Nature of Biomarkers and Surrogate Endpoints in Clinical Trials
*Tom Fleming, University of Washington 

Keywords: Biomarkers, Surrogates, Replacement Endpoints

One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function, and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures, and radiological tests, often are considered as replacement endpoints or ‘surrogates’ for clinically meaningful endpoints. Definitions of clinically meaningful endpoints and surrogate endpoints will be discussed. Insight will be provided into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. The nature of evidence will be identified that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and insights will be provided into why this reliability is specific to the context of use of the biomarker. Finally, consideration will be given to the various uses of biomarkers in clinical development.