Leveraging existing registry resources to facilitate clinical trials

这项建议的中心目标是：1)设计和实施围手术期的“登记内试验” 类固醇用于改善新生儿体外循环(CPB)手术后的预后；2)开发 以注册为基础的儿科心脏手术试验网络的基础设施；以及3)定义一个新的成本模型- 可用于研究未得到充分研究的疾病和状况的有效临床试验。拟议的工作将 通过三个CTSA中心(杜克大学、约翰霍普金斯大学)之间的合作完成 范德比尔特大学，以及胸科外科学会及其分析中心，杜克临床 研究所。 临床试验是资源密集型和成本高昂的。因此，许多患者群体仍然没有得到充分的研究 指导临床实践的证据有限。改善证据基础的一种机制是利用 现有登记处资源，用于进行简单、高效和低成本的审判。这种“在登记处进行审判”的概念 可以：1)通过使用注册数据为临床试验模拟提供信息来优化试验设计；2)改善研究机会 学科和中心；3)提供质量控制机制，确保高效、准确和成本效益 数据收集；以及4)提供成熟和经过测试的基础设施，以汇编、分析和传播试验数据。 拟议的工作将展示“登记处内审判”办法在未得到充分研究的 脆弱患者群体，在体外循环下接受心脏手术的新生儿。新生儿心脏病后死亡率 手术发生率为10%，主要并发症发生率为23%。这些糟糕的结果与严重的 新生儿CPB全身炎症反应。几十年来，大剂量的全身类固醇药物一直在使用 减少新生儿心脏手术后CPB后的炎症反应。然而，支持这一观点的数据有限。 实践；以前的试验都是小规模的，都依赖于替代结果衡量标准。最近的数据来自 接受体外循环的成年人表示，类固醇会导致更糟糕的结果。有一个紧急的和未得到满足的 新生儿体外循环术后是否需要进行大规模、确凿的类固醇试验具有临床意义 终端。这项试验可以很容易地以典型临床试验的一小部分成本进行，通过利用 现有的基础设施的胸部外科医生协会的先天性心脏病手术数据库。

The central objectives of this proposal are to: 1) design and conduct a “trial within a registry” of perioperative steroids to improve outcomes after neonatal cardiopulmonary bypass (CPB) surgery; 2) develop the infrastructure for a registry-based pediatric heart surgery trials network; and 3) define a new model for cost- effective clinical trials that may be used to study understudied diseases and conditions. The proposed work will be accomplished through collaboration between three CTSA hubs, Duke University, Johns Hopkins University and Vanderbilt University, as well as the Society of Thoracic Surgeons and its analytic center, the Duke Clinical Research Institute. Clinical trials are resource-intensive and costly. Consequently many patient populations remain understudied with limited evidence to guide clinical practice. One mechanism to improve the evidence base is to leverage existing registry resources to conduct simple, efficient and low cost trials. This “trial within a registry” concept can: 1) optimize trial design by using registry data to inform clinical trial simulations; 2) improve access to study subjects and centers; 3) provide quality control mechanisms ensuring efficient, accurate, and cost-effective data collection; and 4) provide mature and tested infrastructure to compile, analyze and disseminate trial data. The proposed work will demonstrate the benefits of the “trial within a registry” approach in an understudied and vulnerable patient population, neonates undergoing heart surgery with CPB. Mortality after neonatal heart surgery occurs in 10% with major complications in 23%. These poor outcomes are related to the severe neonatal systemic inflammatory response to CPB. For decades high-dose systemic steroids have been used to reduce post-CPB inflammation after neonatal heart surgery. However there are limited data to support this practice; prior trials have all been small and have relied upon surrogate outcome measures. Recent data from adults undergoing CPB suggest that steroids contribute to worse outcomes. There is an urgent and unmet need for a large scale, conclusive trial of steroids after neonatal CPB focused on clinically meaningful endpoints. This trial can be readily conducted at a fraction of the cost of a typical clinical trial by leveraging the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database.