July 1, 2020 PAP-Q2-20-NI-005
The COVID-19 outbreak has increased the responsibilities of clinical trials sponsors to ensure the safety of trials participants and staff, while the public health response, supply chain disruptions, and ongoing mosaic of broader impacts — including quarantines, site closures, and travel limitations — have created additional barriers to the execution of trials. To help clinical trial sponsors, investigators, logistics companies, institutional review boards/independent ethics committees (IRBs/ IECs), and other stakeholders to make rapid and informed decisions about their ongoing trials, the U.S. Food and Drug Administration (FDA) released the FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency.1 The guidance was first implemented in March 2020, without the usual process of prior public participation, owing to the exigency of the need for an immediate response on behalf of the agency, and was updated in early June.
The guidance implores stakeholders to focus on the safety, welfare, and rights of clinical trial participants by determining whether their needs are best served through continued participation in a given trial or by delaying or discontinuing enrollment and/or participation. These decisions must be made on a case-by-case basis, factoring in the nature of the disease under study and that of the investigational product, the ability to ensure safety, and further supply chain considerations.
For trials that are deemed critical and appropriate to continue, the FDA recommends modifying study conduct according to best practices. Traditional, centralized trial models may not be feasible during the pandemic, as travel restrictions may prevent participants from visiting an investigational site for treatment or monitoring, and sites may not be responsibly equipped to guarantee protection of patients and staff from exposure to SARS-CoV-2. The agency recommends that sponsors evaluate alternative protocols and consider virtual trials models that limit or avoid in-person visits to trial sites, including phone contact, alternative locations for assessment (e.g., local labs), direct-to-patient (DTP) treatment and direct-from-patient (DFP) sampling and monitoring, provided that these methods enhance, rather than reduce, the assurance of the safety of trial participants. In some cases, the transition from traditional to alternative methods for the delivery of investigational products may require consultation with the FDA for further guidance and approval.
Since changes to protocols generally require review and approval by relevant IRBs/IECs, the guidance urges sponsors and clinical investigators to be proactive and to consult with IRBs/ IECs as early as possible to ensure consensus approval of any modifications to protocols. Exigent changes that must be enacted to prevent immediate hazards to patients can be implemented without board approval, but these changes must still be reported afterward.
The guidance further recognizes that the various disruptions to schedules and patient visits may, in some cases, result in the loss of specific data, including assessments of efficacy endpoints, that would typically be required for proper evaluation of a clinical trial, and the agency urges investigators to document missing data and the basis for their absence in all cases.
IIn this guidance, the FDA wisely synthesized concrete recommendations for best practices for clinical trials during the COVID-19 pandemic with pragmatic acknowledgments that individual trials and patients — and challenges not yet foreseen — may require a tolerance for changes that would potentially invalidate the legitimacy of clinical trials under other circumstances, along with proactive recommendations for documentation and transparency about changes to or deviations from protocols that may be unavoidable. It is too early to say how significant the disruptions caused by SARS-CoV-2 will be to the power of the data generated in ongoing trials, but the FDA is striving to minimize negative outcomes..
David is Scientific Editor in Chief of the Pharma’s Almanac content enterprise, responsible for directing and generating industry, scientific and research-based content, including client-owned strategic content, in addition to serving as Scientific Research Director for That's Nice. Before joining That’s Nice, David served as a scientific editor for the multidisciplinary scientific journal Annals of the New York Academy of Sciences. He received a B.A. in Biology from New York University in 1999 and a Ph.D. in Genetics and Development from Columbia University in 2008.