Methods for dealing with unequal cluster sizes in cluster randomized trials: A scoping review

PLoS One. 2021 Jul 29;16(7):e0255389. doi: 10.1371/journal.pone.0255389. eCollection 2021.

Abstract

In a cluster-randomized trial (CRT), the number of participants enrolled often varies across clusters. This variation should be considered during both trial design and data analysis to ensure statistical performance goals are achieved. Most methodological literature on the CRT design has assumed equal cluster sizes. This scoping review focuses on methodology for unequal cluster size CRTs. EMBASE, Medline, Google Scholar, MathSciNet and Web of Science databases were searched to identify English-language articles reporting on methodology for unequal cluster size CRTs published until March 2021. We extracted data on the focus of the paper (power calculation, Type I error etc.), the type of CRT, the type and the range of parameter values investigated (number of clusters, mean cluster size, cluster size coefficient of variation, intra-cluster correlation coefficient, etc.), and the main conclusions. Seventy-nine of 5032 identified papers met the inclusion criteria. Papers primarily focused on the parallel-arm CRT (p-CRT, n = 60, 76%) and the stepped-wedge CRT (n = 14, 18%). Roughly 75% of the papers addressed trial design issues (sample size/power calculation) while 25% focused on analysis considerations (Type I error, bias, etc.). The ranges of parameter values explored varied substantially across different studies. Methods for accounting for unequal cluster sizes in the p-CRT have been investigated extensively for Gaussian and binary outcomes. Synthesizing the findings of these works is difficult as the magnitude of impact of the unequal cluster sizes varies substantially across the combinations and ranges of input parameters. Limited investigations have been done for other combinations of a CRT design by outcome type, particularly methodology involving binary outcomes-the most commonly used type of primary outcome in trials. The paucity of methodological papers outside of the p-CRT with Gaussian or binary outcomes highlights the need for further methodological development to fill the gaps.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cluster Analysis
  • Humans
  • Randomized Controlled Trials as Topic*
  • Sample Size

Grants and funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the BC SUPPORT Unit [grant number RWCT-204]. The funders had no involvement in study design, collection, analysis and interpretation of data, reporting or the decision to publish.