Clinical trials are designed to evaluate the efficacy, safety, or other characteristics associated with medical products. Trials are usually complex and require a large group of professionals to follow a clinical trial protocol, standard operating procedures, and study-specific manuals, guidelines, and plans. Clinical trial protocols prospectively describe the background and rationale for conducting the trial, the objectives of the trial, the trial design, the equipment to be used, the procedures to be performed, and the statistical methods on how the trial data are to be analyzed. Deviations from the protocol can result in harm to subjects, biased or inaccurate results, and possible rejection of all or part of the trial data by the sponsor or regulatory authorities. Despite preventive efforts, protocol deviations are likely to occur in most trials. This position paper proposes a common definition of protocol deviations and recommends best practices for their detection, classification, and management as part of their life cycle, with a goal of reducing their impact on subject safety and data integrity. The information contained herein is drawn globally from industry experts within the DIA Good Clinical Practice and Quality Assurance community, an industry-wide survey, and presentations with discussions at various industry meetings.
Keywords: corrective action; corrective action preventive action; departure; deviation; fraud; good clinical practice; noncompliance; preventive action; professional misconduct; protocol deviations; protocol violations; serious breach; variance; violation; waiver.