A Bayesian platform trial design to simultaneously evaluate multiple drugs in multiple indications with mixed endpoints

In the era of targeted therapies and immunotherapies, the traditional drug development paradigm of testing one drug at a time in one indication has become increasingly inefficient. Motivated by a real-world application, we propose a master-protocol-based Bayesian platform trial design with mixed endpoints (PDME) to simultaneously evaluate multiple drugs in multiple indications, where different subsets of efficacy measures (eg, objective response and landmark progression-free survival) may be used by different indications as single or multiple endpoints. We propose a Bayesian hierarchical model to accommodate mixed endpoints and reflect the trial structure of indications that are nested within treatments. We develop a two-stage approach that first clusters the indications into homogeneous subgroups and then applies the Bayesian hierarchical model to each subgroup to achieve precision information borrowing. Patients are enrolled in a group-sequential way and adaptively assigned to treatments according to their efficacy estimates. At each interim analysis, the posterior probabilities that the treatment effect exceeds prespecified clinically relevant thresholds are used to drop ineffective treatments and graduate effective treatments. Simulations show that the PDME design has desirable operating characteristics compared to existing method.

Automated summary

In the era of targeted therapies and immunotherapies, the traditional drug development paradigm is inefficient. This paper proposes a master-protocol-based Bayesian platform trial design to simultaneously evaluate multiple drugs in multiple indications. It introduces a Bayesian hierarchical model to accommodate mixed endpoints and reflects the trial structure of nested indications.