A general Bayesian approach to design adaptive clinical trials with time-to-event outcomes (2303.00901v1)

Abstract: Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive clinical trials (i.e. trials that can be altered based on evidence that has accrued) are often more efficient, informative and ethical than standard or non-adaptive trials because they require fewer participants, target more promising treatments, and can stop early with sufficient evidence of effectiveness or harm. The design of adaptive trials requires the pre-specification of adaptions that are permissible throughout the conduct of the trial. Proposed adaptive designs are then usually evaluated through simulation which provides indicative metrics of performance (e.g. statistical power and type-1 error) under different scenarios. Trial simulation requires assumptions about the data generating process to be specified but correctly specifying these in practice can be difficult, particularly for new and emerging diseases. To address this, we propose an approach to design adaptive clinical trials without needing to specify the complete data generating process. To facilitate this, we consider a general Bayesian framework where inference about the treatment effect on a time-to-event outcome can be performed via the partial likelihood. As a consequence, the proposed approach to evaluate trial designs is robust to the specific form of the baseline hazard function. The benefits of this approach are demonstrated through the redesign of a recent clinical trial to evaluate whether a third dose of a vaccine provides improved protection against gastroenteritis in Australian Indigenous infants.