02431nas a2200349   4500000000100000000000100001008004100002260001200043653001200055653002700067653003300094653001100127653002700138653002300165653002700188653001100215653002000226653001100246653002200257100002600279700002300305700002300328700001900351700002500370700002100395245005000416856005800466300001200524490000700536520152400543022001402067       2006                            d  c2006-0310aAnimals10aDisease Models, Animal10aDrug Evaluation, Preclinical10aHumans10aMeta-Analysis as Topic10aModels, Biological10aNeuroprotective Agents10aPubMed10aResearch Design10aStroke10aTreatment Outcome1 aVictoria E. O'Collins1 aMalcolm R. Macleod1 aGeoffrey A. Donnan1 aLaura L. Horky1 aBart H. van der Worp1 aDavid W. Howells00a1,026 experimental treatments in acute stroke  uhttps://onlinelibrary.wiley.com/doi/10.1002/ana.20741  a467-4770 v593 aOBJECTIVE: 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.  a0364-5134