Rationale, Methodological Quality, and Reporting of Cluster-Randomized Controlled Trials in Critical Care Medicine: A Systematic Review

Abstract

Objective: Compared with individual-patient randomized controlled trials, cluster randomized controlled trials have unique methodological and ethical considerations. We evaluated the rationale, methodological quality, and reporting of cluster randomized controlled trials in critical care studies.

Data sources: Systematic searches of Medline, Embase, and Cochrane Central Register were performed.

Study selection: We included all cluster randomized controlled trials conducted in adult, pediatric, or neonatal critical care units from January 2005 to September 2019.

Data extraction: Two reviewers independently screened citations, reviewed full texts, protocols, and supplements of potentially eligible studies, abstracted data, and assessed methodology of included studies.

Data synthesis: From 1,902 citations, 59 cluster randomized controlled trials met criteria. Most focused on quality improvement (24, 41%), antimicrobial therapy (9, 15%), or infection control (9, 15%) interventions. Designs included parallel-group (25, 42%), crossover (21, 36%), and stepped-wedge (13, 22%). Concealment of allocation was reported in 21 studies (36%). Thirteen studies (22%) reported at least one method of blinding. The median total sample size was 1,660 patients (interquartile range, 813-4,295); the median number of clusters was 12 (interquartile range, 5-24); and the median patients per cluster was 141 (interquartile range, 54-452). Sample size calculations were reported in 90% of trials, but only 54% met Consolidated Standards of Reporting Trials guidance for sample size reporting. Twenty-seven of the studies (46%) identified a fixed number of available clusters prior to trial commencement, and only nine (15%) prespecified both the number of clusters and patients required to detect the expected effect size. Overall, 36 trials (68%) achieved the total prespecified sample size. When analyzing data, 44 studies (75%) appropriately adjusted for clustering when analyzing the primary outcome. Only 12 (20%) reported an intracluster coefficient (median 0.047 [interquartile range, 0.01-0.13]).

Conclusions: Cluster randomized controlled trials in critical care typically involve a small and fixed number of relatively large clusters. The reporting of key methodological aspects of these trials is often inadequate.