On March 18, 2020, the U.S. Food and Drug Administration (FDA) issued a new guidance on clinical trials of medical products during the COVID-19 pandemic, which provides general considerations to help sponsors assure the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity during the pandemic.

Notably, COVID-19 screening procedures mandated by a healthcare system in which a clinical trial is being conducted do not need to be reported as an amendment to the protocol, unless the sponsor plans to incorporate the data collected as part of a new research objective. Changes to the protocol or investigational plan to address immediate hazards or to protect the well-being of research participants, such as limiting exposure to COVID-19, may be implemented without institutional review board (IRB) approval or before filing an amendment to an investigational new drug (IND) application or an investigational device exemption (IDE), but must be reported afterwards.

For all clinical trials impacted by the pandemic, the clinical study report (or in a separate document) should describe:

1. Contingency measures implemented to manage study conduct during disruption of the study as a result of COVID-19 control measures.
2. A list of all participants affected by COVID-19-related study disruption by unique subject number identifier and by investigational site, and a description of how the individual's participation was altered.
3. Analyses and corresponding discussions that address the impact of implemented contingency measures (e.g., participant discontinuation from investigational product and/or study, alternative procedures used to collect critical safety and/or efficacy data) on the safety and efficacy results reported for the study.

Recognizing that some protocol modifications or deviations may be required or are unavoidable during the pandemic, the FDA provides a number of general considerations for clinical trial sponsors, including:

• Keep participants informed of changes to the study and monitoring plans.
• Work with clinical investigators and IRBs or independent ethics committees (IECs) to determine whether to continue a study as per protocol or discontinue the use of an investigational product in view of the specific circumstances, including:
  • Ability to conduct appropriate safety monitoring; and
  • Impact on the investigational product supply chain;
• Consider whether to delay some assessments for ongoing trials, or, if the study cannot be properly conducted under the existing protocol; or to stop ongoing recruitment or withdraw trial participants;
• Evaluate feasibility and necessity of alternative methods for safety assessments, such as phone contact, virtual visit, or alternative location for assessment;
• Consider whether additional safety monitoring is needed for trial participants who no longer have access to the investigational product or the investigational site;
• Address statistical analysis plan and how protocol deviations related to COVID-19 will be handled for prespecified analyses before locking clinical trial database;
• Consult with FDA review divisions regarding protocol modifications regarding the collection of efficacy endpoints, such as use of virtual assessments, delays in assessments, and alternative collection of research-specific specimens, if feasible;
• Document changes in study visit schedules, missed visits, patient discontinuations that may lead to missing information as well as basis for failing to obtain efficacy assessments (e.g., COVID-19 restrictions leading to the inability to perform certain protocol-specified assessments); and
• Document specific information in the case report form that explains the basis of the missing data (e.g., missed study visits or study discontinuations due to COVID-19).

Eva F. Yin contributed to the preparation of this Wilson Sonsini alert.