Bayesian inference for a principal stratum estimand on recurrent events truncated by death

• Published in: Biometrics Vol. 79; no. 4; pp. 3792 - 3802
• Main Authors: Lyu, Tianmeng, Bornkamp, Björn, Mueller‐Velten, Guenther, Schmidli, Heinz
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2023
• Subjects: Bayes Theorem; Bayesian analysis; Bayesian theory; causal inference; Chronic Disease; Clinical trials; Congestive heart failure; Death; Health services; heart failure; Heart Failure - drug therapy; Humans; principal stratum; recurrent events; Statistical inference; principal stratum; recurrent events; causal inference; Bayesian analysis
• ISSN: 0006-341X; 1541-0420; 1541-0420
• DOI: 10.1111/biom.13831

Recurrent events are often important endpoints in randomized clinical trials. For example, the number of recurrent disease‐related hospitalizations may be considered as a clinically meaningful endpoint in cardiovascular studies. In some settings, the recurrent event process may be terminated by an event such as death, which makes it more challenging to define and estimate a causal treatment effect on recurrent event endpoints. In this paper, we focus on the principal stratum estimand, where the treatment effect of interest on recurrent events is defined among subjects who would be alive regardless of the assigned treatment. For the estimation of the principal stratum effect in randomized clinical trials, we propose a Bayesian approach based on a joint model of the recurrent event and death processes with a frailty term accounting for within‐subject correlation. We also present Bayesian posterior predictive check procedures for assessing the model fit. The proposed approaches are demonstrated in the randomized Phase III chronic heart failure trial PARAGON‐HF (NCT01920711).