Investigating the longitudinal patterns of use and comparative effectiveness of beta blocker therapy in the hemodialysis population

 描述(由申请者提供)：NIH博士后奖学金(F32)申请旨在促进北卡罗来纳大学药学博士、硕士、博士后和流行病学博士研究生的培训，并为她的独立研究生涯奠定基础。应聘者是一名训练有素的肾病药剂师，具有临床研究经验。她的目标是将这些技能与药物流行病学的重点培训结合起来，成为一名独立科学家，进行专注于药物安全性和有效性的透析结果研究。在F32培训期间，候选人将在她的赞助人M.Alan Brookhart博士，博士，流行病学教授的指导下完成她的博士学位。此外，医学助理教授、公共卫生硕士詹妮弗·弗莱斯博士将提供协作临床指导。拟议的项目是一项回溯性队列研究，使用与美国肾脏数据系统相连的一家大型美国透析提供商的临床丰富的研究数据库，评估在2.1万名普遍存在的血液透析(HD)患者中使用β-肾上腺素能阻滞剂治疗的比较有效性。心血管疾病仍然是HD患者发病率和死亡率的主要原因，每年有30%的人住院治疗，50%的人死亡。在普通人群中，药物干预，如β受体阻滞剂，可改善心力衰竭、心房颤动的临床结果。 和心肌梗塞后。在HD患者中，β受体阻滞剂治疗的心脏保护益处尚未通过大规模临床试验进行评估，HD患者是一个具有独特药物剂量考虑的人群。不同β-受体阻滞剂亚类之间的药代动力学和药理学差异可能会改变这些个体的药物疗效和安全性。尽管证据无效，但超过60%的HD患者接受了β受体阻滞剂。为了改进临床决策，迫切需要清楚地了解β受体阻滞剂在现实世界中的纵向使用模式，并结合对β受体阻滞剂亚类的比较有效性的严格评估。利用现代研究设计和创新的统计方法，这项建议旨在：1)检查HD人群中β受体阻滞剂的长期使用模式，以及2)评估HD患者中心脏选择性β受体阻滞剂与α-β受体阻滞剂治疗的死亡率和住院风险的比较。拟议的工作有很大的潜力产生重大影响。研究目的的完成将促进我们对可能为HD患者提供更好临床益处的β受体阻滞剂亚型的理解，并将为指导未来随机试验的设计提供数据。建议的工作在授权期内是切合实际和可行的。重要的是，拟议的研究和多方面的职业发展活动将通过允许阿西蒙博士成为一名独立的临床研究员来促进她的成长 开发新的研究技能，创建协作研究网络并生成初步数据，这些数据将作为未来职业发展奖申请的基础。

 DESCRIPTION (provided by applicant): This NIH post-doctoral fellowship (F32) application is designed to promote the training of Dr. Magdalene Assimon, PharmD, MS, post-doctoral fellow and concurrent Epidemiology PhD student at the University of North Carolina, and to provide her with a foundation for an independent research career. The Candidate is a trained nephrology pharmacist with experience in clinical research. Her goal is to integrate these skills with focused training in pharmacoepidemiology to become an independent scientist who conducts dialysis outcomes research focused on drug safety and effectiveness. During the F32 training period, the Candidate will complete her PhD degree under the mentorship of her sponsor Dr. M. Alan Brookhart, PhD, Professor of Epidemiology. In addition, collaborative clinical mentorship will be provided by Dr. Jennifer Flythe, MD, MPH, Assistant Professor of Medicine. The proposed project is a retrospective cohort study assessing the comparative effectiveness of beta adrenergic blocker therapy in a cohort of 21,000 prevalent hemodialysis (HD) patients using the clinically rich research database of a large United States dialysis provider linked with the United States Renal Data System. Cardiovascular disease remains the leading cause of morbidity and mortality among HD patients, accounting for 30% hospitalizations and 50% of deaths annually. In the general population, pharmaceutical interventions such as beta blockers improve clinical outcomes in heart failure, atrial fibrillation and post-myocardial infarction. The cardioprotective benefit of beta blocker therapy has not been evaluated by large-scale clinical trials in HD patients, a population with unique drug dosing considerations. Pharmacokinetic and pharmacologic differences across beta blocker subclasses may alter drug efficacy and safety profiles in these individuals. Despite the evidence void, over 60% of HD patients receive beta blockers. A clear understanding of the longitudinal patterns of beta blocker use in the real-world setting combined with a rigorous assessment of the comparative effectiveness of beta blocker subclasses is urgently needed to improve clinical decision making. Using modern study designs and innovative statistical methods, this proposal aims to: 1) examine long-term beta blocker utilization patterns in the HD population, and 2) assess the comparative mortality and hospitalization risks of cardioselective beta blocker versus alpha-beta blocker therapy among HD patients. The proposed work has high potential to make a significant impact. Completion of the study aims will advance our understanding of the beta blocker subtype that may offer superior clinical benefits to HD patients, and will provide data to guide the design of future randomized trials. The proposed work is realistic and feasible within the award period. Importantly, the proposed research and multifaceted career development activities will foster Dr. Assimon's growth as an independent clinical investigator by allowing her to develop new research skills, create collaborative research networks and generate preliminary data which will serve as the foundation for a future career development award application.