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

BACKGROUND: Cervical 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. METHODS: The 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. RESULTS: Introduction 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. CONCLUSIONS: Introducing 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 and value-based prices of the 9-valent human papillomavirus vaccine for the prevention of cervical cancer in China: an economic modelling analysis.

OBJECTIVES: To evaluate the cost-effectiveness of the 9-valent human papillomavirus (HPV) vaccine for the prevention of cervical cancer in China. DESIGN: Health economic modelling using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model populated with China-specific data. SETTING: Individual cervical cancer prevention in China using the 9-valent HPV vaccine from the perspective of private sector purchasers in relation to receiving other HPV vaccines and not receiving vaccination for 16-year-old girls in China who had not been previously infected with HPV. PARTICIPANTS: Not applicable. INTERVENTIONS: Vaccination using the 9-valent, the quadrivalent and the bivalent vaccines. PRIMARY OUTCOME MEASURE: Incremental costs per disability-adjusted life year (DALY) prevented. RESULTS: In the base case, the incremental costs per DALY prevented were, respectively, US$35 000 and US$50 455 compared with the quadrivalent and the bivalent vaccines, both of which were above the cost-effective threshold of US$25 920/DALY prevented. To be cost-effective in these comparisons, the 9-valent vaccine should be priced at $550 and $450 for the full doses, respectively. To be highly cost-effective, the price thresholds were $435 and $335. The incremental costs per DALY prevented in relation to no vaccination was US$23 012, making the 9-valent vaccine marginally cost-effective. The results were robust in most one-way sensitivity analyses including changing vaccination age to 13 and 26 years. CONCLUSIONS: At the current price, the 9-valent HPV vaccine is not cost-effective compared with the quadrivalent and the bivalent vaccines for young girls in China who had not been previously infected with HPV. Policymakers and clinicians should keep potential vaccine recipients informed about the economic profile of the 9-valent vaccine and carefully consider expanding its use in China at the current price.

The cost-effectiveness of controlling cervical cancer using a new 9-valent human papillomavirus vaccine among school-aged girls in Australia.

INTRODUCTION: Cervical cancer imposes a substantial health burden worldwide including in Australia and is caused by persistent infection with one of 13 sexually transmitted high-risk human papillomavirus (HPV) types. The objective of this study was to assess the cost-effectiveness of adding a nonavalent new Gardasil-9® (9vHPV) vaccine to the national immunisation schedule in Australia across three different delivery strategies. MATERIALS AND METHODS: The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to examine the cost-effectiveness of 9vHPV vaccine introduction to prevent HPV infection. Academic literature and anecdotal evidence were included on the demographic variables, cervical cancer incidence and mortality, treatment costs, and vaccine delivery costs. The incremental cost-effectiveness ratios (ICERs) were measured per disability-adjusted life years (DALYs) averted, using the heuristic cost-effectiveness threshold defined by the World Health Organisation (WHO). Analyses and data from international agencies were used in scenario analysis from the health system and societal perspectives. RESULTS: The 9vHPV vaccination was estimated to prevent 113 new cases of cervical cancer (discounted) during a 20-year period. From the health system and societal perspectives, the 9vHPV vaccination was very cost-effective in comparison with the status quo, with an ICER of A$47,008 and A$44,678 per DALY averted, respectively, using the heuristic cost-effectiveness threshold level. Considering delivery strategies, the ICERs per DALY averted were A$47,605, A$46,682, and A$46,738 for school, health facilities, and outreach-based vaccination programs from the health system perspective, wherein, from the societal perspective, the ICERs per DALY averted were A$46,378, A$43,729, A$43,930, respectively. All estimates of ICERs fell below the threshold level (A$73,267). CONCLUSIONS: This cost-effectiveness evaluation suggests that the routine two-dose 9vHPV vaccination strategy of preadolescent girls against HPV is very cost-effective in Australia from both the health system and societal perspectives. If equally priced, the 9vHPV option is the most economically viable vaccine. Overall, this analysis seeks to contribute to an evidence-based recommendation about the new 9vHPV vaccination in the national immunisation program in Australia.

(Un)contested evidence: scientific literature, systematic reviews and the politics of evidence in the introduction of HPV vaccines in Colombia.

This paper analyses the tensions between scientific literature and systematic reviews in the production of evidence in healthcare. Systematic reviews are devices developed - within evidence-based medicine - to navigate the complexities of scientific literature promising a clear and simple account of the knowledge on a particular issue. However, in practice, systematic reviews have a more complex relation with literature. Systematic reviews are shaped according to the interest of the local groups that produce them. In this paper, I explore the formatting, making and managing of systematic reviews of evidence relating to HPV vaccines in Colombia. This case shows the ways in which systematic reviews mediate between the requirement of presenting the evidence that emerges from the international literature and the necessity of having data locally relevant.

Cost-Effectiveness Analysis of the Introduction of HPV Vaccination of 9-Year-Old-Girls in Iran.

OBJECTIVES: To estimate the cost effectiveness of introducing the quadrivalent human papillomavirus (HPV) vaccine into the national immunization program of Iran. METHODS: The CERVIVAC cost-effectiveness model was used to calculate incremental cost per averted disability-adjusted life-year by vaccination compared with no vaccination from both governmental and societal perspectives. Calculations were based on epidemiologic parameters from the Iran National Cancer Registry and other national data sources as well as from literature review. We estimated all direct and indirect costs of cervical cancer treatment and vaccination program. All future costs and benefits were discounted at 3% per year and deterministic sensitivity analysis was used. RESULTS: During a 10-year period, HPV vaccination was estimated to avert 182 cervical cancer cases and 20 deaths at a total vaccination cost of US $23,459,897; total health service cost prevented because of HPV vaccination was estimated to be US $378,646 and US $691,741 from the governmental and societal perspective, respectively. Incremental cost per disability-adjusted life-year averted within 10 years was estimated to be US $15,205 and US $14,999 from the governmental and societal perspective, respectively, and both are higher than 3 times the gross domestic product per capita of Iran (US $14,289). Sensitivity analysis showed variation in vaccine price, and the number of doses has the greatest volatility on the incremental cost-effectiveness ratio. Using a two-dose vaccination program could be cost-effective from the societal perspective (incremental cost-effectiveness ratio = US $11,849). CONCLUSIONS: Introducing a three-dose HPV vaccination program is currently not cost-effective in Iran. Because vaccine supplies cost is the most important parameter in this evaluation, considering a two-dose schedule or reducing vaccine prices has an impact on final conclusions.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule.

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Manufacturing costs of HPV vaccines for developing countries.

BACKGROUND: Nearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs. METHODS: Searches in published and commercial literature for information about the manufacturing of these vaccines. Interviews with experts in vaccine manufacturing. FINDINGS: This detailed sensitivity analysis, based on the best available evidence, finds that after a first set of batches for affluent markets, manufacturing costs of Gardasil for developing countries range between $0.48 and $0.59 a dose, a fraction of its alleged costs of $4.50. Because volume of Cervarix is low, its per unit costs are much higher, though at comparable volumes, its costs would be similar. INTERPRETATION: Given the recovery of fixed and annual costs from sales in affluent markets, Merck's break-even price to Gavi could be $0.50-$0.60, not $4.50. These savings could support Gavi programs to strengthen delivery and increase coverage. Outside Gavi, prices to lower- and middle-income countries, with profit, could also be lowered and made available to millions more adolescents at risk. These estimates and their policy implications deserve further discussion.

Quantitative benefit-risk assessment by MCDA of the quadrivalent HPV vaccine for preventing anal cancer in males.

OBJECTIVES: To quantify the benefit-risk (BR) balance of the quadrivalent human papillomavirus (qHPV) vaccine for use in males, including anal cancer prevention, by using the multicriteria decision analysis (MCDA). METHODS: Value tree and an effect table were compiled using relevant qHPV vaccine efficacy/safety data. An expert panel validated the final model inputs. RESULTS: On a scale of 0-100, the MCDA qHPV vaccine score (66) was superior to the no vaccination score (46), indicating a more favorable BR balance for the qHPV vaccine. Significant changes in weight of individual outcomes were needed to change BR balance in sensitivity analyses. The qHPV vaccine maintained a better BR profile in all alternative models. CONCLUSIONS: MCDA can be used to transparently evaluate BR balance of vaccines. The qHPV vaccine had a favorable BR balance in males. Including anal cancer as a new indication further improves the BR profile of the qHPV vaccine.

Health and Economic Impact of Switching from a 4-Valent to a 9-Valent HPV Vaccination Program in the United States.

BACKGROUND: Randomized clinical trials have shown the 9-valent human papillomavirus (HPV) vaccine to be highly effective against types 31/33/45/52/58 compared with the 4-valent. Evidence on the added health and economic benefit of the 9-valent is required for policy decisions. We compare population-level effectiveness and cost-effectiveness of 9- and 4-valent HPV vaccination in the United States. METHODS: We used a multitype individual-based transmission-dynamic model of HPV infection and disease (anogenital warts and cervical, anogenital, and oropharyngeal cancers), 3% discount rate, and societal perspective. The model was calibrated to sexual behavior and epidemiologic data from the United States. In our base-case, we assumed 95% vaccine-type efficacy, lifelong protection, and a cost/dose of $145 and $158 for the 4- and 9-valent vaccine, respectively. Predictions are presented using the mean (80% uncertainty interval [UI] = 10(th)-90(th) percentiles) of simulations. RESULTS: Under base-case assumptions, the 4-valent gender-neutral vaccination program is estimated to cost $5500 (80% UI = 2400-9400) and $7300 (80% UI = 4300-11 000)/quality-adjusted life-year (QALY) gained with and without cross-protection, respectively. Switching to a 9-valent gender-neutral program is estimated to be cost-saving irrespective of cross-protection assumptions. Finally, the incremental cost/QALY gained of switching to a 9-valent gender-neutral program (vs 9-valent girls/4-valent boys) is estimated to be $140 200 (80% UI = 4200->1 million) and $31 100 (80% UI = 2100->1 million) with and without cross-protection, respectively. Results are robust to assumptions about HPV natural history, screening methods, duration of protection, and healthcare costs. CONCLUSIONS: Switching to a 9-valent gender-neutral HPV vaccination program is likely to be cost-saving if the additional cost/dose of the 9-valent is less than $13. Giving females the 9-valent vaccine provides the majority of benefits of a gender-neutral strategy.

[Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model]. / Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión.

OBJECTIVE: To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. MATERIALS AND METHODS: A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. RESULTS: Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. CONCLUSIONS: Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión / Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model

Objetivo. Evaluar la costo-efectividad (CE) de la vacuna tetravalente contra el virus de papiloma humano (VPH) en Argentina, desde la perspectiva del sistema de salud. Material y métodos. Se utilizó un modelo dinámico de transmisión para estimar el impacto en la incidencia de cáncer de cuello uterino (Cacu), verrugas y otras lesiones, en los años de vida ajustados por calidad (AVAC) y en costos sanitarios. Resultados. La vacuna podría reducir en 60% el riesgo de muerte por Cacu y en 67% el de padecer verrugas genitales. Comparada con no vacunar, la estrategia de vacunación mostró un beneficio incremental promedio de 0.00234 AVAC por persona a un costo incremental de 2.36 dólares, con una CE de 1007.55 dólares por AVAC ganado. Los resultados demostraron ser robustos en el análisis de sensibilidad. Conclusiones. La inmunización resultaría costo-efectiva, con una CE inferior a un producto interno bruto per cápita (15 009 dólares) por AVAC ganado.

Objective. To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. Materials and methods. A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. Results. Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. Conclusions. Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination.

OBJECTIVE: Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented. METHODS AND MATERIALS: Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts. RESULTS: From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million. CONCLUSION: Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.

Immunization costs and programmatic barriers at an urban HIV clinic.

BACKGROUND: Although the increasing number of recommended immunizations is essential for patients infected with human immunodeficiency virus (HIV), the potentially uncompensated costs of expanded immunizations will present significant challenges for clinics and health systems serving HIV-infected patients. METHODS: We estimated costs of providing Gardasil, Prevnar, and Zostavax to eligible patients at a US Ryan White Part C academically affiliated HIV clinic in 2013. Clinic expenditures were calculated using vaccine price and administrative fees. Revenue was calculated using insurance reimbursement data for vaccination and administration. Three scenarios were used: 100% uptake of vaccines, adjusted uptake based on published rates, and adjusted reimbursement according to pre-Affordable Care Act (ACA) insurance status. RESULTS: 2887 patients (27% Medicare, 13% Alabama Medicaid, 26% Commercial, 34% Uninsured), received care with wide variation in immunization reimbursement ($0 to $210) by insurance and vaccine. The net yield (revenue minus expenditure) was calculated for each vaccine. Prevnar was most costly: annual net yield of -$60 691. Provision of all 3 vaccines would lead to a net yield of -$97 122. Adjusting for reduced uptake led to annual clinic losses of $44 119. Using pre-ACA reimbursement for immunization of the uninsured led to reduced clinic losses (-$62 326), attributable to reimbursement via Ryan White funds. CONCLUSIONS: A cost analysis of 3 vaccines shows great variation in insurance coverage, with potential losses of almost $100 000 for one HIV clinic if eligible patients received vaccinations in one calendar year. Adequate, cost neutral reimbursement should be instituted if medical providers and health systems are to achieve Advisory Committee on Immunization Practices immunization recommendations for both HIV positive and negative adults.

Cost-effectiveness of HPV vaccination in Belize.

OBJECTIVE: Among women in Belize, cervical cancer is both the leading cancer and the leading cause of cancer deaths. Both the quadrivalent and bivalent human papillomavirus (HPV) vaccines are licensed in Belize. The Ministry of Health of Belize convened a multidisciplinary team to estimate the costs, health benefits, and cost-effectiveness of adding an HPV vaccine to the national immunization schedule. METHODOLOGY: The CERVIVAC cost-effectiveness model (Version 1.123) was used to assess the lifetime health and economic outcomes of vaccinating one cohort of girls aged 10 years against HPV. The comparator was no HPV vaccination. The PAHO Revolving Fund negotiated price of US$ 13.79 per dose was used (for the quadrivalent vaccine) and national data sources were used to define demography, cervical cancer incidence and mortality, cervical cancer treatment costs, and vaccine delivery costs. Estimates from international agencies were used in scenario analysis. RESULTS: In a cohort of ∼4000 Belizean girls tracked over a lifetime, HPV vaccination is estimated to prevent 69 new cases of cervical cancer (undiscounted), and 51 cervical cancer deaths (undiscounted). Considering the potential cervical cancer treatment costs and lost wages avoided by households (societal perspective), the cost per disability-adjusted life year (DALY) averted was estimated to be US$ 429. This increased to US$ 1320 when cervical cancer treatment costs and lost wages were excluded from the analysis. Both estimates are far below the gross domestic product (GDP) per capita of Belize (US$ 4795). The lifetime health care costs saved by the women and their families represent more than 60% of the investment cost needed by the Government for the vaccine. CONCLUSION: Routine HPV vaccination would be highly cost-effective in Belize. If affordable, efforts should be made to expedite the introduction of this vaccine into the Belizean national immunization program.