Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

Abstract

BackgroundThe Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy).ObjectiveTo describe the data management process and statistical analysis plan.MethodsThe statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes.ConclusionAccording to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results.Trial registrationClinicalTrials.gov number, NCT01374022.

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome

“…We conducted a randomized clinical trial in 120 intensive care units (ICUs) from 9 countries (Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay). The protocol and statistical analysis plan (in Supplement 1) were published previously . Data analysis started after the statistical analysis plan was accepted for publication (see eAppendix in Supplement 2 for details).…”

“…Length of ICU stay (secondary outcome) and all other exploratory outcomes were included in our statistical analysis plan and ClinicalTrials.gov, although they were not originally in our study protocol (see eAppendix in Supplement 2 for details).…”

High frequency percussive ventilation increases alveolar recruitment in early acute respiratory distress syndrome: an experimental, physiological and CT scan study

“…Different strategies can be used to perform OLV. Conventional ventilation, combining low tidal volume [ 2 ], tailored positive end-expiratory pressure (PEEP) [ 3 ], prone positioning [ 4 ] and recruitment maneuvers (RM) [ 5 ] currently comprise the regular approach. High frequency ventilation, including high frequency oscillatory ventilation (HFO), high frequency percussive ventilation (HFPV) and jet ventilation, have been used.…”

Should the ART trial change our practice?

“…The second critic raised by Dr Villar and colleagues is the fact that although our main results (using Cox proportional hazards model) showed significant harm, P values are slightly higher than 0.05 using other statistical tests. We defined a priori in our SAP that the main analysis would be a Cox proportional hazards model (5,10). Therefore, the best approach to avoid multiple hypothesis testing error is to stick with the pre-specified analysis.…”