Estimating and Communicating Risk about Biologic DMARDs for Rheumatoid Arthritis

描述(申请人提供)：这份K24申请的具体目标有两个。首先，我将进一步制定研究培训计划，为下一代临床研究人员进行药物流行病学分析和改善治疗关节炎和骨质疏松症药物安全性的沟通做准备。在过去的七年里，我在许多项目上指导了27名不同的实习生和初级教员。这项工作是令人满意的，也是富有成效的。这份K24提案给了我一个机会，让我有机会制定一个正式的有资金支持的指导计划。实现这一目标的指导计划包括对潜在学员的详细描述，一个多方面的教学和以项目为基础的教育计划，以及一个评估系统。其次，我将扩大我目前以患者为中心的研究计划，检查类风湿性关节炎(RA)的疾病改良型抗风湿药物(DMARD)疗法的安全性，并开发更好地沟通潜在药物风险的方法。为了实现第二个目标，我提出了与新研究有关的三个目标。第一个目标将侧重于改进使用大型医疗保健利用数据库时研究类风湿关节炎患者药物安全性的方法。方法学问题包括改进定义类风湿性关节炎的算法，评估生物DMARDS用户之间的通道偏见，以及验证评估类风湿性关节炎严重性的方法。第二个目标是评估与生物DMARD相关的癌症、感染和充血性心力衰竭(CHF)的风险，并将其与传统DMARD进行比较。我假设特定的生物DMARDS将与癌症、感染和CHF的风险增加相关。这些分析将集中在TNFa拮抗剂以及其他新兴的生物疗法上，如阿巴塔塞普和利妥昔单抗。虽然过去也进行了类似的研究，但它们通常包括的RA患者队列比我们建议的要少。此外，先前的研究没有充分处理引导偏见和疾病严重性的可能性。第三个目标建议调查患者和临床医生对DMARD风险的看法，并探索如何最好地传达风险。风险沟通是一个研究较少的领域。最近备受瞩目的停药事件突出表明，需要更好的方法来传达与所有药物相关的潜在风险，并将这些风险置于适当的背景下。我假设a)患者对风险的感知与他们使用特定的生物DMARD有关，b)医生对风险的感知比患者低得多。

DESCRIPTION (provided by applicant): The specific goals of this K24 application are twofold. First, I will further develop a research training program to prepare the next generation of clinical investigators for pharmaco-epidemiologic analyses and improved communication about the safety of drugs used for arthritis and osteoporosis. Over the prior decade seven years, I have mentored 27 different trainees and junior faculty on many projects. This work has been gratifying and productive. This K24 proposal gives me the opportunity to develop a formal program of mentoring with financial support. The mentoring plan to achieve this goal includes detailed descriptions of potential trainees, a multi-faceted program of didactic and project- based education, as well as an evaluation system. Second, I will expand my current patient-oriented research program examining the safety of disease modifying anti-rheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) and developing methods for better communication of potential drug risk. To achieve the second goal, I propose three aims pertaining to new research. The first aim will focus on improving the methods for studying drug safety among patients with RA when using large health care utilization databases. The methodologic issues include improving algorithms for defining RA, assessing for channeling bias among users of biologic DMARDs, and validating a method for assessing RA severity. The second aim will estimate the risk of cancer, infection and congestive heart failure (CHF) associated with biologic DMARDs compared with each other and compared with traditional DMARDs. I hypothesize that specific biologic DMARDs will be associated with increased risk of cancer, infection, and CHF. These analyses will focus on both the TNFa antagonists as well as the other emerging biologic therapies, such as abatacept and rituximab. While similar studies have been conducted in the past, they have generally included smaller cohorts of patients with RA than what we have proposed. Moreover, prior studies have not adequately dealt with the potential for channeling bias and for disease severity. The third aim proposes to survey patients and clinicians regarding their perceptions of DMARD risk and to explores how best to communicate risk. Risk communication is a poorly researched area. Recent high profile drug withdrawals underscore the need for better methods to communicate the potential risks associated with all medications and to place those risks in the proper context. I hypothesize a) that patient's perceptions of risk are associated with their use of specific biologic DMARDs and b) that physicians' perception of risk is much lower than patients'.