Identification of an Optimal COVID-19 Booster Allocation Strategy to Minimize Hospital Bed-Days with a Fixed Healthcare Budget.

Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B1, costing US $1 per dose, B2, costing US $2, and no booster (NB), costing US $0. B1 and B2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B1, B2, or NB for all. Brazil was the base-case country. The model demonstrated that B1 for those aged <70 years and B2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.

Risk factors for cervical cancer in women in China: A meta-model.

OBJECTIVES: Cervical cancer is a leading cause of cancer-related mortality in women in China. This analysis is a quantitative evidence synthesis pooling information about each cervical cancer risk factor. METHODS: A meta-model was developed to estimate the risk of cervical cancer for a woman aged 18-85 years in Mainland China based on her risk profile at the time of assessment. The meta-model was built using findings of a systematic literature review that identified 21 case-control studies reporting data on 105 groups of cervical cancer risk factors in Chinese women. Extracted risk factors were ranked, and 17 were selected by Chinese clinical experts for inclusion in the meta-model. Risk equations were developed for each selected study. Predicted risks for each study were dependent on the risk profile under consideration and study-specific risks were pooled to an overall risk estimate using a random-effects meta-analysis. Sensitivity analysis was conducted using 100 artificial patient profiles (in the absence of patient data). RESULTS: Predicted risks for the 100 profiles suggested that the model had good face validity and could differentiate between high and non-high cervical cancer risk profiles. CONCLUSION: This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.

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

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

The burden of pertussis in older adults: what is the role of vaccination? A systematic literature review.

INTRODUCTION: Pertussis (whooping cough) is a vaccine-preventable disease; however, neither natural- nor vaccine-induced protection is life-long. Although generally not severe in adults, pertussis can be associated with complications in patients with chronic conditions such as asthma or chronic obstructive pulmonary disease, and can be readily transmitted to more vulnerable populations, including neonates before they complete their primary vaccination. Furthermore, as the global population ages, the health and economic burden of the disease is expected to rise. Areas covered: A systematic literature review was conducted to ascertain the current epidemiological and financial burden of pertussis in older adults and to discuss the potential value of a booster vaccination in this population. Expert commentary: Our review indicates a considerable underestimation of the pertussis burden amongst older adults. Seroprevalence studies consistently demonstrate that the reported incidence may be much lower than the actual incidence. Tetanus toxoid-reduced diphtheria toxoid and acellular pertussis vaccines are immunogenic in older adults, induce high booster responses and are well-tolerated. There is therefore a good rationale for the advocacy of booster pertussis vaccination throughout life to prevent pertussis infection and its transmission, especially in adults aged ≥50 years.

Is adding maternal vaccination to prevent whooping cough cost-effective in Australia?

Pertussis or whooping cough, a highly infectious respiratory infection, causes significant morbidity and mortality in infants. In adolescents and adults, pertussis presents with atypical symptoms often resulting in under-diagnosis and under-reporting, increasing the risk of transmission to more vulnerable groups. Maternal vaccination against pertussis protects mothers and newborns. This evaluation assessed the cost-effectiveness of adding maternal dTpa (reduced antigen diphtheria, Tetanus, acellular pertussis) vaccination to the 2016 nationally-funded pertussis program (DTPa [Diphtheria, Tetanus, acellular Pertussis] at 2, 4, 6, 18 months, 4 years and dTpa at 12-13 years) in Australia. A static cross-sectional population model was developed using a one-year period at steady-state. The model considered the total Australian population, stratified by age. Vaccine effectiveness against pertussis infection was assumed to be 92% in mothers and 91% in newborns, based on observational and case-control studies. The model included conservative assumptions around unreported cases. With 70% coverage, adding maternal vaccination to the existing pertussis program would prevent 8,847 pertussis cases, 422 outpatient cases, 146 hospitalizations and 0.54 deaths per year at the population level. With a 5% discount rate, 138.5 quality-adjusted life-years (QALYs) would be gained at an extra cost of AUS$ 4.44 million and an incremental cost-effectiveness ratio of AUS$ 32,065 per QALY gained. Sensitivity and scenario analyses demonstrated that outcomes were most sensitive to assumptions around vaccine effectiveness, duration of protection in mothers, and disutility of unreported cases. In conclusion, dTpa vaccination in the third trimester of pregnancy is likely to be cost-effective from a healthcare payer perspective in Australia.

Cost-effectiveness analysis of human papillomavirus vaccination in South Africa accounting for human immunodeficiency virus prevalence.

BACKGROUND: This study aims at evaluating the cost-effectiveness of a 2-dose schedule human papillomavirus (HPV) vaccination programme of HPV and human immunodeficiency virus (HIV) naïve 12-year-old girls, in addition to cervical cancer (CC) screening alone, in South Africa. The study aims to account for both the impact of the vaccine among girls who are HIV-positive (HIV+) as well as HIV-negative (HIV-) population. METHODS: A previously published Markov cohort model was adapted to assess the impact and cost-effectiveness of a HPV vaccination programme in girls aged 12 years (N = 527 900) using the AS04-adjuvanted HPV-16/18 vaccine from a public payer perspective. Two subpopulations were considered: HIV- and HIV+ women. Each population followed the HPV natural history with different transition probabilities. Model input data were obtained from the literature, local databases and Delphi panel. Costs and outcomes were discounted at 5 %. Extensive sensitivity analyses were conducted to assess the robustness of the evaluation. RESULTS: Implementation of the AS04-adjuvanted HPV-16/18 vaccine in combination with current cytological screening in South African girls could prevent up to 8 869 CC cases and 5 436 CC deaths over the lifetime of a single cohort. Without discounting, this HPV vaccine is dominant over screening alone; with discounting, the incremental cost-effectiveness ratio is ZAR 81 978 (South African Rand) per quality-adjusted life years (QALY) gained. HPV vaccination can be considered cost-effective based on World Health Organization (WHO) recommended threshold (3 x gross domestic product/capita = ZAR 200 293). In a scenario with a hypothetical targeted vaccination in a HIV+ subpopulation alone, the modelled outcomes suggest that HPV vaccination is still cost-effective, although the incremental cost-effectiveness ratio increases to ZAR 102 479. Results were sensitive to discount rate, vaccine efficacy, HIV incidence and mortality rates, and HPV-related disease transition probabilities. CONCLUSIONS: The AS04-adjuvanted HPV-16/18 vaccine can be considered cost-effective in a South African context although the cost-effectiveness is expected to be lower in the HIV+ subpopulation than in the overall female population. With improved access to HIV treatment, the HIV mortality and incidence rates are likely to be reduced, which could improve cost-effectiveness of the vaccination programme in South Africa.

Vaccination of boys or catch-up of girls above 11 years of age with the HPV-16/18 AS04-adjuvanted vaccine: where is the greatest benefit for cervical cancer prevention in Italy?

BACKGROUND: Since 2007, a Human Papillomavirus (HPV) vaccination programme against cervical cancer (CC) is implemented in Italy in 11-year-old girls. The extension of HPV vaccination to young adult women, or to 11-year-old boys could further reduce the CC burden, in the latter case from indirect effect on HPV transmission. The objective of the study was to compare the potential CC cases prevention from HPV-16/18 AS04-adjuvanted vaccination of adding catch-up targeting 15- or 25-year-old girls to the addition of boys vaccination in Italy. The models assessing the impact of these alternative vaccination strategies are usually dynamic models requiring numerous input data. Simpler models could however provide some insight into this question, as reported in the current study. METHODS: A published cohort model adapted to the Italian setting was used to estimate the potential CC reduction following different HPV vaccination strategies with a HPV-16/18 AS04-adjuvanted vaccine: vaccination of 11-year-old girls, female aged 15 or 25 years. The model assumed that the maximum benefit obtained from vaccinating boys equals the CC reduction that would result from immunisation of all non-vaccinated girls of the same age. Each cohort of 11-year-olds (either girls or boys) was assumed to include 281,000 individuals and a 70% vaccination coverage was applied. Sensitivity analysis was performed by varying the vaccination coverage and the overlap in potential sexual contacts between vaccinated boys and girls of the same age-group. RESULTS: Under base case, compared with the screening-only scenario, HPV vaccination of 11-year-old girls, 15-year-old females, 25-year-old females or 11-year-old boys, would prevent 1,146, 1,082, 788 or 491 CC cases respectively. HPV vaccination of boys could result in more CC cases prevented than adding a female catch-up only in scenarios with low vaccination coverage in the primary target cohort and when combined with small overlap between vaccinated boys and girls of the same age cohort. CONCLUSIONS: For a fixed limited additional budget allowing the inclusion of a single catch-up cohort, the extension of HPV vaccination to girls or young women instead of boys was estimated to maximise the number of CC cases prevented.

Evaluation of serogroup C and ACWY meningococcal vaccine programs: projected impact on disease burden according to a stochastic two-strain dynamic model.

OBJECTIVE: Advisory committees in Canada and the United States have updated recommendations for quadrivalent meningococcal conjugate vaccines against serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective meningococcal vaccination policies using a stochastic dynamic model. Canada was used as an example. METHODS: Our stochastic dynamic model of Neisseria meningitidis (Nm) transmission in an age-structured population assumed partial cross-immunity among two aggregated serogroup categories: 'AWY' containing A, W135, and Y; and 'Other' containing B, C, and ungroupable types. We compared the impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and invasive meningococcal disease (IMD). Our model was parameterized with Canadian epidemiological and demographic data and employed probabilistic sensitivity analysis. RESULTS: Routine infant immunization at 12 months and boosting at 15 years with a quadrivalent vaccine is projected to have the largest impact on total IMD incidence: a 74% reduction over 40 years. Routine infant immunization with a monovalent vaccine at 12 months only has much less impact and also generates strain replacement appearing after approximately ten years of continuous use. CONCLUSIONS: Immunizing infants at 12 months and boosting adolescents at 15 years with an ACWY vaccine is predicted to be most effective at reducing IMD incidence.

Health economic analysis of human papillomavirus vaccines in women of Chile: perspective of the health care payer using a Markov model.

BACKGROUND: In Chile, significant reductions in cervical cancer incidence and mortality have been observed due to implementation of a well-organized screening program. However, it has been suggested that the inclusion of human papillomavirus (HPV) vaccination for young adolescent women may be the best prospect to further reduce the burden of cervical cancer. This cost-effectiveness study comparing two available HPV vaccines in Chile was performed to support decision making on the implementation of universal HPV vaccination. METHODS: The present analysis used an existing static Markov model to assess the effect of screening and vaccination. This analysis includes the epidemiology of low-risk HPV types allowing for the comparison between the two vaccines (HPV-16/18 AS04-adjuvanted vaccine and the HPV-6/11/16/18 vaccine), latest cross-protection data on HPV vaccines, treatment costs for cervical cancer, vaccine costs and 6% discounting per the health economic guideline for Chile. RESULTS: Projected incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICERs) for the HPV-16/18 AS04-adjuvanted vaccine was 116 United States (US) dollars per quality-adjusted life years (QALY) gained or 147 US dollars per life-years (LY) saved, while the projected ICUR/ICER for the HPV-6/11/16/18 vaccine was 541 US dollars per QALY gained or 726 US dollars per LY saved. Introduction of any HPV vaccine to the present cervical cancer prevention program of Chile is estimated to be highly cost-effective (below 1X gross domestic product [GDP] per capita, 14278 US dollars). In Chile, the addition of HPV-16/18 AS04-adjuvanted vaccine to the existing screening program dominated the addition of HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analysis results show that the HPV-16/18 AS04-adjuvanted vaccine is expected to be dominant and cost-saving in 69.3% and 77.6% of the replicates respectively. CONCLUSIONS: The findings indicate that the addition of any HPV vaccine to the current cervical screening program of Chile will be advantageous. However, this cost-effectiveness model shows that the HPV-16/18 AS04-adjuvanted vaccine dominated the HPV-6/11/16/18 vaccine. Beyond the context of Chile, the data from this modelling exercise may support healthcare policy and decision-making pertaining to introduction of HPV vaccination in similar resource settings in the region.

Modeling optimal cervical cancer prevention strategies in Nigeria.

BACKGROUND: This study aims to assess the most efficient combinations of vaccination and screening coverage for the prevention of cervical cancer (CC) at different levels of expenditure in Nigeria. METHODS: An optimization procedure, using a linear programming approach and requiring the use of two models (an evaluation and an optimization model), was developed. The evaluation model, a Markov model, estimated the annual number of CC cases at steady state in a population of 100,000 women for four alternative strategies: screening only; vaccination only; screening and vaccination; and no prevention. The results of the Markov model for each scenario were used as inputs to the optimization model determining the optimal proportion of the population to receive screening and/or vaccination under different scenarios. The scenarios varied by available budget, maximum screening and vaccination coverage, and overall reachable population. RESULTS: In the base-case optimization model analyses, with a coverage constraint of 20% for one lifetime screening, 95% for vaccination and a budget constraint of $1 per woman per year to minimize CC incidence, the optimal mix of prevention strategies would result in a reduction of CC incidence of 31% (3-dose vaccination available) or 46% (2-dose vaccination available) compared with CC incidence pre-vaccination. With a 3-dose vaccination schedule, the optimal combination of the different strategies across the population would be 20% screening alone, 39% vaccination alone and 41% with no prevention, while with a 2-dose vaccination schedule the optimal combination would be 71% vaccination alone, and 29% with no prevention. Sensitivity analyses indicated that the results are sensitive to the constraints included in the optimization model as well as the cervical intraepithelial neoplasia (CIN) and CC treatment cost. CONCLUSIONS: The results of the optimization model indicate that, in Nigeria, the most efficient allocation of a limited budget would be to invest in both vaccination and screening with a 3-dose vaccination schedule, and in vaccination alone before implementing a screening program with a 2-dose vaccination schedule.

Estimation of the potential overall impact of human papillomavirus vaccination on cervical cancer cases and deaths.

BACKGROUND: Human papillomavirus (HPV) vaccination offers potential for primary prevention of HPV-related pre-cancers and cancers as demonstrated in clinical trials. Mathematical models have estimated the potential real-life impact of vaccination on the burden of cervical cancer (CC). However, these are restricted to evaluations in a limited number of countries. METHODS: Potential decline in CC cases and deaths with the AS04-adjuvanted HPV-16/18 vaccine of young girls naïve to HPV, was estimated at steady-state (vaccine coverage: 0-100%) based on clinical trial and country-specific incidence data. Data on vaccine efficacy were taken from the end of study PATRICIA trial of the AS04-adjuvanted HPV-16/18 vaccine. The numbers of cases and deaths due to HPV-16/18 were estimated and compared with those due to any HPV type to estimate the additional cases prevented. This difference estimates CC cases and deaths avoided due to protection against non-vaccine HPV types. Cost-offsets due to reductions in CC treatment were estimated for five countries (Brazil, Canada, Italy, Malaysia and South African Republic) using country-specific unit cost data. Additionally, cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3)-related burden (cases and treatment costs) prevented by vaccination were estimated for two countries (Italy and Malaysia). RESULTS: HPV vaccination could prevent a substantial number of CC cases and deaths in countries worldwide, with associated cost-offsets due to reduced CC treatment. Cross-protection increased the estimated potential number of CC cases and deaths prevented by 34 and 18% in Africa and Oceania, respectively. Moreover, vaccination could result in a substantial reduction in the number of CIN2/3 lesions and associated costs. CONCLUSION: HPV vaccination could reduce the burden of CC and precancerous lesions in countries worldwide, part of disease burden reduction being related to protection against non HPV-16/18 related types.

Incremental cost-effectiveness evaluation of vaccinating girls against cervical cancer pre- and post-sexual debut in Belgium.

BACKGROUND: Vaccination against human papillomavirus (HPV) to prevent cervical cancer (CC) primarily targets young girls before sexual debut and is cost-effective. We assessed whether vaccination with the HPV-16/18 AS04-adjuvanted vaccine added to screening remains cost-effective in females after sexual debut compared to screening alone in Belgium. The role of protection against non-HPV-16/18 was also investigated. METHODS: A published Markov cohort model was adapted to Belgium. The model replicated the natural history of HPV infection, the effects of screening, and vaccination. Vaccine efficacy (VE) included non-HPV-16/18 protection based on the PATRICIA clinical trial data. Pre- and post-HPV exposure VE were differentiated. Lifetime vaccine protection was assumed. Input data were obtained from literature review, national databases and a Delphi panel. Costing was from a healthcare payer perspective. Costs were discounted at 3% and effects at 1.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the number of lesions prevented with vaccination from age 12 to 40 was evaluated. The specific effect of non-HPV-16/18 protection was investigated. Univariate sensitivity analysis was performed on key variables. RESULTS: The model estimated that vaccinating a cohort of 100,000 girls at age 12 would prevent 646 CC cases over a lifetime (102 non-HPV-16/18) with an ICER of €9171/QALY. Vaccinating at age 26 would prevent 340 CC cases (40 non-HPV-16/18) with an ICER of €17,348/QALY and vaccinating at age 40 would prevent 146 CC cases (17 non-HPV-16/18) with an ICER of €42,847/QALY. The ICER remained under the highly cost-effective threshold (1×GDP/capita) until age 33 years and under the cost-effective threshold (3×GDP/capita) beyond age 40. CONCLUSION: Extending HPV vaccination to females post-sexual debut could lead to a substantial reduction in CC-related burden and would be cost-effective in Belgium.

The cost and public health burden of invasive meningococcal disease outbreaks: a systematic review.

BACKGROUND: Invasive meningococcal disease (IMD) is a serious disease with a rapid onset, high mortality rate, and risk of long-term complications. Numerous reports in the literature conclude that IMD outbreaks are associated with substantial costs to society and significant burden on communities due to the cost associated with the prevention of secondary cases. OBJECTIVE: To systematically review the literature on the costs and public health burden associated with IMD outbreaks. METHODS: Studies were primarily identified through searching MEDLINE and EMBASE. Reports were included if they provided cost data related to the containment of an IMD outbreak after 1990 and were written in English, French, or Spanish. Costs were converted to 2010 United States dollars. Outbreaks were categorized by low-income countries (LIC) and high-income countries (HIC) based on gross domestic product per capita. Outbreak containment strategies were classified as small (e.g., targeting members of the school/institution where the outbreak occurred) or large (e.g., targeting everyone in the community). RESULTS: Sixteen articles reporting data on 93 IMD outbreaks fulfilled the eligibility criteria and were included. The majority of outbreaks occurred in HIC. Five studies reported the use of small containment strategies including targeted vaccination and chemoprophylaxis, all occurring in HIC. The average cost per small containment strategy was $299,641 and the average cost per IMD case was $41,857. Eight studies reported large containment strategies involving widespread vaccination targeting a specific age group or community. For HIC, the average cost per large containment strategy was $579,851 and the average cost per IMD case was $55,755. In LIC, the average cost per large containment strategy was $3,407,590 and the average cost per IMD case was $2,222. CONCLUSION: IMD outbreaks were associated with substantial costs. We found that although there were numerous reports on IMD outbreaks, data on containment costs were very limited. More research in this area is warranted.

Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada.

BACKGROUND: In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV) types -16 and -18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW) while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting. METHODS: A Markov model of the natural history of HPV infection among women, cervical cancer (CC) and GW was used to estimate the impact of vaccinating a cohort of 100,000 12-year-old females on lifetime outcomes and healthcare system costs (no indirect benefit in males included). A budget impact model was used to estimate the impact of each vaccine by province. RESULTS: In the base case, vaccination with the HPV-16/18 vaccine was predicted to prevent 48 additional CC cases, and 16 additional CC deaths, while vaccination with the HPV-6/11/16/18 vaccine was predicted to prevent 6,933 additional GW cases. Vaccination with the HPV-16/18 vaccine was estimated to save 1 additional discounted quality adjusted life year (QALY) at an overall lower lifetime cost to the healthcare system compared to the HPV-6/11/16/18 vaccine (assuming vaccine price parity). In sensitivity analyses, the HPV-6/11/16/18 vaccine was associated with greater QALYs saved when the cross-protection efficacy of the HPV-16/18 vaccine was reduced, or the burden of GW due to HPV-6/11 was increased. In most scenarios with price parity, the lifetime healthcare cost of the strategy with the HPV-16/18 vaccine was predicted to be lower than the HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analyses, the HPV-16/18 vaccine provided more QALY benefit than the HPV-6/11/16/18 vaccine in 49.2% of scenarios, with lower relative lifetime costs in 83.5% of scenarios. CONCLUSIONS: Overall, the predicted lifetime healthcare costs and QALYs saved by implementing each of the vaccines are similar. Vaccination with the HPV-16/18 vaccine is expected to be associated with reduced CC disease morbidity and mortality compared to vaccination with the HPV-6/11/16/18 vaccine. Differences in these outcomes depend on the extent of cervical disease prevented by cross-protection and the burden of GW caused by HPV-6/11.

Cost-effectiveness analysis of the bivalent compared with the quadrivalent human papillomavirus vaccines in Taiwan.

OBJECTIVE: To compare the epidemiological and economic impact of additional cross-protection against oncogenic human papillomavirus (HPV) types beyond 16/18 of the bivalent vaccine (BV) versus protection against nononcogenic HPV types 6/11 of the quadrivalent vaccine (QV) in Taiwan. METHODS: A lifetime Markov model calibrated to the Taiwanese setting simulated the natural history of low-risk (engendering cervical intraepithelial neoplasia [CIN] 1 and genital warts) and high-risk HPV (engendering CIN1, CIN2/3, and cervical cancer [CC]) infections, screening, and vaccination (100% coverage) for a cohort of 12-year-old girls (N = 153,000). Transition probabilities, costs, and utilities were estimated from published data and expert opinion. Vaccine efficacy was obtained from each vaccine's respective clinical trials. Price-parity and lifelong protection was assumed for both vaccines. The number of CIN lesions, CC cases, CC deaths and genital wart (GW) cases, and quality-adjusted life-years were estimated. Costs and outcomes (discounted at 3% and 1.5%, respectively) were compared from a payer's perspective. RESULTS: The model estimated that the BV led to an additional, undiscounted, 11,484 CIN1, 1,779 (+34.3% vs. QV) CIN2/3, 188 (+29.0% vs. QV) CC, and 69 (+29.0% vs. QV) CC deaths prevented compared with the QV, while the QV prevented 4,150 GW (+71%). This resulted in an additional 768 quality-adjusted life-years (QALY) and 11.6 million new Taiwan dollars costs saved for the BV versus the QV after discounting. CONCLUSION: Both vaccines have a different epidemiological impact with an increased number of CC-related lesions potentially prevented for the BV because of additional cross-protection. In the Taiwanese setting, HPV mass vaccination using the BV was estimated to dominate vaccination using the QV.

Selecting a mix of prevention strategies against cervical cancer for maximum efficiency with an optimization program.

BACKGROUND: Screening and vaccination against human papillomavirus (HPV) can protect against cervical cancer. Neither alone can provide 100% protection. Consequently it raises the important question about the most efficient combination of screening at specified time intervals and vaccination to prevent cervical cancer. OBJECTIVE: Our objective was to identify the mix of cervical cancer prevention strategies (screening and/or vaccination against HPV) that achieves maximum reduction in cancer cases within a fixed budget. METHODS: We assessed the optimal mix of strategies for the prevention of cervical cancer using an optimization program. The evaluation used two models. One was a Markov cohort model used as the evaluation model to estimate the costs and outcomes of 52 different prevention strategies. The other was an optimization model in which the results of each prevention strategy of the previous model were entered as input data. The latter model determined the combination of the different prevention options to minimize cervical cancer under budget, screening coverage and vaccination coverage constraints. We applied the model in two countries with different healthcare organizations, epidemiology, screening practices, resource settings and treatment costs: the UK and Brazil. 100,000 women aged 12 years and above across the whole population over a 1-year period at steady state were included. The intervention was papanicolaou (Pap) smear screening programmes and/or vaccination against HPV with the bivalent HPV 16/18 vaccine (Cervarix® [Cervarix is a registered trademark of the GlaxoSmithKline group of companies]). The main outcome measures were optimal distribution of the population between different interventions (screening, vaccination, screening plus vaccination and no screening or vaccination) with the resulting number of cervical cancer and associated costs. RESULTS: In the base-case analysis (= same budget as today), the optimal prevention strategy would be, after introducing vaccination with a coverage rate of 80% in girls aged 12 years and retaining screening coverage at pre-vaccination levels (65% in the UK, 50% in Brazil), to increase the screening interval to 6 years (from 3) in the UK and to 5 years (from 3) in Brazil. This would result in a reduction of cervical cancer by 41% in the UK and by 54% in Brazil from pre-vaccination levels with no budget increase. Sensitivity analysis shows that vaccination alone at 80% coverage with no screening would achieve a cervical cancer reduction rate of 20% in the UK and 43% in Brazil compared with the pre-vaccination situation with a budget reduction of 30% and 14%, respectively. In both countries, the sharp reduction in cervical cancer is seen when the vaccine coverage rate exceeds the maximum screening coverage rate, or when screening coverage rate exceeds the maximum vaccine coverage rate, while maintaining the budget. As with any model, there are limitations to the value of predictions depending upon the assumptions made in each model. CONCLUSIONS: Spending the same budget that was used for screening and treatment of cervical cancer in the pre-vaccination era, results of the optimization program show that it would be possible to substantially reduce the number of cases by implementing an optimal combination of HPV vaccination (80% coverage) and screening at pre-vaccination coverage (65% UK, 50% Brazil) while extending the screening interval to every 6 years in the UK and 5 years in Brazil.

Public health impact of human papillomavirus vaccination on prevention of cervical cancer in France.

OBJECTIVE: To evaluate the cervical cancer (CC) reduction at individual and population level following different prevention strategies (age-specific vaccination and/or screening) in France. METHODS: A lifetime Markov model was constructed with 11 health states covering the progression from human papillomavirus (HPV) infection to the development of precancerous lesions, CC and death. A screening module took into account the effects of detection and early treatment. Cohorts of girls were entered into the model at age 11 years; the model was run for 95 years using one-year cycles. RESULTS: Vaccination combined with screening substantially reduced the incidence of precancerous lesions and CC compared with screening alone. Vaccination was beneficial regardless of age at vaccination, but the greatest benefit was obtained with an early vaccination. The clinical results were the best for vaccination at 11-13 years when lifetime horizon was considered, and for vaccination at 15-17 years for shorter observation period. CONCLUSION: The model results indicate that HPV vaccination offers additional protection against CC when combined with screening. The optimum starting age for vaccination varies depending on the observation period duration.

Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models.

BACKGROUND: The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability. METHODS: A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios. RESULTS: None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries. CONCLUSIONS: The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries. Please see related article: http://www.biomedcentral.com/1741-7007/9/55.

A generally applicable cost-effectiveness model for the evaluation of vaccines against cervical cancer.

OBJECTIVE: This study aimed at evaluating the cost-effectiveness of human papillomavirus virus (HPV) vaccination in France, using a generally applicable succinct cohort model. METHODS: A lifetime Markov cohort model, adapted to the French setting, simulate the natural history of oncogenic HPV infection towards cervical cancer (CC). Additional modules account for the effects of screening and vaccination. The girls' cohort is vaccinated at age 12 and follows current screening. Costs and outcomes (discounted at 3 and 1.5%, respectively) were compared with a cohort receiving screening alone. RESULTS: The model results agreed well with real-life data. Vaccination in addition to screening would substantially reduce the incidence of and mortality from CC, compared with screening alone, at an estimated cost-effectiveness of 9,706 per quality-adjusted-life-year. Sensitivity analysis showed that the discount rate and the parameters related to the disease history have the largest impact on the results. CONCLUSION: This succinct cohort model indicated that HPV vaccination would be a cost-effective policy option in France. It uses readily available data and should be generally applicable to the evaluation of HPV vaccination in a variety of countries and settings.

Modelling the effect of conjugate vaccines in pneumococcal disease: cohort or population models?

Cohort and population models estimate vaccine impact on disease events, and yield different estimates in countries with different demographic compositions. We compared administration of the new 10-valent pneumococcal Haemophilus influenzae-protein D conjugate vaccine (PHiD-CV) with no vaccination in two countries, the United Kingdom (UK) and Mexico, using two modelling strategies: a cohort model and a population model. The cohort model followed a birth cohort over a lifetime, beginning 10 years after initiation of the vaccine program, when vaccine efficacy steady state had been reached. The population model examined the country-specific population over 1 year, also beginning 10 years after initiation of the vaccine program. Both models included the same age-specific disease rates of meningitis, bacteraemia, pneumonia, and otitis media. The output variables were the numbers of specific events, with and without indirect vaccine effects. Without indirect effects, the cohort and population models produced similar results for both countries (deviation of <20% difference per output measure for most outcomes). The difference between the model types was much greater when indirect vaccine effects were included, especially in Mexico (up to 120% difference). Cohort and population modelling methods produce different results depending on the disease, the intervention, the demographic composition, and the time horizon evaluated. Results from the two model types provide different information about the impact of interventions on events: accumulated vaccine benefit for an individual in a cohort model; vaccine benefit for a whole population at a specific time point in a population model.