Evaluating the reactogenicity of COVID-19 vaccines from network-meta analyses.

BACKGROUND: Evidence-based reassurances addressing vaccine-related concerns are crucial to promoting primary vaccination, completion of the primary series, and booster vaccination. By summarizing and comparing the reactogenicity of COVID-19 vaccines authorized by the European Medicines Agency, this analysis aims to support in-formed decision-making by the lay public and help overcome vaccine hesitancy. RESEARCH DESIGN AND METHODS: A systematic literature review identified 24 records reporting solicited adverse events for AZD1222, BNT162b2, mRNA-1273, NVX-Cov2373, and VLA2001 in individuals aged 16 or older. Network meta-analyses were conducted for each solicited adverse events reported for at least two vaccines that were not compared head-to-head but could be connected through a common comparator. RESULTS: A total of 56 adverse events were investigated through network meta-analyses within a Bayesian framework with random-effects models. Overall, the two mRNA vaccines were found to be the most reactogenic vaccines. VLA2001 had the highest likelihood of being the least reactogenic vaccine after the first and second vaccine dose, especially for systemic adverse events after the first dose. CONCLUSIONS: The reduced chance of experiencing an adverse event with some COVID-19 vaccines may help to overcome vaccine hesitancy in population groups with concerns about the side effects of vaccines.

Investing in the Prevention of Communicable Disease Outbreaks: Fiscal Health Modelling-The Tool of Choice for Assessing Public Finance Sustainability.

National strategies for preparedness for future outbreaks of COVID-19 often include timely preparedness with vaccines. Fiscal health modelling (FHM) has recently been brought forward as an additional analysis by defining the public economic impact from a governmental perspective. As governments are the main decision-makers concerning pandemic preparedness, this study aimed to develop an FHM framework for infectious diseases in the Netherlands. Based on the Dutch COVID-19 outbreak of 2020 and 2021 and publicly available data on tax income and gross domestic product (GDP), the fiscal impact of COVID-19 was assessed using two approaches. Approach I: Prospective modelling of future fiscal impact based on publicly available laboratory-confirmed COVID-19 cases; and Approach II: Retrospective assessment of the extrapolated tax and benefit income and GDP. Approach I estimated the consequences that can be causally linked to the population counts reducing income taxes by EUR 266 million. The total fiscal loss amounted to EUR 164 million over 2 years (excluding pension payments averted). The total losses in terms of tax income (2020 and 2021) and GDP (2020) (Approach II), were estimated at, respectively, EUR 13.58 billion and EUR 96.3 billion. This study analysed different aspects of a communicable disease outbreak and its influence on government public accounts. The choice of the two presented approaches depends on the perspective of the analysis, the time horizon of the analysis and the availability of data.

Capturing the value of vaccination within health technology assessment and health economics: Literature review and novel conceptual framework.

BACKGROUND: Vaccination provides significant health gains to individuals and society and can potentially improve health equity, healthcare systems and national economies. Policy decisions, however, are rarely informed by comprehensive economic evaluations (EE) including vaccination's wide-ranging value. The objective of this analysis was to focus on health technology assessment systems to identify relevant value concepts in order to improve current EE of non-pandemic vaccines. METHODS: Following a literature review, a novel Value of Vaccination (VoV) framework was developed with experts in vaccine EE from developed countries with established health technology assessment systems. RESULTS: Forty-four studies presenting value frameworks or concepts applicable to vaccination were included. Eighteen unique value concepts relevant to EE were identified and defined. These were categorised within the VoV framework using three dimensions, moving from a narrow payer perspective to a more expansive and societal perspective. The dimensions were: (I) conventional payer perspective concepts (e.g., health gains in vaccinees, direct medical costs); (II) conventional societal perspective concepts (e.g., indirect health/economic gains to caregivers/households, productivity in vaccinees); and (III) novel societal concepts (e.g., financial risk protection, peace of mind, societal health gains, healthcare systems security, political stability, social equity and macroeconomic gains). While good quality evidence and methods are available to support concepts in Dimensions I and II, further work is needed to generate the required evidence for vaccination impact on Dimension III concepts. CONCLUSIONS: The devastating effect on nations of the COVID-19 pandemic has helped to highlight the potential far-reaching benefits that many vaccination programmes can offer. This VoV framework is particularly relevant to policy decisions considering EE, and the potential future expansion of non-pandemic vaccination value considerations. The framework helps to understand and compare current value considerations across countries and payer versus societal perspectives. It provides decision-makers with a transparent and logical path to broaden consideration of VoV in EE.

Economic evaluation of COVID-19 vaccination: A systematic review.

Background: Safe and effective vaccination is considered to be the most critical strategy to fight coronavirus disease 2019 (COVID-19), leading to individual and herd immunity protection. We aimed to systematically review the economic evaluation of COVID-19 vaccination globally. Methods: We performed a systematic search to identify relevant studies in two major databases (MEDLINE/PubMed and EBSCO) published until September 8, 2022. After deduplication, two researchers independently screened the study titles and abstracts according to pre-determined inclusion and exclusion criteria. The remaining full-text studies were assessed for eligibility. We assessed their quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and summarized and narratively presented the results. Results: We identified 25 studies that assessed the economic evaluation of COVID-19 vaccination worldwide by considering several input parameters, including vaccine cost, vaccine efficacy, utility value, and the size of the targeted population. All studies suggested that COVID-19 vaccination was a cost-effective or cost-saving intervention for mitigating coronavirus transmission and its effect in many countries within certain conditions. Most studies reported vaccine efficacy values ranging from 65% to 75%. Conclusions: Given the favorable cost-effectiveness profile of COVID-19 vaccines and disparities in affordability across countries, considering prioritization has become paramount. This review provides comprehensive insights into the economic evaluation of COVID-19 vaccination that will be useful to policymakers, particularly in highlighting preventive measures and preparedness plans for the next possible pandemic.

Estimates of the Global Burden of COVID-19 and the Value of Broad and Equitable Access to COVID-19 Vaccines.

The objectives of this research were to produce a macro-level overview of the global COVID-19 burden and estimate the value of access to COVID-19 vaccines. A targeted literature review collated evidence of the burden. Linear modelling and data analysis estimated the health and economic effects of COVID-19 vaccines delivered in 2021, and whether additional value could have been achieved with broader and more equitable access. By 1 December 2020, there had been an estimated 17 million excess deaths due to COVID-19. Low-income countries allocated more than 30% of their healthcare budgets to COVID-19, compared to 8% in high-income countries. All country income groups experienced gross domestic product (GDP) growth lower than predicted in 2020. If all 92 countries eligible for COVAX Advance Market Committee (AMC), access had reached 40% vaccination coverage in 2021, 120% more excess deaths would have been averted, equivalent to USD 5 billion (109) in savings to healthcare systems. Every USD spent by advanced economies on vaccinations for less advanced economies averted USD 28 of economic losses in advanced economies and USD 29 in less advanced economies. The cost to high-income countries when not all countries are vaccinated far outweighs the cost of manufacturing and distributing vaccines globally.

Capturing the value of vaccination within health technology assessment and health economics: Country analysis and priority value concepts.

BACKGROUND: A value of vaccination framework for economic evaluation (EE) identified unique value concepts for the broad benefits vaccination provides to individuals, society, healthcare systems and national economies. The objectives of this paper were to work with experts in developed countries to objectively identify three priority concepts to extend current EE. METHODS: The previously developed classification of value concepts in vaccination distinguished 18 concepts, categorised as conventional payer and societal perspective concepts and novel broader societal concepts. Their inclusion in current EE guidelines was assessed. Experts identified eight criteria relevant to decision-making and measurement feasibility, which were weighted and used to score each concept. The relative ranking of concepts by importance and the gaps in guidelines were used to identify three priority concepts on which to focus immediate efforts to extend EE. RESULTS: The EE guidelines review highlighted differences across countries and between guidelines and practice. Conventional payer perspective concepts (e.g., individual and societal health gains and medical costs) were generally included, while gaps were evident for conventional societal perspective concepts (e.g., family/caregiver health and economic gains). Few novel broader societal benefits were considered, and only in ad hoc cases. The top-three concepts for near-term consideration: macroeconomic gains (e.g., benefiting the economy, tourism), social equity and ethics (e.g., equal distribution of health outcomes, reduced health/financial equity gaps) and health systems strengthening, resilience and security (e.g., efficiency gains, reduced disruption, increased capacity). CONCLUSIONS: Gaps, inconsistencies and limited assessment of vaccination value in EE can lead to differences in policy and vaccination access. The three priority concepts identified provide a feasible approach for capturing VoV more broadly in the near-term. Robust methods for measuring and valuing these concepts in future assessments will help strengthen the evidence used to inform decisions, improving access to vaccines that are demonstrably good value for money from society's point of view.

Parents' Knowledge, Attitude, and Practice on Childhood Vaccination During the COVID-19 Pandemic in Indonesia.

BACKGROUND: Vaccination is known to have an enormous impact on improving child health. In Indonesia, the government has included several vaccines in the national immunization program. OBJECTIVE: This study aimed to investigate parents' knowledge, attitude, and practice on childhood immunization during the COVID-19 pandemic in Indonesia. METHODS: A valid and reliable questionnaire was delivered to approximately 276 parents in Jakarta and Bandung, representing the epicenter of the pandemic. This study was conducted from June 2020 to February 2021. The correlations between parents' knowledge, attitudes, and practice with the characteristics of the respondents were investigated. In addition, multiple regression analysis was performed to identify the variables associated with good vaccination practice. RESULTS: The results showed that the mean scores of parents' knowledge, attitude, and practice on childhood vaccinations were 7.22 (± 1.30) out of 9 points, 3.93 (± 0.31) out of 4 points, and 3.59 (± 0.97) out of 5 points, respectively. Respondents graduated from university were more knowledgeable than those graduated from senior high school (p-value <0.05). Employed participants had better scores in knowledge and practice, compared to unemployed participants (p-value <0.05). CONCLUSION: In conclusion, this study found positive correlations between participants' knowledge and attitude, knowledge and practice, and attitude and practice on childhood vaccination during the COVID-19 pandemic in Indonesia.

Applying systems thinking to identify enablers and challenges to scale-up interventions for hypertension and diabetes in low-income and middle-income countries: protocol for a longitudinal mixed-methods study.

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions. METHODS AND ANALYSIS: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (TP), initiation of implementation (T0) and 1-year postinitiation (T1). We will extract project-related data from secondary documents at TP and conduct multistakeholder qualitative interviews to gather data at T0 and T1. We will undertake descriptive statistical analysis of TP data and analyse T0 and T1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks. ETHICS AND DISSEMINATION: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network.

Mental health and health-related quality of life among healthcare workers in Indonesia during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVES: Healthcare workers (HCWs) are the front lines during the COVID-19 pandemic. They are more exposed to COVID-19 than other professions. Studies from other countries have shown that the mental health and health-related quality of life (HRQoL) of HCWs were affected during this pandemic. However, studies on mental health in Indonesia remain scarce and no study has evaluated the HRQoL among HCWs. Thus, this study was designed to explore the mental health status and HRQoL among HCWs in Indonesia. DESIGN: This was a cross-sectional study. SETTING: This was an open online survey in Indonesia conducted from December 2020 to February 2021. PARTICIPANTS: This study involved HCWs who worked during the COVID-19 pandemic. Of the 502 respondents who accessed the online questionnaire, 392 were included in the analysis. OUTCOMES: Mental health status was measured using the 21-item Depression, Anxiety and Stress Scale and HRQoL was measured using the second version of the 12-item Short-Form Health Survey (SF12v2). RESULTS: The prevalence of depression, anxiety and stress among HCWs was 29.4%, 44.9% and 31.8%, respectively. Using the SF12v2 questionnaire, 354 (90.3%) HCWs were found to have impaired physical component and 156 (39.8%) HCWs have impaired mental component. CONCLUSION: The prevalence of mental health problems among HCWs was high in Indonesia. HRQoL, particularly the physical component, was affected in most HCWs. Thus, policymakers should give more attention to the mental health and HRQoL of HCWs during the COVID-19 pandemic.

Reconstructing the Effectiveness of Policy Measures to Avoid Next-Wave COVID-19 Infections and Deaths Using a Dynamic Simulation Model: Implications for Health Technology Assessment.

OBJECTIVE: The goal of this study was to dynamically model next-wave scenarios to observe the impact of different lockdown measures on the infection rates (IR) and mortality for two different prototype countries, mimicking the 1st year of the COVID-19 pandemic in Europe. METHODS: A dynamic simulation SIRD model was designed to assess the effectiveness of policy measures on four next-wave scenarios, each preceded by two different lockdowns. The four scenarios were (1) no-measures, (2) uniform measures, (3) differential measures based on isolating > 60 years of age group, and (4) differential measures with additional contact reduction measures for the 20-60 years of age group. The dynamic simulation model was prepared for two prototype European countries, Northwestern (NW) and Southern (S) country. Both prototype countries were characterized based on age composition and contact matrix. RESULTS: The results show that the outcomes of the next-wave scenarios depend on number of infections of previous lockdowns. All scenarios reduce the incremental deaths compared with a no-measures scenario. Differential measures show lower number of deaths despite an increase of infections. Additionally, prototype S shows overall more deaths compared with prototype NW due to a higher share of older citizens. CONCLUSION: This study shows that differential measures are a worthwhile option for controlling the COVID-19 epidemic. This may also be the case in situations where relevant parts of the population have taken up vaccination. Additionally, the effectiveness of interventions strongly depends on the number of previously infected individuals. The results of this study may be useful when planning and forecasting the impact of non-pharmacological interventions and vaccination campaigns.

Comparing the Clinical and Economic Outcomes Associated with Adjuvanted versus High-Dose Trivalent Influenza Vaccine among Adults Aged ≥ 65 Years in the US during the 2019-20 Influenza Season-A Retrospective Cohort Analysis.

The burden of influenza is disproportionally higher among older adults. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent (aIIV3) compared to high-dose trivalent influenza vaccine (HD-IIV3e) against influenza and cardio-respiratory disease (CRD)-related hospitalizations/ER visits among adults ≥65 years during the 2019-2020 influenza season. Economic outcomes were also compared. A retrospective cohort analysis was conducted using prescription, professional fee claims, and hospital data. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding. IPTW-adjusted Poisson regression was used to evaluate the adjusted rVE of aIIV3 versus HD-IIV3e. All-cause and influenza-related healthcare resource utilization (HCRU) and costs were examined post-IPTW. Recycled predictions from generalized linear models were used to estimate adjusted costs. Adjusted analysis showed that aIIV3 (n = 798,987) was similarly effective compared to HD-IIV3e (n = 1,655,979) in preventing influenza-related hospitalizations/ER visits (rVE 3.1%; 95% CI: -2.8%; 8.6%), hospitalizations due to any cause (-0.7%; 95% CI: -1.6%; 0.3%), and any CRD-related hospitalization/ER visit (0.9%; 95% CI: 0.01%; 1.7%). Adjusted HCRU and annualized costs were also statistically insignificant between the two cohorts. The adjusted clinical and economic outcomes evaluated in this study were comparable between aIIV3 and HD-IIV3e during the 2019-2020 influenza season.

Vaccine market access pathways in the EU27 and the United Kingdom - analysis and recommendations for improvements.

BACKGROUND: Vaccine market access (VMA) pathways across the European Union (EU) and the United Kingdom (UK) are complex, lengthy, and heterogeneous, particularly when compared with pharmaceuticals. The knowledge base to inform recommendations for optimization of VMA is lacking. We therefore conducted a comprehensive evaluation of EU VMA pathways. METHODS: Research in two phases included: (1) mapping VMA pathways in each EU member state (including the UK) based on a literature review, expert interviews, and mathematical archetyping; and (2) interviews with vaccine experts to identify barriers, drivers, and recommendations for regional VMA alignments. RESULTS: Key steps in VMA across the EU include horizon scanning, early advice, National Immunization Technical Advisory Group (NITAG) recommendation for inclusion in national immunization programs, health technology assessment (HTA), final decision and procurement. We found significant complexity and heterogeneity, particularly for early advice, and in the roles, decision-making criteria, and transparency of NITAGs and HTA bodies. The most important drivers for rapid VMA included demonstration of disease burden and vaccine benefit (e.g., efficacy, safety, economic). Key barriers were budget limitations and complexity/clarity of VMA processes (e.g., need for national-regional consensus, clarity on process initiation, and clarity on the role of HTA). Recommendations for alignment at EU and member-state levels include information sharing, joint clinical assessment, initiatives to address funding and political barriers, and improved transparency by decision-making bodies. Early engagement with vaccine stakeholders was a key recommendation for manufacturers. CONCLUSIONS: There is significant potential for alignment, collaboration, and improvement of VMA across the EU. Roles, responsibilities, and transparency of key bodies can be clarified. The COVID-19 pandemic response should stimulate policies to improve access to all vaccines, including routine ones, and form the foundation upon which a consistent vaccine ecosystem can be created for the EU, one that is resilient, consistent between member states, and fit for purpose.

Economic Analyses of Respiratory Tract Infection Diagnostics: A Systematic Review.

BACKGROUND: Diagnostic testing for respiratory tract infections is a tool to manage the current COVID-19 pandemic, as well as the rising incidence of antimicrobial resistance. At the same time, new European regulations for market entry of in vitro diagnostics, in the form of the in vitro diagnostic regulation, may lead to more clinical evidence supporting health-economic analyses. OBJECTIVE: The objective of this systematic review was to review the methods used in economic evaluations of applied diagnostic techniques, for all patients seeking care for infectious diseases of the respiratory tract (such as pneumonia, pulmonary tuberculosis, influenza, sinusitis, pharyngitis, sore throats and general respiratory tract infections). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles from three large databases of scientific literature were included (Scopus, Web of Science and PubMed) for the period January 2000 to May 2020. RESULTS: A total of 70 economic analyses are included, most of which use decision tree modelling for diagnostic testing for respiratory tract infections in the community-care setting. Many studies do not incorporate a generally comparable clinical outcome in their cost-effectiveness analysis: fewer than half the studies (33/70) used generalisable outcomes such as quality-adjusted life-years. Other papers consider outcomes related to the accuracy of the test or outcomes related to the prescribed treatment. The time horizons of the studies generally are limited. CONCLUSIONS: The methods to economically assess diagnostic tests for respiratory tract infections vary and would benefit from clear recommendations from policy makers on the assessed time horizon and outcomes used.

The Role of Administrative and Secondary Data in Estimating the Costs and Effects of School and Workplace Closures due to the COVID-19 Pandemic

As a part of mitigation strategies during a COVID-19 pandemic, the WHO currently recommends social distancing measures through school closures (SC) and work closures (WC) to control the infection spread and reduce the illness attack rate. Focusing on the use of administrative and secondary data, this study aimed to estimate the costs and effects of alternative strategies for mitigating the COVID-19 pandemic in Jakarta, Indonesia, by comparing the baseline (no intervention) with SC + WC for 2, 4, and 8 weeks as respective scenarios. A modified Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model accounting for the spread of infection during the latent period was applied by taking into account a 1-year time horizon. To estimate the total pandemic cost of all scenarios, we took into account the cost of healthcare, SC, and productivity loss due to WC and illness. Next to costs, averted deaths were considered as the effect measure. In comparison with the baseline, the result showed that total savings in scenarios of SC + WC for 2, 4, and 8 weeks would be approximately $24 billion, $25 billion, and $34 billion, respectively. In addition, increasing the duration of SC and WC would increase the number of averted deaths. Scenarios of SC + WC for 2, 4, and 8 weeks would result in approximately 159,075, 173,963, and 250,842 averted deaths, respectively. A sensitivity analysis showed that the wage per day, infectious period, basic reproduction number, incubation period, and case fatality rate were found to be the most influential parameters affecting the savings and number of averted deaths. It can be concluded that all the mitigation scenarios were considered to be cost-saving, and increasing the duration of SC and WC would increase both the savings and the number of averted deaths.