Following up on 2013 guidance, the FDA has issued a new question-and-answer guidance with additional recommendations for trial monitoring approaches, monitoring plan content and follow-up/communication of issues caught through risk-based monitoring.

The 13-page final guidance rehashes FDA’s expectations that sponsors use a risk-based approach to developing and revising trial monitoring plans to ensure data integrity and participant protections, then delves into a number of Q&As on implementing risk-based monitoring and communicating and pursuing identified issues.

For example, the guidance directs sponsors on how to address and share serious issues their monitoring systems catch. The guidance advises sponsors to evaluate issues in depth, in a timely fashion, at the appropriate level (such as the sponsor or site level) and according to the trial’s monitoring plan, with a prompt root cause analysis followed by appropriate corrective and preventive actions (CAPA).

In addition, the guidance advises that the risk assessment and monitoring plan should be reevaluated and revised as needed to reduce or eliminate the chance of an issue recurring. Sponsors should document and share any significant issues uncovered through monitoring — as well as their respective CAPAs — with the appropriate parties, the guidance says.

The guidance also expands on the content for monitoring plans beyond the 2013 guidance, advising that sponsors include:

• A description of the trial design, including blinding and randomization procedures if applicable;
• Processes for confirming randomization is done per the protocol and investigational plans;
• Sampling plans used to identify specific records and data that will be monitored, including rationale and implementation strategy;
• A description of the types of issues identified through monitoring that would be immediately escalated; and
• An approach for determining whether a significant issue identified at one site may be present at other sites and whether the finding suggests a systemic-level problem with the protocol or associated trial plans that needs to be addressed.

Read the guidance here: https://bit.ly/30VaGE8.