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Chapter 8 194 The EuroQol-5D (EQ-5D-5L) was used to measure patients’ health-related QoL at baseline, four and eight weeks of treatment. The EQ-5D-5L measures five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and has shown good performance in IBS patients. 16 Dutch social tariffs were used to transform raw EQ-5D-5L scores to utility scores. 17 The IBS-QoL questionnaire consists of 34 items with a 5-point Likert scale, and was used to determine the impact of IBS and treatment on QoL. 18 All data was collected electronically using web-based questionnaires and a smartphone- based symptom diary. Statistical analysis Statistical analyses were performed using SPSS 25.0 (Armonk, NY, USA) and Microsoft Excel 16.16.7. The proportion of missing data and the missing data pattern were investigated using descriptives and patterns function in SPSS, and associations between missingness and baseline and outcome variables were investigated with logistic regression, to inform on the missing data mechanism. Missing values missing (completely) at random were handled by multivariate imputation by chained equations using predictive mean matching 19 with gender, IBS-subtype, age, baseline IBS severity, baseline utility, and treatment group. QALYs were calculated by the area under the curve, in which the time in a certain health state was multiplied by the utility of this health state. The time horizon was the eight-week treatment period. For the QALY calculation, utility values were corrected for baseline differences between groups with the mean absolute difference method. 20 ICER was calculated as the difference in costs divided by the difference in QALYs between peppermint oil and placebo. Nonparametric bootstrapping with 10.000 and 1.000 simulations was used to calculate the difference in costs between groups and to examine the uncertainty surrounding the ICER, respectively. This method requires resampling and derives a cost-effectiveness ratio from each of the generated repeated samples 21-23 , thereby increasing the robustness of the results and accounting for within and between imputation variability. 19 Results of the bootstrap analysis are presented in cost-effectiveness planes and net benefit acceptability curves. A cost-effectiveness plane is a scatterplot of simulated ICERs and presents the four situations of additional costs and additional QALY’s of peppermint oil compared to placebo. If the majority of the ICERs appear in the southeast quadrant, this indicates higher effectiveness at lower costs, i.e. peppermint oil dominates placebo. The northwest quadrant on the other hand indicates lower effectiveness at higher costs, i.e. peppermint oil is inferior compared to placebo. With