Accelerating medicines to patients: A Bayesian quantitative evidence-based decision-making framework with interim...

Proof of Concept (POC) trials should be designed to inform a drug's targeted benefit-risk profile and ability to fulfill unmet medical needs, rather than simply achieving statistical significance. Pulkstenis et al. [1] proposed a unified Bayesian framework for decision-making in Proof of Concept (POC) trials to weigh evidence regarding a dual-level Target Product Profile (TPP). To accelerate decision-making while evidence is still emerging from a Phase 2 trial, we generalize this framework by incorporating interim monitoring leveraging predictive probability. An accelerated Go-decision can be achieved to initiate Phase 3 studies earlier if sufficiently promising results are observed, while an early No-Go or wait decision can be made when supporting evidence indictates. Practical guidance for implementing the approach is demonstrated by simulation studies of binary and continuous endpoints.