Design, Analysis, and Presentation of Crossover Trials

Objective: Although crossover trials enjoy wide use, standards for analysis and reporting have notbeen established. We reviewed methodological aspects and quality of reporting in a representativesample of published crossover trials. Methods: We searched MEDLINE for December 2000 and identified all randomized crossovertrials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and14 criteria assessing the data presentation. Results: We identified 526 randomized controlled trials, of which 116 were crossover trials. Trialswere drug efficacy (48%), pharmacokinetic (28%), and nonpharmacologic (30%). The median samplesize was 15 (interquartile range 8–38). Most (72%) trials used 2 treatments and had 2 periods (64%).Few trials reported allocation concealment (17%) or sequence generation (7%). Only 20% of trialsreported a sample size calculation and only 31% of these considered pairing of data in thecalculation. Carry-over issues were addressed in 29% of trial\u27s methods. Most trials reported anddefended a washout period (70%). Almost all trials (93%) tested for treatment effects using paireddata and also presented details on by-group results (95%). Only 29% presented CIs or SE so thatdata could be entered into a meta-analysis. Conclusion: Reports of crossover trials frequently omit important methodological issues indesign, analysis, and presentation. Guidelines for the conduct and reporting of crossover trialsmight improve the conduct and reporting of studies using this important trial design