a Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, 3050 Australia.
b Communicable Diseases Section, Public Health Division, Department of Human Services Victoria, Australia.
c National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.
Dr Susan Skull, Epidemiology Division, Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. E-mail: sue.skull{at}mh.org.au
Abstract
Background Disease due to serogroup C Neisseria meningitidis is life-threatening and potentially preventable by vaccination. In 1999, the UK instigated mass vaccination after a sustained increase in serogroup C meningococcal disease. In the same year, Victoria, Australia experienced a similar change in disease epidemiology. It is timely to undertake an economic evaluation of options for community vaccination in Australia based on local data.
Methods Cost-effectiveness and cost-benefit analyses of three options for use of polysaccharide vaccine were undertaken for a hypothetical population aged 1519 years. Baseline analyses assumed 5 years' duration of vaccine protection following a single year of programme implementation. Sensitivity analyses of key variables were performed, including vaccine coverage and effectiveness, case fatality rate and the discount rate. Outcomes included the number of people vaccinated, cases averted, life-years saved and disability-adjusted life-years (DALY) averted. Cost-benefit analysis used lost earnings avoided as a measure of vaccination benefit.
Results Vaccination of people aged 1519 years in a defined population with a high rate of disease was the most cost-effective option. Compared with no vaccination and assuming 5 years' duration of protection and exclusion of direct cost savings, this resulted in a discounted cost per life-year saved of $23 623, a cost per DALY avoided of $21 097 and benefits exceeding costs in discounted terms. The break-even incidence rate for this option with exclusion of direct cost savings was 14.0/100 000.
Conclusions Community use of polysaccharide vaccination may be cost effective in Australia under certain conditions. Economic evidence favours use of vaccination in well-defined populations with a high rate of disease. Policy decision-making also requires consideration of non-economic factors, including feasibility of implementation and risk perception by the community.
KEY MESSAGES
Keywords Neisseria meningitidis, cost-effectiveness analysis, immunization programmes, health planning
Accepted 22 December 2000
Background
Neisseria meningitidis (meningococcus) can cause meningitis, septicaemia and severe complications including death in otherwise healthy individuals. The mortality rate is high even with appropriate antibiotic therapy. Intensive public health follow-up of each case is required to conduct contact tracing and provide chemoprophylaxis to close contacts. In Australia cases occur at a rate of approximately 2/100 000, with a usual pattern of two-thirds due to serogroup B and one-third due to serogroup C.1 A general upward trend in incidence rate has occurred over the 12 years to 1997, with a more recent increase in the proportion due to serogroup C (National Notifiable Disease Surveillance System data). In Victoria, the case fatality rate (CFR) for meningococcal disease varied from 3% to 12% between 1991 and 1999 (Department of Human Services [DHS] Victoria).
While development of vaccines against serogroup B disease has proved very difficult,2 meningococcal serogroup C disease is potentially preventable by vaccination. A polysaccharide vaccine against serogroups A, C, Y and W-135 is available for use in Australia and is effective in preventing disease in those aged 2 years or more.3 New conjugated vaccines against serogroup C are now available outside Australia that are also effective in younger children and may have a longer duration of protection.48 In the UK, vaccination with polysaccharide vaccine is recommended if four or more cases due to vaccine-preventable strains are confirmed within 3 months in a defined population, and where there is a high age-specific attack rate.9 The US recommends use of polysaccharide vaccination where three or more cases occur in a defined population in 3 months and where the age-specific attack rate is more than 10/100 000.10,11 National Health and Medical Research Council guidelines for community vaccination in Australia are similar to those of the US.12
In 1998, New South Wales (state adjacent to Victoria, Australia) experienced an increase in the rate of serogroup C disease.11 The following year, Victoria experienced a sustained increase in the rate of meningococcal disease attributable to serogroup C associated with a right shift in age (affecting predominantly young adults aged 1519 years) (DHS Victoria data). Cases in this age group had a high incidence rate of 6/100 000 and CFR of 24%, possibly attributable to the appearance of a new strain (or strains) of higher virulence(DHS Victoria data).
In response to a similar change in disease epidemiology to that seen in Victoria, a mass vaccination campaign against serogroup C disease was instigated in the UK in 1999 (including addition to the routine childhood schedule).13 There are no published data on the economic effectiveness of community-level vaccination against serogroup C meningococcal disease. It is timely to undertake an economic evaluation of options for vaccination based on Australian data. Options for use of meningococcal polysaccharide vaccine were considered for the 1519 year age group given the maximal rate of disease observed in this group in Victoria (DHS Victoria data). The options considered were chosen based upon the most accessible subgroups within the target population and feasibility of implementation.
Methods
The model
Three options using different target populations were considered in 1519-year-olds: (1) vaccination of students in years 1012 (secondary school) and first year university from a defined regional population with a high incidence of disease; (2) vaccination of all year 12 students in a larger population approximating a state or territory with a lower incidence (and which contains the regional area); and (3) both. The sizes and disease incidence without vaccination of the target populations under each option for this analysis are given in Table 1.
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Cost of vaccination programme implementation
For each of the three vaccine programme options, the following costs of vaccination were considered: the cost of the vaccine (number of units required based on population size and likely coverage), the cost of its administration (staff, travel, equipment), the cost of managing vaccine side-effects and the cost of campaign promotion (Table 1).
Direct cost savings arise from two sources: cost savings attributable to averted cases of meningococcal meningitis for (1) treatment (including complications), and (2) public health follow-up (attributable to contact tracing and provision of rifampicin chemoprophylaxis and/or immunoprophylaxis for epidemiologically-linked cases).
Treatment cost savings are based on the disease model shown in Figure 1. Based upon data from the Victorian Burden of Disease Study,14 all cases of meningitis are assumed to comprise an acute episode lasting for one month followed by after-effects that last for 6 months (including recovery time following hospital discharge). The CFR during this period is 11% based upon the mean annual mortality from meningitis in Australia over the 5-year period 19941998 (unpublished data provided by the Australian Bureau of Statistics [ABS] for ICD-10 codes 320322) and an incidence rate of 2.0/100 000 applied to the estimated Australian population as at 30 June 1999.15,16 The unit cost of treatment for the acute episode and short-term complications is assumed to be the same for both fatal and non-fatal cases ($7410, Table 1). Four per cent of non-fatal cases are assumed to experience long-term sequellae resulting in scarring/ deformities.14 The short-term unit cost of treating these long-term sequellae is estimated to be $3896.
Public health follow-up costs arise from the avoidance of tracing and providing chemoprophylaxis to close contacts, and predominantly from the avoidance of epidemiologically linked cases requiring closed-community chemo- and immunoprophylaxis (Table 1). The model assumes one such episode occurs per year for all options.
Cost-effectiveness and cost-benefit analyses
A cost-effectiveness analysis of each option compared with no vaccination was undertaken.
The cost-effectiveness ratio was determined by dividing the net direct costs of the vaccination programme in the target population by the number of cases averted (intermediate health outcome), and life-years saved or disability-adjusted life-years (DALYs) (final health outcomes) attributable to meningococcal meningitis. The number of cases averted was based upon the vaccine coverage achieved, vaccine efficacy and the incidence of disease in the target population. The number of life-years saved was calculated using the age at death and life expectancy at that age. Years lived with disability were calculated using disability weights on a 01 scale (0 = perfect health; 1 = death). The disability weights employed were: acute episode 0.913; after-effects 0.226; and long-term sequelae 0.133.1416 The number of DALYs avoided due to vaccination was taken as the sum of avoided years lived with disability and years of life lost due to premature mortality attributable to meningitis. No age weighting was applied in the calculation of DALYs, and those who experienced long-term sequelae were assumed to have the same life expectancy as those who did not.
Cost-benefit analyses of each option were undertaken by comparing the net costs of the vaccination programme (cost of vaccination less direct cost savings) with the benefits (indirect cost savings) attributable to averted cases. Indirect cost savings considered were the avoided lost earnings due to morbidity and premature mortality from meningitis (unpublished data from this survey provided by ABS).17 Cost-benefit ratios and the absolute difference between benefits and costs are presented.
Discounting
Undiscounted and discounted results are reported to demonstrate the effect on costs of immediate versus delayed benefits of vaccination. Discrete time discounting was employed throughout the model using one year as the unit of time. The baseline discount rate used was 5% per annum.18 Costs and events occurring in the first year of the programme were assumed to be unaffected by discounting.
Sensitivity analyses
One-way sensitivity analyses were performed by varying vaccine efficacy, incidence rates, duration of protection, the CFR and the discount rate. Two-way sensitivity analyses were performed by varying simultaneously the incidence rates in the high risk sub-group and the general population, the CFR and the duration of vaccine efficacy, and the discount rate and the duration of vaccine efficacy.
Results
Cost of vaccination programme and direct cost savings
The total costs and associated direct cost savings of each vaccination programme are shown in Table 2. Option 3 is the most expensive, and Option 1 the cheapest programme to implement in terms of total and net costs, and cost-saving in undiscounted terms. Options 2 and 3 are considerably more expensive to implement than Option 1, reflecting their larger target populations.
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Compared with no vaccination, the average cost per person vaccinated is similar across all three options (around $35) with no direct cost savings (treatment and public health follow-up costs) deducted (Table 4). However, the average cost per case averted is much greater under Options 2 and 3. Discounting increases this difference. The cost per life-year saved and cost per DALY averted are also considerably greater for Options 2 and 3. When all direct cost savings are deducted, Option 1 is a cost-saving intervention in undiscounted terms. With discounting, the cost per life-year saved under Option 1 is $2042 and the cost per DALY averted is $1823. The costs per life-year saved/ DALY averted for Options 2 and 3 are considerably higher.
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The two-way sensitivity analyses show the combined effect of simultaneous variation in two parameters in the model (Table 8). Reducing both incidence rates in the 1519-year-old group from 6.0/20.0 to 4.0/10.0 per 100 000 population for the general/high-risk populations respectively, increases the cost per DALY averted over baseline, while increasing the incidence rates to 8.0/30.0 reduces it. A higher CFR of 20% combined with a lower duration of efficacy results in a reduction in the cost per DALY, the higher CFR more than offsetting the effect of the reduction in duration of efficacy. A higher discount rate (8%) combined with a reduction in the duration of efficacy to 3 years more than doubles the cost per DALY averted for Option 1.
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Community use of polysaccharide meningococcal vaccination is cost effective in Australia under certain conditions. Our analyses indicate that community-level vaccination for those aged 1519 years would generate cost savings for Option 1 (vaccination of students in Years 1012 and first-year university students in a defined regional area with a high rate of disease) when direct cost offsets are taken into account. Cost-benefit analyses show that benefits (measured as the lost earnings avoided due to morbidity and premature mortality) also exceed the net costs of vaccination in discounted terms for this option. The remaining options have benefits in excess of costs only when the results are undiscounted.
The cost-effectiveness of Option 1 compares favourably with drug interventions approved for inclusion on the Pharmaceutical Benefits Scheme where many drugs with a cost per life-year saved less than $50 000 have been listed.19 The cost per DALY averted is not very sensitive to a five percentage point change in vaccine efficacy either side of the baseline value, but is more sensitive to changes in the incidence rates in the general population and the high-risk group, the CFR, the duration of vaccine efficacy and the discount rate. The cost per DALY averted for Option 1 remained within reasonable bounds for all variations considered in the sensitivity analyses. These analyses included the currently recommended threshold incidence rate for vaccination of 10/100 000 population, and an increase in the discount rate combined with a reduction in duration of vaccine efficacy.
While economic considerations are important in deciding whether to implement public health policy for community vaccination, other factors must be considered. These include the effects of current best practice, predictions of changes in the rate of disease, feasibility of programme implementation (including surveillance), and risk perception by community and government. The effect of mass community vaccination on disease epidemiology; prioritization along with other new vaccines and the possibility of combination vaccines or a vaccine with a longer duration of protection also need to be taken into account.
In conclusion, community-level meningococcal vaccination may be cost effective in Australia, particularly when indirect cost savings are considered. Economic evidence supports consideration of a policy favouring vaccination of a well-defined population with a high rate of disease. Policy decision-making for use of vaccination also requires consideration of non-economic factors, including feasibility of implementation and community risk perception.
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1 Anonymous. Annual report of the Australian Meningococcal Surveillance Programme, 1998. Commun Dis Intell 1999;23:31723.[Medline]
2 Al'Aldeen DA, Cartwright KA. Neisseria meningitidis: vaccines and vaccine candidates. J Infect 1996;33:15357.[ISI][Medline]
3 Centers for Disease Control and Prevention. Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46:121.[Medline]
4 Twumasi PA, Kumah S, Leach A et al. A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J Infect Dis 1995;171:63238.[ISI][Medline]
5 Anderson EL, Bowers T, Mink CM et al. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun 1994;62:339195.[Abstract]
6 Granoff DM, Gupta RK, Belshe RB, Anderson EL. Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination. J Infect Dis 1998;178:87074.[ISI][Medline]
7
MacDonald NE, Halperin SA, Law BJ, Forrest B, Danzig LE, Granoff DM. Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers. A randomized controlled trial. JAMA 1998;280:168589.
8 Leach AJ, Twumasi PA, Kumah S et al. Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine. J Infect Dis 1997;75:20004.
9 Stuart JM, Monk PN, Lewis DA, Constantine C, Kaczmarski EB, Cartwright KAV. Management of clusters of meningococcal disease. Commun Dis Rep 1997;7:R34.
10 American Academy of Pediatrics. Meningococcal Infections. In: Peter G (ed.). 1997 Red Book: Report of the Committee on Infectious Diseases. 24th Edn. Elk Grove Village, IL: American Academy of Pediatrics, 1997, pp.35762.
11 Anonymous. Annual report of the Australian Meningococcal Surveillance Programme, 1998. The Australian Meningococcal Surveillance Programme. Commun Dis Intell 1999;23:1723.
12 National Health and Medical Research Council. Guidelines for the Control of Meningococcal Disease in Australia. Vol. Canberra: Australian Government Publishing Service, 1996, pp.168.
13
Begg N. Policies for public health management of meningococcal disease. J Epidemiol Community Health 1999;53:516.
14 Victorian Government Department of Human Services. Victorian Burden of Disease Study: Mortality. Health Intelligence Series. Vol. 3. Melbourne: Department of Human Services, 1999, p.39.
15 Australian Government Actuary. Australian Life Tables 19959. Canberra: Australian Prudential Regulation Authority, 1999.
16 Australian Bureau of Statistics. Estimated Resident Population by Single Year of Age, Australia. Vol. 2000. AUSSTATS, 2000.
17 Australian Bureau of Statistics. Employee Earnings, Benefits and Trade Union Membership, Australia 1998. Canberra: Australian Bureau of Statistics, 1998.
18 Commonwealth Department of Human Services and Health. Guidelines for the Pharmaceutical Industry on Preparation of Submissions to the Pharmaceutical Benefits Advisory Committee. Canberra: Australian Government Printing Service, 1995.
19 George B, Harris A, Mitchell A. Reimbursement decisions and the implied value of life: cost-effectiveness analysis and decisions to reimburse pharmaceuticals in Australia 19931996. In: Economics and Health: 1997; Australian Studies in Health Service Administration, Economics and Health: 1997; Nineteenth Australian Conference of Health Economists, School of Health Services Management, University of New South Wales, Sydney, 1998. University of New South Wales.
20
Rosenstein N, Levine O, Taylor JP et al. Efficacy of meningococcal vaccine and barriers to vaccination. JAMA 1998;279:43539.
21 WHO Working Group. Control of Epidemic Meningococcal Disease. WHO Practical Guidelines. 2nd Edn. Geneva: World Health Organization, Emerging and Other Communicable Diseases, Surveillance and Control, 1999.
22 Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States. An emerging threat. JAMA 1995;273:41921.[ISI][Medline]