A Bayesian approach to the survivor average causal effect in cluster-randomized crossover trials

TL;DR

This paper introduces a Bayesian framework for estimating the survivor average causal effect in cluster-randomized crossover trials, addressing issues of truncation by death and improving causal inference in health studies.

Contribution

It develops novel Bayesian methods and assumptions for estimating the SACE in CRXO trials, accounting for non-survivors and enhancing causal analysis accuracy.

Findings

Bayesian approach effectively estimates SACE in simulated CRXO data.

Method applied successfully to real clinical data on medication effects.

Proposed model improves causal inference in the presence of truncation by death.

Abstract

In cluster-randomized crossover (CRXO) trials, groups of individuals are randomly assigned to two or more sequences of alternating treatments. Since clusters serve as their own control, the CRXO design is typically more statistically efficient than the usual parallel-arm design. CRXO trials are increasingly popular in many areas of health research where the number of available clusters is limited. Further, in trials among severely ill patients, researchers often want to assess the effect of treatments on secondary non-terminal outcomes, but frequently in these studies, there are patients who do not survive to have these measurements fully recorded. In this paper, we provide a causal inference framework and treatment effect estimation methods for addressing truncation by death in the setting of CRXO trials. We target the survivor average causal effect (SACE) estimand, a well-defined subgroup treatment effect obtained via principal stratification. We propose novel structural and standard modeling assumptions that enable estimating the SACE within a Bayesian paradigm. We evaluate the small-sample performance of our proposed Bayesian approach for estimation of the SACE in CRXO trial settings via simulation studies. We apply our methods to a previously conducted two-period cross-sectional CRXO study examining the impact of proton pump inhibitors compared to histamine-2 receptor blockers on length of hospitalization among adults requiring invasive mechanical ventilation.