Title:
[A full economic evaluation of extensive vaccination against rotavirus with RIX4414 vaccine at National and Regional level in Italy].

Abstract:
Vaccination of all healthy children against rotavirus (RV) has been recommended, since the availability of vaccines, both in Europe (PIDJ) and Italy (pediatricians). The aims of universal vaccination against RV include the protection of children against moderate/severe gastroenteritis forms by RV (GARV), prevent hospitalizations, reduce the severity and duration of the disease, and reduce morbidity and socioeconomic costs. Payers need to informed regarding the efficacy and the healthcare utilization related to RV vaccination in order to decide in favour of its extensive implementation. The aim of this paper is to assess the clinical and financial impact of the extensive vaccination aganist RV both at National and Regional level. Particular attention, compared to the previous analysis (Standaert et al, 2008) has been given to the influence of herd immunity (HI) on cost-utility results of vaccination against-RV. Methods. The analysis was conducted with the Markovian model previously used by Standaert B et al and updated for comparing costs and benefits associated with a situation of vaccination anti-RV that includes efficacy data due to HI, with a situation without vaccination. For the base case is assumed an annual coverage of 90%, where the effect of HI is present in the population at risk (0-5 years) and extended to children who have not been vaccinated, adding as conservative assumption, a further 10% to the efficacy of the vaccine, compared to 15% determined by several published studies. Two analysis have been made based on this model: a cost-utility analysis that compared vaccination with two doses of RIX441410 administered at 2 and 3 months after birth compared with no vaccination from National Health Service and Society perspective; a budget impact analysis at National and Regional level. The evaluation has as its main element the reduction of cases of infection through universal vaccination and consequent reduction of Garv events and nosocomial infections. Results. From the NHS perspective, in a cohort of 555,791 born in Italy in 2011, the annual number of hospitalizations due to RV infections in the absence of vaccination is estimated to be 14,550 units. Assuming that 90% of newborns receive two doses of the vaccine, and including an additional effect of HI to the efficacy of the vaccine, vaccination would lead to a reduction of 71% of cases of Garv (176,804 cases in less) and a 86% of hospitalizations due to Garv (12,913 fewer cases), with an impact on quality of life and mortality as a consequence of vaccination. The introduction of the vaccine would lead to a gain of 0.0014 QALYs and 0.0022 life-years gained per child compared to a situation without vaccination (assuming a discount rate of 3% on future benefits). The reduction of GARV also would lead to a strong economic impact. The introduction of the vaccine would lead to a saving of € 25.41 per child or a saving of more than € 14 million for the whole population included in the analysis. Cost reduction increase significantly from the perspective of society and introducing the indirect costs due to lost productivity. In this case, the savings due to the introduction of vaccination would increase to € 67,747,654 in the total cohort, or € 121.89 per child. In an alternative scenario, where HI is excluded, RIX4414 remains dominant (0.0013 QALYs gained and € 22.14 per child saved). The budget impact analysis shows that, as early as the second year, the additional cost of the vaccine is more than offset by a reduction in costs of the disease, which leads to savings for the NHS, which increases from year 3. In a time horizon of 5 years (without the discount rate), the savings for the NHS amount to € 34,440,314. These savings would amount to a cost reduction of € 4.64 per child over 5 years (€ 0.93 per year). The savings due to the introduction of the vaccine were mainly due to a reduction in costs associated with hospitalizations. The budget impact analysis at regional level, has taken a vaccine cost of € 30.00 per dose. Cases of diarrhoea before after vaccination are reduced in each region, based on the number of births, ranging from a minimum of 399 cases avoided for Valle d'Aosta to a maximum of 31,116 cases avoided in Lombardy. In a similar way, the number of hospitalizations due to GARV are reduced considerably, from a minimum of 36 cases in Valle d'Aosta to a maximum of 3,096 in Lombardy. Obviously, these reductions are greater in regions with 30,000 or more births per year. Conclusions. This study suggests that a universal vaccination anti-RV with 2 doses of RIX4414 brings significant clinical and economic benefits both at National and Regional level. The indirect effects of the vaccine (HI) could generate protection even in unvaccinated children with health gain and a number of cases by GARV much less than those that would vaccinating small groups of children and with a cost of illness, for NHS, which would be reduced significantly, despite the additional costs of the vaccine as early as the second year of vaccination. Productivity losses due to absence from work of a parent, as well as all other costs included in the model, show that is precisely the society to pay the consequences, from economic and social point of view. Considering the citizen in the role of private payer, we must stress as for him, the savings generated by vaccination, whether universal or with demand for cost-sharing by the health service, prove significant with a major health gain for the population under study.