Advice for Consideration of Quadrivalent (A, C, Y, W135) Meningococcal Conjugate Vaccine, for use by Provinces and Territories

Cost-effectiveness

IMD cases are not frequent in Canada but are associated with substantive societal costs and losses of healthy life years (De Wals et al., 2007). Average short-term medical costs per IMD case have been estimated at $13,000 and the annual treatment costs for a survivor with permanent physical sequelae at $17,000 below 18 years of age and $4,000 at 18 years of age and over (De Wals et al., 2007). In addition, indirect costs related to productivity losses caused by premature death or permanent physical sequelae should be taken into account.

New vaccines have somewhat of a disadvantage compared with older products, whose development costs have already been paid off. In particular, multivalent conjugate vaccines are more complex to produce than monovalent products. Also, the production capacity of Men4-DT is limited while there are three production facilities for monovalent serogroup C products. For publicly funded immunization programs, provinces and territories invite vaccine manufacturers to submit proposals (usually for short-term contracts), and the company offering the lowest price is selected. This purchasing process results in very low prices in a market where there is fierce competition, as was observed with MenC-C, the cost of which rapidly decreased from $50 to under $20. The expected market price of Men4-DT for the public sector in Canada is $70 per dose (De Wals et al., 2007). In the future, however, the differential price between monovalent C and quadrivalent conjugate vaccines may decrease, especially when several quadrivalent products enter the market.

Costs associated with these potential vaccination programs mainly include vaccine purchase and administration costs. In a recent cost-effectiveness analysis, the marginal opportunity costs for the administration of Men4-DT vaccine to a teenager along with another recommended vaccine were estimated to $8.50 (De Wals et al., 2007). Using this value and a vaccine purchase price of $70 per dose, program costs for provincial governments according to different levels of vaccine coverage of teenagers are shown in Table 2. Overall, program costs would range between $19 and $29 million. Vaccine delivery and administration costs in Canadian territories may be higher than in more densely populated provinces and there are no good data to provide reliable estimates of total program costs in these regions. Adverse reactions associated with the administration of meningococcal conjugate vaccines in adolescents requiring medical attention are rare, and associated costs do not affect total program costs significantly (De Wals et al., 2007).

Table 2: Estimated program cost* to the health system according to different population coverage of teenagers with a quadrivalent meningococcal conjugate vaccine in Canada

Province	Population (2006 estimate)	Vaccination Coverage
		60%	70%	80%	90%
Newfoundland and Labrador	6 000	$ 283	$ 330	$ 377	$ 424
Prince Edward Island	2 000	$ 94	$ 110	$ 126	$ 141
Nova Scotia	11 000	$ 518	$ 604	$ 691	$ 777
New Brunswick	9 000	$ 424	$ 495	$ 565	$ 636
Quebec	95 000	$ 4 475	$ 5 220	$ 5 966	$ 6 712
Ontario	162 000	$ 7 630	$ 8 902	$ 10 174	$ 11 445
Manitoba	16 000	$ 754	$ 879	$ 1 005	$ 1 130
Saskatchewan	14 000	$ 659	$ 769	$ 879	$ 989
Alberta	45 000	$ 2 120	$ 2 473	$ 2 826	$ 3 179
British Columbia	51 000	$ 2 402	$ 2 802	$ 3 203	$ 3 603
All 10 provinces	411 000	$ 19 358	$ 22 584	$ 25 811	$ 29 037

* Costs are expressed in thousands of Canadian $

Currently, the most attractive option for use of Men4-DT in Canada would be vaccination around 12 years of age of naïve subjects or revaccination of subjects primed with a monovalent serogroup C conjugate vaccine (MenC-C) at a young age. A simulation model was developed for assessing both the direct and indirect effects of a booster dose at 12 years of age with either a monovalent C or a quadrivalent ACYW135 meningococcal conjugate vaccine in a cohort of Canadians immunized at 12 months with MenC-C (De Wals et al., 2007). Age and serogroup-specific incidence and fatality rates were derived from Canadian surveillance data. Vaccine efficacy was estimated from data from the UK and Spain, assuming an age-dependent decline of vaccine efficacy over time. Expected vaccine coverage rates were 90% at 12 months, and 70% at 12 years. Herd immunity was modeled using UK data. Vaccine purchase price per dose was $23 for MenC-C and $70 for Men4-DT. Costs and health outcomes were discounted at 3% per year. Results, expressed in 2004 Canadian dollars and from a societal perspective, were presented for a steady-state situation and a population of one million.

As seen in Table 3, 5.7 cases of vaccine-preventable meningococcal disease would occur each year under the “no vaccination” base scenario. Vaccination at 12 months using MenC-C would reduce the burden of disease by 32%. Adding MenC-C at 12 years of age would reduce the number of cases by 55% at no marginal cost (a minor saving is predicted). Using Men4-DT for the booster dose would result in a disease reduction of 78% for a marginal cost of $31 000 per QALY gained compared to one dose of MenC-C at 12 months. Comparing Men4-DT with MenC-C as a booster dose, the incremental cost-effectiveness ratio would be $113 000 per QALY.

Table 3: Cost-effectiveness of different immunization strategies using the serogroup C meningococcal conjugate vaccine (MenC-C) or quadrivalent meningococcal conjugate vaccine (Men4-DT) in a population of one million in Canada, in base model scenario (De Wals et al., 2007).

Outcome	No vaccination	MenC-C at 12 mo	MenC-C at 12 mo & 12 yr	MenC-C at 12 mo & Men4-DT at 12 yr
Number doses MenC-C	—	12000	21000	12000
Number doses MenC-4	—	—	—	9000
Program cost	—	$ 316 000	$ 604 000	$ 1 033 000
IMD cases averted (direct)	—	1.0	1.7	2.0
IMD cases averted (indirect)	—	0.6	2.2	2.8
Residual IMD cases	5.7	4.1	1.8	0.9
Incremental net cost/QALY (95% confidence interval)	—	Ref	$ -1000 ($-15 000 to $ 82 000)	$ 31 000 ($ 12 000 to $ 111 000)
			Ref	$ 113 000 ($ 72 000 to $ 198 000)

Results of sensitivity analyses showed that the vaccine effectiveness and the differential price between the two vaccines were the parameters having the strongest impact on the cost/QALY ratios. Any increase in the incidence of serogroup Y would also improve the marginal cost-effectiveness ratio associated with Men4-DT. In all scenarios, however, revaccination with MenC-C was associated with more favourable cost-effectiveness indices than with Men4-DT, and in the current epidemiological situation the differential price between the two vaccines would have to be markedly reduced to reverse this conclusion.

Different simulation models of variable complexity have been developed to analyse the future impact of different immunization strategies (Trotter at al., 2002; De Wals et al. 2004; Trotter et al., 2005; De Wals et al., 2006; De Wals et al., 2007; Caro et al. 2007). There are significant limitations in these models, the most important being the unpredictable epidemiology of Neisseria meningitidis, uncertainty regarding the long term effectiveness of meningococcal conjugate vaccine, and the level of herd immunity provided by routine vaccination. Results can thus provide a rough comparison of the relative impact of different strategies within a specified model but comparisons between models and absolute cost-effectiveness indices should be regarded with great care.