Optimizing the use of biomarkers, surrogate endpoints, and clinical endpoints for more efficient drug development

Biomarkers and surrogate endpoints are critical to the future of efficient drug development. Definitions, a conceptual model, and a conceptual framewo rk for validating and bridging biomarkers to clinical endpoints are provide d in this presentation. In addition, a few examples are provided to support the development concept. Poor correlation between a biomarker and its clin ical endpoint may result from (1) poor measurement of one or bo th, (2) sel ection of an inappropriate biomarker, or, more important, (3) use of an ina ppropriate clinical endpoint. Pharmacokinetic/pharmacodynamic (PK/PD) model ing output can be no better than biomarkers or surrogate endpoints used for the modeling. As we increase our understanding of biomarkers, surrogate ma rkers, and the mechanistic basis for the processes of interest, biomarker a nd surrogate endpoint predictive power will no longer be on issue and PK/PD modeling inputs and outputs will improve. (C)2000 the American College of Clinical Pharmacology.