Chapter 20 – Animal Models of Ischemic Stroke Versus Clinical Stroke: Comparison of Infarct Size, Cause, Location, Study Design, and Efficacy of Experimental Therapies

You'll have to ask your doctor if this analysis covered Dr. Michael Tymianski of the Toronto Western Hospital Research Institute in Canada referencing 1000+ failed neuroprotective clinical trials.
https://www.sciencedirect.com/science/article/pii/B9780128094686000206

• Victoria E. O’Collins^*,
• Geoffrey A. Donnan^*,
• Malcolm R. Macleod^**,
• David W. Howells^{*, †}

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https://doi.org/10.1016/B978-0-12-809468-6.00020-6

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Abstract

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.

Keywords

• animal models;
• cerebral ischemia;
• focal ischemia;
• infarct size;
• metaanalysis;
• neuroprotection;
• stroke;
• thrombolysis

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