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Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age. Electronic supplementary material The online version of this article (10.1186/s12889-019-7458-x) contains supplementary material, which is available to authorized users.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany â a mathematical modelling study (technical appendix). (DOCX 1750 kb)

Supplementary information. (PDF 2648 kb)

Background The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. Methods Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys. Results From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls. Conclusions Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.

BACKGROUND: A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies.; METHODS: A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries.; RESULTS: A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold.; CONCLUSIONS: While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.

Hintergrund: Herpes Zoster (HZ) ist ein schmerzhafter Hautausschlag verursacht durch Reaktivierung des Varizella-Zoster-Virus. Die häufigste Komplikation ist die postherpetische Neuralgie (PHN), ein lang anhaltender Schmerz in der betroffenen Hautregion. In Europa erhielt 2006 ein Impfstoff zur Prävention von HZ und PHN bei Personen ≥50 Jahren die Zulassung, der aber erst Ende 2013 in Deutschland verfügbar wurde. Ziel dieser Dissertation war es, neben der Erhebung der HZ- und PHN-assoziierten epidemiologischen und ökonomischen Krankheitslast eine gesundheitsökonomische Evaluation der neuen Impfung im Kontext des gesetzlichen Krankenversicherungssystems (GKV) in Deutschland durchzuführen. Methodik: Die Dissertation wurde in 3 aufeinander aufbauenden Publikationen bearbeitet. 1) Zur Erhebung der alters-spezifischen HZ Inzidenz und der HZ bedingten Sterblichkeit wurde eine Analyse von Abrechnungsdaten für die Jahre 2006-08 der kassenärztlichen Vereinigungen (KV) und der Gesundheitsberichterstattung des Bundes durchgeführt. HZ Patienten ≥50 Jahre wurden über die ICD-10 Diagnosecodes identifiziert. 2) Behandlungskosten des HZ einschließ-lich der PHN sowie der Anteil an PHN Fällen an HZ Patienten wurde für die Jahre 2004-09 mit-tels einer Stichprobe von 240.000 Personen aus Krankenkassenabrechnungsdaten erhoben. Alle relevanten Kostenfaktoren wurden berücksichtigt und getrennt nach der Perspektive der GKV und der gesellschaftlichen Perspektive ausgewertet. 3) Ein mathematisches Modell wurde entwickelt, mit dem die gesundheitsökonomischen Effekte der Impfung vorausberechnet und Impfstrategien miteinander verglichen werden konnten. Die Ergebnisse der 1. und 2. Publikation fungierten hierbei als Inputdaten. Ergebnisse: Bei ≥50-Jährigen wurde eine HZ Inzidenz von 9,6/1.000 Personen und Jahre (PJ) erhoben. Etwa 5% der HZ Fälle entwickeln eine PHN. Für die etwa 400.000 HZ- und 20.000 PHN-Fälle p.a. entstehen aus GKV- (gesellschaftlicher) Perspektive Kosten in Höhe von ca. 105 (180) Millionen Euro. Wenn 20% einer hypothetischen Kohorte von 1 Million 50-Jähriger im Alter von 60 Jahren geimpft würden, könnten in dieser Kohorte ca. 20.000 HZ-Fälle verhindert werden. Um ein qualitäts-adjustiertes Lebensjahr (QALY) zu gewinnen müssen 28.146 Euro (gesellschaftliche Perspektive) aufgewendet werden. Neben dem Impfstoff-Preis ist auch die Dauer des Impfschutzes ein kritischer Faktor. Verschiedene Sub-Analysen zeigten, dass das Impfen im Alter von 60 Jahren am kosten-effektivsten wäre. Schlussfolgerung: Die medizinische und auch ökonomische Krankheitslast aufgrund von HZ und PHN ist in Deutschland hoch. Die HZ Impfung kann eine substantielle Zahl von Fällen verhindern, jedoch zu höheren Kosten im Vergleich zum Nicht-Impfen., Background: Herpes zoster (HZ) is a painful skin-rash caused by a reactivation of the varicella-zoster-virus. The main complication of HZ is postherpetic neuralgia (PHN), a long-term persisting pain in the affected skin area. In 2006, a vaccine for the prevention of HZ and PHN got licensed in Europe for individuals aged ≥50 years but was not available on the German market before the end of 2013. Objective of this dissertation was the assessment of the HZ- and PHN-related epidemiological and economic burden in Germany and the health economic evaluation of the new vaccine in the context of the German statutory health insurance (SHI) system. Methods: The dissertation consisted of three consecutive publications. 1) For the estima-tion of age-specific HZ incidence and HZ related mortality data from the Association of Statutory Health Insurance Physicians (ASHIP) and the Federal Health Monitoring System (FHM) for the years 2006-08 were analyzed. HZ cases were identified via ICD-10 codes. 2) Treatment costs for HZ and PHN cases were analyzed for the years 2004-09 from a study sample (240,000 individuals) of one SHI fund. All treatment sectors and patient co-payments were considered and evaluated separately according to the SHI- and the societal perspective (SP). 3): A mathematical model was developed to predict the health economic effects of the vaccination and to identify most critical and uncertain input factors. Results from 1st and 2nd publications served as input data for the mathematical model. Results: HZ incidence in ≥50 year old individuals is 9.6/1,000 persons per year (PY). About 5% of HZ cases develop a PHN. Costs for the estimated total 400,000 HZ and 20,000 PHN cases p.a. range between 105 and 180 million Euros from SHI and societal perspective. If 20% of a cohort of 1 million individuals aged 50 years gets vaccinated at age 60, about 20,000 HZ cases can be prevented. To gain one quality-adjusted life year (QALY) 28,146 Euros have to be invested (SP). Besides vaccine price, the duration of vaccine induced immunity is a critical factor. Several analyses indicated 60 to be the most cost-effective age at vaccination. Conclusion: The medical and economic burden caused by HZ/PHN in Germany is high. The vaccination can avoid a substantial number of cases, however, at higher costs compared to no vaccination.

Background: Quadrivalent influenza vaccines (QIVs) contain antigens derived from an additional influenza type B virus as compared with currently used trivalent influenza vaccines (TIVs). This should overcome a potential reduced vaccine protection due to mismatches between TIV and circulating B viruses. In this study, we systematically reviewed the available literature on health economic evaluations of switching from TIV to QIV. Areas covered: The databases of Medline and Embase were searched systematically to identify health economic evaluations of QIV versus TIV published before September 2016.A total of sixteen studies were included, thirteen cost-effectiveness analyses and three cost-comparisons. Expert commentary: Published evidence on the cost-effectiveness of QIV suggests that switching from TIV to QIV would be a valuable intervention from both the public health and economic viewpoint. However, more research seems mandatory. Our main recommendations for future research include: 1) more extensive use of dynamic models in order to estimate the full impact of QIV on influenza transmission including indirect effects, 2) improved availability of data on disease outcomes and costs related to influenza type B viruses, and 3) more research on immunogenicity of natural influenza infection and vaccination, with emphasis on cross-reactivity between different influenza B viruses and duration of protection.

Background: Incremental cost-effectiveness and cost-utility analyses [health economic evaluations (HEEs)] of vaccines are routinely considered in decision making on immunization in various industrialized countries. While guidelines advocating more standardization of such HEEs (mainly for curative drugs) exist, several immunization-specific aspects (e.g. indirect effects or discounting approach) are still a subject of debate within the scientific community. Objective: The objective of this study was to develop a consensus framework for HEEs of vaccines to support the development of national guidelines in Europe. Methods: A systematic literature review was conducted to identify prevailing issues related to HEEs of vaccines. Furthermore, European experts in the field of health economics and immunization decision making were nominated and asked to select relevant aspects for discussion. Based on this, a workshop was held with these experts. Aspects on ‘mathematical modelling’, ‘health economics’ and ‘decision making’ were debated in group-work sessions (GWS) to formulate recommendations and/or—if applicable—to state ‘pros’ and ‘contras’. Results: A total of 13 different aspects were identified for modelling and HEE: model selection, time horizon of models, natural disease history, measures of vaccine-induced protection, duration of vaccine-induced protection, indirect effects apart from herd protection, target population, model calibration and validation, handling uncertainty, discounting, health-related quality of life, cost components, and perspectives. For decision making, there were four aspects regarding the purpose and the integration of HEEs of vaccines in decision making as well as the variation of parameters within uncertainty analyses and the reporting of results from HEEs. For each aspect, background information and an expert consensus were formulated. Conclusions: There was consensus that when HEEs are used to prioritize healthcare funding, this should be done in a consistent way across all interventions, including vaccines. However, proper evaluation of vaccines implies using tools that are not commonly used for therapeutic drugs. Due to the complexity of and uncertainties around vaccination, transparency in the documentation of HEEs and during subsequent decision making is essential. © 2015, The Author(s).

Background: Quadrivalent influenza vaccines (QIVs) contain antigens derived from an additional influenza type B virus as compared with currently used trivalent influenza vaccines (TIVs). This should overcome a potential reduced vaccine protection due to mismatches between TIV and circulating B viruses. In this study, we systematically reviewed the available literature on health economic evaluations of switching from TIV to QIV. Areas covered: The databases of Medline and Embase were searched systematically to identify health economic evaluations of QIV versus TIV published before September 2016.A total of sixteen studies were included, thirteen cost-effectiveness analyses and three cost-comparisons. Expert commentary: Published evidence on the cost-effectiveness of QIV suggests that switching from TIV to QIV would be a valuable intervention from both the public health and economic viewpoint. However, more research seems mandatory. Our main recommendations for future research include: 1) more extensive use of dynamic models in order to estimate the full impact of QIV on influenza transmission including indirect effects, 2) improved availability of data on disease outcomes and costs related to influenza type B viruses, and 3) more research on immunogenicity of natural influenza infection and vaccination, with emphasis on cross-reactivity between different influenza B viruses and duration of protection.