A comparison of the statistical power of different methods for the analysis of cluster randomization trials with binary outcomes

Cluster randomization trials are randomized controlled trials (RCTs) in which intact clusters of subjects are randomized to either the intervention or to the control.  Cluster randomization trials require different statistical methods of analysis than do conventional randomized controlled trials due to the potential presence of within-cluster homogeneity in responses.  A variety of statistical methods have been proposed in the literature for the analysis of cluster randomization trials with binary outcomes.  However, little is known about the relative statistical power of these methods to detect a statistically significant intervention effect.

Investigators conducted a series of Monte Carlo simulations to examine the statistical power of three methods that compare cluster-specific response rates between arms of the trial: the t-test, the Wilcoxon rank sum test, and the permutation test; and three methods that compare subject-level response rates: an adjusted chi-square test, a logistic-normal random effects model, and a generalized estimating equations (GEE) method.  In the simulations, investigators allowed the number of clusters, the number of subjects per cluster, the intraclass correlation coefficient, and the magnitude of the intervention effect to vary.

The authors demonstrated that the GEE approach tended to have the highest power for detecting a statistically significant intervention effect.  However, in most of the 240 scenarios examined, the differences between the competing statistical methods were negligible.  The largest mean difference in power between any two different statistical methods across the 240 scenarios was 0.02.  The largest observed difference in power between two different statistical methods across the 240 scenarios and 15 pair-wise comparisons of methods was 0.14.