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Figure 4e: Trial sequential analysis on secondary outcomes: Trial sequential analysis on the rate of skin irritation, involving 21 randomized controlled trials illustrated that the cumulative Zcurve had not crossed the monitoring boundary. The required information size was calculated to 26,534. (NOTE: The red line is the trial sequential analysis monitor boundary according to a relative risk reduction of 20%, type I error of 5% and type II error of 20%. The red horizontal line is the Zscore of ±1.96, equal to twosided P = 0.05. Xaxis: The number of patients randomized, Yaxis: the Zscore) 
