The FDA has issued a guidance regarding clinical trials during the Coronavirus disease 2019 pandemic in recognition of the challenges that may impact standard clinical trial procedures. The guidance acts as a set of recommendations to maintain the safety of patients enrolled onto trials and the trial’s integrity.
The FDA has issued a guidance regarding clinical trials during the Coronavirus disease 2019 (COVID-19) pandemic in recognition of the challenges that may impact standard clinical trial procedures. The guidance acts as a set of recommendations to maintain the safety of patients enrolled onto trials and the trial’s integrity.
The agency suggested in the guidance that the pandemic is likely to create obstacles for many trials’ set protocols, but trial modifications must be made to ensure the safety of all trial participants.
“With this guidance issued, the FDA is helping industry and investigators navigate the COVID-19 pandemic and help assess how to move forward with critical clinical trials,” Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs, said in a statement.2“The FDA released this guidance to emphasize that at all times, patients’ safety should continue to be at the forefront of considerations. We want to support the continuance of these clinical trials in compliance with good clinical practice and minimizing risks to trial integrity, while also safeguarding the health and well-being of study participants.”
Sponsors are encouraged to consider patients’ safety when making determinations about trial recruitment and continued participation and drug administration. Changes to the conduct of each trial and the participation of its patients depend on the various circumstances of the trial, including the nature of the disease being studied and the drug being administered, potential changes in the product’s supply chain, the regions where the trial is conducted, and more.
The FDA urged sponsors to engage with institutional review boards and independent ethics committees on all urgent changes necessary due to COVID-19, especially in relation to efficacy end points. Sponsors need to be able to explain why the protocol changes are needed and how any patients are impacted. Life-saving measures could be implemented without prior approval, although reporting these incidents to the agency is required.
Standard monitoring proceduresincluding in-person visits with trial investigators—may no longer be feasible for many patients. Sponsors should consider alternative monitoring methods, such as virtual visits, switching to local lab or imaging centers, and using remote monitoring programs if possible and advisable for the patients’ safety. This may, however, result in missing information; reasons for such missing data should be defined in the case reports.
The FDA recommended alerting the FDA review division of changes in protocol that may result in modified statistical analyses and provide explanation for how deviations will be handled in the analyses.
Alternative methods of administering the investigational products, such as by home nursing aids or at alternative local sites, should also be considered in the case of disrupted patient visits.
All sponsors, investigators, and review boards should establish, implement, and revise where necessary, policies explaining how participants will be protected and how the study will continue with possible COVID-19related disruptions at study sites. Such policies and procedures may relate to data collection, patient monitoring, adverse-event reporting, staff changes due to quarantine measures or illnesses, informed consent, and more.
For any trial affected by the pandemic, study reports should include notes of all contingency measures put in place to maintain the trial, a list of participants affected by changes related to COVID-19 disruptions, and analyses addressing how changes made to the trial impact the trial’s safety and efficacy results.
Impacts on the trial’s integrity should be minimized where possible, but necessary protocol deviations must still be made and documented where unavoidable.
Although FDA guidance documents usually have an initial public comment period, the FDA issued the guidance to go into effect immediately upon its publication and determined that prior comments were not appropriate in this case. Subsequent comments, however, are being accepted.