AGE is a frequent disease, with rotavirus being the main cause in children under 5 years of age. The burden of RVGE is considerable both in terms of clinical and economic considerations[6, 46, 47]. To our knowledge this is the first study to estimate the burden of paediatric RVGE, the associated direct and indirect costs, and the potential health and economic benefits of a universal rotavirus vaccination programme in Spain. The model predicted that RVGE would be responsible for more than 181,600 infections for every new birth cohort in Spain followed up to 5 years of age and would result in intensive use of health care services as well as more than 210,000 work days lost by parents. The implementation of a universal vaccination programme for infants in Spain could potentially reduce the overall clinical burden of RVGE by 75% and save 76% of costs from both the NHS and the societal perspectives.
We estimate that RVGE is responsible for more than 14,000 hospitalisations a year in children up to 5 years old in Spain. This incidence is higher than that previously reported, which was 9,000 days of hospitalisation a year in children of the same age group. The difference might be explained by the methodology used since in the previous study hospitalisation for RVGE was estimated using data on laboratory reports and hospital admissions due to AGE. Our data were based on the results from a recent prospective epidemiological and cost-of-illness study (REVEAL), which included all children aged up to 5 years old with RVGE over a one year period in one Spanish region, so our estimation might reflect the current burden of hospitalisations due to RVGE in Spain.
The annual incidence rates for PCC consultations in patients with RVGE seeking medical attention assumed in this study based on REVEAL, is very similar to the results in other previous studies performed in Spain[48, 35].
Furthermore a recent review of prospective studies suggested that the total burden of symptomatic rotavirus infection does not differ significantly between studies in different countries around the world, even though use of health care by infected patients does .
A recent study in the Galician area of Spain estimated that the mean indirect cost per case due to RVGE was €428. This cost included productivity loss, travel expenses, cost of caregivers, meals and materials. Although our definition of indirect costs referred only to productivity loss, our model included transportation, extra nappies and baby sitting in terms of non-medical costs. Taking these costs together, our estimated cost is lower, ranging form €139 to €289 (PCC and hospital cases, respectively). The work days lost by parents accounted for 69% and 75% of the overall cost in studies conducted in the United States and in Italy, respectively, whereas in our model this was only 39% of the overall cost of €19.6 million. This suggests that our analysis might underestimate the real burden of RVGE in Spain.
Although there are no other studies evaluating the impact of a universal rotavirus vaccination in Spain, our findings are consistent with studies performed in France, UK and Germany, that estimated that a universal vaccination programme, with a 90% coverage, would reduce the burden of disease by 74% to 75%.
The main objective of the study was to assess the economic burden of rotavirus disease and to describe the potential benefits of rotavirus vaccination, but not its cost-effectiveness. A cost effectiveness analysis is usually used as a decision making tool for resource allocation in a situation of limited resources. In order to perform a cost effectiveness analysis, a reliable vaccine price should be considered. However, the current situation in Spain is that the vaccine is currently available on an out-of-pocket market, i.e., not reimbursed by the national health system with different prices depending on the region. It is consequently difficult to assess the current market price. Also, the expected tender price under reimbursement from national health system would be lower than the current market price. Therefore, using the current market price for the vaccine would substantially unfavour the cost-effectiveness results, and even more, results would not be reliable because of the use of un real vaccine price.
However, a cost-effectiveness analysis would be of interest using various price assumptions and correct methods to assess at best the impact of uncertainty related to rotavirus epidemiology and estimation of quality of life in children aged under five years old on the cost-effectiveness ratios.
As most of economic models, one limitation of this study is that it relies on assumptions for some parameters which induce uncertainty around the estimates. Due to lack of evidence, data from nearby countries was used as proxy for Spain; this is the case for the percentage of working mothers (51%), which is based on Italian data, or the percentage of cases not seeking for medical attention (41.4%), based on French information. In both cases, differences in health behaviour within countries might be observed; for example, it is possible that more than 51% of mothers in Spain work although this parameter did not have any impact in the results. Secondly, we considered a coverage rate of 90% as indicated by the World Health Organization (WHO) for common compulsory vaccinations. However, according to Martin A, average paediatric coverage rates might be higher in Spain (97%) due to higher reimbursement rates from the national healthcare payer compared with those in other European countries. This mainly implies that our results are certainly conservative and underestimate the real benefit of the vaccination.
Furthermore, the model did not consider additional indirect benefits due to rotavirus vaccination programme. For example, it is noteworthy that the epidemic peak of RVGE overlaps with that of other seasonal diseases such as influenza and respiratory syncytial diseases thus increasing the load for health services which are already overcrowded at this period. By decreasing substantially the number of RVGE cases, the vaccination contributes to a better organisation of paediatric services at hospital as well as in PCCs.
Potential herd immunity resulting from transmission of vaccine strains has not been considered in this study. As rotavirus is transmitted by infants and children, it spreads within families and day care centres, the possibility of herd immunity would contribute substantially to the burden reduction. Preliminary data from the United States show that 2 years after the introduction of RV vaccination into the immunization schedule, the reduction in severe rotavirus disease appears to approximate that seen in phase III clinical trials. More over there also been reductions in rotavirus disease in older and unimmunised age groups[54, 55]. In a recent study performed in five European countries where authors were evaluating cost -effectiveness of the rotavirus vaccination, the results show that incorporating the effect of possible indirect protection has overall a moderate impact on the cost-effectiveness ratio in all the countries. However, in some countries where the vaccination is not cost-effective but near to the threshold of 30.000€ per QALY the inclusion of indirect benefits of the vaccine could change the overall conclusion. Although there have been reports of symptomatic cases due to transmission of vaccine rotavirus reported among family members, we did not take this into account due to the lack of available data. Generally, the limitations discussed would tend to lead to an underestimation of the vaccine benefits.