Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Shanghai, China.
Discovery Medicine, GlaxoSmithKline, Upper Providence, Pennsylvania, United States of America.
PLoS One. 2020 Oct 12;15(10):e0240234. doi: 10.1371/journal.pone.0240234. eCollection 2020.
The Probability of Pharmacology Success, or PoPS, is a powerful metric to inform progression decisions by quantifying a compound's overall pharmacological strength based on its mechanism. It is defined as the probability that X level of pharmacology is achieved in Y proportion of patients at a safe dose. The importance of adequate drug exposure, target engagement and functional pharmacology for enabling a compound's efficacy is widely recognized. The PoPS estimates how well these conditions are met by integrating the compound's pharmacological properties and the target's modulation needs for the intended indication, in a pharmacometric model that includes the knowledge uncertainty. We use examples to illustrate how it can be used to compare drug candidates under specified benefit and risk conditions, support first-in-human decisions based on exposure limits, advise preclinical lead optimisation, and define clinical-trial populations.
药理学成功率（PoPS）是一种强大的指标，可以通过根据化合物的机制量化其整体药理学强度来告知进展决策。它被定义为在安全剂量下，达到 X 水平的药理学在 Y 比例的患者中实现的概率。人们普遍认识到，充分的药物暴露、靶标结合和功能药理学对于使化合物具有疗效是至关重要的。PoPS 通过在包含知识不确定性的药物计量模型中整合化合物的药理学特性和目标对预期适应症的调节需求，来估计这些条件的满足程度。我们使用示例来说明如何在特定的获益和风险条件下比较候选药物，根据暴露限制支持首次人体决策，为临床前先导优化提供建议，并定义临床试验人群。
