Objective
Preclinical evaluation of neuroprotectants fostered high
expectations of clinical efficacy. When not matched, the question arises
whether experiments are poor indicators of clinical outcome or whether
the best drugs were not taken forward to clinical trial. Therefore, we
endeavored to contrast experimental efficacy and scope of testing of
drugs used clinically and those tested only experimentally.
Methods
We identified neuroprotectants and reports of
experimental efficacy via a systematic search. Controlled in vivo and in
vitro experiments using functional or histological end points were
selected for analysis. Relationships between outcome, drug mechanism,
scope of testing, and clinical trial status were assessed statistically.
Results
There was no evidence that drugs used clinically (114
drugs) were more effective experimentally than those tested only in
animal models (912 drugs), for example, improvement in focal models
averaged 31.3 ± 16.7% versus 24.4 ± 32.9%, p > 0.05,
respectively. Scope of testing using Stroke Therapy Academic Industry
Roundtable (STAIR) criteria was highly variable, and no relationship was
found between mechanism and efficacy.
Interpretation
The results question whether the most efficacious drugs
are being selected for stroke clinical trials. This may partially
explain the slow progress in developing treatments. Greater rigor in the
conduct, reporting, and analysis of animal data will improve the
transition of scientific advances from bench to bedside. Ann Neurol 2006
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