Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of health interventions. Three main analysis approaches are: cluster-level analyses, mixed-models and generalized estimating equations (GEEs). Mixed models and GEEs can lead to inflated type I error rates with a small number of clusters, and numerous small-sample corrections have been proposed to circumvent this problem. However, the impact of these methods on power is still unclear.
Methods: We performed a simulation study to assess the performance of 12 analysis approaches for CRTs with a continuous outcome and 40 or fewer clusters. These included weighted and unweighted cluster-level analyses, mixed-effects models with different degree-of-freedom corrections, and GEEs with and without a small-sample correction. We assessed these approaches across different values of the intraclass correlation coefficient (ICC), numbers of clusters and variability in cluster sizes.
Results: Unweighted and variance-weighted cluster-level analysis, mixed models with degree-of-freedom corrections, and GEE with a small-sample correction all maintained the type I error rate at or below 5% across most scenarios, whereas uncorrected approaches lead to inflated type I error rates. However, these analyses had low power (below 50% in some scenarios) when fewer than 20 clusters were randomized, with none reaching the expected 80% power.
Conclusions: Small-sample corrections or variance-weighted cluster-level analyses are recommended for the analysis of continuous outcomes in CRTs with a small number of clusters. The use of these corrections should be incorporated into the sample size calculation to prevent studies from being underpowered.
© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association