Joint modeling and analysis of longitudinal data with informative observation times.

SUMMARY: In analysis of longitudinal data, it is often assumed that observation times are predetermined and are the same across study subjects. Such an assumption, however, is often violated in practice. As a result, the observation times may be highly irregular. It is well known that if the sampling scheme is correlated with the outcome values, the usual statistical analysis may yield bias. In this article, we propose joint modeling and analysis of longitudinal data with possibly informative observation times via latent variables. A two-step estimation procedure is developed for parameter estimation. We show that the resulting estimators are consistent and asymptotically normal, and that the asymptotic variance can be consistently estimated using the bootstrap method. Simulation studies and a real data analysis demonstrate that our method performs well with realistic sample sizes and is appropriate for practical use.