TY - JOUR
T1 - Empirical evidence of bias in the design of experimental stroke studies - A metaepidemiologic approach
AU - Crossley, Nicolas A.
AU - Sena, Emily
AU - Goehler, Jos
AU - Horn, Jannekke
AU - van der Worp, Bart
AU - Bath, Philip M. W.
AU - Macleod, Malcolm
AU - Dirnagl, Ulrich
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - https://doi.org/10.1161/STROKEAHA.107.498725
DO - https://doi.org/10.1161/STROKEAHA.107.498725
M3 - Article
C2 - 18239164
SN - 0039-2499
VL - 39
SP - 929
EP - 934
JO - Stroke; a journal of cerebral circulation
JF - Stroke; a journal of cerebral circulation
IS - 3
ER -