Two-state mixed renewal processes for chronic disease.

We develop a model based on a two-state mixed renewal process and propose its use for modelling disease activity in studies of chronic conditions. We specify Weibull forms for the conditional transition intensities to allow for time trends, and bivariate frailties to accommodate subject-to-subject variability in the disease process. Extensions of this model are considered for stratified analyses in which strata are defined by the number of past exacerbations. Data from a motivating study of chronic bronchitis are analysed to illustrate the methodology.