Hierarchical Bayesian modeling of heterogeneous outcome variance in cluster randomized trials.

ABSTRACT

BACKGROUND: Heterogeneous outcome correlations across treatment arms and clusters have been increasingly acknowledged in cluster randomized trials with binary endpoints, where analytical methods have been developed to study such heterogeneity. However, cluster-specific outcome variances and correlations have yet to be studied for cluster randomized trials with continuous outcomes. METHODS: This article proposes models fitted in the Bayesian setting with hierarchical variance structure to quantify heterogeneous variances across clusters and explain it with cluster-level covariates when the outcome is continuous. The models can also be extended to analyzing heterogeneous variances in individually randomized group treatment trials, with arm-specific cluster-level covariates, or in partially nested designs. Simulation studies are carried out to validate the performance of the newly introduced models across different settings. RESULTS: Simulations showed that overall the newly introduced models have good performance, reporting low bias and approximately 95% coverage for the intraclass correlation coefficients and regression parameters in the variance model. When variances are heterogeneous, our proposed models had improved model fit over models with homogeneous variances. When used to analyze data from the Kerala Diabetes Prevention Program study, our models identified heterogeneous variances and intraclass correlation coefficients across clusters and examined cluster-level characteristics associated with such heterogeneity. CONCLUSION: We proposed new hierarchical Bayesian variance models to accommodate cluster-specific variances in cluster randomized trials. The newly developed methods inform the understanding of how an intervention strategy is implemented and disseminated differently across clusters and can help improve future trial design.