1 Coyne Scientific, Atlanta, GA, USA.
SLAS Discov. 2018 Sep;23(8):765-776. doi: 10.1177/2472555218775028. Epub 2018 Jun 4.
The pharmaceutical industry is facing unprecedented challenges as the cost of developing new drugs has reached unsustainable levels, fueled in large parts by a high attrition rate in clinical development. Strategies to bridge studies between preclinical testing and clinical trials are needed to reduce the knowledge gap and allow earlier decisions to be made on the continuation or discontinuation of further development of drugs. The discovery and development of human induced pluripotent stem cells (hiPSCs) have opened up new avenues that support the concept of screening for cell-based safety and toxicity at the level of a population. This approach, termed "Clinical Trials in a Dish" (CTiD), allows testing medical therapies for safety or efficacy on cells collected from a representative sample of human patients, before moving into actual clinical trials. It can be applied to the development of drugs for specific populations, and it allows predicting not only the magnitude of effects but also the incidence of patients in a population who will benefit or be harmed by these drugs. This, in turn, can lead to the selection of safer drugs to move into clinical development, resulting in a reduction in attrition. The current article offers a perspective of this new model for "humanized" preclinical drug development.
制药行业正面临着前所未有的挑战，因为开发新药的成本已经达到了不可持续的水平，这在很大程度上是由于临床开发中的高淘汰率所致。需要采取策略来弥合临床前测试和临床试验之间的研究差距，以缩小知识差距，并允许更早地决定是否继续或停止进一步开发药物。人类诱导多能干细胞（hiPSC）的发现和开发开辟了新途径，支持在人群水平上进行基于细胞的安全性和毒性筛选的概念。这种方法称为“盘中临床试验”（CTiD），允许在实际临床试验之前，用从代表性的人类患者样本中收集的细胞来测试医疗疗法的安全性或疗效。它可用于开发针对特定人群的药物，不仅可以预测效果的幅度，还可以预测人群中受益或受到这些药物影响的患者的发生率。反过来，这可以导致选择更安全的药物进入临床开发，从而降低淘汰率。本文提供了一种新的“人性化”临床前药物开发模式的视角。
