title: Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice.
abstract: In this issue, Bath et al. use state of the art meta-analytical tools to address the pressing question of why NXY-059, a compound at the time considered to fulfil all the recommendations for the evaluation of preclinical data regarding neuroprotective drugs, has failed clinically. They demonstrate quantitatively that a negative publication bias existed, that the compound was indeed neuroprotective in experimental stroke, but that bias may have resulted in an overestimation of efficacy, and that efficacy in healthy, male, adolescent animals is a poor predictor of success in clinical trial. The study contains important messages for researchers, journal editors, the pharmaceutical industry and science policy makers. Bias is both prevalent and relevant in experiments modelling human stroke. Simple measures can reduce, perhaps substantially, the impact of such bias. The decision to proceed to clinical trial should be based on a thorough and systematic review of the animal data.
authors: Department of Neurology, Charite University Medicine, Berlin, Germany. ulrich.dirnagl@charite.de
authors: Ulrich
authors: U
authors: Dirnagl
authors: Malcolm R
authors: MR
authors: Macleod
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D015201:Meta-Analysis as Topic; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D001557:Benzenesulfonates; D018696:Neuroprotective Agents; C120851:disufenton sodium