What Constitutes Risk in Implementation Research? Perspectives from a Qualitative Key-Informant Study

Background As implementation research increasingly occurs within routine care settings, determining what constitutes minimal risk is critical to ensuring that ethical oversight is appropriate and proportional. Current regulatory definitions often do not reflect the unique features of implementation studies, including implementation strategy-related risks and system-level effects. Yet, little empirical evidence exists on how researchers themselves interpret minimal risk in this context. Methods We conducted semi-structured qualitative interviews with 11 key informants, including investigators and research administrators with experience in domestic and global implementation research. Participants were recruited through purposive sampling. Interviews explored how participants interpret the concept of minimal risk, identify potential ethical concerns, and experience regulatory review processes. Data were analyzed thematically using a grounded theory approach. Results Participants generally accepted the Common Rule definition of minimal risk but viewed its application to implementation research as complex and context-dependent. Three major themes emerged: (1) ambiguity in defining usual care, especially in low-resource or inequitable settings; (2) a need to differentiate risks stemming from evidence-based interventions versus those from implementation strategies; and (3) the importance of recognizing risk at multiple levels, including patients, providers, and health systems. Participants expressed concern that strategy-related risks, such as staff burden or organizational disruption, are poorly conceptualized, underreported, and inconsistently reviewed by ethics review committees. At the same time, they raised unresolved questions about who should bear responsibility for monitoring risks tied to the evidence-based intervention itself. Conclusions Greater clarity is needed to guide ethical review, particularly regarding implementation strategy-related risks and the responsibilities of researchers for intervention-related harms. We recommend that implementation researchers begin systematically documenting and publishing on unintended harms related to implementation strategies, and that the field invest in building ethical frameworks and training specific to these challenges. Without such efforts, implementation science risks undermining the very systems and communities it seeks to improve.