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

被引:53
作者
Dirnagl, Ulrich [1 ,2 ,3 ]
Macleod, Malcolm R. [4 ,5 ]
机构
[1] Charite Univ Med Berlin, Dept Neurol, D-13353 Berlin, Germany
[2] Charite Univ Med Berlin, Dept Expt Neurol, D-13353 Berlin, Germany
[3] Charite Univ Med Berlin, Ctr Stroke Res, D-13353 Berlin, Germany
[4] NHS Forth Valley, Dept Neurol, Stirling, Scotland
[5] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland
关键词
bench-to-bedside translation; bias; good laboratory practice; meta-analysis; neuroprotection; preclinical; systematic review; stroke; ACUTE ISCHEMIC-STROKE; NXY-059; QUALITY; BENCH; BIAS;
D O I
10.1111/j.1476-5381.2009.00211.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1154 / 1156
页数:3
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