Biomarker based clinical trial design

Abstract

The established molecular heterogeneity of human cancers and the subsequent stratification of conventional diagnostic categories require the development of new paradigms for the development of a reliable basis for predictive medicine. We review clinical trial designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are phase III clinical trials involving both genome-wide discovery and internal validation of a predictive classifier that identifies the patients most likely and unlikely to benefit from the new drug.

Keywords: Predictive biomarker; adaptive design; clinical trial design; companion diagnostic; enrichment trial.