Mentoring Patient-Oriented Pharmacoepidemiologic Research in Rheumatic Diseases

项目摘要 风湿性关节炎（RA）是一种慢性炎症性关节炎，目前尚无治愈方法。但随着 在过去几十年里，医学上的突破，十几种不同的生物和靶向合成（TS）疾病- 针对免疫系统特定成分的修饰性抗风湿药（DMARD）， 目前可用于中度至重度RA患者。虽然所有这些生物和ts-DMARD都是高度 这些药物在控制RA的炎症方面是有效的，但它们具有广泛的安全性问题，包括感染， 心血管疾病、血栓形成、心力衰竭、下肠穿孔和恶性肿瘤。鉴于 显著扩大了类风湿性关节炎的医疗设施，并越来越重视治疗目标，以实现缓解 或低RA疾病活动性，临床医生和患者都必须了解有关药物治疗的数据， 有效性和安全性然而，关于如何直接比较 在没有临床试验的情况下，这些不同的DMARD的获益和风险。此外，少数 研究已经定量地评估并将患者偏好纳入到权衡益处与危害中， 这些药物。因此，申请人提出了一个为期五年的K24奖项目，其中有三个具体的研究目标 这将：1）模拟目标试验，以评估生物制剂的头对头比较有效性和安全性， 和ts-DMARD; 2）确定安全性事件的重要预测因素 与使用生物制剂或ts-DMARD相关;和3）进行以患者为中心的获益-风险评估， 这些药物结合了患者的相对治疗偏好。此外，申请人的目标是发展和 加强药物流行病学和以患者为导向的结果研究方面的研究培训计划， 风湿性疾病申请人Seoyoung C博士Kim是一位流变学家， 药物流行病学家她曾担任小学或中学的研究导师超过30前和后， 博士研究生在过去的十年里。申请人的许多正在进行的研究项目， 药物流行病学和以患者为导向的研究，对指导的高度承诺， 特殊的机构资源将为青少年的发展提供良好的环境 investigators.此外，申请人还组建了一支由高素质合作者组成的强大团队， 作为她的学员的共同导师，她将继续完善她的指导计划和技能， 奖励期间学员的反馈。这项K24奖研究将有助于产生基于现实世界的证据， 关于使用生物制剂和ts-DMARD管理RA的建议，包括患者治疗 偏好和支持申请人的能力，建立一个强大的临床研究平台，以指导下一个 培养药物流行病学临床研究人员和以患者为导向的风湿病学研究人员， 促进他们成功过渡到独立。

PROJECT SUMMARY Rheumatoid arthritis (RA) is a chronic inflammatory arthritis for which there is no known cure. However, with medical breakthroughs in the past few decades, a dozen different biologic and targeted synthetic (ts) disease- modifying antirheumatic drugs (DMARDs) directed toward specific components of the immune system are currently available for patients with moderate-to-severe RA. While all these biologic and ts-DMARDs are highly effective in controlling inflammation in RA, these agents carry a wide range of safety concerns including infections, cardiovascular disease, thrombosis, heart failure, lower intestinal perforations, and malignancies. Given the significantly expanded armamentarium for RA and increasing emphasis on treating to target to achieve remission or low RA disease activity, it is important for both clinicians and patients to understand the data regarding drug effectiveness and safety. However, there is a knowledge gap in concerning how one can compare directly across these different DMARDs with regard to their benefits and risks in the absence of clinical trials. Moreover, few studies have quantitatively assessed and incorporated patient preferences into weighing benefits vs. harms of these drugs. The applicant, therefore, proposes a 5-year K24 award project with three specific research aims which will: 1) emulate a target trial to evaluate head-to-head comparative effectiveness and safety of biologic and ts-DMARDs in patients with RA using real-world data; 2) identify important predictors of safety events associated with use of biologic or ts-DMARDs; and 3) conduct a patient-centered benefit-risk assessment of these drugs incorporating patients’ relative treatment preferences. In addition, the applicant aims to grow and strengthen a research training program in pharmacoepidemiology and patient-oriented outcome research in rheumatic diseases. The applicant, Dr. Seoyoung C. Kim, is a rheumatologist and a doctoral trained pharmacoepidemiologist. She has served as primary or secondary research mentor for over 30 pre- and post- doctoral research trainees in the past decade. The applicant’s many ongoing research projects for pharmacoepidemiologic and patient-oriented research, high degree of commitment to mentoring, and the exceptional institutional resources will provide an outstanding environment for the development of junior investigators. Furthermore, the applicant has assembled a strong team of highly qualified collaborators who can serve as co-mentors for her trainees, and she will continue to refine her mentoring program and skills using trainee feedback during the award period. This K24 award study will help generate real-world evidence-based recommendations for the management of RA with biologic and ts-DMARDs, incorporating patients’ treatment preferences and support the applicant’s ability to build a strong clinical research platform to mentor the next generation of clinical researchers in pharmacoepidemiology and patient-oriented research in rheumatology and promote their successful transition to independence.