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.
Acute Respiratory Distress Syndrome (ARDS) is a life threatening lung condition that may develop after severe infections or trauma and requires mechanical ventilation and admission to an ICU. Each year in the United States there are an estimated 190,600 cases of ARDS which are associated with 74,500 deaths and 3.6 million hospital days. The proposed PETAL Network will seek to find the first specific treatment for ARDS or a method of prevention and has the potential to save thousands of lives annually. .