Vaccination against pandemic influenza A/H1N1v in England: A real-time economic evaluation

doi:10.1016/j.vaccine.2010.01.002

Vaccine

Volume 28, Issue 12, 11 March 2010, Pages 2370-2384

https://doi.org/10.1016/j.vaccine.2010.01.002 Get rights and content

Abstract

Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26–67), and save around 2900 QALYs (80% credibility interval 1600–4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.

Introduction

In March 2009, an outbreak of a novel strain of influenza A/H1N1 (hereafter H1N1v) linked to swine influenza was detected in Mexico. By 12 June 2009, the infection had shown sustained human-to-human transmission across the world, leading the World Health Organisation to declare an influenza pandemic. The first wave of the outbreak of H1N1v in the United Kingdom (UK) appeared to peak around 25 July 2009, but cases began to increase again in September.

Vaccines specific to pandemic influenza have been successfully developed. The UK has a contract with two vaccine manufacturers (GlaxoSmithKline and Baxter) to procure H1N1v vaccines. On 7 August 2009, the Joint Committee on Vaccination and Immunisation (JCVI) recommended that high-risk individuals be prioritised for vaccination [1]. These individuals consist of everyone in the current seasonal influenza vaccine clinical at-risk groups (those with chronic respiratory, heart, kidney, liver neurological disease, diabetes, and immunosuppression), excluding the low-risk elderly but including pregnant women and household contacts of immunocompromised individuals. The vaccination programme was rolled out on 21 October with primary care surgeries receiving the vaccine in the following week [2]. The UK has ordered sufficient doses to cover the entire population, so there is the opportunity to extend these recommendations to lower risk individuals. However, the extent of vaccination is restricted by other considerations including the timeliness of the arrival of vaccine doses, the cost of distribution and likely vaccine uptake among different population groups.

Decisions about extending vaccination to low-risk individuals depend partly on the epidemiological impact and cost-effectiveness of such options. Here we describe how we fit an epidemic model to the estimated number of cases in real-time to predict the impact and cost-effectiveness of a range of vaccination options.

Section snippets

Epidemiological modelling

An age and risk group structured deterministic transmission dynamic model was used to estimate the impact of vaccination. The model has a modified SEIR structure, meaning that it has compartments for individuals who are susceptible to being infected by H1N1v (S), latently infected (E), infectious (I), and recovered (R). The population is also split into three risk groups – those in a seasonal influenza risk group, pregnant women, and those who are not in a risk group, with random mixing (within

Results

Fig. 1(e) shows the estimated impact of the different vaccination programmes on number of infections during the second wave of the H1N1 epidemic. The impact of vaccination is attenuated by the fact that vaccination can only occur late in the epidemic. Table 2 shows the estimated number of cases and deaths prevented, QALYs gained and treatment costs averted for the different vaccination strategies, compared with the no vaccination alternative. Vaccination of the high-risk groups is estimated to

Discussion

The model suggests that a significant fraction of individuals were infected in the first wave of the epidemic, and that the peak height of the autumn wave is likely to be similar to that observed in summer (subsequent data confirmed this model prediction, see Appendix B). As the risk of serious consequences following infection is much higher in the risk groups, it appears that vaccinating these groups is likely to be effective at reducing deaths and cost-effective, when compared to widely used

Competing interest

WJE's partner works for GlaxoSmithKline and therefore he declares a possible competing interest. He has no other competing interests. All other authors declare that the answer to the questions on your competing interest form are all No and therefore have nothing to declare.

Acknowledgements

We thank Elizabeth Miller for many helpful discussions, Elizabeth Miller, Pauline Kaye and Rashmi Malkani for providing data from the follow up of cases confirmed by the HPA Regional Microbiology Network (RMN); Elizabeth Miller, Katja Hoschler, Pia Hardelid and Elaine Stanford for data on the H1N1v serological survey; Shirley Cole, Anthony Underwood and other members of the HPA Immunisation, Hepatitis & Blood Safety Department for contributing to the EQ-5D study; the EU FP7 EPIWORK grant 231807

References (33)

J.P. Harris et al.
Evaluating rotavirus vaccination in England and Wales. Part I. Estimating the burden of disease
Vaccine
(2007)
J. Maurer et al.
Does receipt of seasonal influenza vaccine predict intention to receive novel H1N1 vaccine: evidence from a nationally representative survey of U.S. adults
Vaccine
(2009)
Department of Health. Advice from the Joint Committee on Vaccination and Immunisation on swine flu vaccination. Friday...
Department of Health. More than 11 million people in England will be offered it first. Available from:...
Health Protection Agency. HPA weekly national influenza report....
C. Fraser et al.
Pandemic potential of a strain of Influenza A (H1N1): early findings
Science
(2009)
J. Mossong et al.
Social contacts and mixing patterns relevant to the spread of infectious diseases
PLoS Med
(2008)
N. Hens et al.
Estimating the impact of school closure on social mixing behaviour and the transmission of close contact infections in eight european countries
BMC Infect Dis
(2009)
Directgov. Directgov: Find out school term dates. Available from:...
National Institute for Health and Clinical Excellence. Updated guide to the methods of technology appraisal. June 2008....

Curtis L. Unit Costs of Health and Social Care 2008. Kent: Personal Social Services Research Unit, University of Kent...

F. Carrat et al.

Time lines of infection and disease in human influenza: a review of volunteer challenge studies

Am J Epidemiol

(2008)

Z. Kmietowicz

England to launch special flu service next week to take pressure off primary care

BMJ

(2009)

Flusurvey. www.flusurvey.org.uk. (Accessed...

M.G. Baker et al.

Pandemic H1N1 influenza lessons from the southern hemisphere

Eurosurveillance

(2009)

T. Garske et al.

Assessing the severity of the novel influenza A/H1N1 pandemic

BMJ

(2009)

Cited by (160)

Developing a novel composite index for monitoring occupational health and wellbeing: A case study in the rail sector in Great Britain
2021, Safety Science
The high economic and social burden of poor physical and mental health among workers calls for strategies to support and protect workforce health. Monitoring occupational health and wellbeing through the consistent and systematic use of data is considered to contribute substantially to designing evidence-based policies that improve outcomes for workers. The purpose of this paper is to expand on current efforts to enhance monitoring practices by introducing a novel approach to developing a composite Health and Wellbeing Index (HWI). HWI can combine a range of areas (for example, sickness absence, exposure to health risks, key health and mental wellbeing) based on valuation methodologies from health economics. The cost of different outcomes to companies, individuals and society is identified using Willingness to Pay (WTP) and Quality Adjusted Life Year (QALY) methods. These costs are compared with estimates of the value society attaches to preventing a fatality to arrive at weightings that reflect each HWI component’s monetary equivalence to the cost of a fatality. Based on this method, different components are transformed into comparable units and are added together to calculate a headline metric. A version of HWI that is tailored to the needs of the rail sector in Great Britain was developed in collaboration with the Rail Safety and Standards Board (RSSB) to drive improvements in the sector’s performance. The new index can be used to track progress over time, benchmark against best practice, identify areas for improvement and develop a robust evidence base for policy design and investment decisions.
Lessons learned from the A (H1N1) influenza pandemic
2021, Best Practice and Research: Clinical Obstetrics and Gynaecology
Citation Excerpt :
A pooled analysis of three RCTs undertaken in LMIC reported that maternal influenza immunisation is also 20% effective at protecting young infants against severe pneumonia [48] and reduces the risk of hospital admission with all cause acute lower respiratory illness by 44% (95% CI 1%–68%) [46]. Influenza immunisation in pregnancy has been demonstrated to be cost-effective for both seasonal and pandemic influenza [49–51]. A study in the UK found that to immunise pregnant women against seasonal influenza was associated with an incremental cost-effectiveness ratio of around £23,000.
Influenza in pregnancy is a common condition that is associated with an increased risk of hospital admission. Women with comorbidities are at a greater risk of severe outcomes. There are substantial gaps in our knowledge of the impact of severe influenza on perinatal outcomes, particularly in low- and middle-income countries, but preterm birth, fetal death, infant respiratory infection and hospital admission may be increased. Thus, influenza is a major burden on health services. Immunisation is cost-effective, safe and effective in preventing influenza in pregnant women and their infants but policies and uptake vary worldwide. Operational challenges and concern over the safety, efficacy and necessity of immunisation are common, and there is a lack of evidence on how to overcome these barriers. This review identifies learning points that are relevant to the current coronavirus disease-2019 pandemic through describing the epidemiology and impact of seasonal and A(H1N1)pdm09 influenza in pregnancy, alongside the effectiveness and use of immunisation.
The impact of Covid-19, associated behaviours and policies on the UK economy: A computable general equilibrium model
2020, SSM - Population Health
We estimate the potential impact of COVID-19 on the United Kingdom economy, including direct disease effects, preventive public actions and associated policies. A sectoral, whole-economy macroeconomic model was linked to a population-wide epidemiological demographic model to assess the potential macroeconomic impact of COVID-19, together with policies to mitigate or suppress the pandemic by means of home quarantine, school closures, social distancing and accompanying business closures.
Our simulations indicate that, assuming a clinical attack rate of 48% and a case fatality ratio of 1.5%, COVID-19 alone would impose a direct health-related economic burden of £39.6bn (1.73% of GDP) on the UK economy. Mitigation strategies imposed for 12 weeks reduce case fatalities by 29%, but the total cost to the economy is £308bn (13.5% of GDP); £66bn (2.9% of GDP) of which is attributable to labour lost from working parents during school closures, and £201bn (8.8% of GDP) of which is attributable to business closures. Suppressing the pandemic over a longer period of time may reduce deaths by 95%, but the total cost to the UK economy also increases to £668bn (29.2% of GDP), where £166bn (7.3% of GDP) is attributable to school closures and 502bn (21.9% of GDP) to business closures.
Our analyses suggest Covid-19 has the potential to impose unprecedented economic costs on the UK economy, and whilst public actions are necessary to minimise mortality, the duration of school and business closures are key to determining the economic cost. The initial economic support package promised by the UK government may be proportionate to the costs of mitigating Covid-19, but without alternative measures to reduce the scale and duration of school and business closures, the economic support may be insufficient to compensate for longer term suppression of the pandemic which could generate an even greater health impact through major recession.
A review of the costs of delivering maternal immunisation during pregnancy
2020, Vaccine
Routine maternal immunisation against influenza and pertussis are recommended by the WHO to protect mother and child, and new vaccines are under development. Introducing maternal vaccines into national programmes requires an understanding of vaccine delivery costs – particularly in low resource settings.
We searched Medline, Embase, Econlit, and Global Health for studies reporting costs of delivering vaccination during pregnancy but excluded studies that did not separate the vaccine purchase price. Extracted costs were inflated and converted to 2018 US dollars.
Sixteen studies were included, of which two used primary data to estimate vaccine delivery costs. Costs per dose ranged from $0.55 to $0.64 in low-income countries, from $1.25 to $6.55 for middle-income countries, and from $5.76 to $39.87 in high-income countries.
More research is needed on the costs of delivering maternal immunisation during pregnancy, and of integrating vaccine delivery into existing programmes of antenatal care especially in low and middle-income countries.
Exploring the role of mass immunisation in influenza pandemic preparedness: A modelling study for the UK context
2020, Vaccine
The nature and timing of the next influenza pandemic is unknown. This makes it difficult for policy makers to assess whether spending money now to prepare for mass immunisation in the event of a pandemic is worthwhile. We used simple epidemiological modelling and health economic analysis to identify the range of pandemic and policy scenarios under which plans to immunise the general UK population would have net benefit if a stockpiled vaccine or, alternatively, a responsively purchased vaccine were used.
Each scenario we studied comprised a combination of pandemic, vaccine and immunisation programme characteristics in presence or absence of access to effective antivirals, with the chance of there being a pandemic each year fixed. Monetarised health benefits and cost savings from any influenza cases averted were set against the option, purchase, storage, distribution, administration, and disposal costs relevant for each scenario to give a discounted net present value over 10 years for planning to immunise, accounting for the possibility that there may be no pandemic over the period considered. To support understanding and exploration of model output, an interactive visualisation tool was devised and made available online.
We evaluated over 29 million combinations of pandemic and policy characteristics. Preparedness plans incorporating mass immunisation show positive net present value for a wide range of scenarios, predominantly in the absence of effective antivirals. Plans based on the responsive purchase of vaccine have wider benefit than plans reliant on the purchase and maintenance of a stockpile if immunisation can start without extensive delays. This finding is not dependent on responsively purchased vaccine being more effective than stockpiled vaccine, but rather is driven by avoiding the costs of storing and replenishing a stockpile.
Cost-effectiveness of inactivated influenza vaccination in children with medical risk conditions in the Netherlands
2020, Vaccine
In many countries, annual immunization with inactivated influenza vaccine (IIV) is recommended for children with medical risk conditions. Prior cost-effectiveness analyses found such immunization to be cost saving, but assumed effectiveness against non-severe influenza outcomes and a higher effectiveness against severe influenza outcomes than recent studies would suggest. However, recent vaccine studies do not indicate any reduction in community or outpatient disease episodes in IIV immunized individuals. We therefore evaluated cost-effectiveness of IIV immunization in children with medical risk conditions in the Netherlands, assuming that IIV reduces influenza-related hospitalization and death, but has no meaningful impact on non-severe health outcomes.
A health economic decision tree model was developed to evaluate health effects and costs of annual IIV immunization versus no immunization. Model inputs were based on our study on influenza-related primary care visits and other literature. Immunization was considered cost effective if associated costs were less than €20,000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses were performed to assess robustness of results, and one-way sensitivity analyses and scenario analyses were done to assess the influence of individual parameters.
Annual IIV prevents an average of 1.59 influenza-related hospitalizations and 0.02 deaths per 1,000 children with medical risk conditions. This results in an expected QALY gain of 0.43 at incremental costs of €21,564 per 1,000 children, corresponding to an incremental cost-effectiveness ratio (ICER) of €50,297/QALY compared to no immunization. Under base case assumptions, immunization had a 5% probability of being cost effective. Results were most influenced by vaccine efficacy against fatal influenza, QALY loss due to death, and mortality rate.
If IIV only reduces severe disease outcomes, as current evidence suggests, annual immunization of medical risk children is unlikely to be cost effective. Results should however be interpreted with caution as cost-effectiveness is largely dependent on incidence and QALY losses for fatal influenza, for which evidence is scarce.

View all citing articles on Scopus

¹: Both authors contributed equally to this work. The order of their names on this paper was decided by a coin toss.

View full text

Vaccination against pandemic influenza A/H1N1v in England: A real-time economic evaluation

Abstract

Introduction

Section snippets

Epidemiological modelling

Results

Discussion

Competing interest

Acknowledgements

Vaccine

Vaccine

Pandemic potential of a strain of Influenza A (H1N1): early findings

Science

Social contacts and mixing patterns relevant to the spread of infectious diseases

PLoS Med

Estimating the impact of school closure on social mixing behaviour and the transmission of close contact infections in eight european countries

BMC Infect Dis

Time lines of infection and disease in human influenza: a review of volunteer challenge studies

Am J Epidemiol

England to launch special flu service next week to take pressure off primary care

BMJ

Pandemic H1N1 influenza lessons from the southern hemisphere

Eurosurveillance

Assessing the severity of the novel influenza A/H1N1 pandemic

BMJ