Nicolas A. Crossley
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
Emily S. Sena
H. Bart van der Worp
Philip M.W. Bath
Malcolm R Macleod
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|
|Publisher||American Heart Association|
|Peer Reviewed||Peer Reviewed|
|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|
|Keywords||animal experimentation, cerebrovascular accident, meta-analysis|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf|
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf