    [House Hearing, 116 Congress]
    [From the U.S. Government Publishing Office]

                         REPURPOSING THERAPEUTIC DRUGS
                             FOR COVID-19: RESEARCH
                          CHALLENGES AND OPPORTUNITIES

    =======================================================================

                                    HEARING

                                   BEFORE THE

                         SUBCOMMITTEE ON INVESTIGATIONS
                                 AND OVERSIGHT

                                     OF THE

                          COMMITTEE ON SCIENCE, SPACE,
                                 AND TECHNOLOGY
                            HOUSE OF REPRESENTATIVES

                         ONE HUNDRED SIXTEENTH CONGRESS

                                 SECOND SESSION

                                   __________

                                 JUNE 19, 2020

                                   __________

                               Serial No. 116-74

                                   __________

     Printed for the use of the Committee on Science, Space, and Technology

     [GRAPHIC NOT AVAILABLE IN TIFF FORMAT]

           Available via the World Wide Web: http://science.house.gov

                                   __________

                        U.S. GOVERNMENT PUBLISHING OFFICE
    40-634PDF                  WASHINGTON : 2021

    --------------------------------------------------------------------------------------

                  COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY

                 HON. EDDIE BERNICE JOHNSON, Texas, Chairwoman
    ZOE LOFGREN, California              FRANK D. LUCAS, Oklahoma,
    DANIEL LIPINSKI, Illinois                Ranking Member
    SUZANNE BONAMICI, Oregon             MO BROOKS, Alabama
    AMI BERA, California,                BILL POSEY, Florida
        Vice Chair                       RANDY WEBER, Texas
    LIZZIE FLETCHER, Texas               BRIAN BABIN, Texas
    HALEY STEVENS, Michigan              ANDY BIGGS, Arizona
    KENDRA HORN, Oklahoma                ROGER MARSHALL, Kansas
    MIKIE SHERRILL, New Jersey           RALPH NORMAN, South Carolina
    BRAD SHERMAN, California             MICHAEL CLOUD, Texas
    STEVE COHEN, Tennessee               TROY BALDERSON, Ohio
    JERRY McNERNEY, California           PETE OLSON, Texas
    ED PERLMUTTER, Colorado              ANTHONY GONZALEZ, Ohio
    PAUL TONKO, New York                 MICHAEL WALTZ, Florida
    BILL FOSTER, Illinois                JIM BAIRD, Indiana
    DON BEYER, Virginia                  FRANCIS ROONEY, Florida
    CHARLIE CRIST, Florida               GREGORY F. MURPHY, North Carolina
    SEAN CASTEN, Illinois                MIKE GARCIA, California
    BEN McADAMS, Utah                    THOMAS P. TIFFANY, Wisconsin
    JENNIFER WEXTON, Virginia
    CONOR LAMB, Pennsylvania
                                     ------

                  Subcommittee on Investigations and Oversight

                      HON. BILL FOSTER, Illinois, Chairman
    SUZANNE BONAMICI, Oregon             RALPH NORMAN, South Carolina,
    STEVE COHEN, Tennessee                   Ranking Member
    DON BEYER, Virginia                  ANDY BIGGS, Arizona
    JENNIFER WEXTON, Virginia            MICHAEL WALTZ, Florida

                             C  O  N  T  E  N  T  S

                                 June 19, 2020

                                                                       Page

    Hearing Charter..................................................     2

                               Opening Statements

    Statement by Representative Bill Foster, Chairman, Subcommittee
      on Investigations and Oversight, Committee on Science, Space,
      and Technology, U.S. House of Representatives..................     8
        Written Statement............................................     9

    Statement by Representative Frank D. Lucas, Ranking Member,
      Committee on Science, Space, and Technology, U.S. House of
      Representatives................................................    10
        Written Statement............................................    11

    Written statement by Representative Eddie Bernice Johnson,
      Chairwoman, Committee on Science, Space, and Technology, U.S.
      House of Representatives.......................................    12

                                   Witnesses:

    Dr. Peter Lurie, President, Center for Science in the Public
      Interest
        Oral Statement...............................................    13
        Written Statement............................................    16

    Dr. James Finigan, Director of the Respiratory Centers of
      Excellence, National Jewish Health
        Oral Statement...............................................    24
        Written Statement............................................    26

    Dr. Rick L. Stevens, Associate Laboratory Director for Computing,
      Environment and Life Sciences, Argonne National Laboratory
        Oral Statement...............................................    29
        Written Statement............................................    31

    Dr. Benjamin Rome, Associate Physician, Brigham and Women's
      Hospital; Postdoctoral Research Fellow, Harvard Medical School
        Oral Statement...............................................    39
        Written Statement............................................    41

    Discussion.......................................................    59

                         REPURPOSING THERAPEUTIC DRUGS
                             FOR COVID-19: RESEARCH
                          CHALLENGES AND OPPORTUNITIES

                                  ----------

                             FRIDAY, JUNE 19, 2020

                      House of Representatives,
          Subcommittee on Investigations and Oversight,
                   Committee on Science, Space, and Technology,
                                                       Washington, D.C.

         The Subcommittee met, pursuant to notice, at 1:30 p.m.,
    via Webex, Hon. Bill Foster [Chairman of the Subcommittee]
    presiding.
    [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

         Chairman Foster. Without objection, the Chair is
    authorized to declare recess at any time.
         Before I deliver my opening remarks, I wanted to note the
    unusual circumstances under which we're meeting today. Pursuant
    to Resolution 965, today, the Subcommittee will be meeting
    virtually. This is not how any of us would prefer to perform
    our duties, but remote work is unfortunately a necessity at the
    current moment and a reflection of the part we all have to play
    in slowing the spread of COVID-19.
         In light of this remote format, I want to offer some
    reminders to the Members about the conduct of the hearing.
    Members should keep their video feed on as long as they are
    present at the hearing. Members are responsible for muting and
    unmuting their own microphones, and please keep your
    microphones muted unless you're speaking. You know, much as we
    love your family dog [audio malfunction].
         And finally, if Members have documents they wish to submit
    for the record, please email them to the Committee Clerk, whose
    email address was circulated prior to the hearing.
         Well, good afternoon and welcome to the first virtual
    hearing of the Committee on Investigations and Oversight.
    Today, we're discussing a critical issue: research into
    repurposing of existing therapeutic drugs for COVID-19
    treatment, as well as the scientific basis for the Federal
    Government's evaluation of such drugs.
         I appreciate our witnesses being here under these unusual
    circumstances, but these are very important issues, and we look
    forward to your testimony.
         Today's hearing revolves around one of humanity's most
    promising tools in its public health response to the current
    pandemic: repurposing existing therapeutic drugs to treat
    COVID-19. The appeal of repurposing existing therapeutics is
    obvious. These drugs have already been developed, they have
    already been manufactured, and in some cases can quickly be
    accessed in large quantities. And for drugs that have already
    been approved to treat other diseases, a certain amount of
    safety data is often available to regulators.
         In the absence of any COVID-19 vaccine or novel treatment,
    existing therapeutics could potentially offer critical
    assistance for severely ill patients and bridge the gap until
    more prevention and treatment options become available. But
    with great promise comes great concerns. Since existing
    therapeutics rest at our fingertips and have demonstrated
    benefits in other circumstances, it can be all too easy in the
    midst of a pandemic to cut corners and to seek shortcuts to
    longstanding regulatory processes, and we can't allow that to
    happen. The evaluation process to repurpose approved drugs is
    there for a reason: to ensure that existing therapeutics, which
    could carry significant health risks for COVID-19 patients, are
    assessed through the prism of scientific and medical data and
    sanctioned on the basis of factual evidence regarding safety
    and efficacy in their new context. And while the process itself
    should be flexible and as fast as possible, the integrity of
    the process must be firmly upheld.
         The research community's evidence-based evaluation of
    existing therapeutics must be paramount, and political
    considerations must never enter into the equation for any
    specific treatment. If politics is allowed to interfere,
    scientific research may be distorted, patients may be placed at
    risk, and the faith of the public in our whole public health
    mechanism may be shaken.
         Unfortunately, we're seeing the consequences of some
    political interference in the controversy surrounding two
    existing therapeutic drugs, chloroquine and hydroxychloroquine.
    In March, the FDA (Food and Drug Administration) issued an
    emergency use authorization (EUA) for these drugs as COVID-19
    treatments. The scientific evidence to support this decision
    was dangerously thin, but the political considerations were
    clear. And our President became the world's loudest cheerleader
    for both drugs. Researchers, experts, and former FDA officials
    all questioned the decision for lacking a sufficient scientific
    basis.
         And now, nearly 3 months later, the FDA just this week
    revoked the emergency use authorization, acknowledging the
    clinical data showing the drugs, quote, ``may not be effective
    to treat COVID-19'' and that, quote, the ``potential benefits
    for such use do not outweigh the known and potential risks.''
    This is a clear example of the dangers of allowing political
    considerations to distort what should be a scientific process
    reliant upon unbiased scientific evaluation.
         This hearing will explore the importance of supporting
    scientific research into repurposing existing therapeutics as
    COVID-19 treatments and the cost of neglecting science when
    politics intrudes. The research community is currently engaged
    in a heroic effort to explore as many therapeutics as possible
    in the search for a COVID treatment. The Federal Government
    supports many of these efforts, but there may be more that we
    can do as policymakers to provide researchers with the funding
    and the conditions that they need to make progress. And there
    may also be more that we can do to uphold the integrity in the
    role of science as the foundation for Federal efforts in this
    area.
         Our witnesses bring diverse perspectives with deep
    experience in these areas. I look forward to learning from them
    about the most effective way for the Federal Government to
    support research into repurposing existing therapeutics for
    this pandemic and probably--unfortunately, probably for the
    next one. Well, thank you all.
         [The prepared statement of Chairman Foster follows:]

        Today's hearing revolves around one of humanity's most
    promising tools in its public health response to the current
    pandemic: repurposing existing therapeutic drugs to treat
    COVID-19. The appeal of repurposing existing therapeutics is
    obvious. These drugs have already been developed; they have
    already been manufactured, and in many cases can quickly be
    accessed in large quantities; and for drugs that have already
    been approved to treat other diseases, a certain amount of
    safety data is already available to regulators. In the absence
    of any COVID-19 vaccine or novel treatment, existing
    therapeutics could potentially offer critical assistance for
    severely ill patients and bridge the gap until more prevention
    and treatment options become available.
        But with great promise comes great temptation. Since
    existing therapeutics rest at our fingertips and have
    demonstrated benefits in other circumstances, it can be all too
    easy in the midst of a pandemic to cut corners and seek
    shortcuts to longstanding regulatory processes. We cannot allow
    this to happen. The evaluation process to repurpose approved
    drugs exists for a reason: to ensure that existing
    therapeutics, which could carry significant health risks for
    COVID-19 patients, are assessed through the prism of scientific
    and medical data and sanctioned on the basis of factual
    evidence regarding safety and efficacy in their new context.
    While the process itself should be flexible, the integrity of
    the process must be firmly upheld. The research community's
    evidence-based evaluation of existing therapeutics must be
    paramount, and political considerations must never enter into
    the equation for any specific treatment. If politics is allowed
    to interfere, scientific research may be distorted, patients
    may be placed at risk, and the faith of the public may be
    shaken.
        Unfortunately, we are seeing the consequences of political
    interference in the controversy surrounding two existing
    therapeutic drugs, chloroquine and hydroxychloroquine. In
    March, the FDA issued an Emergency Use Authorization for the
    drugs as COVID-19 treatments. The scientific evidence to
    support this decision was dangerously thin, but the political
    considerations were clear: President Trump had become the
    world's loudest cheerleader for both drugs. Researchers,
    experts, and former FDA officials all criticized the decision
    for lacking a sufficient scientific basis. Now, nearly three
    months later, the FDA just this week revoked the EUA,
    acknowledging clinical data showing that the drugs ``may not be
    effective to treat COVID-19'' and that the ``potential benefits
    for such use do not outweigh its known and potential risks.''
    This is a clear example of the dangers of allowing political
    considerations to distort a process reliant upon unbiased
    scientific evaluation.
        This hearing will explore the importance of supporting
    scientific research into repurposing existing therapeutics as
    COVID-19 treatments, and the costs of neglecting science when
    politics intrudes. The research community is currently engaged
    in a heroic effort to explore as many existing therapeutics as
    possible in the search for a COVID treatment. The federal
    government supports some of these efforts, but there may be
    more we can do as policymakers to provide researchers with the
    funding and the conditions they need to make progress. There
    may also be more we can do to uphold the integrity of the role
    of science as the foundation for federal efforts in this area.
    Our witnesses bring diverse perspectives with deep experience
    on these issues. I look forward to learning from them about the
    most effective way for the federal government to support
    research into repurposing existing therapeutics, now and for
    the next pandemic.

         Chairman Foster. And the Chair will now recognize Mr.
    Lucas, the Chair of the Full Committee, for an opening
    statement.
         Mr. Lucas. Thank you, Chairman Foster, and thank you to
    our witnesses for their participation today.
         The COVID-19 pandemic is unlike anything we've faced since
    the 1918 Spanish flu. In those days, we had very few tools to
    slow the spread of the virus, develop treatments, or produce a
    vaccine to make ourselves immune to it. Thankfully, that has
    changed. Our Nation's research enterprise, including
    government, academia, and industry, is the expertise,
    resources, and talent needed to fight this pandemic. The work
    they're doing to model the virus, screen potential treatments,
    and engineer new medical equipment is truly lifesaving.
         We have supercomputers, advanced manufacturing techniques,
    and even advanced photon sources being used to fight COVID-19.
    From PPE (personal protective equipment) manufacturing and new
    vaccine developments to repurpose existing therapeutics,
    America's scientific community has heeded the call to action.
         An excellent example of the public-private collaboration,
    leveraging technology to fight a common cause, is the COVID-19
    High-Performance Computing Consortium. Though this OSTP (Office
    of Science and Technology Policy)-led collaboration, COVID-19
    researchers can access the world's most powerful computing
    resources to run complex models and develop large numbers of
    calculations at astonishing speeds. By leveraging these
    computing resources and deploying artificial intelligence (AI)
    and machine-learning techniques, researchers can determine
    which drugs have the potential to be repurposed against COVID-
    19 at a speed and scale previously unthinkable. Technology will
    continue to play a critical role in saving lives and preventing
    the spread of COVID-19. And our Federal research enterprise
    must have access to the resources and the technology necessary
    to do their jobs and to do it well.
         That's why I introduced the ``COVID Research Act of
    2020'', which would create an interagency working group and
    establish a national strategy to address infectious diseases.
    Additionally, this bill authorizes $50 million for DOE's
    (Department of Energy's) infectious disease research program
    over the next two years. Working together with NASA (National
    Aeronautics and Space Administration) and the NSF (National
    Science Foundation), this program gives us the ability to
    utilize the Federal Government's computing resources to respond
    to infectious diseases.
         Our national labs have already demonstrated the value of
    using high-performance computing and advanced research
    facilities to model novel coronavirus, understand its effects
    on human cells, and predict its spread. I'm pleased to learn
    that there is work underway at Argonne National Lab that is
    particularly relevant to repurposing therapeutics to fight
    COVID-19.
         And thank you, Dr. Stevens, for being here today. I look
    forward to learning more about this important work.
         And, more broadly, I'd like to extend my thanks to the
    entire scientific community, researcher after researcher, lab
    after lab pivoting immediately to fight COVID-19 when it
    reached our shores.
         When I began serving as Ranking Member of the Committee, I
    said one of our most important responsibilities is to tell the
    story of science and to make sure our constituents understand
    the tremendous research being done and why it matters to the
    next generation of Americans. This story in particular, how
    American scientists, researchers, and engineers responded to
    COVID-19 is one everyone should know, and I hope my colleagues
    will use this hearing as one more opportunity to share this
    work.
         And with that, Mr. Chairman, I yield back.
         [The prepared statement of Mr. Lucas follows:]

        Thank you, Chairman Foster. And thank you to our witnesses
    for your participation today.The COVID-19 pandemic is unlike
    anything we have faced since the 1918 Spanish flu. At the time,
    we had very few tools to slow the spread of the virus, develop
    treatments, or produce a vaccine to make ourselves immune to
    it. Thankfully, that has changed.
        Our nation's research enterprise, including government,
    academia, and industry, has the expertise, resources, and
    talent needed to fight this pandemic. The work they're doing to
    model the virus, screen potential treatments, and engineer new
    medical equipment is truly lifesaving.
        We have supercomputers, advanced manufacturing techniques,
    and even advanced photon sources being used to fight COVID-19.
    From PPE manufacturing and new vaccine development to
    repurposing existing therapeutics, America's scientific
    community has heeded the call to action.
        An excellent example of public-private collaboration
    leveraging technology to fight a common cause is the COVID-19
    High Performance Computing Consortium. Through this OSTP-led
    collaboration, COVID-19 researchers can access the world's most
    powerful computing resources to run complex models and perform
    large numbers of calculations at astounding speeds.
        By leveraging these computing resources and employing
    artificial intelligence and machine learning techniques,
    researchers can determine which drugs have the potential to be
    repurposed against COVID-19, at a speed and scale previously
    unthinkable. Technology will continue to play a critical role
    in saving lives and preventing the spread of COVID-19. And our
    federal research enterprise must have access to the resources
    and technology necessary to do their jobs, and to do it well.
        That's why I introduced the COVID Research Act of 2020,
    which would create an interagency working group and establish a
    national strategy to address infectious diseases. Additionally,
    this bill authorizes $50 million for DOE's Infectious Disease
    Research Program over the next two years. Working together with
    NASA and NSF, this program gives us the ability to fully
    utilize the federal government's computing resources to respond
    to infectious diseases.
        Our National Labs have already demonstrated the value of
    using high-performance supercomputing and advanced research
    facilities to model the novel coronavirus, understand its
    effects on human cells, and predict its spread. I'm pleased to
    learn that there is work underway at Argonne National Lab that
    is particularly relevant to repurposing therapeutics to fight
    COVID-19. Thank you, Dr. Stevens, for being here today. I look
    forward to learning more about this important work. And, more
    broadly, I'd like to extend my thanks to the entire scientific
    community. Researcher after researcher and lab after lab
    pivoted immediately to fight COVID-19 when it reached our
    shores.
        When I began serving as Ranking Member of this Committee, I
    said that one of our most important responsibilities is to tell
    the story of science and make sure our constituents understand
    the tremendous research being done, and why it matters to the
    next generation of Americans.
        This story in particular--how American scientists,
    researchers, and engineers responded to COVID-19--is one
    everyone should know, and I hope my colleagues will use this
    hearing as one more opportunity to share this work.
        I yield back.

         Chairman Foster. Thank you. And if there are Members who
    wish to submit additional opening statements, your statements
    will be added to the record at this point.
         [The prepared statement of Chairwoman Johnson follows:]

        Thank you, Chairman, Foster, and thank you to all of our
    esteemed witnesses for appearing before the Subcommittee today.
    It is so important to learn from experts about these critical
    issues because the threat of COVID-19 has not diminished. I
    have seen in recent days, in Dallas and throughout the state of
    Texas, how precarious our situation truly is and how we all
    must reinforce our commitment to combating the pandemic. It has
    been clear from the beginning and it remains clear today:
    science-based policymaking, rooted in facts and guided by the
    best efforts of the scientific community, is the key to
    overcoming this challenge. I am glad that today's hearing can
    help inform the federal government's response to the pandemic
    in the months to come.
        Repurposing existing therapeutics for COVID-19 treatment
    would be an important tool in the world's pandemic toolkit.
    Until a vaccine emerges, we must do everything possible to
    develop treatments that can save lives, and it makes a great
    deal of sense to evaluate drugs that have already been approved
    in other circumstances. I have been encouraged by the immense
    effort and resources that America's research community has
    dedicated to this cause. The federal government should be doing
    everything in its power to promote these research efforts, and
    I am eager to learn how we can do more to support the research
    community's critical work.
        I also want to better understand how the federal government
    can work with the research community to prepare for the next
    pandemic. There may be opportunities for the federal government
    to collaborate with the research community on broad issues such
    as prioritizing certain drug candidates, efficiently deploying
    limited resources, and coordinating efforts among the vast
    network of research institutions engaged in this work. These
    questions must be approached in a deliberative manner, and we
    should start to consider them now so that we are better
    prepared next time.
        As we think about these issues, we must never lose sight of
    the paramount importance of upholding scientific integrity at
    all times. Repurposing existing drugs in the midst of a
    pandemic carries high stakes, and federal policymaking must be
    done the right way, based solely on thebest available science
    and free from any political interference. The controversy
    surrounding the FDA's Emergency Use Authorization for
    hydroxychloroquine demonstrates all too well the damage that
    can occur when political considerations inappropriately
    influence the process. The government's actions to address the
    nation's needs during this public health crisis must only be
    guided by scientific evidence--never political pressure.
        The research community is rising to the challenge of COVID-
    19, and I have no doubt that it will continue to perform
    magnificently. Thank you again to all of the witnesses. I yield
    back.

         Chairman Foster. At this point I'd like to introduce the
    witnesses. Our first witness is Dr. Peter Lurie. Dr. Lurie is
    the President of the Center for Science in the Public Interest
    (CSPI), a nonprofit health advocacy group based in Washington,
    DC. Before joining CSPI, he held several positions at the Food
    and Drug Administration, including a stint at the--as the FDA's
    Associate Commissioner for Public Health Strategy and Analysis.
    He served nearly 8 years as a top official of the FDA.
         Our next witness is Dr. James Finigan. Dr. Finigan is the
    Director of the Respiratory Centers of Excellence at National
    Jewish Health, the Nation's leading respiratory hospital. He's
    also the Medical Director of the Lung Cancer Screening Program
    at the National Jewish Health. Dr. Finigan is a pulmonologist
    with a research focus on lung cancer and injury.
         Our third witness is Dr. Rick Stevens. Dr. Stevens is the
    Associate Laboratory Director for Computing, Environment, and
    Life Sciences at Argonne National Laboratory. He also serves as
    the leader of Argonne's Exascale Computing initiative. He's
    worked at Argonne Lab since 1982.
         Our final witness is Dr. Benjamin Rome. Dr. Rome is an
    Associate Physician at Brigham and Women's Hospital in Boston,
    Massachusetts. He's also a Postdoctoral Research Fellow at
    Harvard Medical School. Dr. Rome's academic research focuses on
    the FDA approval process for drugs and medical devices, as well
    as the effect of Federal policies and regulations on drug
    pricing and utilization.
         As our witnesses should know, each of you have 5 minutes
    for your spoken testimony. Your written testimony will be
    included in the record for the hearing. And when you've all
    completed your spoken testimony, we will begin with questions.
    Each Member will have 5 minutes to question the panel. And if
    there is time, we may be able to have a second round of
    questions from those Members who are in attendance.
         And we'll now start with Dr. Lurie.

                TESTIMONY OF DR. PETER LURIE, PRESIDENT,

               CENTER FOR SCIENCE IN THE PUBLIC INTEREST

         Dr. Lurie. Well, thank you, Chairman Foster, Ranking
    Member Lucas, and other Committee Members, for inviting me to
    testify on this important topic. For this testimony, I'm
    defining repurposed drugs as approved drugs for which a second
    indication for COVID-19 is sought. Some other witnesses may use
    other definitions.
         Unfortunately, the unmistakable allure of repurposed drugs
    is not enough on its own. Effectiveness for one condition does
    not guarantee effectiveness for a second even closely related
    condition. Target populations may be demographically and
    medically different, and so even the existing safety databases
    may have only limited relevance. The product may be
    administered in different doses or by different routes than for
    the first condition.
         So, let's look at two repurposed drugs. The antimalarial
    drugs chloroquine and hydroxychloroquine, which I'm considering
    together, would likely have languished well down the list of
    candidates for COVID-19 had they not been catapulted to
    prominence by President Trump's comments. On March 21st, the
    President described them as, quote, ``one of the biggest
    gamechangers in the history of medicine'' and later stated that
    he was taking the drug himself, the ultimate celebrity
    endorsement.
         On March 28th, under pressure from the Administration, FDA
    granted the drugs an emergency use authorization, EUA, but the
    evidence provided for this EUA was less than that provided for
    many previous EUAs.
         Eventually, the scientific process played itself out with
    several observational studies that demonstrated either no
    benefit from the drugs or even indicated that mortality rates
    were higher. FDA issued a warning that the drugs cause life-
    threatening arrhythmias. And finally, there were two randomized
    controlled trials, the gold standard for scientific evidence.
    The first suggested that the product was ineffective in
    preventing infection among those exposed to the virus, and the
    second, that it was also ineffective in treating SARS-CoV-2
    infection itself. On June 15th, FDA revoked the EUA.
         What can we learn from this embarrassment? Well, first, we
    should adhere to accepted methods of drug discovery even in a
    pandemic. It is the painstaking process of conducting
    randomized control trials that ultimately produces definitive
    evidence even if it is definitive evidence of lack of
    effectiveness.
         Second, the patients in the President's phrase did have a
    lot to lose. Life-threatening arrhythmias were fairly common.
    Even patients without COVID-19 suffered as those needing
    hydroxychloroquine for its FDA-approved conditions had
    difficulty obtaining the drug due to increased demand.
         Finally, the President's announcements distorted the
    overall research effort for COVID-19. It is inconceivable that,
    left to their own devices, scientists would have designed over
    150 randomized controlled trials assessing the effectiveness of
    these drugs. How many more promising drugs were left unstudied
    or understudied as researchers pivoted to address the
    headlines?
         A second problematic repurposed drug is famotidine, an
    over-the-counter heartburn drug also known as Pepcid, a
    seemingly unlikely drug for COVID-19. One of its primary
    advocates is a Boston physician named Dr. Michael Callahan, who
    was also a consultant on the Staff of the Assistant Secretary
    for Preparedness and Response, ASPR, Dr. Robert Kadlec. Under
    Dr. Kadlec's direction, Dr. Callahan, having advocated for the
    drug, assisted a pharmaceutical company and a hospital to
    prepare an application for funding to ASPR to conduct a trial
    of famotidine. Shortly thereafter, Dr. Kadlec ordered a hefty
    $21 million contract to these entities. Senior officials were
    cut out of the granting process.
         There are two other prominent drugs worth mentioning here.
    The first, remdesivir, is the only drug so far proved effective
    against SARS-CoV-2, but it is not a repurposed drug at least in
    my definition. Rather, it is an unapproved drug with known
    antiviral activity demonstrated to be effective in a study
    funded by NIH (National Institutes of Health).
         The second drug, dexamethasone, is the first drug to
    reduce mortality in patients with COVID-19. Whether it's a
    repurposed drug is a matter of definition as it's long been
    approved but is often considered as a general treatment for
    severe respiratory illness based on its anti-inflammatory
    activity and is not directed to SARS-CoV-2 itself.
         But the benefits of these two drugs were demonstrated the
    old-fashioned way, through rigorous, randomized controlled
    trials. Interestingly, the dexamethasone results are derived
    from the same British study that reported the ineffectiveness
    of hydroxychloroquine. That trial is very large and able to
    test multiple candidate therapies simultaneously. In contrast,
    the clinical trials effort in the United States has been
    fragmented and poorly prioritized, resulting in many relatively
    small studies often testing the same drugs with some patients
    struggling--some studies struggling to enroll patients.
         In conclusion, so far in this pandemic, effective
    treatments have not been identified by anecdote, by wishful
    thinking, by Presidential pronouncement, or by questionable
    contracting practices. They were identified instead by the
    fair, transparent, and systematic application of the very
    scientific principles that for decades have delivered so many
    safe and effective treatments. But when we departed from these
    principles, precious time was lost, resources were squandered,
    and some patients paid with their lives. Thank you.
         [The prepared statement of Dr. Lurie follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

         Chairman Foster. Thank you. And our next witness is Dr.
    Finigan, now recognized for 5 minutes.

                     TESTIMONY OF DR. JAMES FINIGAN,

                  DIRECTOR OF THE RESPIRATORY CENTERS

                 OF EXCELLENCE, NATIONAL JEWISH HEALTH

         Dr. Finigan. Thank you. I would like to thank the Members
    of the Subcommittee for inviting me to speak on my experiences
    as a clinical investigator during the COVID-19 pandemic. I am a
    pulmonary and critical care physician at National Jewish Health
    in Denver, Colorado, where I see patients in our pulmonary
    clinic and intensive care units. National Jewish Health is the
    leading respiratory hospital in the Nation and is the only
    facility in the world dedicated exclusively to medical research
    and to the treatment of patients with respiratory, cardiac,
    immune, and related disorders. We work with several hospitals
    in Colorado, including our flagship St. Joseph Hospital, to
    provide pulmonary and critical care medicine and have
    established respiratory institutes in New York in partnership
    with Mount Sinai Health System and in Philadelphia with
    Jefferson Health.
         I have close to two decades of basic, translational, and
    clinical research experience and currently help lead our COVID-
    19 clinical research program. Responding to this pandemic has
    required a complete reorientation of our clinical and research
    programs at National Jewish. Clinically, we reorganized our
    workforce and physical plant to diagnose and treat COVID-19
    patients while simultaneously planning for the worst-case
    scenario. For our research operations, it meant halting
    existing studies and starting up new studies as quickly as
    possible, all with much of our staff working remotely. Many of
    these studies are basic science investigations to identify new
    targets for treatment.
         At National Jewish Health, we've gone from zero COVID-19
    clinical studies to 10 or more therapeutic trials in various
    stages of development over the past 12 weeks. Prior to
    embarking on any specific research study, each trial requires a
    number of time-consuming steps, including formal protocol
    review, assessment of our ability to perform the trial as
    designed, determination of any conflicts with ongoing trials,
    budget negotiation, and agreement on contracting terms. This
    process ordinarily takes 3 months or longer. During this
    crisis, we've been able to cut that time to a few weeks. For a
    pharmaceutical company or other study sponsor, this process
    must be repeated at every study site. As an example, the
    recently published remdesivir study had 60 sites.
         And reflecting on our experience at National Jewish Health
    during this pandemic, I believe three points should be
    highlighted. First, to rapidly deploy clinical trials of new or
    repurposed drugs, a pre-existing, organized network of research
    sites is essential. The recently announced NIH-led ACTIV
    program is an example of this. ACTIV stands for Accelerating
    COVID-19 Therapeutic Interventions and Vaccines. It is a
    public-private partnership to create a collaborative framework
    for prioritizing vaccine and therapeutic candidates and
    streamlining clinical trials using existing clinical methods.
         Another example is the Prevention and Treatment of Acute
    Lung Injury, or PETAL network. PETAL is an NIH-funded network
    of academic medical centers dedicated to studying acute lung
    injury and the acute respiratory distress syndrome, the disease
    caused by SARS-CoV-2. This network has been repurposed to study
    the clinical features and possible treatments of COVID-19. For
    the past month, the PETAL network developed and launched two
    research protocols, and both studies will likely be completed
    in the coming weeks. Networks like these can be used in
    collaboration with industry as a platform to launch quickly new
    studies on promising treatments.
         Second, we need ongoing investigation of SARS-CoV-2 and
    COVID-19 to understand the virus and mechanisms of this
    disease. Much of this research will be what we call preclinical
    studies, bench research in cells and animal models to expand
    our understanding of COVID-19 pathophysiology. However, this
    can only exist if we maintain a robust national medical
    research mission and infrastructure.
         Dividends from this kind of research are not always
    immediately apparent. However, a basic understanding of the
    underlying science of this disease will drive development of
    new therapeutics moving forward both for this pandemic and to
    prepare us for the next one. These studies can help identify
    which new drugs are most promising and can inform a rational
    strategy for prioritizing drugs for clinical trials.
         Third, another pandemic is likely in our future. What that
    will be we don't know, but we should be planning now on how to
    incorporate a full research operation into any future pandemic
    response. I've been impressed with the research community
    reaction to this crisis. However, even with this effort, an
    organized national response was not launched until several
    months into the pandemic. Coordination of what research will be
    performed and how it will be executed, the respective roles of
    organizations such as the FDA, NIH, CDC, BARDA (Biomedical
    Advanced Research and Development Authority), as well as
    industry, should be considered prospectively. Research is as
    important to defeating this pandemic and being ready for the
    next one as personal protective equipment, intensive care
    units, and ventilators. Thank you.
         [The prepared statement of Dr. Finigan follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

         Chairman Foster. Thank you. That was beautifully timed.
    The Chairman appreciates the accuracy of your time estimate and
    will now recognize Dr. Stevens for 5 minutes. Whoops, Rick,
    mute.

                    TESTIMONY OF DR. RICK L. STEVENS,

                     ASSOCIATE LABORATORY DIRECTOR

             FOR COMPUTING, ENVIRONMENT AND LIFE SCIENCES,

                      ARGONNE NATIONAL LABORATORY

         Dr. Stevens. OK. I thought they were going to unmute me.
    So, thank you, Chairman Foster, Ranking Member Lucas, and
    Members of the Subcommittee, for inviting me here to talk about
    our work relating to COVID-19. My group and collaborators work
    primarily in the development of methods for high-performance
    computing and artificial intelligence applied to problems in
    biology and medicine, so let me talk a little bit about what
    we're doing.
         I should say that I'm speaking for Argonne, myself and for
    Argonne. I'm not speaking for the Department of Energy. My work
    focuses on applying high-performance computing methods to
    problems in science and medicine, and I've worked in this
    combination space for over 25 years. And related to COVID-19,
    I'm the co-PI (principal investigator) on a DOE, CARES Act-
    funded, nine-laboratory consortium project that is working on
    molecular design for COVID. As part of that effort, we're
    looking at repurpose-able drugs, as well as de novo compounds.
         Now, let me tell you a little bit about the virus and why
    it--why this drug search process is actually challenging. The
    virus is a single-stranded RNA (ribonucleic acid) virus. It
    codes for about 30 proteins. About 2/3 of those proteins
    commandeer host cell machinery to make copies of the virus, and
    about 1/3 of them are involved in packaging and formulating the
    virus. Of those proteins, there's perhaps 10, maybe a little
    bit more than that in the virus that the virus codes for that
    are plausible drug targets. The virus proteins also interact
    with the host. Perhaps as many as 300 protein interactions
    appear to occur, and a number of those host proteins could also
    be drug targets.
         Now, it's also important to know this virus is very
    closely related to SARS-1, and so since around 2003 the
    scientific community has had access to information about its
    genome and its proteome and has been working on this. And
    thanks to the DOE light sources and light sources elsewhere, we
    have very detailed atomic structural maps of these proteins,
    and in the last few months we've acquired more of these
    structural maps. But what's not known is essentially how
    existing drugs interact with these virus targets. That has not
    been the subject of large-scale computational work prior to now
    and has not been the study of large-scale experimental work.
         So, what I'm working in and my collaborators at the
    University of Chicago and at the nine national laboratories
    that are collaborating with us are really looking at how we can
    apply high-performance computing to scan not only the 2,500 or
    so licensed drugs worldwide and the 7,000 or so drugs that are
    in the pipeline but literally billions of molecules that we
    know can exist.
         Now, in this effort, it's also critical to recognize the
    three main infrastructures that we're using. We're using
    supercomputers, the fastest machines in the world that exist at
    the DOE labs like at Argonne and at Oak Ridge. The famous
    Summit computer at Oak Ridge is a workhorse for us but also
    machines that the NSF supports. We also use the light sources.
    These are critical for determining structures of proteins and
    for determining structure with molecules, potential inhibitors,
    bound into these proteins so we can understand their mechanism
    of action.
         And the third resource that's critical for this effort is
    the NIH-funded biocontainment laboratories, the regional
    biocontainment laboratories that were stood up after 9/11,
    after the scare--after the anthrax scare and concern about
    emerging pathogens, and these exist at various locations in the
    country. The one that is close to me is the H.T. Ricketts lab
    operated by the University of Chicago here at Argonne. We're
    also using the Regional Biocontainment Laboratory that's at the
    University of Tennessee Health Sciences Center. Those centers
    are critical because they can work on active virus, virus
    that's--viruses are not alive, but viruses where we can look at
    the entire lifecycle and whole cell assays and animal-based
    assays.
         So, essentially, what our program is, is to use the
    computers to search for molecules, including all the
    repurposing drugs. They get scored on each individual molecular
    target. The drugs that appear to have high potential get
    forwarded to our experimental collaborators where they get
    assayed biochemically and then ultimately through whole cell
    assays.
         I should point out one more thing. There's lots of advice
    we could give about future pandemics, but one thing that's
    holding us back, that's holding back the scientific community
    right now is the lack of biochemical assays for these specific
    virus protein functions. The National Institutes of Health are
    investing in development of these assays. They have the NCATS
    (National Center for Advancing Translational Sciences) program
    working on that. The national laboratories are also investing
    in assay development, but that is a major bottleneck. In the
    future, we need to invest in assays up front. They need to be
    stockpiled. They should become part of the national critical
    infrastructure and made available to these biocontainment
    laboratories so that, in the future, rapid screening can happen
    on any new outbreak. And I'll leave it at that. Thank you.
         [The prepared statement of Dr. Stevens follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

         Chairman Foster. Well, thank you. Well, at this point
    we'll begin our first round of questions, and the Chair will
    recognize himself for 5 minutes here.
         Dr. Rome and Dr. Lurie, you know, there have been--there's
    been mention of the--what is being set up in Europe and
    internationally and as opposed to what has happened in the
    United States in terms of the coordination of the large number
    of clinical trials. Can either of you say little bit about what
    we get right that's gotten--you know, that's better or worse
    than what's done in other countries and other international
    collaborations and whether we're insufficiently or more than--
    or sufficiently connected to those?
         Dr. Lurie. Let me let Mr.--Dr. Rome answer because, sir, I
    think you neglected to give him the chance to read his
    statement.
         Chairman Foster. Oh, goodness. My apologies. My apologies.
    Thank you, Dr. Rome. I was fumbling multiple windows here and
    neglected, so--and thank you for that, Dr. Lurie.
         All right. Dr. Rome, you're now recognized for 5 minutes.

                    TESTIMONY OF DR. BENJAMIN ROME,

           ASSOCIATE PHYSICIAN, BRIGHAM AND WOMEN'S HOSPITAL;

                     POSTDOCTORAL RESEARCH FELLOW,

                         HARVARD MEDICAL SCHOOL

         Dr. Rome. Thank you. Sorry about that. So, Chairman
    Foster, Ranking Member Lucas, and Members of the Subcommittee,
    thank you for inviting me. I'm a practicing primary care
    physician and a health policy researcher at Harvard Medical
    School and Brigham and Women's Hospital in Boston. I'm a member
    of the division of pharmacoepidemiology and pharmacoeconomics
    and the Program on Regulation, Therapeutics, and Law for
    PORTAL, an interdisciplinary research group that studies
    prescription drug development, regulation, use, and cost. I am
    honored to be here today to talk with you about the process for
    studying and approving repurposed drugs during the COVID-19
    pandemic.
         Drug development can be a lengthy process, and repurposing
    several medications with existing data about safe use in humans
    allowed clinical trials to begin early in the pandemic. As a
    result, just 4 months after the first COVID-19 patient was
    reported in the United States, several high-quality clinical
    trials have provided solid evidence relating to at least four
    drugs, two of which have proven effective: dexamethasone, a
    low-cost generic corticosteroid that can be readily prescribed
    by clinicians; and remdesivir, an antiviral that has not yet
    been approved for any indication by the FDA but is now
    available under an emergency use authorization.
         However, we have also witnessed examples of how the
    process for testing and approving drugs can go awry, as
    exemplified by the case of hydroxychloroquine. We should learn
    from our past missteps as we move forward, and our experiences
    so far suggest four key actions Congress should take.
         First, Congress should hold all government agencies and
    officials accountable for making statements and acting based on
    the best available scientific evidence. Hydroxychloroquine was
    widely touted by President Donald Trump and was issued an
    emergency use authorization by the FDA based on preclinical and
    limited anecdotal evidence that turned out to be unreliable.
    These actions led to widespread use of the drug, which exposed
    patients to risk, led to shortages at pharmacies, and diverted
    attention and resources that might have been dedicated to other
    potential therapies.
         Second, Congress should invest heavily in high-quality
    clinical trials which are necessary for determining whether
    drugs are safe and effective. Notably, most of the high-quality
    evidence generated so far during the pandemic has resulted from
    public funding, including the U.S. Government in the case of
    remdesivir and the United Kingdom Government in the case of
    dexamethasone.
         While the pharmaceutical industry will continue to have a
    role to play, the Federal Government's leadership and
    involvement are crucial, particularly for repurposed drugs
    which industry may have little or no financial incentive to
    study. However, such public investment should be made with the
    assurance that any medications that are found effective will be
    priced fairly and distributed equitably to patients who need
    them. No American should be prevented from accessing
    potentially lifesaving treatment for COVID-19 due to cost.
         Third, Congress should invest in a public health
    infrastructure and national clinical trial network that can
    help shape the research agenda, facilitate research across
    multiple sites, and limit duplicative efforts. In several
    European countries, government and academics have collaborated
    on large clinical trials that test multiple repurposed drugs
    simultaneous. A prime example is the RECOVERY Trial based out
    of the University of Oxford. This trial has already provided
    useful information about the lack of effectiveness of
    hydroxychloroquine and the effectiveness of dexamethasone.
         Finally, Congress should amend the process by which the
    FDA issues emergency use authorizations or EUAs. The level of
    evidence required to meet the standard of an EUA should be
    clarified. And to increase transparency, Congress should compel
    the FDA to make all related data public at the time that the
    EUA is issued.
         As new evidence emerges, the FDA should be directed to
    apply the same standards for revoking an EUA as was required
    for issuing it. EUAs should be accompanied by a clear and
    transparent plan for how the drug will be fairly and equitably
    distributed to patients, something that was lacking for both
    hydroxychloroquine and remdesivir.
         Finally, issuance of an EUA should be accompanied by
    collection of data on treated patients to gain additional
    insight about the drug's safety and effectiveness.
         Our experiences so far studying repurposed drugs during
    the COVID-19 pandemic have shown that we need not choose
    between rigorous scientific evidence and speed. We can have
    both. As our fight to control the COVID-19 pandemic continues,
    Congress must assure that we uphold a drug approval process
    that follows the science and promotes the practice of evidence-
    based medicine.
         In a recent viewpoint published in the New England Journal
    of Medicine, Dr. Jerry Avorn and I argued that, quote, ``The
    health of individual patients and the public at large will be
    best served by remaining true to our time-tested approach in
    clinical trial evidence and drug evaluation.'' Thank you.
         [The prepared statement of Dr. Rome follows:]
        [GRAPHICS NOT AVAILABLE IN TIFF FORMAT]

         Chairman Foster. Thank you. And my apologies again for
    having skipped your testimony in the order. That's, I guess,
    the danger that occurs when I've read your testimony in advance
    and feel less need to hear it directly from you.
         And so I guess I will repeat my question, which is largely
    directed at your testimony to say a little bit more about the
    differences in the way things are being done internationally
    versus in the United States and what lessons we might learn
    from that.
         Dr. Rome. Thank you, yes, I am appreciative. So, the--your
    question is a good one. We have had two successes in this
    pandemic so far with dexamethasone and remdesivir. One was
    primarily driven out of the United States, but the other,
    dexamethasone came from funding from other countries. And I can
    say that most of the large clinical trials that are being
    conducted, especially the ones that were started very, very
    early in the pandemic and are likely to get us results in a
    timely fashion, were led by our peers in Europe and other
    countries. And definitely the United States should, in going
    forward in this pandemic and in future pandemics, lead those
    efforts and become a leader in the world for running these
    sorts of clinical trials.
         Chairman Foster. Now, in the case of the drug that worked,
    the anti-inflammatory that worked in England, was that funded
    by the manufacturer? Because one of the things that worries me
    here is that if all--if the majority of our clinical trials are
    funded by manufacturers, you will naturally--they will prefer
    drugs for which they have an intellectual property or a
    manufacturing position in and that we may forgo equally
    promising drugs that are, for example, off patent or just
    become generic drugs. And is that handled differently in other
    countries than the United States or are essentially all trials
    worldwide funded by the manufacturer?
         Dr. Rome. No, not all trials are funded by the
    manufacturer. And the trial out of Oxford was funded by the
    U.K. Government. Dexamethasone is a generic drug. There's very
    little skin in the game for any manufacturer to conduct a
    clinical trial, and that's likely to be true of many of these
    repurposed drugs, which may be older, off patent, generic
    drugs, which are widely available and great for patients but
    not necessarily a good investment from the perspective of a
    manufacturer.
         But not only that, the clinical trial for remdesivir,
    which is still a patented drug owed by Gilead, the key clinical
    trial upon which we are using the drug and an EUA was based was
    funded by the U.S. Government, by the NIAID (National Institute
    of Allergy and Infectious Diseases), and so--and this is a case
    where Gilead should have been running the key clinical trials
    and instead ran a clinical trial testing two different doses of
    the medication against itself and leaving the key clinical
    trial to come to the U.S. Government. And they have a patent on
    that drug and can financially benefit from it when it--or if
    and when it gets FDA approved.
         Chairman Foster. Thank you. Yes, Dr. Lurie, any comments
    on what's done internationally versus the United States and
    lessons we might learn?
         Dr. Lurie. Well, I think what Dr. Rome said is spot on the
    money. Unfortunately, things have been to a certain extent
    delegated to the pharmaceutical industry and even to individual
    academic institutions in this country. What we really need is
    somebody to coordinate the whole thing. I know that the NIH
    would like to do that. I know that the British Government has
    done so very successfully, particularly in the Recovery Trial,
    but we need a stronger hand on the rudder, somebody to
    prioritize the drugs, figure out the ones that matter the most,
    and then do proper trials on them.
         I guess I'd add it to what Dr. Rome said in the following
    way. It's tempting in the setting of a pandemic to say that we
    need to cut corners, but actually, the pandemic is almost the
    best place to stick with the usual game plan because there are
    so many patients, I'm sorry to say, and the disease makes you
    ill so quickly, I'm sorry to say, that there's more than enough
    statistical power for people to do the randomized controlled
    trials which we expect drug approval to be based upon.
         So, let's stick with the methods that work. Let's not use
    the pandemic as some excuse for corner-cutting or for
    deregulation.
         Chairman Foster. All right. So, yes, that's interesting.
    Do you think that there may be opportunities that we're
    overlooking for sort of lightweight outpatient clinical trials?
    You know, you can imagine to have a quick but scientifically
    valid look at hydroxychloroquine, for example, if you had any
    one of the--some fraction of the large number of people who
    have tested positive were immediately given the option of being
    screened and just on an outpatient basis given that we could've
    rapidly understood and, you know, with a lot of safety concern.
    Are there opportunities there we should think about?
         Dr. Lurie. I think there are, but so far if you look at
    the totality of the research that's been done, most of it is
    based on the inpatient setting, and that makes a certain kind
    of sense. These are the sickest patients after all. They're the
    patients in whom you can demonstrate benefit most easily. So, I
    agree there's opportunity, but I don't mean that as a criticism
    of the research enterprise to date.
         Chairman Foster. All right. And that exceeds my 5 minutes,
    and so I'd like to recognize Representative Lucas--Chairman
    Lucas for 5 minutes.
         Mr. Lucas. Thank you, Mr. Chairman.
         Dr. Stevens, could you provide us with an example of a
    cutting-edge research capability unique to the Argonne National
    Lab and how it is helping researchers work forward toward
    repurposing existing drugs to treat COVID-19?
         Dr. Stevens. Well, the--probably the best example is the
    use of the advanced photon source to quickly within a few days,
    assuming we can get a good crystal, produce a new structure of
    a viral protein bound to a drug. This is critical to understand
    whether or not the target is in fact the target that the drug
    is working on to understand how it changes the structure of the
    protein, how it might interrupt its function, so that's a
    pretty unique capability. There's only a handful of places in
    the United States and the world that can do that and can do it
    quickly.
         And after the pandemic became apparent and Argonne went
    into a lowered level of operation, we kept the advanced photon
    source up, and we kept that team working on determining protein
    structures critical to the virus. That's a really good example.
         Mr. Lucas. Well, could you, along those lines, explain how
    Argonne National Lab is working collaboratively with other
    research entities toward identifying COVID-19 drug candidates?
         Dr. Stevens. So, we have a nine-lab consortium that
    includes Argonne, Oak Ridge, Berkeley, Brookhaven, Los Alamos,
    Livermore, Sandia National Laboratories, SLAC, and Pacific
    Northwest Labs, nine labs all working together. We are using
    large-scale computation to computationally screen drugs,
    billions of drugs--or billions of potential drugs. All the
    existing drugs and billions of molecules that can become
    potential drugs. The drugs that look interesting from a
    computational standpoint are immediately procured and turned
    over to experimentalists that can assay the drug to determine
    if it is a viable inhibitor of function.
         And for things that succeed at that functional screen are
    forwarded to whole cell assays that can test full virus
    replication. Things that would succeed there would get passed
    on to animal models and then passed on for additional
    refinement and development. But I point out that it takes a
    large team to do this with virologists, physicians, medicinal
    chemists, computer scientists, and so on, and because of that
    large team--in fact, an important strategy is to consider
    repurposing existing drugs alongside new compounds. Existing
    drugs are of particular interest to clinicians due to them
    already being available.
         Mr. Lucas. As I mentioned earlier, my bill, H.R. 6599,
    focuses on collaboration among Federal agencies and aims to
    create a national strategy for any infectious disease outbreaks
    we face in the future, and certainly we will face those in the
    future again, as the Chairman alluded to. Are there any other
    collaborations that we're not thinking about that would help
    you, Dr. Stevens?
         Dr. Stevens. Well, we--early on, we established a
    collaboration between the DOE national labs, and the NIH, which
    has laboratory activities and research groups, so there's
    linkage. I think what's needed in the framework of your bill is
    a sustained, ongoing network of research collaborations that's
    consistently working on problems and is sharing data, sharing
    research, sharing assays, sharing information and would involve
    the DOE, it would involve the NIH, it probably would involve
    NSF resources in some cases, the DOD (Department of Defense),
    essentially all the players that are necessary for integrated
    public health in this country--some kind of ongoing
    collaboration around emerging threats.
         Mr. Lucas. One last question, Dr. Stevens. Is there
    anything Congress can do to help scientists and researchers
    like yourself do their jobs more efficiently during this
    pandemic and bring us one step closer to ultimately a cure?
         Dr. Stevens. I believe that the current activity is
    exactly what's needed. The funding--the ongoing funding support
    for these new efforts is of course critical, extend that
    longer. We're not out of this pandemic yet. I believe the
    interagency coordination process is working quite well. I
    believe that the institutions have put together structures to
    support this. Within the Department of Energy, for example,
    they created the National Virtual Biotechnology Lab
    coordination process across all the national labs in the United
    States to drive them toward a coherent COVID-19 strategy, so I
    believe that's working. So, continued support for that level of
    activity is what I recommend.
         Mr. Lucas. Thank you, Doctor. Thank you, Mr. Chairman. I
    yield back.
         Chairman Foster. Thank you. And I will now recognize
    Representative Bonamici for 5 minutes.
         Ms. Bonamici. Thank you, Mr. Chairman. Can you hear me?
         Chairman Foster. Yes.
         Ms. Bonamici. Terrific. Well, thank you to Chair Foster
    and Ranking Member Lucas and really for--to our witnesses
    today. Thank you for your expertise.
         We know that COVID-19 is disproportionately affecting
    black, Latinx, indigenous, and other people of color and that
    they are contracting the disease and dying at alarming rates.
    And as researchers develop studies and carry out trials, the
    Administration and Congress can and must address these
    disparities and do all we can to encourage or require research
    that's deliberately inclusive of all demographics and
    effectively addresses these inequitable outcomes.
         Recruiting patients to participate in research we
    understand can be challenging even under ideal settings, but
    trials can fail if there's a lack of patient enrollment. There
    are valid reasons why a patient invited to take place in a
    study may not trust medical researchers or feel comfortable
    participating. And even once a willing participant is
    identified, there can be barriers to their inclusion.
         A recent Politico article talked about physicians who were
    conducting NIH-funded clinical trials for remdesivir at sites
    in Boston, New York, and Atlanta. They faced language barriers
    in recruiting patients with limited English proficiency. They
    didn't have consent forms in Spanish. They had to work with
    translators by phone to explain the study and get consent and
    took extra hours per patient.
         So, I know, Dr. Lurie, you mentioned this. Do the
    witnesses all agree that it's important to have diverse
    representation in studies and trials? Do you all acknowledge
    that that's important?
         Dr. Lurie. Well, if I may go, I most certainly do. I've
    not seen specific information about recruitment and how it
    might vary by ethnicity so far in this pandemic, but I do know
    that this is not an equal-opportunity virus. At all stages of
    this disease, African Americans and other people of color are
    at a distinct disadvantage. They're more likely to be exposed
    to the virus in that they're more likely to be living in
    crowded living conditions, more likely to be working in
    meatpacking plants, more likely to be in prison, more likely to
    be healthcare workers at the front lines of exposure to the
    virus.
         After that, they very often have difficulty gaining access
    to treatment in part because of lack of health insurance, and
    then within the hospital, you know, the outcomes have not been
    equal across ethnic groups perhaps because of significant
    underlying health care--health conditions as well.
         So, all the way across----
         Ms. Bonamici. I appreciate that. I'm going to ask--I don't
    mean to interrupt, Dr. Lurie, but I'm also going to ask you and
    Dr. Finigan, are there strategies to get diverse representation
    in testing and trials? And, if not, what could not only the
    government but what can the medical community do? Do you have
    suggestions on how to build trust in the communities that may
    have been historically excluded from government-funded
    research? I want to get your thoughts and also Dr. Finigan.
         Dr. Lurie. Well, Dr. Finigan, go ahead.
         Dr. Finigan. Thank you. So, first off, you're correct. So,
    I would--I have seen firsthand in the COVID-19 pandemic where
    we--there have been examples of people who were not recruited
    adequately or were not recruited because there was a language
    barrier, there was not an appropriate consent form. That was
    particularly challenging for people who only spoke Spanish. One
    important thing to note is that there's often--there's always a
    time window in which you can recruit somebody, so, you--
    typically, you can't recruit somebody into a study in an
    unlimited time window, that you may have to do it within, let's
    say, 24 or 48 hours of them being positive, and so there's a
    little bit of a race against the clock in this. And so those
    kinds of barriers really can have significant meaning. I think
    those things need to be taken into account ahead of time.
         It is relatively common that African Americans, Latinos,
    nonwhites are sort of underrepresented in studies, and so being
    ready for that kind of thing ahead of time to make sure they
    can get adequately enrolled, all the resources are available to
    them, those things are critical. I know of studies where they
    got those kinds of resources, those consent forms, but it
    happened weeks into the trial, and so you lost time, you lost
    patients.
         And the other critical piece there that I think you're
    also getting at is that's a lost opportunity for that person to
    be in a trial. Our goal is to give every patient the
    opportunity to enroll in a trial if they want to. And if you
    can't enroll them because there's not an adequate consent form,
    let's say, that's a missed opportunity for that patient, and
    they may lose the chance of being in a trial, let's say, on
    remdesivir where there's a potential benefit.
         Ms. Bonamici. I appreciate that. And there was just an
    article this morning in Axios Health Newsletter that there's
    all this--now there's talk this week about this steroid that's
    been hailed as a breakthrough treatment, but there's also
    evidence, according to the Chair of Pharmacology at Johns
    Hopkins University School of Medicine that African Americans
    may respond differently to this type of steroid. So, it's so
    critical that we address this issue because, as we know, COVID-
    19 doesn't discriminate based on somebody's race. I mean, it's
    disproportionately affecting people of color.
         And real quickly, Dr. Finigan, we know that repurposing
    existing drugs is an attractive option because medications have
    already gone through testing. Can you tell us more about how
    preclinical testing in clinical trial phases can be safely
    accelerated if the drug has already been approved for another
    use?
         Dr. Finigan. So, there are--so there are different ways
    this can be done, but I think the key is to have sort of
    integrated networks so you can hit all the phases at once. So,
    as has been described, there are things you can do, Insilico,
    in a computer where you can try to rationally identify drugs.
    So, for example, I was a part of a study where one of our
    investigators built essentially a Google program where you
    could put in drugs and then put in the kind of drug you wanted
    or the kind of protein you wanted to target, and then this
    computer program would sort of spit out the drug that you
    wanted, and then you could marry that to an assay that you
    could do in a lab where you might have, let's say, 500 little
    wells, and you could test different drugs in each one of those
    wells. And so being able to marry those different things
    together and being able to do that and then rapidly move that
    into an animal model, those things are important, to have that
    whole spectrum represented. Whether or not that requires one
    institution or multiple institutions is important.
         And I think, as was said earlier, having these assays sort
    of ready to go is important, and so thinking about what these
    might be, they often have to do with toxicity, whether or not
    they kill cells or something like that, those are the things
    that need to be thought about ahead of time so they can be
    ready to go.
         Chairman Foster. OK. So, I'm afraid I have to----
         Ms. Bonamici. OK. My--yes, my time is expired. I yield
    back, Mr. Chairman, thank you.
         Chairman Foster. That's all right. And we'll have a little
    bit of forbearance with Representatives who are coming in on
    the telephone because they can't see the timer.
         And we'll now recognize Representative Biggs for 5
    minutes.
         Mr. Biggs. Thank you, Mr. Chairman, and thanks, Ranking
    Member Lucas, and thank you to each Member of the panel. This
    has been very interesting.
         And as we're trying to develop vaccine or cures for the
    COVID, I see we're moving fairly rapidly. It looks like we're
    moving rapidly. And I appreciate Dr. Lurie talking through
    this, maintaining some standards and normalcy.
         But I guess my question that I want to ask here is, as we
    go through this and we accelerate these processes, can you
    address, and I'll just open it up to whoever wants to answer
    this. How can we maintain scientific rigor while we're
    accelerating the development of vaccines and curatives? And
    each one of you have nibbled around the edges here, but I'm
    wondering if there's any way that you see that we can maintain
    that scientific rigor that's so necessary if we're going to
    really get a handle on this?
         Dr. Lurie. Well, you know, I think the playbook is clear.
    The playbook is the playbook that we've had for decades, the
    playbook that has produced effective therapy through following
    that very playbook, through keeping to strong standards. So,
    all I think we really need to do is to coordinate better,
    obviously speed things up the way researchers collectively have
    decided to do by turning their attention to this. And if we
    keep our standards up, I like to think that ultimately we'll
    have the products that we need.
         Mr. Biggs. Well, and so that gets me to Dr. Rome, who I
    think mentioned something I'm in total agreement with if you'd
    maybe expand on that. You said in EUAs one of the things that
    we need to do is be more transparent. And so, Dr. Rome, if you
    would just address that, how we do that and how can we best be
    more transparent?
         Dr. Rome. Yes, thank you. I totally agree. Transparency is
    key with EUAs. We had two examples of EUAs or emergency use
    authorizations so far during this pandemic, so
    hydroxychloroquine and chloroquine was the first one. That was
    based on very little evidence. But when the EUA came out, it
    wasn't clear what evidence the FDA had considered, and it sort
    of--only later did we sort of learn a little bit about what
    they--what was going through the minds of the folks at the FDA.
         With remdesivir, we had a top-line result published by the
    clinical trial, but we--not until 3 weeks later did we have the
    full data that was released in the New England Journal of
    Medicine. And during those 3 weeks the drug was already being
    shipped out to hospitals and humans, and we didn't know
    necessarily how to best target the drug toward particular
    patients or if there was--and we had a limited supply.
         So, absolutely, transparency is key. The FDA should make
    decisions in a consistent way that meet the standard. The
    standard for any EUA is that it is reasonable to believe, based
    on the totality of evidence, that the drug is likely to be
    effective. So, that reasonable-to-believe standard needs to be
    enforced. When new data comes out, we need to reassess. And we
    need the--whatever data that the FDA is using to make those
    decisions should be public at the same moment that the EUA
    letter is issued.
         Mr. Biggs. Great. Thank you. And I'm just going to go to
    Dr. Stevens. Dr. Stevens, you mentioned that although
    repurposing existing drugs may be a fast route to possible
    treatments, it's highly likely that we're going to still need
    purpose-built drugs for treating COVID-19. Can you expand on
    how the work that you're doing at Argonne be leveraged by
    pharmaceutical companies to help develop purpose-built drugs
    specifically?
         Dr. Stevens. Yes. So, what the team is doing is we are
    trying to produce a set of qualified leads. That would be
    compounds that show some promise in the computational work,
    they show some promise in initial functional assays and initial
    whole cell assays but are not fully refined as drugs. These
    would be compounds that we would essentially handover to the
    pharmaceutical industry and say here's all the data that we've
    computed and that we've measured on these compounds and let
    them take it from there.
         And this--that kind of handoff has been discussed between
    the labs and pharma, and it's the kind of thing that pharma is
    very interested in because you think of the--the drug and all
    the processes is a giant funnel, and at the top of the funnel
    you've got billions of possible molecules out of the--out of 10
    to the 60th possible drug molecules, we know of a few billion
    of them that we've thought about in some sense, and we have to
    narrow that down to handfuls, you know, 10's or 20's of
    compounds the pharmaceutical industry can take and do more
    advanced studies on, can refine and improve the molecules,
    improve their safety, improve their effectiveness, improve the
    therapeutic window.
         And so what we're doing in the public sector is
    essentially that big top part of the funnel and reducing it
    down in a very public way, in a very open way, to set of
    priorities that they can then take and invest private money
    into drugs. That's the strategy.
         Mr. Biggs. Right. Thank you. And with that, Mr. Chairman,
    I'll yield back.
         Chairman Foster. Thank you. And I will now recognize Mr.
    Beyer for 5 minutes.
         Mr. Beyer. Thank you, Mr. Chairman, and thanks, all of
    you, for being with us.
         Let me begin with Dr. Rome. One of the things in your
    testimony you said it's imperative that we establish a clinical
    trial network. Does one not already exist, and isn't that part
    of the function of NIH to have established that over the years?
         Dr. Rome. Thank you for the question. Yes, so, certainly,
    we have small networks of clinical trials, and I think that Dr.
    Finigan could probably speak to this more as a trialist
    himself, but I would say that the NIH does in fact do direct
    research itself in some cases, as was the case in remdesivir.
    But in other cases it will outsource to academics. And, as was
    already mentioned, when a study is done at multiple sites,
    there's a lot of regulatory things that need to happen. You
    need to assure safety of the clinical trial through
    institutional review boards, and that can take a long time.
         And so by--what I think the--where I think the efforts
    need to be is, you know, clinical trialists and scientists are
    ready to go and want to act. What needs to be cut down on are
    the things that are super important like maintaining patient
    safety, but the time to do those things and the time to
    correlate across different sites can definitely be cut down on
    by investing further in those infrastructures.
         Mr. Beyer. The vision has to be that there is an existing
    national network of clinical sites, say, 50, 100, 300, that in
    a future crisis, click, you turn it on.
         So, to Dr. Finigan, you mentioned that at National Jewish
    Health you're working on delineating the structure of the
    protein. Why would an individual hospital do that rather than
    the national labs that have all the--you know, the big
    computing machines, the neutron devices and the light devices?
         Dr. Finigan. You know, I mean, it has to--so it has to do
    with a couple things. No. 1, ability and interest. We have
    people who have that ability and can do it. And, as I said,
    everything is sort of reoriented toward COVID-19, so everybody
    in the hospital dropped what they were doing and started to do
    new things directed toward COVID-19. So, people who had that
    ability here worked on that.
         I think it also speaks to a little bit of a lack of
    coordination of how this would be attacked from the beginning,
    and so from the beginning there was not a sort of--at least not
    a publicly announced kind of strategy that was clear to
    everybody in terms of how things were going to happen, how
    things were going to get laid out from sort of basic science,
    understanding some of those basic facts to driving it into
    clinical trials, and that creates a fair amount of duplication.
         And an example of that, just to answer the question you
    brought up earlier, there are clinical networks that have
    existed, and there are lots of them that still exist. It's just
    that it took several months to utilize those for COVID-19. They
    sat not being used for COVID-19 trials for a period of time,
    and now they're starting to get used. And so it may not be
    creating a new network. It just means understanding that these
    things exist and you have a strategy ready to go that you're
    going to use.
         Mr. Beyer. Great, thank you. Thank you. Dr. Stevens, I was
    fascinated by the notion that the COVID--you know, the RNA
    translates into 30 specific proteins. You understand the
    structure, how they're folded, that 10 to 20 of them are what
    creates this issue. And you talk about purpose-built. Is it--
    are you thinking or is it possible to think--and I think
    mathematically with your supercomputers about how to tear apart
    one of those 20 proteins?
         Dr. Stevens. Well, we're building both physics-based
    models and AI models to essentially design--custom design
    inhibitor molecules for each of those proteins using the power
    of supercomputing. I mean, that's what the community that can
    do this type of biophysical modeling and AI is working on.
    There are many groups that are collaborating on this task, and
    I believe in the near future--I can't say exactly how long this
    will take--we will have new compounds that are the result of
    this process that will go into the experimental screening
    pipelines.
         Mr. Beyer. But do you have to disrupt more than one of
    those 20 proteins to make a----
         Dr. Stevens. Yes, you have to. If you look at state-of-
    the-art antiviral therapies, often they're a cocktail of drugs,
    and so we think the best strategy is probably a multiple
    therapeutic mix that would go after multiple targets, maybe a
    target that would help in blocking viral entry, one that might
    block replication, one that might block some host process that
    is a problem, and so forth. And so you would probably end up at
    the end of the day with a mixture of compounds in a future
    drug--or future drug treatment.
         I think it's really important, though, to say that to
    develop the kind of drugs that we're imagining will take a long
    time. If you think about in the case of HIV, it took many, many
    years before there were effective HIV therapies, over a decade,
    and while we're moving faster, and we have better tools, this
    is a very hard problem. And while the scientific community has
    been working the last few months in a kind of crisis mode on
    this, they can't work in crisis mode for many years, and so we
    have to put institutional structures around this to get it
    done.
         Mr. Beyer. Thank you very much. And I yield back, Mr.
    Chairman.
         Chairman Foster. Thank you. I'll recognize Representative
    Wexton for 5 minutes. Mute. Whoops, microphone. Mute. You're
    muted.
         Ms. Wexton. Shame on me. Hi. Thank you, Mr. Chairman, for
    yielding and for not charging me my 5 minutes quite yet. And to
    the panelists for joining us today, this is a really
    fascinating discussion, and I'm glad to be here for it.
         You know, the controversy surrounding the FDA's EUA for
    hydroxychloroquine has caused a lot of people to question the
    scientific integrity of FDA's process, and so the policymaking
    especially during this pandemic. Dr. Lurie and Dr. Rome, could
    you please give us your general assessment of the rigor of FDA
    policymaking and public communications regarding the
    repurposing of therapeutic drugs during this pandemic and then
    what needs to be done better, if anything?
         Dr. Lurie. Well, I certainly agree that it has been a
    disappointment, and I don't think it's because of the career
    officials in FDA, who I believe are completely committed to
    scientific integrity and proper regulatory procedures in this
    pandemic. But I do think that people have turned out to be
    susceptible to political pressure.
         The hydroxychloroquine example is frankly an
    embarrassment. The standard for approving the EUA was
    considerably below what it was in previous EUAs, and I say this
    based on talking to people who granted EUAs in previous
    Administrations. And so, in the end, that turned out to be a
    black eye for the agency.
         Another embarrassment I think has turned out to be
    antibody tests where for a while the agency allowed these
    products to come on the market without even an EUA. And then
    that turned out to be a disaster when it turned out that they
    were plagued by false positives, so now they have an EUA.
         What I hope is that from the combination of those two
    experiences we'll get a proper use of the EUA process, which I
    think we are now seeing for remdesivir, and I sincerely believe
    and hope that my former colleagues at FDA will be able to stand
    up to the political pressure, because it is certainly searing.
         Ms. Wexton. And Dr. Rome, how about you?
         Dr. Rome. Yes, thank you for the question. I think what
    you're getting at is actually an issue that has come up again
    and again, which is sort of the standards of evidence sort of
    required for any drug approval even before COVID-19, which
    traditionally were statutorily supposed to be based on sort of
    substantial evidence, so it means that traditionally that meant
    two clinical trials, two large randomized clinical trials to
    make sure that even if one trial got the answer wrong, that we
    wouldn't get it wrong twice. And that has changed over time.
         There are many drugs now that are expedited through the
    FDA process, and that's something that needs to be considered.
    And that's sort of the background for when--you know, when
    COVID-19 came, we've already experienced the fact that 80-plus
    percent of drugs are approved through some expedited pathway
    may be based on more limited evidence than that traditional two
    clinical trials. So, during COVID-19, we've relied, you know,
    on the EUA to sort of cutoff the FDA approval process and act
    before the FDA sort of carefully considers all the evidence.
         It makes total sense, and certainly time is of the
    essence, but to your point, we actually have very little
    experience using EUAs in--for drugs. It was done during a swine
    flu pandemic of 2009, 2010. There, a drug was issued an EUA,
    and the--but data that later came out from the clinical trials
    showed that the drug was not actually effective for the type of
    patients the EUA was issued for.
         Now, we have hydroxychloroquine and remdesivir, so we've
    maybe hit one out of three potentially that we don't know the
    full story on remdesivir, but certainly this is the time for
    Congress to take a look at the way the EUAs have been utilized
    and tune up the regulations on the FDA to make sure it's done
    appropriately in the context of the speed that's needed.
         Ms. Wexton. So, in this final minute I guess my question
    is also there's going to be a lot of financial incentives for
    various firms to get their drugs through this EUA process and
    get them approved. What--how does the FDA assess and eliminate
    conflicts of interest in its drug approval process, make sure
    that there's no conflicts in the decisionmaking process?
         Dr. Lurie. Well, I--quite frankly, the process is infected
    with conflict of interest, and there's not very much that can
    be done about it in the following sense. We accept the idea
    that drug trials, trials of diagnostics and vaccines, are
    conducted in general by the manufacturers themselves, and so
    it's a given that there will be that kind of conflict of
    interest in that the companies will come in with an interest in
    depicting the data in the way that best suits them.
         But that's where the FDA comes in. That's where the FDA's
    review of the actual data itself, which no other country in the
    world claims to do, that's where that kind of review, that kind
    of insulating of the reviewers from the manufacturers is so
    important. And that's the way it's managed. But it's a given
    that most of the time the studies will be done by the
    manufacturers themselves.
         Ms. Wexton. Thank you very much. I see my time has
    expired, and I will yield back.
         Chairman Foster. Well, thank you. And I will now recognize
    Representative Perlmutter to unmute and----
         Mr. Perlmutter. Thanks, Mr. Chair. And to the panelists,
    thank you all for your testimony. I've been watching you all
    listen and watch each other, and it's been interesting.
         So, the first question I have--and, Dr. Finigan, you
    brought up a couple networks, and you say there are networks in
    place, but they really didn't get activated promptly. So, you
    talked about ACTIV and you talked about PETAL I guess, sort of
    the acronyms for these things. And to everybody but start with
    you, Dr. Finigan, a pandemic comes, we see this thing starting
    to roll, how is there--is there some lead agency, is it CDC, is
    it NIH, is it BARDA, is it--who is it that says to these
    networks, OK, everybody's got to jump to whether it's hospitals
    or the laboratories or who says ``get going?''
         Dr. Finigan. So, I think to a certain degree the exact
    agency that does it doesn't matter. I think it just needs to be
    understood out of time. And so whether or not it is the NIH or
    BARDA, it--you know, or another agency, I don't think really
    matters. It's just a function of thinking ahead of time and
    knowing ahead of time that these networks exist and that you
    want to put them into action and especially in a situation like
    this where you actually have some lead time. So, we knew about
    this pandemic for some time, and we could have been planning
    it, and so it doesn't necessarily matter that it's the CDC or a
    different agency. Whichever agency, let's say, funds that
    network or if you need to bring in more than one network and
    you might need to have cross agency, those things just need to
    be thought of ahead of time.
         Other aspects like how you would do consenting for
    patients and those things also should be thought of ahead of
    time so that that can be streamlined as quickly as possible for
    when you need to utilize those networks.
         Mr. Perlmutter. So, Dr. Stevens, when were the labs sort
    of kicked into gear on this thing?
         Dr. Stevens. The labs started to self-organize around the
    1st of March ahead of the official proclamations. We have a bit
    of internal flexibility at the labs and we used that
    flexibility to get started. That's why the labs exist, to do
    large-scale science, interdisciplinary, and so--and we're used
    to taking initiatives on our own, taking our own initiatives,
    so the labs started talking to each other, we started arranging
    computer time, we started pulling together teams actually long
    before the pandemic was declared. And DOE headquarters was very
    supportive that we were already moving.
         And so I think the community--I think the others would--
    panelists would agree. The community saw this coming and
    started to do things that they could do within the realm of
    their degrees of freedom of action, and the agencies then came
    up to speed to start resourcing things. So, I think, you know,
    it all sort of happened in parallel.
         Mr. Perlmutter. So, to all of you, from our--so our
    Science Committee we have a little bit of jurisdiction with
    respect to hospitals but not a lot, but we do have definitely
    jurisdiction over the laboratories. So, is there any connection
    in these networks that you talked about, Dr. Finigan, or you
    talked about the nine labs that you're collaborating with, Dr.
    Stevens? Is there any connection between sort of these hospital
    networks and our laboratories? Are you guys talking to each
    other?
         Dr. Stevens. Not so much. The Department of Energy
    typically doesn't get involved in clinical research. Our
    laboratory doesn't have ongoing internal projects related to
    clinical work. This is largely due to the distinctions between
    the different agencies that fund that work. We do have a lot of
    collaborators in universities, and so the way in which we--and
    I personally have a joint appointment at the University of
    Chicago where I have colleagues in clinical trials and I have
    funding from NIH and connections to clinical work via my
    university appointment and from talking to those people so,
    personally, we have contacts. But, institutionally, the
    Department of Energy, typically, the DOE laboratories that they
    support aren't involved in clinical work.
         Mr. Perlmutter. All right. Well, let me turn to Dr. Rome
    for my last 45 seconds. So, at Harvard--so National Jewish
    collaborates with lots of hospitals, the University of
    Colorado, a bunch of other stuff. Harvard obviously
    collaborates with everything around the world. When did your
    medical school and when did you sort of--or how--get engaged in
    this thing, I mean, the minute we heard about it from China or
    how did that go?
         Dr. Rome. I agree with what's been said that the
    scientific community acted early, but acting early involves
    having information, and I think the information comes from the
    top in this case. The information out of China was challenging,
    I think, for medical professionals to understand, and so by the
    time in March that people started to gear up here, that might
    have been unfortunately pushed earlier had the Administration
    and everyone else in the government sort of set the ball moving
    and pushed for action earlier on.
         Mr. Perlmutter. And I guess I was remiss to say Dr.
    Finigan helped me on a telephone town hall where we had 10,000
    people on the line, and so I just wanted to mention that and
    thank all of you for your testimony today. I really appreciate
    it.
         Chairman Foster. Well, thank you all. At this point I
    guess there's probably enough Member interest for another round
    of questioning for those Members who wish, and so we can
    quickly--all right. Mr. Perlmutter and Beyer. OK. So, this may
    be a brief round of questions here, but I would like to follow
    up on a couple of points.
         The--Dr. Finigan, you sort of mentioned the idea, the
    concept that there--instead of having to replicate the approval
    of the remdesivir trial at 60 different locations, that there
    could be some single point of approval. And are you--is it
    realistic to expect that individual institutions will buy into
    that mechanism, that they'll be willing to outsource the
    approval of a clinical trial that may or may not, you know, be
    safe, which is one of their concerns?
         Dr. Finigan. So, the answer is no, they're not going to
    give it up, but I think there's things you can do ahead of time
    to make it go much faster. So, what happens with a trial like
    the remdesivir trial or other trials that we have going on is
    an industry sponsor in these instances reaches out to us, asks
    us if we want to be a part of it. We say yes, and then there--
    at that point you begin the back-and-forth of we get the
    protocol, we read it, it goes through our process, we have to
    approve it and make sure it's safe, we have to discuss the
    budget, we need to make sure we have to do it. While we're--
    they're doing that with us, they're doing that individually at
    all the different sites. If we spend, let's say, 3 weeks
    working on it and then decide we can't do it, that's wasted
    time for everybody.
         So, if this--so if you have a network like, let's say, the
    PETAL network that I mentioned, this exists already in place. A
    lot of that work has been taken care of already, and so a lot
    of that immediate work and legwork in terms of getting things
    approved and contracting and budgeting, that stuff might be
    taken care of. And so you can imagine a situation where a drug
    company might say I have a drug, I think it's promising, I want
    to use this federally funded network and maybe there's some
    mechanism by which they have to pay in to use that to help keep
    that funded but allows them to very rapidly get their drug out
    there and not have to go through the process every time.
         Chairman Foster. All right. And so, yes, you touched on
    the issue of getting the commercial incentives right, because
    that must be very delicate in this because, you know, obviously
    if a drug company can get the Federal taxpayer to pay for a
    clinical trial for a drug that they'll eventually make money
    on, you know, say this is something which is a currently
    unapproved use, you'd think that there ought to be a mechanism
    in place somehow to have the drug--the Federal taxpayer, you
    know, have some benefit from the fact that they paid for this
    trial.
         And are there countries anywhere that have a different
    model that might be more effective for dealing with the--you
    know, the commercial interest to fund trials, or do they just
    fully federalize it and there's a big pot of money that--and a
    group of scientists who decide what is the most scientifically
    promising and allocate some fraction of the clinical trials
    that way?
         Dr. Finigan. So, I can't speak to what happens very
    knowledgeably in other countries. I'll let other people address
    that if they know that. What I will say briefly is that there
    are some examples of--I don't know if it's quite public-private
    partnerships but, for example, in cystic fibrosis, the Cystic
    Fibrosis Foundation, which really sort of regulates a lot of
    the trials that happen in cystic fibrosis in kids and adults,
    partnered with an industry sponsor on new drugs so that they
    could rapidly get those drugs sort of tested, and then those
    were successful and approved, and so the drug company and the
    Cystic Fibrosis Foundation both benefited from that. And I
    think that's an example that could be replicated in other
    instances. And I'll let others talk about other countries.
         Chairman Foster. Dr. Rome, any comments?
         Dr. Rome. Yes, I guess I would say that I don't know of
    another country sort of to your question of sort of how that
    balance is made other than other countries do a much better job
    negotiating for value-based prices of drugs so that we do not
    sort of double pay, paying sort of through the roof for
    clinical research to develop the drug and then secondarily for
    high prices, so that's one comment.
         The other is that not just in COVID-19, again, I mentioned
    the example of remdesivir, which is exactly what you said. A
    government is funding the late stage sort of clinical trial
    development. That occurs in one in four drugs that have been
    developed over the last decade where the Federal Government is
    involved late in the development of a drug. And almost every
    drug has some sort of Federal involvement in the early stages
    of development, so this is absolutely a problem. It's going to
    be highlighted in COVID-19, and it's going to affect how the
    drugs are able to be accessed by patients once we have to--you
    know, once patients and insurance companies have to pay for
    them, so it's definitely something that needs to be addressed.
         Chairman Foster. Well, thank you. And I think one of the
    most potentially tragic outcomes is that promising drugs just
    won't get looked into that should if you don't set this up
    right. All right.
         And at this point I'm happy to recognize Chairman Lucas
    for 5 minutes of additional questions.
         Mr. Lucas. Mr. Chairman, I will yield back but simply note
    our constituents out in the countryside are frantically looking
    for ways to protect themselves from this or cures to address
    it. I'd like to think that all the discussion here today about
    the challenges we face to this point, still the underlying
    issue is we're making progress, diligently working to address
    the needs of our constituents, and that they should have faith
    in the institutions both inside and outside the Federal
    Government that are working together, healthcare industry
    included, to try and address their needs, needs that are
    brought on through issues by no fault of their own, just the
    world we live in at this time.
         And with that, Mr. Chairman, I yield back.
         Chairman Foster. Thank you. And I'll now recognize
    Representative Beyer for 5 minutes.
         Mr. Beyer. Thank you, Mr. Chairman, very much.
         Dr. Stevens, in your testimony you talked about us paying
    attention in the long term to emerging pathogens. How do you
    define emerging pathogens? Does someone have to get sick before
    we do it? And given the billions of different viruses that are
    out there, what constitutes an emerging one?
         Dr. Stevens. Well, it's--there are several definitions,
    but the one that I think most people would agree with, it's
    pathogens that are relatively new to science, so these could be
    pathogens, zoonotic pathogens that are endemic in wild animals,
    maybe in places people don't normally live, and as humans,
    human development, and economic development pushes large
    numbers of people closer to these previously wild areas,
    there's lots of opportunity for contact with these animal
    species, and new pathogens can emerge that way. That's the
    primary mechanism.
         If you think over the last couple of decades, the viral
    pathogens, Ebola, Zika, SARS, COVID-2--SARS-CoV-2, these have
    all emerged from animal reservoirs, and so my recommendation is
    that we mount a scientifically based international program to
    surveille wild populations, understand their microbiomes, the
    natural viruses that coexist with them, and study them. We have
    the technology for doing that. We could easily sequence these
    things. We can produce the structures. We can get ahead of the
    curve. We can understand the reservoirs much better than we do
    currently, and that would leave us more time to be ready for
    the next one.
         Mr. Beyer. Thank you. You also mentioned that there are 10
    million molecules available for experimental validation. Well,
    you can't--are you--and you talked about the windowing, the
    funneling.
         Dr. Stevens. That's right.
         Mr. Beyer. Is the first funnel going to be a mathematical
    one, the physical one rather than experimental----
         Dr. Stevens. Well, the top of the funnel occurs in some
    theoretical sense as every molecule that's possibly drug like
    is about 10 to the 60th. The drug companies and the academic
    community have an understanding of maybe 4 to 5 billion
    molecules. Of that, maybe 10 million are something I can get my
    hands on in a couple of weeks. Of course, synthetic chemists
    can make new things roughly in that timeframe as well, so it
    would be conceivable to create ahead of time panels, that is,
    collections of molecules that are ready but essentially
    standing by in the freezers.
         And if you have an emerging outbreak and you develop
    assays quickly, you could screen a very large set of molecules
    in a few months and have a lot of possible leads to chase down.
    And combining that with computation would create a much better
    situation in terms of future therapeutic development, and
    that's something I think the community would be very excited to
    work towards.
         Mr. Beyer. Excellent. Thank you. And it is amazing trying
    to get your arms around 100 million molecules.
         One last question. Dr. Rome, your fourth point was making
    improvements to FDA's EUA process, and you talked about the
    bullets, clarifying and standardizing transparency, equitable
    distribution, and then patient outcome data. Is this something
    that should be done regulatorily or is this a perfect piece of
    legislation for the House Science Committee?
         Dr. Rome. So, the FDA has the ability to do some of these
    things but has not done so. They have the ability to collect
    information about the drugs, but they're not required to and--
    other than adverse event or safety reporting of sort of major
    events like deaths that occur from the drug, so that has
    happened, but further data has not been required as part of the
    EUAs. The FDA has broad authority to write into the EUA sort of
    what it wants in terms of requirements, but certainly those
    requirements--you know, that sort of broad authority could be
    better regulated by Congress by sort of more directing and
    saying when you issue an EUA, these are the things that we
    think are necessary.
         And we've learned a great deal about what would be
    helpful. I would say, again, more transparency at the outset so
    that physicians who are using the drugs from an EUA have access
    to data, you know, not just the data that's, you know, on the
    internet but actually like the raw data, the published studies.
         Mr. Beyer. And you wouldn't think that we were guilty of
    micromanagement if we led that?
         Dr. Rome. I mean, I think that these things need to
    happen, and so I think if Congress wants to step up and say
    that for all future EUAs that these are some tweaks that we
    think are necessary, I think that's reasonable. I would say the
    EUA is not just to drugs. The EUA applies to diagnostics,
    testing equipment that has been mentioned before, ventilators,
    other things. So, again, drugs are a minority of cases over the
    history of the EUA that have been--where it's been used, so we
    only have really three examples, two of which, you know, are
    for this pandemic alone. So, we are--you know, I do think it's
    time to reevaluate how that was used and decide if change--
    small changes, legislative changes need to be made.
         Mr. Beyer. All right. Thank you very much. Mr. Chairman, I
    yield back.
         Chairman Foster. Thank you. And I'll now recognize
    Representative Perlmutter for 5 minutes.
         Mr. Perlmutter. Just one question, and start with you, Dr.
    Lurie. Anybody can jump in. The serologic tests, the antibody
    tests I guess, there are a whole bunch of them. Some have been
    approved, I guess, and some have not been approved. So, going
    to the diagnostics that you were talking about, Dr. Rome, did
    we do this right or not or is there now sort of doubt about
    these tests and their validity? Dr. Lurie?
         Dr. Lurie. Well, in referring to the antibody tests
    specifically, I don't think that has been well-handled by FDA.
    I think that, feeling the pressure to press ahead, they gave
    the antibody tests a free pass to begin with, not even
    requiring an EUA for them. And it didn't take long for evidence
    to mount that, particularly in low-prevalence populations,
    certain of these tests could actually produce more false
    positives than true positives. And I think that first the
    agency took a look at what they'd done and then they slapped an
    EUA upon them giving the companies 10 days to comply. I don't
    know how many of them have met the EUA requirements at this
    point, but I expect that certain of those products will just
    disappear because they couldn't meet the standards.
         So, again, what I'm sorry to say has happened is that the
    FDA has been--you know, they're kind of flip-flopping or, if
    you like, course-correcting, you know, to try and get this
    exactly right. They've made some mistakes. Hopefully, it will
    be better going forward.
         Mr. Perlmutter. OK. Thank you. I don't know if anybody
    else has any comments. I just want to thank the panel, and I'm
    happy to yield back to you, Mr. Chairman.
         Chairman Foster. Well, thank you. And I--you know, I have
    to say that I was a little bit surprised when the antibody
    tests came out so flawed, that there was no one responsible for
    making--for--in the government for establishing a test panel
    that you run every one of the proposed tests against just blood
    samples of positive and negative people that would be just
    prepared and at least given to every manufacturer to test
    against and report their results. And, you know, that seems
    like the sort of infrastructure that should exist somewhere in
    the future when this sort of thing happens.
         And I was also fascinated by Representative Beyer's
    suggestion of potential legislation coming out of this, that
    there may be something sensible that could be done there. And,
    let's see, I can--now can--have about one remaining minute of
    Representative Perlmutter's time, so I'd just like--Dr.
    Stevens, how leaky is the funnel? How often do you see a drug
    that works wonderfully in practice and not at all in theory?
         Dr. Stevens. Well, it usually means our theory is wrong,
    so we have to go back and fix the theory if that happens. The
    funnel is pretty leaky in the sense that things fall out that
    we have to filter out because we're using approximate rules
    often to do this. But, you know, most of what we look at
    doesn't work. I mean, that's the reality of drug development.
    Most compounds don't work. And so it is a needle-in-a-haystack
    type of problem, and occasionally, you will find drugs that
    defy our, you know, initial view, but those usually don't come
    from the computational process because we filter those out.
    They would come through physical screens and natural products,
    for example, and then you have to go back and rethink them. So,
    you need combinations of both. This can't all be
    computationally driven. As I mentioned before, large chemical
    libraries that would be screened in public I think is another
    resource that we need as infrastructure.
         Chairman Foster. All right. Well, anyway, I just want to
    thank all of our witnesses at this point before bringing the
    hearing to a close. It's very important. And keep thinking, as
    you're doing your daytime job here, what changes you'd like to
    see in place for the next pandemic because I think that's going
    to be a big part of our job is to try to preserve the attention
    span of Congress so that we're better prepared.
         I guess someone smart once said you go to war with the
    army you have, and next time--next pandemic I'd like a slightly
    better army. And just thank you all for being part of the army
    that we have.
         So, the record here will be open--remain open for 2 weeks
    for additional statements from Members for any additional
    questions that the Committee may ask the witnesses, and the
    witnesses are now excused, and the hearing is adjourned.
         [Whereupon, at 3:04 p.m., the Subcommittee was adjourned.]

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