Data Fusion: A Sustainable, Scalable, Open Source Registry Advancing PVD Research

描述（由申请人提供）：儿童肺血管疾病（PVD），包括儿童肺动脉高压（PH），是高发病率和死亡率的疾病，但治疗选择有限。尽管有新的药物治疗，严重PH患者的生存率仍然很低。尽管大多数临床研究都强调成人的疾病，但儿科PVD可能是毁灭性的，在新生儿、婴儿和儿童中造成的不良后果与成人截然不同。不幸的是，很少有研究涉及儿童PVD治疗的安全性和有效性。目前的PVD治疗方法受到少数PH患者的限制，并且在任何单个中心，PH与各种儿科疾病和亚专科之间存在关联；很少有成熟的儿科PH多学科项目；以及现有PVD计划之间有限的相互作用。多中心调查对充分有力的介入研究是必要的，但由于缺乏对疾病表型、临床过程、结果和年龄相适应的终点的了解，研究设计受到限制。因此，我们的目标是建立和运营一个生物信息学临床协调中心（BCCC），以促进对儿童PVD的理解和治疗，该中心由儿科肺脏和心脏医学、信息学、生物统计学以及基于注册和电子健康记录（EHR）的临床研究领域的国家领导者组成。我们利用和扩展现有的儿科肺动脉高压网络（PPHnet）进行大规模注册和基于ehr的研究，使用经过良好测试和广泛采用的开源数据仓库技术基础设施（i2b2/SHRINE），通过NIH国家生物计算中心和临床和转化科学奖（CTSA）项目开发。该提案的目标有三个方面：(1)在8个PPHnet站点上建立一个可持续的、开源的、可重用的注册基础设施，以获取大型前瞻性儿科肺动脉高压（PH）观察队列中的多源电子病历、“传统的”前瞻性患者数据和患者报告的结果（PROs）；(2)在8个PPHnet站点上登记500名注册主体，并捕获750名EHR受试者的数据，将3个站点的EHR与注册数据联系起来；(3)解决对PH的表征和管理至关重要的三类未解决的问题，比较注册表与EHR与注册表/EHR/PROs融合数据在PH合并症谱、PH指标和发病率和死亡率终点以及PH治疗反应方面的信息价值。

DESCRIPTION (provided by applicant): Pediatric pulmonary vascular diseases (PVD), including pediatric pulmonary hypertension (PH), are high morbidity and mortality conditions, yet treatment options are limited. Despite new drug therapies, survival of patients with severe PH remains poor. Although most clinical studies have emphasized disease in adults, pediatric PVD can be devastating, contributing substantially to poor outcomes in newborns, infants and children that are strikingly different from those encountered in adults. Unfortunately, very few studies have addressed the safety and efficacy of PVD therapies in children. Current approaches to PVD are limited by small numbers of patients with PH and the association of PH with a variety of pediatric disorders and subspecialties at any individual center; by few established, multidisciplinary programs in pediatric PH; and by limited interactions among existing PVD programs. Multi-center investigations are necessary for sufficiently powered interventional studies, but study designs have been restricted by lack of knowledge as to disease phenotypes, clinical course, outcomes, and age-appropriate endpoints. Our objective, therefore, is the establishment and operation of a Bioinformatics Clinical Coordinating Center (BCCC) for advancing the understanding and treatment of PVD in children, comprised of national leaders in pediatric pulmonary and cardiac medicine, informatics, and biostatistics as well as registry-based and electronic health records (EHR) clinical research. We leverage and extend the existing Pediatric Pulmonary Hypertension Network (PPHnet) for large-scale registry and EHR-based research, using a well tested and widely adopted open-source data warehouse technology infrastructure (i2b2/SHRINE), developed through the NIH National Centers for Biocomputing and Clinical and Translational Science Award (CTSA) Programs. The goal of this proposal is three-fold: (1) establish a sustainable, open source, reusable registry infrastructure across 8 PPHnet sites to capture multi-sourced EHR, "traditional" prospective patient-based data, and patient reported outcomes (PROs) across a large, prospective, pediatric pulmonary hypertension (PH) observational cohort; (2) enroll >500 registry subjects and capture data on >750 EHR subjects across 8 PPHnet sites, linking EHR with registry data at 3 sites; (3) address three classes of unanswered questions crucial for the characterization and management of PH, comparing the information value of registry vs. EHR vs. fused data across registry/EHR/PROs, in the domains of spectrum of PH comorbidities, PH indicators and endpoints of morbidity and mortality, and response to therapies in PH.