Look back in anger - what clinical studies tell us about preclinical work.
Look back in anger - what clinical studies tell us about preclinical work.
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DOI：
10.14573/altex.2013.3.275
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hartung T
中科院分区：
文献类型：
--
作者：
Hartung T
被动物研究和基础研究误导了？每当我们仔细研究某个领域的临床试验结果时，例如最近的中风或感染性休克，我们就会看到我们的临床前模型的价值是多么有限。对于所有适应症，95%进入临床试验的药物没有进入市场，尽管用于开发它们的（动物）模型有很大的希望。药物开发已经开始减少对动物模型的依赖：例如，在欧洲，尽管研发支出增加，但制药公司的动物使用从2005年到2008年下降了25%以上。体外研究同样受到限制：可疑的细胞真实性、过度传代、支原体感染和缺乏分化以及非稳态和非生理培养条件危及这些模型的相关性。统计和报告的标准往往很差，进一步损害了可靠性。来自行业的令人震惊的研究显示，里程碑式的研究的重现性很差。本文讨论了导致临床前研究缺乏可重复性和相关性的因素。结论是：发表更少，但质量更好，不要依赖于动物研究的表面价值。
Misled by animal studies and basic research? Whenever we take a closer look at the outcome of clinical trials in a field such as, most recently, stroke or septic shock, we see how limited the value of our preclinical models was. For all indications, 95% of drugs that enter clinical trials do not make it to the market, despite all promise of the (animal) models used to develop them. Drug development has started already to decrease its reliance on animal models: In Europe, for example, despite increasing R&D expenditure, animal use by pharmaceutical companies dropped by more than 25% from 2005 to 2008. In vitro studies are likewise limited: questionable cell authenticity, over-passaging, mycoplasma infections, and lack of differentiation as well as non-homeostatic and non-physiologic culture conditions endanger the relevance of these models. The standards of statistics and reporting often are poor, further impairing reliability. Alarming studies from industry show miserable reproducibility of landmark studies. This paper discusses factors contributing to the lack of reproducibility and relevance of pre-clinical research. The conclusion: Publish less but of better quality and do not rely on the face value of animal studies.
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影响因子：
2.7
作者：
Ersson, Clara;Moller, Peter;Moller, Lennart
通讯作者：
Moller, Lennart
影响因子：
4.4
作者：
Bebarta, V;Luyten, D;Heard, K
通讯作者：
Heard, K
DOI：
10.1073/pnas.1212247109
发表时间：
2012-10-16
影响因子：
11.1
作者：
Fang, Ferric C.;Steen, R. Grant;Casadevall, Arturo
通讯作者：
Casadevall, Arturo
影响因子：
3.7
作者：
Briel M;Müller KF;Meerpohl JJ;von Elm E;Lang B;Motschall E;Gloy V;Lamontagne F;Schwarzer G;Bassler D;OPEN Consortium
通讯作者：
OPEN Consortium
影响因子：
2.7
作者：
Coecke, S;Balls, M;Stokes, W
通讯作者：
Stokes, W