Josephine van Dongen

Chapter 8 194 Overall benefit of rotavirus vaccination for medical risk infants Rotavirus vaccination for infants with MRC in this study did not result in a significant reduction in hospitalization due to rotavirus AGE, although a 30% reduction (the point estimate of our study) could have some clinical relevance. In addition, no difference in incidence of rotavirus AGE of any severity was observed between vaccinated and unvaccinated infants. Vaccination coverage using a hospital-based targeted vaccination strategy reached 52%. Therefore, the assumptions on vaccination effectiveness and coverage in the updated cost-effectiveness analysis ( chapter 3 ) no longer apply. It is highly unlikely that targeted rotavirus vaccination would be cost-effective from either a healthcare or societal perspective at the free market price given the vaccine effectiveness estimate of 30%.Targeted vaccination could be more favorable if reductions in hospitalizations could be achieved through non-specific effects. However, such non-specific beneficial effects of rotavirus vaccination could not be demonstrated in our study. Safety and tolerability profile Some safety signals were detected in our study and have also been described earlier. 58 An evaluation of repor ts from the vaccine adverse event repor ting systems in America and Europe covering ten years, concluded that most adverse events following rotavirus vaccination were gastrointestinal, non-serious and were already included in the Summary of Product Characteristics (SPCs), like vomiting and diarrhea (n>1000). Respiratory tract infections, Kawasaki disease and neurological disorders were also repor ted, although causality is difficult to establish and the authors recommend fur ther investigation. The repor ted odds ratios, for rotavirus vaccines compared to other vaccines, were 8.8, 14.6 and 2.3 for respiratory tract, Kawasaki and neurological diseases respectively. These passive adverse event surveillance databases do not include information on patient characteristics (such as presence of MRC) and stratified risk assessment for comparison was therefore not possible. Our tolerability results also showed most adverse events were gastrointestinal and non-serious (i.e. did not require healthcare attendance).Yet the few severe (mainly gastrointestinal) adverse events we observed cannot be ignored. Risk-benefit ratios The combined results on vaccine effectiveness, overall health benefits and safety risks of rotavirus vaccination for infants with MRC warrant recalculation and weighing of the risk- benefit ratios. If we conservatively consider only those serious adverse events (SAE) for which a link with other routine national immunization program vaccines is unlikely given the nature of events (gastrointestinal), there were eight vaccine related SAE among 2077 vaccinated infants (described in chapter 5 ). This translates to a population attributable risk of vaccine related SAE after rotavirus vaccination of 0.4%. Which means that four in 1000 vaccinated