EVALUATING SURROGATE MARKERS

We discuss approaches for efficiently evaluating potential surrogate m arkers; in particular, we focus on case-cohort designs in which marker evaluation is undertaken only for a random sample of subjects within a randomized trial and for all other subjects who develop a major clin ical outcome. These designs will be useful in clinical trials in which a highly significant treatment difference on clinical outcome has bee n obtained. In addition, we describe a method for using data from all available studies using a meta-analysis to explore the association of treatment effects on the potential marker and on clinical outcome. Thi s may be the most effective approach for marker evaluation because it uses data from both large and small trials and incorporates informatio n from trials in which nonsignificant treatment differences on the maj or clinical outcome are obtained.