The ICC is closely linked to the sample size necessary to conduct the trial with adequate statistical power. The ICC ranges from complete correlation (ICC = 1) to no correlation (ICC = 0). In the extreme case of an ICC of 1, all participants in a cluster are likely to have exactly the same outcome; thus, sampling 1 participant from that cluster is as informative as sampling the whole cluster. In other words, each cluster contributes a single data point to the study, and the effective sample size for the study is the number of clusters. On the other hand, if participants in a cluster behave essentially independently of each other and their outcomes are no more related than if they were from different clusters, then the ICC is 0 and the available sample size for the study is the total number of participants. There is a substantial literature on taking account of the ICC when determining sample size requirements for cluster randomized trials. It is critical to have preliminary data that provide some estimate of the likely ICC.

The level at which to cluster creates a trade-off between potential contamination and bias on the one hand and available sample size on the other. For example, in one NIH Collaboratory Trial, the researchers originally intended to randomize at the provider level. However, because the providers shared clinic staff and facilities, a preliminary evaluation of the ICC demonstrated more than negligible correlation between clinics in the potential outcomes. So the researchers needed to randomize at the clinic level rather than the provider level and to recruit additional clinics to meet their expectations for statistical power. In contrast, another NIH Collaboratory Trial study team intended to randomize at the clinic level but found negligible correlation in outcomes between providers within clinics and were able to randomize providers.

Much depends on the type of intervention, and it is always prudent to obtain a preliminary estimate of the ICC before planning the study.