Animal Models of Ischemic Stroke Versus Clinical Stroke: Comparison of Infarct Size, Cause, Location, Study Design, and Efficacy of Experimental Therapies

A quantitative and qualitative comparison of contemporary neuroprotection and thrombolytic stroke trials and their preclinical animal counterparts has been undertaken, with metaanalysis [DerSimonian, R., Laird, N., 1986. Metaanalysis in clinical trials. Control. Clin. Trials 7 (3), 177-188.] used to evaluate imaging and histological outcomes.Results from 35 clinical trials including 5,532 patients were compared with data from 3,145 preclinical acute-stroke experiments in 45,476 animals. While clinical trials tended to be of higher methodological quality and have larger sample sizes than animal experiments (71 patients vs. 7 animals per group), both were similarly underpowered owing to the greater variability in human stroke (average standard deviation of mean in humans 99% vs. 30% in animals). Proportionally, animal infarcts were almost 4 times larger than human infarcts in untreated control groups (27% vs. 8% of the hemisphere) although there was considerable variability in size owing to comorbidities and stroke type. Eighty-six percent of animal studies and 54% of clinical trials reported smaller infarcts in groups receiving treatment, with 41% of clinical trials reporting an improvement in the prespecified hypothesis. Animal experiments were not effective in predicting individual trial results, nor the level of neuroprotection, however, there was a fair agreement between the direction of the animal and clinical outcomes when looking at the overall direction of drug outcome. As a drug-screening tool, experimental stroke studies need refinement. Rational frameworks for translational research will help.