Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

Financing for pandemic preparedness and response measures: a systematic scoping review.

Objective: To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and economic costs comparable to those of the coronavirus disease. Methods: We conducted a systematic scoping review using the databases ScienceDirect, Scopus, JSTOR, PubMed® and EconLit. We included articles published in any language until 1 August 2023, and excluded grey literature and publications on epidemics. We categorized eligible studies according to the elements of a framework proposed by the World Health Organization Council on the Economy of Health for All: (i) root/structural causes; (ii) social position/foundations; (iii) infrastructure and systems; and (iv) communities, households and individuals. Findings: Of the 188 initially identified articles, we included 60 in our review. Most (53/60) were published after 2020, when academic interest had shifted towards global financing mechanisms. Most (37/60) addressed two or more of the council framework elements. The most frequently addressed element was infrastructure and systems (54/60), discussing topics such as health systems, financial markets and innovation ecosystems. The roots/structural causes were discussed in 25 articles; communities, households and individuals in 22 articles; and social positions/foundations in 11. Conclusion: Our review identified three important gaps: a formal definition of pandemic preparedness and response, impeding the accurate quantification of the financing shortfall; research on the extent to which financing for pandemic preparedness and response has been targeted at the most vulnerable households; and an analysis of specific financial instruments and an evaluation of the feasibility of their implementation.

Maternal immunisation against Group B Streptococcus: A global analysis of health impact and cost-effectiveness.

BACKGROUND: Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally. METHODS AND FINDINGS: We assessed the health impact and value (using net monetary benefit (NMB), which measures both health and economic effects of vaccination into monetary units) of GBS maternal vaccination in an annual cohort of 140 million pregnant women across 183 countries in 2020. Our analysis uses a decision tree model, incorporating risks of GBS-related health outcomes from an existing Bayesian disease burden model. We extrapolated country-specific GBS-related healthcare costs using data from a previous systematic review and calculated quality-adjusted life years (QALYs) lost due to infant mortality and long-term disability. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least 4 antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle-income countries. We estimated NMB using alternative normative assumptions that may be adopted by policymakers. Vaccinating pregnant women could avert 127,000 (95% uncertainty range 63,300 to 248,000) early-onset and 87,300 (38,100 to 209,000) late-onset infant iGBS cases, 31,100 deaths (14,400 to 66,400), 17,900 (6,380 to 49,900) cases of moderate and severe neurodevelopmental impairment, and 23,000 (10,000 to 56,400) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 185,000 (13,500 to 407,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 to 3.8 billion) under the least favourable normative assumptions to $17 billion ($9.1 to 31 billion) under the most favourable normative assumptions. The main limitation of our analysis was the scarcity of data to inform some of the model parameters such as those governing health-related quality of life and long-term costs from disability, and how these parameters may vary across country contexts. CONCLUSIONS: In this study, we found that maternal GBS vaccination could have a large impact on infant morbidity and mortality. Globally, a GBS maternal vaccine at reasonable prices is likely to be a cost-effective intervention.

The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study.

BACKGROUND: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies. METHODS AND FINDINGS: We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a "no-new-vaccine" counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs. CONCLUSIONS: TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines.

The Full Value of Vaccine Assessments (FVVA): a framework for assessing and communicating the value of vaccines for investment and introduction decision-making.

BACKGROUND: Several economic obstacles can deter the development and use of vaccines. This can lead to limited product options for some diseases, delays in new product development, and inequitable access to vaccines. Although seemingly distinct, these obstacles are actually interrelated and therefore need to be addressed through a single over-arching strategy encompassing all stakeholders. METHODS: To help overcome these obstacles, we propose a new approach, the Full Value of Vaccines Assessments (FVVA) framework, to guide the assessment and communication of the value of a vaccine. The FVVA framework is designed to facilitate alignment across key stakeholders and to enhance decision-making around investment in vaccine development, policy-making, procurement, and introduction, particularly for vaccines intended for use in low- and middle-income countries. RESULTS: The FVVA framework has three key elements. First, to enhance assessment, existing value-assessment methods and tools are adapted to include broader benefits of vaccines as well as opportunity costs borne by stakeholders. Second, to improve decision-making, a deliberative process is required to recognize the agency of stakeholders and to ensure country ownership of decision-making and priority setting. Third, the FVVA framework provides a consistent and evidence-based approach that facilitates communication about the full value of vaccines, helping to enhance alignment and coordination across diverse stakeholders. CONCLUSIONS: The FVVA framework provides guidance for stakeholders organizing global-level efforts to promote investment in vaccines that are priorities for LMICs. By providing a more holistic view of the benefits of vaccines, its application also has the potential to encourage greater take-up by countries, thereby leading to more sustainable and equitable impacts of vaccines and immunization programmes.

Estimating the delivery costs of COVID-19 vaccination using the COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool: the Lao People's Democratic Republic experience.

BACKGROUND: The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People's Democratic Republic (Lao PDR). METHODS: From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar. RESULTS: From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79-0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15-34% and 15-24% of the total costs in all scenarios, respectively. 17-26% went to data management, monitoring and evaluation, and oversight, and 13-22% to vaccine delivery. CONCLUSIONS: With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost-benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.

Comprehensive approach to costing cervical cancer prevention and control: a case study in the United Republic of Tanzania using the Cervical Cancer Prevention and Control Costing (C4P) tool.

BACKGROUND: The World Health Organization (WHO) has developed a costing tool, the Cervical Cancer Prevention and Control Costing (C4P) tool, to estimate the comprehensive cost of cervical cancer primary, secondary and tertiary prevention in low- and middle-income countries. The tool was piloted in the United Republic of Tanzania, a country with a high incidence of cervical cancer with 62.5 cases per 100,000 women in 2020. This paper presents the costing tool methods as well as the results from the pilot in Tanzania. METHODS: The C4P tool estimates the incremental costs of cervical cancer prevention and control programmes. It estimates the financial (monetary costs to the government) and economic costs (opportunity costs). For the pilot, the study team collected data on costs and programme assumptions for human papillomavirus (HPV) vaccination of 14-year-old girls and scaling up of cervical cancer screening (visual inspection with acetic acid and HPV-DNA testing) and treatment for women for 2020-2024. Assumptions were made on how vaccination coverage would increase over the 5 years as well as developing additional screening and treatment capacity through health personnel training and infrastructure strengthening. RESULTS: The total financial and economic costs of the comprehensive programme during 2020-2024 are projected to be US$68 million and US$124 million, respectively. The financial and economic costs of a fully immunized girl with HPV vaccine are estimated to be US$6.68 and US$17.31, respectively, while the costs per woman screened for cervical cancer are, on average, US$4.02 and US$5.83, respectively; US$6.44 and US$9.37 for pre-cancer treatment, respectively; and US$101 and US$107 for diagnosis of invasive cancer, respectively. The cost of treating and managing invasive cancer range from US$7.05 and US$7.83 for outpatient palliative care to US$800.21 and US$893.80 for radiotherapy, respectively. CONCLUSIONS: The C4P costing tool can assist national cervical cancer programmes to estimate monetary resources needed as well as opportunity costs of reducing national cervical cancer incidence through primary, secondary and tertiary prevention.

WHO-led consensus statement on vaccine delivery costing: process, methods, and findings.

BACKGROUND: Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization's (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement. METHODS: The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed. RESULTS: The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made. CONCLUSIONS: Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context.

The impact of pharmacist involvement on immunization uptake and other outcomes: An updated systematic review and meta-analysis.

BACKGROUND: The underutilization of immunization services remains a big public health concern. Pharmacists can address this concern by playing an active role in immunization administration. OBJECTIVE: We performed a systematic review and meta-analysis to assess the impact of pharmacist-involved interventions on immunization rates and other outcomes indirectly related to vaccine uptake. METHODS: A systematic literature search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception to February 2022 to identify randomized controlled trials (RCTs) and observational studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms. Meta-analyses were performed using a random-effects model. RESULTS: A total of 14 RCTs and 79 observational studies were included. Several types of immunizations were provided, including influenza, pneumococcal, herpes zoster, Tdap, and others in a variety of settings (community pharmacy, hospital, clinic, others). Pooled analyses from RCTs indicated that a pharmacist as immunizer (risk ratio 1.14 [95% CI 1.12-1.15]), advocator (1.31 [1.17-1.48]), or both (1.14 [1.12-1.15]) significantly increased immunization rates compared with usual care or non-pharmacist-involved interventions. The quality of evidence was assessed as moderate or low for those meta-analyses. Evidence from observational studies was consistent with the results found in the analysis of the RCTs. CONCLUSION: Pharmacist involvement as immunizer, advocator, or both roles has favorable effects on immunization uptake, especially with influenza vaccines in the United States and some high-income countries. As the practice of pharmacists in immunization has been expanded globally, further research on investigating the impact of pharmacist involvement in immunization in other countries, especially developing ones, is warranted.

Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries.

BACKGROUND: The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. FINDINGS: Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination. INTERPRETATION: Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

Mortality impact of achieving WHO cervical cancer elimination targets: a comparative modelling analysis in 78 low-income and lower-middle-income countries.

BACKGROUND: WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. FINDINGS: In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120. INTERPRETATION: These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.

Effectiveness and cost-effectiveness of eliminating cervical cancer through a tailored optimal pathway: a modeling study.

BACKGROUND: The World Health Assembly has adopted a global strategy to eliminate cervical cancer. However, neither the optimal pathway nor the corresponding economic and health benefits have been evaluated. We take China as an example to assess the optimal pathway towards elimination and the cost-effectiveness of tailored actions. METHODS: A validated hybrid model was used to assess the costs and benefits of alternative strategies combining human papillomavirus vaccination, cervical screening, and treatment of pre-invasive lesions and invasive cancer for females with different immunization history. All Chinese females living or projected to be born during 2015-2100, under projected trends in aging, urbanization, and sexual activity, were considered. Optimal strategies were determined by cost-effectiveness efficiency frontiers. Primary outcomes were cervical cancer cases and deaths averted and incremental cost-effectiveness ratios (ICERs). We employed a lifetime horizon from a societal perspective. One-way and probabilistic sensitivity analyses evaluate model uncertainty. RESULTS: The optimal pathway represents an integration of multiple tailored strategies from females with different immunization history. If China adopts the optimal pathway, the age-standardized incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100,000 women (i.e., elimination) by 2047 (95% confidence interval 2043 to 2050). Compared to the status quo, the optimal pathway would avert a total of 7,509,192 (6,922,744 to 8,359,074) cervical cancer cases and 2,529,873 (2,366,826 to 2,802,604) cervical cancer deaths in 2021-2100, with the discounted ICER being $- 339 (- 687 to - 79) per quality-adjusted life-year. CONCLUSIONS: By adopting an optimal pathway from 2021 (namely, the year of the first Chinese Centennial Goals) onwards, cervical cancer could be eliminated by the late 2040s (namely, ahead of the second Chinese Centennial Goals) while saving net economic costs in China.

The CAPACITI Decision-Support Tool for National Immunization Programs.

OBJECTIVES: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies. METHODS: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas. RESULTS: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership. CONCLUSIONS: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.

Guidelines for multi-model comparisons of the impact of infectious disease interventions.

BACKGROUND: Despite the increasing popularity of multi-model comparison studies and their ability to inform policy recommendations, clear guidance on how to conduct multi-model comparisons is not available. Herein, we present guidelines to provide a structured approach to comparisons of multiple models of interventions against infectious diseases. The primary target audience for these guidelines are researchers carrying out model comparison studies and policy-makers using model comparison studies to inform policy decisions. METHODS: The consensus process used for the development of the guidelines included a systematic review of existing model comparison studies on effectiveness and cost-effectiveness of vaccination, a 2-day meeting and guideline development workshop during which mathematical modellers from different disease areas critically discussed and debated the guideline content and wording, and several rounds of comments on sequential versions of the guidelines by all authors. RESULTS: The guidelines provide principles for multi-model comparisons, with specific practice statements on what modellers should do for six domains. The guidelines provide explanation and elaboration of the principles and practice statements as well as some examples to illustrate these. The principles are (1) the policy and research question - the model comparison should address a relevant, clearly defined policy question; (2) model identification and selection - the identification and selection of models for inclusion in the model comparison should be transparent and minimise selection bias; (3) harmonisation - standardisation of input data and outputs should be determined by the research question and value of the effort needed for this step; (4) exploring variability - between- and within-model variability and uncertainty should be explored; (5) presenting and pooling results - results should be presented in an appropriate way to support decision-making; and (6) interpretation - results should be interpreted to inform the policy question. CONCLUSION: These guidelines should help researchers plan, conduct and report model comparisons of infectious diseases and related interventions in a systematic and structured manner for the purpose of supporting health policy decisions. Adherence to these guidelines will contribute to greater consistency and objectivity in the approach and methods used in multi-model comparisons, and as such improve the quality of modelled evidence for policy.

A Scoping Review of Investment Cases for Vaccines and Immunization Programs.

BACKGROUND: Many investment cases have recently been published intending to show the value of new health investments, but without consistent methodological approaches. OBJECTIVES: To conduct a scoping review of existing investment cases (using vaccines and immunization programs as an example), identify common characteristics that define these investment cases, and examine their role within the broader context of the vaccine development and introduction. METHODS: A systematic search was conducted from January 1980 to November 2017 to identify investment cases in the area of vaccines and immunization programs from gray literature and electronic bibliographic databases. Investment case outcomes, objectives, key variables, target audiences, and funding sources were extracted and analyzed according to their reporting frequency. RESULTS: We found 24 investment cases, and most of them aim to provide information for decisions (12 cases) or advocate for a specific agenda (9 cases). Outcomes presented fell into 4 broad categories-burden of disease, cost of investment, impact of investment, and other considerations for implementation. Number of deaths averted (70%), incremental cost-effectiveness ratios (67%), and reduction in health and socioeconomic inequalities (54%) were the most frequently reported outcome measures for impact of investment. Health system capacity (79%) and vaccine financing landscape (75%) were the most common considerations for implementation. A sizable proportion (41.4%) of investment cases did not reveal their funding sources. CONCLUSIONS: This review describes information that is critical to decision making about resource mobilization and allocation concerning vaccines. Global efforts to harmonize investment cases more broadly will increase transparency and comparability.

Model Comparisons of the Effectiveness and Cost-Effectiveness of Vaccination: A Systematic Review of the Literature.

OBJECTIVES: To describe all published articles that have conducted comparisons of model-based effectiveness and cost-effectiveness results in the field of vaccination. Specific objectives were to 1) describe the methodologies used and 2) identify the strengths and limitations of the studies. METHODS: We systematically searched MEDLINE and Embase databases for studies that compared predictions of effectiveness and cost-effectiveness of vaccination of two or more mathematical models. We categorized studies into two groups on the basis of their data source for comparison (previously published results or new simulation results) and performed a qualitative synthesis of study conclusions. RESULTS: We identified 115 eligible articles (only 5% generated new simulations from the reviewed models) examining the effectiveness and cost-effectiveness of vaccination against 14 pathogens (69% of studies examined human papillomavirus, influenza, and/or pneumococcal vaccines). The goal of most of studies was to summarize evidence for vaccination policy decisions, and cost-effectiveness was the most frequent outcome examined. Only 33%, 25%, and 3% of studies followed a systematic approach to identify eligible studies, assessed the quality of studies, and performed a quantitative synthesis of results, respectively. A greater proportion of model comparisons using published studies followed a systematic approach to identify eligible studies and to assess their quality, whereas more studies using new simulations performed quantitative synthesis of results and identified drivers of model conclusions. Most comparative modeling studies concluded that vaccination was cost-effective. CONCLUSIONS: Given the variability in methods used to conduct/report comparative modeling studies, guidelines are required to enhance their quality and transparency and to provide better tools for decision making.

Economic Analysis of Vaccination Programs: An ISPOR Good Practices for Outcomes Research Task Force Report.

This report provides recommendations for budget holders and decision makers in high-, middle, and low-income countries requiring economic analyses of new vaccination programs to allocate scarce resources given budget constraints. ISPOR's Economic Evaluation of Vaccines Designed to Prevent Infectious Disease: Good Practices Task Force wrote guidelines for three analytic methods and solicited comments on them from external reviewers. Cost-effectiveness analyses use decision-analytic models to estimate cumulative changes in resource use, costs, and changes in quality- or disability-adjusted life-years attributable to changes in disease outcomes. Constrained optimization modeling uses a mathematical objective function to be optimized (e.g. disease cases avoided) for a target population for a set of interventions including vaccination programs within established constraints. Fiscal health modeling estimates changes in net present value of government revenues and expenditures attributable to changes in disease outcomes. The task force recommends that those designing economic analyses for new vaccination programs take into account the decision maker's policy objectives and country-specific decision context when estimating: uptake rate in the target population; vaccination program's impact on disease cases in the population over time using a dynamic transmission epidemiologic model; vaccination program implementation and operating costs; and the changes in costs and health outcomes of the target disease(s). The three approaches to economic analysis are complementary and can be used alone or together to estimate a vaccination program's economic value for national, regional, or subregional decision makers in high-, middle-, and low-income countries.

Cost-effectiveness thresholds: pros and cons.

Cost-effectiveness analysis is used to compare the costs and outcomes of alternative policy options. Each resulting cost-effectiveness ratio represents the magnitude of additional health gained per additional unit of resources spent. Cost-effectiveness thresholds allow cost-effectiveness ratios that represent good or very good value for money to be identified. In 2001, the World Health Organization's Commission on Macroeconomics in Health suggested cost-effectiveness thresholds based on multiples of a country's per-capita gross domestic product (GDP). In some contexts, in choosing which health interventions to fund and which not to fund, these thresholds have been used as decision rules. However, experience with the use of such GDP-based thresholds in decision-making processes at country level shows them to lack country specificity and this - in addition to uncertainty in the modelled cost-effectiveness ratios - can lead to the wrong decision on how to spend health-care resources. Cost-effectiveness information should be used alongside other considerations - e.g. budget impact and feasibility considerations - in a transparent decision-making process, rather than in isolation based on a single threshold value. Although cost-effectiveness ratios are undoubtedly informative in assessing value for money, countries should be encouraged to develop a context-specific process for decision-making that is supported by legislation, has stakeholder buy-in, for example the involvement of civil society organizations and patient groups, and is transparent, consistent and fair.

Les analyses de rentabilité permettent de comparer les coûts et les résultats de différentes options politiques. Chaque ratio coût-efficacité qui en découle indique l'importance des avantages supplémentaires pour la santé par unité supplémentaire de ressources dépensée. Les seuils de rentabilité permettent de déterminer les ratios coût-efficacité qui représentent une bonne ou une très bonne rentabilité. En 2001, la Commission macroéconomie et santé de l'Organisation mondiale de la Santé a suggéré des seuils de rentabilité définis d'après des multiples du produit intérieur brut (PIB) par habitant d'un pays. Dans certains pays, ces seuils ont servi de règles pour décider quelles interventions financer ou non. Cependant, l'expérience d'utilisation de ces seuils fondés sur le PIB dans les processus décisionnels des pays montre qu'ils ne tiennent pas compte des spécificités des pays; cela, ajouté à une certaine incertitude concernant la modélisation des ratios coût-efficacité, peut entraîner la prise de mauvaises décisions quant à l'utilisation des ressources sanitaires. Les informations sur la rentabilité des interventions devraient être prises en compte parallèlement à d'autres considérations, comme l'impact budgétaire et la faisabilité, dans le cadre d'un processus décisionnel transparent et non de façon isolée sur la base d'une seule valeur seuil. Bien que le caractère informatif des ratios coût-efficacité soit indéniable lorsqu'il s'agit d'évaluer la rentabilité des interventions, les pays devraient être encouragés à développer un processus de prise de décision spécifique au contexte, qui soit encadré par la législation et qui ait l'adhésion des parties intéressées, avec par exemple l'implication d'organisations de la société civile et de groupes de patients, et qui soit transparent, cohérent et équitable.

El análisis de rentabilidad se utiliza para comparar los costes y resultados de opciones políticas alternativas. Cada relación de rentabilidad resultante representa la magnitud de sanidad adicional obtenida por unidad adicional de recursos utilizados. Los umbrales de rentabilidad permiten la identificación de las relaciones de rentabilidad que representan un valor bueno o muy bueno del capital. En 2001, los umbrales de rentabilidad propuestos por la Comisión sobre Macroeconomía y Salud de la Organización Mundial de la Salud se basaron en múltiplos del producto interior bruto (PIB) per cápita de un país. En algunos contextos, se han utilizado estos umbrales para decidir qué intervenciones sanitarias financiar y cuáles no. No obstante, la experiencia con el uso de dichos umbrales basados en el PIB en los procesos de toma de decisiones a nivel nacional muestra la ausencia de especificidad según el país. Esto, además de la incertidumbre de las relaciones de rentabilidad modelo, puede dar lugar a una toma de decisiones equivocada sobre cómo emplear los recursos sanitarios. La información relativa a la rentabilidad debería utilizarse teniendo en cuenta otros factores (por ejemplo, el impacto presupuestario y aspectos de viabilidad) en un proceso transparente de toma de decisiones, en lugar de únicamente teniendo como referencia un solo valor del umbral. A pesar de que las relaciones de rentabilidad son indudablemente esclarecedoras a la hora de evaluar el valor del capital, es necesario fomentar que los países desarrollen un proceso específico del contexto apoyado por la legislación para tomar decisiones, como, por ejemplo, si las partes interesadas han aceptado la implicación de las organizaciones de la sociedad civil y grupos de pacientes y si es transparente, coherente y justa.

Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

OBJECTIVES: To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. METHODS: The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. RESULTS: We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. CONCLUSION: We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency.