Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Cost-effectiveness of the cell-based quadrivalent versus the standard egg-based quadrivalent influenza vaccine in Germany.

BACKGROUND: Standard influenza vaccines are produced using egg-based manufacturing methods. Through the process, the resulting egg-adapted viral strains may differ from the selected vaccine strain. Cell-derived influenza vaccine manufacturing prevents egg-adaptation of the antigen which can improve vaccine effectiveness. We evaluated the cost-effectiveness of quadrivalent cell-derived influenza vaccine (QIVc) versus an egg-based quadrivalent influenza vaccine (QIVe) in preventing seasonal influenza from German societal and payer perspectives. METHODS: Adapted version of the individual-based dynamic 4Flu transmission model was combined with a decision-tree to calculate the impact of QIVc versus QIVe on influenza over 20 seasons in Germany. Egg-adaptation, resulting in lower effectiveness of QIVe versus QIVc towards the H3N2 influenza strain, is sourced from a US retrospective study and assumed in 100% (base case) or 55% (conservative scenario) of years. Influenza-related probabilities of outpatient visits, hospitalizations, productivity loss, and mortality, with associated (dis)utilities/costs, were extracted from literature. Costs and outcomes were discounted 3.0%/year. RESULTS: Replacing QIVe with QIVc in subjects aged ≥ 9 years can annually prevent 167,265 symptomatic cases, 51,114 outpatient visits, 2,091 hospitalizations, and 103 deaths in Germany. The annual number of quality-adjusted life-years (QALYs) increased by 1,628 and healthcare costs decreased by €178 M from societal perspective. From payer perspective, the incremental cost-effectiveness ratio was €2,285 per QALY. Scenario analyses confirmed results robustness. CONCLUSIONS: The use of QIVc compared to QIVe, in the German Immunization Program, could significantly prevent outpatient visits and hospitalizations and would enable substantial savings from a societal perspective.

Simulation studies to assess the long-term effects of Japan's change from trivalent to quadrivalent influenza vaccination.

BACKGROUND: Since 2013/2014, the WHO has been recommending quadrivalent influenza vaccines (QIV) to prevent seasonal influenza. In 2015, Japan replaced trivalent influenza vaccines (TIV) by QIV. We used computer simulations to calculate how this impacted the epidemiology and to assess its cost-effectiveness. METHODS: We simulated the seasonal transmission of the four influenza strains A(H1N1), A(H3N2), B/Yamagata and B/Victoria with the individual-based simulation tool 4Flu, using official demographic data and Japanese contact patterns. The model considered maternal protection, immunity boosting, new drift variants and different immunity durations for naturally acquired and vaccination-derived immunity. Starting with the 2015/16 season, simulations were evaluated for 20 years, using either TIV or QIV with the reported vaccination coverage. Costs and years of life saved (YOLSs) were calculated and discounted at 2%, using 2015 as base year. RESULTS: QIV annually prevents on average 548 influenza cases (4.7% of cases which occur when using TIV; 11.9% of influenza B), 1.62 hospitalizations and 0.078 deaths per 100,000 individuals. In Japan's population of 125.35 million, annually 915.06 YOLYs are gained by QIV and 107.52 million USD are saved (societal perspective) [corrected]. From payer perspective, the ICER is 3698 USD/YOLS. CONCLUSIONS: QIV is cost-effective (payer perspective) or even cost-saving (societal perspective) in Japan.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

[Public Health initiative for improved vaccination for asylum seekers]. / ÖGD-Initiative zur Verbesserung der Durchimpfung bei Asylsuchenden.

The number of asylum seekers in Germany has increased dramatically in 2015. Their medical care includes the officially recommended vaccinations; yet, no detailed information on this is yet available in Germany. In light of the rising number of asylum seekers, we have developed a concept to facilitate their vaccination. This concept includes the coordination of different partners, the supply of vaccines and other materials through the local health office, and the cooperation with the local physicians' association. To evaluate and accelerate progress, we compared the number of vaccinations conducted by physicians independently of the vaccination concept with those conducted within the new concept. For the period of investigation, 2,256 new asylum seekers were temporarily accommodated in the facilities. The vaccination concept was applied in only some of the facilities. Twenty-eight percent of all asylum seekers (642) were vaccinated at least once; 89 % of the vaccinees (571) were vaccinated within the newly developed concept. In the facilities that were not included in this concept, only 6 % of the refugees were vaccinated, whereas in the facilities that were included up to 58 % were vaccinated. Even though the new concept has started successfully, further innovations are required to reach sufficient vaccination coverage among asylum seekers. In view of the large number of new asylum seekers expected, the adjustment and expansion of the new concept requires professional planning and coordination. Furthermore, additional resources are required.

Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany.

In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50% would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was 1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of 3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into consideration.

The influenza pandemic preparedness planning tool InfluSim.

BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software http://www.influsim.info which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability.