Innovative Trial Designs

Promising innovative trial designs such as Trials within Cohorts (TwiC) and Platform Trials have the potential to overcome some of the problems common to traditional Randomized Controlled Trials (RCTs).

Trials within Cohorts (TwiC) are a randomized trial design in which a trial is set up and conducted within an existing or newly started cohort. In a cohort that uses the TwiCs approach a group of participants with a particular condition of interest may agree to regular data collection and observation – and to random assignment into a future intervention. Once an intervention is trialed, only the cohort participants who have been assigned to the intervention group will be informed of their role as the trial group and an additional consent will be obtained. The control group receives the standard treatment according to the cohort procedures. Because of the multi-staged consent process, which differs from classic randomized controlled trials, TwiCs may better mimic clinical practice and improve recruitment of study participants. However, TwiCs-specific ethical, statistical and methodological challenges need to be addressed. We are currently conducting three TwiCs in a cohort in Lesotho and are exploring the option of two TwiCs in the Swiss HIV Cohort Study.

Platform trials can be perpetual in nature, in which they allow for the dropping of treatment arms with ineffective interventions and the inclusion of new treatment arms with promising interventions. They assess several drugs/interventions simultaneously and may include a common control arm. Platform trial planning and conduct is very complex and requires consideration of its distinct trial features. This includes the potential use of non-concurrent control data, the statistical framework (Bayesian and/or frequentist), in silico trials (simulations), response adaptive randomization (RAR, the change of the randomization ratio based on data collected during the trial); sample size reassessment; seamless study phase transition (seamless design) and modification of eligibility criteria (adaptive enrichment). Platform trials are stipulated to be more time- and cost-efficient, as well as able to increase the output of the clinical research pipeline. We are involved in several pan-European platform trial initiatives.

Scientific publications and registrations