Limitations
SECONDARY, RECRUITMENT
This study has limitations. The statistical power of the trial was limited because we were only able to include 510 participants in the ITT analysis of the primary outcome instead of the 608 we had originally planned. This was due to a smaller number of recruited participants and a higher dropout rate than expected. However, based on the available results, it can be assumed that even if the target number of individuals had been reached, there would not have been a chance to show a statistically significant difference in the primary end point.In addition, the limited statistical power results in a lower certainty to detect a statistically significant difference between the intervention and control group in the other direction and to exclude a harmful effect of the COFRAIL intervention. Another limitation is that comprehensive information about the reasons for each hospital admission could not be collected in our study setting.The analyses of the secondary end points were performed for the PP population and not for the ITT population due to the lack of measurement options for the dropout participants, which could lead to an overestimation of the observed effects. The switch in data collection by the study nurses from home visits to telephone interviews because of the COVID-19 pandemic may have contributed to comparatively high dropout rates and led to limitations in data quality.At the patient level, it is possible that the GPs included more patients in whom they expected to see a high level of adherence to the study, which limits the representativeness of the study. To minimize selection bias, neither the study physicians nor the patients were informed about the intervention elements at the time of recruitment.