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Abstract Background Globally, herpes simplex virus (HSV)-2 and -1 infections contribute to a large disease burden, but their full economic consequences remain unclear. This study aims to estimate the global economic impact of genital HSV-2 and HSV-1 infection and its consequences for people with genital ulcer disease, neonatal herpes, and human immunodeficiency virus (HIV) infection attributable to HSV-2. Methods Using a societal perspective, the economic burden was calculated at the country level and presented by World Health Organization (WHO) regions and World-Bank income levels. The disease burden was obtained from previously published global disease burden studies in 2016 and disaggregated for 194 countries. Estimates of healthcare resource utilisation were sourced from a literature review, and online interviews were conducted with 20 experts from all 6 WHO regions. Relevant costs were obtained from the literature and estimated in 2016 international dollars (I$). Results Both genital HSV-2 (I$31·2 billion) and HSV-1 (I$4·0 billion) infections and their consequences were estimated to cost I$35·3 billion globally in 2016. The major economic burden was from the Americas and Western Pacific regions combined, accounting for almost two-thirds of the global burden (I$20·8 billion). High- and upper-middle-income countries bore a large proportion of the economic burden (76·6% or I$27·0 billion). Costs were driven by the large number of HSV-2 recurrences; however, even assuming conservatively that people with symptomatic herpes have on average only one episode a year, global costs were estimated at I$16·5 billion. Conclusions The global costs of genital HSV infection and its consequences are substantial. HSV prevention interventions have the potential to avert a large economic burden in addition to disease burden; thus, efforts to accelerate HSV vaccine development are crucial.

Introduction The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction.Methods The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis.Results Six studies reported a positive benefit–cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost.Conclusions Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers.PROSPERO Registration CRD42020200669

Abstract 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.

For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities.

To ensure that limited domestic resources are invested in the most effective interventions, immunization programs in low- and middle-income countries (LMICs) must prioritize a growing number of new vaccines while considering opportunities to optimize the vaccine portfolio, as well as other components of the health system. There is a strong impetus for immunization decision-making to engage and coordinate various stakeholders across the health system in prioritization. To address this, national immunization program decision-makers in LMICs collaborated with WHO to structure deliberation among stakeholders and document an evidence-based, context-specific, and transparent process for prioritization or selection among multiple vaccination products, services, or strategies. The output of this effort is the Country-led Assessment for Prioritization on Immunization (CAPACITI) decision-support tool, which supports using multiple criteria and stakeholder perspectives to evaluate trade-offs affecting health interventions, taking into account variable data quality. Here, we describe the user feedback from Indonesia and Ethiopia, two initial countries that piloted the CAPACITI decision-support tool, highlighting enabling and constraining factors. Potential immunization program benefits and lessons learned are also summarized for consideration in other settings.

Background Studies assessing the indirect impact of COVID-19 using mathematical models have increased in recent years. This scoping review aims to identify modelling studies assessing the potential impact of disruptions to essential health services caused by COVID-19 and to summarise the characteristics of disruption and the models used to assess the disruptions.Methods Eligible studies were included if they used any models to assess the impact of COVID-19 disruptions on any health services. Articles published from January 2020 to December 2022 were identified from PubMed, Embase and CINAHL, using detailed searches with key concepts including COVID-19, modelling and healthcare disruptions. Two reviewers independently extracted the data in four domains. A descriptive analysis of the included studies was performed under the format of a narrative report.Results This scoping review has identified a total of 52 modelling studies that employed several models (n=116) to assess the potential impact of disruptions to essential health services. The majority of the models were simulation models (n=86; 74.1%). Studies covered a wide range of health conditions from infectious diseases to non-communicable diseases. COVID-19 has been reported to disrupt supply of health services, demand for health services and social change affecting factors that influence health. The most common outcomes reported in the studies were clinical outcomes such as mortality and morbidity. Twenty-five studies modelled various mitigation strategies; maintaining critical services by ensuring resources and access to services are found to be a priority for reducing the overall impact.Conclusion A number of models were used to assess the potential impact of disruptions to essential health services on various outcomes. There is a need for collaboration among stakeholders to enhance the usefulness of any modelling. Future studies should consider disparity issues for more comprehensive findings that could ultimately facilitate policy decision-making to maximise benefits to all.

Abstract 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.

Understanding the level of investment needed for the next decade is vital to achieve the goal of Immunization Agenda 2030 (IA2030). Through the immunization funder perspective, this study estimates both global and regional economic resources required to achieve IA2030 coverage among 194 WHO member countries from 2021 to 2030, against 14 pathogens: Hepatitis B (Hep B), Haemophilus influenzae type b (Hib), Human papillomavirus (HPV), Japanese encephalitis (JE), Measles, Meningitis A (Men A), Streptococcus pneumoniae, Rotavirus, Rubella, Yellow Fever (YF), Diphtheria, Tetanus, Pertussis, and Tuberculosis.The total cost of immunization program, routine vaccine, routine delivery, and non-routine costs (SIA and stockpile) were estimated using WHO coverage forecast for IA2030. Incremental costs of achieving IA2030 for all vaccines and cost per immunized child were also assessed. All costs were calculated for each income and regional level, as well as global level. Scenario analysis and sensitivity analysis were conducted to account for uncertainty in future vaccine pricing and delivery costs.The total cost of immunization programs is $269.8 billion (95% confidence interval: $247.1 - $311.8), of which $152.8 billion is considered as routine vaccine cost, $114.9 billion is routine delivery cost. Non– routine cost for LICs and LMICs totaled $2.1 billion. The incremental cost of achieving coverage goals after 2020 is $89.9 billion ($27.7-$110.1), with upper-middle income countries requiring the largest increase in investment (56.2% of incremental costs). The average immunization cost per child across all countries is $192.6. Scenario analysis using the minimum and maximum vaccines price for fully self-financing countries resulted in total costs ranging from $193.6 and $552.2 billion.The immunization program cost among 194 WHO member countries is expected to increase during this decade. The strategy for resource mobilization and increasing investment from country governments and donors are essential to achieving IA2030 coverage and ensuring sustainable immunization programs.

BackgroundGroup 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 findingsWe 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.ConclusionsIn 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.

Navi Mumbai Municipal Corporation (NMMC), a local government in Mumbai, India, implemented the first public sector TCV campaign in 2018. This study estimated the delivery costs of this TCV campaign using a Microsoft Excel-based tool based on a micro-costing approach from the government (NMMC) perspective. The campaign's financial (direct expenditures) and economic costs (financial costs plus the monetized value of additional donated or existing items) incremental to the existing immunization program were collected. The data collection methods involved consultations with NMMC staff, reviews of financial and programmatic records of NMMC and the World Health Organization (WHO), and interviews with the health staff of sampled urban health posts (UHPs). Three UHPs were purposively sampled, representing the three dominant residence types in the catchment area: high-rise, slum, and mixed (high-rise and slum) areas. The high-rise area UHP had lower vaccination coverage (47%) compared with the mixed area (71%) and slum area UHPs (76%). The financial cost of vaccine and vaccination supplies (syringes, safety boxes) was $1.87 per dose, and the economic cost was $2.96 per dose in 2018 US dollars. Excluding the vaccine and vaccination supplies cost, the financial delivery cost across the 3 UHPs ranged from $0.37 to $0.53 per dose, and the economic delivery cost ranged from $1.37 to $3.98 per dose, with the highest delivery costs per dose in the high-rise areas. Across all 11 UHPs included in the campaign, the weighted average financial delivery cost was $0.38 per dose, and the economic delivery cost was $1.49 per dose. WHO has recommended the programmatic use of TCV in typhoid-endemic countries, and Gavi has included TCV in its vaccine portfolio. This first costing study of large-scale TCV introduction within a public sector immunization program provides empirical evidence for policymakers, stakeholders, and future vaccine campaign planning.

Abstract 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.

Background Information on cost-effectiveness allows policy-makers to evaluate if they are using currently available resources effectively and efficiently. Our objective is to examine the cost-effectiveness of health interventions to improve maternal, newborn and child health (MNCH) outcomes, to provide global evidence relative to the context of two geographic regions. Methods We consider interventions across the life course from adolescence to pregnancy and for children up to 5 years old. Interventions included are those that fall within the areas of immunization, child healthcare, nutrition, reproductive health, and maternal/newborn health, and for which it is possible to model impact on MNCH mortality outcomes using the Lives Saved Tool (LiST). Generalized cost-effectiveness analysis (GCEA) was used to derive average cost-effectiveness ratios (ACERs) for individual interventions and combinations (packages). Costs were assessed from the health system perspective and reported in international dollars. Health outcomes were estimated and reported as the gain in healthy life years (HLYs) due to the specific intervention or combination. The model was run for 2 regions: Eastern sub-Saharan Africa (SSA-E) and South-East Asia (SEA). Results The World Health Organization (WHO) recommended interventions to improve MNCH are generally considered cost-effective, with the majority of interventions demonstrating ACERs below I$100/HLY saved in the chosen settings (lowand middle-income countries [LMICs]). Best performing interventions are consistent across the two regions, and include family planning, neonatal resuscitation, management of pneumonia and neonatal infection, vitamin A supplementation, and measles vaccine. ACERs below I$100 can be found across all delivery platforms, from community to hospital level. The combination of interventions into packages (such as antenatal care) produces favorable ACERs. Conclusion Within each region there are interventions which represent very good value for money. There are opportunities to gear investments towards high-impact interventions and packages for MNCH outcomes. Cost-effectiveness tools can be used at national level to inform investment cases and overall priority setting processes.

Background: As SARS-CoV-2 spread in early 2020, uncertainty about the scope, duration, and impact of the unfolding outbreaks caused numerous countries to interrupt many routine activities, including health services. Because immunization is an essential health service, modeling changes in SARS-CoV-2 infections among communities and health workers due to different vaccination activities was undertaken to understand the risks and to inform approaches to resume services. Methods: Agent-based modeling examined the impact of Supplemental Immunization Activities (SIAs) delivery strategies on SARS-CoV-2 transmission in communities and health workers for six countries capturing various demographic profiles and health system performance: Angola, Ecuador, Lao PDR, Nepal, Pakistan, and Ukraine. Results: Urban, fixed-post SIAs during periods of high SARS-CoV-2 prevalence increased infections within the community by around 28 [range:0-79] per 1000 vaccinations. House-to-house SIAs in mixed urban and rural contexts may import infections into previously naïve communities. Infections are elevated by around 60 [range:0-230] per 1000 vaccinations, but outcomes are sensitive to prevalence in health workers and SIA timing relative to peak. Conclusions: Incremental increases in SARS-CoV-2 infection due to SIAs was small and in proportion to overall prevalence. Younger populations experience lower transmission intensity and fewer excess infections per childhood vaccine delivered. Large rural populations have lower transmission intensity but face a greater risk of introduction of SARS-CoV-2 during an SIA.

Summary: Background: A number of cost-effectiveness analysis of influenza vaccination have been conducted to estimate value of influenza vaccines in elderly and health workers (HWs). This study aims to summarize cost-effectiveness evidence by pooling the incremental net monetary benefit (INMB) of influenza vaccination. Methods: A systematic review was performed in electronic databases from their inceptions to February 2022. Cost-effectiveness studies reporting quality-adjusted life year (QALY), or life year (LY) of influenza vaccination were included. Stratified meta-analyses by population, perspective, country income-level, and herd-effect were performed to pool INMB across studies. The protocol was registered at PROSPERO (CRD42021246746). Findings: A total of 21 studies were included. Eighteen studies were conducted in elderly, two studies were conducted in HWs, and one study was conducted in both elderly and HWs. According to pre-specified analyses, studies for elderly in high-income economies (countries) (HIEs) and upper-middle income economies (UMIEs) without herd effect could be pooled. For HIEs under a societal perspective, the perspective which identify all relevant costs occurred in the society including direct medical cost, direct non-medical cost and indirect cost, pooled INMB was $217·38 (206·23, 228·53, I2 =28.2%), while that for healthcare provider/payer perspective was $0·20 (-11,908·67, 11,909·07, I2 = 0.0%). For societal perspective in UMIEs, pooled INMB was $28·39 (-190·65, 133·87, I2 = 92.8%). The findings were robust across a series of sensitivity analyses for HIEs. Studies in HWs indicated that influenza vaccination was cost-effective compared to no vaccination or current practice. Interpretation: Influenza vaccination might be cost-effective for HWs and elderly in HIEs under a societal perspective with relatively small variations among included studies, while there remains limited evidence for healthcare provider/payer perspective or other level of incomes. Further evidence is warranted. Funding: This study was funded by a grant of Immunization, Vaccine and Biologicals department of the World Health Organization. The authors would like to acknowledge the contributions of the US CDC which provided financial support to the development and publication of this report. Grant number US CDC, WHO IVR (U50CK000431).

Abstract 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 Immunization Agenda 2030 prioritizes the populations without access to vaccines. Health equity has been increasingly incorporated into economic evaluations of vaccines to foster equitable access. Robust and standardized methods are needed to evaluate the health equity impact of vaccination programs to ensure monitoring and effective addressing of inequities. However, methods currently in place vary and potentially affect the application of findings to inform policy decision-making. We performed a systematic review by searching PubMed, Embase, Econlit, and the CEA Registry up to 15 December 2022 to identify equity-informative economic evaluations of vaccines. Twenty-one studies were included that performed health equity impact analysis to estimate the distributional impact of vaccines, such as deaths averted and financial risk protection, across equity-relevant subgroups. These studies showed that the introduction of vaccines or improved vaccination coverage resulted in fewer deaths and higher financial risk benefits in subpopulations with higher disease burdens and lower vaccination coverage—particularly poorer income groups and those living in rural areas. In conclusion, methods to incorporate equity have been evolving progressively. Vaccination programs can enhance equity if their design and implementation address existing inequities in order to provide equitable vaccination coverage and achieve health equity.

COVID-19 disease models have aided policymakers in low-and middle-income countries (LMICs) with many critical decisions. Many challenges remain surrounding their use, from inappropriate model selection and adoption, inadequate and untimely reporting of evidence, to the lack of iterative stakeholder engagement in policy formulation and deliberation. These issues can contribute to the misuse of models and hinder effective policy implementation. Without guidance on how to address such challenges, the true potential of such models may not be realised. The COVID-19 Multi-Model Comparison Collaboration (CMCC) was formed to address this gap. CMCC is a global collaboration between decision-makers from LMICs, modellers and researchers, and development partners. To understand the limitations of existing COVID-19 disease models (primarily from high income countries) and how they could be adequately support decision-making in LMICs, a desk review of modelling experience during the COVID-19 and past disease outbreaks, two online surveys, and regular online consultations were held among the collaborators. Three key recommendations from CMCC include: A ‘fitness-for-purpose’ flowchart, a tool that concurrently walks policymakers (or their advisors) and modellers through a model selection and development process. The flowchart is organised around the following: policy aims, modelling feasibility, model implementation, model reporting commitment. Holmdahl and Buckee (2020) A ‘reporting standards trajectory’, which includes three gradually increasing standard of reports, ‘minimum’, ‘acceptable’, and ‘ideal’, and seeks collaboration from funders, modellers, and decision-makers to enhance the quality of reports over time and accountability of researchers. Malla et al. (2018) A framework for “collaborative modelling for effective policy implementation and evaluation” which extends the definition of stakeholders to funders, ground-level implementers, public, and other researchers, and outlines how each can contribute to modelling. We advocate for standardisation of modelling processes and adoption of country-owned model through iterative stakeholder participation and discuss how they can enhance trust, accountability, and public ownership to decisions.

Over the past few years, many innovative vaccines became available that offer protection for diseases which have never been prevented before. While there are several factors that could have an impact on access, the use of health technology assessment (HTA) undoubtedly is also one of the contributing factors. Objectives: To explore the landscape of vaccine access and the role of HTA in new vaccine adoption in Association of Southeast Asian Nations (ASEAN) countries. Results: A great deal of progress has been made in terms of access to new and innovation vaccine in the region. Variation in access to these vaccines comparing between countries, however, is still observed. The use of HTA in supporting new vaccine adoption is still in an early stage especially in Gavi, the Vaccine Alliance-eligible countries. Conclusions: Improving the use of HTA evidences to support decision making could accelerate the efficient adoption of new vaccine in ASEAN region.

Abstract 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.

Innovations in vaccine product attributes could play an important role in addressing coverage and equity (C&E) gaps, but there is currently a poor understanding of the full system impact and trade-offs associated with investing in such technologies, both from the perspective of national immunisation programmes (NIPs) and vaccine developers. Total Systems Effectiveness (TSE) was developed as an approach to evaluate vaccines with different product attributes from a systems perspective, in order to analyse and compare the value of innovative vaccine products in different settings.The TSE approach has been advanced over the years by various stakeholders including the Bill and Melinda Gates Foundation (BMGF), Gavi, PATH, UNICEF and WHO. WHO further developed the TSE approach to incorporate the country perspective into immunisation decision-making, in order for countries to evaluate innovative products for introduction and product switch decisions, and for vaccine development stakeholders to conduct their assessments of product value in line with country preferences. This paper describes the original TSE approach, development of the tool and processes for NIPs to apply the WHO TSE approach, and results from piloting in 12 countries across Africa, Asia and the Americas. The WHO TSE framework emerged from this piloting effort.The WHO TSE approach has been welcomed by NIP and vaccine development stakeholders as a useful tool to evaluate trade-offs between different products. It was emphasised that the concept of “total systems effectiveness” is likely to be context-specific and that TSE is valuable in facilitating a deliberative process to articulate NIP priorities, for decisions around product choice, and for prioritising the development of future vaccine innovations.

Introduction: The cervical cancer-related burden is an important problem in Southeast Asian (SEA) countries. However, only 3 out of 11 countries implement the comprehensive prevention program. Areas covered: This is a retrospective review from all relevant studies until 2015 from two main databases, MEDLINE/Pubmed and Embase in order to provide an evidence on the health economics of HPV vaccination in the region. Expert commentary: The implementation of HPV vaccination will generate substantial health and economic benefit in SEA countries since the number of cervical cancer cases in this region are generally high. Therefore, a clear recommendation on how HPV vaccination should be implemented in a country, for example on how many doses will be used, how much cost is required or is it a school based- or clinical based-delivery, is critically required.

Summary: Background: The incidence of cervical cancer in China is increasing rapidly. We aimed to forecast the age-standardised incidence of cervical cancer in China up to 2100, and to determine the optimal strategy to eliminate cervical cancer under different budget scenarios. Methods: In our modelling study, we developed an adapted and calibrated hybrid model to estimate the incidence of cervical cancer in urban and rural China until 2100. All 1·15 billion Chinese women living or projected to live during 2015–2100, under the projected trends in ageing, urbanisation, and sexual activity were considered. We assessed several scenarios of budget constraints (a current budget [2012–18], twice the current budget, and no budget constraints), implementation of human papillomavirus vaccination (with different target populations and coverage), and cervical cancer screening characteristics (with different target ages, screening intervals, and coverage). We used a budget optimisation process to select the best available combinations of vaccination and screening. The primary outcomes were the annual incidence of cervical cancer in 2015–2100, and the year of elimination (the first year in which the incidence was expected to be lower than four new cases per 100 000 women). Findings: Under the current strategy, by 2100, the age-standardised incidence of cervical cancer is projected to increase to three times the incidence in 2015. However, if China adopts an optimal strategy under the current budget from 2020 onwards (namely, introducing vaccination of 95% coverage for girls aged 12 years, and expanding coverage of once in a lifetime screening for women aged 45 years of 90% in urban areas and 33% in rural areas), the annual age-standardised incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100 000 women (ie, elimination) by 2072 (95% CI 2070–74) in urban China and 2074 (2072–76) in rural China. If the current budget were doubled from 2020 onwards, elimination would be achieved by 2063 (2059–66) in urban China and 2069 (2066–71) in rural China. The earliest possible year of cervical cancer elimination would be 2057 (2053–60) in urban China and 2060 (2057–63) in rural China, if vaccination coverage for girls aged 12 years and coverage of screening at 5-year intervals for women aged 35–64 years was maximised, with no budgetary restrictions. Interpretation: Cervical cancer incidence in China will continue to increase under current cervical cancer prevention strategies. However, under our budget optimisation strategy from 2020 onwards, cervical cancer could be eliminated as a public health problem by the early 2070s. Elimination could be achieved by the late 2050s by increasing the budget towards vaccination against human papillomavirus and cervical cancer screening. Funding: National Natural Science Foundation of China and Chinese Academy of Medical Science Initiative for Innovative Medicine.

This costing study in Malawi is a first evaluation of a Maternal Influenza Immunization Program Costing Tool (Costing Tool) for maternal immunization. The tool was designed to help low- and middle-income countries plan for maternal influenza immunization programs that differ from infant vaccination programs because of differences in the target population and potential differences in delivery strategy or venue.This analysis examines the incremental costs of a prospective seasonal maternal influenza immunization program that is added to a successful routine childhood immunization and antenatal care program. The Costing Tool estimates financial and economic costs for different vaccine delivery scenarios for each of the major components of the expanded immunization program.In our base scenario, which specifies a donated single dose pre-filled vaccine formulation, the total financial cost of a program that would reach 2.3 million women is approximately $1.2 million over five years. The economic cost of the program, including the donated vaccine, is $10.4 million over the same period. The financial and economic costs per immunized pregnancy are $0.52 and $4.58, respectively. Other scenarios examine lower vaccine uptake, reaching 1.2 million women, and a vaccine purchased at $2.80 per dose with an alternative presentation.This study estimates the financial and economic costs associated with a prospective maternal influenza immunization program in a low-income country. In some scenarios, the incremental delivery cost of a maternal influenza immunization program may be as low as some estimates of childhood vaccination programs, assuming the routine childhood immunization and antenatal care systems are capable of serving as the platform for an additional vaccination program. However, purchasing influenza vaccines at the prices assumed in this analysis, instead of having them donated, is likely to be challenging for lower-income countries. This result should be considered as a starting point to understanding the costs of maternal immunization programs in low- and middle-income countries.

OBJECTIVE: To estimate the cost of scaling up childhood immunization services required to reach the WHO-UNICEF Global Immunization Vision and Strategy (GIVS) goal of reducing mortality due to vaccine-preventable diseases by two-thirds by 2015. METHODS: A model was developed to estimate the total cost of reaching GIVS goals by 2015 in 117 low- and lower-middle- income countries. Current spending was estimated by analysing data from country planning documents, and scale-up costs were estimated using a bottom-up, ingredients-based approach. Financial costs were estimated by country and year for reaching 90% coverage with all existing vaccines; introducing a discrete set of new vaccines (rotavirus, conjugate pneumococcal, conjugate meningococcal A and Japanese encephalitis); and conducting immunization campaigns to protect at-risk populations against polio, tetanus, measles, yellow fever and meningococcal meningitis. FINDINGS: The 72 poorest countries of the world spent US$ 2.5 (range: US$ 1.8-4.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.9-1.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.9-6.7) billion. Total immunization costs for 2006-2015 are estimated at US$ 35 (range US$ 13-40) billion; of this, US$ 16.2 billion are incremental costs, comprised of US$ 5.6 billion for system scale-up and US$ 8.7 billion for vaccines; US$ 19.3 billion is required to maintain immunization programmes at 2005 levels. In all 117 low- and lower-middle-income countries, total costs for 2006-2015 are estimated at US$ 76 (range: US$ 23-110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. CONCLUSION: In the 72 poorest countries, US$ 11-15 billion (30%-40%) of the overall resource needs are unmet if the GIVS goals are to be reached. The methods developed in this paper are approximate estimates with limitations, but provide a roadmap of financing gaps that need to be filled to scale up immunization by 2015.

In November 2011, the GAVI Alliance made the decision to add HPV vaccine as one of the new vaccines for which countries eligible for its funding (less than $1520 per capita income) could apply to receive support for national HPV vaccination, provided they could demonstrate the ability to deliver HPV vaccines. This paper describes the data and analysis shared with GAVI policymakers for this decision regarding GAVI HPV vaccine support. The paper reviews why strategies and costs for HPV vaccine delivery are different from other vaccines and what is known about the cost components from available data that originated primarily from HPV vaccine delivery costing studies in low and middle income-countries.Financial costs of HPV vaccine delivery were compared across three sources of data: 1) vaccine delivery costing of pilot projects in five low and lower-middle income countries; 2) cost estimates of national HPV vaccination in two low income countries; and 3) actual expenditure data from national HPV vaccine introduction in a low income country. Both costs of resources required to introduce the vaccine (or initial one-time investment, such as cold chain equipment purchases) and recurrent (ongoing costs that repeat every year) costs, such as transport and health personnel time, were analyzed. The cost per dose, cost per fully immunized girl (FIG) and cost per eligible girl were compared across studies.Costs varied among pilot projects and estimates of national programs due to differences in scale and service delivery strategy. The average introduction costs per fully immunized girl ranged from $1.49 to $18.94 while recurrent costs per girl ranged from $1.00 to $15.69, with both types of costs varying by delivery strategy and country. Evaluating delivery costs along programme characteristics as well as country characteristics (population density, income/cost level, existing service delivery infrastructure) are likely the most informative and useful for anticipating costs for HPV vaccine delivery.This paper demonstrates the importance of country level cost data to inform global donor policies for vaccine introduction support. Such data are also valuable for informing national decisions on HPV vaccine introduction.

BackgroundRecent research in two cholera-endemic communities of Zanzibar has shown that a majority (∼94%) of the adult population was willing to receive free oral cholera vaccines (OCVs). Since OCV uptake in the 2009 campaign reached only ∼50% in these communities, an evaluation of social and cultural factors and of barriers was conducted to understand this difference for future cholera control planning.Methodology/principal findingsA random sample of 367 adult peri-urban and rural community residents (46.6% immunized vs. 53.4% unimmunized) was studied with a semi-structured interview that inquired about social and cultural features of cholera depicted in a vignette and barriers to OCV uptake. Symptoms (rectal pain, loose skin only in rural community) and perceived causes (uncovered food, contact with contaminated water) specific for severe diarrhea were associated with uptake. Purchasing drugs from pharmacies to stop diarrhea and vomiting was negatively associated with uptake. Increasing household size, age and previous enteric illness episode were positively related to uptake, the latter only at the rural site. The most prominent barrier to uptake was competing obligations or priorities (reported by 74.5%, identified as most important barrier by 49.5%). Next most prominent barriers were lacking information about the campaign (29.6%, 12.2%), sickness (14.3%, 13.3%) and fear of possible vaccine side effects (15.3%, 5.6%). The majority of unvaccinated respondents requested repetition of the vaccination with free OCVs.Conclusions/significanceFactors associated with uptake indicated a positive impact of the vaccination campaign and of sensitization activities on vaccine acceptance behavior. Unlike communities opposed to cholera control or settings where public confidence in vaccines is lacking, identified barriers to uptake indicated a good campaign implementation and trust in the health system. Despite prospects and demand for repeating the vaccination, local decision-makers should reconsider how careful logistical arrangements may improve community coverage and thus effectiveness of vaccination campaigns.

BACKGROUND: The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective. METHODOLOGY/PRINCIPAL FINDINGS: Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3). CONCLUSIONS/SIGNIFICANCE: Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.

Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.ClinicalTrials.gov NCT00709410.