FDA recently issued a draft guidance document on “Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices” . The FDA guidance provides recommendations for sponsors, clinical investigators, and Institutional Review Boards (IRBs) on defining, identifying, and reporting protocol deviations in clinical investigations. While FDA regulations do not explicitly define protocol deviations or classify them, this guidance aims to establish consistent classification, reporting, and documentation practices to improve data interpretation and regulatory compliance.
Protocol deviations generally occur unintentionally but may also be planned under rare circumstances with prior approval. The guidance aligns with the International Council for Harmonization (ICH) E3(R1) definitions and provides further clarity on reporting obligations. Key recommendations include defining protocol deviations and distinguishing important deviations that could impact data reliability, participant safety, or regulatory assessments. The guidance outlines which deviations sponsors should report to the FDA, which investigators should report to sponsors and IRBs, and how IRBs should evaluate deviations. To minimize deviations, sponsors are encouraged to design studies with flexible enrollment criteria, streamlined study designs, remote assessments, and reasonable timeframes for data collection.
Read the full guidance here.
