Two-level lognormal frailty model and competing risks model with missing cause of failure

In clustered survival data, unobservable cluster effects may exert powerful influences on the outcomes and thus induce correlation among subjects within the same cluster. The ordinary partial likelihood approach does not account for this dependence. Frailty models, as an extension to Cox regression, incorporate multiplicative random effects, called frailties, into the hazard model and have become a very popular way to account for the dependence within clusters. We particularly study the two-level nested lognormal frailty model and propose an estimation approach based on the complete data likelihood with frailty terms integrated out. We adopt B-splines to model the baseline hazards and adaptive Gauss-Hermite quadrature to approximate the integrals efficiently. Furthermore, in finding the maximum likelihood estimators, instead of the Newton-Raphson iterative algorithm, Gauss-Seidel and BFGS methods are used to improve the stability and efficiency of the estimation procedure. We also study competing risks models with missing cause of failure in the context of Cox proportional hazards models. For competing risks data, there exists more than one cause of failure and each observed failure is exclusively linked to one cause. Conceptually, the causes are interpreted as competing risks before the failure is observed. Competing risks models are constructed based on the proportional hazards model specified for each cause of failure respectively, which can be estimated using partial likelihood approach. However, the ordinary partial likelihood is not applicable when the cause of failure could be missing for some reason. We propose a weighted partial likelihood approach based on complete-case data, where weights are computed as the inverse of selection probability and the selection probability is estimated by a logistic regression model. The asymptotic properties of the regression coefficient estimators are investigated by applying counting process and martingale theory. We further develop a double robust approach based on the full data to improve the efficiency as well as the robustness.