https://www.sciencedirect.com/science/article/pii/B9780128094686000206
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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