The evaluation of multiple surrogate endpoints.
Surrogate endpoints are desirable because they typically result in smaller, faster efficacy studies compared with the ones using the clinical endpoints. Research on surrogate endpoints has received substantial attention lately, but most investigations have focused on the validity of using a single biomarker as a surrogate. Our paper studies whether the use of multiple markers can improve inferences about a treatment's effects on a clinical endpoint. We propose a joint model for a time to clinical event and for repeated measures over time on multiple biomarkers that are potential surrogates. This model extends the formulation of Xu and Zeger (2001, in press) and Fawcett and Thomas (1996, Statistics in Medicine 15, 1663-1685). We propose two complementary measures of the relative benefit of multiple surrogates as opposed to a single one. Markov chain Monte Carlo is implemented to estimate model parameters. The methodology is illustrated with an analysis of data from a schizophrenia clinical trial.
Xu
J
J
Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA. jane_2_xu@sbphrd.com
Zeger
S L
SL
D014150:Antipsychotic Agents / Q000627:therapeutic use; D001699:Biometry; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006801:Humans; D008137:Longitudinal Studies; D008390:Markov Chains; D015233:Models, Statistical; D009010:Monte Carlo Method; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012044:Regression Analysis; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy; D016019:Survival Analysis
D014150:Antipsychotic Agents; D018967:Risperidone