Partially hidden multi-state modelling of a prolonged disease state defined by a composite outcome

Abstract

For rheumatic diseases, Minimal Disease Activity (MDA) is usually defined as a composite outcome which is a function of several individual outcomes describing symptoms or quality of life. There is ever increasing interest in MDA but relatively little has been done to characterise the pattern of MDA over time. Motivated by the aim of improving the modelling of MDA in psoriatic arthritis, the use of a two-state model to estimate characteristics of the MDA process is illustrated when there is particular interest in prolonged periods of MDA. Because not all outcomes necessary to define MDA are measured at all clinic visits, a partially hidden multi-state model with latent states is used. The defining outcomes are modelled as conditionally independent given these latent states, enabling information from all visits, even those with missing data on some variables, to be used. Data from the Toronto Psoriatic Arthritis Clinic are analysed to demonstrate improvements in accuracy and precision from the inclusion of data from visits with incomplete information on MDA. An additional benefit of this model is that it can be extended to incorporate explanatory variables, which allows process characteristics to be compared between groups. In the example, the effect of explanatory variables, modelled through the use of relative risks, is also summarised in a potentially more clinically meaningful manner by comparing times in states, and probabilities of visiting states, between patient groups.