Addressing vaccine supply challenges in Europe: Expert industry perspective and recommendations.

Shortages of medicines are an increasing concern worldwide. In the European Union (EU), several initiatives have been launched by authorities to address this important public health issue. To contribute in finding solutions, Vaccines Europe (VE), representing 14 vaccine companies operating in Europe, conducted an analysis of the main root causes of vaccine shortages in Europe. Vaccines Europe has identified six main causes of vaccine shortages. Finding solutions will require a concerted effort and dialogue with the involvement of all key stakeholders. In this publication, Vaccines Europe is making a series of recommendations aiming at improving vaccine availability for Europe and beyond.

Immunization funding across 28 European countries.

INTRODUCTION: Disease prevention and improving vaccination coverage in Europe are key elements contributing to resilient health systems and ensuring better health outcomes for all. The aim of this study was to describe the immunization funding landscape across all European Union 28 countries (EU28). AREAS COVERED: Data collected in a targeted literature review supported descriptive analysis on the different indicators that were looked at: vaccines included in the EU28 national immunization programs (NIP), national immunization funding, immunization funding per capita (2015-2019) and percentage of health-care budget allocated to immunization. EXPERT OPINION: Immunization funding represents a small proportion of total healthcare spend in Europe (median 0.3%). In the context of the current COVID-19 pandemic, demographic changes, and the potential introduction of new vaccines; the need for adequate financing of immunization programs will be important, to establish resilient immunization systems and provide sustainable protection of the population against vaccine-preventable diseases.

PLAIN LANGUAGE SUMMARYWhat is the context?Herpes zoster, or shingles, is a viral disease characterized by a painful, localized skin rash. It affects approximately 32% of US citizens at least once in their lifetime.The risk of contracting shingles increases with age.Most American adults over 50 years have not received the shingles vaccine, and vaccination rates are especially low for African-Americans.What is new?This is the first study to evaluate what drives shingles vaccination decisions among US adults ≥ 50 years of age. We also assessed the differences between African-American and non-African-American adults, and inside the African-American group.In this choice experiment, 1,454 people ≥ 50 years completed a survey of 8 choice questions, as well as questions on their previous experiences with vaccines, socioeconomic, and demographic characteristics. Seven factors were evaluated.We found that American adults preferred to get vaccinated, and the most influential factors were costs and vaccine effectiveness while location of vaccination was the least important. There were differences in preferences between African-American and non-African-American adults, mainly driven by costs and vaccine effectiveness. 3 different groups of African-American adults with systematically different preferences could be identified; two were likely to vaccinate, with one being more cost sensitive at lower price thresholds, and the third was unlikely to vaccinate.What is the impact?Decisions on shingles vaccination appear to be mostly driven by costs, which could be a barrier to those who do not have appropriate insurance, especially among some African-Americans.However, healthcare professionals should continue to educate patients on other vaccine characteristics, as they also influence vaccination decisions.

From population to public institutions: what needs to be changed to benefit from the full value of vaccination.

The poor perception of the benefits of vaccines, and their subsequent underuse, can result in substantial economic, societal, and political burden. Adequate support and communication from health authorities and governments is essential to promote the benefits of vaccination and reduce the risk of infectious diseases outbreaks. Cost-containment policies in the vaccine procurement processes could also be a threat to the long-term sustainability of the vaccine industry and manufacturing sites in Europe. Biologicals, such as vaccines, are highly technical and complex products to manufacture and only a few industries are engaged in this activity. Developing incentives to encourage vaccine manufacturers and identifying means of taking into consideration the specificities of vaccines in economic evaluations could allow the full value of vaccination to be appreciated. In conclusion, governments, international agencies, and other stakeholders have an important role to play to help society regain confidence in vaccination and ensure that the benefits of vaccination programmes are fully recognised and valued.

Role of vaccination in economic growth.

The health of a population is important from a public health and economic perspective as healthy individuals contribute to economic growth. Vaccination has the potential to contribute substantially to improving population health and thereby economic growth. Childhood vaccination programmes in Europe can offer protection against 15 important infectious diseases, thus preventing child fatalities and any serious temporary and permanent sequelae that can occur. Healthy children are more able to participate in education, thus preparing them to become healthy and productive adults. Vaccination programmes can also prevent infectious diseases in adolescents, thus allowing them to continue their development towards a healthy adulthood. Protecting adults against infectious diseases ensures that they can fully contribute to productivity and economic development by avoiding sick leave and lower productivity. Vaccination in older adults will contribute to the promotion of healthy ageing, enabling them to assist their familiy with, for instance, childcare, and also help them avoid functional decline and the related impacts on health and welfare expenditure. Effective vaccination programmes for all ages in Europe will thus contribute to the European Union's 2020 health and economic strategies. Indeed, beyond their impact on healthcare resources and productivity, reductions in mortality and morbidity also contribute to increased consumption and gross domestic product. Therefore, assessment of the value of vaccines and vaccination needs to consider not just the direct impact on health and healthcare but also the wider impact on economic growth, which requires a macroeconomic analysis of vaccination programmes.

Economic evaluation of vaccines: specificities and future challenges illustrated by recent European examples.

This study reviews the current challenges in the economic evaluation of vaccines with a focus on European countries. In particular, the type of clinical evidence generally available, the impact of discounting for time preference and the use of modeling to derive valid cost-effectiveness assessments are considered. First, the characteristics of evidence for vaccines are discussed, as well as potential difficulties faced when using evidence-based medicine applied to curative drugs to interpret vaccine evidence. Then, discounting is considered and specific examples illustrating issues with different types of discounting are described, taking HPV as the example. Finally, the need for sometimes complex dynamic models for vaccines is explored, and specific types of models are reviewed, keeping into consideration the adage "complex when needed, straightforward if allowed."

A critical literature review of health economic evaluations of rotavirus vaccination.

Two licensed vaccines are available to prevent RVGE in infants. A worldwide critical review of economic evaluations of these vaccines was conducted. The objective was to describe differences in methodologies, assumptions and inputs and determine the key factors driving differences in conclusions. 68 economic evaluations were reviewed. RV vaccination was found to be cost-effective in developing countries, while conclusions varied between studies in developed countries. Many studies found that vaccination was likely to be cost-effective under some scenarios, such as lower prices scenarios, inclusion of herd protection, and/or adoption of a societal perspective. Other reasons for variability included uncertainty around healthcare visits incidence and lack of consensus on quality of life (QoL) valuation for infants and caregivers. New evidence on the vaccination effectiveness in real-world, new ways of modeling herd protection and assessments of QoL in children could help more precisely define the conditions under which RV vaccination would be cost-effective in developed countries.

The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales.

Rotavirus vaccines have shown great potential for reducing the disease burden of the major cause of severe childhood gastroenteritis. The decision regarding whether rotavirus vaccination will be introduced into the national immunization program is currently being reviewed. The conclusions of previous evaluations of rotavirus vaccination cost-effectiveness contradict each other. This is the first analysis to incorporate a dynamic transmission model to assess the cost-effectiveness of rotavirus vaccination in England and Wales. Most previously reported models do not include herd protection, and thus may underestimate the cost-effectiveness of vaccination against rotavirus. We incorporate a dynamic model of rotavirus transmission in England and Wales into a cost-effectiveness analysis to determine the probability that the pentavalent rotavirus vaccination will be cost-effective over a range of full-course vaccine prices. This novel approach allows the cost-effectiveness analysis to include a feasible level of herd protection provided by a vaccination program. Our base case model predicts that pentavalent rotavirus vaccination is likely to be cost-effective in England and Wales at £ 60 per course. In some scenarios the vaccination is predicted to be not only cost-effective but also cost-saving. These savings could be generated within ten years after vaccine introduction. Our budget impact analysis demonstrates that for the realistic base case scenarios, 58-96% of the cost outlay for vaccination will be recouped within the first four years of a program. Our results indicate that rotavirus vaccination would be beneficial to public health and could be economically sound. Since rotavirus vaccination is not presently on the immunization schedule for England and Wales but is currently under review, this study can inform policymakers of the cost-effectiveness and budget impact of implementing a mass rotavirus vaccine strategy.

A critical literature review of health economic evaluations in pertussis booster vaccination.

A review of worldwide economic evaluations of pertussis booster vaccination for adolescents and adults was conducted. Thirteen cost-effectiveness, cost-utility and economic impact models were identified. The most frequently studied strategies were adolescent booster, one-time adult booster, adult decennial boosters and cocoon strategy. All studies evaluating adolescent booster suggested this was a cost-effective or cost-saving strategy compared with no booster vaccination. Conclusions concerning adult vaccination, alone or in combination with adolescent vaccination, vary between studies. Studies were often strongly affected by assumptions regarding the amount of unreported cases and lack of reliable input data on real incidence, other epidemiological inputs, costs associated with mild disease and herd immunity effects. Reviewed studies were generally in favor of pertussis booster vaccination, but did not identify any optimal vaccination strategy. Future economic evaluations should explore a wider range of strategies, taking into account country-specific considerations.

Cost–effectiveness of catch-up programs in human papillomavirus vaccination.

We reviewed cost–effectiveness models that combine routine vaccination with the human papillomavirus (HPV) vaccine with temporary catch-up programs. Cost–effectiveness results of catch-up programs are variable, and we reviewed methods and underlying assumptions to get more insight into any factor with a potential impact on cost-effectiveness. Results were dependent on differences between models used, their design and input data. Modeling aspects and assumptions were not always sufficiently described, making comparison difficult. Despite this, several differences between models likely to impact results were identified. All models used dynamic transmission modeling techniques except for one, which did not incorporate the effect of herd immunity. Catch-up strategies varied between models and comparator strategies were not necessarily the same. Cervical diseases outcomes were considered in all base cases, but the impact of genital warts was not always considered. Our article suggests that a conclusion on cost–effectiveness should be based on a fully transparent model including all possible benefits of vaccination.

Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

BACKGROUND: Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator. METHODS: We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation. RESULTS: Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences. CONCLUSION: From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.

A cost-effectiveness analysis of antimicrobial treatment of community-acquired pneumonia taking into account resistance in Belgium.

OBJECTIVE: This article assesses the cost-effectiveness of outpatient antimicrobial treatment of community-acquired pneumonia (CAP) taking into account resistance in Belgium. RESEARCH DESIGN AND METHODS: Our decision analytic model focused on mild to moderate CAP, but did not consider severe CAP. Treatment pathways reflected empirical treatment initiated in the absence of data on CAP aetiology. First-line treatment consisted of moxifloxacin, co-amoxiclav, cefuroxime or clarithromycin. If first-line treatment was unsuccessful, patients were either hospitalised or second-line treatment with a different antimicrobial was initiated. Clinical failure rates were obtained from the published literature or expert opinion. Costs were calculated using published sources from the third-party payer perspective. MAIN OUTCOME MEASURES: Effectiveness measures included first-line clinical failure avoided, second-line treatment avoided, hospitalisation avoided and death avoided. Healthcare costs were included, but costs of productivity loss were not considered. RESULTS: Costs of treating a CAP episode amounted to 144E with moxifloxacin/co-amoxiclav; 222E with co-amoxiclav/clarithromycin; 211E with cefuroxime/moxifloxacin; and 193E with clarithromycin/moxifloxacin. The rate of first-line failure was 5%, 16%, 19% and 18% for these four treatment strategies, respectively. The rate of second-line treatment amounted to 4%, 13%, 16% and 15%, respectively. The hospitalisation rate was 1%, 4%, 4% and 4%, respectively. The death rate was 0.01%, 0.04%, 0.03% and 0.03%, respectively. Sensitivity analyses supported the dominance of moxifloxacin/co-amoxiclav in nearly all scenarios. CONCLUSIONS: First-line treatment of CAP patients with moxifloxacin followed by co-amoxiclav or hospitalisation if required was more effective and less costly as compared with first-line treatment with co-amoxiclav, cefuroxime or clarithromycin.

Cost-effectiveness of empirical prescribing of antimicrobials in community-acquired pneumonia in three countries in the presence of resistance.

OBJECTIVES: To assess the cost-effectiveness of empirical outpatient treatment options for community-acquired pneumonia (CAP) in France, the USA and Germany, representing high, moderate and low antimicrobial resistance prevalence, respectively. METHODS: A decision analytic model was developed for mild-to-moderate CAP outpatient treatment. Treatment algorithms incorporated follow-up after treatment failure due to resistance or other reasons. First-line treatment included moxifloxacin, beta-lactams, macrolides or doxycycline; second-line treatment used a different antimicrobial class. Country-specific resistance and co-resistance prevalences to first- and second-line therapy for the major CAP pathogens were derived from surveillance studies. Clinical failure rates due to antimicrobial-susceptible and -resistant pathogens were obtained from the literature or estimated. Total costs were estimated using standard sources and a third-party payer perspective. Outcome measures included first-line clinical failures avoided, second-line treatments avoided and hospitalizations avoided. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: First-line moxifloxacin treatment followed by co-amoxiclav dominated all other treatments in France, the USA and in Germany for all outcome measures. Sensitivity analyses maintained moxifloxacin dominance in France and the USA but affected ICERs in some cases in Germany. CONCLUSIONS: Antimicrobial resistance/spectrum have a significant impact on outcomes and costs in empirical outpatient CAP treatment. Despite low acquisition costs for generic antibiotics, first-line treatment effective against the major CAP pathogens, including strains resistant to other antimicrobials, resulted in better clinical outcomes in all countries and lower treatment costs for all.