-hit 
states in the substance use disorder epidemic, with one of the highest 
overdose death rates in the country. I am very supportive of the 
ongoing work at the National Institute on Drug Abuse (NIDA) to research 
potential non-addictive alternatives to opioids for pain management.
    Could you discuss progress on any research within NIDA to study 
these types of alternatives?
    Answer. The National Institutes of Health (NIH) recognizes the need 
to improve pain management without risk of addiction and other serious 
side effects. NIH is taking a multi-pronged approach to develop safe 
and effective therapies to reduce our reliance on opioids.
    To avoid replay of the spike in opioid deaths related to over-use 
of medical opioids for pain management we need more effective, non-
addictive pain medications and data that can inform best practices in 
pain care. The NIH Helping to End Addiction Long-term (HEAL) Initiative 
was launched in 2018 and significantly expanded research to discover 
and accelerate development of non-addictive pharmacological and non-
pharmacological pain treatments. HEAL has awarded over $1.5 billion for 
research to improve pain management and address opioid use disorder and 
overdose. Studies supported by HEAL, the Blueprint Neurotherapeutics 
Program, and multiple NIH Institutes, in particular the National 
Institute for Neurological Disorders and Stroke (NINDS), are underway 
to identify, optimize and test promising molecules, biologics, and 
devices that target non-opioid pain pathways in the nervous system. 
Biomarker studies to help with diagnosis of pain conditions and to 
identify patients most likely to respond to a particular treatment will 
enhance pain clinical trials and improve best practices are moving 
forward. In addition, non-pharmacological approaches to manage many 
different pain conditions are being evaluated through effectiveness and 
implementation research approaches.
    The NIH HEAL initiative established essential pain research 
infrastructure to accelerate development of new medications and devices 
to treat pain. An analgesic screening platform uses animal- and human 
cell-based models such as neural tissue chips for rapid screening of 
molecules or devices for analgesic relevant biological and pain 
behavioral activity. HEAL, with input from academic and industry 
partners, established an Early Phase Pain Investigation Clinical 
research network (phase 2 studies) to test safety and efficacy of novel 
therapeutics and a later stage pain management Effectiveness Research 
Network (ERN) to compare effectiveness of pharmacological and non-
pharmacological approaches in many different pain conditions. The ERN 
is supporting eight large trials for various pain management 
strategies. The Pragmatic and Implementation Studies for the Management 
of Pain to Reduce Opioid Prescribing (PRISM) network focuses on 
clinical trials of non-pharmacologic pain therapies in healthcare 
systems.
    The Phase 2 network will launch trials on two new analgesics in 
2021. The ERN is supporting eight large trials for various pain 
management strategies. PRISM is supporting six large trials in 
healthcare systems. In addition, HEAL established an analgesic 
development pipeline to accelerate the development and testing of novel 
drugs and devices. This program uses team-based science coupled with a 
comprehensive set of research resources to bring new therapeutics 
rapidly to the clinic. To advance the discovery and validation of new 
drug targets, HEAL has funded over 30 projects to discover and verify a 
diverse set of drug target types across multiple pain conditions, six 
drug optimization studies on new safe and effective pain treatments, 
and 11 projects to test the effectiveness of implanted devices and 
noninvasive stimulation of nerves in the brain or throughout the body 
to reduce perception of pain. This effort greatly expands on NINDS 
supported studies in these areas.
    Recent HEAL accomplishments toward new therapeutics include two 
patent filings for small molecule modulators of pain receptors involved 
in chronic pain and migraine. One ongoing study received 
Investigational New Drug (IND) approval for use of buprenorphine with 
nonpharmacological treatment to relieve pain in patients undergoing 
kidney dialysis. Through the NIH Blueprint Neurotherapeutics Program 
researchers are developing non-addictive kappa opioid receptor 
antagonists for treatment of migraine and a safe, non-opioid epoxide 
hydrolase inhibitor to reduce diabetic nerve pain. Earlier, NIH 
supported basic science research led to calcitonin gene-related peptide 
therapy for migraine and nerve growth factor therapy for inflammatory 
pain. Drugs that target these molecules are now approved by the U.S. 
Food and Drug Administration to treat migraine and osteoarthritis pain. 
Through the Brain Research through Advancing Innovative 
Neurotechnologies (BRAIN) Initiative, which is a major effort to 
develop tools to map, monitor, and modulate neural circuits, NIH has 
supported studies that will enhance diagnostics and therapies for 
chronic pain and other neural circuit disorders.
    Question. The Institutional Development Award (IDeA) program at NIH 
has proven critical in funding New Hampshire researchers, including 
especially the innovative work at Dartmouth College and Dartmouth-
Hitchcock Health. I am hopeful that Congress can continue to support 
funding for this program.
    Can you provide any insight into how NIH is currently making use of 
Institutional Development Award funds and whether more funding for the 
program would be helpful?
    Answer. The Institutional Development Award (IDeA) supports basic, 
clinical, and translational research, faculty development, and 
infrastructure improvements at institutions in states and territories 
that have historically received a lower aggregate level of NIH funding. 
The program aims to strengthen biomedical research capacity, enhance 
the competitiveness of investigators in securing research funding, and 
enable clinical and translational research that addresses the specific 
needs of rural and medically underserved communities. Currently, 
institutions in 23 States and Puerto Rico are eligible for funding 
through the IDeA Program, the various components of which include:
  --IDeA Networks of Biomedical Research Excellence (INBRE). INBRE 
        enhances, extends, and strengthens the research capabilities of 
        biomedical research faculty in IDeA states through a statewide 
        program that links a research-intensive institution with 
        primarily undergraduate institutions. INBRE supports 
        institutional research and infrastructure development; research 
        by faculty, postdoctoral scientists, and students at 
        participating institutions; and targeted outreach to build 
        science and technology knowledge within a state's workforce. 
        Only one INBRE award is made per IDeA-eligible state. The New 
        Hampshire INBRE, which is led by Dartmouth and co-led by the 
        University of New Hampshire, is in its twelfth year of 
        operation and has used the program's support to improve and 
        expand research capacity at all eight of its partner 
        institutions, including adding additional labs, cores and 
        instrumentation/infrastructure; establishing fully functional 
        Office of Sponsored Programs for faculty members to 
        competitively seek extramural grants; training and mentoring of 
        both faculty and students; and enhancing a vibrant 
        institutional research culture. In fiscal year 2020, the 
        National Institute of General Medical Sciences (NIGMS) 
        supported 24 INBRE awards.
  --Centers of Biomedical Research Excellence (COBRE--Phases I, II, and 
        III). COBRE supports the establishment and development of 
        innovative, state-of-the-art biomedical and behavioral research 
        centers at institutions in IDeA-eligible states that: (a) 
        galvanize multidisciplinary research to develop a critical mass 
        of investigators that are competitive for peer-reviewed 
        research funding; (b) provide improvements to research 
        infrastructure; and (c) maintain research cores to sustain a 
        collaborative, multidisciplinary research environment that 
        includes pilot project programs, mentoring, and workforce 
        training. In fiscal year 2020, NIGMS supported 112 COBRE 
        awards. One such example, a Phase I COBRE at Dartmouth's Geisel 
        School of Medicine called iTarget (Institute for Biomolecular 
        Targeting), aims to catalyze the development of new therapeutic 
        approaches to address cancer, chronic obstructive pulmonary 
        disease, and respiratory syncytial virus, a common viral 
        infection that can be dangerous to young children and the 
        elderly. This COBRE is providing unique resources to 
        investigators at Dartmouth and its IDeA partners, thus 
        enhancing research productivity and funding competitiveness 
        across the region.
  --IDeA Networks for Clinical and Translational Research (IDeA-CTR). 
        IDeA-CTRs develop a network infrastructure and capacity in 
        IDeA-eligible states to conduct clinical and translational 
        research focused on health concerns that disproportionately 
        affect rural and medically underserved populations and/or that 
        are prevalent in IDeA states. IDeA-CTR awards support mentoring 
        and career development activities in clinical and translational 
        research. In fiscal year 2020, NIGMS supported 12 IDeA-CTR 
        awards.
  --Regional Technology Transfer Accelerator Hubs. NIGMS established 
        the Regional Technology Transfer Accelerator Hubs for IDeA 
        states in each of the four IDeA regions (central, northeast, 
        southeast, and western regions). The hubs provide both 
        consulting services and skills development in entrepreneurship, 
        technology transfer, small business finance, and other areas 
        needed to transform important discoveries made in the 
        laboratory into potentially viable commercial products that 
        address human health. In fiscal year 2020, NIGMS supported four 
        accelerator hubs. The northeast hub is located at Celdara 
        Medical in Lebanon, New Hampshire.
  --Research Co-Funding. NIGMS provides co-funding for applications 
        from IDeA state institutions that have been judged meritorious 
        by NIH peer-review committees and national advisory councils 
        but that may also fall outside the usual range of support by a 
        given NIH Institute or Center (IC). In fiscal year 2020, NIGMS 
        co-funded 42 research project grants at 20 NIH ICs; one of 
        these was at Dartmouth College.
                                 ______
                                 
                Questions Submitted to Dr. Ned Sharpless
              Questions Submitted by Senator Patty Murray
    Question. The American Cancer Society's Annual Report to the Nation 
on the Status of Cancer highlighted that we are making good progress in 
the battle against cancer, with the incidence and mortality rates for 
most cancers have dropped significantly. However, among the 20 most 
common cancers, relative survival for patients significantly improved 
since the mid-1970s except for those with uterine cancer.
    What plans does the NCI have in fiscal year 2022 to develop a 
paradigm of increased research to improve hope for survival for 
patients with uterine cancer?
    Answer. The National Cancer Institute (NCI) shares the committee's 
commitment to research on uterine cancers, including endometrial cancer 
(cancer of the inner lining of the uterus), and improving outcomes for 
patients.
    Today, nearly 40 percent of adults are obese, and without 
intervention, the obesity epidemic will result in more cancers. Uterine 
cancer incidence and mortality have increased in recent years,\40\ 
believed to be partially associated with rising rates of obesity.\41\ 
Women who are obese or overweight are approximately two to four times 
as likely as normal weight women to develop uterine cancer, including 
endometrial cancer, making interventions to address weight and obesity 
vital to combatting uterine cancer incidence and mortality. Examples of 
NCI-supported research on this topic include a study of how changes in 
body composition following weight loss impact inflammatory biomarkers 
in biopsy-collected endometrial tissue and blood samples and whether 
these processes differ between Black and White women; \42\ the 
development of a weight loss intervention among Appalachian residents; 
\43\ and a study of the Deep South Interactive Voice Response (IVR)-
supported Active Lifestyle (DIAL) Intervention to increase physical 
activity levels among residents of the Deep South.\44\
---------------------------------------------------------------------------
    \40\ pubmed.ncbi.nlm.nih.gov/30521505/,seer.cancer.gov/
report_to_nation/statistics.html#
factors.
    \41\ www.cancer.gov/about-cancer/causes-prevention/risk/obesity/
obesity-fact-sheet.
    \42\ reporter.nih.gov/project-details/10129305.
    \43\ reporter.nih.gov/project-details/10065366.
    \44\ reporter.nih.gov/project-details/10163139.
---------------------------------------------------------------------------
    Researchers at the University of North Carolina Lineberger 
Comprehensive Cancer Center are directly examining the metabolic and 
molecular differences of endometrial tumors in obese and non-obese 
women. In addition, this research team is exploring how metformin, 
widely used to treat type II diabetes, may also exhibit anti-tumor 
activity through its effects on a patient's metabolism.\45\
---------------------------------------------------------------------------
    \45\ reporter.nih.gov/project-details/10104456.
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    Translational research to bridge the gap between basic research on 
endometrial cancer and potential therapies is also essential to 
improving outcomes for patients. NCI supports a Specialized Program of 
Research Excellence (SPORE) focused on translational research for 
endometrial cancer at the University of Texas/MD Anderson Cancer 
Center. This SPORE is conducting research aimed at developing 
therapeutic strategies for advanced/recurrent endometrial cancer and 
aggressive subtypes, addressing unmet clinical needs in prevention and 
conservative therapy of high-risk precancerous lesions and low-grade 
endometrial cancer, and incorporating molecular diagnostics into 
clinical decisionmaking.\46\
---------------------------------------------------------------------------
    \46\ trp.cancer.gov/spores/endometrial.htm.
---------------------------------------------------------------------------
    As of July 2021, NCI is supporting over 150 clinical trials with a 
primary focus on uterine (including endometrial) cancer. Examples of 
these projects include studies of the use of an immunotherapy agent, in 
combination with other cancer therapies, to treat high risk endometrial 
cancer; \47,48\ a trial examining a combination therapy to treat 
endometrial cancers that express the HER2 protein; \49\ and a study 
evaluating the use of the experimental therapy triapine to treat 
endometrial serous adenocarcinoma, a difficult to treat subtype of 
uterine cancer.\50\ Clinical trials are an integral part of advancing 
research in this important topic area, and NCI is committed to reaching 
out to disparate, at-risk communities to explain, educate, and 
encourage clinical trial participation.
---------------------------------------------------------------------------
    \47\ clinicaltrials.gov/ct2/show/NCT04214067.
    \48\ clinicaltrials.gov/ct2/show/NCT03914612.
    \49\ clinicaltrials.gov/ct2/show/NCT04585958.
    \50\ clinicaltrials.gov/ct2/show/NCT04494113.
---------------------------------------------------------------------------
    As part of the National Institutes of Health (NIH) efforts to 
identify future research directions, NCI and the Eunice Kennedy Shriver 
National Institute of Child Health and Human Development (NICHD) 
explored research opportunities into the progression of benign 
gynecologic conditions to cancers through a collaborative workshop in 
April 2019. Currently, NICHD funds research on benign gynecologic 
conditions such as endometriosis and uterine fibroids, while NCI funds 
research on women's cancers. The workshop sought to bridge the two 
research areas and identify gaps in the biologic, epidemiologic, and 
clinical understanding of progression from benign conditions to cancer. 
The workshop addressed three gynecologic disease types: (1) 
endometriosis or endometrial cancer and endometrial-associated ovarian 
cancer, (2) uterine fibroids (leiomyoma) or leiomyosarcoma, and (3) 
denomyosis or adenocarcinoma. Working groups were formed for each 
disease type, and key questions and current challenges that emerged 
from the discussions, along with potential research opportunities to 
advance understanding of progression of gynecologic benign conditions 
to cancer, were published. Specific research questions and gaps were 
identified in all three focus areas, and several cross-cutting topics 
emerged. The results of this workshop, as well as ongoing horizon- 
scanning activities, will continue to inform NIH's next steps to 
address uterine cancer.
    Question. Non-Hispanic Black women are two time as likely as non-
Hispanic White women to die from uterine or cervical cancer (https://
www.ajog.org/article/S0002-9378(16)46212- 5/pdf).
    Can NIH/NCI please share with the Committee the research activities 
the NCI is supporting to address this disparity, particularly with 
regards to access to care, prevention, early diagnosis, treatment 
completion and developmental therapeutics?
    Answer. The National Cancer Institute (NCI) shares the Committee's 
concern regarding cervical and uterine/endometrial cancer disparities 
and is working to support research to eliminate these disparities, as 
well as cancer disparities more broadly. Examples of research aimed at 
addressing disparities in uterine and cervical cancer outcomes are 
provided below.
    NCI is a leader in developing and supporting definitive, practice-
changing gynecologic (GYN) clinical trials, as well as responding to 
areas of scientific inquiry that are unaddressed by private industry. 
The NCI GYN Cancers Steering Committee sets clinical trials strategic 
priorities that address areas of unmet clinical need, important 
unanswered clinical questions, and potential new approaches to disease 
treatment.\51\ The Institute has supported and advanced GYN cancer 
research that will provide greater insight into these cancers, 
additional options for drug therapies, and improved surgical techniques 
with the intent of increasing survivorship and quality of life. As of 
July 2021, NCI is supporting over 150 interventional clinical trials 
with a primary focus on uterine (including endometrial) cancer, two 
trials on the rare uterine sarcoma, and nearly 100 trials for cervical 
cancer patients. NCI also has several trials that are ``disease 
agnostic,'' meaning that they are open to patients with certain genetic 
alterations rather than traditional cancer types, creating 
opportunities for patients to potentially benefit from precision 
medicine and targeted therapy.
---------------------------------------------------------------------------
    \51\ www.cancer.gov/about-nci/organization/ccct/steering-
committees/nctn/gynecologic.
---------------------------------------------------------------------------
    A recent study led by NCI intramural researchers used population 
data from NCI's Surveillance, Epidemiology, and End Results (SEER) 
database to evaluate trends of hysterectomy-corrected uterine cancer 
incidence rates for women overall and by race and ethnicity, geographic 
region, and histologic subtype. Correct estimation of these rates 
requires accounting for hysterectomy prevalence, which varies by race, 
ethnicity, and region. The researchers found that incidence rates of 
common subtypes of uterine cancer were stable in non-Hispanic White 
women over the study period and increased in women of other racial/
ethnic groups. By contrast, incidence rates of aggressive subtypes have 
been increasing dramatically over time in all racial/ethnic groups; in 
particular, much higher rates of these aggressive subtypes were 
observed in Black women than in other racial/ethnic groups. The 
researchers also observed that survival rates were lower among all 
women with aggressive subtypes than among women with common subtypes, 
and Black women had the lowest survival rates within each stage at 
diagnosis or histologic subtype.
    Uterine serous carcinoma (USC) is a rare but aggressive type of 
endometrial cancer. In about one-third of women with USC, their tumor 
cells overproduce a protein called HER2 (human epidermal growth factor 
receptor 2), which is associated with poor prognosis in women with 
endometrial cancer. Black women with endometrial cancer are more likely 
than White women to be diagnosed with UCS and are more likely than 
women of other races/ethnicities to have HER2 overproducing UCS tumors. 
NCI clinical studies for patients with HER2 overproducing uterine 
serous cancer and carcinosarcoma are currently in development.
    NCI-supported researchers are working to describe additional 
differences in subtypes of uterine and endometrial cancers, with the 
eventual goal of targeting therapies to treat each disease subtype. For 
example, investigators at Brigham and Women's Hospital, using data from 
the NCI-supported Epidemiology of Endometrial Cancer Consortium 
(E2C2),\52\ are studying genomic variation across the full spectrum of 
endometrial tumors, distinct risk factor profiles across tumor types, 
and the role of underlying tumor biology to better understand the 
disparities in outcomes between African-American and non-African-
American women.\53\ NCI-supported investigators at Wayne State 
University are examining aggressive subtypes of high-grade endometrial 
tumors, including endometrioid, serous, clear cell and mixed 
carcinomas, by analyzing both clinical and genetic data in 500 women 
(250 African-American, 250 White) diagnosed with these cancers.\54\ In 
addition, NCI is supporting a planning grant to establish a Specialized 
Program of Research Excellence (SPORE) at Northwestern University 
focused on gynecologic cancer disparities. One of the pilot projects 
will focus on the tumor genomics of endometrial cancer.\55\
---------------------------------------------------------------------------
    \52\ epi.grants.cancer.gov/eecc/.
    \53\ reporter.nih.gov/search/o5KPkwNzZUavBogOfHXfCgproject-details/
10156374.
    \54\ reporter.nih.gov/search/frdhnx_EQkONjxE8GPyxvQ/project-
details/9916725.
    \55\ reporter.nih.gov/search/-UP_KUgEu0G9_0Zt655Nsg/project-
details/9961257.
---------------------------------------------------------------------------
    To more accurately evaluate the risk of cervical precancer and 
study novel biomarkers in women undergoing cervical cancer screening, 
intramural researchers in NCI's Division of Cancer Epidemiology and 
Genetics have partnered with the University of Mississippi Medical 
Center and the Mississippi State Department of Health in the STRIDES 
Study (Studying Risks to Improve Disparities of cervical cancer in 
Mississippi). This study, based in one of the top five states for 
cervical cancer incidence and mortality, combines the expertise of 
clinicians, laboratory scientists, epidemiologists, and implementation 
scientists to address all aspects of cervical cancer prevention and 
control.\56\
---------------------------------------------------------------------------
    \56\ dceg.cancer.gov/research/cancer-types/cervix/cervix-
mississippi.
---------------------------------------------------------------------------
    In 2020, NCI launched the ``Last Mile Initiative,'' with the goal 
of improving cervical cancer screening coverage to underserved, never 
screened, and under-screened women. This initiative will evaluate an 
alternative cervical cancer screening approach: self-collection of 
samples (self- sampling) by women, which are then sent to labs for 
human papillomavirus (HPV) testing. This approach aims to identify 
cervical cancer cases in these groups of women, which account for over 
half of cervical cancer cases in the United States each year. Self-
sampling offers several benefits, including ease of collection at the 
time and place of the patient's choosing, without the need for a clinic 
appointment or speculum exam. To conduct this assessment, NCI 
established a public-private partnership between Federal agencies, 
industry partners, and professional societies/clinical guidelines 
organizations, and will support a nationwide, multicentric screening 
trial in diverse settings, the Last Mile Initiative Self-sampling for 
HPV Testing to Improve Cervical Cancer Prevention Trial (LMI-SHIP 
Trial).\57\
---------------------------------------------------------------------------
    \57\ prevention.cancer.gov/major-programs/nci-cervical-cancer-last-
mile-initiative.
---------------------------------------------------------------------------
    Additionally, NCI is collaborating with the NIH Office of Research 
on Women's Health (ORWH) and other NIH Institutes and Centers to 
participate in an ORWH Advisory Committee on Research on Women's Health 
Consensus Conference to be held in October 2021. The conference will 
include a focus on cervical cancer disparities and research 
opportunities to continue to address disparities in incidence and 
mortality.
    NCI will continue to identify opportunities to better understand 
and address cancer health disparities, including for cervical and 
uterine/endometrial cancers.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
    Question. Approximately 20,000 people in the United States have 
germline mutations in the gene RUNX1. Patients with RUNX1-familial 
platelet disorder are at a heightened risk for developing blood 
cancers. NCI supports a longitudinal natural history study of patients 
with such germline mutations and their families. While germline RUNX1 
mutations are rare, I understand that NIH-funded research in this area 
holds promise for the fields of hematology and oncology.
    How can deepening our understanding of, and ultimately developing 
cancer prevention strategies for, inherited blood cancer predisposition 
syndromes like RUNX1 familiar platelet disorder advance the entire 
cancer research field forward?
    Answer. The RUNX1 gene regulates the development of blood cells 
(hematopoiesis), controlling other genes that help determine the fate 
of hematopoietic stem cells, which have the potential to develop into 
all types of mature blood cells, including platelets. Platelets are 
cells that help blood to clot. Inherited mutations in the RUNX1 gene 
cause familial platelet disorder with associated myeloid malignancies 
(RUNX1-FPDMM) and predispose individuals to some types of blood 
cancers. Although genetic predisposition to solid tumors such as breast 
and colon cancers has been widely recognized over the past several 
decades, the contribution of inherited genetic disorders related to 
blood cancer is a more recent field of study.
    There are many instances where understanding the molecular basis 
for a rare inherited disease has provided insight into more common 
forms of a particular disease. For example, BRCA1 and BRCA2 mutations 
were discovered as hereditary breast cancer genes but are also relevant 
to sporadic (non-hereditary) breast cancers, ovarian cancers, and some 
hereditary forms of colon cancer. Similarly, understanding the blood 
cancers associated with RUNX1-FPDMM may lead to improved understanding 
of other types of blood cancers as well.
    Research efforts across the National Institutes of Health (NIH) are 
underway to better understand RUNX1-FPDMM. Investigators funded by the 
National Heart, Lung, and Blood Institute (NHLBI) are studying cells 
from people with this disorder to better understand key target genes 
regulated by RUNX1 and their role in hematopoiesis.\58\ This work could 
also yield a better understanding of genetic pathways that lead to 
blood cancers, as well as the blood clotting mechanisms that contribute 
to cardiovascular disease. Investigators at the National Human Genome 
Research Institute (NHGRI), along with intramural scientists at the 
National Cancer Institute (NCI), are conducting a natural history study 
at the NIH Clinical Center that is intended to identify and follow 
patients with RUNX1 mutations to hopefully identify biomarkers that can 
predict which patients will develop cancers.\59\ To date, the study has 
enrolled 198 patients from 55 families, representing the largest FPDMM 
cohort being followed prospectively at a single institution in the 
world.
---------------------------------------------------------------------------
    \58\ reporter.nih.gov/project-details/10083753.
    \59\ www.genome.gov/Current-NHGRI-Clinical-Studies/hematologic-and-
premalignant-conditions-associated-with-RUNX1-
mutation;clinicalstudies.info.nih.gov/ProtocolDetails.
aspx?id=2019-HG-0059; clinicaltrials.gov/ct2/show/NCT03854318.
---------------------------------------------------------------------------
    Studying RUNX1-FPDMM will have broader significance than just this 
rare disease. Germline (inherited) predisposition to hematopoietic 
malignancies is often under-diagnosed, with recent studies indicating 
that 10-30 percent of RUNX1 mutations detected in acute myeloid 
leukemias are inherited, which is much more common than previously 
appreciated.\60\ In addition, FPDMM can serve as a model to study the 
development of leukemia, since researchers can monitor individuals with 
the RUNX1 mutation before they develop leukemia to identify factors 
associated with cancer risk and to map tumor evolution.
---------------------------------------------------------------------------
    \60\ pubmed.ncbi.nlm.nih.gov/32315381/.
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                                 ______
                                 
                Questions Submitted by Senator Jack Reed
    Question. The fiscal year 2021 Appropriations law included full 
funding--$30 million--for the Childhood Cancer STAR Act, which I 
authored.
    Could you provide an update on how that funding will be spent in 
the coming year?
    How will that work be coordinated with the childhood cancer data 
initiative?
    Answer. NCI is supporting several new and ongoing Childhood Cancer 
STAR Act research projects in fiscal year 2021, for a total planned 
investment of $28 million. The Centers for Disease Control and 
Prevention continues to support enhancements to expand capacity within 
the National Program of Cancer Registries (NPCR) to help cancer 
registries collect and make the data on pediatric cancer cases 
available more rapidly, a $2 million effort in fiscal year 2021.
    Consistent with provisions in Section 101 of the STAR Act, NCI's 
fiscal year 2021 appropriation for STAR Act activities is supporting 
new and expanded projects focused on the collection and storage of 
biospecimens for future research. Several projects are conducted 
through the NCI-supported Children's Oncology Group (COG) to focus 
additional attention to rare cancer subtypes that are currently 
underrepresented in NCI-supported biorepositories, as well as tumor 
types with a high risk of treatment failure. For example, particularly 
rare subtypes of pediatric cancers for which COG does not have open 
clinical trials, tumor tissue collection options are limited. STAR Act 
appropriations are supporting the COG Rare and Under-Represented Cancer 
Tissue Banking project to enable tumor tissue and associated germline 
(e.g., blood) sample collection for specific groups of patients for 
which current tumor tissue collection is lacking or inadequate, with 
priority for tumor types such as sarcomas and brain and central nervous 
system (CNS) tumors, which have high risk of treatment failure.
    The COG Rare and Under-Represented Cancer Tissue Banking project 
was launched in fiscal year 2020 and is expanding in scope in fiscal 
year 2021. This initiative is collaborating closely with CCDI, and with 
the use of fiscal year 2021 CCDI funds, tumor tissue will undergo 
clinically-relevant molecular profiling through the CCDI Molecular 
Characterization Protocol. The data generated will be returned to 
treating physicians to help guide the diagnosis and treatment of 
patients, and the data will additionally be stored and made available 
to the research community through CCDI data platforms. In addition to 
rare cancer populations, the CCDI Molecular Characterization Protocol 
will initially support characterization of tumors from children with 
CNS tumors and from children with soft tissue sarcomas. The Protocol 
aims to collect, store, and make available detailed clinical and 
molecular information for each child participating in the study, 
including data that will help a pediatric oncologist treat that patient 
and help researchers learn more about childhood cancers.
    NCI is continuing support in fiscal year 2021 for other STAR Act 
biobanking projects launched in fiscal year 2020. Through the COG Rapid 
Autopsy Specimen Collection project, NCI and COG are working with 
patient organizations to support rapid autopsy collection of tumor 
samples from children and adolescents and young adults (AYAs) who have 
died of their disease. Foundations and families within the pediatric 
brain tumor community have been leaders in such programs, and NCI 
continues 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 advance science and help other families.
    NCI is also supporting the COG to continue to expand the collection 
of specimens taken at the time of relapse, as well as collecting 
diagnostic samples for children and AYAs who have already submitted 
samples at relapse through NCI's Pediatric Molecular Analysis for 
Therapy and Choice (MATCH) Precision Medicine Trial. 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. Through CCDI, Pediatric MATCH tumor 
specimens from diagnosis and from relapse are being molecularly 
characterized to identify the changes in gene mutations and gene 
expression that occur between diagnosis and relapse, which could inform 
better treatments.
    Consistent with Section 202 of the STAR Act, in fiscal year 2021, 
NCI will continue to conduct and support childhood cancer survivorship 
research. NCI has supported two new Requests for Applications (RFAs) 
since fiscal year 2019 that are directly aligned with survivorship 
research areas emphasized in the STAR Act. Issued in fiscal year 2019, 
RFA CA-19-033: \61\ Improving Outcomes for Pediatric, Adolescent and 
Young Adult Cancer Survivors focused on projects to develop and test 
interventions that prevent, mitigate or manage adverse outcomes in 
pediatric and/or AYA cancer survivors and/or evaluate models of care 
that strengthen coordination, continuity, and quality, or that reduce 
access barriers to needed services including follow-up care, and that 
improve outcomes across the survivor's lifespan. Development of 
interventions to address disparities in outcomes and/or access to 
needed care, and to address the needs of minority or medically 
underserved pediatric and/or AYA populations were also prioritized. NCI 
is supporting seven awards in response to this RFA, and the awards will 
focus on various patient sub-populations (e.g. disease site), 
developmental groups, specific late and long-term effects, and the 
types of interventions (both preventive and supportive care).
---------------------------------------------------------------------------
    \61\ grants.nih.gov/grants/guide/rfa-files/RFA-ca-19-033.html.
---------------------------------------------------------------------------
    Issued in fiscal year 2020, RFA CA-20-027 \62\ and RFA CA-20-028: 
\63\ Research to Reduce Morbidity and Improve Care for Pediatric, and 
Adolescent and Young Adult (AYA) Cancer Survivors invite applications 
for research projects to improve care and health-related quality of 
life for childhood and AYA cancer survivors, with a focus on six key 
domains that align with research priorities emphasized in the STAR Act: 
(1) disparities in survivor outcomes; (2) barriers to follow-up care 
(e.g. access, adherence); (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.
---------------------------------------------------------------------------
    \62\ grants.nih.gov/grants/guide/rfa-files/RFA-CA-20-027.html.
    \63\ grants.nih.gov/grants/guide/rfa-files/rfa-ca-20-028.html.
---------------------------------------------------------------------------
    In fiscal year 2021, NCI will support subsequent years for grants 
initially awarded in fiscal year 2019 and fiscal year 2020, as awards 
were made for five-year terms, and the Institute will be making several 
new grant awards through the RFA launched in fiscal year 2020. The 
first round of applications is in the final stages of review, and 
awards will be made before the close of fiscal year 2021. The second 
round of applications are due on July 30, 2021, and awards are 
anticipated to be made in fiscal year 2022.
    NCI also continues to make additional investments in childhood 
cancer survivorship research beyond the STAR Act appropriation, funding 
several notable initiatives and projects with resources provided 
through the Institute's general appropriation. For example, NCI 
continues to fund long-standing investments in the Childhood Cancer 
Survivor Study (CCSS),\64\ which the Institute has supported 
continuously since establishing CCSS in 1994. This cohort of more than 
38,000 childhood cancer survivors diagnosed between 1970 and 1999 (and 
5,000 siblings of survivors who serve as the comparison group for the 
study) serves as a foundational resource for the survivorship research 
community.
---------------------------------------------------------------------------
    \64\ cancer.gov/types/childhood-cancers/ccss.
---------------------------------------------------------------------------
    Additionally, NCI continues to support research projects that 
investigators develop and submit independent of specific childhood and 
AYA cancer survivorship funding opportunities such as the STAR Act RFAs 
described above. These investigator-initiated research projects provide 
critical contributions to this field, and awards made to date in fiscal 
year 2021 include a project to compare symptom burdens (toxicity), 
neurocognitive change, and functional outcomes in children with 
pediatric brain tumors treated with proton versus photon radiotherapy. 
Proton beam radiotherapy (PBRT) is often thought to be a promising 
treatment for children with brain tumors as it may preserve cognitive 
functioning without sacrificing disease control. This will be the first 
large-scale study to prospectively compare the two therapies to assess 
important measures of daily functioning that will quantify the clinical 
significance of any differences identified between groups in 
survivorship. This project aims to help physicians and families better 
understand the relative effect of PBRT on symptoms and neurocognitive 
functioning to inform treatment decisions.\65\ Another award is 
supporting further study of psychosocial risk in young survivors of 
pediatric cancer diagnosed in early childhood, including the role of 
both physical and neurocognitive late effects. This project aims to 
identify specific medical and neurocognitive late effects that increase 
psychosocial morbidity, as well as protective factors, to inform more 
effective interventions to optimize quality of life in children 
affected by cancers diagnosed in early childhood.\66\ In addition, the 
NCI-supported ASPIRES (Activating cancer Survivors and their Primary 
care providers to Increase coloREctal cancer Screening) study aims to 
prevent the development of subsequent cancers among childhood cancer 
survivors treated with abdominal or pelvic radiotherapy, who are almost 
four times more likely to develop colorectal cancer (CRC) compared to 
the general population. The study will test a remote intervention aimed 
at promoting early CRC screening and detection.\67\
---------------------------------------------------------------------------
    \65\ reporter.nih.gov/search/kPIDddsyREmcoShhVEYN4Q/project-
details/10146799.
    \66\ reporter.nih.gov/search/5Nb7PgFn7kyHJnjYOFzMQA/project-
details/10122486.
    \67\ reporter.nih.gov/search/5Nb7PgFn7kyHJnjYOFzMQA/project-
details/10096080.
---------------------------------------------------------------------------
    NCI remains committed to implementing the research sections of the 
STAR Act directed toward the Institute, and to ensuring that these 
efforts continue to complement the Institute's broader portfolio of 
childhood and AYA cancer research. This includes CCDI, the COG, the 
CCSS, and many other research programs and projects working together to 
support much needed progress for children with cancer and their 
families, including survivors and caregivers facing the challenges of 
managing the late effects of cancer and its treatments.
                                 ______
                                 
                Questions Submitted by Senator Roy Blunt
    Question. Dr. Sharpless, one of the goals I had when I was Chairman 
of this Subcommittee was to increase NIH funding, in an effort to 
increase the success rates of grants--meaning more research grants 
would be funded. This is important because the NIH peer review system 
does not always reward high-risk science or young researchers' grant 
applications. But, if you have additional funding, you can fund more 
than just the `safest' science grants from the most established 
researchers. NCI has seen an increase of more than 50 percent in the 
number of grant applications since 2013, keeping your success rates and 
paylines lower than most NIH Institutes. While the positive aspect of 
this statistic is that the cancer research community is energized and 
applying for NCI funding, you can only fund a certain amount of 
applications because of the significant increase in grant applications. 
The last two LHHS bills have included specific funding for NCI to 
increase their Research Project Grants.
    How has this allowed you to increase success rates, raise the 
payline, and make more awards?
    Answer. The intense competition and demand for NCI funding reflects 
incredible scientific opportunities in cancer research and presents a 
major challenge for the NCI to carefully balance increasing demand for 
competing grant funding while sustaining previous years' commitments to 
multi-year grants.
    Investigator-initiated research has proven itself to be one of the 
biggest drivers of progress in cancer research, and accordingly is the 
biggest driver of NCI's budget, with long-term investments into funding 
new and continuing awards constituting more than 40 percent of NCI's 
annual budget. These awards have been the source of some of the most 
innovative and transformative ideas in cancer research, leading to 
direct benefits for patients in the form of new oncology drug 
approvals, the development of immune checkpoint inhibitor therapy 
(Nobel Laureate Jim Allison), CAR-T (chimeric antigen receptor-T) cell 
immunotherapy (Carl June), and novel drug design strategies such as 
PROTACs (proteolysis targeting chimeras) \68\ that use normal cellular 
processes to identify and destroy proteins in cancer cells that drive 
cancer growth (Raymond DeShais and Craig Crews).
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    \68\ www.cancer.gov/research/annual-plan/scientific-topics/protac-
infographic.
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    Considering all funding mechanisms, NCI supported 109 additional 
awards in fiscal year 2020 as compared to fiscal year 2019 (from 6,053 
in fiscal year 2019 \69\ to 6,162 in fiscal year 2020 \70\). Across 
fiscal year 2020 and 2021, the successive funding increases allowed NCI 
to increase the R01 payline from the 8th percentile in fiscal year 2019 
to the 11th percentile in fiscal year 2021. With the fiscal year 2020 
budget increase, NCI increased R01 paylines by 25 percent compared to 
fiscal year 2019 and restored continuing grants to 100 percent of their 
committed level, providing researchers the full fiscal year 2020 budget 
approved during the initial grant award. Funding increases in fiscal 
year 2021 allowed NCI to further raise the payline for R01 research 
awards, for an overall 35 percent increase compared to 2019, as well as 
to keep funding continuing awards at 100 percent. In addition, for 
those two consecutive years (fiscal year 2020 and fiscal year 2021), 
NCI also raised the payline for Early-Stage Investigators, reflecting 
NCI's commitment to developing and supporting early career scientists 
to build the next generation of cancer researchers.
---------------------------------------------------------------------------
    \69\ www.cancer.gov/about-nci/budget/congressional-justification/
fy2021-nci-congressional-justification.pdf.
    \70\ www.cancer.gov/about-nci/budget/congressional-justification/
fy2022-nci-congressional-justification.pdf.
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    We have the final success rate and total number of awards results 
for fiscal year 2020, the year when Congress targeted an additional 
$212.5 million for new and continuing grants, but we will not have 
final results for fiscal year 2021 until after the first quarter of 
fiscal year 2022. Our fiscal year 2020 results show that NCI increased 
the number of competing R01s we issued within the payline by more than 
100 awards, a jump of more than 15 percent from the prior year. The 
funding increase also allowed us to pay other meritorious R01 
applications that scored just outside the payline. Overall, our success 
rate for fiscal year 2020 rose to 12.7 percent, from 11.6 percent in 
the prior year.
    The targeted increases that Congress has provided allows NCI to 
increase paylines, achieve a corresponding increase in the overall NCI 
application success rate, and issue more grant awards. This funding has 
been critical to awarding new grants, while also allowing NCI to 
support ongoing research and the breadth of core NCI research 
investments, such as NCI's designated cancer centers, Specialized 
Programs of Research Excellence (SPOREs), and large national networks 
of clinical trials. All of these awards and programs will continue to 
fuel broad, sustained progress that serves the needs of individuals 
with cancer and those at risk of cancer, leading to a deeper 
understanding of the biology of cancer and new strategies to prevent, 
screen, diagnose, and treat cancer, in all its forms.
                                 ______
                                 
          Questions Submitted by Senator Shelley Moore Capito
    Question. The NCI is doing tremendous work in implementing the new 
Childhood Cancer Data Initiative, which holds the promise of vastly 
improving the treatment of childhood cancer and the quality of life for 
survivors. The Childhood Cancer STAR Act calls for a major investment 
in biorepository and bio-specimen collection.
    Can you tell us how these two vital initiatives are working 
together? NIH Response:
    Answer. The National Cancer Institute (NCI) agrees that it is vital 
for biospecimen collection and storage efforts supported through the 
STAR Act and data generation, analysis, and sharing supported through 
Childhood Cancer Data Initiative (CCDI) to continue to contribute to 
and enhance each initiative's progress in a complementary manner. To 
that end, NCI is utilizing STAR Act appropriations to support the 
Children's Oncology Group (COG) Rare Tumor Populations Biobanking 
project, which enables tumor tissue and germline (e.g., blood) 
collection for specific groups of patients for which current tumor 
tissue collection is lacking or inadequate, with priority for tumor 
types such as sarcomas and brain and central nervous system tumors, 
which often have the highest risk of treatment failure.
    The COG Rare Tumor Populations Biobank was launched in fiscal year 
2020 and is expanding in scope in fiscal year 2021. This initiative is 
collaborating closely with CCDI, and with the use of fiscal year 2021 
CCDI funds, tumor tissue will undergo clinically-relevant molecular 
profiling through the CCDI Molecular Characterization Protocol. The COG 
Rare Tumor Populations Biobank provides a critical foundation for these 
characterization efforts within CCDI. The data generated will be 
returned to treating physicians to help guide the diagnosis and 
treatment of patients, and the data will be stored and made available 
to the research community through CCDI data platforms. In addition to 
rare cancer populations, the CCDI Molecular Characterization Protocol 
will initially support characterization of tumors from children with 
Central Nervous System (CNS) tumors and from children with soft tissue 
sarcomas. The Protocol aims to collect, store, and make available 
detailed clinical and molecular information for each child 
participating in the study, including data that will help a pediatric 
oncologist treat that patient and help researchers learn more about 
childhood cancers.
    NCI is also supporting a STAR Act biobanking project through the 
COG to continue to expand the collection of specimens taken at the time 
of relapse, as well as collecting diagnostic samples for children and 
adolescents and young adults (AYAs) who have already submitted samples 
at relapse through NCI's Pediatric Molecular Analysis for Therapy and 
Choice (MATCH) Precision Medicine Trial. 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. Through CCDI, Pediatric MATCH tumor 
specimens from diagnosis and from relapse are being molecularly 
characterized to identify the changes in gene mutations and gene 
expression that occur between diagnosis and relapse, which could inform 
better treatments.
    These are specific examples of early and ongoing collaboration 
between STAR Act and CCDI- supported projects, and more broadly, there 
will be additional opportunities for data generated through STAR Act 
specimen collection and survivorship research efforts to contribute to 
the CCDI data ecosystem. For example, other STAR Act biobanking 
projects have supported additional biospecimen collection within the 
NCI-supported Childhood Cancer Survivor Study (CCSS), focused on 
subsequent cancers and chronic health conditions. CCDI funds were used 
to molecularly characterize specimens from patients who developed 
second cancers to enhance understanding of the genetic factors that 
lead to increased risk of second malignant tumors. Additionally, CCDI 
funds have supported submission and management of CCSS data to NCI and 
other NIH repositories so that they can be linked within the CCDI data 
ecosystem and more easily shared with the broader research community.
    As NCI's CCDI continues to link data resources across the childhood 
cancer research field, we envision these linkages and the data 
ecosystem they create serving as a resource for continued research, and 
as a growing repository for all types of data generated through NCI and 
other funded childhood and AYA cancer research. Similar to the CCSS, 
individual research projects, including preclinical studies and 
clinical trials, will have the opportunity to contribute data to CCDI, 
linking this additional data to CCDI resources such as the Molecular 
Characterization Protocol and the National Childhood Cancer Registry, 
two foundational CCDI initiatives.
                                 ______
                                 
            Questions Submitted by Senator Cindy Hyde-Smith
    Question. I, along with many members of the committee remain 
concerned with the lack of targeted therapies for rare cancer patients. 
It is my understanding that rare cancers account for 380 of 400 
distinct forms of cancer and almost 1/3 of all diagnoses and include 
all pediatric cancers. A recent analysis showed that 80 percent of all 
patients who lacked an FDA-targeted therapy were rare cancer patients. 
In addition, of the 3,994 clinical trials in phases 1, 2, and 3 from 
January 1, 2012 to January 1, 2017, almost 75 percent did not include a 
rare cancer by name. While rare cancer affects every population, 
translational research and commercial drug development has 
traditionally neglected small patient populations. Each subtype of 
cancer requires a targeted therapy in order to save a life or to 
significantly improve lifespan.
    What is NIH's plan to ensure there are adequate investments for 
treatments for rare cancer patients and what can Congress and this 
committee do to help?
    Answer. The National Institutes of Health (NIH) remains committed 
to supporting research to advance the understanding of all cancers, 
including rare cancers, and to inform the development of targeted 
cancer therapies for rare cancers and rare subtypes of cancers, 
including pediatric cancers (all types and subtypes of pediatric 
cancers are considered ``rare'' by definition).
    The cancer research community--thanks to NIH-supported developments 
in understanding the specific genes, proteins, and other unique 
molecular characteristics driving certain cancer subtypes--continues to 
recognize that cancer is made up of a collection of hundreds, if not 
thousands, of subtypes defined by these characteristics. As a result of 
National Cancer Institute (NCI)-supported efforts and other relevant 
research, ``cancer'' is increasingly becoming a collection of rare 
cancer subtypes.
    This evolved understanding of cancer is reflected in NCI's current 
clinical trials portfolio and investments in translational and basic 
research, including several initiatives in the intramural Center for 
Cancer Research (CCR).
    Increasingly, clinical trials are examining targeted therapies 
based on molecular subtypes. For example, NCI's National Clinical 
Trials Network (NCTN) is currently supporting trials assessing 
therapies to treat gliomas with certain genetic alterations \71\ and 
pancreatic cancers with specific gene alterations.\72,73\ NCI also 
supports trials that are dedicated to patients with rare tumors, 
including the NCTN-supported Dual Anti-CTLA-4 and Anti-PD1-Blockade in 
Rare Tumors (DART) Trial \74\ and the Rapid Analysis and Response 
Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE 
CANCER) Trial,\75\ which is supported by NCI's Experimental 
Therapeutics Clinical Trials Network.
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    \71\ www.clinicaltrials.gov/ct2/show/NCT00887146.
    \72\ www.clinicaltrials.gov/ct2/show/NCT04858334.
    \73\ www.clinicaltrials.gov/ct2/show/NCT04548752.
    \74\ www.clinicaltrials.gov/ct2/show/NCT02834013.
    \75\ www.clinicaltrials.gov/ct2/show/NCT04449549.
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    To ensure that researchers have a strong pipeline of therapy 
candidates to consider for use in clinical trials, NCI supports several 
initiatives to support the preclinical stage of development of 
therapeutics to treat rare cancers, including the NCI Experimental 
Therapeutics (NeXT) Program and the Pediatric Preclinical Testing 
Consortium (PPTC). The mission of NeXT is to advance clinical practice 
and bring improved therapies to patients with cancer by supporting the 
most promising new drug discovery and development projects. The PPTC 
addresses key challenges associated with the development of new 
therapies for children with cancer by developing reliable preclinical 
testing data for pediatric drug candidates that can be used to inform 
new agent prioritization decisions.
    The first step in identifying new therapeutic targets, however, is 
elucidating the basic biological mechanisms that give rise to cancers. 
To further these research efforts, NCI supports the development of 
resources for broad use across the cancer research community. These 
resources include cell lines, organoid models, patient derived 
xenograft (PDX) models, biospecimens, and other biological samples. NCI 
makes drug information summaries available on its website, along with 
extensive cancer treatment summaries. Additional resources include the 
Developmental Therapeutics Program, the National Clinical Trials 
Network (NCTN) Navigator, Patient-Derived Xenograft (PDX) Centers, PDX 
Finder, the NCI Mouse Repository, and the Physician Data Query (PDQ) 
Database.\76\
---------------------------------------------------------------------------
    \76\ A more extensive list is available at www.cancer.gov/research/
resources/.
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    The Rare Tumor Patient Engagement Network, launched in fiscal year 
2018 and part of NCI's CCR, leverages the resources of the NCI 
intramural research program and the NIH Clinical Center to bring 
together investigators, patients, and advocacy groups to study rare 
tumors. Under the umbrella of this effort, NCI launched the My 
Pediatric, Adolescent, and Adult Rare Tumor (MyPART) Network, a 
collaboration of scientists, patients, family members, advocates, and 
healthcare providers to find treatments for rare cancers. The MyPART 
Network collects samples like blood, saliva, and archived biopsy tissue 
from people with rare solid tumors as part of the Natural History Study 
of Rare Solid Tumors. The purpose of the study is to engage rare tumor 
patients and their families in the research process, study how rare 
tumors grow, track participants' health history over a long period of 
time, share data with other scientists, build new ways of testing new 
treatments, and design new clinical trials for rare cancers. MyPART 
scientists also hold clinics on rare tumors to facilitate 
collaborations between researchers, patients, and advocacy 
organizations; to date, MyPART has hosted clinics on chordomas, SDH-
deficient gastrointestinal stromal tumors, and medullary thyroid 
cancer, and more clinics are in the planning stages. Additionally, the 
NCI Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-
CONNECT) program aims to advance the understanding of rare adult 
central nervous system (CNS) cancers by establishing and fostering 
patient-advocacy-provider partnerships and networks to improve 
approaches to care and treatment; seven clinical studies and trials are 
currently open through NCI-CONNECT.\77\
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    \77\ www.cancer.gov/rare-brain-spine-tumor/refer-participate/
clinical-studies.
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    Because of these and similar investments, the U.S. Food and Drug 
Administration (FDA) has approved a number of therapies in recent years 
for patients with rare cancer subtypes and related conditions. For 
example, in May 2021, the FDA granted accelerated approval to sotorasib 
(Lumakras) for patients with locally advanced or metastatic non-small 
cell lung cancer (NSCLC) with alterations in the KRAS G12-C gene, a 
mutation which is present in only 13.8 percentsa of NSCLC patients. 
Similarly, the FDA approved selumetinib (Koselugo) in 2020 for the rare 
tumor condition neurofibromatosis type 1, in patients over the age of 
two, as the first approved treatment for this condition. In 2018, the 
FDA granted accelerated approval to larotrectinib (Vitrakvi) for adult 
and pediatric patients with solid tumors with a neurotrophic receptor 
tyrosine kinase (NTRK) gene fusion. NTRK gene fusions are prevalent in 
nearly all cases of certain rare cancer subtypes, including secretory 
carcinoma of the breast or salivary gland and infantile fibrosarcoma; 
they have also been observed in some patients with more common types of 
cancer, such as glioma, melanoma, and carcinomas of the thyroid, lung, 
and colon.\78\
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    \78\ www.ncbi.nlm.nih.gov/pmc/articles/PMC6859817/.
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    NIH will continue to support research efforts that reflect the 
scientific understanding of the many subtypes of cancers, including 
work that will enable the development of therapies for rare tumor 
subtypes.
                                 ______
                                 
                Questions Submitted to Dr. Gary Gibbons
                Questions Submitted by Senator Roy Blunt
    Question. Dr. Gibbons, we have all heard about the plight of COVID-
19 ``long-haulers'' who have symptoms after their acute COVID-19 
infection has subsided. A growing number of studies suggest that many 
patients experience some type of heart damage after contracting the 
infection, even in those not sick enough to be hospitalized. According 
to the American Heart Association, nearly one-fourth of those 
hospitalized with COVID-19 have been diagnosed with cardiovascular 
complications. A study in the Journal of the American Medical 
Association stated that researchers found abnormalities in the hearts 
of 79 percent of recovered patients and ``ongoing myocardial 
inflammation'' in 60 percent.
    Who is most at-risk of this type of heart damage, and is there 
indication that this damage is permanent?
    With heart damage appearing to be widespread, will screenings to 
detect cardiovascular damage be included as routine follow-up care for 
COVID-19 patients?
    Do you have any sense of how long longitudinal studies should last 
to follow long-haulers?
    Answer. While severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) enters the body through the respiratory tract, the virus 
also infects many other cell types and can damage multiple organs and 
tissues, including the heart and blood vessels. In rare cases, acute 
infection has been associated with cardiovascular complications 
including acute myocardial injury, myocarditis (heart inflammation), 
and arrhythmias (irregular heartbeat). This is not surprising given 
that viruses frequently trigger inflammation, and as the body's immune 
system fights off the virus, the inflammatory process can damage 
healthy tissues, including the heart. Many different viruses are known 
to cause myocardial injury and myocarditis.
    Many patients with coronavirus disease 2019 (COVID-19) experience 
damage to their blood vessels, leading to the formation of blood clots 
(thrombosis) that can develop in or travel to vital organs, including 
the heart. Blood clots in the coronary arteries can starve the heart of 
oxygen and damage the heart muscle. NIH's ACTIV-4 Antithrombotics 
adaptive master protocols have made progress in evaluating the safety 
and effectiveness of various types of blood thinners (e.g., aspirin, 
heparin, apixaban) for treating adults with signs of blood vessel 
damage and thrombosis from COVID-19, known as COVID-19-associated 
coagulopathy.\79\ Clinical trials are ongoing across three patient 
populations (inpatient, outpatient, and convalescent or patients 
recovering from COVID-19). These trials are providing valuable 
information about how to help prevent moderately ill patients with 
COVID-19 from progressing to intensive care, and could perhaps help 
mitigate future cardiac complications. For example, ACTIV-4 has shown 
that full-dose heparin is safe and effective at preventing blood clots 
in moderately ill hospitalized patients and reduced the need for life 
support.
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    \79\ www.nih.gov/research-training/medical-research-initiatives/
activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ4.
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    Studies have shown that patients with COVID-19 may show signs of 
cardiac injury, detected by a release of the cardiac muscle protein 
troponin into the bloodstream.\80\ Such injury is associated with worse 
short-term outcomes and higher mortality. An analysis of more than 40 
studies involving more than 8,000 COVID-19 patients found that venous 
thromboembolism (VTE; blood clots originating in a vein) occurred in 
approximately 21 percent of patients.\81\ Among COVID-19 patients 
admitted to intensive care, the VTE rate was as high as 31 percent. A 
review of myocarditis associated with acute COVID-19 estimated that the 
incidence is less than five percent; although less than previously 
thought, this could still mean a large number of patients with acute 
myocarditis given that COVID-19 cases in the United States have 
surpassed 33 million.
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    \80\ www.heartrhythmjournal.com/article/S1547-5271(20)30625-1/
fulltext#tbl1.
    \81\ pubmed.ncbi.nlm.nih.gov/33251499/.
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    The incidence of continuing or new cardiac problems after COVID-19 
or asymptomatic SARS-CoV-2 infection remains unknown. Although most 
people with COVID-19 get better within weeks of illness, some people 
experience post-acute sequelae, including chest pains, shortness of 
breath, exhaustion, heart palpitations, and chest pain. In addition, 
patients diagnosed with cardiac injury, thrombosis, or myocarditis 
during acute COVID-19 could sustain damage to the heart that persists 
long after the acute illness has passed. There is still much to be 
learned about the long-term cardiovascular consequences of SARS-CoV-2 
infection.
    NIH's Researching COVID to Enhance Recovery (RECOVER) initiative 
seeks to understand, and ultimately to prevent and treat, long COVID 
and other post-acute sequelae of SARS-CoV-2 (PASC) across the 
lifespan.\82\ At the center of the Initiative is an observational study 
that will include adults and children recruited from ongoing studies of 
COVID-19, long COVID clinics, and other cohorts. RECOVER is designed to 
significantly expand both our knowledge about the full clinical 
spectrum, long term outcomes, and underlying biology of PASC; as well 
as our ability to provide safe and effective therapeutic interventions.
---------------------------------------------------------------------------
    \82\ recovercovid.org/.
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    Current diagnostic protocols generally include physical, cognitive, 
and psychological assessments. The evaluation of patients hospitalized 
with COVID-19 includes elements of a cardiovascular evaluation, 
including assessment of known cardiovascular disease and risk factors 
for cardiovascular disease, assessment of symptoms that may be caused 
by respiratory or cardiac disease, laboratory testing (including a 
complete blood count and complete metabolic panel), chest radiograph, 
electrocardiogram (ECG), and troponin testing (which is followed if 
elevated). A more targeted cardiac evaluation may be needed depending 
on the patient's symptoms. Patients who develop new onset heart 
failure, for example, may need an echocardiogram (echo) to determine 
the best course of action. One of the goals of the RECOVER meta-cohort 
study is to develop core defining characteristics and diagnostic 
criteria for long COVID and other forms of post-acute sequelae of SARS-
CoV-2 infection (PASC), including understanding the impact the virus 
has on the cardiovascular system.
    NIH plans to, and has support to follow the RECOVER meta-cohort for 
at least 3 years. In addition to addressing the public health impact of 
SARS-CoV-2 infection, RECOVER also has the potential to enhance our 
understanding of other chronic syndromes theorized to have a viral 
origin, at least in some individuals, such as chronic fatigue syndrome 
and postural orthostatic tachycardia syndrome (POTS).
                                 ______
                                 
          Questions Submitted by Senator Shelley Moore Capito
    Question. Pulmonary fibrosis (PF) means scarring in the lungs. Over 
time, the scar tissue can destroy the normal lung and make it hard for 
oxygen to pass through the walls of the air sacs into the bloodstream. 
PF is not just one disease--it is a group of more than 200 different 
lung diseases that all look very much alike.
    The most recent studies show that more than 200,000 Americans are 
living with PF today. Approximately 50,000 new cases are diagnosed each 
year and as many as 40,000 Americans die each year. With no known cure, 
certain forms of PF, such as idiopathic pulmonary fibrosis, (IPF), may 
take the lives of patients within three to 5 years from diagnosis.
    PRECISIONS is the first-ever clinical trial to apply the principles 
of precision medicine to the diagnosis and treatment of idiopathic 
pulmonary fibrosis. PRECISIONS is supported by a $22 million grant from 
the National Institutes of Health (NHLBI grant number HL145266) and 
Three Lakes Foundation, a philanthropic organization.
    PRECISIONS is designed as a double-blind, multi-center, randomized, 
placebo-controlled trial investigating the safety and efficacy of NAC 
in patients with IPF who have a specific genetic variant which is 
present in 25 percent of IPF patients. The trial will enroll 200 
patients from approximately 20 PFF Care Center Network (CCN) sites. 
Initial recruitment into the study is being facilitated by looking at 
phenotypic data from patients that are enrolled in the PFF Registry.
    Can you provide an update on the NHLBI-funded PRECISIONS grant, 
which seeks to shed more light on the role of genetics in pulmonary 
fibrosis?
    How has the COVID pandemic affected this study?
    Answer. The National Heart, Lung, and Blood Institute (NHLBI) is 
committed to supporting research on pulmonary fibrosis, which leads to 
progressive scarring of the lungs that makes it increasingly more 
difficult to breathe. PRECISIONS \83\ is a five-year study that aims to 
enroll 200 patients with idiopathic pulmonary fibrosis (IPF) and use 
genetic testing to identify those patients most likely to respond to an 
experimental treatment, an antioxidant known as N-acetylcysteine or 
NAC. This first-of-its-kind precision medicine trial builds on an 
earlier study suggesting that a gene called TOLLIP influences how 
patients respond to NAC, such that it might be helpful only for a 
subgroup of patients who have a particular version of the gene. The 
trial will enroll only that subgroup, in order to increase the 
likelihood of detecting a benefit.
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    \83\ reporter.nih.gov/project-details/9822535.
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    PRECISIONS is co-funded by the Three Lakes Foundation, a non-profit 
philanthropy that supports education and research efforts to improve 
the time to diagnosis and accelerate new therapies for IPF. The study 
also involves a partnership with the Pulmonary Fibrosis Foundation, 
whose patient registry is being leveraged to perform molecular analyses 
on biospecimens obtained from patients with IPF. These analyses are 
intended to uncover novel genetic risk factors that will improve IPF 
diagnosis, predict its clinical course, and understand its underlying 
disease mechanisms--all of which could yield further insight into 
potential targeted therapies.
    The study was delayed in the latter half of fiscal year 2020 due to 
COVID-19-related institutional research restrictions, which led to 
NHLBI approval of a six-month interim no-cost extension. By December 
2020, the investigators had successfully completed all pre-specified 
project milestones for the first phase of their biphasic research plan, 
including enrollment of the first study participant. NHLBI approved the 
transition to the second phase of the project in March 2021. To date, 
six study sites have been activated, the percentage of eligible 
participants who meet the study's genotype inclusion criteria has been 
exactly as expected, and recruitment has proceeded on target.
    During COVID-19-related delays and uncertainty regarding the 
feasibility of in-person lung function assessments (spirometry), 
PRECISIONS initiated an ancillary study to understand the utility of 
home spirometry to monitor patients with IPF. The study also intends to 
add a COVID-19--specific questionnaire to baseline and follow-up visits 
in the clinical trial as a means of leveraging this existing patient 
cohort to capture additional data on the epidemiological and clinical 
characteristics of COVID-19.
                                 ______
                                 
            Questions Submitted by Senator Cindy Hyde-Smith
    Question. Concerned about other countries' ability to obtain 
vaccines quickly for their populations, the Administration recently 
announced that it will support a waiver of the World Trade Organization 
TRIPS Agreement, which would waive intellectual property protections 
for COVID-19 vaccines. It is my understanding, however, that there are 
no guarantees that the companies or countries who seek to use vaccine 
manufacturer's intellectual property to make copies will be able to 
deliver safe and effective vaccines, or that their manufacturing 
processes will meet the strict regulatory standards necessary for 
authorization. Furthermore, there are already reports of counterfeit 
vaccines being used to exploit vulnerable populations in the U.S. and 
around the world.
    Are you concerned that giving away intellectual property via a 
TRIPS waiver could make worse the problem of counterfeit and low-
quality vaccines in the market? What effect could this have on 
endangering lives and undermining public confidence in the vaccines 
that have been proven safe and effective?
    Answer. The National Institutes of Health (NIH) is concerned about 
counterfeit and low-quality vaccines; however, NIH does not have the 
expertise or authority to investigate these matters. The degree to 
which any TRIPS waiver addresses these issues of concern will not be 
known unless and until the terms are agreed upon.
    Question. The Administration recently endorsed the idea of waiving 
intellectual property (IP) protections for COVID-19 vaccines, in the 
hopes that it will speed up manufacturing of the vaccines around world. 
However, it is my understanding that some vaccine developers are 
already experiencing constraints in everything from raw materials to 
fill-finish capacity critical to producing and administering vaccines.
    Are you concerned that diverting critical supplies from 
manufacturers with proven track records for delivering high-quality, 
safe and effective vaccines could actually worsen the supply chain 
constraints we're currently seeing, and not just for COVID vaccines, 
but also non-COVID-19 medicines such as oncology and other infectious 
diseases?
    Answer. The National Institutes of Health (NIH) fully supports 
efforts to ensure reliable supply chains for vaccines and other 
medicines; however, NIH is not directly involved in these efforts.
                                 ______
                                 
                Questions Submitted to Dr. Perez-Stable
                Questions Submitted by Senator Roy Blunt
    Question. Dr. Perez-Stable, we typically talk about getting 
researchers into the NIH field and staying there as a pipeline. 
However, when we look at the pipeline for minority researchers, it can 
easily be called a funnel. We have a lot of work to do in increasing 
the diversity of NIH researchers. And as the COVID-19 pandemic has 
highlighted, NIH must also focus on health disparities research. The 
problems to these two solutions may go hand-in-hand. I know that Dr. 
Collins has started the UNITE program to look at racial inequities 
within the NIH community and has started a Common Fund program to fund 
transformative research into health disparities. While I commend these 
steps, many of the fundamental issues these programs are trying to 
address are reasons we started the Institute you fund--the National 
Institute for Minority Health and Health Disparities.
    Can you provide your perspective on how we get more minority 
scientists into the NIH community?
    And, specifically, what role should NIH take in making sure 
minorities have the educational background necessary to go into STEM 
fields--which often starts at the high school level, if not earlier?
    Answer. The National Institutes of Health (NIH) is committed to 
diversifying the research workforce and will continue to identify 
opportunities to increase its focus on building and supporting a 
diverse scientific workforce. The NIH UNITE initiative was developed to 
address inequity in biomedical research and will help NIH to identify 
more strategies and opportunities to strengthen its efforts to 
diversify the research workforce and attract and prepare more students 
from underrepresented backgrounds for STEM careers. The NIH already has 
several efforts to diversify the STEM pipeline and to train students at 
all levels of education as described below.
    NIH supports several initiatives to attract and recruit more 
minority scientists into the NIH intramural community. For example, the 
NIH Equity Committee systematically tracks and evaluates diversity, 
inclusion, and equity metrics in the intramural research program. In 
addition, the Distinguished Scholars Program (DSP) enhances the 
diversity of principal investigators in the NIH Intramural Research 
Program (IRP) by supporting first year tenure-track investigators with 
supplemental funds to start their research lab and engaging in 
activities designed to foster a sense of belonging and to promote 
research and career success. Moreover, the IRP provides a diverse 
environment for NIH-wide scientific recruitments through the Stadtman 
Tenure-Track Investigators, Lasker Clinical Research Scholars, and 
Early Independent Scientists recruitment programs. This approach has 
led to a greater proportion of women and scientists from 
underrepresented backgrounds recruited to NIH. The 2019 DSP cohort was 
comprised of approximately 7 percent Hispanics or Latinos, 27 percent 
African Americans or Blacks, 27 percent Asians, 40 percent White, and 
73 percent female. Among the fiscal year 2020 cohort, 21 percent was 
African American or Black, 21 percent Hispanic or Latino, 21 percent 
Asian, 36 percent White, and 50 percent female. Of the 15 Distinguished 
Scholars selected in the 2019 cohort, nine were Stadtman Tenure-Track 
Investigators, and two were Lasker Clinical Research Scholars. Of the 
14 Distinguished Scholars selected in the 2020 cohort, 10 were Stadtman 
Investigators, and three were Lasker Scholars.
    Extramurally, NIH has dedicated efforts to recruit diverse 
scientists from underrepresented groups to prepare successful NIH 
grants. NIH provides Diversity Research Supplements to enhance the 
diversity of the research workforce by recruiting and supporting 
graduate students, post-doctoral fellows, and eligible investigators 
from diverse backgrounds, including those from groups that have been 
shown to be underrepresented in health-related research. These 
supplements to existing grants provide a pathway to career success for 
scientists from diverse backgrounds and remains relatively 
underutilized. There are several other NIH programs that promote 
diversifying the research workforce and some are highlighted below. 
First, the NIH/National Institute on Minority Health and Health 
Disparities Loan Repayment Program (NIMHD LRP), which aims to increase 
the pool of qualified researchers who conduct health disparities 
research. Over a 15-year period, recipients of an LRP award from NIMHD 
are more likely to be awarded a subsequent NIH grant than their 
counterparts who were not successful. The LRP Health Disparities 
applications have now been extended to all NIH Institutes as of 2019. 
Second, the Native American Research Centers for Health promote a cadre 
of scientists and health research professionals interested in American 
Indian/Alaska Native health research. Third, NIMHD established the 
NIMHD Health Disparities Research Institute to support the research 
career development of promising early-career minority health and health 
disparities research scientists. Fourth, the NIH's Faculty 
Institutional Recruitment for Sustainable Transformation (FIRST) 
program, announced in 2020, will increase the participation of 
researchers dedicated to inclusive excellence, including minority 
researchers, in biomedical research at NIH-funded institutions. The aim 
of the program is to enhance institutional inclusive excellence, with 
diversity and equity at its core enabling biomedical research 
institutions to hire a diverse cohort of early-stage research faculty 
committed to inclusive excellence and diversity. The current pipeline 
of underrepresented scientists is not empty with about 14 percent of 
new U.S.-granted Science, Technology, Engineering and Math (STEM) PhDs 
awarded to underrepresented groups and similarly 14 percent of current 
medical students are from these groups.Lastly, the Science Education 
Partnership Award (SEPA) Program funds innovative pre-kindergarten to 
grade 12 science, technology, engineering, and mathematics (STEM) and 
Informal Science Education (ISE) educational projects. SEPA projects 
create partnerships among biomedical and clinical researchers and 
teachers and schools, museums and science centers, media experts, and 
other educational organizations. The NIH will continue to identify 
opportunities to increase its focus on building and supporting a 
diverse scientific workforce.

                          SUBCOMMITTEE RECESS

    Senator Murray. The meeting is adjourned. Thank you.
    [Whereupon, at 12:08 p.m., Wednesday, May 26, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]