A protocol deviation represents any instance where trial conduct does not conform to the approved protocol requirements. These departures from the protocol may range from minor administrative variations, such as a visit occurring slightly outside the specified window, to significant violations that may compromise participant safety or data integrity. Understanding and properly managing protocol deviations is essential for maintaining the scientific and ethical integrity of clinical trials.

Protocol deviations may result from various causes, including site error, participant non-compliance, system failures, or circumstances beyond anyone's control. Some deviations occur proactively to protect participant safety when following the protocol would pose unacceptable risk; the protocol itself typically authorizes such departures without requiring prior approval when immediate action is necessary. Other deviations represent failures to follow required procedures and may indicate inadequate training, insufficient resources, or protocol requirements that are impractical to implement.

The management of protocol deviations involves detection, documentation, assessment, reporting, and corrective action. Sites must have systems in place to identify deviations promptly and document them completely. Each deviation must be assessed to determine its impact on participant safety, data integrity, and overall trial validity. Significant deviations require reporting to the sponsor, IRB/IEC, and potentially regulatory authorities. Perhaps most importantly, the root causes of deviations must be analyzed and addressed through corrective and preventive actions to reduce the likelihood of recurrence.