Multi-state modelling of repeated hospitalisation and death in patients with heart failure: The use of large administrative databases in clinical epidemiology.

In chronic diseases like heart failure (HF), the disease course and associated clinical event histories for the patient population vary widely. To improve understanding of the prognosis of patients and enable health care providers to assess and manage resources, we wish to jointly model disease progression, mortality and their relation with patient characteristics. We show how episodes of hospitalisation for disease-related events, obtained from administrative data, can be used as a surrogate for disease status. We propose flexible multi-state models for serial hospital admissions and death in HF patients, that are able to accommodate important features of disease progression, such as multiple ordered events and competing risks. Fully parametric and semi-parametric semi-Markov models are implemented using freely available software in R. The models were applied to a dataset from the administrative data bank of the Lombardia region in Northern Italy, which included 15,298 patients who had a first hospitalisation ending in 2006 and 4 years of follow-up thereafter. This provided estimates of the associations of age and gender with rates of hospital admission and length of stay in hospital, and estimates of the expected total time spent in hospital over five years. For example, older patients and men were readmitted more frequently, though the total time in hospital was roughly constant with age. We also discuss the relative merits of parametric and semi-parametric multi-state models, and model assessment and comparison.