A random effects model for multivariate failure time data from multicenterclinical trials

A random effects model for analyzing multivariate failure time data is prop osed. The work is motivated by the need for assessing the mean treatment ef fect in a multicenter clinical trial study, assuming that the centers are a random sample from an underlying population. An estimating equation for th e mean hazard ratio parameter is proposed. The proposed estimator is shown to be consistent and asymptotically normally distributed A variance estimat or, based on large sample theory, is proposed. Simulation results indicate that the proposed estimator performs well in finite samples. The proposed v ariance estimator effectively corrects the bias of the naive variance estim ator, which assumes independence of individuals within a group. The methodo logy is illustrated with a clinical trial data set from the Studies of Left Ventricular Dysfunction. This shows that the variability of the treatment effect is higher than found by means of simpler models.