The pharmaceutical industry is tackling increasingly complex multifactorial diseases, resulting in increases in research & development (R&D) costs and reductions in the success rates for drug candidates during Phase 2 and 3 clinical trials, with a lack of efficacy being the primary reason for drug candidate failure. This implies that the predictive power of current preclinical assays for drug candidate efficacy is suboptimal and, therefore, that alternatives should be developed. Here, I review emerging in vitro, imaging, and in silico technologies and discuss their potential contribution to drug efficacy assessment. Importantly, these technologies are complimentary and can be bundled into the preclinical platform. In particular, patient-on-a-chip recapitulates both human genetics and physiology. The response of a patient-on-a-chip to drug candidate treatment is monitored with light-sheet fluorescent microscopy and fed into the image-analysis pipeline to reconstruct an image-based systems-level model for disease pathophysiology and drug candidate mode of action. Thus, such models could be useful tools for assessing drug candidate efficacy and safety in humans.

制药行业正在应对日益复杂的多因素疾病，从而导致研究和开发（R＆D）成本的增加以及候选药物在2期和3期临床试验中的成功率下降，而缺乏功效是候选药物的主要原因失败。这暗示了当前临床前测定对于候选药物功效的预测能力不是最理想的，因此，应该开发替代方法。在这里，我回顾了新兴的体外，成像和计算机模拟技术，并讨论它们对药物功效评估的潜在贡献。重要的是，这些技术是互补的，可以捆绑到临床前平台中。特别地，单片患者概括了人类遗传学和生理学。用光片荧光显微镜监测片上患者对候选药物的反应，并将其输入到图像分析管道中，以重建基于图像的系统级模型，用于疾病病理生理学和候选药物的作用方式。因此，此类模型可能是用于评估候选药物在人体中的功效和安全性的有用工具。