Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
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DOI：
10.1016/j.joca.2010.08.019
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发表时间：
2011-05-01
影响因子：
7
通讯作者：
Todman, M.
中科院分区：
文献类型：
--
作者：
Kraus, V. B.;Burnett, B.;Todman, M.
目的：骨关节炎（OA）是一种慢性且缓慢进展的疾病，生物标志物可能能够比目前可用的治疗方法更快地指示治疗反应；这可以加速和促进 OA 药物的发现和开发计划。本文件的目的是对体外（生化和其他可溶性）生物标志物在 OA 药物开发中的应用提供总结和指导，并概述和推动推动这一目标的研究议程。方法：代表来自学术界和工业界的 OA 生物标志物研究领域专家的生物标志物工作组在骨关节炎研究协会国际联邦药物管理局倡议的要求下于 2007 年至 2009 年之间制定了这份共识文件。 （OARSI FDA 倡议）。结果：本文件总结了生物标志物的定义和分类系统、OA 临床试验中使用的当前结果测量、生物标志物在 OA 治疗开发中的应用和潜在效用、OA 相关生物标志物的资格现状、生物标志物资格的途径、推进生物标志物在药物开发中的使用的关键需求、有关实践和临床试验的建议以及推进 OA 相关生物标志物科学的研究议程。 结论： OA 相关生物标志物目前已上市，它们处于各种资格和验证状态。可能对临床试验最早产生有益影响的生物标志物分为两大类，一类是允许在临床研究的合理且可管理的时间范围内（例如 OA 试验在 1-2 年内）针对最有可能做出反应和/或进展（预后值）的受试者，另一类是为临床前决策和试验组织者提供药物具有所需生化效果的早期反馈。随着在特定药物治疗背景下越来越多地研究体外生物标志物，预计该领域的进步将导致可用生物标志物列表的快速扩展，并加深对它们所代表的分子过程的了解。 (C) 2011 年国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal.Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative).Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers.Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.