IJE Advance Access originally published online on February 14, 2007
International Journal of Epidemiology 2007 36(2):422-430; doi:10.1093/ije/dym001
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Evidence from crossover trials: empirical evaluation and comparison against parallel arm trials
1 Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
2 Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
* Corresponding author. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. E-mail: jioannid{at}cc.uoi.gr
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Abstract |
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Background We aimed to evaluate empirically how crossover trial results are analysed in meta-analyses of randomized evidence and whether their results agree with parallel arm studies on the same questions.
Methods We used a systematic sample of Cochrane meta-analyses including crossover trials. We evaluated the methods of analysis for crossover results and compared the concordance of the estimated effect sizes in crossover vs parallel arm trials.
Results Of 334 screened reviews, 62 had crossover trials. Of those, 33 meta-analyses performed quantitative syntheses involving two-arm two-period crossover trials. There was large variability on how these trials were analysed; only one of the 33 meta-analyses stated that they used the data from both the first and second period with an appropriate paired approach. Nine meta-analyses used the first period data only and 14 gave no information at all on what they had done. Twenty-eight meta-analyses had both crossover (n = 137, sample size n = 7162) and parallel arm (n = 132, sample size n = 11 398) trials. Effect sizes correlated well with the two types of designs (
= 0.72). Differences on whether the summary effect had a P < 0.05 or not were common due to limited sample sizes. The summary relative odds ratio for parallel arm vs crossover designs for favourable outcomes was 0.87 (95% CI, 0.74–1.02).
Conclusions Crossover designs may contribute evidence in a fifth of systematic reviews, but few meta-analyses make use of their full data. The results of crossover trials tend to agree with those of parallel arm trials, although there was a trend for more conservative treatment effect estimates in parallel arm trials.
Keywords Crossover studies, parallel studies, meta-analysis, empirical evaluation
Accepted 20 December 2006