Zsa Zsa Weerts

Smart Data Collection for the Assessment of Treatment Effects in IBS 225 9 In terms of electronic diary usage in clinical trials, the adherence rate found in this IBS study is at least comparable to or even higher than rates previously reported rates. 5,14,15 Most people in the Netherlands own a mobile phone, i.e. 90.3% (Statistics Netherlands). 21 Only few patients ( N =4) needed a device from the investigator team to participate in the study and only a single patient stated the digital data-collection as a reason not to participate. Mean adherence to the digital symptom diary decreased with +/-11% from the first week of the pre-treatment period, to the last week of the eight- week treatment period ( Figure 9.4 ). A slight decrease in adherence to the diary during a study period, i.e. logging fatigability, is not uncommon and has also been observed in other studies investigating digital diaries. 5,22 Regarding the usage of digital diaries in RCTs to assess treatment response (according to FDA-recommended definitions) in IBS patients specifically, we are aware of one recent IBS study that applied an electronic diary to assess treatment effect. However, a direct comparison with this study was not possible, as details on the type of device, application, or adherence to the diary were not provided. 23 With regard to sociodemographic and clinical patient characteristics associated with completing the daily entries in the diary, we found no evidence for a statistically significant effect of gender, age, or educational level on adherence. This differs from the results of some prior studies and meta-analysis, which observed for example a statistically significant positive effect of age on adherence. 15,17 Our interpretation is that this may be caused by the relatively young patient population in the current study. We observed that patients with higher anxiety scores had lower adherence to the digital symptom diary. These data are in line with those of Aaron et al., showing that participants with higher stress levels may have lower completion rates. 24 Interestingly, a negative association was found between one inclusion center and adherence. All four inclusion centers were located in urban areas, but with a wide geographical spread throughout the Netherlands as shown in Supplementary Figure S9.2 . The center with the negative association (C) was the center in the most urban and populated area, i.e. the Amsterdam-The Hague-Rotterdam-Utrecht urban agglomeration. No obvious demographical or baseline differences were observed between study populations in different inclusion centers. No significant association was found between the lower adherence and the investigator by whom the instructions were given. Although the reason for a lower adherence of patients included in this center is unclear, religious and cultural backgrounds of inhabitants of this agglomeration may have differed from those of the inhabitants of other geographical areas. 25-27 Nevertheless, overall mean (SD) adherence during the treatment period in this inclusion center was still good, i.e. 82.3% (12.5).