Fig. 4

Trial sequential analysis of 8 trials comparing NOM vs. OM for overall treatment efficacy. The cumulative Z-curve crossed the conventional boundary for benefit and required information size but did not cross the trial sequential monitoring boundary for benefit, suggesting that the current evidence is statistically significant but does not support a superiority of OM and further trials will not change this conclusion. A diversity adjusted required information size of 2805 patients was calculated using an alpha = 0.05 (two sided) and a beta = 0.20 (power 80%), and empirical estimation from TSA software