Notice2022-23110
Request for Information; Clinical Research Infrastructure and Emergency Clinical Trials
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
October 26, 2022
Issuing agencies
Science and Technology Policy Office
Abstract
In accordance with the 2022 National Biodefense Strategy for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health Security (National Biodefense Strategy) and the American Pandemic Preparedness Plan (AP3), the White House Office of Science and Technology Policy (OSTP), in partnership with the National Security Council (NSC), is leading efforts to ensure that coordinated and large-scale clinical trials can be efficiently carried out across a range of institutions and sites to address outbreaks of disease and other emergencies. Efforts in this area could include the establishment of a U.S.-level governance structure and outreach to a wide range of institutions, clinical trial networks, and other potential trial sites that can participate in emergency research, both domestically and internationally. A further goal of this emergency clinical trials initiative is to support the expansion of clinical research into underserved communities, and increase diversity among both trial participants and clinical trial investigators. Building U.S. capacity to carry out emergency clinical trials will enlarge and strengthen the U.S. clinical trials infrastructure overall.
Full Text
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<title>Federal Register, Volume 87 Issue 206 (Wednesday, October 26, 2022)</title>
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[Federal Register Volume 87, Number 206 (Wednesday, October 26, 2022)]
[Notices]
[Pages 64821-64824]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-23110]
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OFFICE OF SCIENCE AND TECHNOLOGY POLICY
Request for Information; Clinical Research Infrastructure and
Emergency Clinical Trials
AGENCY: Office of Science and Technology Policy (OSTP).
ACTION: Notice of Request for Information (RFI) on clinical research
infrastructure and emergency clinical trials.
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SUMMARY: In accordance with the 2022 National Biodefense Strategy for
Countering Biological Threats, Enhancing Pandemic Preparedness, and
Achieving Global Health Security (National Biodefense Strategy) and the
American Pandemic Preparedness Plan (AP3), the White House Office of
Science and Technology Policy (OSTP), in partnership with the National
Security Council (NSC), is leading efforts to ensure that coordinated
and large-scale clinical trials can be efficiently carried out across a
range of institutions and sites to address outbreaks of disease and
other emergencies. Efforts in this area could include the establishment
of a U.S.-level governance structure and outreach to a wide range of
institutions, clinical trial networks, and other potential trial sites
that can participate in emergency research, both domestically and
internationally. A further goal of this emergency clinical trials
initiative is to support the expansion of clinical research into
underserved communities, and increase diversity among both trial
participants and clinical trial investigators. Building U.S. capacity
to carry out emergency clinical trials will enlarge and strengthen the
U.S. clinical trials infrastructure overall.
DATES: Interested persons and organizations are invited to submit
comments on or before 5 p.m. ET on December 27, 2022.
ADDRESSES: Interested individuals and organizations should submit
comments electronically to <a href="/cdn-cgi/l/email-protection#acc9c1c9decbc9c2cfd5cfc0c5c2c5cfcdc0d8dec5cdc0dfecc3dfd8dc82c9c3dc82cbc3da"><span class="__cf_email__" data-cfemail="680d050d1a0f0d060b110b040106010b09041c1a0109041b28071b1c18460d0718460f071e">[email protected]</span></a> and
include ``Emergency Clinical Trials RFI'' in the subject line of the
email. Due to time constraints, mailed paper submissions will not be
accepted, and electronic submissions received after the deadline cannot
be ensured to be incorporated or taken into consideration.
Instructions
Response to this RFI is voluntary. Each responding entity
(individual or organization) is requested to submit only one response.
Please feel free to respond to one or as many prompts as you choose.
Please be concise with your submissions, which must not exceed 8
pages in 12-point or larger font, with a page number on each page.
Responses should include the name of the person(s) or organization(s)
filing the comment.
OSTP invites input from all stakeholders, including members of the
public, representing all backgrounds and perspectives. In particular,
OSTP is interested in input from research institutions, clinical
trialists, health care providers interested in clinical research,
contract research organizations (CROs) and other clinical trial service
providers, pharmaceutical and biotechnology companies, and community
health care organizations. Please indicate which of these stakeholder
types, or what other description, best fits you as a respondent. If a
comment is submitted on behalf of an organization, the individual
respondent's role in the organization may also be provided on a
voluntary basis.
Comments containing references, studies, research, and other
empirical data that are not widely published should include copies or
electronic links of the referenced materials. No business proprietary
information, copyrighted information, or personally identifiable
information should be submitted in response to this RFI. Please be
aware that comments submitted in response to this RFI may be posted on
OSTP's website or otherwise released publicly.
In accordance with FAR 15.202(3), responses to this notice are not
offers and cannot be accepted by the Federal Government to form a
binding contract. Additionally, those submitting responses are solely
responsible for all expenses associated with response preparation.
FOR FURTHER INFORMATION CONTACT: For additional information, please
direct questions to Grail Sipes at 202-456-4444 or
<a href="/cdn-cgi/l/email-protection#f59098908792909b968c96999c9b9c96949981879c949986b59a868185db909a85db929a83"><span class="__cf_email__" data-cfemail="adc8c0c8dfcac8c3ced4cec1c4c3c4ceccc1d9dfc4ccc1deedc2ded9dd83c8c2dd83cac2db">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
Background: Currently, the U.S. clinical trials infrastructure is
not well prepared to carry out coordinated, large-scale clinical
research in the event of an outbreak of infectious disease or other
public health emergency. As was seen in the initial stages of the
COVID-19 outbreak, different institutions and networks tend to
implement their own research protocols and capture and store their own
data. The lack of a coordinated approach to clinical trials research in
emergency settings has slowed the development of actionable
information, which has in turn delayed the availability of vaccines,
therapeutics, and diagnostics; and may also impede the tracking of the
outbreaks themselves. Without some mechanism to coordinate and organize
research on a larger scale in an emergency setting, researchers and
decisionmakers are left with a series of relatively small, often
inconclusive studies, and assembling data for larger-scale analysis is
challenging. In addition, and very significantly, our current approach
to clinical research in the emergency setting excludes many patients
and health care providers in underserved areas, and has contributed to
a lack of diversity among clinical trial participants and among the
investigators who lead clinical trials.
The National Biodefense Strategy calls for the U.S. government to
maintain and build upon the domestic clinical trials infrastructure,
with the addition of international sites as appropriate, to ensure
readiness to ``expedite the evaluation of safe and effective vaccines,
therapeutics, and diagnostics for all segments of the population during
a nationally or internationally significant biological incident.'' \1\
In addition, establishing an
[[Page 64822]]
emergency clinical trials governance structure, developing the terms of
an Emergency Master Agreement to accelerate response, and identifying a
network of available sites are among the key goals towards
implementation of AP3.\2\ In line with these provisions, OSTP (in
partnership with the NSC and other EOP components) is leading an effort
to ensure that the U.S. can carry out more coordinated and potentially
larger-scale clinical trials in emergency situations. These emergency
situations could include emerging outbreaks with epidemic or pandemic
potential, even in advance of any declaration of a public health
emergency (PHE) under section 319 of the Public Health Services Act. By
strengthening U.S. capacity to address such outbreaks and other
biological incidents, OSTP's emergency clinical trials effort also aims
to build and enhance U.S. clinical research capacity overall.
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\1\ 2022 National Biodefense Strategy for Countering Biological
Threats, Enhancing Pandemic Preparedness, and Achieving Global
Health Security (October 2022), section 4.1.4.
\2\ First Annual Report on Progress Towards Implementation of
the American Pandemic Preparedness Plan (September 2022), at 22-23.
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We seek comment below on potential governance models for the
emergency clinical trials effort. One possible approach would include a
centralized U.S.-level structure drawing membership from Federal
agencies with relevant expertise. Governance functions might include
determining when coordinated and potentially large-scale clinical
research is needed, including research on countermeasures, to address
outbreaks of disease or other biological incidents. As noted above,
research on an outbreak or incident may sometimes be needed in advance
of any section 319 PHE declaration; we solicit comments below on the
criteria that should be applied to determine when emergency clinical
research may be needed, and how that determination might be
communicated to institutions and clinical trial networks that can
participate in carrying out the research.
Another governance function might be to oversee the development of
emergency clinical trial protocols, in coordination with stakeholders
external to the U.S. government. The trials and other studies needed in
emergency settings could vary in complexity. Some might be relatively
simple studies designed to measure the scope of an outbreak or the
course of a disease, in which the data captured from patients might
overlap to a large extent with the data that would be gathered in the
course of treatment. Other studies, including those designed to
evaluate the efficacy and safety of investigational vaccines,
therapeutics or diagnostics, would be more complex and could require
more or different data elements from those that would be captured in
the course of standard medical treatment. In some cases, study designs
used in connection with prior outbreaks could provide useful models for
developing protocols to address a new emergency. We request comment
below on how a governing entity could best work with stakeholders to
develop emergency clinical trial protocols.
We also seek comment below on how emergency clinical trial data
should be managed to facilitate researchers' access to data and the
analysis of results across a range of participating sites. One
potential model would be to collect data from emergency clinical trials
in a centralized data repository or small set of repositories, with a
central biorepository for biospecimens collected during trials.
In order to ensure that coordinated, large-scale clinical trials
can be carried out in the event of an emergency, OSTP seeks comment on
how best to identify institutions and networks that have an interest in
participating in these studies, and how to create or enhance incentives
for them to participate wherever possible. In particular, OSTP seeks
comment on how to ensure that trial sites in underserved areas are
included, and how to increase diversity both among study participants
and among the investigators who lead trials to completion. We also
solicit feedback below on how to identify an adequate number and
distribution of clinical trial sites, including trial sites located
outside of the U.S. This could include sites that may currently be
affiliated with a U.S.-based trial network, as well as other
international sites. We would appreciate receiving comments on how the
domestic emergency clinical trials effort overall can be designed to
coordinate with international research and preparedness initiatives.
We are aware that in advance of an outbreak or other emergency,
there may be value in having networks and sites begin carrying out
clinical trials to create a ``warm base'' of clinical research
capacity. ``Warm base'' is a term used to refer to studies that not
only gather data under a particular clinical research protocol, but
also serve the function of keeping trial sites in a state of readiness
to undertake additional or future research. ``Warm base'' studies could
address infectious diseases such as influenza, or other medical
conditions that are of interest to researchers and communities, such as
cancer and heart disease.
To participate in a clinical trial, a site needs to have staff
familiar with applicable regulatory requirements and with the
appropriate procedures for collecting data and submitting it to a study
sponsor. When ``warm base'' research is initiated, site staff have an
opportunity to gain familiarity with these procedures. ``Warm base''
research is a way to expand the number of sites that are able to
participate in clinical trial research, which builds U.S. clinical
trial capacity overall while enlarging the network of sites that can be
available to carry out emergency clinical trial research when the need
arises. We request comment below on a variety of issues related to
``warm base'' research, including disease areas that might be targeted
and how ``warm base'' research can be implemented to provide targeted
training for trial sites, as appropriate to staff roles. Given OSTP's
goals of increasing diversity among clinical trial participants and
among investigators, and of increasing capacity for clinical research
in underserved areas, we are particularly interested in how those goals
might be served through the implementation of ``warm base'' research.
In recent emergency settings, we have seen that the launch of
clinical trials across separate institutions or networks can be delayed
by the process of coming to agreement on certain key issues, such as
data sharing and the publication of results. We seek comment below on
the possibility of developing a framework of key terms that can be
developed in advance of an emergency and integrated into clinical trial
agreements for emergency clinical trials when needed. For purposes of
this RFI, we refer to such a framework as an ``Emergency Master
Agreement.'' The goal of an Emergency Master Agreement would be to
shorten the time it takes to get emergency clinical trial research
started across a range of sites, by facilitating agreement on key terms
in advance. Certain basic terms could be relevant for any coordinated
or large-scale emergency clinical trial, such as provisions that allow
data gathered under common protocols from a range of sites to be
collected and made readily accessible to researchers beyond the
institutions where the trial was conducted. Other basic terms might
include central management of biospecimens and the use of a single
Institutional Review Board (IRB). In addition to these basic, core
terms, an Emergency Master Agreement could include additional terms
that might only be needed for certain types of study protocols (e.g.,
if an investigational
[[Page 64823]]
agent is being tested). We solicit input below on a range of issues
related to the potential creation of an Emergency Master Agreement.
From a technical perspective, OSTP is also seeking input on how
best to operationalize both protocol distribution and data capture in a
forthcoming RFI.
Information Requested: Respondents may provide information for one
or as many topics below as they choose.
1. Governance for emergency clinical trials response.
a. Descriptions of models that could be used to establish a U.S.-
level governance structure for emergency clinical trials. As noted
above, one possible approach would be a centralized U.S.-level
structure drawing membership from Federal agencies with relevant
expertise.
b. Criteria that should be applied in determining when coordinated
and potentially large-scale clinical research is needed to address an
outbreak of disease or other biological incident, including signals or
indicators that should be taken into account.
c. Once a need for emergency clinical research is determined,
factors relating to the outbreak or incident (e.g., scope, location,
severity) that should be considered in determining what types of
studies are needed.
d. Methods for communicating the decision to begin emergency
clinical research to institutions and clinical trial networks that can
participate in carrying out the research.
e. Mechanisms for tracking institutions, networks and sites that
might be able to participate in emergency research, to ensure adequate
potential for enrollment and adequate geographic coverage, domestically
and internationally.
i. Criteria for establishing a target number and location of sites
needed to support clinical trials in case of emergency.
f. Procedures whereby the U.S. Government, together with external
stakeholders, could oversee the development of clinical trial protocols
and, where appropriate, the selection of investigational agents. It
would be particularly helpful to get input on whether there is a role
for public-private partnerships in this context.
g. Best practices, including ``quality by design'' principles, for
designing trials so that they capture the data needed without
unnecessary complexity that can complicate execution.
h. Best practices for designing trials that can enroll vulnerable
populations, such as the pediatric population, as needed in particular
circumstances.
i. Optimal ways to manage interactions with domestic and
international regulatory bodies.
j. Appropriate entities to handle projecting and tracking
enrollment at study sites, monitoring the progress of clinical trials,
and data management; whether existing entities could be engaged or
adapted to carry out these functions for coordinated, large-scale
emergency clinical trials.
k. Appropriate ways to structure a data repository and a
biorepository for emergency clinical trial data and specimens. As noted
above, one potential model would be to collect data and biospecimens in
centralized repositories. We would also appreciate input on whether
existing entities could be engaged or adapted to handle these
repository functions.
l. Criteria that should be applied to govern researchers' access to
emergency clinical trial research data.
2. Identifying and Incentivizing Research Institutions and
Networks; Building Diversity and Equity.
a. Methods for identifying institutions and sites that may have an
existing interest in or familiarity with emergency clinical trial
research. This might include those that currently receive government
funding, those with a focus on infectious disease research, and/or
those that have worked with CROs.
b. Effective ways to increase diversity among study participants
and investigators, and to expand clinical research sites into
underserved areas. It would be helpful to get input on whether and how
the following approaches could be useful:
i. Community outreach.
ii. Use of decentralized clinical trial (DCT) design elements, or
other innovative approaches such as trials conducted at the point of
care.
iii. Use of technological innovations, such as digital health
technologies (DHTs), that would allow remote participation or otherwise
limit the need for participants to travel.
iv. Building on existing programs that target diversity in clinical
research, including initiatives within research institutions and
public-private collaborations.
v. Leveraging the networks and community access of retail chains,
including retail pharmacy chains.
vi. Leveraging community-based care networks such as Practice-Based
Research Networks (PBRNs) and Federally Qualified Health Centers
(FQHCs).
c. Incentives that can be identified or enhanced to encourage
participation in emergency clinical trial research.
i. As described above and in the forthcoming RFI on data capture
for Emergency Clinical Trials and Data Collection Pilot, we are seeking
information on how to create a pilot program enabling clinical trial
data collection across a wide variety of trial sites that is easy for
health care providers to use and can be scaled up for use in emergency
research settings. It would be helpful to receive comments on whether
the opportunity to participate in such a pilot could create an
incentive for institutions and sites to participate in emergency
clinical research studies.
d. Once interested institutions or networks are identified,
i. Effective ways to recognize and communicate their commitment to
emergency clinical research to the health care community and to the
public.
ii. Information that should be collected from interested sites, for
example by means of a short questionnaire to assess characteristics of
patient population, level of training that would be required, etc.
e. The best ways to provide training in clinical trial practice
(including regulatory requirements such as Good Clinical Practice
(GCP)) where needed, targeted as appropriate to staffs' roles,
including staff at sites that may not have participated in clinical
trials previously.
3. ``Warm Base'' Research.
a. Disease areas that should be targeted in protocols for ``warm
base'' clinical research. It would be helpful to get comments on:
i. Disease areas that are most relevant to communities, including
underserved communities and those that may have little experience with
participating in clinical research.
ii. The extent to which ``warm base'' research should target
infectious disease, versus other conditions such as cancer, heart
disease, or rare disease; and the size or scope of site networks that
would be needed to study various conditions.
b. How ``warm base'' research could best be implemented to provide
training to sites that are inexperienced with clinical trial research,
and to create a basic level of surge capacity at the staff level for
emergency clinical trial research. We would appreciate input on other
training mechanisms that could be used as well.
c. Whether ``warm base'' research could be appropriately supported
as
i. A demonstration project with commercial partnership.
ii. A public-private partnership.
iii. An agency-funded program.
4. Emergency Master Agreement.
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a. Basic terms that might form part of an Emergency Master
Agreement, including the following.
i. Data collection and use, including ownership of the study data
and biospecimens; entities that have the right to collect, store, and
use the data and specimens; banking of biospecimens for further
research.
ii. Publication/accessibility of trial data, including availability
of data prior to publication and publication rights.
iii. Use of a single IRB across all participating trial sites. As a
related point, it would be helpful to get feedback on whether an IRB
should be established that is primarily devoted to emergency clinical
trials.
b. Additional terms for an Emergency Master Agreement that could be
added or modified depending on the complexity of the protocol, and on
other factors such as whether a private sector sponsor or an
investigational agent is involved. It would be helpful to have input on
terms such as the following:
i. Confidentiality.
ii. Patents/intellectual property.
iii. Control of study drug.
iv. Indemnification.
v. Compensation for injury.
c. The best ways to get the input of research institutions,
clinical researchers, community groups, and other key stakeholders on
the content of Emergency Master Agreement terms.
d. Approaches to facilitating stakeholders' understanding and
adoption of the Emergency Master Agreement framework.
i. Any models for such adoption in related areas, such as the NCATS
SMART IRB Platform.
5. Identifying viable technical strategies for data capture;
gathering information about a potential data capture pilot. This topic
will be the subject of a separate RFI on data capture.
6. International coordination and capacity.
a. Designing the overall domestic emergency clinical trials effort
in a way that coordinates with international clinical research efforts.
It would be helpful to receive comments on how to facilitate the
participation of foreign-run clinical trial networks and other foreign
bodies in coordinated, large-scale emergency clinical trial protocols
initiated by the U.S.
b. Methods for identifying international sites that might be
available to participate in emergency clinical trials, including
international sites associated with U.S.-run networks as well as
foreign-run international sites.
c. Overcoming regulatory barriers that delay expansion of U.S.
trials into international sites, or otherwise interfere with clinical
research across borders.
d. The best way to track the clinical trial research initiatives
being pursued under the G7 Trials Charter and Quad leaders' commitment
to pandemic preparedness, and to harmonize U.S. emergency clinical
trials efforts with these international initiatives.
Dated: October 19, 2022.
Stacy Murphy,
Operations Manager.
[FR Doc. 2022-23110 Filed 10-25-22; 8:45 am]
BILLING CODE 3270-F1-P
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