Cluster-Randomized Studies

Abstract

Background: Cluster-randomized trials (CRT) are needed to compare interventions that are allocated to entire groups of subjects, rather than to individuals. Publications about CRT have become steadily more common over the past decade. Readers of such publications should be able to categorize and interpret the findings of CRT correctly while considering the methodological requirements applicable to this type of study.

Methods: This review is based on a selection of pertinent literature and on the authors' expertise. CRT-specific methodological aspects of the planning, performance, and interpretation of studies are discussed.

Results: Readers of publications on CRT should check whether due consideration has been given to correlations within and between the clusters during the planning of the study. These correlations enable the determination whether persons within a cluster resemble each other more closely, or respond more similarly to the study intervention, than persons drawn from different clusters. It should also be checked whether the randomization for the study has been carried out with such methods as stratification and covariate-adjusted randomization. CRT can be analyzed on either the individual or the cluster level. The rationale for the choice of a clusterrandomized design should be explained, and intracluster correlation coefficients (ICC) should be reported as an aid to the planning of future studies. Particular requirements are also described in an extended version of the CONSORT guidelines that has been developed specifically for CRT.

Conclusion: Readers of publications on CRT should be aware of the special requirements mentioned above with respect to the design, performance, and analysis of this type of study as opposed to individually randomized studies. If no special techniques are applied in the design, performance, and analysis of a CRT, or if the assumptions underlying each of these steps have not been properly checked, then the findings of the study may well be misleading.

Figure

Matching and stratification: The clusters shaded dark green (region 1) and light green (region 2) represent the two study regions in our example of a study of care homes. The different-colored contours (red, orange, yellow) of the clusters show homogeneous cluster pairs. The various colors of the individuals in each cluster (light red, medium red, dark red) identify the various age groups. Matching in cluster-randomized studies: In the matching process, the maximally homogeneous cluster pairs are divided randomly between the intervention and control arms of the study with regard to the predefined participant characteristics (in this example: age). Stratification in cluster-randomized studies: In stratified randomization, care homes from a region are randomly selected from the whole set of care homes in that region and divided equally between the two study arms.