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

描述(申请人提供)：儿科肺血管疾病(PVD)，包括儿科肺动脉高压(PH)，发病率和死亡率都很高，但治疗选择有限。尽管有新的药物治疗，重度PH患者的存活率仍然很低。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，在很大程度上导致新生儿、婴儿和儿童的不良结局，这些结果与成人截然不同。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治疗方法受到以下因素的限制：PH患者数量较少，以及PH与各种儿科疾病和亚专科之间的联系；儿科PH中建立的多学科计划很少；以及现有PVD计划之间的互动有限。对于足够有力的介入研究来说，多中心研究是必要的，但由于缺乏关于疾病表型、临床病程、结果和适合年龄的终点的知识，研究设计一直受到限制。因此，我们的目标是建立和运作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，该中心由儿科心肺医学、信息学、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者组成。我们利用并扩展现有的儿科肺动脉高压网络(PPHnet)，用于大规模注册和基于EHR的研究，使用经过充分测试和广泛采用的开源数据仓库技术基础设施(i2b2/Shorine)，该基础设施通过NIH国家生物计算中心、临床和翻译科学奖(CTSA)计划开发。这项建议的目标有三个：(1)在8个PPHnet站点建立可持续、开源、可重复使用的注册基础设施，以获取来自多个来源的EHR、“传统的”基于患者的预期数据和在大型、预期的儿科肺动脉高压(PH)观察队列中的患者报告结果(PRO)；(2)在8个PPHnet站点登记500个注册受试者，并捕获有关&gt；750个EHR受试者的数据，将EHR与3个站点的注册数据联系起来；(3)解决对PH的特征和管理至关重要的三类悬而未决的问题，在PH合并症的范围、PH指标和发病率和死亡率的终点以及对PH治疗的反应等领域，比较登记册与EHR和跨登记册/EHR/PROS的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.