Key considerations for designing, conducting and analysing a cluster randomized trial

Abstract

Not only do cluster randomized trials require a larger sample size than individually randomized trials, they also face many additional complexities. The potential for contamination is the most commonly used justification for using cluster randomization, but the risk of contamination should be carefully weighed against the more serious problem of questionable scientific validity in settings with post-randomization identification or recruitment of participants unblinded to the treatment allocation. In this paper we provide some simple guidelines to help researchers conduct cluster trials in a way that minimizes potential biases and maximizes statistical efficiency. The overarching theme of this guidance is that methods that apply to individually randomized trials rarely apply to cluster randomized trials. We recommend that cluster randomization be only used when necessary—balancing the benefits of cluster randomization with its increased risks of bias and increased sample size. Researchers should also randomize at the lowest possible level—balancing the risks of contamination with ensuring an adequate number of randomization units—as well as exploring other options for statistically efficient designs. Clustering should always be allowed for in the sample size calculation; and the use of restricted randomization (and adjustment in the analysis for covariates used in the randomization) should be considered. Where possible, participants should be recruited before randomizing clusters and, when recruiting (or identifying) participants post-randomization, recruiters should be masked to the allocation. In the analysis, the target of inference should align with the research question, and adjustment for clustering and small sample corrections should be used when the trial includes less than about 40 clusters.

Effect of modified basic package of oral care on adolescents’ dental caries status in Copperbelt Province, Zambia; A Cluster Randomized Trial

“…The findings of this study need to be interpreted within the strengths and limitations of a cluster randomized trial. The study involved a large sample size from a total of twenty-two clusters which exceed the recommended minimum number of clusters for a parallel randomized cluster trials of four per arm in order to obtain a p-value less than 0.05 under a randomization-based test [32]. The findings can probably be generalized to adolescents attending public secondary schools in Copperbelt Province, Zambia, due to random selection and a large sample size.…”

Hand Hygiene Education Components Among First-Year Nursing Students

“…We conducted a cluster randomized clinical trial, with each cluster representing a single hand hygiene training session. This design was adopted to address difficulties associated with implementing distinct interventions for individually randomized nursing students and potential cross-contamination . The trial was reviewed and approved by the institutional review board of Hong Kong Polytechnic University.…”

“…This design was adopted to address difficulties associated with implementing distinct interventions for individually randomized nursing students and potential cross-contamination. 19 , 20 The trial was reviewed and approved by the institutional review board of Hong Kong Polytechnic University. Before enrolment, all participants gave written informed consent.…”