Animal models in translational medicine: Validation and prediction
Animal models in translational medicine: Validation and prediction
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DOI：
10.1016/j.nhtm.2014.08.001
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发表时间：
2014-09-01
期刊：
影响因子：
--
通讯作者：
Van Roy, Maarten
中科院分区：
文献类型：
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作者：
Denayer, Tinneke;Stoehr, Thomas;Van Roy, Maarten
尽管在药物开发方面投入了大量资金，但药物在临床开发期间的总体成功率仍然很低。一个突出的解释是有缺陷的临床前研究，在这些研究中，动物模型的使用和结果是弥合临床转化差距的关键。因此，选择一个有效的和可预测的动物模型对于解决临床问题至关重要。在这篇综述中，讨论了目前动物模型的挑战和局限性，重点是适合目的的验证。此外，还提供了关于动物模型的选择、设计和实施的指导，包括评估有效性和安全性终点的建议。为了提高临床翻译水平，本文讨论了人源化小鼠模型的使用和临床前应用的临床特点。最重要的是，当与新兴的替代翻译方法相结合时，动物模型的翻译价值可以进一步提高。
Despite large investments in drug development, the overall success rate of drugs during clinical development remains low. One prominent explanation is flawed preclinical research, in which the use and outcome of animal models is pivotal to bridge the translational gap to the clinic. Therefore, the selection of a validated and predictive animal model is essential to address the clinical question. In this review, the current challenges and limitations of animal models are discussed, with a focus on the fit-for purpose validation. Moreover, guidance is provided on the selection, design and conduct of an animal model, including the recommendation of assessing both efficacy and safety endpoints. In order to improve the clinical translation, the use of humanized mouse models and preclinical applications of clinical features are discussed. On top, the translational value of animal models could be further enhanced when combined with emerging alternative translational approaches.