Collider Bias and the Risk Factor Paradoxes in Rheumatic Disease Research

风湿病研究中的碰撞偏差和危险因素悖论

基本信息

批准号：
8636403
负责人：
Uyen-Sa Duc Tran Nguyen
金额：
$ 12.32万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8636403
关键词：
Area Arthritis Biological Birth Weight Body mass index Cardiovascular Diseases Cardiovascular system Clinical Databases Degenerative polyarthritis Development Diagnosis Disease Disease Outcome Disease Progression Dyslipidemias Ensure Environment Equilibrium Event Foundations Funding Future General Population Goals Health Individual Infant Infant Mortality Journals Knee Osteoarthritis Knowledge Left Low Birth Weight Infant Measures Mentored Research Scientist Development Award Mentors Methods Morbidity - disease rate Myocardial Infarction Obesity Outcome Outcomes Research Pathway interactions Population Database Population Study Premature Mortality Psoriasis Psoriatic Arthritis Publications Recommendation Recurrence Research Research Design Research Infrastructure Research Methodology Research Personnel Research Project Grants Research Training Resources Rheumatism Rheumatoid Arthritis Rheumatology Risk Risk Factors Selection Bias Smoker Smoking Smoking Status Staging Stratification Techniques Time Training United States National Institutes of Health burden of illness cardiovascular risk factor career development clinical epidemiology cohort design evidence base experience interest maternal cigarette smoking modifiable risk mortality novel obesity risk organizational structure prevent prospective protective effect public health relevance simulation symposium

项目摘要

DESCRIPTION (provided by applicant): Rheumatic conditions and their sequelae, including rheumatoid arthritis (RA), psoriatic arthritis, and knee osteoarthritis (OA), constitute a tremendous disease burden in the US and worldwide. Unlike the results of studies on risk factors for incident rheumatic conditions, findings on risk factors for disease sequelae among individuals with rheumatic conditions have been contradictory or paradoxical. Although biological explanations for these unexpected results may exist, an enticing alternative methodological explanation is a type of selection bias called collider-stratification bias (hereaftr referred to as collider bias), which occurs when one evaluates the effect of a risk factor on disease sequelae among those in an intermediate stage of disease (e.g., studying smoking effects in people with RA on the risk of a CV event). Little research has methodologically investigated the paradoxical phenomena of risk factors for sequelae events in the context of rheumatic conditions, leaving a crucial gap in knowledge on this important topic. Unless an appropriate design or analytic method is used to ascertain the true impact of suspected risk factors in these major rheumatic conditions, much research funds, time, and effort may be depleted without providing useful evidence for clinical recommendations. To overcome the methodological challenges associated with assessing the risk conferred by purported risk factors for sequela events among people with rheumatic diseases, we will investigate paradoxical findings in 3 key rheumatic disease contexts (smoking and risk of CV events in RA; smoking and risk of psoriatic arthritis in psoriasis; and obesity and risk of disease progression i knee OA). We will use three large databases: a prospective cohort (the Norfolk Arthritis Register [NOAR]), a general population database (The Health Improvement Network [THIN]), and a prospective OA cohort (the Multicenter Osteoarthritis Study [MOST]). The specific aims of proposed research are as follows: (1) to determine and quantify collider bias in the paradoxical phenomena of 3 key rheumatic conditions of interest (smoking and risk of CV events in RA; smoking and risk of psoriatic arthritis in people with psoriasis; and obesity and risk of disease progression in people with knee OA); (2) to determine the true impact of smoking status and BMI on the disease sequelae by evaluating the change in exposure status measured after the diagnosis of the 3 key rheumatic conditions. The proposed research will help the candidate develop expertise in rheumatic disease research and gain hands-on research experience in advanced study design and analytic methods. Further, the training component of this K01 award will help advance the candidate's career development. The proposed training experiences have five aims: (1) to develop advanced knowledge of rheumatic diseases through coursework and national conference attendance; (2) to obtain relevant didactic training in rheumatology and clinical epidemiology through Rheumatology Grand Rounds and journal clubs; (3) to gain knowledge and experience in advanced analytic techniques through coursework in methods; (4) to build the credentials to become an independent investigator including first- authored publications and presentations; (5) to submit an NIH R01 proposal by the end of the proposed training period to pursue related research. The experience and expertise of the mentoring team will help ensure that the goals and objectives of this research and training will be achieved within the proposed timeframe. Further, the organizational structure of the research environment provides a nurturing balance of independent research with intellectual and resource support and infrastructure. By leveraging the expertise of the research mentors, the available databases, the novel design, and the analytic methods of this study, the expected results will fill crucial gaps i our understanding of the true impact of modifiable risk factors on key outcomes of interest, and provide relevant evidence-based clinical recommendations. The rigorous training in the methods and content areas of this proposed research project will help lay the foundation for future studies of risk factors and sequelae of other rheumatic diseases.

描述（由申请人提供）：风湿病及其后遗症，包括类风湿关节炎（RA），银屑病关节炎和膝关节骨关节炎（OA），在美国和全球构成了巨大的疾病负担。与有关发生流变状况的危险因素的研究结果不同，风湿病患者对疾病后遗症的危险因素的发现是矛盾或矛盾的。 Although biological explanations for these unexpected results may exist, an enticing alternative methodological explanation is a type of selection bias called collider-stratification bias (hereaftr referred to as collider bias), which occurs when one evaluates the effect of a risk factor on disease sequelae among those in an intermediate stage of disease (e.g., studying smoking effects in people with RA on the risk of a CV event).在风湿条件下，几乎没有研究在方法论上研究了后遗症事件风险因素的悖论现象，从而在这一重要主题上留下了重要的差距。除非使用适当的设计或分析方法来确定在这些主要风湿性条件下可疑危险因素的真正影响，否则可能会耗尽大量的研究基金，时间和精力，而无需为临床建议提供有用的证据。为了克服与评估风湿性疾病患者续签事件所赋予的风险因素相关的方法论挑战，我们将研究3种风湿性疾病环境中的矛盾发现（RA中的CV和CV事件的风险；在RA中吸烟和风险的风险；吸烟和牛皮癣和obe病风险和风险疾病的流行症和脑海的风险;我们将使用三个大数据库：前瞻性队列（Norfolk关节炎登记册[NOAR]），一个普通人群数据库（健康改善网络[thin]）和前瞻性OA队列（多中心骨关节炎研究[最多]）。拟议研究的具体目的如下：（1）确定和量化3个关键风湿性疾病的矛盾现象中的碰撞者偏见（RA中的吸烟和CV事件的风险；在膝盖OA OA的患者中肥胖和疾病进展的肥胖症患者的吸烟和银屑病的风险；（2）通过评估诊断出3种关键风湿性疾病后测得的暴露状态的变化，确定吸烟状况和BMI对疾病后遗症的真正影响。拟议的研究将有助于候选人在风湿病研究方面发展专业知识，并在高级研究设计和分析方法方面获得动手研究经验。此外，该K01奖的培训组成部分将有助于促进候选人的职业发展。拟议的培训经验有五个目的：（1）通过课程和全国会议出席发展风湿性疾病的先进知识；（2）通过风湿病学和期刊俱乐部获得风湿病学和临床流行病学方面的相关教学培训；（3）通过方法的课程工作获得高级分析技术的知识和经验；（4）建立凭证成为一名独立研究者，包括第一本书的出版物和演示；（5）在拟议的培训期结束前提交NIH R01提案以进行相关研究。指导团队的经验和专业知识将有助于确保在拟议的时间范围内实现这项研究和培训的目标和目标。此外，研究环境的组织结构提供了独立研究与知识和资源支持和基础设施的培养平衡。通过利用研究导师的专业知识，可用数据库，新颖的设计以及本研究的分析方法，预期结果将填补关键的空白，这是我们对可修改风险因素对关键感兴趣结果的真正影响的理解，并提供相关证据基于证据的临床建议。在该提出的研究项目的方法和内容领域进行的严格培训将有助于为未来的其他风湿性疾病的危险因素和后遗症研究奠定基础。