Department of Clinical Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Biomark Med. 2010 Dec;4(6):815-27. doi: 10.2217/bmm.10.107.
Biomarkers are now increasingly employed in drug development for decision-making. New targets and candidate drugs should not only have drug-like properties (i.e., be 'drugable'), but the supporting biomarker platform should be 'decisionable'. For example, biomarkers for target engagement have supported the biologic plausibility for novel mechanisms and have aided in accelerated proof of concept. In many other circumstances, biomarkers have aided in the elucidation of mechanisms of action and disease progression. In this article, decisonable biomarker principles that aid in decision-making within the realm of early discovery through to clinical proof of concept are discussed. Case studies of applications of both target engagement and disease-related biomarkers are illustrated in the field of cardiovascular drug discovery and translational development. We propose that biomarkers, if prospectively implemented in an early development program, have the potential to accelerate drug development, facilitate the design of informative trials and dose selection for accelerated development, and establish an overall increase in probability of developmental success and efficiency.
生物标志物现在越来越多地被应用于药物开发中的决策。新的靶点和候选药物不仅应具有类药性（即“可成药”），而且支持的生物标志物平台也应“可决策”。例如，用于靶标结合的生物标志物支持了新型机制的生物学合理性，并有助于加速验证概念。在许多其他情况下，生物标志物有助于阐明作用机制和疾病进展。本文讨论了在早期发现到临床验证概念的范围内，有助于决策的可决策生物标志物原则。心血管药物发现和转化开发领域中，应用靶标结合和疾病相关生物标志物的案例研究进行了说明。我们提出，如果在早期开发计划中前瞻性地实施生物标志物，有可能加速药物开发，为信息丰富的试验设计和加速开发的剂量选择提供便利，并提高开发成功率和效率的整体概率。
