title: 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.
authors.affiliation: Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA. rsimon@nih.gov.
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
keywords: Predictive biomarker; adaptive design; clinical trial design; companion diagnostic; enrichment trial