On March 27, 2020, the U.S. Food & Drug Administration (“FDA”) updated its prior guidance on the “Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic,” with an appendix adding a series of questions and answers (“Q&A”). The original guidance, issued on March 18, 2020, outlined important considerations for assuring the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity during the COVID-19 pandemic, as outlined in our prior alert.
Key takeaways from the new Q&A are as follows:
- In determining whether to start a trial, a sponsor should consider whether initiation of the trial could interfere with public health measures implemented by federal and state authorities to control the COVID-19 pandemic. While the original FDA guidance and this update focus on trial participant health and safety, here the FDA also appears to be taking into account how the conduct of trials relate to broader efforts to combat COVID-19, including social distancing advisories and the allocation of scarce resources.
- In determining whether to continue the conduct of a trial, a sponsor should consider the assessment by the trial’s data monitoring committee (“DMC”) (if one has been established) of the impact of proposed protocol modifications on patient safety.
- In determining whether participants should continue to use an investigational product, a sponsor should consider risks and benefits on an individual participant basis, including whether a participant appears to be benefitting from the investigational product, whether there are reasonable alternative treatments, the seriousness of the participant’s disease or condition, and the risks involved in switching to an alternative treatment if necessary. After discussion with the relevant FDA review division, the sponsor should consider amending the protocol to limit investigational product use to those participants with apparent benefit. The Q&A does not specifically address assessment of individual clinical benefits in the context of blinded studies or return of individual results in-study; however, any considerations involving unblinding and return of results should be made in consultation with the FDA and in compliance with requirements of the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
- For clinical trials conducted under an Investigational New Drug (“IND”) application, FDA clarified that pausing enrollment to decrease potential exposure to COVID-19 generally would not necessitate a protocol amendment. The Q&A also includes a suggested format for formal IND amendments, if needed, related to the COVID-19 pandemic.
- For clinical trials conducted under an Investigational Device Exemption (“IDE”), FDA has indicated some flexibility for those modifications normally requiring notice to the FDA within 5 working days of implementation. FDA acknowledges that notice within that window may be difficult and allows for consolidating implemented changes when submitting notices and updating the IDE as soon as possible. The Q&A also includes a suggested format for formal IDE supplements, if needed, related to the COVID-19 pandemic.
- If investigational products are normally dispensed at a pharmacy for at-home administration, direct-to-participant shipping may be possible, subject to FDA storage and accountability requirements. If these changes will be required for all participants, the protocol should be amended to reflect direct-to-participant delivery, but if changes will be for only certain participants, documentation of a protocol deviation may be sufficient. We would note that direct-to-participant shipping may raise state licensure issues and, for drug products, can also implicate DEA and state controlled substances requirements, depending on the type of compound.
- If investigational products are normally infused at the clinical trial site, any change of setting should only be made in consultation with the applicable FDA review division, as noted in the original guidance. FDA strongly advises consultation for complex investigational products (e.g. cellular therapy and gene therapy products) where potentially altered storage and handling conditions could adversely affect product stability.
- If researchers need to obtain informed consent from patients in COVID-19 isolation, the guidance provides for alternative methods of obtaining consent and documenting that consent, without risking the health or safety of study staff. Procedures for consent remain available under 21 CFR 50.23 (for life-threatening situations) or 21 CFR 50.24 (for emergency research). For electronic consent, 21 C.F.R. Part 11 requirements also need to be considered.
We expect that additional questions on conducting clinical trials during the COVID-19 pandemic will arise in the coming weeks and months. The FDA intends to update the Q&A to assist investigators, IRBs, and sponsors grappling with these difficult decisions. For assistance, please contact your regular Verrill attorney.