Impact,cost-effectiveness,and budget implications of HPV vaccination in Kenya: A modelling study

BackgroundSub-Saharan Africa has the highest rate of cervical cancer cases and deaths worldwide. Kenya introduced a quadrivalent HPV vaccine (GARDASIL, hereafter referred to as GARDASIL-4) for ten-year-old girls in late 2019 with donor support from Gavi, the Vaccine Alliance. As Kenya may soon graduate from Gavi support, it is important to evaluate the potential cost-effectiveness and budget impact of the current HPV vaccine, and potential alternatives.MethodsWe used a proportionate outcomes static cohort model to evaluate the annual budget impact and lifetime cost-effectiveness of vaccinating ten-year-old girls over the period 2020–2029. We included a catch-up campaign for girls aged 11–14 years in 2020. We estimated cervical cancer cases, deaths, disability adjusted life years (DALYs), and healthcare costs (government and societal perspective) expected to occur with and without vaccination over the lifetimes of each cohort of vaccinated girls. For each of the four products available globally (CECOLIN©, CERVARIX©, GARDASIL-4©, and GARDASIL-9 ©), we estimated the cost (2021 US$) per DALY averted compared to no vaccine and to each other. Model inputs were obtained from published sources, as well as local stakeholders.ResultsWe estimated 320,000 cases and 225,000 deaths attributed to cervical cancer over the lifetimes of the 14 evaluated birth cohorts. HPV vaccination could reduce this burden by 42–60 %. Without cross-protection, CECOLIN had the lowest net cost and most attractive cost-effectiveness. With cross-protection, CERVARIX was the most cost-effective. Under either scenario the most cost-effective vaccine had a 100 % probability of being cost-effective at a willingness-to-pay threshold of US$ 100 (5 % of Kenya’s national gross domestic product per capita) compared to no vaccination. Should Kenya reach its target of 90 % coverage and graduate from Gavi support, the undiscounted annual vaccine program cost could exceed US$ 10 million per year. For all three vaccines currently supported by Gavi, a single-dose strategy would be cost-saving compared to no vaccination.ConclusionHPV vaccination for girls is highly cost-effective in Kenya. Compared to GARDASIL-4, alternative products could provide similar or greater health benefits at lower net costs. Substantial government funding will be required to reach and sustain coverage targets as Kenya graduates from Gavi support. A single dose strategy is likely to have similar benefits for less cost.     

Potential health impact and cost-effectiveness of bivalent human papillomavirus (HPV) vaccination in Afghanistan

IntroductionHuman papillomavirus (HPV) vaccination has not been introduced in many countries in South-Central Asia, including Afghanistan, despite the sub-region having the highest incidence rate of cervical cancer in Asia. This study estimates the potential health impact and cost-effectiveness of HPV vaccination in Afghanistan to inform national decision-making.MethodAn Excel-based static cohort model was used to estimate the lifetime costs and health outcomes of vaccinating a single cohort of 9-year-old girls in the year 2018 with the bivalent HPV vaccine, compared to no vaccination. We also explored a scenario with a catch-up campaign for girls aged 10–14 years. Input parameters were based on local sources, published literature, or assumptions when no data was available. The primary outcome measure was the discounted cost per disability-adjusted life-year (DALY) averted, evaluated from both government and societal perspectives.ResultsVaccinating a single cohort of 9-year-old girls against HPV in Afghanistan could avert 1718 cervical cancer cases, 125 hospitalizations, and 1612 deaths over the lifetime of the cohort. The incremental cost-effectiveness ratio was US$426 per DALY averted from the government perspective and US$400 per DALY averted from the societal perspective. The estimated annual cost of the HPV vaccination program (US$3,343,311) represents approximately 3.53% of the country′s total immunization budget for 2018 or 0.13% of total health expenditures.ConclusionIn Afghanistan, HPV vaccine introduction targeting a single cohort is potentially cost-effective (0.7 times the GDP per capita of $586) from both the government and societal perspective with additional health benefits generated by a catch-up campaign, depending on the government′s willingness to pay for the projected health outcomes.     

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh

IntroductionDiarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners.MethodsThis analysis used Pan American Health Organization’s TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates.ResultsOver ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted.ConclusionThe discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh.     

Cost-effectiveness of rotavirus vaccination in Mozambique

IntroductionRotavirus is one of the most common cause of severe gastroenteritis in children, with the largest mortality burden in low- and middle-income countries. To prevent rotavirus gastroenteritis, Mozambique introduced ROTARIX® vaccine in 2015, however, its cost-effectiveness has never been established in the country. In 2018, additional vaccines became available globally. This study estimates the cost-effectiveness of the recently introduced ROTARIX in Mozambique and compares the cost-effectiveness of ROTARIX®, ROTAVAC®, and ROTASIIL® to inform future use.MethodsWe used a decision-support model to calculate the potential cost-effectiveness of vaccination with ROTARIX compared to no vaccination over a five-year period (2016–2020) and to compare the cost-effectiveness of ROTARIX, ROTAVAC, and ROTASIIL to no vaccination and to each other over a ten-year period (2021–2030). The primary outcome was the incremental cost per disability-adjusted life-year (DALY) averted from a government perspective. We assessed uncertainty through sensitivity analyses.ResultsFrom 2016 to 2020, we estimate the vaccine program with ROTARIX cost US$12.3 million, prevented 4,628 deaths, and averted US$3.1 million in healthcare costs. The cost per DALY averted was US$70. From 2021 to 2030, we estimate all three vaccines could prevent 9,000 deaths and avert US$7.8 million in healthcare costs. With Global Alliance for Vaccines and Immunization (Gavi) support, ROTARIX would have the lowest vaccine program cost (US$31 million) and 98 % probability of being cost-effective at a willingness-to-pay threshold of 0.5x GDP per capita. Without Gavi support, ROTASIIL would have the lowest vaccine program cost (US$75.8 million) and 30 % probability of being cost-effective at the same threshold.ConclusionROTARIX vaccination had a substantial public health impact in Mozambique between 2016 and 2020. ROTARIX is currently estimated to be the most cost-effective product, but the choice of vaccine should be re-evaluated as more evidence emerges on the price, incremental delivery cost, wastage, and impact associated with each of the different rotavirus vaccines.     

Potential impact and cost-effectiveness of rotavirus vaccination in Afghanistan

IntroductionDespite 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.MethodsThis 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$.ResultsRotavirus 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.ConclusionThe introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy.     

Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia

ObjectiveThe Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia.MethodsThe incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3 + 0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance’s advance market commitment tail price.ResultsThe ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025.ConclusionIntroducing PCV13 as part of Mongolia’s national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction.     

Cost-effectiveness of rotavirus vaccination in Ghana: Examining impacts from 2012 to 2031

BackgroundDiarrhea causes about 10% of all deaths in children under five years globally, with rotavirus causing about 40% of all diarrhea deaths. Ghana introduced rotavirus vaccination as part of routine immunization in 2012 and it has been shown to be effective in reducing disease burden in children under five years. Ghana’s transition from low to lower-middle income status in 2010 implies fewer resources from Gavi as well as other major global financing mechanisms. Ghana will soon bear the full cost of vaccines. The aim of this study was to estimate the health impact, costs and cost-effectiveness of rotavirus vaccination in Ghana from introduction and beyond the Gavi transition.MethodsThe TRIVAC model is used to estimate costs and effects of rotavirus vaccination from 2012 through 2031. Model inputs include demographics, disease burden, health system structure, health care utilization and costs as well as vaccine cost, coverage, and efficacy. Model inputs came from local data, the international literature and expert consultation. Costs were examined from the health system and societal perspectives.ResultsThe results show that continued rotavirus vaccination could avert more than 2.2 million cases and 8900 deaths while saving US$6 to US$9 million in costs over a 20-year period. The net cost of vaccination program is approximately US$60 million over the same period. The societal cost per DALY averted is US$238 to US$332 with cost per case averted ranging from US$27 to US$38. The cost per death averted is approximately US$7000.ConclusionThe analysis shows that continued rotavirus vaccination will be highly cost-effective, even for the period during which Ghana will assume responsibility for purchasing vaccines after transition from Gavi support.     

Cost-effectiveness analysis of the nonavalent human papillomavirus vaccine for the prevention of cervical cancer in Singapore

BackgroundThe nonavalent human papillomavirus (HPV) vaccine has been shown to extend protection against oncogenic HPV types 31/33/45/52/58 (HPV-OV) not covered by the bivalent and quadrivalent HPV vaccines. Besides its clinical benefit, evidence on the economic value of the nonavalent vaccine is required to inform local vaccination strategies and funding decisions. This study evaluated the cost-effectiveness of replacing the bivalent vaccine with the nonavalent vaccine in the national school-based HPV vaccination programme in Singapore.MethodsAn existing age-structured dynamic transmission model coupled with stochastic individual-based simulations was adapted to project the health and economic impact of vaccinating 13-year-old girls with two doses of the nonavalent or bivalent HPV vaccines in Singapore. Direct costs (in Singapore dollars, S$) were obtained from public healthcare institutions in Singapore, while health state utilities were sourced from the literature. Incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime horizon, from a healthcare system perspective. Probabilistic sensitivity analysis was performed to obtain the ICERs and corresponding variations across variable uncertainty. Particularly, this study tested the scenarios of lifelong and 20-year vaccine-induced protection, assumed 96.0% and 22.3% cross-protection against HPV-OV by nonavalent and bivalent vaccines respectively, and fixed vaccine prices per dose at S$188 for nonavalent and S$61.50 for bivalent vaccines.ResultsCompared with the bivalent vaccine, the use of the nonavalent vaccine was associated with an ICER of S$61,629 per quality-adjusted life year gained in the base case. The result was robust across a range of plausible input values, and to assumptions regarding the duration of vaccine protection.ConclusionGiven the high ICER, the nonavalent vaccine is unlikely to represent a cost-effective option compared with the bivalent vaccine for school-based HPV vaccination of 13-year old female students in Singapore. Substantial price reductions would be required to justify its inclusion in the school-based programme in the future.     

Cost-effectiveness of human papillomavirus vaccination in Germany

Background

The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model.

Methods

Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys.

Results

From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls.

Conclusions

Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.

     

The cost-effectiveness of human papillomavirus vaccination in the Philippines

Cervical cancer is the second most common cancer among women in the Philippines. Human papillomavirus (HPV) vaccination provides protection from the most common cancer-causing HPV types. This analysis used a proportionate outcomes model to estimate the potential cost-effectiveness of four different HPV vaccine products—Cervarix?, Cecolin®, GARDASIL®, and GARDASIL®9—for routine HPV vaccination of 10 cohorts of 9-year-old girls from the government and societal perspectives. Model parameters included cervical cancer burden, healthcare and program costs, vaccine efficacy with and without potential cross-protection, and vaccination coverage. Univariate and probabilistic sensitivity analyses evaluated the impact of uncertainty on model results. Compared to no vaccination, HPV programs with Cecolin®, Cervarix?, and GARDASIL® are projected to be cost-effective at US$1,210, US$1,300, and US$2,043 per DALY averted, respectively, from the government perspective, and at US$173, US$263, and US$1,006 per DALY averted, respectively, from the societal perspective when cross-protection was considered. When direct comparisons were made across vaccines, GARDASIL® was dominated by Cervarix? and Cecolin®. In a scenario where cross-protection was not considered, results were similar except that Cervarix? and GARDASIL® were both dominated by Cecolin®. GARDASIL®9 was not cost-effective under any of the modeled scenarios.     

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.

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis

BackgroundRotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries.MethodsBeginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars.ResultsVaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147–$38,993) and ranged from $85 per DALY averted (95% UI: $13–$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030–$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39–$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382–$3,118).ConclusionOur findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.     

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage

BackgroundEstonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening.MethodsA Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN 1–3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88 years (up to 100 years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%.ResultsVaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367–21,711, €5142–21,800 and €4563–18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage.ConclusionVaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used.     

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.     

Cost-utility analysis of dengue vaccination in a country with heterogeneous risk of dengue transmission

BackgroundDengue is one of the most important vector-borne diseases worldwide, and annually, nearly 390 million people are infected and 500,000 patients are hospitalized for severe dengue. Argentina has great variability in the risk of dengue transmission due to eco-climatic reasons. Currently no vaccines are available for dengue even though several vaccines are under development.ObjectiveThe aim of this study was to estimate the cost-effectiveness of a dengue vaccine in a country with heterogeneous risk of dengue transmission like Argentina.MethodsThe analysis was carried out from a societal perspective using a Markov model that included both vaccine and disease parameters. Utility was measured as disability adjusted life years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) of the vaccination was expressed in 2014 American dollars (US$) per DALY averted. One-way and probabilistic sensitivity analyses were performed to evaluate uncertainty in model outcomes, and a threshold analysis was conducted to estimate the highest possible price of the vaccine.ResultsThe ICER of the vaccination program was found to be US$ 5714 per DALY averted. This value is lower than 3 times the per capita GDP of Argentina (US$ 38,619 in 2014); 54.9% of the simulations were below this value. If a vaccination program would be implemented the maximum vaccine price per dose has to be US$1.49 for a vaccination at national level or US$28.72 for a targeted vaccination in high transmission areas.ConclusionsThese results demonstrate that vaccination against dengue would be cost-effective in Argentina, especially if carried out in predetermined regions at high risk of dengue transmission. However, these results should be interpreted with caution because the probabilistic sensitivity analysis showed that there was considerable uncertainty around the ICER value. The influence of variations in vaccine efficacy, cost and other important parameters are discussed in the text.     

Cost-effectiveness analyses of monovalent mumps vaccination programs for Japanese children

BackgroundThe most common preventative measure against mumps is vaccination with mumps vaccine. Over 122 countries have implemented mumps vaccine routine immunization programs, mostly via Measles-Mumps-Rubella (MMR) vaccine. In Japan, the unexpectedly high incidence of aseptic meningitis caused by mumps vaccine led to the discontinuation of the MMR national vaccination program in 1993, inadvertently resulting in the re-emergence of mumps. Plans of introducing monovalent mumps vaccine into routine vaccination schedule have become one of the emerging topics in health policy that has warranted the need in evaluating its value for money.MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios (ICERs) of two different vaccination programs (a single-dose program at one-year-old, a two-dose program with second dose uptakes at five) compared to status quo from both payers’ and societal perspectives. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. Costs per vaccination were assumed at ¥6140 (US$58;1US$ = ¥106).ResultsBoth programs reduce disease treatment costs compared to status quo, while the reduction cannot offset vaccination cost. ICER of either program is found to be under ¥5,000,000 (US$47,170)/QALY willingness-to-pay (WTP) threshold from either perspective. Results of probabilistic sensitivity analyses expressed by net monetary benefit indicated that at the WTP threshold, the acceptability is at 92.6% for two-dose vaccination program, 0% for single-dose vaccination program, and 7.4% for current no vaccination program. Two-dose program was optimal among the alternatives. One-way sensitivity analyses revealed that proportion of mumps-related hearing loss among mumps cases and vaccine effectiveness (VE) were key variables in changing the ICERs.ConclusionRoutine vaccination program of single- and two-dose programs were cost-effective from both payers’ and societal perspectives. Between the two, the two-dose vaccination program was observed to be more favorable.     

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

IntroductionDiarrhea 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 methodsWe 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.ResultsThe 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®.ConclusionCountries 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.     

The cost-effectiveness of alternative polio immunization policies in South Africa

AIMS: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. METHODS: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. CONCLUSIONS: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39.     

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.     

Prevention of hepatitis B mother-to-child transmission in Namibia: A cost-effectiveness analysis

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model’s outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.