Appropriate statistical methods were infrequently used in cluster-randomized crossover trials

Abstract

Objective: To assess the design and statistical methods used in cluster-randomized crossover (CRXO) trials.

Study design and setting: We undertook a systematic review of CRXO trials. Searches of MEDLINE, EMBASE, and CINAHL Plus; and citation searches of CRXO methodological articles were conducted to December 2014. We extracted data on design characteristics and statistical methods for sample size, data analysis, and handling of missing data.

Results: Ninety-one trials including 139 end point analyses met the inclusion criteria. Trials had a median of nine clusters [interquartile range (IQR), 4-21] and median cluster-period size of 30 individuals (IQR, 14-77); 58 (69%) trials had two periods, and 27 trials (30%) included the same individuals in all periods. A rationale for the design was reported in only 25 trials (27%). A sample size justification was provided in 53 (58%) trials. Only nine (10%) trials accounted appropriately for the design in their sample size calculation. Ten of the 12 cluster-level analyses used a method that accounted for the clustering and multiple-period aspects of the design. In contrast, only 4 of the 127 individual-level analyses used a potentially appropriate method.

Conclusions: There is a need for improved application of appropriate analysis and sample size methods, and reporting, in CRXO trials.

Keywords: Cluster; Cluster-randomized crossover trial; Crossover; Design; Sample size; Statistical analysis.