The temporal impact of aging on the burden of herpes zoster.

BACKGROUND: The risk of Herpes Zoster (HZ) increases with age and various studies have also demonstrated an increasing HZ incidence globally. Simultaneously, the global trend of an aging population has placed a greater burden on the healthcare system. This study aims to estimate the potential burden of HZ over time accounting for the increasing trends of both HZ incidence and global aging. METHODS: A recent systematic review on HZ incidence identified studies that evaluated the temporal effects of HZ incidence. Data from the identified studies were extracted to estimate the trend of HZ incidence in the ≥65-year-old age cohort. The incidence rates were estimated up to the year 2030 using two scenarios: a linear extrapolation and a last observation carried forward. Three countries were chosen to perform the analysis on: Australia, Japan and the United States. RESULTS: The incidence data from the three countries showed an average annual increase between 2.35 and 3.74% over the time period of the studies selected. The elderly population for the US, Japan and Australia are expected to increase by 55, 10 and 53% respectively by the year 2030 compared to the levels in 2015. Under the first scenario between 2001 and 2030, the number of annual incident cases of HZ in those aged ≥65 years is expected to increase by +343% (293,785 to 1,303,328), +176% (158,616 to 437,867) and +376% (18,105 to 86,268) in the US, Japan and Australia respectively while those for the second scenario are +150%, +83% and +223% respectively. In the US alone, the estimated annual cost of HZ-related cases in the ≥65 age cohort is approximately 4.74 Billion US$ in 2030. CONCLUSIONS: The increasing incidence of HZ coupled with the demographic trends (i.e., aging population and greater life expectancy) in many countries are likely to imply a rising economic burden of HZ on already constrained healthcare budgets.

Cost-effectiveness of add-on empagliflozin versus standard of care in management of CKD in Malaysia, Thailand and Vietnam - findings from a modelling study assessing an EMPA-KIDNEY eligible population, using CKD progression model.

BACKGROUND AND OBJECTIVES: Nearly one in ten individuals in South-East Asia are estimated to be affected by chronic kidney disease (CKD). The burden of end-stage kidney disease is significant and can be heavy on the healthcare system. The recent EMPA-KIDNEY trial demonstrated a significant reduction in the risk of kidney disease progression or cardiovascular death in patients with CKD with a broad range of kidney function using add-on empagliflozin versus standard of care (SoC) alone. The objective of this study was to estimate the economic benefit of empagliflozin for patients with CKD in Malaysia, Thailand and Vietnam. METHODS: An individual patient level simulation model with an annual cycle that estimates the progression of kidney function and associated risk-factors was employed. Local costs and mortality rates were estimated from a wide range of published literature. A healthcare perspective was used over a 50-year time horizon. RESULTS: The use of add-on empagliflozin versus SoC alone was found to be cost-saving in Malaysia and Thailand and cost-effective (ICER: 77,838,407 Vietnam Dong/QALY vs. a willingness to pay threshold of 96,890,026/QALY) in Vietnam. The bulk of the costs avoided over a lifetime is derived from the prevention or delay of dialysis initiation or kidney transplant - the cost offsets were nearly twice the additional treatment cost. The results were similar in patients with and without diabetes and across broad range of albuminuria. CONCLUSIONS: The use of add-on empagliflozin in a broad population of patients with CKD is expected to be cost-saving in Malaysia and Thailand and cost-effective in Vietnam and will help alleviate the increasing burden of CKD in the region.

Cost-Effectiveness of Empagliflozin on Top of Standard of Care for Heart Failure With Reduced Ejection Fraction in Singapore.

OBJECTIVES: The prevalence of heart failure (HF) and its risk factors are high in Singapore. The EMPEROR-Reduced trial demonstrated that add-on empagliflozin resulted in a reduction in the risk of cardiovascular death or hospitalization for HF compared with standard of care (SoC). This study aimed to estimate the cost-effectiveness of empagliflozin+SoC versus SoC in patients with HF with reduced ejection fraction from a Singaporean healthcare perspective. METHODS: A Markov cohort model simulated progression through health states based on New York Heart Association classes over a lifetime horizon using a cycle length of 1 month. Transition probabilities, and the risk of transient events (hospitalization for HF and cardiovascular/all-cause death) were modeled based on the EMPEROR-Reduced trial. Costs for HF-related events, adverse events, and for monitoring were estimated from a combination of published literature and publicly available fees for public hospitals/polyclinics. RESULTS: Empagliflozin+SoC was estimated to be very cost-effective versus SoC alone with an incremental cost-effectiveness ratio of<8000 Singapore Dollars/quality-adjusted life-year gained. The base-case results were robust as evidenced from the consistency of various scenario and sensitivity analyses performed. When using Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score quartiles as the health states, the incremental cost-effectiveness ratio reduced significantly to 4625 Singapore Dollars/quality-adjusted life-year. CONCLUSION: The use of empagliflozin on top of SoC represents a highly cost-effective solution for the treatment of patients with HF with reduced ejection fraction in Singapore when considering its efficacy, relative affordability, and the growing economic burden of HF in Singapore.

How to assess for the full economic value of vaccines? From past to present, drawing lessons for the future.

Background:Cost-effectiveness analysis (CEA) is the economic analysis method most commonly applied today in the context of replacing one treatment with a new one in a developed healthcare system to improve efficiency. CEA is often requested by local healthcare decision-makers to grant reimbursement. New preventative interventions, such as new vaccines, may however have much wider benefits inside and outside healthcare, when compared with treatment. These additional benefits include externalities on indirect clinical impact, reallocation of specific healthcare resources, improved quality of care, better productivity, better disease control, better fiscal revenues, and others. But these effects are sometimes difficult to integrate into a meaningful CEA result. They may appear as specific benefits for specific stakeholders, other than the stakeholders in healthcare. Objective: Based on a historical view about the application of economic assessments for vaccines our objective has been to make the inventory of who was/is interested in knowing the economic value of vaccines, in what those different stakeholders are likely to see the benefit from their perspective and how  were/are we able to measure those benefits and to report them well. Results: The historical view disclosed a limited interest in the economic assessment of vaccines at start, more than 50 years ago, that was comparable to the assessment of looking for more efficiency in new industries through optimization exercises. Today, we are exposed to a very rich panoply of different stakeholders (n= 16). They have their specific interest in many different facets of the vaccine benefit of which some are well known in the conventional economic analysis (n=9), but most outcomes are hidden and not enough evaluated and reported (n=26). Meanwhile we discovered that many different methods of evaluation have been explored to facilitate the measurement and reporting of the benefits (n=18). Conclusion: Our recommendation for future economic evaluations of new vaccines is therefore to find the right combination among the three entities of stakeholder type selection, outcome measure of interest for each stakeholder, and the right method to apply. We present at the end examples that illustrate how successful this approach can be.

Health economic assessment of a rabies pre-exposure prophylaxis program compared with post-exposure prophylaxis alone in high-risk age groups in the Philippines.

OBJECTIVES: Once symptoms appear, rabies is almost always fatal and accounts for 200-300 deaths annually in the Philippines. Available rabies vaccines can be administered either in pre- exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP). After exposure, PrEP-immunized individuals require fewer doses of PEP and no rabies immunoglobulin. METHODS: A static decision-tree model was developed to assess cost-effectiveness of a PrEP+PEP program vs PEP alone. Philippines-specific data for people seeking medical advice at the Research Institute for Tropical Medicine between July 2015 and June 2016 were used in the model, together with data from published literature. RESULTS: Over a 20-year period, in a cohort of 1 million 5-year-old children in the Philippines, PrEP+PEP was expected to prevent 297 deaths compared with PEP alone. From both payer and societal perspectives, the resulting incremental cost-effectiveness ratios were 36 035 (US$759; 2016 US$ conversion) and 18 663 (US$393) Philippine Pesos (PHP) - quality-adjusted life-years gained - respectively, which are both below the willingness-to-pay threshold of PHP140 255 (US$2 953). CONCLUSION: These data suggest that a universal PrEP program targeting 5-year-olds would be cost-effective in the Philippines.

Applying a Constrained Optimization Portfolio Model to Aid Prioritization of Public Health Interventions in Malaysia.

OBJECTIVES: Countries have constrained healthcare budgets and must prioritize new interventions depending on health goals and time frame. This situation is relevant in the sphere of national immunization programs, for which many different vaccines are proposed, budgets are limited, and efficient choices must be made in the order of vaccine introduction. METHODS: A constrained optimization (CO) model for infectious diseases was developed in which different intervention types (prophylaxis and treatment) were combined for consideration in Malaysia. Local experts defined their priority public health issues: pneumococcal disease, dengue, hepatitis B and C, rotavirus, neonatal pertussis, and cholera. Epidemiological, cost, and effectiveness data were informed from local or regionally published literature. The model aimed to maximize quality-adjusted life-year (QALY) gain through the reduction of events in each of the different diseases, under budget and intervention coverage constraints. The QALY impact of the interventions was assessed over 2 periods: lifetime and 20 years. The period of investment was limited to 15 years. RESULTS: The assessment time horizon influenced the prioritization of interventions maximizing QALY gain. The incremental health gains compared with a uninformed prioritization were large for the first 8 years and declined thereafter. Rotaviral and pneumococcal vaccines were identified as key priorities irrespective of time horizon, hepatitis B immune prophylaxis and hepatitis C treatment were priorities with the lifetime horizon, and dengue vaccination replaced these with the 20-year horizon. CONCLUSIONS: CO modeling is a useful tool for making economically efficient decisions within public health programs for the control of infectious diseases by helping prioritize the selection of interventions to maximize health gain under annual budget constraints.

Cost-effectiveness of the recombinant zoster vaccine in the German population aged ≥60 years old.

Each year, around 300,000 Herpes Zoster (HZ) cases are observed in the German population, resulting in costs over €182 million to society. The objective of this study was to estimate the potential public health and economic impact of the new Adjuvanted Recombinant Zoster Vaccine (RZV, Shingrix) in the German population ≥ 60 years of age (YOA) and to identify the optimal age of vaccination. We used a static, multi-cohort Markov model that followed a hypothetical cohort of 1 million people ≥ 60 YOA life-long after vaccination using German-specific inputs. Both costs and outcomes were discounted at 3%, the incremental cost-effectiveness ratio (ICER) was calculated based on the societal perspective. The coverage of RZV was set at 40% with a second-dose compliance of 70%. Vaccinating the population aged ≥ 60 YOA would result in 45,000 HZ cases avoided, 1,713 quality-adjusted life years (QALYs) gained at a total cost of approximately €63 million compared to 38,000 cases avoided, 1,545 QALYs gained at a total cost of approximately €68 million in the population ≥ 70 YOA. This would result in an ICER of approximately €37,000 and €44,000/QALY, for the age cohort ≥ 60 and ≥ 70 YOA, respectively. Scenario analyses demonstrated that vaccinating at age 60 or 65 YOA would show greater public health impact and would result in the lowest observed ICER compared to vaccinating at 70 YOA. In conclusion, starting vaccination with RZV in the German population ≥ 60 YOA would demonstrate the best value from a public health and economic standpoint.

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults.

OBJECTIVES: In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. METHODS: A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. RESULTS: RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. CONCLUSIONS: The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

More than 95% of adults aged 50 are infected with varicella-zoster virus and are at risk of developing herpes zoster, also known as shingles. This risk is higher in older people and in people with a reduced immune system. Shingles causes a painful rash and may trigger persistent pain and other complications that greatly reduce quality of life. In Canada, Zostavax is the only existing approved vaccine against shingles. It has been offered in a publicly funded program in Ontario to those aged 65­70 years since September 2016. Shingrix, is a new shingles vaccine that has recently been approved by Health Canada for adults aged ≥ 50 years. The present model suggests that Shingrix confers higher protection against shingles compared to Zostavax, with a greater reduction in shingles episodes. The increase in vaccination costs would be partially offset by reduced healthcare visit and medication expenses. For these reasons, provincial health plans may consider offering Shingrix to people aged ≥ 50 years.

A Cost-Effectiveness Analysis of the 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Compared to the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) for Universal Mass Vaccination Implementation in New Zealand.

OBJECTIVES: Invasive pneumococcal disease (IPD), pneumonia and acute otitis media (AOM) still represent a significant medical burden in children < 5 years of age in New Zealand (NZ), with marked disparities across socio-economic and ethnic groups. This cost-effectiveness evaluation aims to compare the potential impact of two childhood universal immunisation strategies: vaccination with a 3 + 1 schedule of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix, GSK) and the 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13, Pfizer). METHODS: A static Markov-process cohort model was used to simulate the epidemiological and economic burden of pneumococcal diseases on a single-birth cohort over its lifetime. Costs and outcomes were discounted annually at 3.5%. Epidemiological and cost inputs were extracted from the most recently available NZ data, or derived from the most relevant reference countries' sources. The most updated evidence on the efficacies of the corresponding vaccines were used, particularly the significant effectiveness for PHiD-CV against IPD caused by serotype 19A. RESULTS: The model estimated that both vaccines have a broadly comparable impact on IPD-related diseases and pneumonia. Due to the additional benefits possible through broader impact on AOM, PHiD-CV is estimated to potentially provide additional discounted cost offsets of approximately NZD 0.8 million over the lifetime of the birth cohort. CONCLUSIONS: To ensure health equity in children, given the substantial burden of pneumonia and AOM, decision-makers should also take into account the impact of PCVs on these diseases for decisions relating to routine infant immunization. GSK STUDY IDENTIFIER: HO-15-16775.

Cost Effectiveness of Quadrivalent Influenza Vaccines Compared with Trivalent Influenza Vaccines in Young Children and Older Adults in Korea.

INTRODUCTION: Trivalent influenza vaccines (TIVs) are currently reimbursed for subjects aged ≥ 65 years and children between 6 and 59 months of age under a national immunization program in South Korea. Quadrivalent influenza vaccines (QIVs) are expected to address the potential problem of influenza B-lineage mismatch for TIVs. OBJECTIVE: The objective of this analysis was to compare the cost effectiveness of QIV versus TIV in children aged 6-59 months and older adults ≥ 65 years of age in South Korea. METHODS: A 1-year static population model was employed to compare the costs and outcomes of a QIV vaccination program compared with TIV in children aged 6-59 months and older adults ≥ 65 years of age in South Korea. Influenza-related parameters (probabilities, health resource use, and costs) were derived from an analysis of the National Health Insurance System claims database between 2010 and 2013 under a broad and narrow set of International Classification of Diseases, Tenth Revision (ICD-10) codes used to identify influenza. Other inputs were extracted from published literature. Incremental cost-effectiveness ratios (2016 South Korean Won [KRW] per quality-adjusted life-year [QALY] gained) were estimated using a 'limited' societal perspective as per the Korean pharmacoeconomic guidelines. QALYs lost due to premature mortality were discounted at 5% annually. RESULTS: For both age groups combined, under the narrow definition of influenza, QIV is expected to prevent nearly 16,000 (2923 in children and 13,011 in older adults) medically attended influenza cases, nearly 8000 (672 in children, 7048 in older adults) cases of complications, and over 230 (0 in children, 238 in older adults) deaths annually compared with TIV. The impact of using QIV versus TIV in this setting translates into savings of KRW 24 billion (KRW 0.6 billion in children, KRW 23.4 billion in older adults) in annual medical costs, and over 2100 (18 in children, 2084 in older adults) QALYs. Under the broad definition, the corresponding results are over 190,000 (50,697 in children, 140,644 in older adults) influenza cases, over 37,000 (12,623 in children, 24,526 in older adults) complications, 270 deaths (0 in children, 270 in older adults), KRW 94.22 billion (KRW 16 billion in children, KRW 78.2 billion in older adults), and over 3500 QALYs saved (316 in children, 3260 in older adults). CONCLUSION: The use of QIV over TIV was estimated to not be cost effective in children 6-59 months of age, but cost saving in older adults, using the narrow definition of influenza; however, QIV use was cost saving in both age groups using the broad definition. QIV is expected to yield more benefits in older adults ≥ 65 years of age than in children aged 6-59 months due to higher influenza-related mortality and costs among the older adults. Further analyses considering the indirect effects of influenza vaccination in children are required.

The Potential Public Health Impact of Herpes Zoster Vaccination of People Aged ≥ 50 Years in Japan: Results of a Markov Model Analysis.

INTRODUCTION: The aim of this study was to compare the public health impact of introducing two herpes zoster (HZ) vaccines into the vaccination programs for the Japanese population aged ≥ 50 years: a single-dose Varicella Vaccine Live (VVL) or a two-dose adjuvanted Recombinant Zoster Vaccine (RZV). METHODS: A multi-cohort static Markov model was developed to follow age cohorts (50-59, 60-69, 70-79 and ≥ 80 years) over their remaining lifetime. Japan-specific data inputs for the model were obtained from Japanese data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% for both vaccines, and compliance with second-dose of the RZV vaccine was set to 95%. RESULTS: Vaccination with RZV was projected to prevent approximately 3.3 million HZ cases, 692,000 cases of postherpetic neuralgia (PHN), and 281,000 cases of other complications, compared with the prevention of 0.8 million HZ cases, 216,000 PHN cases, and 57,000 other complications with vaccination with VVL. The number of individuals needed to vaccinate in order to prevent one HZ case ranged from 6 to 14 using RZV (depending on age and assumed second-dose compliance) and from 21 to 138 depending on age using VVL. By preventing a higher number of HZ cases and its complications, RZV vaccination led to fewer outpatient visits and hospitalizations than vaccination with VVL. CONCLUSION: Both vaccines had a positive public health impact compared to no vaccination, but due to its higher vaccine efficacy, RZV demonstrated a superior public health impact compared with VVL. FUNDING: GlaxoSmithKline Biologicals SA.

Assessment of the potential public health impact of Herpes Zoster vaccination in Germany.

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50-59, 60-69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL.

Response to Wu et al. - Cost-effectiveness analysis of infant pneumococcal vaccination in Malaysia and Hong Kong.

A recently published paper that assessed the comparative cost-effectiveness of the 2 pneumococcal conjugate vaccines (PCVs) in Malaysia and Hong Kong reported that the 13-valent PCV vaccine (PCV13) is a better choice compared to the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV or PCV10) from both a payer and societal perspective as well as under various scenarios. However, the analysis relied on a large number of assumptions that were either erroneous or did not take into account the most recent body of evidence available. A rigorous evaluation of the underlying assumptions is necessary to present a fair and balanced analysis for decision-making.