Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach

Crossley, Nicolas A., Sena, Emily S., Goehler, Jos, Horn, Jannekke, van der Worp, H. Bart, Bath, Philip M.W., Macleod, Malcolm R and Dirnagl, Ulrich (2008) Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach. Stroke, 39 . pp. 929-934. ISSN 1524-4628

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Abstract

Background and Purpose: At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size.

Methods: Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta meta-analysis to obtain a summary measure of the impact of the various design characteristics.

Results: Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score.

Conclusions: We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/704496
Keywords: animal experimentation, cerebrovascular accident, meta-analysis
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Clinical Neuroscience
Identification Number: https://doi.org/10.1161/STROKEAHA.107.498725
Depositing User: Sayers, Hazel
Date Deposited: 22 Aug 2008 08:55
Last Modified: 04 May 2020 16:27
URI: https://eprints.nottingham.ac.uk/id/eprint/880

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