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Chapter 8 202 effectiveness, since long-term savings and QALY gains are not taken into account. However, as guidelines do not currently recommend peppermint oil usage for longer than three months 32 , we did not perform any long-term analysis and did not extrapolate the data. Future studies should investigate the safety, effect and QALY gains of longer treatment periods. This economic evaluation additionally investigated cost-effectiveness based on a clinical parameter instead of traditional QALYs. We used the stringent abdominal pain response outcome (FDA-defined) at a willingness-to-pay-threshold of €5000 and showed that while using this outcome, peppermint oil has an 89% probability of being cost-effective. Currently, healthcare policymakers have not defined willingness-to-pay threshold values when clinical effect measures are used instead of QALYs. 24 Nevertheless, given that the FDA-endpoint is recommended by drug regulatory authorities 33,34 and widely accepted as a primary outcome in IBS trials, we anticipate that more economic evaluations will present ICERs based on this endpoint in addition to ICERs based on more traditional QALY outcomes. This would enhance comparisons between treatments further. The results of the current study should be considered in light of potential limitations. First, for the estimation of costs, we relied on self-reported healthcare usage and productivity losses, which may lead to recall- and social desirability bias. However, studies in the UK and the Netherlands have shown good agreement between health registry and self-reported data. 35,36 In addition, the bias would have been present in both groups and is therefore unlikely to have a noticeable effect. Second, a substantial part of the cost-savings within healthcare perspective was driven by differences in mental healthcare costs. This difference results in a higher probability of peppermint oil being cost-effective from a healthcare perspective as shown in the sensitivity analysis. It is questionable however, whether the difference in mental healthcare costs is a mere result of the treatment with peppermint oil in the relatively short period of 8 weeks. Baseline depression and anxiety scores were slightly higher in the placebo compared to the peppermint oil group. Therefore, despite using a valid randomization method stratified for potential effect modifiers, we cannot exclude this difference to be caused by chance and not treatment effect. Third, missing data regarding presenteeism ( Supplementary Table S8.1 ), limits the validity of the results. Fourth, it is not always clear whether patients can make a distinction between IBS-related productivity loss and other comorbidities. Although we used expert opinion to make such distinction for the medical consumption questionnaire, this is not possible for the productivity questionnaire because of the generic questions. Fifth, since this was a trial-based cost-