Perspectives on adverse events reporting in hybrid implementation science (IS) clinical trials of approved medications in Sub-Saharan Africa

Implementation science (IS) hybrid type 2 and 3 clinical trials and pure implementation research of approved medications test strategies to increase uptake of evidence-based interventions (EBIs) with well-established safety profiles. Guidance on adverse event (AE) monitoring and reporting for this type of IS studies has not been well-defined. This research aimed to understand current practices and develop recommendations for AE reporting in hybrid effectiveness-implementation trials of approved medications. We used a multi-step, expert-driven process involving: (1) in-depth interviews conducted between August and December 2023 with stakeholders involved in the National Heart, Lung and Blood Institute HLB-SIMPLe alliance to identify preliminary recommendations ( n = 20), and (2) validation of the recommendations through stakeholder consultations with Botswana Harvard Health Partnership Community Advisory Board (BHP-CAB) members ( n = 16) and purposively selected multisectoral academic, healthcare, government and non-governmental organization stakeholders ( n = 19). Interview participants agreed that better-designed AE reporting guidelines for IS studies are needed for hybrid effectiveness-implementation trials. Most recommended that only severe medication-related AEs be reported by investigators to regulatory bodies, institutional review boards, and funders. Community representatives felt that all AEs, even minor ones unrelated to implementation strategies, should be reported. Comprehensive and appropriate AE reporting guidelines for hybrid type 2 and 3 implementation trials are needed. Such guidelines should incorporate a range of implementation-specific AEs, including unintended consequences of implementation strategies at multiple levels. The study was conducted as a nested sub-study within the InterCARE study which was registered ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022.