Clinical Outcomes for Siblings of Children with Vesico-Ureteral Reflux

描述（由申请人提供）：我的职业目标是通过有效性和医疗保健服务的研究来改善患有泌尿系统问题的儿童的医疗保健。作为一名专注于健康服务研究的儿科泌尿科医生，我寻求获得这个职业发展奖，以便我能够在此类研究尚未充分发挥其潜力的领域建立独立的研究生涯。小儿泌尿外科是一个正在转型的亚专业，从主要基于个人手术经验和病例系列的领域转变为基于综合纵向研究和随机对照试验的领域。我寻求为这一​​过渡过程做出贡献。 在本申请中，我建议调查患有膀胱输尿管反流（VUR）的儿童的兄弟姐妹所带来的临床困境。 VUR 是尿液从膀胱逆流至输尿管和肾脏，与尿路感染 (UTI) 和肾损伤有关。 VUR 既常见又具有家族性，患有 VUR 的儿童的无症状兄弟姐妹本身也有很高的 VUR 发生率。然而，尚不清楚对此类兄弟姐妹进行筛查是否有益。未经筛查的兄弟姐妹的自然史也是未知的。我计划对同胞 VUR 进行一项研究，并通过三种方式利用这项研究。首先，该研究的结果将为我们理解这种有争议的临床病症做出临床上有用的贡献。其次，我打算利用这项研究作为系统扩展我的决策分析工作知识的工具，因为它适用于医疗决策。第三，这项研究以及我的教育发展将为我将来寻求独立研究经费时的后续研究奠定基础。 我的短期目标包括以下内容：（1）进一步发展观察性临床研究、大型管理数据库分析和高级统计建模技术的技术和方法知识，（2）学习和应用决策分析技术，支持有关 SCVUR 的临床决策指南，并指导 SCVUR 经验研究的未来方向； (3) 使用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 SCVUR（筛选和未筛选）的重要临床结果，以及 (b) 确定研究人群中有关 SCVUR 的实践模式； （4）为SCVUR的进一步临床研究奠定基础，支持本研究申请独立资助。 该研究项目将包括对患有 VUR 的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大型地区健康保险公司的索赔数据来识别。我将寻求描述此类兄弟姐妹的护理模式，并记录具体的临床结果。然后，这些发现将应用于决策分析，以确定对无症状兄弟姐妹进行 VUR 筛查是否合适。研究目的是互补的。临床研究将确定关键的临床结果，例如未经筛查的兄弟姐妹中尿路感染的发生率。这些数据在当前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开发。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，结合了该分析的结果，作为帮助定义同级 VUR 的最佳管理方法的工具将具有巨大的价值。 除了提案的研究部分外，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，超越我之前在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的非凡资源的支持。我将受到我的高级顾问团队的指导，该团队由我的主要导师马克·舒斯特（Mark Schuster）医学博士、博士领导，他是一位成就卓著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为后续申请 R01 资金以研究家族 VUR 提供支持和信息。我希望发展专业知识和基础设施来支持积极的、多管齐下的临床和健康服务研究计划，在儿科泌尿外科的关键领域同时进行观察和介入试验，并重点关注影响大量儿童的常见病症。 公共健康相关性：本研究项目旨在更多地了解治疗膀胱输尿管反流 (VUR) 儿童兄弟姐妹中膀胱输尿管反流（尿液从膀胱逆流至肾脏）的最佳方法。 VUR 很常见，并且有家族遗传性，因此根据家族史，有大量的兄弟姐妹可能患有 VUR。尽管有些人主张对这些兄弟姐妹进行 VUR 检测，即使他们看起来很健康，但这种“筛查”将使大量无症状儿童接受侵入性检测，从而产生潜在的不良影响、长期随访、长期抗生素使用以及可能的手术。因此，重要的是我们要更多地了解这些兄弟姐妹的 VUR，以便确定这种筛查是否有意义。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This research project seeks learn more about the best way to manage vesicoureteral reflux (backwards flow of urine from the bladder up to the kidneys) among siblings of children with vesicoureteral reflux (VUR). VUR is quite common, and runs in families, so there are large numbers of siblings who might have VUR based on their family history. Although some people advocate testing these siblings for VUR even if they seem healthy, such "screening" would subject large numbers of asymptomatic children to invasive tests with potentially adverse effects, long-term follow-up, prolonged antibiotic use, and possible surgery. Therefore, it is important that we learn more about VUR in these siblings in order to decide whether such screening makes sense.