On March 18, the U.S. Food and Drug Administration (FDA) issued a final guidance titled FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic, providing important guidance for industry, investigators and institutional review boards on conducting clinical trials amidst the pandemic. The guidance, finalized without a public consultation period, describes FDA’s recognition of likely disruptions to clinical trials due to the pandemic and acknowledges that deviations from protocols will thus occur. It provides FDA’s current thinking on ways to mitigate the risks posed by these disruptions, focusing on patient safety, good clinical practice and trial integrity. The guidance is applicable to all medical products (human drugs, biologics, and medical devices) undergoing clinical trials, including those being developed to prevent or treat COVID-19, and gives recommendations for both ongoing trials and trials for which procedures are not yet established. In recent days, other agencies have also released guidance on clinical studies impacted by COVID-19, including the National Institutes for Health (NIH) and the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA).
FDA recognizes that due to COVID-19, there may be a number of challenges during clinical trial progress, such as quarantines, travel restrictions, supply chain interruptions, infection of trial subjects, and the possibility of resulting protocol modifications and deviations. The guidance emphasizes that patient safety remains paramount. Thus, specifics of each trial – patient conditions, nature of the product – will inform case-by-case decisions related to, for example, discontinuing trial participation. Notably, somewhat general provisions are given to make protocol changes to protect patient safety without Institutional Review Board (IRB) approval or before filing an Investigational New Drug (IND) or Investigational Device Exemption (IDE) amendment.
It also notes the need for robust documentation and justification of contingency plans and protocol deviations, and specific explanations for missing data, particularly those linked to COVID-19. Further, this guidance, like the NIH and MHRA guidance, highlights the opportunity and potential importance of digital means to gather clinical trial information recognizing alternative methods of virtual visits or assessments in safety monitoring and collection of efficacy endpoints.
Given the large number of clinical trials currently underway, including international multi-center clinical trials (with more than 100 trials on COVID-19 related medical products alone), the guidance is an important indication of FDA’s relative flexibility in working with sponsors to manage complex trials that may be impacted by the pandemic to ensure patient safety. However, the guidance is vague regarding regulatory impacts of significant changes or missing data in a trial. Thus, trial sponsors would benefit from proactively identifying and prioritizing risks, developing contingency plans, and discussing these with FDA as early as possible. This would include reviewing and/or conducting risk assessments and considering potential COVID-19 related disruptions within the context of study specifics (e.g., patient demographics, study sites, nature of investigational product). To assist study sponsors and regulators in understanding gaps and potentially reducing risk, study investigators will need to provide and plan for comprehensive documentation and data related to disruptions. If digital data gathering is used, then plans should include consideration of patient data protection and privacy, as well as current FDA expectations for use of software in collecting patient information.
