Healthcare utilisation in people with long COVID: an OpenSAFELY cohort study.

BACKGROUND: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. METHODS: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. RESULTS: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60-£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. CONCLUSIONS: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.

A health technology assessment of COVID-19 vaccination for Nigerian decision-makers: Identifying stakeholders and pathways to support evidence uptake.

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.

Evaluating Scope and Bias of Population-Level Measles Serosurveys: A Systematized Review and Bias Assessment.

BACKGROUND: Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021. METHODS: On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075). RESULTS: We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias. CONCLUSIONS: While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.

Overcoming challenges in the economic evaluation of interventions to optimise antibiotic use.

Bacteria are becoming increasingly resistant to antibiotics, reducing our ability to treat infections and threatening to undermine modern health care. Optimising antibiotic use is a key element in tackling the problem. Traditional economic evaluation methods do not capture many of the benefits from improved antibiotic use and the potential impact on resistance. Not capturing these benefits is a major obstacle to optimising antibiotic use, as it fails to incentivise the development and use of interventions to optimise the use of antibiotics and preserve their effectiveness (stewardship interventions). Estimates of the benefits of improving antibiotic use involve considerable uncertainty as they depend on the evolution of resistance and associated health outcomes and costs. Here we discuss how economic evaluation methods might be adapted, in the face of such uncertainties. We propose a threshold-based approach that estimates the minimum resistance-related costs that would need to be averted by an intervention to make it cost-effective. If it is probable that without the intervention costs will exceed the threshold then the intervention should be deemed cost-effective.

Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

An overview of the perspectives used in health economic evaluations.

The term 'perspective' in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders' viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence.

Equity impact of HPV vaccination on lifetime projections of cervical cancer burden among cohorts in 84 countries by global, regional, and income levels, 2010-22: a modelling study.

Background: While human papillomavirus (HPV) vaccines have been available since 2006, the coverage has varied among countries. Our aim is to analyse the equity impact of HPV vaccination on the lifetime projections of cervical cancer burden among vaccinated cohorts of 2010-22 in 84 countries. Methods: We used WHO and UNICEF estimates of national immunisation coverage for HPV vaccination in 84 countries during 2010-22. We used PRIME (Papillomavirus Rapid Interface for Modelling and Economics) to estimate the lifetime health impact of HPV vaccination on cervical cancer burden in terms of deaths, cases, and disability-adjusted life years (DALYs) averted by vaccination in their respective countries. We generated concentration indices and curves to assess the equity impact of HPV vaccination across 84 countries. Findings: The health impact of HPV vaccination varied across the 84 countries and ranged from Switzerland to Tanzania at 2 to 34 deaths, 4 to 47 cases, and 40 to 735 DALYs averted per 1000 vaccinated adolescent girls over the lifetime of the vaccinated cohorts of 2010-22. The concentration index for the distribution of average coverage during 2010-22 among the 84 countries ranked by vaccine impact was 0.33 (95% CI: 0.27-0.40) and highlights the wide inequities in HPV vaccination coverage. Interpretation: Our findings suggested that countries with a relatively higher cervical cancer burden and thereby a relatively higher need for HPV vaccination had relatively lower coverage during 2010-22. Further, there were significant inequities in HPV vaccination coverage within the Americas, Europe, and Western Pacific regions, and in high- and low-income countries with a pro-advantaged and regressive distribution favouring countries with lower vaccine impact. Funding: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation.

Protecting infants against RSV disease: an impact and cost-effectiveness comparison of long-acting monoclonal antibodies and maternal vaccination.

Background: Two new products for preventing Respiratory Syncytial Virus (RSV) in young children have been licensed: a single-dose long-acting monoclonal antibody (la-mAB) and a maternal vaccine (MV). To facilitate the selection of new RSV intervention programmes for large-scale implementation, this study provides an assessment to compare the costs of potential programmes with the health benefits accrued. Methods: Using an existing dynamic transmission model, we compared maternal vaccination to la-mAB therapy against RSV in England and Wales by calculating the impact and cost-effectiveness. We calibrated a statistical model to the efficacy trial data to accurately capture their immune waning and estimated the impact of seasonal and year-round programmes for la-mAB and MV programmes. Using these impact estimates, we identified the most cost-effective programme across pricing and delivery cost assumptions. Findings: For infants under six months old in England and Wales, a year-round MV programme with 60% coverage would avert 32% (95% CrI 22-41%) of RSV hospital admissions and a year-round la-mAB programme with 90% coverage would avert 57% (95% CrI 41-69%). The MV programme has additional health benefits for pregnant women, which account for 20% of the population-level health burden averted. A seasonal la-mAB programme could be cost-effective for up to £84 for purchasing and administration (CCPA) and a seasonal MV could be cost-effective for up to £80 CCPA. Interpretation: This modelling and cost-effectiveness analysis has shown that both the long-acting monoclonal antibodies and the maternal vaccine could substantially reduce the burden of RSV disease in the infant population. Our analysis has informed JCVI's recommendations for an RSV immunisation programme to protect newborns and infants. Funding: National Institute for Health Research.

COVID-19-related health utility values and changes in COVID-19 patients and the general population: a scoping review.

PURPOSE: To summarise the diverse literature reporting the impact of COVID-19 on health utility in COVID-19 patients as well as in general populations being affected by COVID-19 control policies. METHODS: A literature search up to April 2023 was conducted to identify papers reporting health utility in COVID-19 patients or in COVID-19-affected general populations. We present a narrative synthesis of the health utility values/losses of the retained studies to show the mean health utility values/losses with 95% confidence intervals. Mean utility values/losses for categories defined by medical attendance and data collection time were calculated using random-effects models. RESULTS: In total, 98 studies-68 studies on COVID-19 patients and 30 studies on general populations-were retained for detailed review. Mean (95% CI) health utility values were 0.83 (0.81, 0.86), 0.78 (0.73, 0.83), 0.82 (0.78, 0.86) and 0.71 (0.65, 0.78) for general populations, non-hospitalised, hospitalised and ICU patients, respectively, irrespective of the data collection time. Mean utility losses in patients and general populations ranged from 0.03 to 0.34 and from 0.02 to 0.18, respectively. CONCLUSIONS: This scoping review provides a summary of the health utility impact of COVID-19 and COVID-19 control policies. COVID-19-affected populations were reported to have poor health utility, while a high degree of heterogeneity was observed across studies. Population- and/or country-specific health utility is recommended for use in future economic evaluation on COVID-19-related interventions.

Health-Related Quality of Life and Economic Burden Among Hospitalized Children with Hand, Foot, and Mouth Disease: A Multiregional Study in China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an infectious disease with high morbidity and mortality rates among children under 5 years old. This study aimed to explore the health-related quality of life (HRQOL), economic burden, and related influencing factors among Chinese HFMD patients. METHODS: From January to October 2019, a longitudinal cohort study of 296 hospitalized patients (≤ 5 years old) with HFMD and their guardians was conducted using the proxy version of the 5-level EQ-5D-Y (EQ-5D-Y-5L, Y-5L) in face-to-face interviews in Shanghai, Zhengzhou, and Kunming, representing three regions with different economic development levels. Multiple linear regression was used to explore the factors associated with HRQOL and costs. RESULTS: The mean Y-5L health utility score (HUS) (standard deviation, SD), and visual analogue scale (VAS) score (SD) were 0.730 (0.140) and 60.33 (16.52) at admission and increased to 0.920 (0.120) and 89.95 (11.88) at discharge, respectively. The children from Shanghai had the lowest HUSs at admission and had the best health improvement. The mean hospitalization cost and total cost were 4037 CNY and 5157 CNY, respectively. The children from Shanghai had the highest hospitalization cost (4559 CNY) and total cost (5491 CNY). Multiple regression analysis suggested that medical insurance status, type of employment, residence type, and religious status were significantly associated with the baseline HUS and improvement in the HUS after treatment. Region, loss of work time, and length of stay had a significant impact on the hospitalization cost and total cost. CONCLUSION: Our findings demonstrate that HFMD could lead to poor HRQOL and the economic burden varies in different regions in China. Many pediatric patients still have physical or mental health problems shortly after treatment.

A Scoping Review and Taxonomy of Epidemiological-Macroeconomic Models of COVID-19.

OBJECTIVES: The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact. This article reviews models combining epidemiological and macroeconomic projections to enable policy makers to consider both macroeconomic and health objectives. METHODS: A scoping review of epidemiological-macroeconomic models of COVID-19 was conducted, covering preprints, working articles, and journal publications. We assessed model methodologies, scope, and application to empirical data. RESULTS: We found 80 articles modeling both the epidemiological and macroeconomic outcomes of COVID-19. Model scope is often limited to the impact of lockdown on health and total gross domestic product or aggregate consumption and to high-income countries. Just 14% of models assess disparities or poverty. Most models fall under 4 categories: compartmental-utility-maximization models, epidemiological models with stylized macroeconomic projections, epidemiological models linked to computable general equilibrium or input-output models, and epidemiological-economic agent-based models. We propose a taxonomy comparing these approaches to guide future model development. CONCLUSIONS: The epidemiological-macroeconomic models of COVID-19 identified have varying complexity and meet different modeling needs. Priorities for future modeling include increasing developing country applications, assessing disparities and poverty, and estimating of long-run impacts. This may require better integration between epidemiologists and economists.

Health-related quality of life and economic burden of childhood pneumonia in China: a multiregion study.

OBJECTIVE: To systematically investigate the health-related quality of life (HRQOL) and economic burden of children with pneumonia in different regions of China. STUDY DESIGN: The study recruited a series of children under 5 years hospitalised for pneumonia in Shanghai, Zhengzhou and Kunming from January to October 2019.Health utility was assessed using the proxy version of EQ-5D-Y by interviewing patients' guardians face to face. The assessment was administered twice at patients' admission and discharge. Cost incurred for receiving the hospitalisation was collected. Multiple linear regression and quantile regression were used to explore factors of EQ-5D-Y Health Utility Score (HUS) and costs, respectively. RESULTS: A total of 501 paediatric patients with a median age (IQR) of 1.5 (0.83-2.71) years were included in the analysis. The mean HUS (SD) of the patients was 0.78 (0.18) at admission, and increased to 0.96 (0.10) at discharge. Some patients (14.2%) still felt worried, sad or unhappy after hospitalisation. The mean hospitalisation cost and total cost were RMB5859 (€773) and RMB6439, respectively. The HUS was lower and the economic burden was heavier for the children in Zhengzhou. Apart from region, type of work, insurance status and hospital days were also related to the baseline HUS or HUS increment after treatment; insurance status, Visual Analogue Scale score at discharge, guardians' employment and hospitalisation days were associated with the costs. CONCLUSION: The children with pneumonia have poor baseline HRQOL, and many of them still have psychological well being problems after treatment. The economic burden varied significantly across regions and is heavy for the patients' families in less developed areas (ie, Zhengzhou and Kunming).

Adding new childhood vaccines to China's National Immunization Program: evidence, benefits, and priorities.

China's National Immunization Program has made remarkable achievements but does not include several important childhood vaccines that are readily available in the private market, such as pneumococcal conjugate vaccine (PCV), rotavirus vaccine, Haemophilus influenzae serotype b (Hib) vaccine, and varicella vaccine. We reviewed the literature to assess these four non-National Immunization Program vaccines in terms of their disease burdens, coverage, inequalities, and cost-effectiveness in China and aimed to recommend priorities for introducing them to the National Immunization Program. Based on our calculations using the available evidence, incorporating these vaccines into China's National Immunization Program in 2019 could have averted 11 761 deaths among children younger than 5 years, accounting for 10·29% of the total deaths in children younger than 5 years and reducing the mortality rate from 7·8 per 1000 to 7·0 per 1000. The review showed that 13-valent PCV (PCV13) had the lowest and most inequitable coverage but could prevent the highest number of deaths. In a budgetary analysis for the cohort of newborns in 2023, we estimated that the projected aggregate government costs were US$1954·92 million for PCV13, $1273·13 million for pentavalent rotavirus vaccine, $415·30 million for Hib vaccine, and $221·64 million for varicella vaccine. Our overall multicriteria decision analysis suggested the following priority order for introducing these four non-programme vaccines to the National Immunization Program to benefit the Chinese population: PCV13, rotavirus vaccine, Hib vaccine, and varicella vaccine.

Impact and cost-effectiveness of measles vaccination through microarray patches in 70 low-income and middle-income countries: mathematical modelling and early-stage economic evaluation.

BACKGROUND: Microarray patches (MAPs) are a promising technology being developed to reduce barriers to vaccine delivery based on needles and syringes (N&S). To address the evidence gap on the public health value of applying this potential technology to immunisation programmes, we evaluated the health impact on measles burden and cost-effectiveness of introducing measles-rubella MAPs (MR-MAPs) in 70 low-income and middle-income countries (LMICs). METHODS: We used an age-structured dynamic model of measles transmission and vaccination to project measles cases, deaths and disability-adjusted life-years during 2030-2040. Compared with the baseline scenarios with continuing current N&S-based practice, we evaluated the introduction of MR-MAPs under different measles vaccine coverage projections and MR-MAP introduction strategies. Costs were calculated based on the ingredients approach, including direct cost of measles treatment, vaccine procurement and vaccine delivery. Model-based burden and cost estimates were derived for individual countries and country income groups. We compared the incremental cost-effectiveness ratios of introducing MR-MAPs to health opportunity costs. RESULTS: MR-MAP introduction could prevent 27%-37% of measles burden between 2030 and 2040 in 70 LMICs, compared with the N&S-only immunisation strategy. The largest health impact could be achieved under lower coverage projection and accelerated introduction strategy, with 39 million measles cases averted. Measles treatment cost is a key driver of the net cost of introduction. In countries with a relatively higher income, introducing MR-MAPs could be a cost-saving intervention due to reduced treatment costs. Compared with country-specific health opportunity costs, introducing MR-MAPs would be cost-effective in 16%-81% of LMICs, depending on the MR-MAPs procurement prices and vaccine coverage projections. CONCLUSIONS: Introducing MR-MAPs in LMICs can be a cost-effective strategy to revitalise measles immunisation programmes with stagnant uptake and reach undervaccinated children. Sustainable introduction and uptake of MR-MAPs has the potential to improve vaccine equity within and between countries and accelerate progress towards measles elimination.

Informing Public Health Policies with Models for Disease Burden, Impact Evaluation, and Economic Evaluation.

Conducting real-world public health experiments is often costly, time-consuming, and ethically challenging, so mathematical models have a long-standing history of being used to inform policy. Applications include estimating disease burden, performing economic evaluation of interventions, and responding to health emergencies such as pandemics. Models played a pivotal role during the COVID-19 pandemic, providing early detection of SARS-CoV-2's pandemic potential and informing subsequent public health measures. While models offer valuable policy insights, they often carry limitations, especially when they depend on assumptions and incomplete data. Striking a balance between accuracy and timely decision-making in rapidly evolving situations such as disease outbreaks is challenging. Modelers need to explore the extent to which their models deviate from representing the real world. The uncertainties inherent in models must be effectively communicated to policy makers and the public. As the field becomes increasingly influential, it needs to develop reporting standards that enable rigorous external scrutiny. Expected final online publication date for the Annual Review of Public Health, Volume 45 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Report of the WHO technical consultation on the evaluation of respiratory syncytial virus prevention cost effectiveness in low- and middle-income countries, April 7-8, 2022.

Policymakers often rely on impact and cost-effectiveness evaluations to inform decisions about the introduction of health interventions in low- and middle-income countries (LMICs); however, cost-effectiveness results for the same health intervention can differ by the choice of parameter inputs, modelling assumptions, and geography. Anticipating the near-term availability of new respiratory syncytial virus (RSV) prevention products, WHO convened a two-day virtual consultation in April 2022 with stakeholder groups and global experts in health economics, epidemiology, and vaccine implementation. The objective was to review methods, parameterization, and results of existing cost-effectiveness analyses for RSV prevention in LMICs; identify the most influential inputs and data limitations; and recommend and prioritize future data gathering and research to improve RSV prevention impact estimates in LMICs. Epidemiological parameters identified as both influential and uncertain were those associated with RSV hospitalization and death, specifically setting-specific hospitalization rates and RSV-attributable death rates. Influential economic parameters included product price, delivery costs, willingness-to-pay for health on the part of potential donors, and the cost of RSV-associated hospitalization. Some of the influential parameters identified at this meeting should be more precisely measured by further research. Other influential economic parameters that are highly uncertain may not be resolved, and it is appropriate to use sensitivity analyses to explore these within cost-effectiveness evaluations. This report highlights the presentations and major discussions of the meeting.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis.

BACKGROUND: To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. METHODS: Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme. RESULTS: Over the years 2021-2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1-130.4) and 146.8 million (114.1-161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6-169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14-3.82) USD in low-income countries to 44.83 (3.75-85.64) USD in high-income countries, assuming one dose confers 30-year protection. CONCLUSIONS: Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

The potential cost-effectiveness of next generation influenza vaccines in England and Wales: A modelling analysis.

Next generation influenza vaccines are in development and have the potential for widespread health and economic benefits. Determining the potential health and economic impact for these vaccines is needed to drive investment in bringing these vaccines to the market, and to inform which groups public health policies on influenza vaccination should target. We used a mathematical modelling approach to estimate the epidemiological impact and cost-effectiveness of next generation influenza vaccines in England and Wales. We used data from an existing fitted model, and evaluated new vaccines with different characteristics ranging from improved vaccines with increased efficacy duration and breadth of protection, to universal vaccines, defined in line with the World Health Organisation (WHO) Preferred Product Characteristics (PPC). We calculated the cost effectiveness of new vaccines in comparison to the current seasonal vaccination programme. We calculated and compared the Incremental Cost-Effectiveness Ratio and Incremental Net Monetary Benefit for each new vaccine type. All analysis was conducted in R. We show that next generation influenza vaccines may result in a 21% to 77% reduction in influenza infections, dependent on vaccine characteristics. Our economic modelling shows that using any of these next generation vaccines at 2019 coverage levels would be highly cost-effective at a willingness to pay threshold of £20,000 for a range of vaccine prices. The vaccine threshold price for the best next generation vaccines in £-2019 is £230 (95%CrI £192 - £269) per dose, but even minimally-improved influenza vaccines could be priced at £18 (95%CrI £16 - £21) per dose and still remain cost-effective. This evaluation demonstrates the promise of next generation influenza vaccines for impact on influenza epidemics, and likely cost-effectiveness profiles. We have provided evidence towards a full value of vaccines assessment which bolsters the investment case for development and roll-out of next-generation influenza vaccines.

Correspondence to: Estimating the full health and economic benefits of current and future influenza vaccines.

We recently published an article in BMC Medicine looking at the potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study. In their commentary on our article, Lafond et al. highlight the potential importance of the wider benefits of vaccination on cost-effectiveness. Whilst we agree with many points raised in the commentary, we think it raises further interesting discussion points, specifically around model complexity, model assumptions and data availability. These points are both relevant to this manuscript but have wider implications for vaccine cost-effectiveness studies.

Health and economic impact of delaying large-scale HPV vaccination and screening implementation on cervical cancer in China: a modelling study.

Background: Current uptake of HPV vaccination and screening in China is far below World Health Organization 2030 targets for cervical cancer elimination. We quantified health and economic losses of delaying large-scale HPV vaccination and screening implementation in China. Methods: We used a previously validated transmission model to project lifetime health benefits, costs, effectiveness, and timeline for cervical cancer elimination of alternative scenarios, including combining HPV vaccination initiated from 2022 to 2030 with screening in different modalities and coverage increase rates, as well as screening alone. All women living or projected to be born in China during 2022-2100 were considered. We employed a societal perspective. Findings: Regardless of vaccine type, immediate large-scale vaccination initiated in 2022 and achieving 70% coverage of HPV-based screening in 2030 (no-delay scenario) would be the least costly and most effective. Compared with the no-delay scenario, delaying vaccination by eight years would result in 434,000-543,000 additional cervical cancer cases, 138,000-178,000 deaths, and $2863-4437 million costs, and delay elimination by 9-10 years. Even with immediate vaccination, the gradual scale-up of LBC-based screening to 70% coverage in 2070 would result in 2,530,000-3,060,000 additional cases, 909,000-1,040,000 deaths, and $5098-5714 million costs compared with no-delay scenario, and could not achieve elimination if domestic 2vHPV or 4vHPV vaccines are used (4.09-4.21 cases per 100,000 woman in 2100). Interpretation: Delaying large-scale HPV vaccination and/or high-performance screening implementation has detrimental consequences for cervical cancer morbidity, mortality, and expenditure. These findings should spur health authorities to expedite large-scale vaccine rollout and improve screening. Funding: Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004).