Effectiveness and cost-effectiveness of vaccination against herpes zoster in Canada: a modelling study.

BACKGROUND: Two vaccines against herpes zoster are currently authorized for use in Canada: the recombinant subunit zoster vaccine and live attenuated zoster vaccine. We compared the effectiveness and cost-effectiveness of these 2 vaccines. METHODS: We used a decision analytic static cohort model parametrized with Canadian epidemiologic and economic data. We performed the economic analysis from the health care system perspective, using a lifetime horizon and a 3% discount rate for costs and benefits. The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained, relative to no vaccination. We ran 30 000 simulations varying all model parameters, including vaccine costs, efficacy and waning. RESULTS: The number needed to vaccinate (NNV) was higher for the live attenuated zoster vaccine than for the recombinant subunit zoster vaccine for all herpes zoster-related events at all ages. For example, in persons exactly 65 years old, for herpes zoster, median NNV was 21 (90% uncertainty interval [UI] 13-31) versus 8 (90% UI 6-18), and for postherpetic neuralgia, NNV was 64 (90% UI 33-93) versus 31 (90% UI 23-73). For the recombinant vaccine, the median cost-effectiveness ratios varied between cost-saving and $25 881 per QALY gained for adults aged 50 years or older. For the live vaccine, the cost-effectiveness ratios varied between cost-saving and $130 587 per QALY gained and were less than $45 000 per QALY gained only for those 65 to 75 years old. Given its higher efficacy, we estimated that the cost for the complete series of the recombinant vaccine could be $150 to $200 more than the cost of the live vaccine and still be considered cost-effective. INTERPRETATION: Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older, and is likely more cost-effective than live attenuated zoster vaccine. These results have informed updated national and provincial recommendations on herpes zoster vaccination.

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study.

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.

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.

Cost-effectiveness of Recombinant Zoster Vaccine (RZV) and Varicella Vaccine Live (VVL) against herpes zoster and post-herpetic neuralgia among adults aged 65 and over in Japan.

BACKGROUND: The approval of the extended use of 1-dose varicella vaccine (VVL) in adults aged 50 and older against herpes zoster (HZ) in 2016 and the 2-dose recombinant zoster vaccine (RZV) in 2018 raised the need to evaluate the value for money between these two vaccines. METHODS: We conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of the immunisation programmes from payer's perspective. Eight strategies with different ages to receive VVL or RZV were set, namely: 65-84 year old (y.o.), 70-84 y.o., 75-84 y.o., and 80-84 y.o. VVL- or RZV-strategy. Incremental cost-effectiveness ratios (ICERs) compared with curative care scenario were calculated. The health statuses following the target cohort were as follows: acute HZ followed by recovery, post-herpetic neuralgia followed by recovery, post HZ/PHN, recurrence of HZ, and general death. RESULTS: At the vaccination cost ¥8000 (US$73) for 1-dose ZVL and ¥30,000 (US$273) for 2-dose RZV, ICERs ranged from ¥2,633,587/US$23,942 (age 80-84 y.o.) to ¥3,434,267 or US$31,221 (age 65-84 y.o.)/QALY gained for VVL-strategies; from ¥5,262,227 or US$47,838 (age 80-84 y.o.) to ¥6,278,557 or US$57,078/QALY gained (age 65-84 y.o.) for RZV-strategies. Cost-effectiveness acceptability curves derived from probabilistic sensitivity analyses showed that if the cost-effective threshold was at ¥3,000,000 or US$27,273/QALY, the acceptability was 90.7% and 8.8% for 65-84 VVL-strategy and 65-84 RZV-strategy, respectively; if at ¥5,000,000 or US$45,455/QALY, 56.2% and 43.8%, and if at ¥10,000,000 or US$90,909/QALY 11.9% and 88.1%, respectively. CONCLUSION: Vaccinating individuals aged 65-84 y.o., 70-84 y.o., 75-84 y.o., 80-84 y.o. with VVL or RZV to prevent HZ-associated disease in Japan can be cost-effective from payer's perspective, with vaccination costs at ¥8,000 per shot for VVL, ¥30,000 for 2-dose RZV. While the results suggesting that only 65-84 VVL-strategy and 65-84 RZV strategy should be considered when introducing HZ immunisation programme. The optimal strategy varies depending on the willingness-to-pay threshold.

Budget Impact Analysis of Rotavirus Vaccine Adoption in the Childhood Immunization Schedule of Iran.

OBJECTIVES: To examine the budget impact of introducing the RotaTeq® vaccine (Merck and Co Inc, West Point, PA) to the national immunization program in Iran. METHODS: The pre- and postvaccine introduction costs were compared. The total annual costs included the vaccination and diarrhea treatment costs. The health outcome was the estimated annual cases of the disease. To evaluate the net budget impact, the annual prevaccine introduction cost was reduced from the postvaccine introduction cost. The sensitivity analysis was done to reduce the uncertainties. RESULTS: The total cost of vaccination for 5 years would be more than $184 million. Nevertheless, the financial savings would be about $45 million and $7.5 million because of the reduction in the number of patients after vaccination in inpatient and outpatient sectors, respectively. So the incremental cost would be $131 450 210 during 5 years of immunization. CONCLUSIONS: The results show that the inclusion of rotavirus vaccine in the national vaccination program would have a significant effect on health budgets and would raise government expenditure.

Projected impact, cost-effectiveness, and budget implications of rotavirus vaccination in Mongolia.

INTRODUCTION: Rotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country's limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction. METHODS: The analysis examines the use of the two-dose vaccine ROTARIX®, and three-dose vaccines ROTAVAC® and RotaTeq® compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis. RESULTS: Rotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10 years. Averted visits and hospitalizations represent US$2.4 million in health care costs saved by the government. The vaccination program cost ranges from $6 to $11 million depending on vaccine choice. From the governmental perspective, ICER ranged from $412 to $1050 and from $77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty. CONCLUSION: Introduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia's per capita GDP. From an economic standpoint, ROTAVAC® is the least costly and most cost-effective product choice.

Prospects for rotavirus vaccine introduction in the Philippines: Bridging the available evidence into immunization policy.

Rotavirus (RV) diarrhea is one of the most common cause of childhood morbidity and mortality in the world. The World Health Organization has recommended RV vaccines' use in national immunization programs since 2009. However, access to vaccines remain limited, particularly for most low- and middle-income countries where the burden of the disease is high. The Philippines is a lower-middle income country in Asia where RV vaccination remains limited. Recent studies in the Philippines indicate an estimated vaccine effectiveness of 60% against RV hospitalization, and a 50-60% reduction of all cause diarrhea among children aged under 5 within the population. Furthermore, we estimate that 225 rotavirus cases can be prevented per 1000 children vaccinated against RV. This information will be crucial as policymakers decide on expanding RV vaccination nationwide.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Re-evaluating the cost and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi: A comparison of three rotavirus vaccines.

INTRODUCTION: Diarrhea is a leading cause of mortality worldwide and rotavirus accounts for many of these deaths. As of August 2018, 96 countries have introduced rotavirus vaccines into their immunization programs. Two rotavirus vaccines, Rotarix® and RotaTeq®, have been WHO-prequalified since 2009, with Rotarix® being the preferred product of most Gavi-supported countries. ROTAVAC® and ROTASIIL® have both been prequalified recently. MATERIALS AND METHODS: We reevaluated the costs and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi and compared Rotarix®, ROTAVAC®, and ROTASIIL® in each country. For consistency with previously published analyses in these countries, we used the same Excel-based cohort model and much of the same data as the original analyses. We varied the expected price (with and without Gavi subsidy), wastage, and incremental health system costs associated with each vaccine. We assumed the same efficacy and waning assumptions following administration of two or three doses for the respective product. RESULTS: The discounted cost per DALY averted compared to no vaccination ranged from 0.3 to 1.3 times GNI per capita for each vaccine. With the Gavi subsidy, the average cost-effectiveness ratios were below 0.3 times GNI per capita in all three countries. Though critical empirical cost data are not yet available, Rotarix® is the least costly and most cost-effective product in the countries examined in this modelling study. However, small decreases in the incremental health system cost for other products could result in cost and cost-effectiveness outcomes that match or surpass those of Rotarix®. CONCLUSION: Countries may wish to consider new rotavirus vaccines entering the market. Countries should carefully examine multiple product attributes including price and the incremental health system costs associated with each vaccine. These costs will vary by country and may be a defining factor in determining the least costly and most cost-effective product for the population.

Cost-effectiveness estimates of vaccination against rotavirus in Piedmont, Italy.

BACKGROUND: Rotavirus-induced gastroenteritis (RVGE) represents the most frequent form of severe gastroenteritis in children. In such a scenario, the availability of an efficient anti-Rotavirus (anti-RV) vaccine represents an effective prevention tool able to prevent those complications mainly linked to the moderate-severe forms of this disease, which require hospital care. The aim of the present study is to estimate the cost effectiveness of universal routine infant RV vaccination program and its budget impact on the Regional Health Service (RHS) of Piedmont, Italy, in order to evaluate the opportunity of the implementation of a national anti-Rotavirus vaccination programme. METHODS: The researchers performed a cost-effectiveness analysis comparing costs and benefits of a Rotarix two-dose vaccination versus non vaccination and a budget impact analysis (BIA), complementary to the cost-effectiveness analysis. RESULTS: Our results show that the mass implementation of an anti-RV vaccination in Piedmont, in addition to the expected public health benefits, also allows the RHS to save a considerable amount of money within a short period of time, due to the remarkable reduction of direct health costs associated with RVGE management. In fact, as the analysis shows, a universal vaccination against RV results in money-saving for the RHS already from the 2nd year (with a vaccination coverage of 50%). During the five year period, the active and free offer of the anti-RV vaccination would determine a total saving for RHS of about € 503.000. The cost-effectiveness analysis results showed a cost-saving ICER (incremental cost-effectiveness ratio) relevant to the RHS and equal to - €12.197/QALY. CONCLUSION: In conclusion the adoption of a universal preventive strategy for all the infants in the Piedmont Region may contribute significantly towards the control of RVGE incidence, thus allowing a noteworthy saving of economic and social resources for both the RHS and the general public.

Effects of geographic and economic heterogeneity on rotavirus diarrhea burden and vaccination impact and cost-effectiveness in the Lao People's Democratic Republic.

Rotavirus enteritis is responsible for nearly 200,000 child deaths worldwide in 2015. Globally, many low- and middle-income countries have introduced rotavirus vaccine, resulting in documented reductions in hospitalizations and child mortality. We examined the potential impact and cost-effectiveness of introducing rotavirus vaccination in Lao People's Democratic Republic using an Excel-based spreadsheet model. We estimated mortality risk factors, patterns of care seeking, and vaccination access to predict outcomes for regional, provincial, and socioeconomic subpopulations for one birth cohort through their first five years of life and life course in Disability-Adjusted Life Years estimates. Socioeconomic status was defined by categorizing households into regional wealth quintiles based on a national asset index. We modeled a two-dose ROTARIX vaccine under current Gavi pricing and efficacy estimates from Bangladesh and Vietnam. DPT1 and DPT2 coverages were used to estimate rotavirus vaccination coverage. Probabilistic sensitivity analysis was used to assess the impact of uncertainty on model parameters on predicted incremental cost-effectiveness ratios (ICERs), including scenarios of increases in vaccination coverage. Rotavirus vaccination would prevent 143 child deaths/year, or 28% of annual rotavirus burden. The estimated national level ICER for rotavirus vaccination was $140/DALY, with regional socioeconomic subpopulation estimates ranging from $72/DALY for the poorest in the Central region to $353/DALY for the richest in the North region, indicating high cost-effectiveness. Within regions, ICERs are most favorable for children in the poorer and poorest quintiles. However, the full benefits of rotavirus vaccination will only be realized by reducing disparities in vaccination coverage, access to treatment, and environmental health. Improving vaccination coverage to equitable levels alone would prevent 87 additional child deaths per year.

Potential impact and cost-effectiveness of rotavirus vaccination in Afghanistan.

INTRODUCTION: Despite progress made in child survival in the past 20 years, 5.9 million children under five years died in 2015, with 9% of these deaths due to diarrhea. Rotavirus is responsible for more than a third of diarrhea deaths. In 2013, rotavirus was estimated to cause 215,000 deaths among children under five years, including 89,000 in Asia. As of April 2017, 92 countries worldwide have introduced rotavirus vaccination in their national immunization program. Afghanistan has applied for Gavi support to introduce rotavirus vaccination nationally. This study estimates the potential impact and cost-effectiveness of a national rotavirus immunization program in Afghanistan. METHODS: This study examined the use of Rotarix® (RV1) administered using a two-dose schedule at 6 and 10 weeks of age. We used the ProVac Initiative's UNIVAC model (version 1.2.09) to evaluate the impact and cost-effectiveness of a rotavirus vaccine program compared with no vaccine over ten birth cohorts from 2017 to 2026 with a 3% annual discount rate. All monetary units are adjusted to 2017 US$. RESULTS: Rotavirus vaccination in Afghanistan has the potential to avert more than one million cases; 660,000 outpatient visits; approximately 50,000 hospital admissions; 650,000 DALYs; and 12,000 deaths, over 10 years. Not accounting for any Gavi subsidy, rotavirus vaccination can avert DALYs at US$82/DALY from the government perspective and US$80/DALY from the societal perspective. With Gavi support, DALYs can be averted at US$29/DALY and US$31/DALY from the societal and government perspective, respectively. The average yearly cost of a rotavirus vaccination program would represent 2.8% of the total immunization budget expected in 2017 and 0.1% of total health expenditure. CONCLUSION: The introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy.

Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England.

BACKGROUND: As part of the national seasonal influenza vaccination programme in England and Wales, children receive a quadrivalent vaccine offering protection against two influenza A strains and two influenza B strains. Healthy children receive a quadrivalent live attenuated influenza vaccine (QLAIV), whilst children with contraindications receive the quadrivalent inactivated influenza vaccine (QIIV). Individuals aged younger than 65 years in the clinical risk populations and elderly individuals aged 65+ years receive either a trivalent inactivated influenza vaccine (TIIV) offering protection from two A strains and one B strain or the QIIV at the choice of their general practitioner. The cost-effectiveness of quadrivalent vaccine programmes is an open question. The original analysis that supported the paediatric programme only considered a trivalent live attenuated vaccine (LAIV). The cost-effectiveness of the QIIV to other patients has not been established. We sought to estimate the cost-effectiveness of these programmes, establishing a maximum incremental total cost per dose of quadrivalent vaccines over trivalent vaccines. METHODS: We used the same mathematical model as the analysis that recommended the introduction of the paediatric influenza vaccination programme. The incremental cost of the quadrivalent vaccine is the additional cost over that of the existing trivalent vaccine currently in use. RESULTS: Introducing quadrivalent vaccines can be cost-effective for all targeted groups. However, the cost-effectiveness of the programme is dependent on the choice of target cohort and the cost of the vaccines: the paediatric programme is cost-effective with an increased cost of £6.36 per dose, though an extension to clinical risk individuals younger than 65 years old and further to all elderly individuals means the maximum incremental cost is £1.84 and £0.20 per dose respectively. CONCLUSIONS: Quadrivalent influenza vaccines will bring substantial health benefits, as they are cost-effective in particular target groups.

Impact of self-financed rotavirus vaccines on hospital stays and costs in Spain after a 3-year introductory period.

Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low-moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003-2005)- and post-vaccine (2007-2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007-2009 (ß-coefficient = -0·43, 95% confidence intervals (95% CI) -0·68 to -0·17; and odds ratio 0·62, 95% CI 0·50-0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI -365 to -123); the decrease in DRG group III was €2269 per patient (95% CI -4098 to -380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.

Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

BACKGROUND: Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. METHODS AND FINDINGS: The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines. CONCLUSIONS: Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.

Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

BACKGROUND: Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. METHODS: An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo. RESULTS: In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. CONCLUSIONS: RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

Validation of current procedural terminology codes for rotavirus vaccination among infants in two commercially insured US populations.

PURPOSE: We validated procedure codes used in health insurance claims for reimbursement of rotavirus vaccination by comparing claims for monovalent live-attenuated human rotavirus vaccine (RV1) and live, oral pentavalent rotavirus vaccine (RV5) to medical records. METHODS: Using administrative data from two commercially insured United States populations, we randomly sampled vaccination claims for RV1 and RV5 from a cohort of infants aged less than 1 year from an ongoing post-licensure safety study of rotavirus vaccines. The codes for RV1 and RV5 found in claims were confirmed through medical record review. The positive predictive value (PPV) of the Current Procedural Terminology codes for RV1 and RV5 was calculated as the number of medical record-confirmed vaccinations divided by the number of medical records obtained. RESULTS: Medical record review confirmed 92 of 104 RV1 vaccination claims (PPV: 88.5%; 95% CI: 80.7-93.9%) and 98 of 113 RV5 vaccination claims (PPV: 86.7%; 95% CI: 79.1-92.4%). Among the 217 medical records abstracted, only three (1.4%) of vaccinations were misclassified in claims-all were RV5 misclassified as RV1. The medical records corresponding to 9 RV1 and 15 RV5 claims contained insufficient information to classify the type of rotavirus vaccine. CONCLUSIONS: Misclassification of rotavirus vaccines is infrequent within claims. The PPVs reported here are conservative estimates as those with insufficient information in the medical records were assumed to be incorrectly coded in the claims. Copyright © 2016 John Wiley & Sons, Ltd.

[Economic evaluation on different two-dose-vaccination-strategies related to Measles, Mumps and Rubella Combined Attenuated Live Vaccine].

OBJECTIVE: To evaluate the economic effect of Measles, Mumps and Rubella Combined Attenuated Live Vaccine (MMR) under different two-dose vaccination programs. METHODS: A hypothetical birth cohort of 750 000 infants over their lifetime, was followed up from birth through death in Zhejiang province. The current MMR vaccination strategie would include three different ones: 1) Childlern were vaccinated with Measles-Rubella Combined Attenuated Live Vaccine and MMR, respectively at the age of 8 months and 18 months. 2) Children receive MMR at 8 months and 18 months, 3) Strategy 1 plus an additional vaccination of MMR at 4 years of age. Incremental cost-effectiveness ratio (ICER), incremental cost-benefit ratio (ICBR) and incremental net benefit (INB) were applied to calculate the health economic difference for Strategy 2 and Strategy 3 as compared to Strategy 1. Univariate sensitivity analysis was used to assess the robustness of results with main parameters, including the rate of immunization coverage, effectiveness of the vaccines, incidence and burdens of the related diseases, cost of vaccines and the vaccination program itself. RESULTS: ICER, ICBR and INB for Strategy 2 and Strategy 3 appeared as 2 012.51∶1 RMB Yuan per case and 4 238.72∶1 RMB Yuan per case, 1∶3.14 and 1∶1.58, 21 277 800 RMB Yuan and 9 276 500 RMB Yuan, respectively. Only slight changes (<20%) were found under the univariate sensitivity analysis, with varied values on main parameters. CONCLUSION: Based on the current national immunization program, infants vaccinated with MMR at 8 months of age, generated more health economic effects than the Strategy 3.

The Clinical Impact and Cost Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in Finland.

BACKGROUND: Trivalent influenza vaccines encompass one influenza B lineage; however, predictions have been unreliable on which of two antigenically distinct circulating lineages will dominate. Quadrivalent seasonal influenza vaccines contain strains from both lineages. This analysis assesses the cost effectiveness of switching from trivalent inactivated influenza vaccination (TIV) in Finland to quadrivalent vaccination, using inactivated (QIV) or live-attenuated (Q-LAIV) vaccines. METHODS: A transmission model simulated the dynamics of influenza infection while accounting for indirect (herd) protection. Prior distributions for key transmission parameters were repeatedly sampled and simulations that fitted the available information on influenza in Finland were recorded. The resulting posterior parameter distributions were used in a probabilistic sensitivity analysis in which economic parameters were sampled, simultaneously encompassing uncertainty in the transmission and economic parameters. The cost effectiveness of a range of trivalent and quadrivalent vaccine policies over a 20-year time horizon was assessed from both a societal and payer perspective in 2014 Euros. RESULTS: The simulated temporal incidence pattern of symptomatic infections corresponded well with case surveillance data. A switch from the current TIV to Q-LAIV in children (2 to <18 years) and to QIV in other ages was estimated to annually avert approximately 76,100 symptomatic infections (95 % range 36,700-146,700), 11,500 primary care consultations (6100-20,000), 540 hospitalisations (240-1180), and 72 deaths (32-160), and was cost-saving relative to TIV (€374 million averted [€161-€752], in 2014 Euros, discounted at 3 %). This scenario had the highest probability of being the most cost-effective scenario considered. CONCLUSIONS: This analysis demonstrates that quadrivalent vaccination is expected to be highly cost effective, reducing the burden of influenza-related disease.