Julie Funch Furberg, Per Kragh Andersen, Thomas Scheike, Henrik Ravn
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Simulation-based sample size calculations of marginal proportional means models for recurrent events with competing risks.
In randomised controlled trials, the outcome of interest could be recurrent events, such as hospitalisations for heart failure. If mortality rates are non-negligible, both recurrent events and competing terminal events need to be addressed when formulating the estimand and statistical analysis is no longer trivial. In order to design future trials with primary recurrent event endpoints with competing risks, it is necessary to be able to perform power calculations to determine sample sizes. This paper introduces a simulation-based approach for power estimation based on a proportional means model for recurrent events and a proportional hazards model for terminal events. The simulation procedure is presented along with a discussion of what the user needs to specify to use the approach. The method is flexible and based on marginal quantities which are easy to specify. However, the method introduces a lack of a certain type of dependence. This is explored in a sensitivity analysis which suggests that the power is robust in spite of that. Data from a randomised controlled trial, LEADER, is used as the basis for generating data for a future trial. Finally, potential power gains of recurrent event methods as opposed to first event methods are discussed.
期刊介绍:
Pharmaceutical Statistics is an industry-led initiative, tackling real problems in statistical applications. The Journal publishes papers that share experiences in the practical application of statistics within the pharmaceutical industry. It covers all aspects of pharmaceutical statistical applications from discovery, through pre-clinical development, clinical development, post-marketing surveillance, consumer health, production, epidemiology, and health economics.
The Journal is both international and multidisciplinary. It includes high quality practical papers, case studies and review papers.