Marshall Lindsay J, Bailey Jarrod, Cassotta Manuela, Herrmann Kathrin, Pistollato Francesca
Animal Research Issues, 94219The Humane Society of the United States, Gaithersburg, MD, USA.
380235Cruelty Free International, London, UK; 542332Animal Free Research UK, London, UK.
Altern Lab Anim. 2023 Mar;51(2):102-135. doi: 10.1177/02611929231157756. Epub 2023 Mar 7.
The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity - that is, safety issues revealed in human trials that were not apparent in animal tests - or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.
从动物试验到人体治疗的药物转化率在过去几十年一直保持在92%以上。这些失败大多是由于意外毒性——即在人体试验中发现的动物试验中未显现的安全问题——或缺乏疗效。然而,在临床前药物测试流程中使用更多创新工具,如芯片上的器官,已表明这些工具在临床试验前更能预测意外安全事件,因此可用于此目的以及疗效测试。在这里,我们回顾了几个疾病领域,并思考动物模型为何未能提供有效的新疗法。我们还就如何应用更贴近人体的新方法学来解决这一问题提出了一些建议。