Preventability, predictability, severity, and causality analysis of serious adverse events reported to the institute ethics committee of a tertiary health care center in central India: A retrospective study

Abstract Background: Serious adverse events (SAEs) are critical safety indicators in clinical trials, necessitating multidimensional evaluation beyond conventional causality assessment. Objective: The objective of this study was to analyze SAEs reported to the institute ethics committee of a tertiary healthcare center for preventability, predictability, severity, and causality using standardized tools. Methodology: This retrospective analysis included 133 SAEs reported between February 1, 2021, and January 30, 2024. SAE was assessed using the Modified Hartwig and Siegel Scale (severity), Modified Schumock and Thornton Scale (preventability), World Health Organization-Uppsala Monitoring Centre (WHO-UMC), Naranjo scales (causality), and adverse drug reaction type classification (predictability). Statistical analyses included descriptive statistics, ordinal logistic regression, Cox proportional hazards modeling, and Cohen’s kappa for interscale agreement. Results: The mean patient age was 54.13 ± 17.01 years, 73.68% were male. Most SAEs (87.97%) arose from regulatory clinical trials. Severity assessment classified 56.39% as severe and 43.60% as moderate. Preventable SAEs accounted for 18.5%, and 18.80% were predictable. Causality assessments showed poor agreement between the WHO-UMC and Naranjo scales (κ =0.124). Older age (odds ratio [OR] =1.77, P = 0.006) and preventability (OR = 2.44, P = 0.026) significantly predicted SAE severity. Cox analysis indicated severe SAEs occurred later during follow-up than moderate ones. Conclusion: Multifaceted SAE evaluation offers deeper insights than single-method causality assessments. The associations of age and preventability with severity suggest opportunities for preemptive safety strategies. Integrating such comprehensive SAE analysis into ethics committee reviews may enhance trial oversight and participant safety.