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提供的研究，改善对有泌尿系统问题的儿童的医疗保健。作为一名专注于卫生服务研究的儿科泌尿科医生，我寻求获得这一职业发展奖，以便在这类研究尚未充分发挥其潜力的领域建立独立的研究生涯。儿科泌尿科是一个过渡中的子专业，从一个主要基于个人手术经验和病例系列的领域，转变为一个基于全面的纵向研究和随机对照试验的领域。我寻求为这一过渡进程做出贡献。 在这项应用中，我建议调查患有膀胱输尿管反流(VUR)的儿童的兄弟姐妹造成的临床困境。尿路返流是指尿液从膀胱逆行流入输尿管和肾脏，与尿路感染(UTI)和肾脏损伤有关。VUR既是常见的，也是家族性的，VUR儿童的无症状兄弟姐妹本身也有很高的VUR发生率。然而，目前还不知道对这些兄弟姐妹进行筛查是否有益。未经筛查的兄弟姐妹的自然历史也是未知的。我计划对兄弟姐妹VUR进行一项研究，并从三个方面利用这项研究。首先，这项研究的发现将对我们理解这一有争议的临床疾病做出临床上的有益贡献。其次，我打算利用这项研究作为一种工具，系统地扩展我在决策分析方面的工作知识，因为它适用于医疗决策。第三，这项研究和我的教育发展，将作为我未来寻求独立研究资金时后续研究的基础。 我的短期目标包括：(1)进一步发展我对观察性临床研究、大型行政数据库分析和高级统计建模技术的技术和方法的知识，(2)学习和应用决策分析技术，支持关于SCVUR的临床决策指南，并指导SCVUR的经验研究的未来方向；(3)使用来自特定人群的医疗索赔数据进行回溯性队列研究，以便(A)确定SCVUR中筛选和未筛选的重要临床结果，以及(B)确定研究人群中关于SCVUR的实践模式；(4)为SCVUR的进一步临床研究奠定基础，并支持本研究的独立资金申请。 该研究项目将包括一项对VUR儿童兄弟姐妹的回溯性队列研究。这些儿童将通过分析一家大型地区性健康保险公司的索赔数据来确定。我将努力描述这些兄弟姐妹的护理模式，并记录具体的临床结果。然后，这些发现将被应用于决策分析，以确定是否适合筛查无症状的VUR兄弟姐妹。研究目的是相辅相成的。这项临床研究将确定关键的临床结果，如未筛查的兄弟姐妹中尿路感染的发生率。这些数据在目前的文献中根本不可用。这些结果反过来将促进决策分析模型的发展。目前，由于缺乏有关VUR兄弟姐妹结果的数据，此类模型受到严重限制。更复杂的模型，结合这一分析的结果，将是非常有价值的工具，有助于确定兄弟姐妹VUR的最佳管理方法。 除了提案中的研究部分，我还将获得高级临床研究技术、决策分析和生物统计学方面的正式培训。哈佛大学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，特别是决策分析方法方面的知识，而不是我在之前的公共卫生硕士课程中学到的知识。 在这些努力中，我将得到波士顿儿童医院和哈佛医学院的非凡资源的支持。我将由我的主要导师、医学博士马克·舒斯特领导的我的高级顾问团队指导我，他是一位非常有成就的儿科卫生服务研究员。 从长远来看，我预计这项提案中描述的活动将支持并为随后的R01资金申请提供信息，以研究家族性VUR。我希望发展专业知识和基础设施，以支持积极的、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步的观察性和干预性试验，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.