A retrospective audit to analyze protocol deviations that occurred in regulatory clinical trials at a tertiary referral center in India

Abstract Context: Protocol deviations (PDs) are not uncommon in clinical trials (CTs) and understanding their nature can help mitigate their occurrence. Aims: To audit PDs in archived regulatory CTs conducted at a single research department over a 25-year period. Subjects and Methods: We included archived regulatory CTs and excluded ongoing studies and academic studies. Data were extracted from trial master files and PD forms filed with the Institutional Ethics Committee. PDs were categorized by type, category, and whether corrective and preventive actions (CAPAs) were taken. Statistical Analysis: Both descriptive and inferential statistics were applied to the data. Chi-square tests compared PD frequencies between pandemic and nonpandemic periods and content analysis was used for qualitative categorization. Results: A total of 21 regulatory CTs yielded 526 PDs, of which 85.2% were minor and 14.8% were major, respectively. The majority (42%) related to follow-up visits beyond the allowed window, and 37% to sample collection, processing, and storage. Only 0.8% were consent-related. There was a significant increase in PDs during the coronavirus disease 2019 (COVID-19) pandemic ( P < 0.00001), with 85% of PDs in six trials attributed to pandemic-related disruptions. The most frequent CAPA was re-counselling participants (39%). Conclusions: Most PDs were minor and manageable, but the COVID-19 pandemic led to a significant rise in deviations.