CCC for NHLBI Prevention and Early Treatment of Acute Lung Injury PETAL Network

描述（由申请人提供）：本提案是对急性肺损伤预防和早期治疗临床试验网络（PETAL）网络协调中心的RFA-HL-14-015的回应。我们建议在设计、分析和开展PETAL网络研究方面发挥领导作用，并提供基础设施和通信，以创建一个具有凝聚力和生产力的小组。在过去的18年里，我们一直是急性呼吸窘迫综合征（ARDS）网络的协调中心，在一位经验丰富的临床试验统计学家和一位急性护理医生的领导下。我们最近发表了我们对ARDS网络的统计和物流问题的方法。我们建议对这些方法进行改进，以提高PETAL的这些活动的性能。我们对PETAL网络的建议侧重于预防试验的新挑战。我们建议，预防试验的可行性取决于终点的选择，特别是使用死亡率作为主要终点的研究在常规试验设计中是不可行的，其他临床终点可能存在问题。最佳终点是ARDS的发生或衡量ARDS的临床后果。该提案讨论了集群随机试验和自适应设计的问题。我们讨论了为PETAL网络创建生物标志物资源的统计和科学问题。我们还描述了通过实施有效的IRB审查流程来提高网络生产力的建议，应用计算机辅助技术来设置网络优先级的计划，以及在持续的基础上征求社区参与的计划。我们描述了我们将使用的方法，以提供所需的基础设施（如远程数据和试验管理系统）和所有网络活动的协调：数据质量控制、协议遵守、协议启动、随机化、药物分发、样本管理、不良事件报告、统计报告、数据传播、通信和物流。

DESCRIPTION (provided by applicant): This proposal is a response to the RFA-HL-14-015 for the coordinating center of the Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. We propose to provide leadership in the design, analysis and conduct of the studies of the PETAL Network and to provide the infrastructure and communications that will create a cohesive and productive group. Over the past 18 years we have served as the coordinating center of the Acute Respiratory Distress Syndrome (ARDS) Network under the leadership of an experienced clinical trials statistician and an acute care physician. We recently published our approach to the statistical and logistics issues of the ARDS Network. We propose to enhance those methods to improve performance of these activities for PETAL. Our proposal for the PETAL network focuses on the novel challenges of prevention trials. We suggest that the feasibility of a prevention trial depends on the choice of endpoint, in particular that studies using mortality as the primary endpoint would not be feasible with a conventional trial design and other clinical endpoints may be problematic. The optimal endpoint would be the occurrence of ARDS or a measure of the clinical consequences of ARDS. The proposal discusses the issues of cluster randomized trials and adaptive designs. We discuss the statistical and scientific issues in creating a biomarker resource for the PETAL Network. We also describe our proposals to increase productivity of the network by implementing an efficient IRB review process, plans for applying a computer-assisted technique to set network priorities, and plans for soliciting community involvement on an ongoing basis. We describe the methods we will use to provide the needed infrastructure (such as a remote data and trial management system) and the coordination of all network activities: data quality control, protocol compliance, protocol initiation, randomization, drug distribution, sample management, adverse event reporting, statistical reporting, data dissemination, communication, and logistics.