FDA unveils guidance for Covid-19 trials
The FDA on Wednesday issued new final guidance to help sponsors assure the safety of trial participants, maintain compliance with good clinical practice (GCP) and minimize the risks to trial integrity during the Covid-19 pandemic.
The guidance comes as the National Institutes of Health last week initiated the first Covid-19 vaccine Phase 1 trial in Seattle. Sanofi and Regeneron Pharmaceuticals also announced on Monday they have started a Phase 2/3 trial at medical centers in New York evaluating the IL-6 targeted Kevzara (sarilumab) in patients hospitalized with severe Covid-19.
In addition, Gilead has initiated two Phase 3 studies at sites across Asia to evaluate the safety and efficacy of the antiviral remdesivir in adults diagnosed with Covid-19, as well as in Nebraska, while Eusa Pharma said Wednesday that it initiated a study at a hospital in Bergamo, Italy for siltuximab, another IL-6 targeted monoclonal antibody, for the treatment of patients with Covid-19 who have developed serious respiratory complications.
FDA Guidance Details
While recognizing that protocol modifications may be required, and that there may be unavoidable protocol deviations due to Covid-19 illness and/or Covid-19 control measures, FDA urges sponsors and clinical investigators to engage with Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs) “as early as possible when urgent or emergent changes to the protocol or informed consent are anticipated as a result of COVID-19.”
But FDA also says that such changes to the protocol or investigational plan to minimize or eliminate immediate hazards or to protect the life and well-being of research participants (e.g., to limit exposure to Covid-19) “may be implemented without IRB approval or before filing an amendment to the IND or IDE, but are required to be reported afterwards.”
David Borasky, VP of IRB Compliance at WCG, said in a webinar on Covid-19 trials on Wednesday that IRBs want to know about changes as soon as possible and hope that they’ll be reported within five days, but they understand the circumstances.
He added that IRBs should not be a roadblock to making changes that are essential to maintaining research that is ethically appropriate, maximizes the safety of study participants and research teams, scientifically valid and compliant with the regulations.
As far as efficacy assessments, FDA’s guidance “recommends consultation with the appropriate review division regarding protocol modifications for the collection of efficacy endpoints, such as use of virtual assessments, delays in assessments, and alternative collection of research-specific specimens, if feasible. For individual instances where efficacy endpoints are not collected, the reasons for failing to obtain the efficacy assessment should be documented (e.g., identifying the specific limitation imposed by COVID-19 leading to the inability to perform the protocol-specified assessment).”
And prior to locking the database, the 9-page guidance says sponsors should use its statistical analysis plan to address how protocol deviations related to Covid-19 will be handled for the prespecified analyses.
In addition, the guidance adds that sponsors and clinical investigators should document how Covid-19-related restrictions led to changes in study conduct and the duration of those changes, as well as indicating which trial participants were impacted and how those trial participants were impacted.
“Sponsors, in consultation with clinical investigators and, may determine that the protection of a participant’s safety, welfare, and rights is best served by continuing a study participant in the trial as per the protocol or by discontinuing the administration or use of the investigational product or even participation in the trial. Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring, the potential impact on the investigational product supply chain, and the nature of the disease under study in the trial,” the guidance adds.
Difficulties in getting prospective patients to trial sites also mean that sponsors should evaluate whether alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for assessment, including local labs or imaging centers) could be implemented when necessary and feasible, and would be sufficient to assure the safety of trial participants, FDA says.
“COVID-19 screening procedures that may be mandated by the health care system in which a clinical trial is being conducted do not need to be reported as an amendment to the protocol even if done during clinical study visits unless the sponsor is incorporating the data collected as part of a new research objective,” the guidance adds.
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RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.