Felix Weidemann

Health economic evaluation of vaccination strategies for the prevention of herpes zoster and postherpetic neuralgia in Germany.

BackgroundHerpes zoster (HZ) is a self-limiting painful skin rash affecting mostly individuals from 50 years of age. The main complication is postherpetic neuralgia (PHN), a long-lasting pain after rash has resolved. A HZ-vaccine has recently been licensed in Europe for individuals older than 50 years. To support an informed decision-making for a potential vaccination recommendation, we conducted a health economic evaluation to identify the most cost-effective vaccination strategy.MethodsWe developed a static Markov-cohort model, which compared a vaccine-scenario with no vaccination. The cohort entering the model was 50 years of age, vaccinated at age 60, and stayed over life-time in the model. Transition probabilities were based on HZ/PHN-epidemiology and demographic data from Germany, as well as vaccine efficacy (VE) data from clinical trials. Costs for vaccination and HZ/PHN-treatment (in Euros; 2010), as well as outcomes were discounted equally with 3% p.a. We accounted results from both, payer and societal perspective. We calculated benefit-cost-ratio (BCR), number-needed-to-vaccinate (NNV), and incremental cost-effectiveness ratios (ICERs) for costs per HZ-case avoided, per PHN-case avoided, and per quality-adjusted life-year (QALY) gained. Different target age-groups were compared to identify the most cost-effective vaccination strategy. Base-case-analysis as well as structural, descriptive-, and probabilistic-sensitivity-analyses (DSA, PSA) were performed.ResultsWhen vaccinating 20% of a cohort of 1 million 50 year old individuals at the age of 60 years, approximately 20,000 HZ-cases will be avoided over life-time. The NNV to avoid one HZ (PHN)-case was 10 (144). However, with a BCR of 0.34 this vaccination-strategy did not save costs. The base-case-analysis yielded an ICER of 1,419 (20,809) Euros per avoided HZ (PHN)-case and 28,146 Euros per QALY gained. Vaccination at the age of 60 was identified in most (sensitivity) analyses to be the most cost-effective vaccination strategy. In DSA, vaccine price and VE were shown to be the most critical input-data.ConclusionsAccording to our evaluation, HZ-vaccination is expected to avoid HZ/PHN-cases and gain QALYs to higher costs. However, the vaccine price had the highest impact on the ICERs. Among different scenarios, targeting individuals aged 60 years seems to represent the most cost-effective vaccination-strategy.

Cost-effectiveness of childhood rotavirus vaccination in Germany

BACKGROUND Rotavirus (RV) causes a highly contagious gastroenteritis especially in children under five years of age. Since 2006 two RV-vaccines are available in Europe (Rotarix(®) and RotaTeq(®)). To support informed decision-making within the German Standing Committee on Vaccination (STIKO) the cost-effectiveness of these two vaccines was evaluated for the German healthcare setting. METHODS A Markov model was developed to evaluate the cost-effectiveness from the statutory health insurance (SHI) and from the societal perspective. RV-cases prevented, RV-associated hospitalizations avoided, and quality-adjusted life years (QALY) gained were considered as health outcomes. RV-incidences were calculated based on data from the national mandatory disease reporting system. RV-vaccine efficacy was determined as pooled estimates based on data from randomized controlled trials. Vaccine list prices and price catalogues were used for cost-assessment. Effects and costs were discounted with an annual discount rate of 3%. RESULTS The base-case analysis (SHI-perspective) resulted in an incremental cost-effectiveness and cost-utility ratio for Rotarix(®) of € 184 per RV-case prevented, € 2457 per RV-associated hospitalization avoided, and € 116,973 per QALY gained. For RotaTeq(®), the results were € 234 per RV-case prevented, € 2622 per RV-associated hospitalization avoided, and € 142,732 per QALY gained. Variation of various parameters in sensitivity analyses showed effects on the ICERs without changing the overall trend of base-case results. When applying base-case results to the 2012 birthcohort in Germany with 80% vaccination coverage, an estimated 206,000-242,000 RV-cases and 18,000 RV-associated hospitalizations can be prevented in this birthcohort over five years for an incremental cost of 44.5-48.2 million €. CONCLUSION Our analyses demonstrate that routine RV-vaccination could prevent a substantial number of RV-cases and hospitalizations in the German healthcare system, but the saved treatment costs are counteracted by costs for vaccination. However, with vaccine prices reduced by ∼62-66%, RV-vaccination could even become a cost-saving preventive measure.

Modelling the epidemiological impact of rotavirus vaccination in Germany--a Bayesian approach.

BACKGROUND Rotavirus (RV) infection is the primary cause of severe gastroenteritis in children aged <5 years in Germany and worldwide. In 2013 the German Standing Committee on Vaccination (STIKO) developed a national recommendation for routine RV-immunization of infants. To support informed decision-making we predicted the epidemiological impact of routine RV-vaccination in Germany using statistical modelling. METHODS We developed a population-based model for the dynamic transmission of RV-infection in a vaccination setting. Using data from the communicable disease reporting system and survey records on the vaccination coverage from the eastern federal states, where the vaccine was widely used before recommended at national level, we first estimated RV vaccine effectiveness (VE) within a Bayesian framework utilizing adaptive Markov Chain Monte Carlo inference. The calibrated model was then used to compute the predictive distribution of RV-incidence after achieving high vaccination coverage with the introduction of routine vaccination. RESULTS Our model estimated that RV-vaccination provides high protection against symptomatic RV-infection (VE=96%; 95% credibility interval (CI): 91-99%) that remains at its maximum level for three years (95% CI: 1.43-5.80 years) and is fully waned after twelve years. At population level, routine vaccination at 90% coverage is predicted to reduce symptomatic RV-incidence among children aged <5 years by 84% (95% prediction interval (PI): 71-90%) including a 2.5% decrease due to herd protection. Ten years after vaccine introduction an increase in RV incidences of 12% (95% PI: -16 to 85%) among persons aged 5-59 years and 14% (95% PI: -6 to 109%) within the age-group >60 years was predicted. CONCLUSION Routine infant RV-vaccination is predicted to considerably reduce RV-incidence in Germany among children <5 years. Our work generated estimates of RV VE in the field and predicted the population-level impact, while adequately addressing the role of model and prediction uncertainty when making statements about the future.

Current and future effects of varicella and herpes zoster vaccination in Germany – Insights from a mathematical model in a country with universal varicella vaccination

ABSTRACT Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the models results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero® to reduce meningococcal group B disease in Germany

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute number of cases, at a high overall cost.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany – a mathematical modelling study

BackgroundEpidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years.MethodsWe used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population.ResultsProjected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios.ConclusionDemographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.

Is the impact of childhood influenza vaccination less than expected: a transmission modelling study

BackgroundTo reduce the burden of severe influenza, most industrialized countries target specific risk-groups with influenza vaccines, e.g. the elderly or individuals with comorbidities. Since children are the main spreaders, some countries have recently implemented childhood vaccination programs to reduce overall virus transmission and thereby influenza disease in the whole population. The introduction of childhood vaccination programs was often supported by modelling studies that predicted substantial incidence reductions. We developed a mathematical transmission model to examine the potential impact of childhood influenza vaccination in Germany, while also challenging established modelling assumptions.MethodsWe developed an age-stratified SEIR-type transmission model to reproduce the epidemic influenza seasons between 2003/04 and 2013/14. The model was built upon German population counts, contact patterns, and vaccination history and was fitted to seasonal data on influenza-attributable medically attended acute respiratory infections (I-MAARI) and strain distribution using Bayesian methods. As novelties we (i) implemented a stratified model structure enabling seasonal variability and (ii) deviated from the commonly assumed mass-action-principle by employing a phenomenological transmission rate.ResultsAccording to the model, by vaccinating primarily the elderly over ten seasons 4 million (95% prediction interval: 3.84 – 4.19) I-MAARI were prevented which corresponds to an 8.6% (8.3% – 8.9%) reduction compared to a no-vaccination scenario and a number-needed-to-vaccinate (NNV) to prevent one I-MAARI of 37.1 (35.5 – 38.7). Additional vaccination of 2-10 year-old children at 40% coverage would have led to an overall I-MAARI reduction of 17.8% (17.1 – 18.7%) mostly due to indirect effects with a NNV of 20.7 (19.6 – 21.6). When employing the traditional mass-action-principle, the model predicted a more than 3-fold higher I-MAARI reduction (55.6%) due to childhood vaccination.ConclusionIn Germany, the introduction of routine childhood influenza vaccination could considerably reduce I-MAARI among all age-groups and improve the NNV. However, the predicted impact is much lower compared to previous studies, which is primarily caused by our phenomenological approach to modelling influenza virus transmission.

Analysing published global Ebola Virus Disease research using social network analysis

Introduction The 2014/2015 West African Ebola Virus Disease (EVD) outbreak attracted global attention. Numerous opinions claimed that the global response was impaired, in part because, the EVD research was neglected, although quantitative or qualitative studies did not exist. Our objective was to analyse how the EVD research landscape evolved by exploring the existing research network and its communities before and during the outbreak in West Africa. Methods/ Principal findings Social network analysis (SNA) was used to analyse collaborations between institutions named by co-authors as affiliations in publications on EVD. Bibliometric data of publications on EVD between 1976 and 2015 was collected from Thomson Reuters’ Web of Science Core Collection (WoS). Freely available software was used for network analysis at a global-level and for 10-year periods. The networks are presented as undirected-weighted graphs. Rankings by degree and betweenness were calculated to identify central and powerful network positions; modularity function was used to identify research communities. Overall 4,587 publications were identified, of which 2,528 were original research articles. Those yielded 1,644 authors’ affiliated institutions and 9,907 connections for co-authorship network construction. The majority of institutions were from the USA, Canada and Europe. Collaborations with research partners on the African continent did exist, but less frequently. Around six highly connected organisations in the network were identified with powerful and broker positions. Network characteristics varied widely among the 10-year periods and evolved from 30 to 1,489 institutions and 60 to 9,176 connections respectively. Most influential actors are from public or governmental institutions whereas private sector actors, in particular the pharmaceutical industry, are largely absent. Conclusion/ Significance Research output on EVD has increased over time and surged during the 2014/2015 outbreak. The overall EVD research network is organised around a few key actors, signalling a concentration of expertise but leaving room for increased cooperation with other institutions especially from affected countries. Finding innovative ways to maintain support for these pivotal actors while steering the global EVD research network towards an agenda driven by agreed, prioritized needs and finding ways to better integrate currently peripheral and newer expertise may accelerate the translation of research into the development of necessary live saving products for EVD ahead of the next outbreak.