[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
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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.]
[all]