Long-term Outcomes of Knee OA in the OAI Cohort

 描述（由申请人提供）：膝关节骨关节炎（OA）是疼痛、功能限制和残疾的主要原因，也是最昂贵的肌肉骨骼疾病之一。膝关节骨性关节炎患者人数的迅速增加以及缺乏有效治疗的临床结局不佳是膝关节置换率和成本飙升的关键驱动因素。膝关节OA病理学和临床结局通常会持续数十年，并且具有高度变化的时间过程。了解导致膝关节骨性关节炎不良和良好结局的因素范围是一个优先事项，但对该疾病的长期病程及其决定因素的了解存在重大差距。将预防和治疗目标对准那些最有可能导致不良结果的人是明智的。然而，缺乏足够长时间（≥10年）的纵向研究，使用标准化措施进行频繁评估，以获取结局的完整轨迹、范围和变异性，并研究其决定因素。此外，调查 这些问题受到膝关节OA严重程度和影响的基线异质性的阻碍，这可能是疾病预后观察性研究中不精确和偏倚的来源。OAI始于2002年，是一项独特的队列研究，纳入了4796名膝关节OA患者或有膝关节OA风险的患者，具有来自年度评估的统一、丰富的临床和影像学数据，并已全面随访长达8年，保持良好。我们现在建议在基线后继续评估膝关节OA的结局长达15年，主要通过电话和邮件，这是一种有效且负担较轻的方法，在该老龄化队列中，这种方法将比单独的诊所访视产生更完整的随访。对一部分参与者进行一次简短的临床访问，将使我们能够研究功能的性能指标作为长期结果。我们的目标是利用这一前所未有的长期随访机会，描述疾病不同阶段结局的完整轨迹和概率，识别长期病程中易受攻击和受保护的表型，并研究这些结局的潜在可修改预测因素。结果将涵盖一系列健康领域，包括：膝关节OA相关（疼痛、功能限制和性能、OA全球影响、膝关节置换）、残疾/参与和一般健康。延长的随访期为分析设计提供了机会，通过允许使用从基线到第4年的变化来定义“起始事件”，例如向膝关节疼痛或结构性OA的更晚期阶段的转变或风险因素的有利和不利轨迹的发展，降低了疾病预后研究中常见偏倚和不精确性来源的风险（膝关节OA相关、体能、一般健康和心理社会变量）。然后将在以一系列基线膝关节OA相关和其他协变量为条件的分析中评价这些变化与第5年至第15年发生的后续结局的相关性，其中碰撞者分层偏倚风险最小。使用这种方法，我们将调查的问题，可以告知新兴的预防和治疗策略，重点是改善膝关节骨性关节炎的人的结果。这些包括描述膝关节疼痛和结构性OA不同阶段的不良和良好长期结局的概率，比较近期过渡到更晚期阶段的患者与病程稳定的患者的结局，并确定疾病不同阶段长期结局的可改变决定因素以及这些因素是否因阶段而异，从而表明需要量身定制的干预措施来改善结局。

 DESCRIPTION (provided by applicant): Knee osteoarthritis (OA) is a major cause of pain, functional limitation and disability and among the most costly musculoskeletal conditions. A burgeoning population with knee OA and poor clinical outcomes in the absence of effective treatments are key drivers of the soaring rates and costs of knee replacement. Knee OA pathology and clinical outcomes typically unfold over decades and have a highly varied time course. It is a priority to understand the range of factors that contribute to poor and good outcomes in knee OA, but there are critical gaps in knowledge about the long-term course of the disease and its determinants. It is sensible to target prevention and treatment on those most at risk for poor outcomes. However, there is a paucity of longitudinal studies long enough (≥10 years) with frequent assessment using standardized measures to capture the full trajectory, range and variability of outcomes and investigate their determinants. In addition, investigation of these questions is hampered by baseline heterogeneity in knee OA severity and impact, which can be a source of imprecision and bias in observational studies of disease prognosis. Started in 2002, the OAI is a unique cohort study of 4796 persons with or at risk for knee OA that has uniform, rich clinical and imaging data from annual assessments and has been followed comprehensively for up to 8 years with good retention. We now propose to continue assessment of outcomes of knee OA for up to 15 years after baseline, primarily by phone and mail, an efficient and less burdensome approach that will yield more complete follow-up than clinic visits alone in this aging cohort. A brief clinic visit in a subset of participants will enale us to study performance measures of function as a long-term outcome. Our goal is to take advantage of this unprecedented opportunity for long-term follow-up to describe the full trajectory and probability of outcomes at different stages of disease, to identify vulnerable and protected phenotypes in its long-term course and investigate potentially modifiable predictors of these outcomes. Outcomes will span a range of health domains, including: knee-OA related (pain, functional limitation and performance, OA global impact, knee replacement), disability/participation and general health. The extended follow-up provides the opportunity for an analysis design that reduces the risk of common sources of bias and imprecision in studies of disease prognosis by allowing the use of changes from baseline to year 4 to define "inception events," such as the transition to more advanced stages of knee pain or structural OA or the development of favorable and unfavorable trajectories of risk factors (knee OA-related, physical performance, general health and psychosocial variables). These changes will then be evaluated for their association with subsequent outcomes occurring from year 5 to year 15 in analyses conditioned on a range of baseline knee OA-related and other covariates with a minimal risk of collider stratification bias. Using this approach we will investigate questions that can inform emerging strategies for prevention and treatment that are focused on improving outcomes in persons with knee OA. These include describing the probabilities of both poor and good long-term outcomes at different stages of knee pain and structural OA, comparing outcomes in those with recent transitions to more advanced stages with those whose course has been stable, and identifying the modifiable determinants of long-term outcomes at different stages of disease and whether these differ by stage, thus suggesting the need for tailored interventions to improve outcomes.