A semiparametric marginal mixture cure model for clustered survival data.

We consider a marginal model for the regression analysis of clustered failure time data with a cure fraction. We propose to use novel generalized estimating equations in an expectation-maximization algorithm to estimate regression parameters in a semiparametric proportional hazards mixture cure model. The dependence among the cure statuses and among the survival times of uncured patients within clusters are modeled by working correlation matrices in the estimating equations. We use a bootstrap method to obtain the variances of the estimates. We report a simulation study to demonstrate a substantial efficiency gain of the proposed method over an existing marginal method. Finally, we apply the model and the proposed method to a set of data from a multi-institutional study of tonsil cancer patients treated with a radiation therapy.