Biomarker Driven Response Adaptive Platform Trials

Music City Center 

There has been an increasing trend in the development of targeted therapies. Platform trial designs have previously established efficiency in identifying efficacious treatments and delivering these options to patients quicker than traditional designs. Here we present an adaptive biomarker-driven platform trial design. In this setting, we have several candidate therapies each with a prospective predictive biomarker. As the trial progresses, we use a statistical model to estimate the efficacy of each drug/biomarker pair and use response adaptive randomization to preferentially assign patients to the optimal drug based on their entire biomarker profile. Compared to existing methods, this design has several advantages. First, it graduates efficacious treatments early and allows for ineffective treatments to be dropped, which produces better patient outcomes. Second, our methods can be used for biomarkers that are either binary or continuous. Finally, the flexibility of our design allows for Go/No Go decisions to advance treatments to either the total population or only to biomarker subgroups. We demonstrate the utility of our method through several simulation case studies.

adaptive design

multiple testing

master protocol

precision medicine 

Biopharmaceutical Section