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1,026 Experimental treatments in acute stroke

Annals of neurology, 2006-03, Vol.59 (3), p.467-477 [Peer Reviewed Journal]

Copyright © 2006 American Neurological Association ;2006 INIST-CNRS ;ISSN: 0364-5134 ;EISSN: 1531-8249 ;DOI: 10.1002/ana.20741 ;PMID: 16453316 ;CODEN: ANNED3

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Title:
1,026 Experimental treatments in acute stroke
Author: O'Collins, Victoria E. ; Macleod, Malcolm R. ; Donnan, Geoffrey A. ; Horky, Laura L. ; van der Worp, Bart H. ; Howells, David W.
Subjects: Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Disease Models, Animal ; Drug Evaluation, Preclinical - methods ; Humans ; Medical sciences ; Meta-Analysis as Topic ; Models, Biological ; Neurology ; Neuroprotective Agents - therapeutic use ; Pharmacology. Drug treatments ; PubMed - statistics & numerical data ; Research Design ; Stroke - drug therapy ; Treatment Outcome ; Vascular diseases and vascular malformations of the nervous system
Is Part Of: Annals of neurology, 2006-03, Vol.59 (3), p.467-477
Description: 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
Publisher: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Language: English
Identifier: ISSN: 0364-5134
EISSN: 1531-8249
DOI: 10.1002/ana.20741
PMID: 16453316
CODEN: ANNED3
Source: MEDLINE
Alma/SFX Local Collection

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1,026 Experimental treatments in acute stroke

Copyright © 2006 American Neurological Association ;2006 INIST-CNRS ;ISSN: 0364-5134 ;EISSN: 1531-8249 ;DOI: 10.1002/ana.20741 ;PMID: 16453316 ;CODEN: ANNED3

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