Statistical Issues in Modeling Chronic Disease in Cohort Studies
Cook, Richard J.
Lawless, Jerald F.
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Observational cohort studies of individuals with chronic disease provide information on rates of disease progression, the effect of fixed and time-varying risk factors, and the extent of heterogeneity in the course of disease. Analysis of this information is often facilitated by the use of multistate models with intensity functions governing transition between disease states. We discuss modeling and analysis issues for such models when individuals are observed intermittently. Frameworks for dealing with heterogeneity and measurement error are discussed including random effect models, finite mixture models, and hidden Markov models. Cohorts are often defined by convenience and ways of addressing outcome-dependent sampling or observation of individuals are also discussed. Data on progression of joint damage in psoriatic arthritis and retinopathy in diabetes are analysed to illustrate these issues and related methodology.