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Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice.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。
Br J Pharmacol. 2009 Aug;157(7):1154-6. doi: 10.1111/j.1476-5381.2009.00211.x. Epub 2009 Jun 23.
2
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.
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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.
2
Update of the stroke therapy academic industry roundtable preclinical recommendations.中风治疗学术产业圆桌会议临床前建议更新
Stroke. 2009 Jun;40(6):2244-50. doi: 10.1161/STROKEAHA.108.541128. Epub 2009 Feb 26.
3
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.急性缺血性卒中发病3至4.5小时后使用阿替普酶进行溶栓治疗。
N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
4
Reprint: Good laboratory practice: preventing introduction of bias at the bench.转载:良好实验室规范:防止实验台引入偏差。
J Cereb Blood Flow Metab. 2009 Feb;29(2):221-3. doi: 10.1038/jcbfm.2008.101. Epub 2008 Sep 17.
5
Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality.NXY - 059在实验性局灶性脑缺血中的疗效证据因研究质量而混淆。
Stroke. 2008 Oct;39(10):2824-9. doi: 10.1161/STROKEAHA.108.515957. Epub 2008 Jul 17.
6
Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.初始严重程度与抗抑郁药疗效:对提交给美国食品药品监督管理局的数据进行的荟萃分析。
PLoS Med. 2008 Feb;5(2):e45. doi: 10.1371/journal.pmed.0050045.
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.
8
Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach.实验性中风研究设计中偏倚的实证证据:一种元流行病学方法。
Stroke. 2008 Mar;39(3):929-34. doi: 10.1161/STROKEAHA.107.498725. Epub 2008 Jan 31.
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.
10
A critical appraisal of the NXY-059 neuroprotection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke.对急性中风的NXY-059神经保护研究的批判性评估:需要在中风动物模型中对神经保护剂进行更严格的测试。
Exp Neurol. 2007 May;205(1):20-5. doi: 10.1016/j.expneurol.2007.03.003. Epub 2007 Mar 12.

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.

DOI:10.1111/j.1476-5381.2009.00211.x
PMID:19664136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2743833/
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。