title: 1,026 experimental treatments in acute stroke.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroscience Lab, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: O'Collins
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Laura L
authors.initials: LL
authors.lastname: Horky
authors.forename: Bart H
authors.initials: BH
authors.lastname: van der Worp
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D015201:Meta-Analysis as Topic; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D039781:PubMed / Q000706:statistics & numerical data; D012107:Research Design; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents