PROTECT was conducted over four years from May 2006 to June 2010 in 67 ICUs in Canada, the United definitely States, the United Kingdom, Australia, Brazil and Saudi Arabia, as published previously [9].Ethical approval was obtained from each participating Institutional Research Board (listed at the end of the manuscript under PROTECT Collaborators). In-person informed consent was required prior to randomization. Deferred consent was not permitted. For substitute decision-makers not in hospital, initial telephone consent, followed by in-person consent when possible, was approved in 16 of the 67 (23.9%) centers.Beginning and throughout the trial, the PROTECT Steering Committee reviewed each multicenter protocol to decide whether co-enrollment was admissible, using Canadian Critical Care Trials Group guidelines [10].

These guidelines outline important scientific (for example, interacting interventions), psychosocial (for example, family stress) and logistic (for example, research coordinator workload) factors to consider. The general approach to co-enrollment was that all reasonable efforts should be made to minimize the exclusion of patients co-enrolled in another trial if they would likely represent those patients to whom trial results would possibly be applied in practice, as long as biologic interaction of the interventions being tested in the two trials seemed highly implausible. Dialogue between the principal investigator and steering committees of each multicenter study determined whether co-enrollment would impact the scientific integrity of either study.

When relevant, this was reasoned at the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group meetings for refutation or ratification. If co-enrollment was endorsed, each participating center handled the relevant study governed by formal or informal co-enrollment policies of their ICU or hospital Institutional Review Board. Local policies could deny co-enrollment approved centrally. Local, single-center study co-enrollment could also be approved after agreement with the PROTECT Steering Committee and the relevant consortium. Decisions were revisited if emerging evidence required reconsideration (Figure (Figure2).2). All other studies into which patients were enrolled before, concurrent with, or subsequent to PROTECT were documented on case report forms.

Figure 2Co-enrollment schema. In this figure, we outline steps taken to consider co-enrollment of one patient into one or more additional studies. ABLE Trial, Age of Blood Evaluation Trial; ANZICS, Australian and New Zealand Intensive Care Society Clinical Trials …One example was co-enrollment into the Age of Blood Evaluation Study (ABLE, ISRCTN44878718). ABLE is a randomized trial evaluating mortality following transfusion Anacetrapib of red blood cells stored up to one week versus stored up to 42 days [11].