Our model estimated that seasonal influenza vaccination in Europe currently averts each year between 1.6 to 2.1 million cases, and prevent between 25,200 and 37,200 deaths, with corresponding significant impact on hospitalisations, GP visits and costs avoided (between €248 and €332 million saved annually). The number of avertable events was within a same range regardless if effectiveness or efficacy values were used and the benefits were substantive even at the lowest estimated values, supporting the strong public health interest of influenza prevention.
Raising the VCR from current levels in Europe to the recommended 75% target, in all WHO- recommended vaccination target groups, would avert an additional average annual +1.6 to +1.7 million cases, +678,482 to +767,787 physician visits, +23,793 to +31,350 hospitalization, +9,843 to +14,342 deaths, and +883,750 to 1,015,145 lost days of work. Influenza-related costs would be offset by an additional + €190 to + €226 million over currently averted costs.
While the purpose of our study was not to estimate the net budget impact of influenza vaccination, our results are complementary to the WHO position  and to recent papers demonstrating that influenza vaccination is cost effective or even cost-savings in EU countries [52, 53]. Estimating the cost of increasing vaccination coverage will be very specific to the healthcare system. In some countries, increasing coverage using existing infrastructure will require minimum investments compared to the net public health and economic savings generated. In other countries, particularly where vaccination coverage is very low, a greater initial investment will be necessarily but it will also improve access to preventive services for the most vulnerable. Where additional resources are required to achieve the recommended 75% VCR, countries should consider who is currently covering the curative costs of influenza because those payors will have the greatest incentive to invest in prevention.
It has been argued that increased effectiveness/efficacy of seasonal influenza vaccines is needed . We estimated the impact of a hypothetical vaccine with 80% effectiveness/efficacy compared to the impact of increasing vaccination coverage with current trivalent influenza vaccines to 75%. Overall, the impacts were similar but this does not consider the possible impact that increasing vaccine effectiveness might have on vaccination acceptance. Furthermore, there are challenges associated with achieving 80% vaccine effectiveness, particularly in the elderly with immuno-senescence, and with seasonal strain drift, and with vaccine strain mismatches. Further vaccine research and development is ongoing to overcome the associated challenges, but in the meantime increasing coverage with existing vaccines remain the best present solution to fight against a preventable disease.
In the current analysis the following limitations apply: a simplified approach was used which did not account for the indirect benefits of influenza vaccination linked to herd immunity. This underestimates the potential benefits of influenza vaccination. The model also only estimated some of the indirect costs (from work days lost) and some of the direct costs (GP visits and hospitalisations), providing underestimated figure of the possible economic benefits.
Additional limits relate to lack of data in EU and country-specific data and the methods used to account for missing data. The choice of estimating average values across seasons was clearly driven by the absence of season specific data and aimed at reflecting an estimate of influenza vaccination benefits across years. Different sources were taken for effectiveness and efficacy to account for variability between seasons and sources, and results were described accordingly however they might not be relevant for seasons with extreme viral circulation or vaccine mismatch. The model also did not account for the impact of increasing vaccination coverage which can result in a decreasing risk in the unvaccinated and decrease vaccine effectiveness, but this impact is expected to be small.
To deal with local data scarcity, country-specific missing data were usually replaced by similar data from neighboring countries or from another risk group in the same country, and for missing data in other target groups, the average coverage rates from all other countries were applied. This may lead to an overestimate of current VCR in the chronically ill group, for these countries, meaning that annual benefits from seasonal vaccination might be overestimated but meaning also that the benefits from increasing VCR and raising EU Council recommendation are underestimated. On the other hand, the use of incidence data on influenza-related events from surveillance networks in countries may underestimate the actual number of GP visits, since not all events will have been detected.
Kastova et al.  conducted a similar study to ours in the US. They collected surveillance data from six influenza seasons in the US. They defined impact as both the number of averted outcomes and the prevented disease fraction. Presenting impact as the prevented disease fraction allows to control for the relative severity of different seasons. They showed that a greater fraction of disease was prevented as greater fractions of the population were vaccinated.
As in our model, Kastova et al. used an annual vaccine effectiveness estimate based on the range of available vaccine effectiveness estimates in the literature for each season. They also performed sensitivity analyses around their assumptions for missing data to account for uncertainty. In their study, influenza illnesses averted by vaccination ranged from approximately 1.1 million to 5 million (or 357 – 1,641 per 100,000 population) during a season while the number of averted hospitalizations ranged from a 7,700 to 40,400 (2 – 13 per 100,000). This compares with an estimate from our study of approximately 311 – 409 averted cases and 9 – 13 averted hospitalizations per 100,000 population in Europe. Our findings are corroborated by those of Kastova et al. who found that influenza vaccination programs produce a substantial health benefit in terms of averted cases, clinic visits, hospitalizations, and deaths. Both Kastova et al. and our model support the need for improvements in vaccination coverage among non- elderly persons and improvements in vaccine effectiveness among the elderly to improve vaccination program effectiveness.