The public health impact of recombinant herpes zoster vaccination in adults over 50 years in Spain.

The recombinant zoster vaccine (RZV) is included in the Spanish National Immunisation Programme for adults 65 years of age (years), with a potential progressive catch-up program for adults 66-80 years, starting with 80 years. However, the risk of herpes zoster (HZ) increases significantly from 50 years. We estimated the public health impact (PHI) of vaccinating adults ≥50 years in Spain versus no vaccination, using a Markov model adapted to the Spanish setting. The model simulated a hypothetical ≥50 years cohort over a lifetime, with inputs from Spanish publications, databases, or publications from other countries where Spanish data were unavailable. Base case inputs included 67.7% RZV coverage and 61.1% second dose compliance. Outputs included clinical outcomes avoided, healthcare resource use avoided, and number-needed-to-vaccinate (NNV) to prevent one HZ case. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. The model estimated that, compared with no vaccination, vaccinating adults ≥50 years in Spain (N = 19,850,213) with RZV could prevent 1,533,353 HZ cases, 261,610 postherpetic neuralgia episodes, 274,159 other complications, and 138 deaths through the cohorts' remaining lifetime, mostly in the 50-59 years cohort. Furthermore, 3,500,492 primary care visits and 71,156 hospitalizations could be avoided, with NNV = 9 to prevent one HZ case. DSA predicted NNV = 7 to prevent one HZ case when second dose compliance was increased to 100%. PSA demonstrated ≥200,000 and ≥1,400,000 cases could be prevented in 86.9% and 18.4% of simulations, respectively. Starting RZV from 50 years could therefore prevent a substantial number of HZ cases and complications. Increasing RZV coverage and second dose compliance could further alleviate PHI of HZ.

The epidemiologic and economic impact of varicella and herpes zoster vaccination in South Korea: A mathematical modelling study.

BACKGROUND: In South Korea, the National Immunization Program has included one-dose varicella vaccination for 1-year-olds since 2005. This study examines the potential impact of introducing a two-dose varicella vaccination for children, along with zoster vaccination for adults, using either the zoster vaccine live (ZVL) or recombinant zoster vaccine (RZV). METHODS: The investigation considered four strategies in a base case scenario. The first involved introducing zoster vaccination for 60-year-olds, with a 60 % coverage. The second strategy combined zoster vaccination with a second-dose varicella vaccination for 4-year-olds, with a 90 % coverage. An age-structured model spanning 50 years was employed, assuming a zoster vaccine catch-up campaign over the initial 5 years. Cost-effectiveness analyses were conducted, assessing incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs), and net loss under different ages at zoster vaccination (50, 60, 65, and 70 years) and varying willingness-to-pay (WTP) levels from ₩40 million ($34,998) to ₩84 million ($74,000). RESULTS: All strategies were cost-effective and significantly reduced herpes zoster (HZ) incidence, preventing approximately 3,077,000 to 7,609,000 cases, depending on the chosen strategy. The combined strategy prevented around 4,950,000 varicella and 653,000 HZ cases additionally. RZV outperformed ZVL by preventing twice as many HZ cases and offering greater QALY gains. However, ZVL was more cost-effective due to its lower cost. Probabilistic sensitivity analyses revealed that RZV became more cost-effective at higher WTP thresholds, exceeding ₩60.9 million ($53,193) in terms of ICER and ₩62.5 million ($54,591) for INMBs and net loss. The optimal age for zoster vaccination was 60 years concerning ICER but 50 years regarding INMB. CONCLUSIONS: Combining RZV with a two-dose varicella vaccination strategy reduced the disease burden and improved QALY more effectively, though ZVL remained more cost-effective at lower WTP levels. Decisions regarding vaccination policies should be balanced between the public health needs and WTP levels.

Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain. Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO. Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement. Exposure: Recombinant zoster vaccination. Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure. Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04). Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

ATAGI Targeted Review 2022: Vaccination for prevention of herpes zoster in Australia.

Abstract: In November 2016, herpes zoster (HZ) vaccination for older adults, using the live-attenuated zoster vaccine (Zostavax; ZVL) was added to the Australian National Immunisation Program (NIP) with the aim of reducing morbidity from HZ and its complications, particularly for people at increased risk. Prior to the program, there were on average 5.6 cases of HZ per 1,000 persons annually in Australia, with highest risk of disease in older and in immunocompromised people. The burden of complications of HZ, such as post-herpetic neuralgia (PHN), was also highest in older and immunocompromised groups. No formal comprehensive program evaluation has been undertaken since program commencement. This review examined published literature and available vaccine administration data to summarise the evidence and considerations underpinning current use of HZ vaccines and potential future program directions in Australia. There have been modest reductions in the incidence of HZ and its complications since program introduction. However, five years into the program, challenges remain, including suboptimal vaccine coverage and significant safety concerns arising from inadvertent use of ZVL in immunocompromised people, who are contraindicated to receive this vaccine. This reduces opportunities to offset the burden of HZ-related disease. The recombinant subunit zoster vaccine (Shingrix; RZV), first registered in Australia in 2018, became available on the Australian market in June 2021. This vaccine has higher efficacy than ZVL and, as a non-live vaccine, can be used in both immunocompetent and immunocompromised people. RZV has potential to address the unmet needs of at-risk population groups. However, it has not yet demonstrated cost-effectiveness for inclusion as a funded vaccine under the NIP. The Australian HZ vaccination program has had limited effectiveness in meeting its aim in highest risk groups. Future options and challenges anticipated in using vaccination to reduce the burden of HZ and its complications are discussed in this review.

Cost-effectiveness of varicella and herpes zoster vaccination in Sweden: An economic evaluation using a dynamic transmission model.

OBJECTIVES: Comprehensive cost-effectiveness analyses of introducing varicella and/or herpes zoster vaccination in the Swedish national vaccination programme. DESIGN: Cost-effectiveness analyses based on epidemiological results from a specifically developed transmission model. SETTING: National vaccination programme in Sweden, over an 85- or 20-year time horizon depending on the vaccination strategy. PARTICIPANTS: Hypothetical cohorts of people aged 12 months and 65-years at baseline. INTERVENTIONS: Four alternative vaccination strategies; 1, not to vaccinate; 2, varicella vaccination with one dose of the live attenuated vaccine at age 12 months and a second dose at age 18 months; 3, herpes zoster vaccination with one dose of the live attenuated vaccine at 65 years of age; and 4, both vaccine against varicella and herpes zoster with the before-mentioned strategies. MAIN OUTCOME MEASURES: Accumulated cost and quality-adjusted life years (QALY) for each strategy, and incremental cost-effectiveness ratios (ICER). RESULTS: It would be cost-effective to vaccinate against varicella (dominant), but not to vaccinate against herpes zoster (ICER of EUR 200,000), assuming a cost-effectiveness threshold of EUR 50,000 per QALY. The incremental analysis between varicella vaccination only and the combined programme results in a cost per gained QALY of almost EUR 1.6 million. CONCLUSIONS: The results from this study are central components for policy-relevant decision-making, and suggest that it was cost-effective to introduce varicella vaccination in Sweden, whereas herpes zoster vaccination with the live attenuated vaccine for the elderly was not cost-effective-the health effects of the latter vaccination cannot be considered reasonable in relation to its costs. Future observational and surveillance studies are needed to make reasonable predictions on how boosting affects the herpes zoster incidence in the population, and thus the cost-effectiveness of a vaccination programme against varicella. Also, the link between herpes zoster and sequelae need to be studied in more detail to include it suitably in health economic evaluations.

Effectiveness of the Recombinant Zoster Vaccine for Herpes Zoster Ophthalmicus in the United States.

PURPOSE: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios. MAIN OUTCOME MEASURES: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed. RESULTS: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%). CONCLUSIONS: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.

Herpes Zoster Vaccine Live and Risk of Stroke Among Medicare Beneficiaries: A Population-Based Cohort Study.

Background and Purpose: Herpes zoster (HZ) is associated with increased risk of stroke, and zoster vaccine live (ZVL, Zostavax) reduces the risk of HZ. No study has examined the association between ZVL (Zostavax) and risk of stroke. Present study examined association between receipt of ZVL (Zostavax) and risk of stroke among older US population. Methods: Our study included 1 603 406 US Medicare fee-for-service beneficiaries aged ≥66 years without a history of stroke and who received ZVL (Zostavax) during 2008 to 2014, and 1 603 406 propensity score-matched unvaccinated beneficiaries followed through to December 31, 2017. We used Cox proportional hazard models to examine association between ZVL (Zostavax) and composite fatal or nonfatal incident stroke outcomes. Results: During a median of 5.1 years follow-up (interquartile range, 3.9­6.7), we documented 64 635 stroke events, including 43 954 acute ischemic strokes and 6727 hemorrhagic strokes, among vaccinated beneficiaries during 8 755 331 person-years. The corresponding numbers among unvaccinated beneficiaries were 73 023, 50 476, and 7276, respectively, during 8 517 322 person-years. Incidence comparing vaccinated to unvaccinated beneficiaries were 7.38 versus 8.57 per 1000 person-years for all stroke, 5.00 versus 5.90 for acute ischemic stroke, and 0.76 versus 0.84 for hemorrhagic stroke (P<0.001 for all difference). Adjusted hazard ratios comparing vaccinated to unvaccinated beneficiaries were 0.84 (95% CI, 0.83­0.85), 0.83 (0.82­0.84), and 0.88 (0.85­0.91) for all stroke, acute ischemic stroke, and hemorrhagic stroke, respectively. The association between ZVL (Zostavax) and risk of stroke appeared to be stronger among younger beneficiaries, beneficiaries who did not take antihypertensive or statin medications and who had fewer comorbid conditions (P<0.05 for interaction) but largely consistent across sex, low-income status, and racial groups. Conclusions: Among Medicare fee-for-service beneficiaries, receipt of ZVL (Zostavax) was associated with lower incidence of stroke. Our findings may encourage people to get vaccinated against HZ to reduce HZ and HZ-associated stroke risk.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

Incremental clinical and economic impact of recombinant zoster vaccination: real-world data in a budget impact model.

BACKGROUND: In 2017, the FDA approved the adjuvanted recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in immunocompetent adults aged 50 years and older. RZV joined zoster vaccine live (ZVL) as U.S.-marketed vaccines against HZ. The Advisory Committee on Immunization Practices preferentially recommended use of RZV over ZVL. In order to inform population-based decision makers (PBDMs) about the incremental clinical and economic impact of RZV adoption, budget impact (BI) models may be used. Populating such models with national data can inform PBDMs about the incremental value of RZV adoption nationally; however, heterogeneity across health plans requires the inclusion of plan-specific data to ensure the relevance of modeling outcomes for plan-specific decision makers. OBJECTIVE: To investigate the clinical and economic outcomes associated with the adoption of RZV in nationally representative populations with commercial and Medicare coverage and to demonstrate the effect of the heterogeneity of health plans using real-world data from a large, integrated delivery network (IDN). METHODS: We used a publicly available BI model. The model accounts for national and IDN-collected population characteristics (size, age distribution) and epidemiological data (incidence of HZ and complications, HZ recurrence rate), vaccine characteristics from randomized controlled trials and observational studies (efficacy, waning, second dose compliance for RZV, adverse event rate), national costs (vaccine, direct medical for HZ, complications, and vaccine adverse events), and current and anticipated vaccine coverage. We assessed incremental clinical (HZ cases and complications) and economic (per-member-per-month [PMPM] costs) impact at 5-year to 15-year time horizons, comparing scenarios where RZV is solely implemented with one where only ZVL is utilized. RESULTS: Following the adoption of RZV, the incremental HZ cases avoided over 5 and 15 years were estimated to be 1,800 and 15,000 for a commercial plan, 3,800 and 21,000 for a Medicare plan, and 8,600 and 71,000 for a specific IDN. The incremental PMPM budget impact over the same time horizons was estimated to be $0.42 and $0.31, respectively, for a commercial plan, $0.35 and $0.10 for a Medicare plan, and $0.39 and $0.25 for a specific IDN. The differences in results across plans resulted from the population age distribution, the vaccine copay (applied in the Medicare scenario only), the vaccine coverage in the plan, and other plan-specific factors affecting disease epidemiology and costs per case of HZ. CONCLUSIONS: Model projections indicated that RZV adoption avoided HZ cases and related complications, with the PMPM budget impact dependent on plan-specific factors. As health gains increased over time, the incremental costs incurred were found to decrease as the shorter-term costs of adopting the new vaccine were increasingly offset by the longer-term benefits of vaccination. DISCLOSURES: GlaxoSmithKline Biologicals SA funded this study (GSK study identifier: HO-17-18378) and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs associated with the development and publication of this manuscript. Patterson, Van Oorschot, and Curran are employees of the GSK group of companies and hold shares in the GSK group of companies. Herring, Carrico, and Zhang are employees of RTI Health Solutions, which received funding via a contractual agreement with the GSK group of companies to perform the work contributing to this research. Ackerson, Bruxvoort, Sy, and Tseng are employees of Kaiser Permanente Southern California, which was contracted by the GSK group of companies for the conduct of this study and were members of the KPSC study team. Ackerson, Bruxvoort, Sy, and Tseng report research contracts with the following pharmaceutical companies unrelated to this study: Dynavax (Ackerson, Bruxvoort, and Sy); the GSK group of companies (Ackerson, Bruxvoort, Sy, and Tseng); Novavax (Ackerson, Sy, and Tseng); and Seqirus (Ackerson, Bruxvoort, Sy, and Tseng). Tseng reports having served as a paid consultant for the GSK group of companies. The authors declare no other financial and nonfinancial relationships and activities. Findings from this study were presented at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

Burden-of-illness vaccine efficacy.

In recent years, many vaccines have been developed for the prevention of a variety of diseases. Although the primary objective of vaccination is to prevent disease, vaccination can also reduce the severity of disease in those individuals who develop breakthrough disease. Observations of apparent mitigation of breakthrough disease in vaccine recipients have been reported for a number of vaccine-preventable diseases such as Herpes Zoster, Influenza, Rotavirus, and Pertussis. The burden-of-illness (BOI) score was developed to incorporate the incidence of disease as well as the severity and duration of disease. A severity-of-illness score S > 0 is assigned to individuals who develop disease and a score of 0 is assigned to uninfected individuals. In this article, we derive the vaccine efficacy statistic (which is the standard statistic for presenting efficacy outcomes in vaccine clinical trials) based on BOI scores, and we extend the method to adjust for baseline covariates. Also, we illustrate it with data from a clinical trial in which the efficacy of a Herpes Zoster vaccine was evaluated.

Estimating the fiscal impact of three vaccination strategies in Italy.

OBJECTIVES: When assessing the economic value of vaccines, decision makers should adopt a full societal perspective. One approach for estimation of the fiscal impact of a disease is to use the human capital method to determine productivity losses. The aim of this study was to test an analytical framework developed for the estimation of the fiscal impacts of vaccination programs for influenza (FLU), pneumococcus (PC), and herpes zoster (HZ), in Italy. METHODS: We tested the framework in a two-stage analysis. First, we estimated the fiscal impact of the disease, second we performed a cost-benefit analysis of the individual benefits of vaccination against the cost of the vaccine. To estimate the fiscal impact of the diseases, the human capital approach was used. Epidemiological data were extrapolated from the literature. A Monte Carlo simulation enabled exploration of the uncertainty in the model variables. RESULTS: For FLU, assuming 2.1 million people infected, the total expected impact was EUR 999,371,520; the estimated fiscal impact was EUR 159,563,520. For PC, assuming 90,000 people infected, the total impact was EUR 148,055,040 and the estimated fiscal impact was EUR 23,639,040. For HZ, assuming 6,400 people infected, the total impact was EUR 4,777,200, with EUR 630,000 resulting from a decrease in fiscal taxation. CONCLUSIONS: In conclusion, our work shows how traditional methods aimed at estimating the cost of illness from a social perspective can be improved by additionally considering the fiscal impact, which accounts for the decrease in fiscal revenues due to illness.

Cost and utility in immunocompromised subjects who developed herpes zoster during the randomized V212 inactivated varicella-zoster vaccine (ZVIN) trial.

Objectives: Immunocompromised subjects are at increased risk for herpes zoster (HZ) and HZ-related complications, such as post-herpetic neuralgia (PHN). We describe health utilities, health care resource utilization (HCRU), productivity loss and health care costs in recipients of autologous hematopoietic stem-cell transplantation (Auto-HSCT) who developed confirmed HZ in the phase 3 clinical trial. Methods: HCRU, costs, and EQ-5D-3L utility were assessed for 155 confirmed HZ cases observed after receiving inactivated varicella-zoster virus (VZV) vaccine (ZVIN) or placebo. In a prospective, longitudinal 6-month follow up, costs and utilities were analyzed for two health states, HZ without PHN and HZ with PHN. Results: There was a clinically relevant difference in utility between HZ without PHN (mean 0.814) and HZ with PHN (0.729). The disutility for HZ without PHN was estimated to -0.117 and to -0.186 for HZ with PHN. Direct costs (2017 USD) associated with a HZ without PHN episode and HZ with PHN episode was estimated at $3,412 and $3,711, respectively, of which hospitalizations accounted for 90% of the costs. Expert opinion: Both HZ and PHN are associated with considerable disutility in recipients of Auto-HSCT. Costs were comparable to published estimates in other immunocompromised subjects. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT01229267).

Insurance Reimbursements for Routinely Recommended Adult Vaccines in the Private Sector.

INTRODUCTION: Financial concerns are frequently cited by providers as a barrier to adult vaccination. This study assessed insurance reimbursements to providers for administering vaccines to adults in the private sector. METHODS: This study, conducted in 2018, used the 2016 MarketScan Commercial Claims and Encounters Database and included vaccination visits made by adults aged 19-64 years. Four routinely recommended vaccines targeted at adults were included: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); tetanus and diphtheria toxoids (Td); zoster; and influenza. The mean reimbursements for vaccine purchase and administration were reported and examined by state, metropolitan statistical area, provider type, and insurance plan type. Using the private vaccine purchase price published by the Centers for Disease Control and Prevention (CDC), the study reported the proportion of vaccination visits receiving reimbursements above the CDC-published price. RESULTS: The mean vaccine administration reimbursement was $25.80 for the first dose and $14.71 for additional doses in the same visit. The mean vaccine purchase reimbursement was $44.15 for Tdap, $25.78 for Td, and $216.05 for the zoster vaccine; the unweighted mean for the four examined influenza vaccines was $17.25. Reimbursements varied widely by state. Vaccine reimbursements exceeded the CDC-published price for most visits where Tdap (71.4%), zoster (87.8%), and three of four influenza (61.5%-88.5%) vaccines were administered but only for 25.8% of visits where Td was given. CONCLUSIONS: On average, reimbursements for administering vaccines to privately insured adults were adequate for most private practices. However, providers' financial concerns may vary across geographic locations.

Is patient insurance type related to physician recommendation, administration and referral for adult vaccination? A survey of US physicians.

This study evaluated physician practices and perceived barriers for influenza, tetanus, diphtheria, pertussis (Tdap), and zoster vaccination of adults in the United States (US), with emphasis on patients with Medicare versus commercial insurance. A cross-sectional internet-based survey of board-certified general/family practitioners and internists (N = 1,000) recruited from a national US physician panel was conducted in May 2017. For influenza, rates of physician recommendation (84% of Medicare patients, 82% of commercially-insured patients), administration (80% Medicare, 78% commercial), and referral (11% Medicare, 11% commercial) were similar regardless of insurance type. Tdap recommendation was higher for commercial compared to Medicare patients (59% vs. 54%, p < 0.001); while zoster recommendation was higher for Medicare patients than commercial (59% vs. 55%, p < 0.001). For Tdap and zoster, higher administration rates were reported in commercial patients (64% Tdap, 36% zoster) than Medicare (56% Tdap, 32% zoster), and referral rates were higher for Medicare patients (19% Tdap, 49% zoster) than commercial (14% Tdap, 42% zoster). Over 40% of physicians would be much more likely to administer Tdap and zoster vaccines if they were covered under Medicare Part B, with more physicians indicating financial barriers as "major" or "moderate" for Medicare than commercial patients. These differences may be related to financial barriers associated with adult vaccinations that are covered under Medicare Part D and involve patient out-of-pocket costs. Efforts to reduce financial barriers associated with adult vaccinations covered under Medicare Part D and to improve patient and physician knowledge could positively impact physician recommendation, administration, and referral for adult vaccination in the US.

Vaccination among Medicare-fee-for service beneficiaries: Characteristics and predictors of vaccine receipt, 2014-2017.

BACKGROUND: Vaccination coverage rates for older adults are low. To better understand utilization of Medicare vaccination benefits we examined a retrospective cohort of more than 26 million Medicare fee-for-service beneficiaries age 65 years and older from 2014 to 2017. METHODS: Multivariate logistic regression was used to obtain marginal effects (ME) describing the association between patient-level characteristics and the likelihood of vaccination. Vaccines routinely recommended by the Advisory Committee on Immunization Practices-seasonal influenza, 23-valent pneumococcal polysaccharide, 13-valent pneumococcal conjugate, and herpes zoster vaccines-were examined. Variables considered include demographics (e.g., age, sex, race), use of preventive services, frailty indicators, and co-morbidities. RESULTS: The mean beneficiary age (SD) for each vaccine examined-seasonal influenza (2016-2017), pneumococcal, and herpes zoster-was 75.0 (7.9) years, 74.5 (7.5) years, 74.5 (7.4) years respectively; and 43.7%, 43.2%, and 39.5% were males respectively. Adjusted marginal effects showed that Black beneficiaries were less likely to receive any of the three vaccines compared to White beneficiaries, while North American Native beneficiaries were most likely to receive a pneumococcal vaccine. Trends by race and sex were similar across all ages. Beneficiaries utilizing preventive services, particularly cardiovascular disease screening (ME of 13.8%, 15.6% and 1.5% for influenza, pneumococcal and herpes zoster vaccine respectively), other vaccinations, and the Medicare Annual Wellness Visit (ME of 9.8%, 15.3% and 0.4% respectively) were predictors of vaccination for all three vaccines. For herpes zoster vaccines, beneficiaries in rural settings (ME of 1.0%) and those who are dual-eligible for Medicare and Medicaid insurance (ME of 1.7%) were more likely to receive herpes zoster vaccine than beneficiaries in urban settings and those not dual-eligible, respectively. CONCLUSION: Medicare beneficiaries of certain demographic with selected comorbid conditions are less likely to receive routinely-recommended vaccines. Strategies and interventions can target such sub-populations of Medicare beneficiaries by optimizing the utilization of preventive services.

Cost-Effectiveness of Herpes Zoster Vaccination: A Systematic Review.

BACKGROUND: Herpes zoster (HZ) is one of the most common diseases among adults. Its reactivation is characterized by a severe and painful complication. In addition to the existing herpes zoster vaccine (ZVL), the FDA approved a new adjuvanted subunit zoster vaccine (RZV) in 2017 for use in adults aged 50 years and older. Several studies have assessed the cost-effectiveness of ZVL, many of which were conducted before the long-term vaccine  efficacy data was available in 2014. OBJECTIVE: Our objectives were to (i) summarize and compare the cost-effectiveness analyses (CEAs) of ZVL conducted before and after 2014, (ii) summarize the CEAs of RZV, and (iii) critically assess the cost-effectiveness models and identify key parameters to consider for future CEAs of RZV. METHODS: We searched PubMed and two other databases from inception to March 2018 for original cost-effectiveness, cost-utility, or cost-benefit analyses of HZ vaccines. Three investigators independently reviewed and assessed full-text articles after screening the titles and abstracts to determine eligibility. For all included studies, we assessed study quality using the Drummond and Jefferson's checklist and extracted study characteristics, model structure, vaccine characteristics, incidence of HZ and complications, incremental cost-effectiveness ratio, and sensitivity analyses. We summarized data by type of vaccine, year of publication, and funding sources. RESULTS: Twenty-seven studies met eligibility criteria. All studies were from high-income countries and were of moderate-to-high or high quality. Twenty studies repeatedly used four cost-effectiveness models. The assumption on long-term efficacy of ZVL was not based on clinical trial data in > 50% of studies. Fifteen out of 25 studies concluded that ZVL was cost-effective compared with no vaccine at a vaccine price ranging between US$93 and US$236 per dose (2018 US$), 40% of which were published after 2014. All industry-funded studies favored the use of ZVL. The single study assessing RZV found it to be more effective and less costly than ZVL, and cost-effective compared with no vaccination. More studies conducted after 2014 included various efficacy endpoints for ZVL, adverse reactions, and productivity loss compared with those conducted before 2014. CONCLUSIONS: A majority of studies of ZVL found it to be cost-effective compared with no vaccine using the authors' chosen willingness-to-pay thresholds. RZV was dominant in the single study comparing the two vaccines, but the finding needs to be confirmed with further studies in different settings. Future studies should assume vaccine efficacy in line with clinical data, account for more efficacy endpoints for ZVL, and include other HZ long-term complications, vaccine adverse reactions, and productivity loss.

Differential uptake of herpes zoster vaccination associated with socioeconomic status: A population-based study in Stockholm County, Sweden.

PURPOSE: To investigate whether herpes zoster vaccine (HZV) was associated with socioeconomic status in Stockholm, when the vaccine was reimbursed in Sweden. METHODS: This was an observational retrospective case-control study, using population-based health care registers. During the study period, September 2013 to November 2014, the HZV was reimbursed as part of the National Pharmaceutical Benefits Scheme in Sweden and recommended for individuals over 50 years. A case was any person, living in Stockholm County, who received HZV during the study period. For each case, 10 (unvaccinated) controls living in Stockholm County were selected and matched by age and sex. In total, 9099 cases and 89 736 controls were included. Socioeconomic variables investigated included education, income, immigration status, and marital status. We also investigated whether HZV was associated with the Charlson Comorbidity Index (CCI), and/or previous herpes zoster diagnosis. RESULTS: Mean age at vaccination was 69.8 years, and 65.8% of vaccinees were women. There was a positive association between vaccination and higher education (OR = 3.4 (95% CI 3.0-3.8) for men and OR = 2.8 (95% CI 2.6-3.0) for women, respectively) in comparison to primary education. Higher income and being married were positively associated with vaccination, particularly for men, whereas being an immigrant was negatively associated. There was a negative association between a higher CCI score and HZV, indicating that healthier individuals were more likely to have been vaccinated. CONCLUSIONS: Despite the vaccine being part of the National Pharmaceutical Benefit Scheme, receipt of the HZV was significantly associated with socioeconomic factors.

Herpes zoster vaccine: a protection for the elderly.

The Herpes Zoster vaccine is strongly recommended by the World Health Organization to promote healthy aging by preventing the corresponding age- related disease, also named shingles. The disease is due to the endogenous reactivation of Varicella Zoster Virus, the causal agent of chickenpox, that becomes latent at the peripheral nervous system level. Here, owing to the host's cell-mediated immunity, it may be confined for several decades. However, the immune senescence allows the possibility of virus reactivation, causing the onset of neuropathic pain and skin rash that characterize the acute disease. Sometimes, the neuralgia becomes chronic causing postherpetic neuralgia that has a significant impact on the quality of patient life, analogously to the ophthalmic HZ, a particularly feared form of disease. Due to the causal relationship between decreasing immune defenses and virus reactivation with disease onset, the incidence of Herpes Zoster, in Italy now equal to 6.42 (95%CI: 5.93-6.95) cases per 1,000 people per year will increase steadily in the future due to the longevity rise of the population. Considering epidemiological impact, complications and sequelae in the short- and long-term, costs of clinical-therapeutical management of patients, and, above all, the poor effectiveness of available therapy the only effective intervention is vaccination of the elderly. Currently in the European Union, there is only one vaccine for Herpes Zoster prevention, formed by live attenuated OKA-Merck virus strain that is also used for paediatric vaccine. According to the Health Technology Assessment surveys, the intervention cost (based on "Quality Adjusted Life Years") is clearly below the discriminating threshold value to judge the feasibility and, as predicted by the Italian National Plan of Vaccinal Prevention 2017-2019, the vaccine is offered free to all subjects >65 years.