Guiding Principles for Evaluating Vaccines in Joint Health Technology Assessment in the European Union: Preparing for the EU's Regulation on HTA for Vaccines.

OBJECTIVES: The appraisal of vaccines in the European Union (EU) currently involves many different decision-making bodies and processes. The objective of this study was to help inform the development of standardized methodology and vaccine-specific processes for use in the EU Regulation on health technology assessment (HTA). METHODS: Literature reviews and expert consultation were conducted to identify current practices and gaps related to vaccine appraisals and to develop guiding principles for the joint clinical assessment of vaccines. RESULTS: We found that significant variation exists across the EU Member States in the decision-making processes when clinically evaluating vaccines. Three guiding principles consisting of 13 recommendations were developed to help inform the development of decision-making frameworks for the joint clinical assessment of vaccines in the EU: (1) Support the creation of appropriate terminology and measurements for clinical appraisals of vaccines; (2) Develop inclusive, timely, and transparent vaccine appraisal processes to support stronger evidence generation for vaccine decision-making and appraisal; and (3) Improve the collection and interoperability of real-world data, including robust surveillance, to foster evidence generation and support the standardization of vaccine clinical appraisals. CONCLUSIONS: Given the significance of vaccines for public health, there is an urgency to develop standardized and vaccine-specific methodologies and processes for use in the EU joint HTA framework. The proposed guiding principles could support the effective implementation of the EU Regulation on HTA for vaccines and have the potential to ensure consistent, transparent, and timely access to new vaccines in the EU.

Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.

BACKGROUND: In Italy HPV vaccination with the quadrivalent vaccine (Gardasil®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11. METHODS: A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered. CONCLUSION: The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective. RESULTS: Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.

Systematic review of cost-effectiveness analyses for combinations of prevention strategies against human papillomavirus (HPV) infection: a general trend.

BACKGROUND: Due to the arrival of multi-valent HPV vaccines, it is more and more important to have a better understanding of the relationship between vaccination and screening programmes. This review aimed to: (1) collect published evidence on the cost-effectiveness profile of different HPV prevention strategies and, in particular, those combining vaccination with changes in screening practices; (2) explore the cost-effectiveness of alternative preventive strategies based on screening and vaccination. METHODS: A systematic literature review was conducted in order to identify the relevant studies regarding the cost-effectiveness of prevention strategies against HPV infection. Analysis comparing the modelling approaches between studies was made along with an assessment of the magnitude of impact of several factors on the cost-effectiveness of different screening strategies. RESULTS: A total of 18 papers were quantitatively summarised within the narrative. A high degree of heterogeneity was found in terms of how HPV prevention strategies have been assessed in terms of their economic and epidemiological impact, with variation in screening practice and valence of HPV vaccination found to have large implications in terms of cost-effectiveness. CONCLUSIONS: This review demonstrated synergies between screening and vaccination. New prevention strategies involving multi-valence vaccination, HPV DNA test screening, delayed commencement and frequency of screening could be implemented in the future. Strategies implemented in the future should be chosen with care, and informed knowledge of the potential impact of all possible prevention strategies. Highlighted in this review is the difficulty in assessing multiple strategies. Appropriate modelling techniques will need to be utilised to assess the most cost-effective strategies.

Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe.

BACKGROUND: HPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed. METHODS: The analysis was performed using a model constructed in Microsoft(®)Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed. RESULTS: Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination. CONCLUSIONS: In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination are highly dependent on coverage in girls. Therefore, further analyses should be performed taking into account the country-specific situation. In addition to clinical benefits, substantial economic benefits are also anticipated and warrant further investigation as do the social and ethical implications of including boys in vaccination programs.

Estimated health and economic impact of using high-dose influenza vaccine on respiratory and circulatory plus respiratory hospitalizations of older adults in Australia.

Background: Standard dose influenza vaccine provides moderate protection from infection, but with lower effectiveness among the elderly. High dose and adjuvanted vaccines (HD-TIV and aTIV) were developed to address this. This study aims to estimate the incremental health and economic impact of using HD-TIV (high dose trivalent vaccine) instead of aTIV (adjuvanted trivalent vaccine) on respiratory and circulatory plus respiratory hospitalizations of older people (≥65 years) in Australia. Methods: This is a modelling study comparing predicted hospitalization outcomes in people receiving HD-TIV or aTIV during an average influenza season in Australia. Hospitalization records of Australian adults ≥65 years of age from 01 April to 30 November during 15 influenza seasons (2002-2017 excluding 2009, which was a pandemic) were extracted from the Australian Institute of Health and Welfare [AIHW] and used to calculate hospitalisation rates during an average season. Relative vaccine effectiveness data for aTIV and HD-TIV were used to estimate morbidity burden related to influenza. Results: Between 2002 and 2017, the average respiratory hospitalization rate among older people during influenza season (April-November) was 3,445/100,000 population-seasons, with an average cost of AU$ 7,175 per admission. The average circulatory plus respiratory hospitalization rate among older Australian people during that time was 10,393/100,000 population-seasons, with an average cost of AU$ 7829 per admission. For older Australians, HD-TIV may avert an additional 6,315-9,410 respiratory admissions each year, with an incremental healthcare cost saving of AU$ 15.9-38.2 million per year compared to aTIV. Similar results were also noted for circulatory plus respiratory hospitalizations. Conclusions: From the modelled estimations, HD-TIV was associated with less economic burden and fewer respiratory, and circulatory plus respiratory hospitalizations than aTIV for older Australians.

Economic evaluation of high-dose inactivated influenza vaccine in adults aged ≥65 years: A systematic literature review.

INTRODUCTION: Due to waning immunity, adults aged ≥65 years are at increased risk of seasonal influenza infection and its complications. Adding to this risk, older adults have reduced responses to influenza vaccines. A high-dose trivalent inactivated influenza vaccine (Fluzone High-Dose, Sanofi Pasteur) (IIV3-HD) was developed to improve protection against influenza in adults aged ≥65 years and has been licensed in the US since 2009 and in Canada since 2015. Post-licensure studies have shown that IIV3-HD is more effective than standard-dose trivalent inactivated influenza vaccine (IIV3-SD) at protecting against influenza infection in this population. Here, we performed a systematic review of economic analyses of IIV3-HD in adults aged ≥65 years. METHODS: On June 9, 2019, using the Ovid search platform, we searched Econlit, Embase, and Ovid MEDLINE® for original studies published in peer-reviewed journals examining the economics or cost-effectiveness of IIV3-HD in adults aged ≥65 years. Two reviewers independently selected studies and assessed their quality. RESULTS: Seven studies were selected, all performed in the US or Canada. Five studies were funded by IIV3-HD manufacturer, and the remaining two by the US National Institute of General Medical Sciences. In all studies, IIV3-HD reduces healthcare resource utilization and is cost-effective or cost-saving compared to IIV3-SD. The main driver is reduced hospitalizations for cardiorespiratory events. CONCLUSION: IIV3-HD is cost-saving or cost-effective versus IIV3-SD in adults aged ≥65 years. Reduced cardiorespiratory complications are an important driver of these economic benefits. A video summary of the article can be accessed via the Supplementary data link at the end of this article.

Cost-effectiveness of high dose versus adjuvanted trivalent influenza vaccines in England and Wales.

AIMS: High dose trivalent influenza vaccine (HD TIV) and adjuvant TIV (aTIV) have been developed specifically for adults aged 65 and older (65+) who are at high risk of life-threatening complications. However, there is a scarcity of evidence comparing the clinical and cost-effectiveness of HD TIV and aTIV. The aim of this study was to determine the cost-effectiveness of HD TIV versus aTIV in the England and Wales 65+ population. METHODS: A cost-utility analysis was conducted using a decision tree with two influenza related outcomes: Laboratory confirmed cases that could result in GP consultation, and hospitalizations that may result in premature mortality. Due to a lack of comparative evidence, the effectiveness of HD TIV versus aTIV was calculated indirectly, based on relative effectiveness estimates for each vaccine versus a common comparator, standard dose (SD) TIV. The primary analysis included hospitalizations explicitly due to influenza/pneumonia. Cost-effectiveness was established for three scenarios applying differing relative effectiveness estimates for aTIV versus SD TIV. Uncertainty was analysed in one-way deterministic sensitivity analyses. A secondary analysis included hospitalizations due to any respiratory illness. RESULTS: The minimum population impact of vaccination with HD TIV rather than aTIV was 13,092 fewer influenza cases, 1,109 fewer influenza related deaths, 4,673 fewer hospitalizations, and 3,245 fewer GP appointments. HD TIV was cost-effective versus aTIV for all three effectiveness scenarios, with incremental cost-effectiveness ratios (ICER) equal to £1,932, £4,181, and £8,767 per quality adjusted life year. Results were consistent across the secondary analysis and deterministic sensitivity analyses. LIMITATIONS: The analysis was limited by a lack of robust and consistent effectiveness data for aTIV. CONCLUSION: HD TIV is cost-effective versus aTIV in people aged 65+ in England and Wales. Use of HD TIV over aTIV could increase clinical benefits and reduce the public health and economic burden of influenza.

Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain.

BACKGROUND: Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain. METHODS: A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections. RESULTS: The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: euro22 million from the national health system perspective and euro38 million from the societal perspective. CONCLUSIONS: A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.

Cost-effectiveness evaluation of a quadrivalent human papillomavirus vaccine in Belgium.

BACKGROUND: The introduction of a quadrivalent human papillomavirus (HPV; types 6, 11, 16, 18) vaccine is expected to significantly reduce the burden of cervical cancer, cervical intraepithelial neoplasia (CIN), genital warts and other HPV-related diseases. OBJECTIVE: To determine the cost effectiveness of providing a quadrivalent (6,11,16,18) HPV vaccine programme in adolescent females aged 12 years in addition to the existing cervical cancer screening programme in Belgium. METHODS: A Markov state-transition model was developed for the Belgian context in order to evaluate the long-term impact of vaccinating a cohort of girls aged 12 years alongside the existing screening programme. Women were followed until the age of 85 years. A vaccine that would prevent 100% of diseases associated with HPV-6, -11, -16 and -18, with lifetime duration of efficacy, 80% coverage, in conjunction with current screening, was compared with screening alone. For this analysis, 35% of cases of CIN-1, 55% of CIN-2/3, 75% of cervical cancer and 90% of genital warts were considered to be attributable to HPV-6, -11, -16 or -18. The model estimated lifetime risks and total lifetime healthcare costs, survival and QALYs for cervical cancer, CIN and genital warts. Outcomes validation was applied. Model outcomes also included incremental costs per life-year gained and incremental costs per QALY gained. The analysis was conducted from the perspective of the Belgian healthcare payer, and costs were in year 2006 values. RESULTS: The model estimated a reduction in the lifetime risk of cervical cancer from 0.94% to 0.34%, therefore preventing 362 cases of cervical cancer and 131 related deaths in a cohort of 60,000 girls aged 12 years in Belgium. The base-case scenario suggests quadrivalent HPV vaccination in addition to current cervical screening in Belgium to be cost effective at euro 10,546 per QALY. This is within the accepted range of cost-effective interventions in Europe. This cost effectiveness is maintained for different parameter assumptions in the sensitivity analysis, with the exception of very high discount rates for costs and medical benefits, but, even in the worst case, ratios were still less than euro 50,000 per QALY. Even when a separate scenario modelled the requirement for a booster vaccination to sustain a lifetime duration of protection, the results remained cost effective at eruo 17,388 per QALY. CONCLUSIONS: Vaccination with a quadrivalent HPV vaccine appears to be a cost-effective public health intervention in conjunction with the existing screening programme in Belgium. The additional costs of introducing vaccination to the established screening programme would be offset by the potential savings from not having to treat the diseases caused by HPV-6, -11, -16 or -18.

Epidemiology and costs of cervical cancer screening and cervical dysplasia in Italy.

BACKGROUND: We estimated the number of women undergoing cervical cancer screening annually in Italy, the rates of cervical abnormalities detected, and the costs of screening and management of abnormalities. METHODS: The annual number of screened women was estimated from National Health Interview data. Data from the Italian Group for Cervical Cancer Screening were used to estimate the number of positive, negative and unsatisfactory Pap smears. The incidence of CIN (cervical intra-epithelial neoplasia) was estimated from the Emilia Romagna Cancer Registry. Patterns of follow-up and treatment costs were estimated using a typical disease management approach based on national guidelines and data from the Italian Group for Cervical Cancer Screening. Treatment unit costs were obtained from Italian National Health Service and Hospital Information System of the Lazio Region. RESULTS: An estimated 6.4 million women aged 25-69 years undergo screening annually in Italy (1.2 million and 5.2 million through organized and opportunistic screening programs, respectively). Approximately 2.4% of tests have positive findings. There are approximately 21,000 cases of CIN1 and 7,000-17,000 cases of CIN2/3. Estimated costs to the healthcare service amount to 158.5 million euro for screening and 22.9 million euro for the management of cervical abnormalities. CONCLUSION: Although some cervical abnormalities might have been underestimated, the total annual cost of cervical cancer prevention in Italy is approximately 181.5 million euro, of which 87% is attributable to screening.

Incidence of invasive cervical cancer and direct costs associated with its management in Italy.

AIM AND BACKGROUND: Cervical cancer is the second most common cancer in European women aged 15-44 years. The aim of this study was to estimate the direct cost of managing invasive cervical cancer in Italy. METHODS: Data from the Italian Network of Cancer Registries were used to estimate the annual number of new cervical cancer cases. To assess the management costs, a typical management pathway for each FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) cervical cancer stage was derived from published guidelines. Data from the Modena Cancer Registry were used to estimate the proportion of patients by FIGO stage. This algorithm was combined with tariffs for outpatient and inpatient procedures to obtain a mean cost for each FIGO stage. RESULTS: An estimated 2,927 new cases of cervical cancer occurred in Italy in 2005 (crude incidence 9.7/100,000; world age-standardized incidence 6.0/100,000). The estimated numbers of new cases by FIGO stage were: FIGO I, 1,927; FIGO II, 556; FIGO III, 259; and FIGO IV, 185. Costs for the most frequent procedures were estimated as: Euro 6,041 for radical hysterectomy or other surgery; Euro 4,901 for radio-chemotherapy; Euro 1,588 for brachytherapy; and Euro 3,795 for palliative chemotherapy. Mean management costs for incident cases (including 10 years of follow-up) were estimated at: FIGO I, Euro 6,024; FIGO II, Euro 10,572; FIGO III, Euro 11,367; FIGO IV, Euro 8707; and Euro 5,854 for the terminal phase (1 month). The total direct management cost was estimated at Euro 28.3 million per year. CONCLUSIONS: This is one of the first studies to estimate the direct cost of treating patients newly diagnosed with invasive cervical cancer in Italy. Although according to current management pathways real treatment costs are likely to be underestimated, this information is necessary to design evidence-based vaccination policies able to harmonize primary and secondary prevention of cervical cancer.

Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis.

BACKGROUND: We assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone. METHODS: A Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered. RESULTS: Vaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of pound21,059 per quality adjusted life year (QALY) and pound34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate. CONCLUSION: These analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.

Burden of rotavirus gastroenteritis and potential benefits of a pentavalent rotavirus vaccination in Belgium.

OBJECTIVE AND METHODS: A decision analytic model was built to assess the paediatric rotavirus gastroenteritis (RVGE) burden and potential benefits associated with the introduction of RotaTeq (pentavalent rotavirus vaccine) in Belgium. RESULTS: In the absence of a rotavirus (RV) immunisation programme, paediatric RVGE was estimated to account for about 5,860 hospitalisations, 1,720 cases of nosocomial infections, 9,410 cases treated by general practitioners/paediatricians (GP/P) and 10,790 cases not seeking medical care for a birth cohort followed up to 5 years of age. Paediatric RVGE was estimated to cost about euro9.0 million from the Belgian healthcare provider perspective and euro15.3 million to society. Given a 90% RV vaccination coverage rate, the pentavalent RV vaccine would have a high impact on RV burden by preventing more than 4,850 hospitalisations, 995 cases of nosocomial infections, 7,145 cases treated by GP/P and 8,190 cases not seeking medical care, and reduce RVGE costs by euro7.1 million from the Belgian healthcare provider perspective and euro12.0 million to society.

Economic burden associated with the management of cervical cancer, cervical dysplasia and genital warts in Belgium.

OBJECTIVE: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium. METHOD: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective. RESULTS: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of euro9,716, the total annual cost of CC is euro6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of euro1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of euro2.53 million (HCPP). CONCLUSION: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.

An estimate of the public health impact and cost-effectiveness of universal vaccination with a 9-valent HPV vaccine in Germany.

INTRODUCTION: Since 2007, the German Standing Vaccination Committee recommends HPV vaccination for girls aged 12-17 with a 2- (Cervarix®) or 4-valent (Gardasil®) vaccine. A 9-valent vaccine (Gardasil 9®) recently received a European market authorization in 2015. METHODS: A dynamic transmission model was calibrated to the German setting and used to estimate costs and QALYs associated with vaccination strategies. RESULTS: Compared to the current vaccination program, the 9-valent vaccine extended to boys shows further reductions of 24% in the incidence of cervical cancer, 30% and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new strategy is associated with an ICER of 22,987€ per QALY gained, decreasing to 329€ when considering the vaccine switch for girls-only. CONCLUSION: Universal vaccination with the 9-valent vaccine can yield significant health benefits when compared to the current program.

Public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines compared to trivalent influenza vaccines in Europe.

Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs.

Role of vaccination in the sustainability of healthcare systems.

The use of vaccines to prevent diseases in children, adults, and the elderly results in fewer medical visits, diagnostic tests, treatments, and hospitalisations, which leads to substantial savings in healthcare costs each year in Europe and elsewhere. Vaccines also contribute to reducing resource utilisation by preventing nosocomial infections, such as rotavirus gastroenteritis, which can increase hospital stays by 4-12 days. Vaccination also has an important role in the prevention of cancers with, for example, human papillomavirus or hepatitis B vaccines. Since the financial impact of cancer is high for patients, healthcare systems, and society as a whole, any cases prevented will reduce this impact. Newer vaccines, such as the herpes zoster vaccine, can provide an answer to unmet medical needs by preventing and reducing the severity of shingles and associated post-herpetic neuralgia, which are difficult conditions to treat. Thus, in the context of increasing pressure on healthcare budgets, vaccination can contribute to the sustainability of healthcare systems through reduced and more efficient use of healthcare resources.