Comparative Effectiveness of N-said Treatment Versus No Treatment for PDA in Pret

描述（由申请人提供）：Jonathan L. Slaughter，MD，MPH是全国儿童医院和俄亥俄州州立大学围产期研究中心的助理教授。他的职业目标是通过严格的比较有效性研究（CER）来改善新生儿护理，该研究将评估药物的风险和益处，尽管证据有限，但通常用于治疗早产相关疾病。拟议的为期四年的K 08指导职业发展提案将通过以下方式为Slaughter博士提供CER培训：1）大型住院患者数据库纵向分析的指导和教学培训; 2）高级统计技术培训，以调查观察数据中的因果推断; 3）使用数据库链接来增加结局估计的稳健性。此外，他将获得临床试验设计的基本知识，这是CER研究人员的重要研究技能。Slaughter博士提出的研究调查的目的是利用来自多个地点的“真实世界”患者数据来确定 非甾体抗炎药（NSAID）治疗动脉导管未闭（PDA）与不治疗在死亡率、支气管肺发育不良（BPD）发生率和呼吸支持持续时间方面的比较有效性。早产儿PDA的存在与死亡率增加和BPD发生率升高相关。通过给予NSAID进行导管闭合旨在减少这些并发症。然而，NSAID并非没有副作用，并且缺乏证据证明其在改善以患者为中心的重要结局方面的益处。可能由于缺乏明确的证据，NSAID治疗PDA的医院间实践存在显著差异。主要数据源将是儿科健康信息系统（PHIS），这是一个管理数据库，包括美国大多数大型儿童医院，其中包含有关处方药物和呼吸支持的每日患者特定数据。研究计划的具体目的是：1）确定与NSAID治疗PDA的医院间差异相关的因素，2）确定各种NSAID治疗与不治疗PDA对死亡率和呼吸结局的比较有效性，和3）在PHIS和儿童医院新生儿数据库（CHND）中代表的研究婴儿子集内验证目标1和目标2结果。CHND是一个较小的临床调查数据库，包含额外且更详细的患者特定诊断和手术数据。两位国际知名的流行病学家，马克Klebanoff，医学博士，公共卫生硕士和托马斯纽曼医学博士，公共卫生硕士，和帕特里夏里根，博士，经济学家与纵向数据分析和计量经济学因果推理方法的专业知识，将担任导师。其他顾问将提供心脏病学专业知识（Vidu Garg，MD），并协助合并PHIS和CHND数据库（Matt Hall，PhD）。除了准备Slaughter博士成为新生儿比较有效性研究的独立专家外，我们希望我们的研究结果能够为PDA早产儿的患者护理提供信息，并指导前瞻性研究的发展。

DESCRIPTION (provided by applicant): Jonathan L. Slaughter, MD, MPH is an Assistant Professor in the Center for Perinatal Research at Nationwide Children's Hospital and The Ohio State University. His career goal is to improve neonatal care through rigorous comparative effectiveness research (CER) that will evaluate the risks and benefits of medications that, despite limited evidence, are commonly used in the treatment of prematurity-related disorders. The proposed four-year K08 mentored career development proposal will provide Dr. Slaughter with training in CER through 1) mentorship and didactic training in longitudinal analysis of large inpatient databases 2) training in advanced statistical techniques to investigate causal inference in observational data and 3) the use of database linkages to increase the robustness of outcome estimates. Additionally, he will gain a basic knowledge of clinical trial design, an important research skill for CER investigators. The objective of Dr. Slaughter's proposed research investigation is to utilize "real-world" patient data from multiple sites to determine the comparative effectiveness of non-steroidal anti-inflammatory drug (NSAID) treatment for patent ductus arteriosus (PDA) versus no treatment on mortality, development of bronchopulmonary dysplasia (BPD), and duration of respiratory support. The presence of a PDA in preterm infants is associated with increased mortality and higher rates of BPD. Ductal closure by administration of NSAIDs aims to reduce these complications. However, NSAIDs are not without side effects and evidence for their benefit in improving important patient-centered outcomes is lacking. Likely due to this absence of clear evidence, there is marked between-hospital practice variation for NSAID treatment of PDA. The primary data source will be the Pediatric Health Information System (PHIS), an administrative database inclusive of most large, U.S. children's hospitals that contains daily, patient-specific data on prescribed medications and respiratory support. The specific aims of the research plan are 1) to determine factors associated with between-hospital variation in NSAID treatment for PDA, 2) determine the comparative effectiveness of various NSAID treatments versus no treatment for PDA on mortality and respiratory outcomes, and 3) to validate Aim 1 and Aim 2 results within the subset of study infants represented in both PHIS and the Children's Hospital Neonatal Database (CHND). CHND is a smaller, clinical survey database with additional and more detailed, patient-specific diagnostic and procedural data. Two internationally renowned epidemiologists, Mark Klebanoff, MD, MPH and Thomas Newman MD, MPH, and Patricia Reagan, PhD, an economist with expertise in both longitudinal data analysis and econometric causal inference methods, will serve as mentors. Other consultants will provide cardiologic expertise (Vidu Garg, MD) and assist with merger of the PHIS and CHND databases (Matt Hall, PhD). In addition to preparing Dr. Slaughter to become an independent expert in neonatal comparative effectiveness research, we expect our findings to inform patient care for preterm infants with PDA and guide the development of prospective investigations.