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

描述(申请人提供)：本提案是对RFA-HL-14-015关于急性肺损伤(PEAL)预防和早期治疗临床试验网络协调中心的回应。我们建议在设计、分析和开展花瓣网络研究方面发挥领导作用，并提供基础设施和通信，以建立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，由一名经验丰富的临床试验统计学家和一名急性护理医生领导。我们最近公布了我们对ARDS网络的统计和后勤问题的处理方法。我们建议加强这些方法，以提高这些活动的绩效。我们对Petal网络的建议侧重于预防试验的新挑战。我们认为，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，其他临床终点可能是有问题的。最佳终点将是ARDS的发生或ARDS临床后果的衡量。该提案讨论了整群随机试验和适应性设计的问题。我们讨论了为花瓣网络创建生物标记物资源的统计和科学问题。我们还介绍了我们通过实施有效的IRB审查过程来提高网络生产率的建议，应用计算机辅助技术来确定网络优先事项的计划，以及持续征求社区参与的计划。我们将介绍我们将用于提供所需基础设施(如远程数据和试验管理系统)以及协调所有网络活动的方法：数据质量控制、协议遵从性、协议启动、随机化、药物分配、样本管理、不良事件报告、统计报告、数据传播、通信和后勤。

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.