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Title: 1,026 experimental treatments in acute stroke.
Austin Authors: O'Collins, Victoria E;Macleod, Malcolm R;Donnan, Geoffrey A ;Horky, Laura L;van der Worp, Bart H;Howells, David William
Affiliation: Neuroscience Lab, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia
Issue Date: 1-Mar-2006
Publication information: Annals of Neurology; 59(3): 467-77
Abstract: 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.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.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.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.
Gov't Doc #: 16453316
DOI: 10.1002/ana.20741
Journal: Annals of Neurology
Type: Journal Article
Subjects: Animals
Disease Models, Animal
Drug Evaluation, Preclinical.methods
Meta-Analysis as Topic
Models, Biological
Neuroprotective Agents.therapeutic use
PubMed.statistics & numerical data
Research Design
Stroke.drug therapy
Treatment Outcome
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