How Should The US Government Coordinate Emergency Clinical Trials?
Executive Summary
Research institutions, CROs, biopharma industry and other stakeholders are asked to comment on potential governance structure that would determine when trials are needed to address disease outbreaks and other public health emergencies.
Concerned about the lack of coordination in conducting clinical trials in emergency situations, the US government is seeking to establish a governance structure to ensure large-scale studies can be carried out across a range of institutions and sites to address outbreaks of disease and other emergencies.
The White House Office of Science and Technology Policy, in partnership with the National Security Council, is leading this effort. The OSTP is seeking input from research institutions, clinical trialists, health care providers, contract research organization, pharmaceutical and biotechnology companies and other stakeholders on potential governance models and how to identify institutions and networks that are interested in participating in these studies.
The ambitious idea has no shortage of inspiration from the troubles in data collection during the COVID-19 pandemic, from early debates about the utility of chloroquine, to the shambolic rollout of convalescent plasma, and now lingering questions about how best to use Paxlovid.
US regulators are well aware of the challenges, and hope to be able to duplicate the successes of the UK’s RECOVERY trial the next time that kind of effort is needed. (Also see "US Needed Simple Pragmatic COVID-19 Trial For Repurposing Candidates, Woodcock Says" - Pink Sheet, 18 Mar, 2021.)
“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,” OSTP stated in a notice of request for information published in the Federal Register last month. “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.”
But while the Biden administration wants to focus improving the response for the next potential pandemic, Congress and the public seems like they just want to move on, and funding for new systems is going to be difficult to secure. (Also see "Next-Gen COVID Vaccines Could Be Awesome – If They Ever Get Made" - Pink Sheet, 6 Sep, 2022.)
“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,” OSTP said.
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 that make it challenging to assemble data for larger-scale analysis, OSTP said. The current approach also excludes many patients and healthcare providers in underserved areas and has contributed to a lack of diversity in clinical trial participants and investigators leading the trials.
OSTP said one potential governance model would include a centralized US-level structure with members from federal agencies. The structure might determine when coordinated and large-scale clinical research is needed to address outbreaks of disease or other biological incidents and oversee the development of emergency clinical trial protocols, OSTP stated.
The office asks stakeholders to comment on the criteria for determining when emergency clinical research may be needed, how a governing entity could work with stakeholders to develop trial protocols, and how trial data should be managed to facilitate researchers’ assess to the data and the analysis of results across participating sites.
On the latter point, OSTP said one potential model would be to collect data in a centralized data repository or small set of repositories, with a central biorepository for biospecimens collected during trials.
‘Warm Base’ Clinical Research, Emergency Master Agreement
OSTP said that it might be of value to have networks and sites begin carrying out clinical trials in advance of an outbreak or other emergency to create a “warm base” of clinical research capacity. The office noted that “warm base” refers to studies that gather data under a particular research protocol and also keeps trial sites ready to undertake additional or future research.
The “warm base” concept has also been discussed for ensuring emergency production capacity and seems to have gotten a bit more traction in that area when positioned as effort to re-shore manufacturing jobs. (Also see "US Senate Measure Highlights ‘Warm-Base’ Manufacturing Capacity For Next Pandemic Response" - Pink Sheet, 27 Jan, 2022.)
Stakeholders are asked to comment on disease areas that might be targeted in protocols for “warm base” clinical research. They are also asked how “warm base” research can be implemented to provide training to sites that are inexperienced with clinical trial research, increase diversity among trial participants and investigators, and increase capacity for clinical research in underserved areas.
They are also asked to weigh in on the possibility of developing a framework of key terms that can be integrated into clinical trial agreements for emergency trials. OSTP said the goal of this framework, called an “Emergency Master Agreement,” would be to shorten the time to initiate clinical trial research across a range of sites by facilitating agreement on key terms in advance.
OSTP said such terms could include: data collection and use, including ownership of the study data and biospecimens; publication/accessibility of trial data; and use of a single institutional review board (IRB). OSTP said it would be helpful to get feedback on whether an IRB that is primarily devoted to emergency clinical trials should be established.
The notice says it would also be helpful for stakeholders to comment 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 US.
Data Collection Pilot
OSTP issued a separate notice of request for information on data collection for emergency clinical trials and how to create an interoperability pilot program enabling clinical data collection across a wide variety of trial sites that is easy for health care providers to use.
The office said it seeks input on viable technical strategies to distribute clinical trial protocols and capture trial data using common Health Level 7 (HL7) Fast Healthcare Interoperability Resources-based application programming interfaces in the pre-emergency phase as well as in an emergency setting.
“We seek comment on how to build towards both of these goals in a data capture pilot or demonstration project,” OSTP said. “This pilot, if implemented, could provide training for sites in underserved communities, thereby enlarging and strengthening the overall clinical trials infrastructure.”
The notice asks stakeholders to comment on a hypothetical use case scenario and how much of it could be operationalized in a pilot or demonstration project.
In this scenario, a US-level governing entity would oversee development of a clinical trial protocol for broad distribution across clinical trial networks and sites. Study sites would enroll participants in the trial. Clinical trial data would be sent to the trial sponsor through an electronic case report and to a central data repository or small set of data repositories for researchers to analyze.
Comments on both requests for information are due by 27 December.