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

描述(由申请人提供)：乔纳森·L·斯劳特，医学博士，公共卫生硕士，国立儿童医院和俄亥俄州立大学围产期研究中心助理教授。他的职业目标是通过严格的比较有效性研究(CER)改善新生儿护理，该研究将评估药物的风险和好处，尽管证据有限，但这些药物通常用于治疗早产相关疾病。拟议的为期四年的K08指导职业发展提案将通过以下方式为斯劳特博士提供CER培训：1)大型住院患者数据库纵向分析方面的指导和授课培训；2)高级统计技术培训，以调查观察性数据中的因果推断；3)使用数据库链接提高结果估计的稳健性。此外，他还将获得临床试验设计的基本知识，这是CER研究人员的一项重要研究技能。斯劳特博士提出的研究调查的目标是利用来自多个地点的“真实世界”患者数据来确定 非类固醇抗炎药(NSAID)治疗动脉导管未闭(PDA)与不治疗对死亡率、支气管肺发育不良(BPD)发展和呼吸支持持续时间的疗效比较。早产儿出现动脉导管未闭与死亡率增加和BPD发生率高有关。应用非甾体抗炎药封闭胆管旨在减少这些并发症。然而，非甾体抗炎药并不是没有副作用，缺乏证据表明它们在改善以患者为中心的重要结局方面的好处。可能由于缺乏明确的证据，非甾体类抗炎药治疗PDA的医院间实践有明显的差异。主要数据来源将是儿科健康信息系统(PHIS)，这是一个行政数据库，包括美国大多数大型儿童医院，其中包含每日特定于患者的处方药和呼吸支持数据。该研究计划的具体目标是1)确定与非类固醇抗炎药治疗PDA的医院间差异有关的因素，2)确定各种非类固醇抗炎药治疗与不治疗PDA对死亡率和呼吸结果的比较效果，3)在PHIS和儿童医院新生儿数据库(CHND)中代表的研究婴儿的子集中验证Aim 1和Aim 2的结果。CHND是一个较小的临床调查数据库，具有额外的、更详细的、特定于患者的诊断和程序数据。两位国际知名的流行病学家、医学博士Mark Klebanoff和医学博士Thomas Newman以及在纵向数据分析和计量因果推断方法方面都有专长的经济学家Patricia Reagan博士将担任导师。其他顾问将提供心脏病学专业知识(医学博士Vidu Garg)，并协助PHIS和CHND数据库的合并(马特·霍尔博士)。除了使斯劳特博士成为新生儿比较有效性研究的独立专家外，我们还希望我们的发现能为PDA早产儿的护理提供信息，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.