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Introduction: Thailand was one of the first low- and middle-income countries to publicly fund seasonal influenza vaccines, but the lack of predictability in the timing of epidemics and difficulty in predicting the dominant influenza subtypes present a challenge for existing vaccines. Next-generation influenza vaccines (NGIVs) are being developed with the dual aims of broadening the strain coverage and conferring longer-lasting immunity. However, there are no economic evaluations of NGIVs in Thailand., Methods: We estimated the health impact and cost-effectiveness of NGIVs in Thailand between 2005 and 2009 using a combined epidemiological and economic model. We fitted the model to data on laboratory-confirmed influenza cases and then simulated the number of influenza infections, symptomatic cases, hospitalisations and deaths under different vaccination scenarios based on WHO-preferred product characteristics for NGIVs. We used previous estimates of costs and disability adjusted life years (DALYs) for influenza health outcomes to estimate incremental net monetary benefit, vaccine threshold prices and budget impact., Results: With the current vaccine programme, there were an estimated 61 million influenza infections. Increasing coverage to 50% using improved vaccines reduced infections to between 23 and 57 million, and with universal vaccines to between 21 and 49 million, depending on the age groups targeted. Depending on the comparator, threshold prices for NGIVs ranged from US$2.80 to US$12.90 per dose for minimally improved vaccines and US$24.60 to US$69.90 for universal vaccines., Conclusion: Influenza immunisation programmes using NGIVs are anticipated to provide considerable health benefits and be cost-effective in Thailand. However, although NGIVs might even be cost-saving in the long run, there could be significant budget implications for the Thai government even if the vaccines can be procured at a substantial discount to the maximum threshold price., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction., Methods: We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses., Findings: Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths., Interpretation: The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact., Funding: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests MJ and CC received funding from the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance (INV-009125/OPP1157270) for this study. MJ received research grants to his institution from UK National Institute for Health and Care Research (NIHR), Resuscitation Council UK, Bill & Melinda Gates Foundation, WHO, Gavi, Wellcome Trust, European Commission, InnoHK, Task Force for Global Health, and US Centers for Disease Control and Prevention. JAGS has received research grants from Gavi, the UK Medical Research Council, Wellcome Trust, NIHR, Bill & Melinda Gates Foundation, and Emory University to his institution. CC has received research grants to her institution from the Singapore Ministry of Health's National Medical Research Council (HCSAINV22jul-0005; PHRGOC22Jul-0020), the Ministry of Education (MOE2018-T2–2-070), Singapore Food Agency, Jurong Health Fund, Woodlands Health Campus, and the Thai Health Promotion Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice., Methods and Findings: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza., Conclusions: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bonnet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Nigeria commenced rollout of vaccination for coronavirus disease 2019 (COVID-19) in March 2021 as part of the national public health response to the pandemic. Findings from appropriately contextualized cost-effectiveness analyses (CEA) as part of a wider process involving health technology assessment (HTA) approaches have been important in informing decision-making in this area. In this paper we outline the processes that were followed to identify COVID-19 vaccine stakeholders involved in the selection, approval, funding, procurement and rollout of vaccines in Nigeria, and describe the process routes we identified to support uptake of HTA-related information for evidence-informed policy in Nigeria., Methods: Our approach to engaging with policy-makers and other stakeholders as part of an HTA of COVID vaccination in Nigeria consisted of three steps, namely: (i) informal discussions with key stakeholders; (ii) stakeholder mapping, analysis and engagement; and (iii) communication and dissemination strategies for the HTA-relevant evidence produced. The analysis of the stakeholder mapping uses the power/interest grid framework., Results: The informal discussion with key stakeholders generated six initial policy questions. Further discussions with policy-makers yielded three suitable policy questions for analysis: which COVID-19 vaccines should be bought; what is the optimal mode of delivery of these vaccines; and what are the cost and cost-effectiveness of vaccinating people highlighted in Nigeria's phase 2 vaccine rollout prioritized by the government, especially the inclusion of those aged between 18 and 49 years. The stakeholder mapping exercise highlighted the range of organizations and groups within Nigeria that could use the information from this HTA to guide decision-making. These stakeholders included both public/government, private and international organizations The dissemination plan developed included disseminating the full HTA results to key stakeholders; production of policy briefs; and presentation at different national and international conferences and peer-reviewed publications., Conclusions: HTA processes that involve stakeholder engagement will help ensure important policy questions are taken into account when designing any HTA including any underpinning evidence generation. Further guidance about stakeholder engagement throughout HTA is required, especially for those with low interest in vaccine procurement and use., (© 2024. The Author(s).)

Background: Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million)., Methods and Findings: We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question., Conclusions: COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Incremental cost-effectiveness analyses may inform the optimal choice of healthcare interventions. Nevertheless, for many vaccines, benefits fluctuate with incidence levels over time. Reevaluating a vaccine after it has successfully decreased incidences may eventually cause a disease resurgence if switching to a vaccine with lower indirect benefits. Decisions may successively alternate between vaccines alongside repeated rises and falls in incidence and when indirect effects from historic use are ignored. Our suggested proposal aims to prevent suboptimal decision making., Methods: We used a conceptual model of demand to illustrate alternating decisions between vaccines because of time-varying levels of indirect effects. Similar to the concept of subsidies, we propose internalizing the indirect effects achievable with vaccines. In a case study over 60 years, we simulated a hypothetical 10-year reevaluation of 2 oncogenic human papillomavirus vaccines, of which only 1 protects additionally against anogenital warts., Results: Our case study showed that the vaccine with additional warts protection is initially valued higher than the vaccine without additional warts protection. After 10 years, this differential decreases because of declines in warts incidence, which supports switching to the nonwarts vaccine that causes a warts resurgence eventually. Instead, pricing the indirect effects separately supports continuing with the warts vaccine., Conclusions: Ignoring how the observed incidences depend on the indirect effects achieved with a particular vaccine may lead to repeated changes in vaccines at successive reevaluations, with unintended resurgences, economic inefficiencies, and eroding vaccine confidence. We propose internalizing indirect effects to prevent vaccines falling victim to their own success., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: Cost-effectiveness analysis can guide decision making about health interventions, but the appropriate cost-effectiveness threshold to use is unclear in most countries. The World Health Organization (WHO) recommends vaccinating girls 9 to 14 years against human papillomavirus (HPV), but over half the world's countries have not introduced it. This study aimed to investigate whether country-level decisions about HPV vaccine introduction are consistent with a particular cost-effectiveness threshold, and to estimate what that threshold may be., Methods: The cost-effectiveness of vaccinating 12-year-old girls was estimated in 179 countries using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model, together with vaccine price data from World Health Organization's Market Information for Access to Vaccines database. In each year from 2006 to 2018, countries were categorized based on (1) whether they had introduced HPV vaccination, and (2) whether the incremental cost-effectiveness ratio for HPV vaccine introduction fell below a certain cost-effectiveness threshold., Results: A cost-effectiveness threshold of 60% to 65% of GDP per capita has the best ability to discriminate countries that introduced vaccination, with a diagnostic odds ratio of about 7. For low-income countries the optimal threshold was lower, at 30% to 40% of GDP per capita., Conclusions: A cost-effectiveness threshold has some ability to discriminate between HPV vaccine introducer and non-introducer countries, although the average threshold is below the widely used threshold of 1 GDP per capita. These results help explain the current pattern of HPV vaccine use globally. They also inform the extent to which cost-effectiveness thresholds proposed in the literature reflect countries' actual investment decisions., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: China has an aging population with an increasing number of adults aged ≥ 60 years. Influenza causes a heavy disease burden in older adults, but can be alleviated by vaccination. We assessed the cost-effectiveness of a potential government-funded seasonal influenza vaccination program in older adults in China., Methods: We characterized the health and economic impact of a fully funded influenza vaccination program for older adults using China-specific influenza disease burden, and related cost data, etc. Using a decision tree model, we calculated the incremental costs per quality-adjusted life year (QALY) gained of vaccination from the societal perspective, at a willingness-to-pay threshold equivalent to GDP per capita (US$8840). Moreover, we estimated the threshold vaccination costs, under which the fully funded vaccination program is cost-effective using GDP per capita as the willingness-to-pay threshold., Results: Compared to current self-paid vaccination, a fully funded vaccination program is expected to prevent 19,812 (95% uncertainty interval, 7150-35,783) influenza-like-illness outpatient consultations per year, 9418 (3386-17,068) severe acute respiratory infection hospitalizations per year, and 8800 (5300-11,667) respiratory excess deaths due to influenza per year, and gain 70,212 (42,106-93,635) QALYs per year. Nationally, the incremental costs per QALY gained of the vaccination program is US$4832 (3460-8307), with a 98% probability of being cost-effective. The threshold vaccination cost is US$10.19 (6.08-13.65). However, variations exist between geographical regions, with Northeast and Central China having lower probabilities of cost-effectiveness., Conclusions: Our results support the implementation of a government fully funded older adult vaccination program in China. The regional analysis provides results across settings that may be relevant to other countries with similar disease burden and economic status, especially for low- and middle-income countries where such analysis is limited.

Background: Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, including vaccines and monoclonal antibody (mAb) candidates, are under development, we aim to evaluate the key drivers of the cost-effectiveness of maternal vaccination and infant mAb for 72 Gavi countries., Methods: A static Multi-Country Model Application for RSV Cost-Effectiveness poLicy (MCMARCEL) was developed to follow RSV-related events monthly from birth until 5 years of age. MCMARCEL was parameterised using country- and age-specific demographic, epidemiological, and cost data. The interventions' level and duration of effectiveness were guided by the World Health Organization's preferred product characteristics and other literature. Maternal vaccination and mAb were assumed to require single-dose administration at prices assumed to align with other Gavi-subsidised technologies. The effectiveness and the prices of the interventions were simultaneously varied in extensive scenario analyses. Disability-adjusted life years (DALYs) were the primary health outcomes for cost-effectiveness, integrated with probabilistic sensitivity analyses and Expected Value of Partially Perfect Information analysis., Results: The RSV-associated disease burden among children in these 72 countries is estimated at an average of 20.8 million cases, 1.8 million hospital admissions, 40 thousand deaths, 1.2 million discounted DALYs, and US$611 million discounted direct costs. Strategy 'mAb' is more effective due to its assumed longer duration of protection versus maternal vaccination, but it was also assumed to be more expensive. Given all parameterised uncertainty, the optimal strategy of choice tends to change for increasing willingness to pay (WTP) values per DALY averted from the current situation to maternal vaccination (at WTP > US$1000) to mAB (at WTP > US$3500). The age-specific proportions of cases that are hospitalised and/or die cause most of the uncertainty in the choice of optimal strategy. Results are broadly similar across countries., Conclusions: Both the maternal and mAb strategies need to be competitively priced to be judged as relatively cost-effective. Information on the level and duration of protection is crucial, but also more and better disease burden evidence-especially on RSV-attributable hospitalisation and death rates-is needed to support policy choices when novel RSV products become available.

Background: Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice., Objectives: To compare the diagnostic accuracy and cost-effectiveness of T-SPOT. TB ® (Oxford Immunotec, Abingdon, UK) and QuantiFERON ® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs., Design: Prospective within-patient comparative diagnostic accuracy study., Setting: Secondary care., Participants: Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB., Interventions: The index tests [T-SPOT. TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results., Main Outcome Measures: Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test., Results: A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT. TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT. TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p  < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p  = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT. TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT. TB , the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway., Limitations: The recruitment target for the HIV co-infected population was not achieved., Conclusions: Although T-SPOT. TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise., Future Work: The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK., Competing Interests: Ajit Lalvani is the named inventor for several patents underpinning T-cell-based diagnosis including interferon gamma, enzyme-linked immunospot assay, ESAT-6, CFP-10, Rv3615c, Rv3873 and Rv3879c. He has royalty entitlements from the University of Oxford spin-out company (Oxford Immunotec plc), in which he has held a minority share of equity and he is a member of the Efficacy and Mechanism Evaluation Board. Jonathan J Deeks is a member of the Health Technology Assessment (HTA) Commissioning Board and the HTA Efficient Study Designs Board. Onn Min Kon is chairperson of the UK Joint Tuberculosis Committee. Peter White has received research funding from Otsuka SA for a retrospective study of multidrug-resistant tuberculosis treatment in several eastern European countries outside the submitted work. He received grants from the Medical Research Council during the conduct of the study.

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., (Copyright © 2018 ISPOR--The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in estimating the broader benefits of public health interventions beyond those captured in traditional cost-utility analyses. Cost-benefit analysis (CBA) in principle offers a way to capture such benefits, but a wide variety of methods have been used to monetise benefits in CBAs., Methods: To understand the implications of different CBA approaches for capturing and monetising benefits and their potential impact on public health decision-making, we conducted a CBA of human papillomavirus (HPV) vaccination in the United Kingdom using eight methods for monetising health and economic benefits, valuing productivity loss using either (1) the human capital or (2) the friction cost method, including the value of unpaid work in (3) human capital or (4) friction cost approaches, (5) adjusting for hard-to-fill vacancies in the labour market, (6) using the value of a statistical life, (7) monetising quality-adjusted life years and (8) including both productivity losses and monetised quality-adjusted life years. A previously described transmission dynamic model was used to project the impact of vaccination on cervical cancer outcomes. Probabilistic sensitivity analysis was conducted to capture uncertainty in epidemiologic and economic parameters., Results: Total benefits of vaccination varied by more than 20-fold (£0.6-12.4 billion) across the approaches. The threshold vaccine cost (maximum vaccine cost at which HPV vaccination has a benefit-to-cost ratio above one) ranged from £69 (95% CI £56-£84) to £1417 (£1291-£1541)., Conclusions: Applying different approaches to monetise benefits in CBA can lead to widely varying outcomes on public health interventions such as vaccination. Use of CBA to inform priority setting in public health will require greater convergence around appropriate methodology to achieve consistency and comparability across different studies.

Cost-effectiveness thresholds (CETs) based on the Commission on Macroeconomics and Health (CMH) are extensively used in low- and middle-income countries (LMICs) lacking locally defined CETs. These thresholds were originally intended for global and regional prioritization, and do not reflect local context or affordability at the national level, so their value for informing resource allocation decisions has been questioned. Using these thresholds, rotavirus vaccines are widely regarded as cost-effective interventions in LMICs. However, high vaccine prices remain a barrier towards vaccine introduction. This study aims to evaluate the cost-effectiveness, affordability and threshold price of universal rotavirus vaccination at various CETs in Malaysia. Cost-effectiveness of Rotarix and RotaTeq were evaluated using a multi-cohort model. Pan American Health Organization Revolving Fund's vaccine prices were used as tender price, while the recommended retail price for Malaysia was used as market price. We estimate threshold prices defined as prices at which vaccination becomes cost-effective, at various CETs reflecting economic theories of human capital, societal willingness-to-pay and marginal productivity. A budget impact analysis compared programmatic costs with the healthcare budget. At tender prices, both vaccines were cost-saving. At market prices, cost-effectiveness differed with thresholds used. At market price, using 'CMH thresholds', Rotarix programmes were cost-effective and RotaTeq were not cost-effective from the healthcare provider's perspective, while both vaccines were cost-effective from the societal perspective. Using other CETs, both vaccines were not cost-effective at market price, from the healthcare provider's and societal perspectives. At tender and cost-effective prices, rotavirus vaccination cost ∼1 and 3% of the public health budget, respectively. Using locally defined thresholds, rotavirus vaccination is cost-effective at vaccine prices in line with international tenders, but not at market prices. Thresholds representing marginal productivity are likely to be lower than those reflecting human capital and individual preference measures, and may be useful in determining affordable vaccine prices., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs' total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention.

Background: Men who have sex with men (MSM) have a high lifetime risk of anogenital warts and cancers related to infection with human papillomavirus (HPV). They also benefit less from herd protection than heterosexual males in settings with female-only HPV vaccination., Methods: We evaluated the potential health impact and cost-effectiveness of offering vaccination to MSM who visit genitourinary medicine (GUM) clinics. We used a mathematical model of HPV 6/11/16/18 sexual transmission within an MSM population in England, parameterized with sexual behaviour, GUM attendance, HPV prevalence, HIV prevalence, warts, and cancer incidence data. Interventions considered were offering HPV vaccination to either HIV-positive MSM or MSM regardless of HIV status, for age bands 16-25, 16-30, 16-35, and 16-40 years., Results: Substantial declines in anogenital warts and male HPV-related cancer incidence are projected to occur following an offer of vaccination to MSM. MSM not attending GUM clinics will partially benefit from herd protection. Offering vaccination to HIV-positive MSM up to age 40 is likely to be cost-effective if vaccine procurement and administration costs are below £96.50 a dose. At £48 a dose, offering vaccination to all MSM up to age 40 is likely to be cost-effective., Conclusions: Quadrivalent HPV vaccination of MSM via GUM clinics is likely to be an effective and cost-effective way of reducing the burden of HPV-related disease in MSM., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia., Methods: The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price., Results: The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025., Conclusion: Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Economic evaluation of vaccination is a key tool to inform effective spending on vaccines. However, many evaluations have been criticised for failing to capture features of vaccines which are relevant to decision makers. These include broader societal benefits (such as improved educational achievement, economic growth and political stability), reduced health disparities, medical innovation, reduced hospital beds pressures, greater peace of mind and synergies in economic benefits with non-vaccine interventions. Also, the fiscal implications of vaccination programmes are not always made explicit. Alternative methodological frameworks have been proposed to better capture these benefits. However, any broadening of the methodology for economic evaluation must also involve evaluations of non-vaccine interventions, and hence may not always benefit vaccines given a fixed health-care budget. The scope of an economic evaluation must consider the budget from which vaccines are funded, and the decision-maker's stated aims for that spending to achieve.

Background: Incremental cost-effectiveness and cost-utility analyses [health economic evaluations (HEEs)] of vaccines are routinely considered in decision making on immunization in various industrialized countries. While guidelines advocating more standardization of such HEEs (mainly for curative drugs) exist, several immunization-specific aspects (e.g. indirect effects or discounting approach) are still a subject of debate within the scientific community., Objective: The objective of this study was to develop a consensus framework for HEEs of vaccines to support the development of national guidelines in Europe., Methods: A systematic literature review was conducted to identify prevailing issues related to HEEs of vaccines. Furthermore, European experts in the field of health economics and immunization decision making were nominated and asked to select relevant aspects for discussion. Based on this, a workshop was held with these experts. Aspects on 'mathematical modelling', 'health economics' and 'decision making' were debated in group-work sessions (GWS) to formulate recommendations and/or--if applicable--to state 'pros' and 'contras'., Results: A total of 13 different aspects were identified for modelling and HEE: model selection, time horizon of models, natural disease history, measures of vaccine-induced protection, duration of vaccine-induced protection, indirect effects apart from herd protection, target population, model calibration and validation, handling uncertainty, discounting, health-related quality of life, cost components, and perspectives. For decision making, there were four aspects regarding the purpose and the integration of HEEs of vaccines in decision making as well as the variation of parameters within uncertainty analyses and the reporting of results from HEEs. For each aspect, background information and an expert consensus were formulated., Conclusions: There was consensus that when HEEs are used to prioritize healthcare funding, this should be done in a consistent way across all interventions, including vaccines. However, proper evaluation of vaccines implies using tools that are not commonly used for therapeutic drugs. Due to the complexity of and uncertainties around vaccination, transparency in the documentation of HEEs and during subsequent decision making is essential.

Background: The seasonal influenza vaccine coverage rate in China is only 1.9 %. There is no information available on the economic burden of influenza-associated outpatient visits and hospitalizations at the national level, even though this kind of information is important for informing national-level immunization policy decision-making., Methods: A retrospective telephone survey was conducted in 2013/14 to estimate the direct and indirect costs of seasonal influenza-associated outpatient visits and hospitalizations from a societal perspective. Study participants were laboratory-confirmed cases registered in the National Influenza-like Illness Surveillance Network and Severe Acute Respiratory Infections Sentinel Surveillance Network in China in 2013. Patient-reported costs from the survey were validated by a review of hospital accounts for a small sample of the inpatients., Results: The study enrolled 529 outpatients (median age: eight years; interquartile range [IQR]: five to 20 years) and 254 inpatients (median age: four years; IQR: two to seven years). Among the outpatients, 22.1 % (117/529) had underlying diseases and among the inpatients, 52.8 % (134/254) had underlying diseases. The average total costs related to influenza-associated outpatient visits and inpatient visits were US$ 155 (standard deviation, SD US$ 122) and US$ 1,511 (SD US$ 1,465), respectively. Direct medical costs accounted for 45 and 69 % of the total costs related to influenza-associated outpatient and inpatient visits, respectively. For influenza outpatients, the mean cost per episode in children aged below five years (US$ 196) was higher than that in other age groups (US$ 129-153). For influenza inpatients, the mean cost per episode in adults aged over 60 years (US$ 2,735) was much higher than that in those aged below 60 years (US$ 1,417-1,621). Patients with underlying medical conditions had higher costs per episode than patients without underlying medical conditions (outpatients: US$ 186 vs. US$ 146; inpatients: US$ 1,800 vs. US$ 1,189). In the baseline analysis, inpatients reported costs were 18 % higher than those found in the accounts review (n = 38)., Conclusion: The economic burden of influenza-associated outpatient and inpatient visits in China is substantial, particularly for young children, the elderly, and patients with underlying medical conditions. More widespread influenza vaccination would likely alleviate the economic burden of patients. The actual impact and cost-effectiveness analysis of the influenza immunization program in China merits further investigation.

Background: Optimising population-based cervical screening policies is becoming more complex due to the expanding range of screening technologies available and the interplay with vaccine-induced changes in epidemiology. Mathematical models are increasingly being applied to assess the impact of cervical cancer screening strategies., Methods: We systematically reviewed MEDLINE®, Embase, Web of Science®, EconLit, Health Economic Evaluation Database, and The Cochrane Library databases in order to identify the mathematical models of human papillomavirus (HPV) infection and cervical cancer progression used to assess the effectiveness and/or cost-effectiveness of cervical cancer screening strategies. Key model features and conclusions relevant to decision-making were extracted., Results: We found 153 articles meeting our eligibility criteria published up to May 2013. Most studies (72/153) evaluated the introduction of a new screening technology, with particular focus on the comparison of HPV DNA testing and cytology (n = 58). Twenty-eight in forty of these analyses supported HPV DNA primary screening implementation. A few studies analysed more recent technologies - rapid HPV DNA testing (n = 3), HPV DNA self-sampling (n = 4), and genotyping (n = 1) - and were also supportive of their introduction. However, no study was found on emerging molecular markers and their potential utility in future screening programmes. Most evaluations (113/153) were based on models simulating aggregate groups of women at risk of cervical cancer over time without accounting for HPV infection transmission. Calibration to country-specific outcome data is becoming more common, but has not yet become standard practice., Conclusions: Models of cervical screening are increasingly used, and allow extrapolation of trial data to project the population-level health and economic impact of different screening policy. However, post-vaccination analyses have rarely incorporated transmission dynamics. Model calibration to country-specific data is increasingly common in recent studies.

Background: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada., Methods: We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost., Findings: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated., Interpretation: Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support., Methods: We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects., Findings: In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690,000 cases of cervical cancer and 420,000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200,000 cases of cervical cancer and 100,000 deaths in some of the highest-burden countries., Interpretation: Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions., Funding: WHO., (©2014 World Health Organization; licensee Elsevier. This is an Open Access article published without any waiver of WHO's privileges and immunities under international law, convention, or agreement. This article should not be reproduced for use in association with the promotion of commercial products, services or any legal entity. There should be no suggestion that WHO endorses any specific organisation or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: Economic evaluations on influenza vaccination from low resource settings are scarce and have not been evaluated using a systematic approach. Our objective was to conduct a systematic review on the value for money of influenza vaccination in low- and middle-income countries., Methods: PubMed and EMBASE were searched for economic evaluations published in any language between 1960 and 2011. Main outcome measures were costs per influenza outcome averted, costs per quality-adjusted life years gained or disability-adjusted life years averted, costs per benefit in monetary units or cost-benefit ratios., Results: Nine economic evaluations on seasonal influenza vaccine met the inclusion criteria. These were model- or randomized-controlled-trial (RCT)-based economic evaluations from middle-income countries. Influenza vaccination provided value for money for elderly, infants, adults and children with high-risk conditions. Vaccination was cost-effective and cost-saving for chronic obstructive pulmonary disease patients and in elderly above 65 y from model-based evaluations, but conclusions from RCTs on elderly varied., Conclusion: Economic evaluations from middle income regions differed in population studied, outcomes and definitions used. Most findings are in line with evidence from high-income countries highlighting that influenza vaccine is likely to provide value for money. However, serious methodological limitations do not allow drawing conclusions on cost-effectiveness of influenza vaccination in middle income countries. Evidence on cost-effectiveness from low-income countries is lacking altogether, and more information is needed from full economic evaluations that are conducted in a standardized manner.