Sample Size
To demonstrate a clinically important reduction in the primary outcome, a sample size of 712 is required, assuming a decrease in the proportion of patients receiving invasive mechanical ventilation from 12% to 6%, with power 80% and a two-sided significance level of 0.05.
We plan to perform frequent monitoring and analysis of the accumulating data, with use of Bayesian stopping rules that allow timely decisions without the penalties for multiple data looks and alpha spending associated with the classic randomised controlled trial monitoring approach.[19, 23, 24] At each interim analysis, the posterior distribution of the proportion of patients who were intubated will be reported and the prespecified stopping criteria will guide the recommendations of the CRG’s executive committee.