TAS::75 0888::TAS

骨关节炎（OA）是最常见的关节炎形式，是一种进展缓慢的疾病，临床表现为疼痛、畸形和功能丧失。骨关节炎是导致老年人残疾和丧失独立性的一个重要因素。膝关节骨性关节炎与功能的逐渐下降有关，包括从坐姿到站立姿势的变化困难，活动能力和进行日常生活活动的能力下降。虽然最近的科学进步已经为类风湿关节炎提供了非常有效的疾病改善疗法，但对于骨关节炎还没有这样的疗法。由于疾病的慢性性质和可变的临床结果，需要更好地了解临床相关或以患者为中心的结果-疼痛，僵硬，功能减退，镇痛药的使用，残疾，生活质量和综合评分之间的关系，这些和其他临床相关结果。由于骨性关节炎的慢性性质和缺乏有效的疾病治疗方法，患者使用一系列生物行为、饮食、药物和补充和替代（CAM）疗法来减轻骨性关节炎的症状、疼痛、改善功能和生活质量。尽管CAM疗法被广泛使用，但相对较少的CAM疗法已经被适当的研究设计进行了充分的测试，以评估其在改善以患者为中心的结果方面的有效性。骨关节炎倡议是一项大型流行病学研究，每年对高风险或已发展为膝关节OA的受试者（基线固定屈曲x线片定义）进行评估。此外，在基线时，评估了大量的生物行为、饮食、药物和CAM治疗方法，其中大多数“治疗”在8年的预计随访中每年或每两年评估一次。在研究生物行为、饮食、药理学和CAM治疗对改善膝关节骨关节炎患者为中心的预后的有效性时，在评估流行病学数据时出现了几个分析问题。首先，目前还没有有效的综合结果测量方法来解释膝关节骨关节炎对以患者为中心的结果的全部影响。虽然西安大略和麦克马斯特大学骨关节炎指数（WOMAC）和膝关节损伤和骨关节炎结局评分（oos）总结量表已经开发出来，但它们完全依赖于主观结果，并且高度相互关联，使得总结得分的价值值得怀疑。其次，基线时以患者为中心的预后较差和膝关节骨性关节炎的参与者更有可能使用辅助骨关节炎疗法来缓解症状。这种“指征混淆”使CAM治疗的潜在益处分析偏向于无效，使得难以辨别它们是否对改善膝关节OA疼痛和症状有效。最先进的统计方法已经开发出来，可以合理有效地处理这些分析问题，并将在本项目中使用。

Osteoarthritis (OA), the most common form of arthritis, is a slowly progressing disease characterized clinically by pain, deformity, and loss of function. OA is a significant contributor to disability and loss of independence among the elderly. Knee OA is associated with a progressive reduction in function, including difficulty in changing from the sitting to the standing position, and a decrease in mobility and in the ability to carry out activities of daily living. While recent scientific advances have yielded highly effective disease-modifying therapies for rheumatoid arthritis, no such therapies exist for osteoarthritis. Because of the chronic nature of the disease and variable clinical outcomes, a better understanding of the relationship between various measures of clinically relevant or patient-centered outcomes - pain, stiffness, reduced function, use of analgesics, disability, quality of life and composite scores accounting for these and other clinically relevant outcomes are needed. Due to its chronic nature and the lack of effective disease modifying therapies a range of biobehavioral, dietary, pharmacologic and complementary and alternative (CAM) therapies are used by patients to reduce OA symptoms, pain, and improve function and quality of life. Despite their wide use, relatively few CAM therapies have been tested adequately with appropriate study designs to assess their effectiveness in improving patient-centered outcomes. The Osteoarthritis Initiative is large epidemiologic study with multiple patient-centered outcomes assessed yearly in subjects at high risk or having already developed knee OA as defined by fixed flexion radiographs at baseline. In addition at baseline, a large inventory of biobehavioral, dietary, pharmacologic and CAM therapies was assessed and most of these "treatments" are assessed either yearly or every two years throughout 8 years of projected follow-up. When studying the effectiveness of biobehavioral, dietary, pharmacologic and CAM therapies on improving patient centered outcomes related to knee osteoarthritis several analytic issues arise when evaluating epidemiological data. First no validated composite outcome measure has been developed that accounts for the full impact of knee osteoarthritis on patient-centered outcomes. While Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Knee Injury and Osteoarthritis Outcomes Score (KOOS) summary scales have been developed they rely exclusively on subjective outcomes, and are highly inter-correlated making a summary score of questionable value. Second, participant s at baseline with worse patient-centered outcomes and knee osteoarthritis are more likely to utilize CAM therapies in an attempt to alleviate symptoms. This "confounding by indication" biases analyses of the potential beneficial of CAM therapies effects towards the null, making it difficult to discern whether they are effective for improvement of knee OA pain and symptoms. State-of-the art statistical methods have been developed that deal reasonably effectively with these analytic issues and will be employed in this project.