Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Osteoarthritis Cartilage. 2011 May;19(5):515-42. doi: 10.1016/j.joca.2010.08.019. Epub 2011 Mar 23.
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.
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).
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.
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.
骨关节炎（OA）是一种慢性且进展缓慢的疾病，生物标志物可能能够比目前更快速地提示治疗反应，从而加速和促进 OA 药物的发现和开发计划。本文的目的是总结和指导在 OA 药物开发中应用体外（生化和其他可溶性）生物标志物，并概述和激发进一步实现这一目标的研究议程。
在 2007 年至 2009 年期间，代表 OA 生物标志物研究领域的学术界和工业界专家的生物标志物工作组在国际骨关节炎研究协会联邦药物管理局倡议（OARSI FDA 倡议）的要求下制定了这份共识文件。
本文总结了生物标志物的定义和分类系统、OA 临床试验中目前使用的结局测量指标、生物标志物在 OA 治疗药物开发中的应用和潜在效用、目前 OA 相关生物标志物的资格状态、生物标志物资格的途径、推进生物标志物用于药物开发的关键需求、关于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。
尽管目前有许多 OA 相关生物标志物，但它们处于不同的资格和验证状态。最有可能对临床试验产生早期有益影响的生物标志物可分为两类，一类是那些能够在合理和可管理的临床试验时间框架内（例如 OA 试验 1-2 年内）确定最有可能发生反应和/或进展的受试者（预后价值）的生物标志物，另一类是那些能够为临床前决策和试验组织者提供药物具有预期生化作用的早期反馈的生物标志物。随着体外生物标志物在特定药物治疗的背景下越来越多地被研究，预计该领域将取得进展，从而使更多可用的生物标志物列表得以扩展，并且对它们所代表的分子过程的理解也将不断加深。
