The strategic, fit-for-purpose use of the combination of robust target engagement and well-qualified disease-related biomarkers enhances understanding of the mechanism of action, ties together preclinical and clinical data, enables the assessment of target engagement, facilitates early proof of concept and dose focusing, and increases the efficiency of early clinical development with improved quality of decision making. Significant progress in biomarker discovery, validation, and qualification has increased drug-development decision making and regulatory applications. Target engagement biomarkers are present early in a pathophysiologic cascade and inform on physical or biological interactions with the molecular target of the drug. Disease-related biomarkers are present late in the pathophysiologic cascade and are linked to clinical benefit; thus, they assess a drug's effect on a particular disease. Together, these concepts lay the groundwork for high-quality drug-development decision making and a framework for the acceptance and qualification of biomarkers for regulatory use.

中文翻译：

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药物开发中适合目的的生物标志物的战略方法。

结合有力的靶点参与和合格的疾病相关生物标记物进行战略性，针对目的的使用，可以增强对作用机理的了解，将临床前和临床数据联系在一起，可以评估靶点参与度，并有助于早期证明概念和剂量集中，并通过改善决策质量来提高早期临床开发的效率。生物标志物发现，验证和鉴定方面的重大进展增加了药物开发的决策制定和监管应用。靶标参与生物标记物在病理生理学级联的早期出现，并告知与药物分子靶标的物理或生物相互作用。与疾病相关的生物标志物出现在病理生理学连锁反应的后期，并与临床获益相关。从而，他们评估药物对特定疾病的影响。这些概念共同为高质量药物开发决策奠定了基础，并为接受和鉴定用于监管用途的生物标志物奠定了框架。