Methods for analyzing recurrent and terminal events considering composite and competing endpoints in clinical trials: a practical overview.

Time to event endpoints like time to myocardial infarction, relapse, or death are often of primary interest in clinical trials. To describe the whole disease process and gain a complete picture of treatment effects, methods for recurrent time to event analysis considering terminal events were proposed, i.e. methods considering all events that occur per individual. However, these methods are not often applied in clinical studies. This might be due to the researchers' uncertainties about underlying model assumptions and interpretation of results. We therefore aim to give a comprehensive overview of methods for the analysis of multiple time to events comparing model assumptions and interpretation. We illustrate the methods using a cardiovascular trial and provide the corresponding R code.