Progressive multi-state models for informatively incomplete longitudinal data

Progressive multi-state models provide a convenient framework for characterizing chronic disease processes where the states represent the degree of damage resulting from the disease. Incomplete data often arise in studies of such processes, and standard methods of analysis can lead to biased parameter estimates when observation of data is response-dependent. This paper describes a joint analysis useful for fitting progressive multi-state models to data arising in longitudinal studies in such settings. Likelihood based methods are described and parameters are shown to be identifiable. An EM algorithm is described for parameter estimation, and variance estimation is carried out using the Louis' method. Simulation studies demonstrate that the proposed method works well in practice under a variety of settings. An application to data from a smoking prevention study illustrates the utility of the method. (C) 2010 Elsevier B.V. All rights reserved.