Journal - Biometrics (UNITED STATES )

Abstract :

In certain diseases, outcome is the number of morbid events over the course of follow-up. In epilepsy, e.g., daily seizure counts are often used to reflect disease severity. Follow-up of patients in clinical trials of such diseases is often subject to censoring due to patients dying or dropping out. If the sicker patients tend to be censored in such trials, estimates of the treatment effect that do not incorporate the censoring process may be misleading. We extend the shared random effects approach of Wu and Carroll (1988, Biometrics 44, 175-188) to the setting of repeated counts of events. Three strategies are developed. The first is a likelihood-based approach for jointly modeling the count and censoring processes. A shared random effect is incorporated to introduce dependence between the two processes. The second is a likelihood-based approach that conditions on the dropout times in adjusting for informative dropout. The third is a generalized estimating equations (GEE) approach, which also conditions on the dropout times but makes fewer assumptions about the distribution of the count process. Estimation procedures for each of the approaches are discussed, and the approaches are applied to data from an epilepsy clinical trial. A simulation study is also conducted to compare the various approaches. Through analyses and simulations, we demonstrate the flexibility of the likelihood-based conditional model for analyzing data from the epilepsy trial.