[Federal Register Volume 87, Number 206 (Wednesday, October 26, 2022)]
[Notices]
[Pages 64821-64824]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-23110]


=======================================================================
-----------------------------------------------------------------------

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.

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

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 [email protected] 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 
[email protected].

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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.

[[Page 64824]]

    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