Leveraging existing registry resources to facilitate clinical trials

利用现有注册资源促进临床试验

• 批准号: 9352386
• 负责人: H Scott Baldwin
• 金额: $ 120.23万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352386
• 关键词: Adult; Advocacy; Advocate; Benchmarking; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cardiovascular Diseases; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Collaborations; Conflict (Psychology); Cost Savings; Data; Data Collection; Databases; Disease; Dose; Eligibility Determination; Enrollment; Ensure; Event; Foundations; Grant; Heart; Improve Access; Inflammation; Inflammatory Response; Information Technology; International; Leadership; Length of Stay; Light; Methylprednisolone; Modeling; Monte Carlo Method; Morbidity - disease rate; Neonatal; Operative Surgical Procedures; Outcome; Outcome Measure; Parents; Patients; Perioperative; Placebos; Publications; Quality Control; Randomized; Registries; Research; Research Design; Research Infrastructure; Research Institute; Research Personnel; Resources; Safety; Societies; Steroids; Study Subject; Testing; Thoracic Surgeon; Treatment Protocols; United States; United States National Institutes of Health; Universities; Work; base; clinical practice; cohort; cost; cost effective; data registry; design; evidence base; experience; high risk; improved; improved outcome; innovation; meetings; member; mortality; neonate; patient population; prospective; simulation; success; trial design

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.

该提案的中心目标是：1）设计和进行定期的“注册表中的审判” 新生儿心肺旁路（CPB）手术后改善预后的类固醇； 2）开发 基于注册表的小儿心脏手术试验网络的基础设施； 3）定义一个新模型的成本 - 有效的临床试验可用于研究已知的疾病和病情。拟议的工作将 通过三个CTSA枢纽，杜克大学，约翰·霍普金斯大学的合作来完成 范德比尔特大学以及胸外科医师协会及其分析中心杜克临床 研究所。 临床试验是资源密集且昂贵的。因此，许多患者人口仍然了解 有限的证据指导临床实践。提高证据基础的一种机制是利用 现有的注册资源进行简单，高效和低成本试验。这个“注册表中的试验”概念 可以：1）通过使用注册表数据为临床试验模拟提供优化设计； 2）改善学习的机会 主题和中心； 3）提供质量控制机制，以确保高效，准确和成本效益 数据收集； 4）提供成熟和测试的基础设施以编译，分析和传播试验数据。 拟议的工作将证明在理解的“注册表中审判”方法的好处 脆弱的患者人群，接受CPB心脏手术的新生儿。新生儿之后的死亡率 手术发生在10％，重大并发症为23％。这些不良结果与严重有关 新生儿全身性炎症反应对CPB。数十年来，大剂量全身类固醇一直使用 减少新生儿心脏手术后CPB后炎症。但是，支持这一点的数据有限 实践;先前的试验都很小，并且依靠替代结果指标。最新数据来自 接受CPB的成年人表明，类固醇会导致较差的结果。有一个紧急且未定的 在新生儿CPB之后，需要进行大规模的类固醇的大规模试验，重点是临床上有意义的 端点。该试验可以通过利用典型临床试验成本的一小部分来轻松进行。 胸外科医生先天性心脏外科数据库的现有基础设施。