Department of Neurology, Charite University Medicine, Berlin, Germany.
Br J Pharmacol. 2009 Aug;157(7):1154-6. doi: 10.1111/j.1476-5381.2009.00211.x. Epub 2009 Jun 23.
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.
在本期中,Bath 等人运用最先进的荟萃分析工具来解决一个紧迫的问题:为什么 NXY-059,一种当时被认为完全符合神经保护药物临床前数据评估所有建议的化合物,在临床上却失败了。他们定量地证明存在负向发表偏倚,即该化合物在实验性中风中确实具有神经保护作用,但这种偏倚可能导致对疗效的高估,并且在健康、雄性、青春期动物中的疗效是临床试验成功的不佳预测指标。这项研究为研究人员、期刊编辑、制药行业和科学政策制定者提供了重要信息。在模拟人类中风的实验中,偏倚普遍存在且相关。简单的措施可能会大大减少这种偏倚的影响。进行临床试验的决定应该基于对动物数据的彻底和系统的审查。