Methodologic Remedies for the Risk Factor Paradox in Osteoarthritis Progression

骨关节炎进展中危险因素悖论的方法学补救措施

基本信息

批准号：
9134044
负责人：
HYON K CHOI
金额：
$ 10.2万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9134044
关键词：
Activities of Daily Living Affect Aging Alzheimer&apos s Disease Applications Grants Arthritis Biological Birth Weight Body mass index Bone Density Chronic Obstructive Airway Disease Clinical Coronary Arteriosclerosis Databases Degenerative polyarthritis Development Discipline Disease Event Evidence Based Medicine Excess Mortality Female Funding Future Health Individual Infant Infant Mortality Joints Knee Injuries Knee Osteoarthritis Knowledge Left Low Birth Weight Infant Measures Mediation Methodology Methods Obesity Occupational Outcome Pain Patent Foramen Ovale Patients Physically Handicapped Recommendation Recording of previous events Recurrence Reporting Research Research Project Grants Rheumatoid Arthritis Rheumatology Risk Risk Factors Secondary Prevention Selection Bias Smoking Staging Stress Stroke Time United States National Institutes of Health apolipoprotein E-4 base burden of illness causal model cohort design disability evidence base evidence based guidelines indexing insight knee replacement arthroplasty maternal cigarette smoking mortality prevent protective effect response risk variant sex simulation study population

项目摘要

DESCRIPTION (provided by applicant): This proposal is in response to NIH Research Grant Opportunity PA-13-237 using the Osteoarthritis Initiative (OAI) database. Knee osteoarthritis (OA) constitutes a tremendous disease burden in the US, as it causes pain and decreased mobility, and its progression leads to a loss of independence and functional capacity, disability, and total knee replacement. Thus, OA progression represents a compelling target for secondary prevention; however, unlike the risk factors for incident knee OA, the results of studies on risk factors for the progression of knee OA have been paradoxical. For example, a number of risk factors for incident knee OA have been consistently identified, including female sex, obesity, high bone mineral density, knee injury, and repetitive occupational stress on joints. In contrast, none of these factors have been consistently associated with the risk of OA progression. Further, studies have failed to find a consistent association even between obesity or aging (two well-established risk factors for incident knee OA) and the risk of knee OA progression. Although biological explanations for these counterintuitive results may exist, an enticing methodologic explanation is a type of selection bias called index event bias, which can affect research on disease sequelae (e.g., progression) when there are multiple risk factors for sequelae that are also risk factors for having the disease in the first place (e.g., the effect of MI on the risk of severe OA among mild to moderate OA patients [i.e., those with index events]). To date, little research has methodologically investigated the paradoxical phenomena of risk factors for OA progression, leaving a crucial gap in knowledge on this important topic. Unless an appropriate design and analytic method are used to measure the germane impact of purported risk factors in OA (i.e., the most common form of arthritis), ample research funds, time, and effort can be depleted without providing useful evidence for clinical recommendations and biological insight. To validly characterize and overcome the methodological challenges associated with assessing the risk conferred by purported risk factors for OA progression, we will investigate previously reported paradoxical findings using the OAI cohort for the following specific aims: (1) to determine and quantify the index event bias and to clarify the core mechanisms underlying the risk factor paradoxes; (2) to provide methodological remedies, including sensitivity analyses, assessment of the impact of a change in exposure status, and causal modeling approaches for the unbiased impact of purported risk factors on knee OA progression. Furthermore, we will demonstrate inherent limitations of certain exposures in this key research context. By leveraging our expertise in the relevant advanced methodology and the clinical topic, as well as the strengths and our hands-on knowledge of the OAI database, the proposed project will fill crucial gaps in our understanding of the germane impact of risk factors for knee OA progression, and provide key methodologic advances needed for evidence-based medicine in rheumatology and many other disciplines.

描述（由申请人提供）：该提案是对使用骨关节炎倡议 (OAI) 数据库的 NIH 研究资助机会 PA-13-237 的回应膝骨关节炎 (OA) 在美国构成了巨大的疾病负担，因为它会导致疼痛和疼痛。活动能力下降，其进展会导致独立性和功能能力丧失、残疾和全膝关节置换术，因此，与事件的危险因素不同，OA 进展是二级预防的一个引人注目的目标；膝骨关节炎，关于膝骨关节炎进展的危险因素的研究结果是矛盾的，例如，已经确定了一些膝骨关节炎发生的危险因素，包括女性、肥胖、高骨密度、膝关节损伤。相比之下，这些因素都与骨关节炎进展风险没有一致的关联，甚至在肥胖和衰老（两个公认的事件风险因素）之间也没有发现一致的关联。膝骨关节炎）和膝骨关节炎的风险尽管对这些违反直觉的结果可能存在生物学解释，但一种诱人的方法学解释是一种称为指数事件偏差的选择偏差，当存在多个后遗症风险因素同时也是风险因素时，它可能会影响对疾病后遗症（例如进展）的研究首先，我们要了解 MI 对轻度至中度 OA 患者（即有指标事件的患者）发生严重 OA 风险的影响。迄今为止，很少有研究进行方法学调查。 OA 进展的危险因素的矛盾现象，在这一重要主题上留下了重大的知识空白，除非使用适当的设计和分析方法来衡量所谓的 OA 危险因素（即最常见的关节炎形式）的密切影响。），如果没有提供有效的建议临床和生物学见解的有用证据，大量的研究资金、时间和精力就会被耗尽。为了描述和克服与评估 OA 进展的所谓危险因素所带来的风险相关的方法学挑战，我们将进行调查。先前使用 OAI 队列报告的矛盾发现有以下具体目的：（1）确定和量化指标事件偏差并阐明风险因素悖论背后的核心机制；（2）提供方法补救措施，包括敏感性分析、评估暴露状态变化的影响，以及所谓的风险因素对膝关节 OA 进展的公正影响的因果模型方法。此外，我们将利用我们在相关研究领域的专业知识来证明某些暴露的固有局限性。先进的方法论和临床主题，以及 OAI 数据库的优势和实践知识，拟议的项目将填补我们对膝 OA 进展风险因素的密切影响的理解的关键空白，并提供基于证据的关键方法学进展风湿病学和许多其他学科的医学。