Xavier Bresse

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

BackgroundHPV 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.MethodsThe 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.ResultsCompared 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.ConclusionsIn 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.

Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Abstract Objective: To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium. Methods: A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained. Results: Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold. Discussion: Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published. Conclusions: HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.

Economic evaluation of a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in older adults in Switzerland.

Background: A life-attenuated vaccine aimed at preventing herpes zoster (HZ) and its main complication, post-herpetic neuralgia (PHN), will soon be available in Europe. The study’s objective was to assess the clinical and economic impact of a vaccination program for adults aged 70-79 years in Switzerland. Results: A vaccination strategy compared to a no-vaccination resulted in lifetime incremental cost-effectiveness ratios (ICERs) of 25,538 CHF (23,646 USD) per QALY gained, 6,625 CHF (6,134 USD) per HZ case avoided, and 15,487 CHF (14,340 USD) per PHN3 case avoided under the third-party payer perspective. Sensitivity analyses showed that the model was most sensitive to the discount rates, HZ epidemiological data and vaccine price used. Methods: A Markov model, simulating the natural history of HZ and PHN and the lifetime effects of vaccination, previously developed for the UK was adapted to the Swiss context. The model includes several health states including good health, HZ, PHN, and death. HZ and PHN states reflected pain severity. Conclusion: The model predicts clinical and economic benefits of vaccination in the form of fewer HZ and PHN cases and reductions in healthcare resource use. ICERs were within the commonly accepted thresholds in Switzerland, indicating that a HZ vaccination program would be considered a cost-effective strategy in the Swiss setting.

Universal vaccination with the quadrivalent HPV vaccine in Austria: impact on virus circulation, public health and cost–effectiveness analysis

The International Agency for Research on Cancer acknowledges that HPV is a human carcinogen affecting both sexes. This study aimed to evaluate the public health impact of universal HPV vaccination in Austria, to assess its cost–effectiveness and to estimate the HPV prevalence reduction over time. Vaccinating 65% of 9-year-old boys and girls in Austria would result in a 70% decrease in HPV infections in both males and females, hereby avoiding 9500 cases of genital warts annually and 431 HPV 16/18-related cancers in males and females. This strategy would be cost effective with base case analysis of €26,701/quality-adjusted life year (QALY) gained for cervical cancer only, €15,820/QALY also including vaginal/vulvar cancers and genital warts, and €10,033/QALY also considering anal, oropharyngeal and penile cancers, with an incremental cost–effectiveness ratio ranging from €2500 to €21,000/QALY in sensitivity analyses. HPV circulation would be controlled hereby preventing subsequent HPV-related cancers.

A critical review of cost-effectiveness analyses of vaccinating males against human papillomavirus

A critical review of cost-effectiveness analyses of HPV vaccination in males was conducted and nine studies were identified in different countries. Due to the heterogeneity among these studies in terms of modeling approach, vaccination strategies, health outcomes considered, assumptions and parameters, limited conclusions can be drawn with regard to the absolute cost-effectiveness. Nevertheless, key drivers were identified. More favorable cost-effectiveness appeared when all HPV-related diseases outcomes were considered, a suboptimal vaccine coverage among girls and/or lower vaccine prices were assumed. There was a general lack of transparency to fully describe the details of the methodological approach of modeling and calibration. Further research should be conducted to generate robust evidence-based data sets (HPV-related diseases epidemiology, costs and quality of life). The best modeling practice for HPV vaccination and how to better capture the true economic value of vaccination beyond cost-effectiveness in a broader policy context need to be investigated.

Mind the gaps: what's missing from current economic evaluations of universal HPV vaccination?

BACKGROUND Since the original licensing of human papilloma virus (HPV) vaccination for women, evidence is accumulating of its effectiveness in preventing HPV-related conditions in men, and universal vaccination (vaccinating men and women) is now recommended in some countries. Several models of the cost-effectiveness of universal HPV vaccination have been published, but results have been mixed. This article assesses the extent to which economic studies have captured the range of values associated with universal HPV vaccination, and how this influences estimates of its cost-effectiveness. METHODS Eight published economic evaluations of universal HPV vaccination were reviewed to identify which of the values associated with universal HPV vaccination were included in each analysis. RESULTS Studies of the cost-effectiveness of universal HPV vaccination capture only a fraction of the values generated. Most studies focused on impacts on health and health system cost, and only captured these partially. A range of values is excluded from most studies, including impacts on productivity, patient time and costs, carers and family costs, and broader social values such as the right to access treatment. Further, those studies that attempted to capture these values only did so partially. DISCUSSION Decisions to invest in universal HPV vaccination need to be based on a complete assessment of the value that it generates. This is not provided by existing economic evaluations. Further work is required to understand this value. First, research is required to understand how HPV-related health outcomes impact on society including, for instance, their impact on productivity. Second, consideration should be given to alternative approaches to capture this broader set of values in a manner useful to decisions-makers, such as multi-criteria decision analysis.

Cost–effectiveness of vaccinating adults with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany

The introduction of routine infant vaccination against pneumococcal disease has resulted in a decreased overall invasive pneumococcal disease incidence in adults but also a change in invasive pneumococcal disease serotypes. This study aimed to assess the cost–effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany in this context. A population-based Markov model was developed. A cohort of adults currently eligible for vaccination was followed until death. Adult vaccination with PPV23 was associated with an incremental cost–effectiveness ratio of €17,065/quality-adjusted life years gained from the third-party payer’s perspective. Univariate sensitivity analyses showed that the incremental cost–effectiveness ratio was below €50,000/quality-adjusted life years gained in most test scenarios. The model suggests that adult PPV23 vaccination is cost effective in Germany, due to its broad serotype coverage. This is despite epidemiological changes in Streptococcus pneumoniae serotypes caused by wider use of pneumococcal conjugate vaccines during childhood.

A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany

To assess the comparative public health and budget impact over 5 years of several pneumococcal vaccination strategies (23-valent pneumococcal polysaccharide vaccine [PPV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]) in Germany, within the context of changing invasive pneumococcal disease (IPD) incidence over time. A multi-cohort, population-based Markov model was developed. Uncertainty around vaccine effectiveness, costs and IPD incidence change was handled through scenario analyses. Between 2012 and 2016, the introduction of PCV13 in adults, compared with the use of PPV23, would be associated with a net estimated budget increase of €59.7 million (+6.7%) to €151.6 million (+13.7%). Impact on IPD incidence ranged from -113 cases (-0.8%) to +298 cases (+2.8%). Introducing PCV13 in adults is expected to significantly affect healthcare budgets. Adult vaccination with PPV23 remains the optimal vaccination strategy from public health and budget perspectives.

A comparative analysis of the epidemiological impact and disease cost-savings of HPV vaccines in France

The aim was to compare the epidemiological and economic impact of 16/18 bivalent and 6/11/16/18 quadrivalent HPV vaccination in France, considering differences in licensed outcomes, protection against non-vaccine HPV types and prevention of HPV-6/11-related diseases. The differential impact of the two vaccines was evaluated using a published model adapted to the French setting. The target population was females aged 14–23 y and the time horizon was 100 y. A total of eight different scenarios compared vaccination impact in terms of reduction in HPV-16/18-associated carcinomas (cervical, vulvar, vaginal, anal, penile and head and neck), HPV-6/11-related genital warts and recurrent respiratory papillomatosis, and incremental reduction in cervical cancer due to potential cross-protection. Quadrivalent vaccine was associated with total discounted cost savings ranging from EUR 544–1,020 million vs. EUR 177–538 million with the bivalent vaccination (100-y time horizon). Genital wart prevention thanks to quadrivalent HPV vaccination accounted for EUR 306–380 million savings (37–56% of costs saved). In contrast, the maximal assumed cross-protection against cervical cancer resulted in EUR 13–33 million savings (4%). Prevention of vulvar, vaginal and anal cancers accounted for additional EUR 71–89 million savings (13%). In France, the quadrivalent HPV vaccination would result in significant incremental epidemiological and economic benefits vs. the bivalent vaccination, driven primarily by prevention of genital. The present analysis is the first in the French setting to consider the impact of HPV vaccination on all HPV diseases and non-vaccine types.

A comparative public health and budget impact analysis of pneumococcal vaccines: The French case.

In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy.