An independent Safety and Data Monitoring Committee chaired by Professor Sir Richard Peto at Oxford University, comprising experts in clinical trials, biostatistics, and intensive care has been established. The committee will review unblinded data on patient characteristics, treatment compliance and study outcomes at two interim analyses (availability of primary outcome for 1500 and 3500 patients), at any other time point the committee may deem necessary to protect study participants, and at the final analysis. The committee will be charged with informing the study management committee if at any time there emerges: