Randomized Controlled Trials 5: Biomarkers and Surrogates/Outcomes.

Biomarkers are characteristics that are measured as indicators of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Biomarkers may serve a number of important uses, particularly in diagnosis and prognosis of disease, and as surrogates for clinical outcomes of disease (i.e., outcomes that measure how patient survives, functions, or feels). Establishing the validity of a given biomarker for a specific role requires the conduct of carefully designed clinical studies in which the biomarker and the outcome of interest are measured independently. The design and analysis of such studies is discussed. Surrogate outcomes in clinical trials consist of events or biomarkers intended to reflect important clinical outcomes. Surrogate outcomes may offer advantages in providing statistically robust estimates of treatment effects with smaller sample sizes. However, to be useful, surrogate outcomes have to be validated to ensure that the effect of therapy on them truly reflects the effect of therapy on the important clinical outcomes of interest.