Use of Meta-Analysis for the Validation of Surrogate Endpoints and Biomarkers in Cancer Trials

This article discusses statistical approaches to the validation of surrogate biomarkers and endpoints. One approach that has been successfully used in oncology consists of estimating associations at two levels: the association between the surrogate and the clinical endpoint, called the individual-level association, and the association between the effects of treatment on the surrogate and the clinical endpoint, called the trial-level association. This approach requires data to be available from multiple randomized trials, such as in a meta-analysis of trials based on individual patient data. The approach is illustrated using randomized trials of first-line treatments for advanced tumors of the colon, breast, ovary, and prostate. Data from several meta-analyses suggest that progression-free survival is an acceptable surrogate in advanced colorectal and ovarian cancer, but not in breast and prostate cancer.