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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; Dirnagl, Ulrich

Authors

Nicolas A. Crossley

Emily S. Sena

Jos Goehler

Jannekke Horn

H. Bart van der Worp

Philip M.W. Bath

Malcolm R Macleod

Ulrich Dirnagl



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.

Journal Article Type Article
Publication Date Jan 31, 2008
Journal Stroke
Print ISSN 0039-2499
Electronic ISSN 1524-4628
Publisher American Heart Association
Peer Reviewed Peer Reviewed
Volume 39
Institution Citation Crossley, N. A., Sena, E. S., Goehler, J., Horn, J., van der Worp, H. B., Bath, P. M., …Dirnagl, U. (2008). Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach. Stroke, 39, doi:10.1161/STROKEAHA.107.498725
DOI https://doi.org/10.1161/STROKEAHA.107.498725
Keywords animal experimentation, cerebrovascular accident, meta-analysis
Publisher URL http://stroke.ahajournals.org/content/39/3/929
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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