The development of novel therapeutics is associated with high rates of attrition, with unexpected adverse events being a major cause of failure. Serious adverse events have led to organ failure, cancer development and deaths that were not expected outcomes in clinical trials. These life-threatening events were not identified during therapeutic development due to the lack of preclinical safety tests that faithfully represented human physiology. We highlight the successful application of several novel technologies, including high-throughput screening, organs-on-chips, microbiome-containing drug-testing platforms and humanised mouse models, for mechanistic studies and prediction of toxicity. We propose the incorporation of similar preclinical tests into future drug development to reduce the likelihood of hazardous therapeutics entering later-stage clinical trials.

新疗法的开发与高损耗率有关，意外的不良事件是失败的主要原因。严重的不良事件导致器官衰竭、癌症发展和死亡，这在临床试验中未达到预期结果。由于缺乏忠实代表人类生理学的临床前安全性测试，在治疗开发过程中未发现这些危及生命的事件。我们强调了几种新技术的成功应用，包括高通量筛选、器官芯片、含微生物组的药物测试平台和人源化小鼠模型，用于机制研究和毒性预测。