Covariate-constrained randomization in cluster randomized 2 × 2 factorial trials: application to a diabetes prevention study.

CR should be used instead of simple randomization when performing factorial CRTs to avoid highly imbalanced designs and to obtain more precise inferences. Except when there are a small number of clusters, cluster-level covariates should be included in the analysis model to increase power and maintain coverage and type 1 error rates at their nominal levels.