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Nov 22 -- Comment period extended to January 27, 2023. https://www.federalregister.gov/d/2022-25163

Oct 26 -- 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.

Interested persons and organizations are invited to submit comments on or before 5 p.m. ET on December 27, 2022.

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 2022 National Biodefense Strategy for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health Security (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.” In addition, establishing an 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 the American Pandemic Preparedness Plan (AP3). 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.

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 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.

Respondents may provide information for one or as many topics below as they choose. . . .
FRN: https://www.federalregister.gov/d/2022-23110  Correction https://www.federalregister.gov/d/2022-24666
OSTP blog: https://www.whitehouse.gov/ostp/news-updates/2022/10/25/ostp-and-nsc-seek-input-on-u-s-capacity-for-emergency-clinical-trials-research/
OSTP blog (10.31.22): OSTP, in Partnership with ONC, Seeks Input on Optimizing Data Capture for Clinical Trials

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