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Chapter 7 146 safety assessment. The treatment period was followed by a six months follow-up period in which no treatment was given. An overview of the study design and timing of the questionnaires is given in Supplementary Figure S7.1 . Electronic data capture and data storage Investigators documented all research findings in an Electronic Case Report File (eCRF). An electronic smartphone application was developed for the digital symptom diary in which entering data from previous days was impossible. The eCRF, web-based questionnaires, and diary all featured built-in routing, data validation, and response requirements to stimulate data quality and completeness. Primary efficacy endpoints The primary endpoint was the percentage of abdominal pain responders, according to FDA definition 24 , with a responder being a patient with at least 30% decrease in the weekly average of worst daily abdominal pain (scored on an 11-point NRS) compared to baseline, in at least 50% of the treatment period, i.e. four weeks. In line with EMA recommendations to use a global improvement outcome in trials treating two or more IBS-subtypes 25 , response to global relief of IBS symptoms was included as a co-primary endpoint, using a 7-point NRS. A global relief responder was defined as a patient with a weekly relief of threshold 6 or 7 on the NRS in at least 50% of the treatment period, i.e. four weeks. We expected that peppermint oil would not influence bowel habit substantially. Therefore, improvements in bowel movements and stool consistency were not included into a combined primary efficacy endpoint 24 , but were analyzed separately as secondary outcome measures. Secondary endpoints Secondary endpoints included symptom improvements of abdominal pain, abdominal discomfort, abdominal bloating, abdominal cramping, belching, nausea, and urgency. IBS symptom severity, stool frequency and consistency (based on the BSFS), use of rescue medication, quality of life, and comorbid anxiety and depression scores were also assessed. Another secondary endpoint was defined as moderate relief of IBS symptoms, with a patient being a responder if they had a symptom relief of threshold 5 or higher on the 7-point NRS in at least four of the treatment weeks. In addition, a different