Mentored Patient-Oriented Research in Pulmonary Arterial Hypertension

Steven M. Kawut博士是宾夕法尼亚大学医学和流行病学教授 医学院（宾夕法尼亚州）谁致力于他的职业生涯的研究和护理患者的肺 血管疾病（PVD）。他领导了一个联邦资助的研究项目，该项目基于流行病学和 治疗PVD和右心室功能障碍。他还指导了50多名学员， 以患者为导向的研究（POR），导致出版物和资金，在许多情况下，他们自己的 独立的学术生涯。候选人在此竞争期间的近期和长期职业目标 更新中心，旨在获得在罕见PVD中进行比较有效性研究（CER）的技能， 发展他的指导能力，特别是在将他资助的学员转变为独立和 成为自己学员的导师宾夕法尼亚大学的环境是理想的发展申请人作为一个导师 并促进学员在这些领域的学术发展。 肺动脉高压（PAH）是一种罕见的疾病，影响所有年龄段的人，导致 发病率高，死亡风险高。然而，关于这项研究和治疗的许多问题 PAH的方法仍然没有答案。6分钟步行的最小重要差异（MID） PAH中的6MWD距离尚未明确确定。在早期研究中使用6MWD， 作为临床结果的一个组成部分，即使在长期研究的时代， 研究PAH。随着PAH新疗法的不断涌现，PAH中不同治疗方法的CER 与健康相关的生活质量和临床恶化是主要的关注领域。Kawut博士参与了两个新的 可以解决PAH中这些关键问题的倡议，并作为他自己和他的 学员首先，FDA已经向Kawut博士提供了所有提交的个体患者水平数据（IPD）。 PAH随机临床试验（RCT）。第二，Kawut博士担任肺结核指导委员会主席。 高血压协会登记处（PHAR），这是一项前瞻性登记研究， 肺动脉高压治疗中心的PAH。我们的目标是推导并验证6MWD变化中的MID 并确定不同药物类别对健康相关生活质量的比较有效性 和PAH患者至临床恶化的时间。 本提案的长期目标是通过验证， 6MWD的MID和研究不同治疗方法的比较有效性。这些 目标不仅为导师提供培训机会，而且提供宝贵的培训和研究经验 为各级学员提供培训。在申报的CER中直接参与患者的机会， 患者接触使该项目成为此次K24更新的理想选择。

Steven M. Kawut, MD, MS is a Professor of Medicine and Epidemiology at the University of Pennsylvania School of Medicine (Penn) who has committed his career to the research and care of patients with pulmonary vascular disease (PVD). He heads a federally-funded research program based on the epidemiology and treatment of PVD and right ventricular dysfunction. He has also mentored more than fifty trainees to success in patient-oriented research (POR), resulting in publications and funding and in many cases their own independent academic careers. The candidate's immediate- and long-term career goals during this competitive renewal center on acquiring skills in performing comparative effectiveness research (CER) in rare PVDs and developing his mentorship abilities, specifically in transitioning his funded mentees to independence and in becoming mentors of their own trainees. The environment at Penn is ideal to develop the applicant as a mentor and to foster the academic growth of mentees in these areas. Pulmonary arterial hypertension (PAH) is a rare disease which affects people of all ages, leading to significant morbidity and a high risk of mortality. However, many questions about the study and therapeutic approach to PAH remain unanswered. The minimally important difference (MID) for the six-minute walk distance (6MWD) has not been clearly established in PAH. The use of the 6MWD in early phase studies and as a component of clinical outcomes makes this an important area of research even in the era of long-term studies in PAH. With the proliferation of new therapies for PAH, CER of different treatments in PAH in terms of health-related quality of life and clinical worsening is a major area of interest. Dr. Kawut is involved in two new initiatives which can address these critical questions in PAH and serve as training vehicles for himself and his mentees. First, the FDA has provided Dr. Kawut with individual patient-level data (IPD) from all submitted randomized clinical trials (RCTs) in PAH. Second, Dr. Kawut chairs the Steering Committee of the Pulmonary Hypertension Association Registry (PHAR), which is a prospective registry of newly-diagnosed patients with PAH at Pulmonary Hypertension Care Centers. We aim to derive and validate the MID in the change in 6MWD in PAH and to determine the comparative effectiveness of different drug classes on health-related quality of life and time to clinical worsening in patients with PAH. The long-term goal of this proposal is to refine the conduct of RCTs and clinical care in PAH by validating the MID of the 6MWD and studying the comparative effectiveness of different treatment approaches. These aims provide not only training opportunities for the mentor, but also valuable training and research experiences for mentees at all levels. The opportunities for direct patient involvement in the CER being proposed and direct patient contact make this project ideal for this K24 renewal.