Stroke research at a road block: the streets from adversity should be paved with meta‐analysis and good laboratory practice
- 23 July 2009
- journal article
- editorial
- Published by Wiley in British Journal of Pharmacology
- Vol. 157 (7) , 1154-1156
- https://doi.org/10.1111/j.1476-5381.2009.00211.x
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.Keywords
This publication has 12 references indexed in Scilit:
- Effects of NXY‐059 in experimental stroke: an individual animal meta‐analysisBritish Journal of Pharmacology, 2009
- Update of the Stroke Therapy Academic Industry Roundtable Preclinical RecommendationsStroke, 2009
- Evidence for the Efficacy of NXY-059 in Experimental Focal Cerebral Ischaemia Is Confounded by Study QualityStroke, 2008
- Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic StrokeNew England Journal of Medicine, 2008
- Reprint: Good Laboratory Practice: Preventing Introduction of Bias at the BenchJournal of Cerebral Blood Flow & Metabolism, 2008
- Empirical Evidence of Bias in the Design of Experimental Stroke StudiesStroke, 2008
- Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug AdministrationPLoS Medicine, 2008
- Improving Outcome after Stroke: Overcoming the Translational RoadblockCerebrovascular Diseases, 2008
- Bench to Bedside: The Quest for Quality in Experimental Stroke ResearchJournal of Cerebral Blood Flow & Metabolism, 2006
- Recommendations for Standards Regarding Preclinical Neuroprotective and Restorative Drug DevelopmentStroke, 1999