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Int J Epidemiol. 2007 Apr;36(2):422-30. Epub 2007 Feb 14.

Evidence from crossover trials: empirical evaluation and comparison against parallel arm trials.

Author information

1
Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

Abstract

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 = 7,162) and parallel arm (n = 132, sample size n = 11,398) trials. Effect sizes correlated well with the two types of designs (rho = 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.

PMID:
17301102
DOI:
10.1093/ije/dym001
[Indexed for MEDLINE]

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