Fig. 3

A benchmark ICU mortality of 23% as derived previously is used to represent the background mortality rate without intervention [52]. The intra-cluster coefficient (ICC) used in power calculations in previous mega-CRTs ranged between 0.001 and 0.01 (Table 2). Using these estimates, a study with 104 clusters (ICUs) each with 150 patients (75 directly and 75 indirectly exposed), (or 52 ICUs with a two-period crossover design), and an ICC of 0.001 (left panel), would have an 80% power to detect a 2% absolute increase (or decrease) in mortality at a 0.05 level of significance (using Stata command ‘power twoproportions .23 .25, m1(75) m2(75) rho(0.001)’). A two-period study with crossover would require 52 ICUs for the same power. With an ICC of 0.01 (right panel), the number of ICUs required increases to 168 (‘power twoproportions .23 .25, m1(75) m2(75) rho(0.01)’) (or 84 ICUs for a two-period crossover)