Implementing a randomization consent to enable Trials within Cohorts in the Swiss HIV Cohort Study — A mixed-methods study
Randomized clinical trials are the gold standard for causal inference, but slow recruitment, high costs, and burdensome consent procedures often limit their conduct. Trials within Cohorts (TwiCs) is a pragmatic design that addresses these challenges by asking cohort participants for consent to be randomized into future low-risk interventions tested within the cohort. In a study published in Journal of Clinical Epidemiology, Zehnder and Schönenberger et al. examined the implementation of a randomization consent as part of the TwiCs design in the Swiss HIV Cohort Study.
In July 2024, the SHCS amended its protocol to introduce a randomization consent for participants under care at its seven main centers. Between July 2024 and July 2025, the randomization consent was offered to 5’297 participants, and cohort data were used to characterize those accepting and declining. The mixed-methods design combined a cross-sectional survey of cohort physicians, semistructured interviews with 32 stakeholders (physicians, research staff, participants, and ethics committee members), and observations of cohort visits.
Of the 5’297 participants approached, 3’067 (57.9%) signed the randomization consent and 734 (13.8%) declined, while for 1’496 (28.2%) individuals the decision was postponed, corresponding to an acceptance of 81% among those who were asked to participate. Male sex, younger age, higher education, having had at least three visits with the same physician, and shorter cohort participation time showed higher acceptance rates. The TwiCs design was positively perceived by physicians and research staff, who recognized its potential to simplify the conduct of low-risk trials, and ethical concerns were considered mitigated by the explicit randomization consent. The main barriers were language barriers, participant difficulty understanding the concept, and time constraints during consultations.
In summary, implementing a randomization consent in an existing, large-scale national cohort proved feasible, with high acceptance among participants. These findings highlight the potential of the TwiCs design to simplify future randomized comparisons within the SHCS while preserving participants’ ability to make informed decisions. The approach may also support other established cohorts seeking to adopt TwiCs.