Josephine van Dongen

8 Summary and general discussion 189 Figure 1. Rotavirus vaccine global introduction status. 2020 @WHO. In the following paragraphs the lessons learned from the RIVAR project and its results will be discussed, related to previous literature and translated into future (clinical and research) directions. Vaccine effectiveness The most remarkable finding of this thesis is the low rotavirus vaccine effectiveness for infants with MRC. The results of this study appear in sharp contrast to results from previous (pre- licensure) efficacy studies in (subgroups of) medical risk populations. Impor tantly, efficacy studies (randomized controlled trials) are usually performed in highly selected populations under strictly controlled conditions, whereas in daily practice the intervention applies to more heterogeneous populations. The RIVAR project was specifically designed as an observational phase IV (post-licensure) effectiveness study that is suited to provide real world evidence for a heterogeneous, high-risk population.Where traditional observational study designs may suffer from bias due to confounding by indication, the quasi-experimental design of the RIVAR study was chosen to appropriately avoid this.Therefore, these results are considered representative and generalizable. Differences between the current study and prior “positive” effectiveness studies in medical risk populations are presented in table 1 .