Design, analysis, and presentation of crossover trials.
OBJECTIVE
Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials.


METHODS
We searched MEDLINE for December 2000 and identified all randomized crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation.


RESULTS
We identified 526 randomized controlled trials, of which 116 were crossover trials. Trials were drug efficacy (48%), pharmacokinetic (28%), and nonpharmacologic (30%). The median sample size 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 trials reported a sample size calculation and only 31% of these considered pairing of data in the calculation. Carry-over issues were addressed in 29% of trial's methods. Most trials reported and defended a washout period (70%). Almost all trials (93%) tested for treatment effects using paired data and also presented details on by-group results (95%). Only 29% presented CIs or SE so that data could be entered into a meta-analysis.


CONCLUSIONS
Reports of crossover trials frequently omit important methodological issues in design, analysis, and presentation. Guidelines for the conduct and reporting of crossover trials might improve the conduct and reporting of studies using this important trial design.
Mills
Edward J
EJ
Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. millsej@mcmaster.ca
Chan
An-Wen
AW
Wu
Ping
P
Vail
Andy
A
Guyatt
Gordon H
GH
Altman
Douglas G
DG
D022126:Access to Information; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D030881:Disclosure; D017408:Guidelines as Topic; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D012107:Research Design / Q000592:standards; D018401:Sample Size; D016896:Treatment Outcome