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中风研究遭遇瓶颈:逆境中的出路应是荟萃分析和良好实验室规范。

Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice.

机构信息

Department of Neurology, Charite University Medicine, Berlin, Germany.

出版信息

Br J Pharmacol. 2009 Aug;157(7):1154-6. doi: 10.1111/j.1476-5381.2009.00211.x. Epub 2009 Jun 23.

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.

摘要

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。

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Effects of NXY-059 in experimental stroke: an individual animal meta-analysis.NXY-059 对实验性中风的影响:个体动物荟萃分析。
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NXY-059: brain or vessel protection.
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引用本文的文献

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Revisiting Stem Cell-Based Clinical Trials for Ischemic Stroke.重新审视基于干细胞的缺血性中风临床试验
Front Aging Neurosci. 2020 Dec 14;12:575990. doi: 10.3389/fnagi.2020.575990. eCollection 2020.

本文引用的文献

1
Effects of NXY-059 in experimental stroke: an individual animal meta-analysis.NXY-059 对实验性中风的影响:个体动物荟萃分析。
Br J Pharmacol. 2009 Aug;157(7):1157-71. doi: 10.1111/j.1476-5381.2009.00196.x. Epub 2009 Apr 27.
7
Improving outcome after stroke: overcoming the translational roadblock.改善卒中预后:克服转化障碍。
Cerebrovasc Dis. 2008;25(3):268-78. doi: 10.1159/000118039. Epub 2008 Feb 22.
9
NXY-059 for the treatment of acute ischemic stroke.NXY-059用于治疗急性缺血性中风。
N Engl J Med. 2007 Aug 9;357(6):562-71. doi: 10.1056/NEJMoa070240.

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