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Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

ABSTRACT: BACKGROUND: A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. METHODS: A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. RESULTS: Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination further improved effectiveness and cost effectiveness. CONCLUSIONS: The effectiveness and cost effectiveness consequences of the time-critical interplay of pandemic dynamics, vaccine availability and intervention timing has been quantified. For moderate and extreme pandemics, vaccination combined with rapidly activated antiviral and social distancing interventions of sufficient duration is cost effective from the perspective of life years saved.

SUBMITTER: Kelso JK

PROVIDER: S-EPMC3637125 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning.MethodsA cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ?30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR), using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR.ResultsIntervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS) for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5%) the cost is ?$9 k per LYS; for a low severity pandemic (CFR of 0.1%) this strategy costs ?$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03%) the cost is ?$155 per LYS. With high severity pandemics (CFR >0.75%) the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death.ConclusionsThe most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in reducing the infection rate.

Project description:BackgroundA vaccine matched to a newly emerged pandemic influenza virus would require a production time of at least 6 months with current proven techniques, and so could only be used reactively after the peak of the pandemic. A pre-pandemic vaccine, although probably having lower efficacy, could be produced and used pre-emptively. While several previous studies have investigated the cost effectiveness of pre-emptive vaccination strategies, they have not been directly compared to realistic reactive vaccination strategies.MethodsAn individual-based simulation model of ~30,000 people was used to examine a pre-emptive vaccination strategy, assuming vaccination conducted prior to a pandemic using a low-efficacy vaccine. A reactive vaccination strategy, assuming a 6-month delay between pandemic emergence and availability of a high-efficacy vaccine, was also modelled. Social distancing and antiviral interventions were examined in combination with these alternative vaccination strategies. Moderate and severe pandemics were examined, based on estimates of transmissibility and clinical severity of the 1957 and 1918 pandemics respectively, and the cost effectiveness of each strategy was evaluated.ResultsProvided that a pre-pandemic vaccine achieved at least 30% efficacy, pre-emptive vaccination strategies were found to be more cost effective when compared to reactive vaccination strategies. Reactive vaccination coupled with sustained social distancing and antiviral interventions was found to be as effective at saving lives as pre-emptive vaccination coupled with limited duration social distancing and antiviral use, with both strategies saving approximately 420 life-years per 10,000 population for a moderate pandemic with a basic reproduction number of 1.9 and case fatality rate of 0.25%. Reactive vaccination was however more costly due to larger productivity losses incurred by sustained social distancing, costing $8 million per 10,000 population ($19,074/LYS) versus $6.8 million per 10,000 population ($15,897/LYS) for a pre-emptive vaccination strategy. Similar trends were observed for severe pandemics.ConclusionsCompared to reactive vaccination, pre-emptive strategies would be more effective and more cost effective, conditional on the pre-pandemic vaccine being able to achieve a certain level of coverage and efficacy. Reactive vaccination strategies exist which are as effective at mortality reduction as pre-emptive strategies, though they are less cost effective.

Project description:BackgroundSeasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months.MethodWe employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination.ResultsThe highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden.ConclusionSouth Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.

Project description:BackgroundSeasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly.Methods and findingsWe developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups.ConclusionsVaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.

Project description:ObjectiveTo investigate whether a single optimal vaccination strategy exists across countries to deal with a future influenza pandemic by comparing the cost effectiveness of different strategies in various pandemic scenarios for three European countries.DesignEconomic and epidemic modelling study.SettingsGeneral populations in Germany, the Netherlands, and the United Kingdom.Data sourcesCountry specific patterns of social contact and demographic data.ModelAn age structured susceptible-exposed-infected-recovered transmission model that describes how an influenza A virus will spread in the populations of Germany, the Netherlands, and the United Kingdom.InterventionsComparison of four vaccination strategies: no vaccination, blanket vaccination, vaccination of elderly people (≥ 65 years), and vaccination of high transmitters (5-19 years). The four strategies were evaluated for scenarios in which a vaccine became available early or at the peak of the pandemic, and in which either everyone was initially susceptible or older age groups had pre-existing immunity.Main outcome measureCost per quality adjusted life years (QALYs) gained.ResultsAll vaccination strategies were cost effective (incremental cost per QALY gained, comparing intervention with non-intervention). In scenarios where the vaccine became available at the peak of the pandemic and there was pre-existing immunity among elderly people the incremental cost effectiveness ratios for vaccinating high transmitters were €7325 (£5815; $10,470) per QALY gained for Germany, €10,216 per QALY gained for the Netherlands, and €7280 per QALY gained for the United Kingdom. The most cost effective strategy not only differed across the pandemic scenarios but also between countries. Specifically, when the vaccine was available early in the pandemic and there was no pre-existing immunity, in Germany it would be most cost effective to vaccinate elderly people ( €940 per QALY gained), whereas it would be most cost effective to vaccinate high transmitters in both the Netherlands (€525 per QALY gained) and the United Kingdom (€163 per QALY gained). This difference in optimal strategies was due to differences in the demographic characteristics of the countries: Germany has a significantly higher proportion of elderly people compared with the Netherlands and the United Kingdom.ConclusionsNo single vaccination strategy was most cost effective across countries. With aging populations, pre-existing immunity in particular could be of crucial importance for the cost effectiveness of options to mitigate a future influenza pandemic.

Project description:BackgroundChina has a high burden of influenza-associated illness among children. We aimed to evaluate the cost-effectiveness of introducing government-funded influenza vaccination to children in China (fully-funded policy) compared with the status quo (self-paid policy).MethodsA decision tree model was developed to calculate the economic and health outcomes, from a societal perspective, using national- and provincial-level data. The incremental cost-effectiveness ratio (ICER) [incremental costs per quality-adjusted life year (QALY) gained] was used to compare the fully-funded policy with the self-paid policy under the willingness-to-pay threshold equivalent to national and provincial GDP per capita. Sensitivity analyses were performed and various scenarios were explored based on real-world conditions, including incorporating indirect effect into the analysis.ResultsCompared to the self-paid policy, implementation of a fully-funded policy could prevent 1,444,768 [95% uncertainty range (UR): 1,203,446-1,719,761] symptomatic cases, 92,110 (95% UR: 66,953-122,226) influenza-related hospitalizations, and 6494 (95% UR: 4590-8962) influenza-related death per season. The fully-funded policy was cost-effective nationally (7964 USD per QALY gained) and provincially for 13 of 31 provincial-level administrative divisions (PLADs). The probability of a funded vaccination policy being cost-effective was 56.5% nationally, and the probability in 9 of 31 PLADs was above 75%. The result was most sensitive to the symptomatic influenza rate among children under 5 years [ICER ranging from - 25,612 (cost-saving) to 14,532 USD per QALY gained]. The ICER of the fully-funded policy was substantially lower (becoming cost-saving) if the indirect effects of vaccination were considered.ConclusionsIntroducing a government-funded influenza policy for children is cost-effective in China nationally and in many PLADs. PLADs with high symptomatic influenza rate and influenza-associated mortality would benefit the most from a government-funded influenza vaccination program.

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Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

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