Pneumococcal Vaccination for Children in Asian Countries:A Systematic Review of Economic Evaluation Studies

Background: Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness of implementing and adopting a PCV vaccination program. Methods: We conducted a systematic review from Pubmed and Embase to identify economic evaluation studies of PCV for children in Asian countries up to May 2020. Data extraction included specific characteristics of the study, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement was followed for this systematic review. The reporting quality of the included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Results: After the screening process on both the title and abstract and full text of 518 records, a total of 25 studies fulfilled the inclusion criteria, and were included in the review. The majority of included studies demonstrates that PCV for children is cost-effective in most of the Asian region, and even cost-saving in some countries. Most of the included studies implemented cost utility analysis (CUA) using either quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Overall, the main drivers affecting the cost effectiveness were vaccine price, burden regarding pneumonia-related parameters, and the inclusion of herd effects. Conclusion: The children pneumococcal vaccination program appears to be a cost-effective intervention in Asia, and even cost-saving in certain conditions. Vaccine price, pneumonia-related disease burden, and the inclusion of the herd effect are observed as important key drivers in estimating cost-effectiveness in this region. Incorporating PCV in vaccination programs in this region was found to be highly favorable

Informing decision makers seeking to improve vaccination programs:case-study Serbia

Background: The optimisation of vaccine policies before their implementation is beholden upon public health decision makers, seeking to maximise population health. In this case study in Serbia, the childhood vaccines under consideration included pneumococcal conjugate vaccination (PCV), rotavirus (RV) vaccination and varicella zoster virus (VZV) vaccination.Objective: The objective of this study is to define the optimal order of introduction of vaccines to minimise deaths, quality adjusted life years (QALYs) lost, or hospitalisation days, under budget and vaccine coverage constraints.Methods: A constrained optimisation model was developed including a static multi-cohort decision-tree model for the three infectious diseases. Budget and vaccine coverage were constrained, and to rank the vaccines, the optimal solution to the linear programming problem was based upon the ratio of the outcome (deaths, QALYs or hospitalisation days) per unit of budget. A probabilistic decision analysis Monte Carlo simulation technique was used to test the robustness of the rankings.Results: PCV was the vaccine ranked first to minimise deaths, VZV vaccination for QALY loss minimisation and RV vaccination for hospitalisation day reduction. Sensitivity analysis demonstrated the most robust ranking was that for PCV minimizing deaths.Conclusion: Constrained optimisation modelling, whilst considering all potential interventions currently, provided a comprehensive and rational approach to decision making. (Figure presented.).</p

Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia.

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

Effect and cost-effectiveness of pneumococcal conjugate vaccination: a global modelling analysis.

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) has substantially reduced disease burden due to Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. However, PCVs are among the most expensive vaccines, hindering their introduction in some settings and threatening sustainability in others. We aimed to assess the effect and cost-effectiveness of introduction of 13-valent PCV (PCV13) vaccination globally. METHODS: We assessed the incremental cost-effectiveness ratio of PCV13 introduction by integrating two models: an ecological model (a parsimonious, mechanistic model validated with data from post-seven-valent PCV introduction in 13 high-income settings) to predict the effect of PCV on childhood invasive pneumococcal disease, and a decision-tree model to predict a range of clinical presentations and economic outcomes under vaccination and no-vaccination strategies. The models followed 30 birth cohorts up to age 5 years in 180 countries from 2015 to 2045. One-way scenario and probabilistic sensitivity analyses were done to explore model uncertainties. FINDINGS: We estimate that global PCV13 use could prevent 0·399 million child deaths (95% credible interval 0·208 million to 0·711 million) and 54·6 million disease episodes (51·8 million to 58·1 million) annually. Global vaccine costs (in 2015 international dollars) of $15·5 billion could be partially offset by health-care savings of$3·19 billion (2·62 billion to 3·92 billion) and societal cost savings of $2·64 billion (2·13 billion to 3·28 billion). PCV13 use is probably cost-effective in all six UN regions. The 71 countries eligible for support from Gavi, the Vaccine Alliance, account for 83$16 billion per year. INTERPRETATION: Our findings highlight the value of Gavi's support for PCV introduction in low-income countries and of efforts to improve the affordability of PCVs in countries not eligible for, or transitioning from, Gavi support. FUNDING: World Health Organization; Gavi, the Vaccine Alliance; and the Bill & Melinda Gates Foundation

Systematic review of economic evaluations of vaccination programs in mainland China: Are they sufficient to inform decision making?

The purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland China. We searched for economic evaluations of vaccination in China published prior to August 3, 2015 in eight English-language and three Chinese-language databases. Each article was appraised against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We found 23 papers evaluating vaccines against hepatitis B (8 articles), Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles), Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1 article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six Chinese-language articles conformed to fewer than half of the 19 criteria items. The main criteria that studies failed to conform to included: inappropriate measurement (20 articles) and valuation (18 articles) of treatment and/or vaccination costs, no discussion about distributional implications (18 articles), missing major health outcomes (14 articles), no discussion about generalizability to other contexts (14 articles), and inadequate sensitivity analysis (13 articles). In addition, ten studies did not include major cost components of vaccination programs, and nine did not report outcomes in terms of life years even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a societal perspective for analysis. All studies concluded that the appraised vaccination programs were cost-effective except for one evaluation of universal 7-valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the five studies on PCV-7 showed poor overall quality, and the number of studies on vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion, major methodological flaws and reporting problems exist in current economic evaluations of vaccination programs in China. Local guidelines for good practice and reporting, institutional mechanisms and education may help to improve the overall quality of these evaluations

Application of statistical and decision-analytic models for evidence synthesis for decision-making in public health and the healthcare sector

With the awareness that healthcare is a limited resource, decision-makers are challenged to allocate it rationally and efficiently. Health economic methods of evidence synthesis for decision-making are useful to quantify healthcare resource utilisation, critically evaluate different interventions and ensure the implementation of the most effective or cost-effective strategy. The nine studies included in the present cumulative doctoral thesis aim to demonstrate the capability of statistical and decision-analytic modelling techniques to inform and support rational healthcare decision-making in Germany. Five studies apply statistical modelling in analyses of public health and health economic data. They show that the developed models are valuable instruments for examining patterns in the data and generating knowledge from observable data which can further be used in devising disease management and care programs as well as economic evaluations. Further, two health economic evaluations, which adopt the decision-analytic-modelling approach, show that decision-analytic modelling is a powerful tool to represent the epidemiology of infectious and non-infectious diseases on a population level, quantify the burden of the diseases, generalise the outcomes of clinical trials, and predict how the interventions can change the impact of the diseases on the health of the population. Additionally, two literature reviews examine the application of decision-analytic modelling in health economic evaluations. The first study reviews and empirically analyses health technology assessments by the German Institute for Medical Documentation and Information and demonstrates that the application of decision-analytic models improves the evidence produced for policy-making in the healthcare sector in Germany. The second systematic review focuses on methodological choices made in constructing decision-analytic models and explains how critically the structural and parametrical assumptions can influence the final message of the economic evaluations and shows that building a validated, reliable model as well as the transparent reporting is of high priority in facilitating the communication and implementation of the most cost-effective course of action. Overall, the present thesis shows the relevance and advantage of the application of models in synthesising evidence for decision-making. The included studies contribute to the current and future development of the methods used to address the problems of health economic efficiency. Further advances in the computational modelling techniques and data collection, from one side, will ease the decision-making process, but, from another side, will require increasing competence and understanding within the decision-making bodies

Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic

Background: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods: A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. Results: The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save$7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. Conclusions: PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection

Public health impact and return on investment of Belgium’s pediatric immunization program

ObjectiveWe evaluated the public health impact and return on investment of Belgium’s pediatric immunization program (PIP) from both healthcare-sector and societal perspectives.MethodsWe developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0–10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre–vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit–cost ratio. Scenario analyses considered alternate assumptions for key model inputs.ResultsAcross all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium’s PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs.ConclusionBelgium’s PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact