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

描述（由申请人提供）：儿科肺血管疾病（PVD），包括儿科肺动脉高压（PH），是发病率和死亡率较高的疾病，但治疗选择有限。尽管有新的药物治疗，重度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疾病，但儿科PVD可能是毁灭性的，导致新生儿、婴儿和儿童的不良结局，与成人的结局截然不同。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治疗方法受到以下因素的限制：PH患者数量少，PH与任何单个中心的各种儿科疾病和亚专科相关;儿科PH中已建立的多学科项目很少;现有PVD项目之间的相互作用有限。多中心研究对于充分把握度的干预性研究是必要的，但研究设计受到缺乏疾病表型、临床病程、结局和年龄适当终点知识的限制。因此，我们的目标是建立和运营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，该中心由儿科肺和心脏医学，信息学和生物统计学以及基于注册和电子健康记录（EHR）临床研究的国家领导人组成。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（i2 b2/SHRINE），通过NIH国家生物计算中心和临床与转化科学奖（CTSA）计划开发。该提案的目标有三个方面：（1）在8个PPHnet站点上建立可持续的、开源的、可重复使用的登记基础设施，以在一个大型的、前瞻性的、儿科肺动脉高压（PH）观察队列中捕获多源EHR、“传统的”基于患者的前瞻性数据和患者报告的结局（PRO）;（2）在8个PPHnet站点上招募>500名注册受试者并捕获关于>750名EHR受试者的数据，将EHR与3个站点的注册数据相关联;（3）解决三类对PH的表征和管理至关重要的未回答的问题，在PH合并症谱、PH指标和发病率和死亡率终点以及PH治疗反应等领域，比较登记研究、EHR和登记研究/EHR/PRO融合数据的信息价值。

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.