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 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.     

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.     

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 the introduction of two-dose bi-valent (Cervarix) and quadrivalent (Gardasil) HPV vaccination for adolescent girls in Bangladesh

BackgroundCervical cancer is one of the most prevalent cancers in women caused by the human papillomavirus (HPV) that leads to a substantial disease burden for health systems. Prevention through vaccination can significantly reduce the prevalence of cervical cancer. The objective of this study is to evaluate the potential health and economic impacts of introducing two-dose bivalent (Cervarix) and quadrivalent (Gardasil) HPV vaccines in Bangladesh.MethodsThe study uses the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess the cost-effectiveness of introducing HPV vaccination. The incremental cost-effectiveness ratios (ICERs) were estimated per disability-adjusted life years (DALYs) averted using the cost-effectiveness threshold (CET). The analyses were done from a health system perspective in terms of vaccine delivery routes.ResultsIntroduction of bi-valent HPV vaccination was found highly cost-effective (ICER = US$488/DALY) at Gavi (The Vaccine Alliance for Vaccines and Immunizations) negotiated prices. The value of ICERs were US$710, US$356 and US$397 per DALY averted for school-based, health facility-based, and outreach-based programs, respectively, which is consistent with the CET range (US$67 to US$854). However, bivalent and quadrivalent vaccines at listed prices were not found cost-effective, with ICERs of US$1405 and US$3250 per DALY averted, respectively, that exceeds the CETs values.ConclusionsIntroducing a two-dose bi-valent HPV vaccination program is cost-effective in Bangladesh at Gavi negotiated prices. Vaccine price is the dominating parameter for the cost-effectiveness of bivalent and quadrivalent vaccines. Both vaccines are not cost-effective at listed prices in Bangladesh. The evaluation highlights that introducing the two-dose bivalent HPV vaccine at Gavi negotiated prices into a national immunization program in Bangladesh is economically viable to reduce the burden of cervical cancer.     

Cost-effectiveness of Haemophilus influenzae type b vaccine in Vietnam

BackgroundWith GAVI support, Vietnam introduced Haemophilus influenzae type b (Hib) vaccine in 2010 without evidence on cost-effectiveness. We aimed to analyze the cost-effectiveness of Hib vaccine from societal and governmental perspectives.MethodWe constructed a decision-tree cohort model to estimate the costs and effectiveness of Hib vaccine versus no Hib vaccine for the 2011 birth cohort. The disease burden was estimated from local epidemiologic data and literature. Vaccine delivery costs were calculated from governmental reports and 2013 vaccine prices. A prospective cost-of-illness study was conducted to estimate treatment costs. The human capital approach was employed to estimate productivity loss. The incremental costs of Hib vaccine were divided by cases, deaths, and disability-adjusted life years (DALY) averted. We used the WHO recommended cost-effectiveness thresholds of an intervention being highly cost-effective if incremental costs per DALY were below GDP per capita.ResultFrom the societal perspective, incremental costs per discounted case, death and DALY averted were US$ 6252, US$ 26,476 and US$ 1231, respectively; the break-even vaccine price was US$ 0.69/dose. From the governmental perspective, the results were US$ 6954, US$ 29,449, and US$ 1373, respectively; the break-even vaccine price was US$ 0.48/dose. Vietnam's GDP per capita was US$ 1911 in 2013. In deterministic sensitivity analysis, morbidity and mortality parameters were among the most influential factors. In probabilistic sensitivity analysis, Hib vaccine had an 84% and 78% probability to be highly cost-effective from the societal and governmental perspectives, respectively.ConclusionHib vaccine was highly cost-effective from both societal and governmental perspectives. However, with GAVI support ending in 2016, the government will face a six-fold increase in its vaccine budget at the 2013 vaccine price. The variability of vaccine market prices adds an element of uncertainty. Increased government commitment and improved resource allocation decision making will be necessary to retain Hib vaccine.     

Economic evaluation of hepatitis B vaccination in low-income countries: using cost-effectiveness affordability curves

OBJECTIVE: We sought to describe a method that explicitly considers both a health-care programmes cost-effectiveness and its affordability. For illustration, we apply the method to the programme to vaccinate infants against hepatitis B in the Gambia. METHODS: We synthesized selected data and developed a computer-based model from the societal and payer perspectives to evaluate the cost-effectiveness of routine infant vaccination against hepatitis B in the Gambia compared with no vaccination. The primary outcome measure was cost per averted disability-adjusted life year (DALY), which was expressed in 2002 US dollars. We used Monte Carlo methods for uncertainty analysis to examine the affordability of the programme from the payers perspective, and we derived an affordability curve and cost-effectiveness affordability curves for the programme. FINDINGS: In the Gambia, vaccinating infants against hepatitis B is highly cost-effective. Compared with offering no intervention, the vaccination programme would cost US$ 28 per DALY averted from the societal perspective or US$ 47 per DALY averted from the payers perspective. The programme also has the potential to be affordable, starting at a relatively low budget of US$ 160,000 per year. Combining the two dimensions of the outcome measure, the probability that vaccinating infants would be both cost-effective and affordable is 40% at an annual programme budget of US$ 182,000 (the estimated total programme cost from the payers perspective), given a threshold cost-effectiveness value of US$ 47 per DALY averted. CONCLUSION: In the face of uncertainties about both the health and economic consequences of a vaccine programme, as well as the availability and magnitude of resources needed to fund the programme, cost-effectiveness affordability curves can provide information to decision-makers about the probability that a programme will be both cost-effective and affordable: these are distinct but equally relevant considerations in resource-poor settings.     

Economic evaluation of typhoid vaccination in a prolonged typhoid outbreak setting: The case of Kasese district in Uganda

BackgroundVaccination has been increasingly promoted to help control epidemic and endemic typhoid fever in high-incidence areas. Despite growing recognition that typhoid incidence in some areas of sub-Saharan Africa is similar to high-incidence areas of Asia, no large-scale typhoid vaccination campaigns have been conducted there. We performed an economic evaluation of a hypothetical one-time, fixed-post typhoid vaccination campaign in Kasese, a rural district in Uganda where a large, multi-year outbreak of typhoid fever has been reported.MethodsWe used medical cost and epidemiological data retrieved on-site and campaign costs from previous fixed-post vaccination campaigns in Kasese to account for costs from a public sector health care delivery perspective. We calculated program costs and averted disability-adjusted life years (DALYs) and medical costs as a result of vaccination, to calculate the cost of the intervention per DALY and case averted.ResultsOver the 3 years of projected vaccine efficacy, a one-time vaccination campaign was estimated to avert 1768 (90%CI: 684–4431) typhoid fever cases per year and a total of 3868 (90%CI: 1353–9807) DALYs over the duration of the immunity conferred by the vaccine. The cost of the intervention per DALY averted was US$ 484 (90%CI: 18–1292) and per case averted US$ 341 (90%CI: 13–883).ConclusionWe estimated the vaccination campaign in this setting to be highly cost-effective, according to WHO's cost-effective guidelines. Results may be applicable to other African settings with similar high disease incidence estimates.     

Japanese encephalitis vaccination in the Philippines: A cost-effectiveness analysis comparing alternative delivery strategies

IntroductionJapanese encephalitis (JE) is a mosquito-borne viral infection of the brain that can cause permanent brain damage and death. In the Philippines, efforts are underway to deliver a live attenuated JE vaccine (CD-JEV) to children under five years of age (YOA), who are disproportionately infected. Multiple vaccination strategies are being considered.MethodsWe conducted a cost-effectiveness analysis comparing three vaccination strategies to the current state of no vaccination from the societal and government perspectives: (1) national routine vaccination only, (2) sub-national campaign followed by national routine, and (3) national campaign followed by national routine. We developed a Markov model to estimate impact of vaccination or no vaccination over the child’s lifetime horizon, assuming an annual incidence of 10.6 cases per 100,000.Costs of illness ($859/case), vaccine ($0.50/dose), routine vaccination ($0.95/dose), and campaign vaccination ($0.98/dose) were based on hospital financial records, expert opinion and literature. The societal perspective included transportation and opportunity costs of caregiver time, in addition to costs incurred by the health system.ResultsJE vaccination via national campaign followed by national routine delivery was the most cost-effective strategy modeled with a cost per disability adjusted life year (DALY) averted of $233 and $29 from the government and societal perspectives, respectively. Results were similar for other delivery strategies with cost/DALY ranging from $233 to $265 from the government perspective and $29–$57 from the societal perspective. JE vaccination was projected to prevent 27,856–37,277 cases, 5571–7455 deaths, and 173,233–230,704 DALYs among children under five over 20 consecutive birth cohorts. Total incremental costs of vaccination versus no vaccination over 20 birth cohorts were $6.6–$9.8 million from the societal perspective ($230 K–$440 K annually) and $45.9–$53.9 million ($2.2 M–$2.7 M annually) from the governmental perspective.ConclusionVaccination with CD-JEV in the Philippines is projected to be cost-effective, reducing long-term costs associated with JE illness and improving health outcomes compared to no vaccination.     

Cost-effectiveness of dengue vaccination in ten endemic countries

Following publication of results from two phase-3 clinical trials in 10 countries or territories, endemic countries began licensing the first dengue vaccine in 2015. Using a published mathematical model, we evaluated the cost-effectiveness of dengue vaccination in populations similar to those at the trial sites in those same Latin American and Asian countries. Our main scenarios (30-year horizon, 80% coverage) entailed 3-dose routine vaccinations costing US$20/dose beginning at age 9, potentially supplemented by catch-up programs of 4- or 8-year cohorts. We obtained illness costs per case, dengue mortality, vaccine wastage, and vaccine administration costs from the literature. We estimated that routine vaccination would reduce yearly direct and indirect illness cost per capita by 22% (from US$10.51 to US$8.17) in the Latin American countries and by 23% (from US$5.78 to US$4.44) in the Asian countries. Using a health system perspective, the incremental cost-effectiveness ratio (ICER) averaged US$4,216/disability-adjusted life year (DALY) averted in the five Latin American countries (range: US$666/DALY in Puerto Rico to US$5,865/DALY in Mexico). In the five Asian countries, the ICER averaged US$3,751/DALY (range: US$1,935/DALY in Malaysia to US$5,101/DALY in the Philippines). From a health system perspective, the vaccine proved to be highly cost effective (ICER under one times the per capita GDP) in seven countries and cost effective (ICER 1–3 times the per capita GDP) in the remaining three countries. From a societal perspective, routine vaccination proved cost-saving in three countries. Including catch-up campaigns gave similar ICERs. Thus, this vaccine could have a favorable economic value in sites similar to those in the trials.     

Human health benefits from livestock vaccination for brucellosis: case study

OBJECTIVE: To estimate the economic benefit, cost-effectiveness, and distribution of benefit of improving human health in Mongolia through the control of brucellosis by mass vaccination of livestock. METHODS: Cost-effectiveness and economic benefit for human society and the agricultural sector of mass vaccination against brucellosis was modelled. The intervention consisted of a planned 10-year livestock mass vaccination campaign using Rev-1 livestock vaccine for small ruminants and S19 livestock vaccine for cattle. Cost-effectiveness, expressed as cost per disability-adjusted life year (DALY) averted, was the primary outcome. FINDINGS: In a scenario of 52% reduction of brucellosis transmission between animals achieved by mass vaccination, a total of 49,027 DALYs could be averted. Estimated intervention costs were US$ 8.3 million, and the overall benefit was US$ 26.6 million. This results in a net present value of US$ 18.3 million and an average benefit-cost ratio for society of 3.2 (2.27-4.37). If the costs of the intervention were shared between the sectors in proportion to the benefit to each, the public health sector would contribute 11%, which gives a cost-effectiveness of US$ 19.1 per DALY averted (95% confidence interval 5.3-486.8). If private economic gain because of improved human health was included, the health sector should contribute 42% to the intervention costs and the cost-effectiveness would decrease to US$ 71.4 per DALY averted. CONCLUSION: If the costs of vaccination of livestock against brucellosis were allocated to all sectors in proportion to the benefits, the intervention might be profitable and cost effective for the agricultural and health sectors.     

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 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.     

Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness

Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10–46 % over a 10-year time horizon under an optimistic scenario (95 % initial vaccine efficacy and 19-year mean duration of protection), and by 2–16 % under a pessimistic scenario (82 % initial efficacy and 6-year mean protection). Adding a catch-up campaign predicted a reduction in incidence of 36–90 % and 6–35 % in the optimistic and pessimistic scenarios, respectively. Vaccine impact was predicted to decrease as the relative contribution of chronic carriers to transmission increased. Models A-C all predicted routine vaccination with or without a catch-up campaign to be cost-effective compared to no vaccination, with ICERs varying from $95–789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata.     

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.     

Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries

The risk of dying from cervical cancer is disproportionately borne by women in developing countries. Two new vaccines are highly effective in preventing HPV 16,18 infection, responsible for approximately 70% of cervical cancer, in girls not previously infected. The GAVI Alliance (GAVI) provides technical assistance and financial support for immunization in the world's poorest countries. Using population-based and epidemiologic data for 72 GAVI-eligible countries we estimate averted cervical cancer cases and deaths, disability-adjusted years of life (DALYs) averted and incremental cost-effectiveness ratios (I$/DALY averted) associated with HPV 16,18 vaccination of young adolescent girls. In addition to vaccine coverage and efficacy, relative and absolute cancer reduction depended on underlying incidence, proportion attributable to HPV types 16 and 18, population age-structure and competing mortality. With 70% coverage, mean reduction in the lifetime risk of cancer is below 40% in some countries (e.g., Nigeria, Ghana) and above 50% in others (e.g., India, Uganda, Kenya). At I$10 per vaccinated girl (approximately $2.00 per dose assuming three doses, plus wastage, administration, program support) vaccination was cost-effective in all countries using a per capita GDP threshold; for 49 of 72 countries, the cost per DALY averted was less than I$100 and for 59 countries, it was less than I$200. Taking into account country-specific assumptions (per capita GNI, DPT3 coverage, percentage of girls who are enrolled in fifth grade) for the year of introduction, percent coverage achieved in the first year, and years to maximum coverage, a 10-year modeled scenario prevented the future deaths of approximately 2 million women vaccinated as adolescents. Despite favorable cost-effectiveness, assessment of financial costs raised concerns about affordability; as the cost per vaccinated girl was increased from I$10 to I$25 (approximately $2 to $5 per dose), the financial costs for the 10-year scenario increased from >US$ 900 million to US$ 2.25 billion. Provided high coverage of young adolescent girls is feasible, and vaccine costs are lowered, HPV 16,18 vaccination could be very cost-effective even in the poorest countries, and provide comparable value for resources to other new vaccines such as rotavirus.     

Targeted hepatitis E vaccination for women of childbearing age is cost-effective in China

BackgroundHepatitis E virus (HEV) infection is hyper-endemic in China, it is characterized with a high morbidity of fulminant hepatitis and mortality in pregnant women. The first hepatitis E vaccine, HEV 239, was licensed in China in 2011 which provides an effective preventive measure.ObjectiveTo evaluate the cost-effectiveness of vaccination with HEV 239 in women of childbearing age in China and whether HEV antibody screening should be considered before vaccination.MethodsA decision tree-Markov model was constructed to simulate HEV infection in a closed female cohort with an average first-marriage age of 25 years and evaluate health and economic outcomes of two potential vaccination strategies, direct vaccination and combined screening and vaccination, from a societal perspective. An incremental cost-effectiveness ratio (ICER, additional costs per disability-adjusted life-year (DALY) averted) was calculated for each vaccination strategy versus no vaccination and between two vaccination strategies. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of the model findings.ResultsICERs of direct vaccination and combined screening and vaccination versus no vaccination were $4040 and $3114 per DALY averted, respectively, much lower than 1-time Chinese per-capita GDP ($8127). Direct vaccination would need additional $45,455 for each DALY averted compared with combined screening and vaccination, far more than the 3-time per-capita GDP. Probabilistic sensitivity analyses confirmed our findings that two vaccination strategies would be cost-effective if the willingness-to-pay reached the 1-time per-capita GDP, and that combined screening and vaccination would be more cost-effective than direct vaccination strategy.ConclusionVaccinating women of childbearing age with HEV 239 would cost less than the 1-time per-capita GDP for each DALY averted in China, and the vaccination with a prior screening would be the optimal option.     

Cost-effectiveness of rotavirus vaccination in the Philippines: A modeling study

IntroductionRotavirus gastroenteritis (RVGE) remains a leading cause of hospitalization and death in children under five years of age in the Philippines. Rotavirus (RV) vaccination was introduced into the national immunization program (NIP) in 2012 but has since been limited to one region due to cost considerations and conflicting local cost-effectiveness estimates. Updated estimates of the cost-effectiveness of RV vaccination are required to inform prioritization of national immunization activities.MethodsWe calculated the potential costs and benefits of rotavirus vaccination over a 10-year-period (2021–2031) from a government and societal perspective, comparing four alternative rotavirus vaccines: Rotavac, Rotasiil, Rotarix and Rotateq. For each vaccine, a proportionate outcomes model was used to calculate the expected number of disease events, DALYs, vaccination program costs, and healthcare costs, with and without vaccination. The primary outcome measure was the cost per DALY averted. Assuming each product would generate similar benefits, the dominant (lowest cost) product was identified. We then calculated the cost-effectiveness (US$ per Disability Adjusted Life Year [DALY] averted) of the least costly product and compared it to willingness-to-pay thresholds of 0.5 and 1 times the national GDP per capita ($3,485), and ran deterministic and probabilistic sensitivity analyses.ResultsIntroducing any of the four rotavirus vaccines would avert around 40% of RVGE visits, hospitalizations, and deaths over the period 2021–2031. Over the same ten-year period, the incremental cost of vaccination from a government perspective was estimated to be around $104, $105, $220, and $277 million for Rotavac, Rotasiil, Rotarix and Rotateq, respectively. The equivalent cost from a societal perspective was $58, $60, $178 and $231 million. The cost-effectiveness of the least costly product (Rotavac) was $1,148 ($830–$1682) from a government perspective and $646 ($233–1277) from a societal perspective. All other products offered similar benefits but at a higher cost. There is a >99% probability that Rotavac would be cost-effective at a willingness-to-pay threshold set at 0.5 times the national GDP per capita.ConclusionBoth Rotavac and Rotasiil are likely to be cost-effective options in the Philippines, but it is not possible to say definitively which product should be preferred. Rotarix and Rotateq are expected to offer similar benefits at more cost, so would need to be priced far more competitively to be considered for introduction.     

Economic analysis for evidence-based policy-making on a national immunization program: a case of rotavirus vaccine in Thailand

Severe diarrhea caused by rotavirus is a health problem worldwide, including Thailand. The World Health Organization has recommended incorporating rotavirus vaccination into national immunization programs. This policy has been implemented in several countries, but not in Thailand where the mortality rate is not high. This leads to the question of whether it would be cost-effective to implement such a policy. The Thai National Vaccine Committee, through the Immunization Practice Subcommittee, has conducted an economic analysis. Their study aimed to estimate the costs of rotavirus diarrhea and of a rotavirus vaccination program, and the cost-effectiveness of such a program including budget impact analysis. The study was designed as an economic evaluation, employing modeling technique in both provider and societal perspectives. A birth cohort of Thai children in 2009 was used in the analysis, with a 5-year time horizon. Costs were composed of cost of the illness and the vaccination program. Outcomes were measured in the form of lives saved and DALYs averted. Both costs and outcomes were discounted at 3%. The study found the discounted number of deaths to be 7.02 and 20.52 for vaccinated and unvaccinated cohorts, respectively (13.5 deaths averted). Discounted DALYs were 263.33 and 826.57 for vaccinated and unvaccinated cohorts, respectively (563.24 DALYs averted). Costs of rotavirus diarrhea in a societal perspective were US$6.6 million and US$21.0 million for vaccinated and unvaccinated cohorts, respectively. At base case, the costs per additional death averted were US$5.1 million and US$5.7 for 2-dose and 3-dose vaccines, respectively, in a societal perspective. Costs per additional DALYs averted were US$128,063 and US$142,144, respectively. In a societal perspective, with a cost-effectiveness threshold at 1 GDP per capita per DALYs averted, vaccine prices per dose were US$4.98 and US$3.32 for 2-dose and 3-dose vaccines, respectively; in a provider perspective, they were US$2.90 and US$1.93. One-way and probabilistic sensitivity analyses were included. The budget required for vaccine purchase was calculated for all scenarios.     

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.