Biomarkers Program, Predictive Safety Testing Consortium, Critical Path Institute Tucson, AZ 85718, USA.
Exp Biol Med (Maywood). 2021 Nov;246(22):2391-2398. doi: 10.1177/15353702211002153. Epub 2021 Mar 23.
Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.
安全生物标志物是药物开发的重要工具，无论是在临床前还是临床阶段。将非临床安全生物标志物的性能与组织病理学相关联是一个直接的过程，理想情况下，该生物标志物在所有常用于安全性评估的物种中都有用。在临床验证研究中，由于组织病理学不可行，因此将安全生物标志物与标准生物标志物的反应进行比较，或者与临床判断进行比较。在全球范围内，监管机构已经制定了相关程序来对生物标志物进行鉴定，以确保在药物开发研究中使用和解释生物标志物数据的方式具有信心。本文描述了目前已获得鉴定的安全生物标志物，这些生物标志物可用于监测肾毒性和心脏毒性，以及正在进行的将安全生物标志物鉴定用于肝脏、骨骼肌和血管损伤的项目。在许多情况下，这些关键药物开发工具的开发和使用依赖于合作关系和数据的预竞争共享，以支持鉴定工作。
