title: Use of meta-analysis for the validation of surrogate endpoints and biomarkers in cancer trials.
abstract: 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.
authors.affiliation: From the International Drug Development Institute, Louvain-la-Neuve, Belgium. marc.buyse@iddi.com
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor