Clinical Outcomes for Siblings of Children with Vesico-Ureteral Reflux

我的职业目标是通过对有效性和医疗保健服务的研究，改善泌尿系统疾病儿童的医疗保健。作为一名专注于卫生服务研究的儿科泌尿科医生，我寻求这个职业发展奖，这样我就可以在一个研究尚未充分发挥潜力的领域建立一个独立的研究生涯。小儿泌尿外科是一个过渡中的亚专业，从一个主要基于个人手术经验和病例系列的领域，转向一个基于全面纵向研究和随机对照试验的领域。我希望为这一过渡进程作出贡献。 在这个应用程序中，我建议调查膀胱输尿管反流（VUR）儿童的兄弟姐妹所造成的临床困境。VUR是尿液从膀胱逆行流入输尿管和肾脏，并与尿路感染（UTI）和肾损伤相关。VUR是一种常见的家族性疾病，无症状的VUR患儿的兄弟姐妹自身VUR的发生率也很高。然而，目前尚不清楚筛查这些兄弟姐妹是否有益。未经筛查的兄弟姐妹的自然史也是未知的。我计划对兄弟姐妹VUR进行一项研究，并以三种方式利用这项研究。首先，这项研究的结果将为我们理解这种有争议的临床状况做出临床有用的贡献。其次，我打算利用这项研究作为工具，系统地扩展我的决策分析工作知识，因为它适用于医疗决策。第三，这项研究和我的教育发展，将作为后续研究的基础，因为我在未来寻求独立的研究资金。 我的近期目标包括：（1）进一步发展我对观察性临床研究、大型管理数据库分析和高级统计建模技术的技术和方法学知识;（2）学习和应用决策分析技术，为SCVUR的临床决策提供指导，并为SCVUR的经验性研究指明未来的方向;（3）使用来自特定人群的医疗保健索赔数据进行回顾性队列研究，以便（a）确定筛查和未筛查SCVUR的重要临床结局，以及（B）确定研究人群中SCVUR的实践模式;（4）为SCVUR的进一步临床研究奠定基础，并支持该研究的独立基金申请。 该研究项目将包括对VUR儿童的兄弟姐妹进行回顾性队列研究。这些儿童将通过分析一家大型区域健康保险公司的索赔数据来确定。我将试图描述这种兄弟姐妹的护理模式，并记录具体的临床结果。然后，这些发现将被应用到决策分析，以确定是否筛查无症状的同胞VUR是适当的。研究目的是互补的。该临床研究将确定关键的临床结果，例如未筛查的兄弟姐妹中UTI的发生率。这些数据在目前的文献中根本无法获得。这些结果，反过来，将促进决策分析模型的发展。目前，由于缺乏关于VUR兄弟姐妹之间结果的数据，这种模型受到严重限制。更复杂的模型，结合本分析的结果，将是非常有价值的工具，以帮助确定最佳的管理方法，为兄弟VUR。 除了研究部分的建议，我将获得正规的培训，在先进的临床研究技术，决策分析和生物统计学。在哈佛公共卫生学院的这门课程将扩展我在研究技术方面的知识，特别是在决策分析方法学方面，超越我在以前的公共卫生硕士课程中获得的知识。 在这些努力中，我将得到波士顿儿童医院和哈佛医学院非凡资源的支持。我将由我的上级顾问团队指导，该团队由我的主要导师Mark Schuster领导，他是一位非常有成就的儿科健康服务研究员。 从长远来看，我预计本提案中描述的活动将支持并告知随后的R 01资助申请，以研究家族性VUR。我希望发展专业知识和基础设施，以支持一个积极的，多管齐下的临床和卫生服务研究计划，在儿科泌尿外科的关键领域进行同时观察和干预试验，并专注于影响大量儿童的常见疾病。

My career goal is to improve health care for children with urological problems through research on effectiveness and health care delivery. As a pediatric urologist with a focus in health services research, I seek this Career Development Award so that I can establish an independent research career in a field where such research has not yet reached its full potential. Pediatric urology is a subspecialty in transition, moving from a field based primarily on personal surgical experience and case series, to one based on comprehensive longitudinal studies and randomized controlled trials. I seek to contribute to this transition process. In this application, I propose to investigate the clinical dilemma posed by siblings of children with vesicoureteral reflux (VUR). VUR is the retrograde flow of urine from the bladder into the ureter and kidney, and is associated with urinary tract infection (UTI) and renal injury. VUR is both common and familial, and asymptomatic siblings of children with VUR having high rates of VUR themselves. However, it is not known if screening of such siblings is beneficial. The natural history of unscreened siblings is also unknown. I plan to conduct a research study of sibling VUR, and leverage this research in three ways. First, the findings of the study will make a clinically useful contribution to our understanding of this controversial clinical condition. Second, I intend to use this research as the vehicle for a systematic expansion of my working knowledge of decision analysis as it applies to medical decision-making. Third, this research, and my educational development, will serve as a foundation for follow-up studies as I seek independent research funding in the future. My short term goals include the following: (1) To further develop my knowledge of techniques and methodologies for observational clinical studies, analysis of large administrative databases, and advanced statistical modeling techniques, (2) To learn and apply the techniques of decision analysis, to support guidelines for clinical decision-making regarding SCVUR, and to direct future directions for empiric studies of SCVUR; (3) To use health care claims data from a defined population to conduct a retrospective cohort study in order to (a) determine important clinical outcomes among SCVUR, both screened and unscreened, and (b) to determine practice patterns regarding SCVUR within the studied population; and (4) To lay the foundation for further clinical studies of SCVUR, and support applications for independent funding for this research. The research project will consist of a retrospective cohort study of siblings of children with VUR. These children will be identified via analysis of claims data within a large regional health insurance company. I will seek to characterize patterns of care for such siblings, and document specific clinical outcomes. Then, these findings will be applied to a decision analysis to determine whether screening of asymptomatic siblings for VUR is appropriate. The research aims are complementary. The clinical study will determine critical clinical outcomes, such as the incidence of UTI among unscreened siblings. These data are simply not available in the current literature. These results, in turn, will facilitate the development of decision analysis models. Currently, such models are severely limited by the lack of data regarding outcomes among VUR siblings. More sophisticated models, incorporating the findings from this analysis, would be of great value as tools to help define the optimal management approach for sibling VUR. In addition to the research component of the proposal, I will obtain formal training in advanced clinical research techniques, decision analysis, and biostatistics. This coursework at the Harvard School of Public Health will extend my knowledge of research techniques, particularly in decision analysis methodology, beyond those acquired during my prior MPH curriculum. In these endeavors I will be supported by the extraordinary resources of Children's Hospital Boston and Harvard Medical School. I will be guided by my superior advisory team, led by my primary mentor Mark Schuster, MD, PhD, a highly accomplished pediatric health services researcher. In the long term, I anticipate that the activities described in this proposal will support and inform a subsequent application for R01 funding to study familial VUR. I hope to develop the expertise and infrastructure to support an active, multi-pronged clinical and health services research program, conducting simultaneous observational and interventional trials in key areas of pediatric urology, and focusing on common conditions affecting large numbers of children.